MedWorm: Amyloidosis

Pathologic observations of the duodenum in 615 consecutive duodenal specimens: I. benign lesions.

International Journal of Clinical and Experimental Pathology — Tue, 07 Feb 2012 13:36:02 +0100

Authors: Terada T Abstract The author investigated histopathology of 615 consecutive duodenal specimens in our pathology laboratory. Computer search of the duodenal lesions was performed. Review of histological slides was done, when appropriate. The duodenal specimens were composed of 567 benign lesions and 48 malignant lesions. The 567 benign lesions were composed of chronic non-specific duodenitis in 334 cases (60.0%), duodenal ulcer in 101 cases (17,8%), heterotopic gastric mucosa in 81 cases (14.3%), hyperplastic polyp in 16 cases (2.8%), Brunner's gland hyperplasia in 14 cases (2.5%), Brunner's gland adenoma in 8 cases (1.4%), lymphoid polyp in 5 cases (0.8%), tubular adenoma in 4 cases (0.7%), lymphangioma in 2 cases (0.4%), endocrine nests in 1 case (0.2%), and amyloidosis i...

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Hidradenitis suppurativa resulting in systemic amyloid A amyloidosis: A case report and review of the literature.

Dermatol Online J — Mon, 06 Feb 2012 12:54:18 +0100

We describe a 39-year-old man with a long history of recurrent, tender, erythematous nodules in the axillary and anogenital regions, resulting in abscesses, sinus tract formation, and large areas of scarring. After 21 years of cutaneous disease with concurrent elevated systemic inflammatory markers, the patient was noted to have significant proteinuria. A kidney biopsy and immunostaining revealed deposits of amyloid A. Echocardiogram and electrocardiogram showed ventricular and atrial wall thickening with an appearance consistent with cardiac amyloid deposition. Systemic amyloid A amyloidosis is a serious, but rare, complication of chronic inflammatory disorders, including hidradenitis suppurativa, with potential multi-organ involvement including renal and cardiac manifestations. Amyloid A...

Combined Laryngocele Secondary to Localized Laryngeal Amyloidosis

Indian Journal of Otolaryngology and Head and Neck Surgery — Thu, 02 Feb 2012 18:13:32 +0100

We present a young male patient with a large combined laryngocele secondary to laryngeal amyloidosis. Content Type Journal ArticleCategory Clinical ReportPages 1-4DOI 10.1007/s12070-012-0497-6Authors W. V. B. S. Ramalingam, Department of ENT, Army Hospital (Research and Referral), Delhi, 110010 IndiaSatish Nair, Department of ENT, Army Hospital (Research and Referral), Delhi, 110010 IndiaA. V. Ramesh, Department of ENT, Army Hospital (Research and Referral), Delhi, 110010 IndiaD. K. Gupta, Department of ENT, Army Hospital (Research and Referral), Delhi, 110010 IndiaAnil Kumar, Department of ENT, Army Hospital (Research and Referral), Delhi, 110010 India Journal Indian Journal of Otolaryngology and Head & Neck SurgeryOnline ISSN 0973-7707Print ISSN 2231-3796 (Source: Indian J...

High-dose melphalan and peripheral blood stem cell transplantation for light-chain amyloidosis with cardiac involvement

Blood — Thu, 02 Feb 2012 05:00:00 +0100

High-dose melphalan (HDM) plus stem cell transplantation is an effective treatment for light-chain amyloidosis (AL), but is associated with high treatment-related mortality in patients with cardiac involvement. We studied 187 patients with cardiac involvement with AL who underwent HDM between 1996 and 2008. The median age was 57 years and the median time from diagnosis to HDM was 3.6 months. Half of the patients received reduced-dose melphalan (100-160 mg/m2). The median overall survival (OS) was 66 months, 54 months from diagnosis and HDM, respectively, and 91 patients (49%) were alive at the last follow-up 52 months (median) from HDM. Thirty patients (16%) died within 100 days of transplantation; only low serum albumin predicted early deaths. Overall, hematologic response (HR) and cardia...

Current perspectives on cardiac amyloidosis

AJP: Heart and Circulatory Physiology — Tue, 31 Jan 2012 05:00:00 +0100

Amyloidosis represents a group of diseases in which proteins undergo misfolding to form insoluble fibrils with subsequent tissue deposition. While almost all deposited amyloid fibers share a common nonbranched morphology, the affected end organs, clinical presentation, treatment strategies, and prognosis vary greatly among this group of diseases and are largely dependent on the specific amyloid precursor protein. To date, at least 27 precursor proteins have been identified to result in either local tissue or systemic amyloidosis, with nine of them manifesting in cardiac deposition and resulting in a syndrome termed "cardiac amyloidosis" or "amyloid cardiomyopathy." Although cardiac amyloidosis has been traditionally considered to be a rare disorder, as clinical appreciation and understandi...

Best use of cardiac biomarkers in patients with AL amyloidosis and renal failure

American Journal of Hematology — Tue, 31 Jan 2012 05:00:00 +0100

AbstractIn AL amyloidosis prognosis depends on the severity of heart dysfunction which is best assessed by natriuretic peptides (BNP and NT‐proBNP). However, their clearance relies on glomerular filtration rate (GFR) and their concentration increases with renal failure. We evaluated the diagnostic and prognostic performance of NT‐proBNP and BNP in 248 patients with AL amyloidosis with different degrees of renal failure.Patients were grouped according to GFR. Group 1 comprised 109 patients with GFR ≥60 mL/min/1.73m2, Group 2, 77 subjects with GFR <60 and ≥15 mL/min/1.73m2, and Group 3, 62 patients with GFR <15 mL/min/1.73m2. The ability of natriuretic peptide to detect heart involvement and to predict survival in the 3 groups was assessed.Decreasing eGFR required higher cutoff...

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A Recurrent D‐strand Association Interface is Observed in β‐2 microglobulin Oligomers

FEBS Journal — Tue, 31 Jan 2012 05:00:00 +0100

Summaryβ‐2 microglobulin (β2m) is an amyloidogenic protein responsible for dialysis related amyloidosis in man. In the early stages of amyloid fibril formation, β2m associates into dimers and higher oligomers, but the structural details of such aggregates are poorly understood. To characterize the protein‐protein interactions supporting formation of oligomers, three individual β2m cysteine mutants and their disulphide‐linked homodimers (DIMC20, DIMC50, DIMC60) were prepared. Amyloid propensity, oligomerization state in solution and crystallogenesis were tested for each β2m homodimer: DIMC20 and DIMC50 display a mixture of tetrameric and dimeric species in solution, yield protein crystals and amyloid fibrils, while DIMC60 is dimeric in solution, does not form protein crystals nor...

Localized pleural amyloidosis: report of a case

Surgery Today — Mon, 30 Jan 2012 06:32:13 +0100

Abstract We herein describe an asymptomatic 31-year-old male who was admitted for an investigation of an abnormal pleural tumor detected by chest radiography. We performed various preoperative investigations including fluorodeoxyglucose-positron emission tomography. The maximum standardized uptake value (SUVmax) was 2.2, and malignancy could not be ruled out. We therefore carried out a thoracoscopy-assisted partial resection of the right upper lobe combined with a parietal pleurectomy. The pathological examination showed that there was a tumor localized with pleural amyloidosis. Content Type Journal ArticleCategory Case ReportPages 1-4DOI 10.1007/s00595-012-0122-zAuthors Shohei Yoshiya, Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu Uni...

Magnetic fluid targets insulin-related amyloidosis

Nanotechweb.org journal highlights — Sat, 28 Jan 2012 19:59:33 +0100

Nanoparticles shown to depolymerize aggregates associated with diabetes (Source: Nanotechweb.org journal highlights)

QT interval variability in familial Mediterranean fever: a study in colchicine-responsive and colchicine-resistant patients

Clinical Rheumatology — Tue, 24 Jan 2012 07:54:07 +0100

In conclusion, patients with FMF who are continuously treated with colchicine and have not developed amyloidosis, regardless of their clinical response, have normal QT variability parameters, indicating normal repolarization dynamics and suggesting no increased risk of repolarization-associated cardiac arrhythmias. Content Type Journal ArticleCategory Original ArticlePages 1-5DOI 10.1007/s10067-011-1926-8Authors Udi Nussinovitch, Israel Naval Medical Institute, IDF Medical Corps, Haifa, Israel 31080Keren Kaminer, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, IsraelMoshe Nussinovitch, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, IsraelBenjamin Volovitz, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, IsraelMerav Lidar, Sackler Faculty of Me...

Cardiac positron-emission tomography images with an amyloid-specific tracer in familial transthyretin-related systemic amyloidosis.

Circulation — Tue, 24 Jan 2012 05:00:00 +0100

Authors: Furukawa K, Ikeda S, Okamura N, Tashiro M, Tomita N, Furumoto S, Iwata R, Yanai K, Kudo Y, Arai H PMID: 22271849 [PubMed - in process] (Source: Circulation)

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Renal Amyloidosis in Dogs: A Retrospective Study of 91 Cases with Comparison of the Disease between Shar‐Pei and Non‐Shar‐Pei Dogs

Journal of Veterinary Internal Medicine — Mon, 23 Jan 2012 05:00:00 +0100

Conclusions and Clinical RelevanceThe clinical and pathologic manifestations of amyloidosis differ between CSPs and NSPs. The survival time observed herein was unexpectedly low, and argues for early surveillance and management of the underlying predisposing conditions. (Source: Journal of Veterinary Internal Medicine)

PET imaging with [18F]AV-45 in an APP/PS1-21 murine model of amyloid plaque deposition.

Neurobiology of Aging — Mon, 23 Jan 2012 05:00:00 +0100

This study opens the possibility of [18F]AV-45, coupled with microPET, to visualize and quantitatively measure amyloid deposits in the brains of living APP/PS1 mice. PMID: 22277262 [PubMed - as supplied by publisher] (Source: Neurobiology of Aging)

Duodenal biopsy for diagnosis of renal involvement in amyloidosis.

Clinical Nephrology — Sat, 21 Jan 2012 18:13:37 +0100

In conclusion, duodenal biopsy is sensitive for diagnosing amyloidosis in CKD patients, and highly correlates with renal amyloidosis. PMID: 22257541 [PubMed - in process] (Source: Clinical Nephrology)

Mesangial proliferative glomerulonephritis in familial Mediterranean fever patient with E148Q mutation: the first case report

International Urology and Nephrology — Fri, 20 Jan 2012 07:07:25 +0100

In this report, we present the first case of an FMF patient with heterozygous mutation of E148Q, mesangial proliferative glomerulonephritis, and no amyloidosis. While the association of mutation E148Q with renal involvement is still obscure, colchicine treatment is useful in mesangial proliferative glomerulonephritis with FMF. Content Type Journal ArticleCategory Nephrology – Case ReportPages 1-4DOI 10.1007/s11255-012-0124-1Authors Eray Eroglu, Department of Internal Medicine, Erciyes University Medical School, Kayseri, TurkeyIsmail Kocyigit, Department of Nephrology, Erciyes University Medical School, Kayseri, TurkeyOzturk Ates, Department of Nephrology, Erciyes University Medical School, Kayseri, TurkeyAydin Unal, Department of Nephrology, Erciyes University Medical School, K...

Immunoglobulin light chain amyloidosis: 2012 update on diagnosis, prognosis, and treatment

American Journal of Hematology — Tue, 17 Jan 2012 23:03:32 +0100

AbstractDisease Overview: Immunoglobulin (Ig) light chain amyloidosis is a clonal but nonproliferative plasma cell disorder in which fragments of an Ig light chain are deposited in tissues. The clinical features depend on the organs involved but can include restrictive cardiomyopathy, nephrotic syndrome, hepatic failure, and peripheral/autonomic neuropathy.Diagnosis: Tissue biopsy stained with Congo red demonstrating amyloid deposits with apple‐green birefringence is required for diagnosis. Invasive organ biopsy is not required because amyloid deposits can be found in bone marrow biopsy or subcutaneous fat aspirate in 85% of patients. Prognosis: N‐terminal pro–brain natriuretic peptide and serum troponin T values are used to classify patients into three groups of approximately equal ...

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Concurrent systemic AA amyloidosis can discriminate primary sclerosing cholangitis from IgG4-associated cholangitis.

World Journal of Gastroenterology : WJG — Sat, 14 Jan 2012 05:00:00 +0100

We report a 69-year-old Japanese woman with cirrhosis who was diagnosed with PSC complicated with systemic AA amyloidosis, without any evidence of other inflammatory disorders. As a result of cholestasis in conjunction with biliary strictures and increased serum IgG4, the presence of IgG4(+) plasma cells was examined systemically, resulting in unexpected documentation of Congo-red-positive amyloid deposits, but not IgG4(+) plasma cells, in the liver, stomach and salivary glands. Elevated serum IgG4 is the hallmark of IgG4-related disease, including IgG4-associated cholangitis, but it has also been demonstrated in certain patients with PSC. Amyloid A deposits in multiple organs associated with an indolent clinical course that progresses over many years might have a diagnostic value in discr...

Immunohistochemistry in the classification of systemic forms of amyloidosis: a systematic investigation of 117 patients

Blood — Thu, 12 Jan 2012 05:00:00 +0100

This study evaluated immunohistochemistry as a diagnostic tool for the differentiation of amyloid subentities, which is warranted for accurate treatment. A total of 117 patients were systematically investigated by clinical examination, laboratory tests, genotyping, and immunohistochemistry on biopsy specimens. Immunohistochemistry enabled the classification in 94% of the cases. For subsequent analysis, the patient population was divided into 2 groups. The first group included all patients whose diagnosis could be verified by typical clinical signs or an inherited amyloidogenic mutation. In this group, immunohistochemical subtyping was successful in 49 of 51 cases and proved accurate in each of the 49 cases, corresponding to a sensitivity of 96% and a specificity of 100%. The second group i...

[Renal disorders associated with monoclonal gammopathies: Diagnostic and therapeutic progress.]

Presse Medicale — Thu, 12 Jan 2012 05:00:00 +0100

Authors: Bridoux F, Delbes S, Sirac C, Pourreau F, Puyade M, Desport E, Jaccard A, Fermand JP, Touchard G Abstract Various renal disorders are associated with monoclonal gammopathies, secondary to tissue deposition or precipitation of a monoclonal immunoglobulin (Ig) or a fragment thereof (isolated Ig light chain or heavy chain). They are classified according to the localization of renal lesions, either glomerular or tubular and to the pattern of ultrastructural organization of Ig deposits. Renal disease in monoclonal gammopathies may be isolated, or associated with various systemic symptoms particularly in AL amyloidosis, Randall-type monoclonal Ig deposition disease and monoclonal cryoglobulinemias. Except for myeloma cast nephropathy, which occurs in the setting of high-mass mye...

Role of mitochondrial homeostasis and dynamics in Alzheimer's disease.

Neurobiology of Disease — Tue, 10 Jan 2012 05:00:00 +0100

Authors: Selfridge JE, Lezi E, Lu J, Swerdlow RH Abstract Alzheimer's disease (AD) is a progressive neurodegenerative disease that affects a staggering percentage of the aging population and causes memory loss and cognitive decline. Mitochondrial abnormalities can be observed systemically and in brains of patients suffering from AD, and may account for part of the disease phenotype. In this review, we summarize some of the key findings that indicate mitochondrial dysfunction is present in AD-affected subjects, including cytochrome oxidase deficiency, endophenotype data, and altered mitochondrial morphology. Special attention is given to recently described perturbations in mitochondrial autophagy, fission-fusion dynamics, and biogenesis. We also briefly discuss how mitochondrial dys...

Effects of Age and Amyloid Deposition on A{beta} Dynamics in the Human Central Nervous System [Original Contribution]

Archives of Neurology — Mon, 09 Jan 2012 05:00:00 +0100

Conclusions A reduction in the linear increase in the Aβ levels in CSF samples that is associated with amyloid deposition and a decreased CSF Aβ diurnal pattern associated with increasing age disrupt the normal physiology of Aβ dynamics and may contribute to AD. (Source: Archives of Neurology)

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Primary localized amyloidosis of the nose

Auris, Nasus, Larynx — Sun, 08 Jan 2012 20:04:34 +0100

Abstract: Two rare cases of primary localized amyloidosis of the nose are described. A 14-year-old woman presented with anosmia, facial pain, and recurrent episodes of bilateral epistaxis persisting for 2 years. Endoscopic sinus surgery was performed and amyloidosis was diagnosed. Amyloid was also found in the trachea. A 27-year-old woman presented with decreased bilateral hearing and recurrent episodes of bilateral epistaxis. Tympanostomy tube placement was performed and observation continued. The optimum treatment of amyloidosis of the nose has not yet established. We consider that the treatment should depend on the extent of the amyloidosis. (Source: Auris, Nasus, Larynx)

Effect of Heparin on Conformation of the β2‐Microglobulin Molecule

Therapeutic Apheresis and Dialysis — Thu, 05 Jan 2012 05:00:00 +0100

AbstractHeparin, one of the essential molecules called glycosaminoglycans (GAGs), is the anticoagulant that is commonly used in regular hemodialysis, during which dialysis‐related amyloidosis (DRA) may develop. The pathogenic protein, i.e. precursor protein, in DRA is β2‐microglobulin (β2m). Recent studies defined amyloidosis as a protein misfolding disease of precursor proteins including β2m. Because the analytic technique capillary electrophoresis can identify molecular variants of the folded β2m, i.e. conformational variants, we utilized it to investigate the effect of heparin on β2m conformation and thus determined whether heparin can promote DRA development by inducing a conformational change in the amyloidogenic β2m molecule. Heparin had a slight but significant effect on i...

Immunoglobulin D amyloidosis: a distinct entity

Blood — Thu, 05 Jan 2012 05:00:00 +0100

IgD monoclonal gammopathies are uncommon. They are seen rarely as a monoclonal gammopathy of undetermined significance and are present in 1%-2% of patients with multiple myeloma. In light-chain amyloidosis, IgD monoclonal proteins are found in ap-proximately 1% of patients. When an IgD monoclonal protein is found, amyloidosis is often omitted from the differential diagnosis. In the present study, we reviewed the natural history of IgD-associated amyloidosis among 53 patients seen over 41 years. The distribution of clinical syndromes suggests that these patients have a lower frequency of renal and cardiac involvement. The overall survival of these patients does not appear to be different from that of patients who have light-chain amyloidosis associated with another monoclonal protein. (Sour...

The repertoire of {lambda} light chains causing predominant amyloid heart involvement and identification of a preferentially involved germline gene, IGLV1-44

Blood — Thu, 05 Jan 2012 05:00:00 +0100

Monoclonal Ig light chains (LC) can be responsible for pathologic conditions in humans, as in systemic amyloid light amyloidosis. Protean clinical manifestations characterize this disorder with the most varied combination of symptoms generated by different degrees of diverse organ involvement. Kidney and heart are most frequently interested, with major heart involvement as the most relevant prognostic factor. The identification of the underlying mechanism involved in organ targeting is of major relevance for the pathobiology of this disorder. To this aim, we characterized the repertoire of variable region germline genes of LC preferentially targeting the heart and compared it with the repertoire of LC that do not in a case-control study. We found that the repertoires were highly restricted...

Pancreatic islet cell amyloidosis manifesting as a large pancreas.

Korean J Radiol — Sun, 01 Jan 2012 05:00:00 +0100

Authors: Onur MR, Yalnız M, Poyraz AK, Ozercan IH, Ozkan Y Abstract A 39-year-old female patient presented to our hospital with epigastric pain lasting for two months. Laboratory results showed impaired glucose tolerance. Ultrasonography of the patient showed a hypoechoic, diffusely enlarged pancreas. CT revealed a large pancreas, with multiple calcifications. On MRI, a diffusely enlarged pancreas was seen hypointense on both T1- and T2-weighted images with heterogeneous enhancement after gadolinium administration. A biopsy of the pancreas revealed primary amyloidosis of islet cells. Decreased signal on T1-weighted images without inflammation findings on CT and MRI were clues for the diagnosis. PMID: 22247642 [PubMed - in process] (Source: Korean J Radiol)

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Vitreal deposits in Val71Ala transthyretin amyloidosis

Internal Medicine Journal — Sun, 01 Jan 2012 05:00:00 +0100

(Source: Internal Medicine Journal)

KTP Laser in Laryngeal Amyloidosis: Five Cases with Review of Literature

Indian Journal of Otolaryngology and Head and Neck Surgery — Sat, 31 Dec 2011 16:47:34 +0100

We report five patients who presented with hoarseness of voice and localized laryngeal lesions. The biopsy proven laryngeal amyloidosis lesions were excised microendoscopically using KTP 532 laser in three patients and other two patients were kept only on follow-up as they refused further surgery. The patients were evaluated for systemic amyloidosis. The average duration of follow up was 2.6 years (3 months 6 years). All the five patients in our study were asymptomatic with no evidence of recurrence at their last follow up. In our small case series, KTP 532 laser excision of the laryngeal amyloidosis had a favorable outcome. Long term follow up is required to rule out recurrence and systemic involvement. Content Type Journal ArticleCategory Original ArticlePages 1-...

The machine and the therapy concept.

Contributions to Nephrology — Tue, 27 Dec 2011 08:48:02 +0100

Authors: Greenwood RN Abstract Maintenance haemodialysis became established in mainstream clinical practice in the 1960s. For pragmatic reasons, diffusive dialysis was the technique which underpinned its success. Over the next 15 years it was shown that short- and medium-term survival depended only on a critical level of urea clearance being achieved. Uncomplicated technology with negligible capacity for middle molecule removal could deliver this and the case for developing more sophisticated machines able to broaden the spectrum of solute removal was unconvincing. Dialysis-related amyloidosis which was recognised in the mid-1980s as a devastating complication in long survivors disturbed this complacency. The journey to develop machines which could deliver broad-spectrum solute rem...

κ I light chain AL amyloidosis presenting with rapidly progressive renal and hepatic failure with unusual renal amyloid distribution.

Clinical Nephrology — Tue, 27 Dec 2011 07:57:27 +0100

Authors: Oe Y, Nakaya I, Yahata M, Murata O, Yaegashi H, Sakuma T, Sato H, Liepnieks JJ, Benson MD, Soma J Abstract A 65-year-old man suffering from generalized edema and jaundice was admitted to our hospital. Laboratory findings revealed marked renal dysfunction with heavy proteinuria as well as liver dysfunction with severe obstructive jaundice. On renal biopsy, the diagnosis of AL amyloidosis associated with κ I light chain was made. Interestingly, amyloid deposits were restricted to the glomeruli. Although hemodialysis was initiated, the patient died due to further deterioration of hepatic function. On autopsy, severe intrahepatic cholestasis was observed, and there was marked deposition of AL amyloid in the liver. Literature reviews showed that rapidly progressive renal failu...

Calpastatin modulates APP processing in the brains of β-amyloid depositing but not wild-type mice.

Neurobiology of Aging — Tue, 27 Dec 2011 05:00:00 +0100

We report that neuronal overexpression of the endogenous inhibitor of calpains, calpastatin (CAST), in a mouse model of human Alzheimer's disease (AD) β-amyloidosis, the APP23 mouse, reduces β-amyloid (Aβ) pathology and Aβ levels when comparing aged, double transgenic (tg) APP23/CAST with APP23 mice. Concurrent with Aβ plaque deposition, aged APP23/CAST mice show a decrease in the steady-state brain levels of the amyloid precursor protein (APP) and APP C-terminal fragments (CTFs) when compared with APP23 mice. This CAST-dependent decrease in APP metabolite levels was not observed in single tg CAST mice expressing endogenous APP or in younger, Aβ plaque predepositing APP23/CAST mice. We also determined that the CAST-mediated inhibition of calpain activity in the brain is greater in th...

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Processing of nerve biopsies: A practical guide for neuropathologists.

Clinical Neuropathology — Mon, 26 Dec 2011 11:31:17 +0100

Authors: Weis J, Brandner S, Lammens M, Sommer C, Vallat JM Abstract Nerve biopsy is a valuable tool in the diagnostic work-up of peripheral neuropathies. Currently, major indications include interstitial pathologies such as suspected vasculitis and amyloidosis, atypical cases of inflammatory neuropathy and the differential diagnosis of hereditary neuropathies that cannot be specified otherwise. However, surgical removal of a piece of nerve causes a sensory deficit and - in some cases - chronic pain. Therefore, a nerve biopsy is usually performed only when other clinical, laboratory and electrophysiological methods have failed to clarify the cause of disease. The neuropathological work-up should include at least paraffin and resin semithin histology using a panel of conventional an...

Tonsil amyloidosis revealing a Waldenström macroglobulinemia

European Archives of Oto-Rhino-Laryngology — Sat, 24 Dec 2011 16:44:58 +0100

We report a case of tonsil amyloidosis and review the characteristics of this exceptional pathology. A 74-year-old man consulted for odynophagia, upper dysphagia and deteriorated general health status, which have been evolving for 1 year. Clinical examination found a smooth swelling of the right palatine tonsil. No further abnormalities were noted. The biopsy findings were consistent with amyloidosis. Etiological assessment pointed to Waldenstrom macroglobulinemia. Tonsillectomy was performed. The patient was managed by chemotherapy associating chlorambucil, vincristine and prednisone. The progress after chemotherapy was good. Localized amyloidosis is a rare lesion of the superior aerodigestive tract, predominating in the larynx and tonsil involvement is exceptional. Its diagnos...

Molecular Imaging of Amyloidosis: Will the Heart Be the Next Target After the Brain?

Current Cardiology Reports — Thu, 22 Dec 2011 12:51:49 +0100

Abstract Amyloidosis is a heterogeneous group of diseases with a common feature of extracellular deposition and infiltration of different types of amyloid fibrils in various organs. For example, Alzheimer’s disease is characterized by deposition of amyloid β in the brain. Radiolabeled positron emission tomography (PET) tracers, mainly derivatives of thioflavin-T, were recently introduced for identification of amyloid β plaques in Alzheimer’s patients. Such advances of amyloid β plaque imaging of the brain may shed light into imaging of other organs in amyloidosis patients, such as the heart. Cardiac infiltration of amyloid confers poor clinical outcomes, which renders early diagnosis for appropriate clinical management. At present, nuclear imaging of cardiac amyloid...

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue with amyloid deposition: a clinicopathologic case series.

American Journal of Clinical Pathology — Tue, 20 Dec 2011 15:14:46 +0100

We describe the clinical and pathologic features of 20 cases of MALT lymphoma and associated amyloid deposition across diverse primary sites. Frozen section immunofluorescence performed on 4 cases suggests that these deposits are a localized form of AL amyloid. Clinical follow-up was available for 15 patients. Amyloid deposits distant from the initial site occurred in 5 cases, always at sites also involved by the underlying lymphoma. No definitive evidence of systemic amyloidosis affecting the heart, kidneys, or liver was present in any patient. Given the generally indolent clinical behavior of MALT lymphomas with associated amyloid, we do not recommend extensive follow-up testing for systemic amyloidosis or more aggressive therapy than would be indicated for other MALT lymphomas of simila...

Aged vervet monkeys developing transthyretin amyloidosis with the human disease-causing Ile122 allele: a valid pathological model of the human disease

Laboratory Investigation AOP — Mon, 19 Dec 2011 05:00:00 +0100

Authors: Mitsuharu Ueda, Naohide Ageyama, Shinichiro Nakamura, Minami Nakamura, James Kenn Chambers, Yohei Misumi, Mineyuki Mizuguchi, Satoru Shinriki, Satomi Kawahara, Masayoshi Tasaki, Hirofumi Jono, Konen Obayashi, Erika Sasaki, Yumi Une & Yukio Ando (Source: Laboratory Investigation AOP)

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Finally, a transgenic light chain amyloidosis mouse model

Blood — Thu, 15 Dec 2011 05:00:00 +0100

(Source: Blood)

Doxycycline reduces fibril formation in a transgenic mouse model of AL amyloidosis

Blood — Thu, 15 Dec 2011 05:00:00 +0100

Systemic AL amyloidosis results from the aggregation of an amyloidogenic immunoglobulin (Ig) light chain (LC) usually produced by a plasma cell clone in the bone marrow. AL is the most rapidly fatal of the systemic amyloidoses, as amyloid fibrils can rapidly accumulate in tissues including the heart, kidneys, autonomic or peripheral nervous systems, gastrointestinal tract, and liver. Chemotherapy is used to eradicate the cellular source of the amyloidogenic precursor. Currently, there are no therapies that target the process of LC aggregation, fibril formation, or organ damage. We developed transgenic mice expressing an amyloidogenic 6 LC using the cytomegalovirus (CMV) promoter to circumvent the disruption of B cell development by premature expression of recombined LC. The CMV-6 transgeni...

Cheetahs Have 4 Serum Amyloid A Genes Evolved through Repeated Duplication Events

Journal of Heredity — Fri, 09 Dec 2011 05:00:00 +0100

Amyloid A (AA) amyloidosis is a leading cause of mortality in captive cheetahs (Acinonyx jubatus). We performed genome walking and PCR cloning and revealed that cheetahs have 4 SAA genes (provisionally named SAA1A, SAA1B, SAA3A, and SAA3B). In addition, we identified multiple nucleotide polymorphisms in the 4 SAA genes by screening 51 cheetahs. The polymorphisms defined 4, 7, 6, and 4 alleles for SAA1A, SAA3A, SAA1B, and SAA3B, respectively. Pedigree analysis of the inheritance of genotypes for the SAA genes revealed that specific combinations of alleles for the 4 SAA genes cosegregated as a unit (haplotype) in pedigrees, indicating that the 4 genes were linked on the same chromosome. Notably, cheetah SAA1A and SAA1B were highly homologous in their nucleotide sequences. Likewise, SAA3A and...

Renal Monoclonal Immunoglobulin Deposition Disease: A Report of 64 Patients from a Single Institution.

Clinical Journal of the American Society of Nephrology : CJASN — Thu, 08 Dec 2011 05:00:00 +0100

ConclusionsPatients with MIDD generally present at a younger age than those with light chain amyloidosis or light chain cast nephropathy. Serum free light chain ratio is abnormal in all MIDD patients, whereas only three-quarters have abnormal serum protein electrophoresis. The prognosis for MIDD is improving compared with historical controls, likely reflecting earlier detection and improved therapies. PMID: 22156754 [PubMed - as supplied by publisher] (Source: Clinical Journal of the American Society of Nephrology : CJASN)

NLRP3 E311K mutation in a large family with Muckle-Wells syndrome - description of a heterogeneous phenotype and response to treatment.

Arthritis Research and Therapy — Tue, 06 Dec 2011 05:00:00 +0100

Conclusion: The NLRP3 E311K mutation is associated with a heterogeneous clinical spectrum, which may expand the view on MWS presentation. The leading symptom was hearing loss. Pericarditis, a rare but severe clinical feature of MWS, was diagnosed in three patients. One patient had a severe course, which led to renal failure secondary to amyloidosis. IL-1 inhibition leads to rapid and sustained improvement of symptoms. (Source: Arthritis Research and Therapy)

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Human microvascular dysfunction and apoptotic injury induced by AL amyloidosis light chain proteins

AJP: Heart and Circulatory Physiology — Mon, 05 Dec 2011 05:00:00 +0100

Light chain amyloidosis (AL) involves overproduction of amyloidogenic light chain proteins (LC) leading to heart failure, yet the mechanisms underlying tissue toxicity remain unknown. We hypothesized that LC induces endothelial dysfunction in non-AL human microvasculature and apoptotic injury in human coronary artery endothelial cells (HCAECs). Adipose arterioles (n = 34, 50 ± 3 yr) and atrial coronary arterioles (n = 19, 68 ± 2 yr) from non-AL subjects were cannulated. Adipose arteriole dilator responses to acetylcholine/papaverine were measured at baseline and 1 h exposure to LC (20 μg/ml) from biopsy-proven AL subjects (57 ± 11 yr) without and with antioxidant cotreatment. Coronary arteriole dilation to bradykinin/papaverine was measured post-LC exposure. HCAECs ...

Rapid assessment of longitudinal systolic left ventricular function using speckle tracking of the mitral annulus

Clinical Research in Cardiology — Sat, 03 Dec 2011 16:49:51 +0100

Conclusions Tissue motion annular displacement is a rapid, sensitive and reproducible method for the assessment of LV longitudinal function, which is less dependent on image quality. Content Type Journal ArticleCategory Original PaperPages 1-8DOI 10.1007/s00392-011-0389-xAuthors Sebastian J. Buss, Department of Cardiology, Angiology and Pneumology, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, GermanyDerliz Mereles, Department of Cardiology, University of Heidelberg, INF 410, 69120 Heidelberg, GermanyMostafa Emami, Department of Cardiology, University of Heidelberg, INF 410, 69120 Heidelberg, GermanyGrigorios Korosoglou, Department of Cardiology, University of Heidelberg, INF 410, 69120 Heidelberg, GermanyJohannes H. Riffel, Department of Cardi...

Disseminated amyloidosis presenting with right proximal femur pathological fracture in a haemodialysis end-stage renal failure patient.

Hong Kong Med J — Thu, 01 Dec 2011 05:00:00 +0100

Authors: Chan AP, Cheung TC, Cheung SY, Ho EP, Fan JCh, Wang K, Fung KY Abstract Osteoarticular amyloidosis can be one of the musculoskeletal system manifestations related to dialysis. We share our experience in dealing with a case of disseminated haemodialysis-associated amyloidosis in a 74-year-old end-stage renal failure patient. This patient suffered from a serious complication, namely an unprovoked pathological fracture at the basal neck region of the right femur. Polyarticular cystic and lytic lesions over the contralateral proximal femur, bilateral proximal humerus and the right lunate were noted on further imaging. In view of extensive amyloidotic infiltration into the proximal femur as well as the acetabulum, a cemented total hip arthroplasty operation was performed for pa...

Tocilizumab, a humanized anti‐interleukin‐6 receptor antibody, for the treatment of autoimmune disorders

Drug Development Research — Thu, 01 Dec 2011 05:00:00 +0100

AbstractThe cytokine interleukin (IL)‐6 has a wide range of biological activities. It contributes to host defense against pathogens by inducing immune responses, hematopoiesis, and acute‐phase reactions. However, dysregulation of IL‐6 production plays a significant pathological role in various autoimmune and chronic inflammatory disorders. Because IL‐6 blockade was anticipated to provide a novel strategy for the treatment of such diseases, tocilizumab, a humanized anti‐IL‐6 receptor antibody, was developed. Clinical trials have demonstrated the efficacy of tocilizumab for patients with moderate to severe rheumatoid arthritis, resulting in approval in more than 90 countries worldwide of this innovative biologic for the treatment of rheumatoid arthritis. Tocilizumab was also appr...

Left atrial size is an independent predictor of overall survival in patients with primary systemic amyloidosis.

Archives of Cardiovascular Diseases — Thu, 01 Dec 2011 05:00:00 +0100

CONCLUSION: LA enlargement, a surrogate marker of diastolic dysfunction, is an independent predictor of long-term mortality and may therefore help to enhance risk stratification and management of patients presenting with amyloidosis. PMID: 22152513 [PubMed - in process] (Source: Archives of Cardiovascular Diseases)

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Beta-amyloid carrying the dutch mutation has diverse effects on calpain-mediated toxicity in hippocampal neurons.

Molecular Medicine — Thu, 01 Dec 2011 05:00:00 +0100

BETA-AMYLOID CARRYING THE DUTCH MUTATION HAS DIVERSE EFFECTS ON CALPAIN-MEDIATED TOXICITY IN HIPPOCAMPAL NEURONS. Mol Med. 2011 Dec 1; Authors: Nicholson AM, Wold LA, Walsh DM, Ferreira A Abstract Hereditary cerebral hemorrhage with amyloidosis-Dutch type is a disorder associated with a missense mutation (E693Q) in the beta-amyloid (Aβ)-coding region of the amyloid precursor protein. This familial disease is characterized by cognitive deficits secondary to intracerebral hemorrhage and, in some cases, progressive Alzheimer disease (AD)-like dementia. Although this mutation was the first ever reported in the human APP gene, little is known about the molecular mechanisms underlying the direct toxic effects of this mutated Aβ on central neurons. In the present study, we asses...

Amyloid imaging as a biomarker for cerebral β-amyloidosis and risk prediction for Alzheimer dementia.

Neurobiology of Aging — Thu, 01 Dec 2011 05:00:00 +0100

Authors: Klunk WE Abstract Since the introduction of amyloid imaging nearly 10 years ago, this technique has gained widespread use and acceptance. More recently, published reports have begun to appear in which amyloid imaging is used to detect the effects of antiamyloid therapies. This review will consider the issues involved in the use of amyloid imaging in the development and evaluation of drugs for the treatment of Alzheimer's disease. Current evidence regarding the postmortem correlates of in vivo amyloid imaging data are considered. The application of amyloid imaging to screening subjects for trials and use as an outcome measure is discussed in light of longitudinal changes in the in vivo amyloid signal. While the bulk of this review is directed at symptomatic patients with de...

A case of isolated primary amyloidosis in the medial rectus muscle

Graefe's Archive for Clinical and Experimental Ophthalmology — Sat, 26 Nov 2011 16:46:58 +0100

Content Type Journal ArticleCategory Letter to the EditorPages 1-2DOI 10.1007/s00417-011-1867-6Authors Chan Yang Jeon, Department of Ophthalmology, College of Medicine, Konyang University, Deajeon, KoreaSun Young Jin, Department of Ophthalmology, College of Medicine, Konyang University, Deajeon, KoreaJae Woo Jang, Myung-Gok Eye Research Institute, Department of Ophthalmology, Kim’s Eye Hospital, Konyang University College of Medicine #156, Yeongdeungpo 4-ga, Yeongdeungpo-gu, Seoul, 150-034 KoreaUngsoo Samuel Kim, Myung-Gok Eye Research Institute, Department of Ophthalmology, Kim’s Eye Hospital, Konyang University College of Medicine #156, Yeongdeungpo 4-ga, Yeongdeungpo-gu, Seoul, 150-034 Korea Journal Graefe's Archive for Clinical and Experimental OphthalmologyOnline ISSN 1...

Multiple myeloma-amyloidosis presenting as pseudomyopathy

Revista Brasileira de Reumatologia — Fri, 25 Nov 2011 22:38:28 +0100

We report the case of a patient with amyloidosis associated with multiple myeloma, showing clinical characteristics of pseudomyopathy (Source: Revista Brasileira de Reumatologia)

The renal histopathological spectrum of patients with nephrotic syndrome: an analysis of 1523 patients in a single Chinese centre

Nephrology Dialysis Transplantation — Fri, 25 Nov 2011 05:00:00 +0100

Conclusions. The renal histopathological spectrum of nephrotic syndrome differs between ages. MCD, LN and IMN were the main cause of nephrotic syndrome among younger patients, and IMN was the main cause of nephrotic syndrome among older patients. The proportion of patients with renal amyloidosis increased in parallel with patient age. (Source: Nephrology Dialysis Transplantation)

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Localized AL Amyloidosis in a Patient with Diffuse Large B-cell Lymphoma of the Breast.

Acta Derm Venereol A... — Thu, 24 Nov 2011 05:00:00 +0100

Authors: Chiu HY, Chu CY, Tsai TF PMID: 22113852 [PubMed - as supplied by publisher] (Source: Acta Derm Venereol A...)

Solid‐state NMR reveals differences in the packing arrangements of peptide aggregates derived from the aortic amyloid polypeptide medin

Journal of Peptide Science — Wed, 23 Nov 2011 06:43:44 +0100

Several polypeptides aggregate into insoluble amyloid fibrils associated with pathologies such as Alzheimer's disease, Parkinson's disease and type 2 diabetes. Understanding the structural and sequential motifs that drive fibrillisation may assist in the discovery and refinement of effective therapies. Here we investigate the effects of three predicted amyloidogenic regions on the structure of aggregates formed by medin, a poorly characterised polypeptide associated with aortic medial amyloidosis. Solid‐state NMR is used to compare the dynamics and sheet packing arrangement of the C‐terminal region encompassing residues F43GSV within full‐length medin (Med1‐50) and two shorter peptide fragments, Med30‐50 and Med42‐49, lacking specific sequences predicted to be amyloidogenic.. R...

Irradiation induced modest changes in murine cardiac function despite progressive structural damage to the myocardium and microvasculature.

Mon, 21 Nov 2011 05:00:00 +0100

CONCLUSIONS: Irradiation with 2 and 8Gy induced modest changes in murine cardiac function within 20weeks but this did not deteriorate further, despite progressive structural and microvascular damage. This indicates that heart function can compensate for significant structural damage, although higher doses, eventually lead to sudden death. PMID: 22112779 [PubMed - as supplied by publisher] (Source: Radiotherapy and Oncology : journal of the European Society for Therapeutic Radiology and Oncology)

Value of Electrocardiogram in the Differentiation of Hypertensive Heart Disease, Hypertrophic Cardiomyopathy, Aortic Stenosis, Amyloidosis, and Fabry Disease

The American Journal of Cardiology — Mon, 21 Nov 2011 05:00:00 +0100

Left ventricular hypertrophy is 1 of the most frequent cardiac manifestations associated with an unfavorable prognosis. However, many different causes of left ventricular hypertrophy exist. The aim of the present study was to assess the diagnostic value of common electrocardiographic (ECG) parameters to differentiate Fabry disease (FD), amyloidosis, and nonobstructive hypertrophic cardiomyopathy (HC) from hypertensive heart disease (HHD) and aortic stenosis (AS). In 94 patients with newly diagnosed FD (n = 17), HHD (n = 20), amyloidosis (n = 17), AS (n = 20), and HC (n = 20), common ECG parameters were analyzed and tested for their diagnostic value. A stepwise approach including the Sokolow–Lyon index, corrected QT duration, and PQ interval minus P-wave duration in lead II to overcome P-...

Light chain (AL) amyloidosis: update on diagnosis and management

Journal of Hematology and Oncology — Fri, 18 Nov 2011 05:00:00 +0100

Light chain (AL) amyloidosis is a plasma cell dyscrasia characterized by the pathologic production of fibrillar proteins comprised of monoclonal light chains which deposit in tissues and cause organ dysfunction. The diagnosis can be challenging, requiring a biopsy and often specialized testing to confirm the subtype of systemic disease. The goal of treatment is eradication of the monoclonal plasma cell population and suppression of the pathologic light chains which can result in organ improvement and extend patient survival. Standard treatment approaches include high dose melphalan (HDM) followed by autologous hematopoietic stem cell transplantation (SCT) or oral melphalan with dexamethasone (MDex). The use of novel agents (thalidomide, lenalidomide and bortezomib) alone and in combinat...

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[Review] Familial amyloid polyneuropathy

Lancet Neurology — Thu, 17 Nov 2011 04:38:50 +0100

SummaryFamilial amyloid polyneuropathies (FAPs) are a group of life-threatening multisystem disorders transmitted as an autosomal dominant trait. Nerve lesions are induced by deposits of amyloid fibrils, most commonly due to mutated transthyretin (TTR). Less often the precursor of amyloidosis is mutant apolipoprotein A-1 or gelsolin. The first identified cause of FAP—the TTR Val30Met mutation—is still the most common of more than 100 amyloidogenic point mutations identified worldwide. The penetrance and age at onset of FAP among people carrying the same mutation vary between countries. (Source: Lancet Neurology)

Familial vitreous amyloidosis linked with factor V Leiden deficiency

British Journal of Ophthalmology — Wed, 16 Nov 2011 05:00:00 +0100

Case report A 52-year-old Caucasian woman presented with a 2-year history of floaters in her right eye and severe diminished vision for 2 months. She was treated several times with corticosteroids without success for uveitis. Visual acuity was 0.3 in the right eye and 0.8 in the left. There were no signs of inflammation, and the anterior segment examination result was normal. Fundus examination showed dense vitreous opacities with strings and dots. Fluorescein angiography revealed a normal fluorescence pattern without oedema and with no obvious vasculitis or choroiditis. Pathologic examination of a diagnostic vitrectomy confirmed amyloid. The general examination result was negative for systemic amyloidosis, but a hereditary heterozygote deficiency of factor V Leiden was found. One yea...

Experimentally derived structural constraints for amyloid fibrils of wild-type transthyretin.

Biophysical Journal — Wed, 16 Nov 2011 05:00:00 +0100

Authors: Bateman DA, Tycko R, Wickner RB Abstract Transthyretin (TTR) is a largely β-sheet serum protein responsible for transporting thyroxine and vitamin A. TTR is found in amyloid deposits of patients with senile systemic amyloidosis. TTR mutants lead to familial amyloidotic polyneuropathy and familial amyloid cardiomyopathy, with an earlier age of onset. Studies of amyloid fibrils of familial amyloidotic polyneuropathy mutant TTR suggest a structure similar to the native state with only a simple opening of a β-strand-loop-strand region exposing the two main β-sheets of the protein for fibril elongation. However, we find that the wild-type TTR sequence forms amyloid fibrils that are considerably different from the previously suggested amyloid structure. Using protease digesti...

Letter by falk regarding article, "an unusual heart failure: cardiac amyloidosis due to light chain myeloma".

Circulation — Tue, 15 Nov 2011 05:00:00 +0100

Letter by falk regarding article, "an unusual heart failure: cardiac amyloidosis due to light chain myeloma". Circulation. 2011 Nov 15;124(20):e534 Authors: Falk RH PMID: 22083153 [PubMed - in process] (Source: Circulation)

Plerixafor in AL amyloidosis: improved graft composition and faster lymphocyte recovery after auto-SCT in patient with end-stage renal-disease

Bone Marrow Transplantation — Mon, 14 Nov 2011 05:00:00 +0100

Authors: D Dunn, P Vikas, M Jagasia & B N Savani (Source: Bone Marrow Transplantation)

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A case report: Primary amiloidosis associated with immunoglobulin A type multiple myeloma

Respiratory Medicine CME — Sun, 13 Nov 2011 21:28:38 +0100

Abstract: Primary (AL type) amyloidosis is the most common form of systemic amyloidosis. The morbidity arises from extracellular deposition of immunoglobulin light chain (LC) fibrils in some organs such as the kidneys, heart and bowel. Primary amyloidosis and multiple myeloma both involve clonal plasma cell proliferation. Distinctive haematological and biochemical laboratory findings may help in early diagnosis. Here we present a 60-year-old man with an exceptional clinical course of an Ig A type multiple myeloma with generalized amyloidosis, causing nephrotic syndrome, complete intestinal colitis and malabsorbtion. Our comprehensive overview of this rare and often fatal disease aims to increase the awareness of AL type amyloidosis. This may facilitate earlier diagnosis and thus allow init...

Rotational Mechanics of the Left Ventricle in Amyloid Light Chain Amyloidosis

The American Journal of Cardiology — Sun, 13 Nov 2011 02:35:44 +0100

In their extensive state-of-art report on the echocardiographic evaluation of systolic and diastolic function in patient with cardiac amyloidosis, Liu et al dedicated much space to tissue Doppler imaging, strain rate imagining, and 2-dimensional speckle-tracking imagining but made no mention of a particular behavior of left ventricular (LV) motion defined as twisting and untwisting. It consists of LV torsional deformation around the longitudinal axis, originating from the dynamic interaction between the systolic clockwise rotation of the base and the counterclockwise rotation of the apex, followed by untwisting during diastole. Porciani et al recently published a comprehensively 2-dimensional strain evaluation of patients with amyloid light chain amyloidosis. They demonstrated that LV long...

Primary cutaneous amyloidosis of the external ear: a clinicopathological and immunohistochemical study of 17 cases

Journal of Cutaneous Pathology — Sat, 12 Nov 2011 05:00:00 +0100

This article demonstrates that the amyloid observed in this context is generally positive for Congo red, crystal violet and thioflavin T. It also expresses cytokeratin 34ßE12 via immunohistochemistry. Our immunohistochemical results and review of the literature suggest that the amyloid in amyloidosis of the external ear is the result of basal keratinocyte degeneration and does not signify deposition from a systemic or generalized process.Wenson SF, Jessup CJ, Johnson MM, Cohen LM, Mahmoodi M. Primary cutaneous amyloidosis of the external ear: a clinicopathological and immunohistochemical study of 17 cases. (Source: Journal of Cutaneous Pathology)

Increased regional cerebral glucose uptake in an APP/PS1 model of Alzheimer's disease.

Neurobiology of Aging — Fri, 11 Nov 2011 05:00:00 +0100

Authors: Poisnel G, Hérard AS, El Tannir El Tayara N, Bourrin E, Volk A, Kober F, Delatour B, Delzescaux T, Debeir T, Rooney T, Benavides J, Hantraye P, Dhenain M Abstract Alzheimer's disease (AD), the most common age-related neurodegenerative disorder, is characterized by the invariant cerebral accumulation of β-amyloid peptide. This event occurs early in the disease process. In humans, [18F]-fluoro-2-deoxy-D-glucose ([18F]-FDG) positron emission tomography (PET) is largely used to follow-up in vivo cerebral glucose utilization (CGU) and brain metabolism modifications associated with the Alzheimer's disease pathology. Here, [18F]-FDG positron emission tomography was used to study age-related changes of cerebral glucose utilization under resting conditions in 3-, 6-, and 12-month...

An unusual presentation of macular amyloidosis

Anais Brasileiros de Dermatologia — Thu, 10 Nov 2011 07:13:02 +0100

This report describes the case of a 45year-old female presenting with hyperpigmented macules and lace-like, non-pruritic erythema in the sacral and cervical region as well as on both arms and legs. Histology revealed amyloid deposits in the papillary dermis which exhibited apple-green birefringence after Congo red staining. There were no systemic findings. This is a case of macular amyloidosis with an unusual presentation. The literature on the subject is also reviewed (Source: Anais Brasileiros de Dermatologia)

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Is there a real adrenal axis dysfunction in patients with amyloidosis associated with familial Mediterranean fever?

Rheumatology International — Sat, 05 Nov 2011 17:07:51 +0100

Abstract Systemic amyloidosis with AA-type amyloid deposition is the major complication of FMF, leading to end stage renal disease. There is no clear data on the prevalence of adrenal involvement in patients with FMF amyloidosis. The aim of this study is to determine the adrenal axis function in patients FMF with amyloidosis. Twenty patients with FMF with amyloidosis (F/M: 10/10, mean age; 38 ± 11 SD years), twenty without amyloidosis (F/M: 14/6, mean age 32 ± 10 years), and healthy controls (F/M: 12/8, mean age: 30 ± 7.6 SD years) were recruited. A dose of 250 mg tetracosactide (Synacthen) was then administered intravenously and further blood samples collected 30 and 60 min later. Blood samples were separated and collected at...

Structural insights into a zinc-dependent pathway leading to Leu55Pro transthyretin amyloid fibrils

Acta Crystallographica Section D — Sat, 05 Nov 2011 04:00:00 +0100

Human transthyretin (TTR) is a homotetrameric protein that is responsible for the formation of amyloid in patients with familiar amyloidotic polyneuropathy (FAP), familiar amyloidotic cardiomyopathy (FAC) and senile systemic amyloidosis (SSA). Amyloid fibrils are characterized by a cross-β structure. However, details of how TTR monomers are organized to form such an assembly remain unknown. The effect of Zn2+ in increasing TTR L55P amyloidogenecity has been reported. Crystals of the TTR L55P–Zn2+ complex were grown under conditions similar to those leading to higher amyloidogenic potential of the variant protein and the three-dimensional structure of the complex was determined by X-ray crystallography. Two different tetrahedral Zn2+-binding sites were identified: one cross-links two te...

Current perspectives on cardiac amyloidosis.

American Journal of Physiology. Heart and Circulatory Physiology — Fri, 04 Nov 2011 04:00:00 +0100

Authors: Guan J, Mishra S, Falk RH, Liao R Abstract Amyloidosis represents a group of diseases in which proteins undergo misfolding to form insoluble fibrils with subsequent tissue deposition. While almost all deposited amyloid fibers share a common non-branched morphology, the affected end-organs, clinical presentation, treatment strategies and prognosis vary greatly among this group of diseases and are largely dependent on the specific amyloid precursor protein. To date, at least twenty-seven precursor proteins have been identified to result in either local tissue or systemic amyloidosis, with nine of them manifesting in cardiac deposition and resulting in a syndrome termed cardiac amyloidosis or amyloid cardiomyopathy. Although cardiac amyloidosis has traditionally been consider...

Macroglossia and Generalized Edema not Due to Hypothyroidism

Dysphagia — Thu, 03 Nov 2011 16:54:41 +0100

We present a 69-year-old male patient with the macroglossia, dysphagia and generalized edema. He was seen previously by other physicians and diagnosed as hypothyroidism. With thyroid stimulating hormone in normal range, tongue biopsy revealed primary systemic amyloidosis. Amyloidosis is the most common cause of macroglossia. Primary systemic amyloidosis should be suspected when laboratory does not support hypothyroidism especially if the enlarged tongue is firm and additional findings are present. Content Type Journal ArticleCategory Clinical ConundrumPages 1-3DOI 10.1007/s00455-011-9372-yAuthors Yalcin Alimoglu, Otolaryngology Department, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, TurkeyFadime Sevgi Sacli, Internal Medicine Department, Cerrahpasa Medical Faculty,...

Multiple Cystic Pulmonary Amyloidosis [IMAGES IN CARDIOTHORACIC SURGERY]

The Annals of Thoracic Surgery — Tue, 01 Nov 2011 04:00:00 +0100

(Source: The Annals of Thoracic Surgery)

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Coexistent asymptomatic myeloma and hereditary cardiac amyloidosis: an unusual case of heart failure.

British Journal of Hospital Medicine — Tue, 01 Nov 2011 04:00:00 +0100

This article discusses a rare cause of heart failure and uses this case to illustrate that histological confirmation of the amyloid-causing protein is essential. Mistaken assumption of AL amyloid could have resulted in inappropriate cytotoxic therapy targeting the plasma cell clone. PMID: 22083004 [PubMed - in process] (Source: British Journal of Hospital Medicine)

Splenic amyloidosis: a rare cause of spontaneous splenic rupture.

Singapore Medical Journal — Tue, 01 Nov 2011 04:00:00 +0100

This report describes a patient who could have suffered from a long-standing infected vegetation on a permanent cardiac pacemaker, which led to splenic amyloidosis and spontaneous splenic rupture. PMID: 22173263 [PubMed - in process] (Source: Singapore Medical Journal)

Cardiac involvement with amyloidosis: mechanisms of disease, diagnosis and management.

Connecticut Medicine — Tue, 01 Nov 2011 04:00:00 +0100

Authors: Marcu CB, Niessen HW, Beek AM, Brouwer WP, Robbers LF, Van Rossum AC Abstract The amyloidoses represent a group of clinical disorders of diverse etiologies that have as a common pathophysiologic denominator the deposition of misfolded protein based amyloid fibrils in the interstitial space of various organs. They are uncommon diseases with protean clinical presentations. Cardiac involvement is the determining factor for a patient's prognosis. Clinicians have to maintain a high index of suspicion and actively search for signs and symptoms of cardiac involvement in patients with preexisting conditions known to be associated with the development of amyloidosis. Early diagnosis and accurate fibril typing are the first steps in managing the disease. Judicious use of various dia...

Comparative Analysis of Peptide p5 and Serum Amyloid P Component for Imaging AA Amyloid in Mice Using Dual-Isotope SPECT

Molecular Imaging and Biology — Mon, 31 Oct 2011 17:01:27 +0100

Conclusions Radiolabeled p5 is an effective amyloid-imaging radiotracer as compared to SAP in the murine model of amyloidosis and may be rapidly translated for imaging patients with visceral amyloidosis in the USA. Content Type Journal ArticleCategory Brief ArticlePages 1-6DOI 10.1007/s11307-011-0524-0Authors Jonathan S. Wall, Department of Radiology, University of Tennessee Graduate School of Medicine, 1924 Alcoa Highway, Knoxville, TN 37920-6999, USATina Richey, Department of Medicine, University of Tennessee Graduate School of Medicine, Knoxville, TN 37920, USAAngela Williams, Department of Medicine, University of Tennessee Graduate School of Medicine, Knoxville, TN 37920, USAAlan Stuckey, Department of Radiology, University of Tennessee Graduate School of Medicin...

Proteomics in Molecular Diagnosis: Typing of Amyloidosis

Clinical and Developmental Immunology — Sun, 30 Oct 2011 22:52:59 +0100

Amyloidosis is a group of disorders caused by deposition of misfolded proteins as aggregates in the extracellular tissues of the body, leading to impairment of organ function. Correct identification of the causal amyloid protein is absolutely crucial for clinical management in order to avoid misdiagnosis and inappropriate, potentially harmful treatment, to assess prognosis and to offer genetic counselling if relevant. Current diagnostic methods, including antibody-based amyloid typing, have limited ability to detect the full range of amyloid forming proteins. Recent investigations into proteomic identification of amyloid protein have shown promise. This paper will review the current state of the art in proteomic analysis of amyloidosis, discuss the suitability of techniques based on the pr...

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High-Dose Melphalan And Autologous Stem Cell Transplantation Increases Survival For AL Amyloidosis Patients

Health News from Medical News Today — Fri, 28 Oct 2011 07:00:00 +0100

A team of researchers led by Boston University School of Medicine (BUSM), has found treatment of selected immunoglobulin light chain (AL) amyloidosis patients with high-dose melphalan and autologous stem cell transplantation (HDM/SCT) resulted in a high organ response rate and increased overall survival (OS), even for those patients who did not achieve a hematologic complete response (CR). These findings appear in the current issue of Blood. AL amyloidosis is the most common form of systemic amyloidosis, with an incidence of five to 12 persons per million per year... (Source: Health News from Medical News Today)

Neoplasm Mimics of Rheumatologic Presentations: Sialadenitis, Ocular Masquerade Syndromes, Retroperitoneal Fibrosis, and Regional Pain Syndromes

Rheumatic Disease Clinics of North America — Fri, 28 Oct 2011 04:00:00 +0100

This article reviews a group of miscellaneous malignant conditions that may mimic rheumatologic diseases. Primary salivary gland cancer as well as lymphoproliferative conditions such as lymphoma and IgG4 related syndromes should be considered when evaluating a patient with sialadenosis. Primary intraocular lymphoma and melanoma in adults as well as leukemia and retinoblastoma in children may present as idiopathic ocular inflammation and require a high index of suspicion. Retroperitoneal fibrosis may mimic lymphoma or a solid malignancy and poses diagnostic challenges. Regional pain syndromes, such as complex regional pain and carpal tunnel syndromes, may be a manifestation of cancer and amyloidosis respectively. Awareness of these rare mimics may serve in guiding diagnostic investigations....

AL amyloidosis in a patient with macroglossia

ANZ Journal of Surgery — Thu, 27 Oct 2011 11:39:11 +0100

(Source: ANZ Journal of Surgery)

Preliminary neutron crystallographic study of human transthyretin

Acta Crystallographica Section F — Thu, 27 Oct 2011 04:00:00 +0100

This study will yield important information on hydrogen bonding, amino-acid protonation states and hydration in the protein. Such information will be of general interest for an understanding of the factors that stabilize/destabilize TTR and for the design of ligands that may be used to counter TTR amyloid fibrillogenesis. (Source: Acta Crystallographica Section F)

Effects of collagen-induced rheumatoid arthritis on amyloidosis and microvascular pathology in APP/PS1 mice

BMC Neuroscience - Latest articles — Thu, 27 Oct 2011 04:00:00 +0100

Conclusions: The present findings suggest that RA may exert beneficial effects against Amyloid burden and harmful effects on microvascular pathology in AD. (Source: BMC Neuroscience - Latest articles)

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High-dose melphalan and autologous stem cell transplantation increases survival

EurekAlert! - Medicine and Health — Wed, 26 Oct 2011 04:00:00 +0100

(Boston University Medical Center) A team of researchers led by Boston University School of Medicine, has found treatment of selected immunoglobulin light chain, amyloidosis patients with high-dose melphalan and autologous stem cell transplantation, resulted in a high organ response rate and increased overall survival, even for those patients who did not achieve a hematologic complete response. These findings appear in the current issue of Blood. (Source: EurekAlert! - Medicine and Health)

Anti-amyloidogenic and fibril-destabilizing effects of two manganese-salen derivatives against hen egg-white lysozyme aggregation.

International Journal of Biological Macromolecules — Tue, 25 Oct 2011 04:00:00 +0100

Authors: Bahramikia S, Yazdanparast R Abstract Amyloid depositions of proteins play crucial roles in a wide variety of degenerative disorders called amyloidosis. In the present study, we used hen egg white lysozyme (HEWL), as an in vitro model system, to induce fibrillation under high temperatures and acidic pH conditions, and investigated the inhibitory and disruptive effects of two salen-manganese complexes, namely EUK-8 and EUK-134, with aromatic structures, against fibrilization. Results of this study showed that EUK-8 and EUK-134in a dose-dependent manner inhibited the HEWL aggregation. Similar results were obtained when these compounds were added to pre-formed amyloid fibrils. Docking results also demonstrated that the aromatic rings of EUK-8 and EUK-134 interact with the hyd...

Radiological findings of primary localized amyloidosis of the ureter

Journal of Magnetic Resonance Imaging — Sun, 23 Oct 2011 09:21:20 +0100

AbstractLocalized amyloidosis is a rare condition, especially that involving the ureter. Because of its rarity and the difficulty in differentiating this condition from urothelial carcinoma by intravenous urography and computed tomography, nephroureterectomy has often been performed unnecessarily for this disease. The authors encountered two cases of this disease, both of which showed a negative urine cytology, no obvious mass effect, and a hypointensity on T2‐weighted imaging. Because these findings are very rare in urothelial carcinoma, ureteroscopy‐guided biopsy was performed, which yielded the diagnosis of amyloidosis. The patients were then treated and followed up at our institute. Primary localized amyloidosis of the ureter should be considered when evaluating ureteric lesions vi...

Exogenous seeding of cerebral β‐amyloid deposition in βAPP‐transgenic rats

Journal of Neurochemistry — Sun, 23 Oct 2011 02:09:11 +0100

AbstractDeposition of the Aβ peptide in senile plaques and cerebral Aβ angiopathy can be stimulated in Aβ‐precursor protein‐transgenic mice by the intracerebral injection of dilute brain extracts containing aggregated Aβ seeds. Growing evidence implicates a prion‐like mechanism of corruptive protein templating in this phenomenon, in which aggregated Aβ itself is the seed. Unlike prion disease, which can be induced de novo in animals that are unlikely to spontaneously develop the disease, previous experiments with Aβ seeding have employed animal models that, as they age, eventually will generate Aβ lesions in the absence of seeding. In the present study, we first established that a transgenic rat model expressing human Aβ‐precursor protein (APP21 line) does not manifest endo...

Cardiac Amyloidosis: A Practical Approach to Diagnosis and Management

The American Journal of Medicine — Sun, 23 Oct 2011 00:57:20 +0100

Abstract: Cardiac amyloidosis, the primary determinant of prognosis in systemic amyloidoses, is characterized by infiltration of myocardium by amyloid protein resulting in cardiomyopathy and conduction disturbances. Cardiac involvement is primarily encountered in immunoglobulin (AL) and transthyretin-associated (hereditary/familial and senile) amyloidoses. Although the latter variants could be indolent, untreated AL amyloidosis with clinical cardiac involvement is a rapidly fatal disease. The management decisions of cardiac amyloidosis are based on the underlying cause. Although treatment of senile systemic amyloidosis is largely supportive, the therapeutic approaches for AL amyloidosis include chemotherapy, autologous stem cell transplantation, and, rarely, cardiac transplantation. The fa...

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Bortezomib in a phase 1 trial for patients with relapsed AL amyloidosis: cardiac responses and overall effects

QJM — Sat, 22 Oct 2011 04:00:00 +0100

Conclusions: AL is frequently rapidly progressive; in these patients who had relapsed or progressed following previous conventional therapies, these results suggest that bortezomib may slow the progression of cardiac amyloid with limited toxicity. (Source: QJM)

Outcome of AL amyloidosis after high-dose melphalan and autologous stem cell transplantation: long-term results in a series of 421 patients

Blood — Thu, 20 Oct 2011 04:00:00 +0100

Previous studies have suggested that, in patients with AL amyloidosis treated with high-dose melphalan and autologous stem-cell transplantation (HDM/SCT), the greatest benefit is seen in those patients achieving a hematologic complete response (CR). We analyzed a series of 421 consecutive patients treated with HDM/SCT at a single referral center and compared outcomes for patients with and without CR. Treatment-related mortality was 11.4% overall (5.6% in the last 5 years). By intention-to-treat analysis, the CR rate was 34% and the median event-free survival (EFS) and overall survival (OS) were 2.6 and 6.3 years, respectively. Eighty-one patients died within the first year after HDM/SCT and were not evaluable for hematologic and organ response. Of 340 evaluable patients, 43% achieved CR an...

High-Dose Melphalan and Autologous Stem Cell Transplantation Increases Survival Among AL Amyloidosis Patients

Boston University News Releases — Wed, 19 Oct 2011 17:06:58 +0100

(Boston) - A team of researchers led by Boston University School of Medicine (BUSM), has found treatment of selected immunoglobulin light chain (AL) amyloidosis patients with high-dose melphalan and autologous stem cell transplantation (HDM/SCT) resulted in a high organ response rate and increased overall survival (OS), even for those patients who did not achieve a hematologic complete response (CR). These findings appear in the current issue of Blood. (Source: Boston University News Releases)

Delayed Contrast Enhancement on MR Images of Myocardium: Past, Present, Future [State of the Art]

Radiology — Wed, 19 Oct 2011 04:00:00 +0100

Differential enhancement of myocardial infarction was first recognized on computed tomographic (CT) images obtained with iodinated contrast material in the late 1970s. Gadolinium enhancement of myocardial infarction was initially reported for T1-weighted magnetic resonance (MR) imaging in 1984. The introduction of an inversion-recovery gradient-echo MR sequence for accentuation of the contrast between normal and necrotic myocardium was the impetus for widespread clinical use for demonstrating the extent of myocardial infarction. This sequence has been called delayed-enhancement MR and MR viability imaging. The physiologic basis for differential enhancement of myocardial necrosis is the greater distribution volume of injured myocardium compared with that of normal myocardium. It is now reco...

What is the evidence for the management of urethral amyloidosis? A systematic review of the literature

BJU International — Wed, 19 Oct 2011 04:00:00 +0100

CONCLUSION• Although urethrotomy and dilatation have been proposed in the past, we found these may still lead to disease progression and therefore urethroplasty may be the most appropriate long term management option. (Source: BJU International)

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Extensive bone marrow amyloidosis

Annals of Hematology — Mon, 17 Oct 2011 16:04:53 +0100

Content Type Journal ArticleCategory Letter to the EditorPages 1-2DOI 10.1007/s00277-011-1356-3Authors Stefano Licci, Department of Pathology, “Santo Spirito” Hospital, Lungotevere in Sassia, 1, 00193 Rome, Italy Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555 (Source: Annals of Hematology)

'Silent' carriage of two familial Mediterranean fever gene mutations in large families with only a single identified patient.

Clinical Genetics — Fri, 14 Oct 2011 04:00:00 +0100

Authors: Camus D, Shinar Y, Aamar S, Langevitz P, Ben-Zvi I, Livneh A, Lidar M Abstract Camus D, Shinar Y, Aamar S, Langevitz P, Ben-Zvi I, Livneh A, Lidar M. 'Silent' carriage of two familial Mediterranean fever gene mutations in large families with only a single identified patient. The presence of two mutations in the familial Mediterranean fever gene, without overt familial Mediterranean fever (FMF), designated as phenotype III, predisposes to developing 'silent' AA amyloidosis, recognized as phenotype II, due to the absence of medical supervision and colchicine prophylaxis. We sought to determine the prevalence of phenotype III in large families with only one subject affected with FMF, in order to assess the population at risk for transformation to phenotype II. A total of seve...

Concurrent nephrotic syndrome and acute renal failure caused by chronic lymphocytic leukemia (CLL): a case report and literature review

Diagnostic Pathology — Thu, 13 Oct 2011 04:00:00 +0100

Kidney injury associated with chronic lymphocytic leukemia (CLL) is typically caused by direct tumor infiltration which occasionally results in acute renal failure. Glomerular involvement presenting as proteinuria or even nephrotic syndrome is exceptionally rare. Here we report a case of 54-year-old male CLL patient with nephrotic syndrome and renal failure. The lymph node biopsy confirmed that the patients had CLL with remarkable immunoglobulin light chain amyloid deposition. The renal biopsy demonstrated the concurrence of AL amyloidosis and neoplastic infiltration. Combined treatment of fludarabine, cyclophosphamide and rituximab resulted in remission of CLL, as well as the renal disfunction and nephrotic syndrome, without recurrence during a 12-month follow-up. To our knowledge, this i...

Imaging Evaluation of Amyloidosis of the Urinary Tract and Retroperitoneum [Genitourinary Imaging]

Radiographics recent issues — Wed, 12 Oct 2011 04:00:00 +0100

Amyloidosis is a heterogeneous group of disorders and may be classified as systemic or localized on the basis of the distribution of amyloid deposition. Infrequently, the urinary tract and supporting retroperitoneum may be involved, and the imaging findings are nonspecific and diverse. Localized amyloidosis usually involves the bladder and often mimics malignancy. Less frequently, the ureter, renal pelvis, and urethra are involved. The most common findings of amyloid deposition are focal or diffuse wall thickening in the urinary tract with intramural calcification that often results in ureteral obstruction. When the renal parenchyma is involved, patients generally develop nephrotic-range proteinuria, and the kidneys appear atrophic with cortical thinning. In systemic amyloidosis, amyloid m...

Cardiac Amyloidosis: Evolving Approach to Diagnosis and Management

Current Treatment Options in Cardiovascular Medicine — Tue, 11 Oct 2011 15:53:02 +0100

Opinion statement The systemic amyloidoses are a group of heterogeneous disorders characterized by extracellular deposition of misfolded fibrillar protein that results in organ dysfunction. Involvement of the heart (cardiac amyloidosis) is manifest by increased cardiac wall thickness and impairment of myocardial diastolic and systolic properties, changes that result in heart failure, dysrhythmia, and death. Amyloidosis is classified by precursor protein, with light-chain (AL) and transthyretin (TTR) disease being most common in the United States. TTR amyloid can result from misfolding of variant TTR, a genetically inherited disease, or wild-type TTR, an acquired form of disease (termed senile systemic amyloidosis). In recent years, advances in the diagnosis and treatment o...

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Localized nodular amyloidosis of the lung

General Thoracic and Cardiovascular Surgery — Sat, 08 Oct 2011 05:48:20 +0100

Abstract Pulmonary localized nodular amyloidosis is a rare disorder and is not associated with primary systemic amyloidosis. We herein report a patient with a growing lung nodule who underwent thoracic surgery and was diagnosed with this condition. This case study suggests that localized nodular amyloidosis should be considered during a differential diagnosis of growing lung nodules and that a histological examination should be performed to distinguish this disorder from lung malignancies. Content Type Journal ArticleCategory Case ReportPages 715-717DOI 10.1007/s11748-010-0748-yAuthors Takashi Eguchi, Department of Thoracic Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621 JapanKazuo Yoshida, Department of Thoracic Surgery, Shinshu Univer...

Chemical characterization of pro-inflammatory amyloid-beta peptides in human atherosclerotic lesions and platelets.

Biochimica et Biophysica Acta — Sat, 08 Oct 2011 02:17:49 +0100

Authors: Kokjohn TA, Van Vickle GD, Maarouf CL, Kalback WM, Hunter JM, Daugs ID, Luehrs DC, Lopez J, Brune D, Sue LI, Beach TG, Castaño EM, Roher AE Abstract Amyloid-β (Aβ) peptides are intimately involved in the inflammatory pathology of atherosclerotic vascular disease (AVD) and Alzheimer's disease (AD). Although substantial amounts of these peptides are produced in the periphery, their role and significance to vascular disease outside the brain requires further investigation. Amyloid-β peptides present in the walls of human aorta atherosclerotic lesions as well as activated and non-activated human platelets were isolated using sequential size-exclusion columns and HPLC reverse-phase methods. The Aβ peptide isolates were quantified by ELISA and structurally analyzed using MA...

Systemic but asymptomatic transthyretin amyloidosis 8 years after domino liver transplantation

Journal of Neurology, Neurosurgery and Psychiatry — Thu, 06 Oct 2011 04:00:00 +0100

As familial amyloid polyneuropathy (FAP) is an adult-onset disease, a long period is expected between domino liver transplantation (DLT) and the occurrence of amyloidosis in recipients of a FAP liver. However, as time passes, and increased numbers of patients have undergone DLT, patients with symptoms suggesting amyloidosis have been reported. The authors describe, for the first time, pathological findings in an autopsy case of a recipient of a FAP liver. A male patient with primary sclerosing cholangitis received a liver graft from a FAP patient with the transthyretin (TTR) Tyr114Cys mutation when he was 30 years old. Although a recurrence of primary sclerosing cholangitis was detected at age 34, he had no symptoms indicating amyloidosis. He died from Burkitt's lymphoma at 38 ye...

Tracheobronchial amyloidosis: presentation of a case.

Radiologia — Tue, 04 Oct 2011 04:00:00 +0100

Authors: Díaz Lorenzo I, Alvarez Sanz C PMID: 21978406 [PubMed - as supplied by publisher] (Source: Radiologia)

Reduction of alloantibodies via proteosome inhibition in cardiac transplantation

The Journal of Heart and Lung Transplantation — Tue, 04 Oct 2011 04:00:00 +0100

Conclusions: In this pilot study, use of plasmapheresis and bortezomib appeared to decrease cPRA, even in patients refractory to desensitization with IVIg/rituximab, thus increasing the chances that an acceptable donor heart will be available for the sensitized patient awaiting heart transplantation. However, desensitization is associated with an increased risk of infection. Further studies are warranted to determine whether the benefits of desensitization using this strategy outweigh the risks. (Source: The Journal of Heart and Lung Transplantation)

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Insulin/insulin glargine: Amyloidosis following subcutaneous administration: case report

Reactions — Mon, 03 Oct 2011 06:00:13 +0100

(Source: Reactions)

Hereditary Lysozyme Amyloidosis – Phenotypic Heterogeneity and the Role of Solid Organ Transplantation

Journal of Internal Medicine — Sat, 01 Oct 2011 04:00:00 +0100

Conclusions: ALys is a disease of the gastrointestinal tract, liver and kidneys which has a slow natural history. There was a clear family history in all cases within this cohort, demonstrating a high clinical penetrance in the presence of an amyloidogenic lysozyme mutation. There is currently no amyloid‐specific therapy for the condition which is managed symptomatically. OLT and RTx appear to be successful treatments for patients with liver rupture or end‐stage renal disease respectively, with excellent outcomes in terms of medium‐term graft function and patient survival. (Source: Journal of Internal Medicine)

Pathogenic protein seeding in alzheimer disease and other neurodegenerative disorders

Annals of Neurology — Sat, 01 Oct 2011 04:00:00 +0100

AbstractThe misfolding and aggregation of specific proteins is a seminal occurrence in a remarkable variety of neurodegenerative disorders. In Alzheimer disease (the most prevalent cerebral proteopathy), the two principal aggregating proteins are β‐amyloid (Aβ) and tau. The abnormal assemblies formed by conformational variants of these proteins range in size from small oligomers to the characteristic lesions that are visible by optical microscopy, such as senile plaques and neurofibrillary tangles. Pathologic similarities with prion disease suggest that the formation and spread of these proteinaceous lesions might involve a common molecular mechanism—corruptive protein templating. Experimentally, cerebral β‐amyloidosis can be exogenously induced by exposure to dilute brain extract...

Microfibrillar cardiomyopathy: A rare case.

Indian Journal of Pathology and Microbiology — Sat, 01 Oct 2011 04:00:00 +0100

Authors: Kumar N, Ray R Abstract Microfibrillar cardiomyopathy is a very rare cause of restrictive cardiomyopathy (RCM). The index case was a male patient who presented with shortness of breath and pedal edema. Further clinical investigations favored a clinical diagnosis of RCM. An endomyocardial biopsy revealed subendocardial and interstitial hyaline eosinophillic material resembling amyloid that did not stain with Congo red. An electron microscopic examination showed that this material was composed of twisted linear and bundles of tangled microfibrils. The etiology of the microfibrillar deposition is currently unknown. The pathologists should entertain the diagnosis of microfibrillar cardiomyopathy in suspected cases of amyloidosis that are negative for Congo red. PMID: 22234...

Opportunities and challenges in developing Alzheimer disease therapeutics

Acta Neuropathologica — Fri, 30 Sep 2011 05:53:11 +0100

Abstract Alzheimer disease (AD) is a chronic, progressive disorder with an average disease progression of 7–10 years. However, the histopathological hallmark lesions of this disease, the extracellular Aβ plaques and the intraneuronal neurofibrillary tangles, start as early as childhood in the affected individuals. AD is multifactorial and probably involves many different etiopathogenic mechanisms. Thus, while AD offers a wide window of opportunity that practically includes the whole life span of the affected individuals, and numerous therapeutic targets, the multifactorial nature of this disease also makes the selection of the therapeutic targets an immensely challenging task. In addition to β-amyloidosis and neurofibrillary degeneration, the AD brain also is comp...

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SPECT imaging of peripheral amyloid in mice by targeting hyper-sulfated heparan sulfate proteoglycans with specific scFv antibodies

Nuclear Medicine and Biology — Wed, 28 Sep 2011 04:00:00 +0100

Conclusions: These data indicate that HS expressed in amyloid deposits has unique qualities that can be distinguished from HS in normal tissues. A scFv specific for rare hypersulfated HS was used to selectively image AA amyloid in mice with minimal retention in normal tissue. (Source: Nuclear Medicine and Biology)

Significant association between renal function and area of amyloid deposition in kidney biopsy specimens in reactive amyloidosis associated with rheumatoid arthritis

Rheumatology International — Tue, 27 Sep 2011 05:52:55 +0100

Abstract The kidney is a major target organ for systemic amyloidosis, resulting in proteinuria and an elevated serum creatinine level. In patients with reactive amyloidosis associated with rheumatoid arthritis, a correlation between the amount of amyloid deposits and clinical parameters is not known. The purpose of this study was to clarify the association between various factors including renal function and the area of amyloid deposition in these patients. Fifty-eight patients with an established diagnosis of reactive AA amyloidosis were studied. We retrospectively investigated the correlation between clinical data and the area occupied by amyloid in renal biopsy specimens. All the patients showed amyloid deposits in renal tissues, and the percentage of the area occupied ...

Acute kidney injury is common during leukocyte engraftment after autologous stem cell transplantation in patients with light chain amyloidosis (AL)

American Journal of Hematology — Mon, 26 Sep 2011 04:00:00 +0100

This study was conducted to further investigate the relationship between AKI and ES.Data was collected from 377 AL patients who underwent ASCT from 7/1997 to 10/2009. Patients who experienced an elevation of serum creatinine > 0.5 mg/dl within 4 days of leukocyte engraftment and anyone who presented with signs associated with ES regardless of renal manifestations were included.Forty‐one patients met criteria. Twelve were excluded for positive cultures (10), acute interstitial nephritis (1) and acute cellular rejection (1). In addition to AKI (93.1%), patients also exhibit fever (82.7%), hypotension (51.7%), rash (48.2%), edema (93.1%), diarrhea (69.0%), conjunctival hemorrhage (31.0%), pulmonary edema (31.0%), pulmonary hemorrhage (13.8%) and transient encephalopathy (17.2%). Patient ...

Acute kidney injury during leukocyte engraftment after autologous stem cell transplantation in patients with light‐chain amyloidosis

American Journal of Hematology — Mon, 26 Sep 2011 04:00:00 +0100

This study was conducted to further investigate the relationship between AKI and ES. Data were collected from 377 AL patients who underwent ASCT from 7/1997 to 10/2009. Patients who experienced an elevation of serum creatinine >0.5 mg/dL within 4 days of leukocyte engraftment and anyone who presented with signs associated with ES regardless of renal manifestations were included. Forty‐one patients met criteria. Twelve were excluded for positive cultures (10), acute interstitial nephritis (1), and acute cellular rejection (1). In addition to AKI (93.1%), patients also exhibit fever (82.7%), hypotension (51.7%), rash (48.2%), edema (93.1%), diarrhea (69.0%), conjunctival hemorrhage (31.0%), pulmonary edema (31.0%), pulmonary hemorrhage (13.8%), and transient encephalopathy (17.2%). Pati...

Amyloidosis and exercise intolerance in ANO5 muscular dystrophy

Neuromuscular Disorders — Thu, 22 Sep 2011 04:00:00 +0100

We describe a 53-year-old woman with exercise intolerance since childhood, recurrent rhabdomyolysis and late-onset weakness. Muscle biopsy showed amyloid deposits within the blood vessel walls and around muscle fibers. Mutation analysis identified two pathogenic heterozygous mutations in anoctamin 5 and no mutations in dysferlin. To our knowledge this is the first report of muscle amyloidosis in anoctamin 5 muscular dystrophy. This finding suggests that patients with amyloid in muscle should be screened for anoctamin 5 muscular dystrophy. (Source: Neuromuscular Disorders)

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Specific Bone and Mineral Disorders in Patients with Chronic Kidney Disease

Clinical Reviews in Bone and Mineral Metabolism — Tue, 20 Sep 2011 15:46:35 +0100

Abstract Bone lesions, collectively known as renal osteodystrophy (ROD), are a common complication of chronic kidney disease (CKD). Besides osteitis fibrosa and mixed lesions, other bone and mineral disorders such as adynamic bone disease, osteomalacia, osteoporosis, dialysis-related amyloidosis, and calcific uremic arteriolopathy are increasingly recognized in patients with CKD. Although bone lesions usually begin early in the course of CKD and are progressive, symptoms and signs such as bone pain and fractures may not occur until the patient is already on maintenance dialysis. More importantly, these disorders are associated with increased risk of cardiovascular disease and mortality in patients with CKD. The term ROD does not reflect the full spectrum of bone pathology ...

Case of primary localized cutaneous amyloidosis with protean clinical manifestations: Lichen, poikiloderma‐like, dyschromic and bullous variants

The Journal of Dermatology — Tue, 20 Sep 2011 04:00:00 +0100

We present a case of a 27‐year‐old Chinese woman with cutaneous features of the rarely reported poikiloderma‐like, dyschromic and bullous forms of PLCA, and the commoner lichen variant. There were no syndromic associations or systemic involvement, and the various morphological subtypes occurred in isolation from one another. We review the clinical spectrum of PLCA, highlight its protean clinical manifestations in this patient, and discuss its postulated pathogenesis in relation to its histopathological features. (Source: The Journal of Dermatology)

Primary tracheo-bronchial amyloidosis studied with 64-slice MDCT (2D and 3D reconstructions)

Thorax — Tue, 20 Sep 2011 04:00:00 +0100

A 50-year-old Caucasian man was presented to the emergency department with cough and progressive dyspnoea. Plain chest x-ray showed multiple pseudo-nodular parenchymal opacities, partly confluent and calcified, prominent in the middle-basal lung fields (figure 1A). Volumetric high-resolution computed tomography (HRCT) confirmed multiple bilateral parenchymal nodules with lobulated margins and extensive calcifications due to diffuse bronchiectasis with thickened and calcified walls (figure 1B–C). Airways involvement was evident, characterised by submucosal deposits and lumen distortion mainly in the trachea, without sparing of the posterior membranous portion, and main and segmental bronchi (figure 2). Biopsy specimen from bronchoscopy was striking for amyloid (figure 3), therefore th...

Renal amyloidosis revisited: amyloid distribution, dynamics and biochemical type

Nephrology Dialysis Transplantation — Fri, 16 Sep 2011 04:00:00 +0100

Conclusions. The relevance of the different distribution patterns is unclear at the moment, but they may be due to the physicochemical properties of the amyloid fibrils in a given patient. This may become important in future anti-fibrillar therapies. (Source: Nephrology Dialysis Transplantation)

Effectiveness of β2-Microglobulin Adsorption Column in Treating Dialysis-Related Amyloidosis: A Multicenter Study

Blood Purification — Thu, 15 Sep 2011 23:00:00 +0100

Blood Purif 2011;32:317–322 (DOI:10.1159/000330332) (Source: Blood Purification)

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Neurodegeneration in Familal Amyloidotic Polyneuropathy.

Clinical and Experimental Pharmacology and Physiology — Wed, 14 Sep 2011 04:00:00 +0100

Authors: Gasperini RJ, Small DH Abstract 1. Familial amyloid polyneuropathies (FAP) constitute a group of inherited amyloidoses that affect peripheral nerves. One common form of FAP is caused by transthyretin (TTR) misfolding and deposition in the peripheral nervous system, leading to neuronal toxicity and death. 2. The molecular mechanisms responsible for this toxicity are unclear, however there is good biochemical and histopathological evidence that the toxicity of TTR mutations is correlated to their aggregation state. In addittion, neuronal calcium dysregulation is a mechanism that has been suggested to drive the pathogenesis of FAP. 3. Amyloidogenic TTR mutations cause significant calcium influx via L-type calcium channels in neuronal cell lines, while in primary sensory...

P5.69 Bulbofacial myopathy with anti-amphiphysin 2 (BIN 1) antibodies – A new paraneoplastic neurological syndrome?

Neuromuscular Disorders — Tue, 13 Sep 2011 03:40:12 +0100

A 51year old woman presented with a four year history of slowly progressive dysphagia, dysarthria, mild facial and proximal muscle weakness. Her CK was elevated to >800U/l and EMG demonstrated pathological spontaneous activity in one iliopsoas muscle only, while other muscles were found normal. As work-up for motoneuron disease, amyloidosis and scleroderma did not provide a diagnosis, a deltoid muscle biopsy was taken to rule out myositis. Histology showed a marked, selective type II fibre atrophy without further relevant changes. Work-up for associated disorders revealed bilateral invasive ductal mammary carcinoma. After surgery, radio- and chemotherapy, dysphagia and dysarthria improved. The CK fell to about 400U/l. Serum screening for paraneoplasic diseases associated (’onconeural’)...

P3.28 Baseline neurologic function in symptomatic patients in the Transthyretin Amyloidosis Outcomes Survey (THAOS)

Neuromuscular Disorders — Tue, 13 Sep 2011 03:39:57 +0100

To describe baseline neurologic function of symptomatic patients in an international registry for transthyretin amyloidosis (ATTR). The Transthyretin Amyloidosis Outcomes Survey (THAOS) characterizes the natural history of ATTR, regional differences in disease expression, and genotypic-phenotypic relationships. Eligible patients have confirmed genotyped TTR mutations with or without symptomatic disease, or wild-type ATTR. Recommended minimal neurologic evaluations include pinprick, touch, and vibration of the great toe; ankle and patellar reflexes; muscle strength of toes and ankles. Data are shown for symptomatic patients with five sensory assessments (pinprick, cold, touch, vibration and position sense) performed up to the thigh. Of 592 patients enrolled (38 sites/17 countries), data are...

P2.42 Cys150Arg FHL1 mutation in two brothers affected by the Emery-Dreifuss muscular dystrophy phenotype

Neuromuscular Disorders — Tue, 13 Sep 2011 03:39:56 +0100

Mutations in the four and a half LIM protein 1 (FHL1) gene were recently identified as the cause of four distinct skeletal muscle diseases: reducing body myopathy, X-linked myopathy characterized by postural muscle atrophy, scapuloperoneal myopathy and Emery-Dreifuss muscular dystrophy (EDMD). FHL1 plays multiple roles in the myoblast differentiation. Here we report two male siblings presenting a Emery-Dreifuss muscular dystrophy phenotype. The patients, currently 17 and 14years old were born from a non consanguineous family. Their mother died from gastric bleeding after having been diagnosed of amyloidosis. However she suffered from a cardiomyopathy and had an increased CK level. Onset of clinical symptoms was at six years of age in both brothers, presenting motor clumsiness, progressive ...

Effects of Age and Amyloid Deposition on A{beta} Dynamics in the Human Central Nervous System [Original Contribution]

Archives of Neurology — Mon, 12 Sep 2011 04:00:00 +0100

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An operational approach to NIA‐AA criteria for preclinical Alzheimer's disease

Annals of Neurology — Mon, 12 Sep 2011 04:00:00 +0100

AbstractObjective:A workgroup commissioned by the Alzheimer's Association (AA) and the National Institute on Aging (NIA) recently published research criteria for preclinical Alzheimer's disease (AD). We performed a preliminary assessment of these guidelines.Methods:We employed Pittsburgh compound B positron emission tomography (PET) imaging as our biomarker of cerebral amyloidosis and 18fluorodeoxyglucose PET imaging and hippocampal volume as biomarkers of neurodegeneration. A group of 42 clinically diagnosed AD subjects was used to create imaging biomarker cut‐points. A group of 450 cognitively normal (CN) subjects from a population based sample was used to develop cognitive cut‐points and to assess population frequencies of the different preclinical AD stages using different cut‐po...

Comparative fibril formation of analogs corresponding to the (12–24) segment of the β-amyloid peptide

Neurological Sciences — Fri, 09 Sep 2011 06:05:28 +0100

Abstract The (1–42) β-amyloid peptide is a main component of the plaques found in the brain of patients suffering from the Alzheimer’s disease. As the single substitution of Glu for Gln at position 22 of this peptide seems to be responsible for the manifestation of the more severe amyloidosis (Dutch-type), we decided to evaluate the aggregation characteristics of peptide analogs interchanging Glu and Gln residues at positions 22 and also 15 in the minor (12–24) (VHHQ15KLVFFAE22DV) fragment. The Q15Q22, E15E22, E15Q22 and the native Q15E22 were compared to the (1–42) β-amyloid peptide in terms of fibril or structured aggregates formation propensity. In contrast to a rather similar solubility data measured of all analogs, fluorescence and light scattering methods in...

[Localized gastric amyloidosis].

Korean J Gastroenter... — Fri, 02 Sep 2011 01:24:22 +0100

Authors: Lee YN, Hong SJ, Kim HK PMID: 21873829 [PubMed - in process] (Source: Korean J Gastroenter...)

Renal amyloidosis in a child with neutropenia.

Saudi Journal of Kidney Diseases and Transplantation — Thu, 01 Sep 2011 04:00:00 +0100

Authors: Otukesh H, Hoseini R, Behzadi AH, Fereshtehnejad SM, Mehrazma M, Parvin M, Mojtahedzadeh M, Razizadeh N, Pourfakharan M Abstract Amyloidosis represents a heterogeneous group of disorders of protein metabolism and is characterized by deposition of fibrillar proteins in the intra- and extracellular spaces. Here, a case of generalized amyloidosis associated with neutropenia is presented. She had a medical history of multiple bacterial infections. At the age of 14 years, she developed nephrotic syndrome. An increase of antigenic stimulation during the intermittent bouts of acute infections would have been the main factor responsible for the development of secondary amyloidosis in this case. To the best of our knowledge, coexistence between neutropenic disorders and renal amylo...

Renal AA amyloidosis in a patient with hereditary complete complement C4 deficiency.

Saudi Journal of Kidney Diseases and Transplantation — Thu, 01 Sep 2011 04:00:00 +0100

We present here a 20- year- old female with hereditary complete C4 deficiency. Renal biopsy demonstrated renal AA amyloidosis. This unique case further substantiates that deficiency of classical pathway components predisposes to the development of recurrent microbial infections and that the patients may develop AA amyloidosis. Furthermore, in clinical practice, the nephrotic syndrome occurring in a patient with hereditary complete complement C4 deficiency should lead to the suspicion of renal AA amyloidosis. PMID: 21912034 [PubMed - in process] (Source: Saudi Journal of Kidney Diseases and Transplantation)

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Cutaneous Collagenous Vasculopathy: Report of the First Pediatric Case

Pediatric Dermatology — Thu, 01 Sep 2011 04:00:00 +0100

We describe a 16‐year‐old girl who presented with a 3‐year history of telangiectatic patches on the extremities and trunk. Skin biopsies demonstrated dilated vessels with thickened walls containing hyaline material in the papillary dermis, resembling those seen in systemic amyloidosis, porphyrias, or lipoid proteinosis. A diagnosis of cutaneous collagenous vasculopathy was made. To our knowledge, cutaneous collagenous vasculopathy has previously only been described in adults aged 50 and older. (Source: Pediatric Dermatology)

F-FDG PET/CT in Primary AL Hepatic Amyloidosis Associated with Multiple Myeloma.

Korean J Radiol — Thu, 01 Sep 2011 04:00:00 +0100

We report here on a rare case of primary AL hepatic amyloidosis associated with multiple myeloma in a 64-year-old woman. The patient was referred for evaluating her progressive jaundice and right upper quadrant pain. (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET)/computed tomography (CT) showed diffusely and markedly increased (18)F-FDG uptake in the liver. Although there have been several case studies showing positive (18)F-FDG uptake in pulmonary amyloidosis, to the best of our knowledge, the (18)F-FDG PET/CT findings of hepatic amyloidosis or primary hepatic amyloidosis associated with multiple myeloma have not been reported previously. PMID: 21927567 [PubMed - in process] (Source: Korean J Radiol)

Carpal tunnel syndrome and peripheral polyneuropathy in patients with end stage kidney disease.

J Korean Med Sci — Thu, 01 Sep 2011 04:00:00 +0100

This study was designed to identify the causes of the development of carpal tunnel syndrome (CTS) associated with end stage kidney disease (ESKD). A total of 112 patients with ESKD, 64 on hemodialysis (HD) and 48 on peritoneal dialysis (PD), were enrolled. The duration of ESKD and dialysis, the site of the arteriovenous (A-V) fistula for HD, laboratory data such as blood urea nitrogen, creatinine, and beta-2-microglobulin were determined. Clinical evaluation of CTS and electrophysiological studies for the diagnosis of CTS and peripheral neuropathy were performed. The electrophysiological studies showed that the frequency of CTS was not different in the HD and PD groups (P = 0.823) and the frequency of CTS was not different in the limb with the A-V fistula compared to the contralateral limb...

Serum free light chains in myeloma patients with an intact M protein by immunofixation: potential roles for response assessment and prognosis during induction therapy with novel agents

Hematological Oncology — Thu, 01 Sep 2011 04:00:00 +0100

AbstractThe ascertainment of serum free light chain (sFLC) levels has been shown to be valuable in screening for the presence of plasma cell dyscrasia as well as for baseline prognosis in newly diagnosed patients. For patients with amyloidosis and those with oligo‐secretory or non‐secretory multiple myeloma (MM), serial measurement of sFLC has also been shown to be valuable in monitoring disease status. However, in patients with a measureable, intact monoclonal protein by immunofixation (M protein), the serial measurement of sFLC remains undefined and is currently not recommended in professional guidelines. Herein, we provide data comparing sFLC with M protein as biomarkers of response in newly diagnosed patients with MM undergoing induction therapy with the novel agents thalidomide, l...

[Bilateral pleurisy revealing a myelome with free light chains complicated with an osseous amylase].

Annales de Biologie Clinique — Thu, 01 Sep 2011 04:00:00 +0100

We report a case of an association of these three disease entities for discussion. A 75-year-old man was admitted for chest pain and dyspnea with left sacred bone pain. The radiological assessment reported pleurisy and bilateral lytic images of the sacrum with soft tissue invasion, the biochemical tests showed a lambda free light chain myeloma and bone biopsy reported amyloidosis. The occurrence of systemic amyloidosis in myeloma is well documented, but the osseous location is rare and rarely revealed. Pleural effusion is a known complication of myeloma but is exceptionally revealing; it is usually seen in the myeloma IgG and IgA but very rarely in free light chain myeloma. We reported here a case that represents an exceptional situation of complications of light chains myeloma to remember...

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Nodular cutaneous amyloidosis.

Skinmed — Thu, 01 Sep 2011 04:00:00 +0100

Authors: Borowicz J, Shama L, Miller R Abstract A 56-year-old white man presented with a lesion on the right shoulder. The lesion developed during a short period and recently became irritated with occasional bleeding and mild pruritus. The patient denied pain. Medical history included melanoma, nonmelanoma skin cancer, diabetes mellitus type II, hyperlipidemia, multinodular thyroid goiter, and obesity. Medications and family and social history were noncontributory. Review of systems was negative. Examination revealed a slightly raised, friable yellow-pink waxy plaque located on the right shoulder (Figure 1). There was no evidence of excoriation, secondary infection, drainage, scale, crust, atrophy, lichenification, or telangiectasia. The patient had no mucosal or nail changes and t...

Cardiac amyloidosis: a treatable disease, often overlooked.

Circulation — Mon, 29 Aug 2011 23:00:00 +0100

Authors: Falk RH PMID: 21875922 [PubMed - in process] (Source: Circulation)

Localized Primary Cutaneous Nodular Amyloidosis in a Patient With Paraproteinemia.

Actas Dermo-Sifiliograficas — Mon, 29 Aug 2011 23:00:00 +0100

Authors: Villar M, Burgués M, Rodríguez-Peralto JL, Rivera R, Vanaclocha F PMID: 21885025 [PubMed - as supplied by publisher] (Source: Actas Dermo-Sifiliograficas)

A large-sized bubbling appearance of the glomerular basement membrane in a patient with pulmonary limited AL amyloidosis and a past history of lupus nephritis

Clinical and Experimental Nephrology — Mon, 29 Aug 2011 05:37:45 +0100

We report an unusual pathological finding, a large-sized bubbling appearance of the glomerular basement membrane (GBM), in a patient with pulmonary limited AL amyloidosis and a past history of lupus nephritis. The first renal biopsy specimen from 10 years ago, when systemic lupus erythematosus was diagnosed, demonstrated mild mesangial proliferation and subepithelial deposits (WHO classification: III + V). Light microscopy of the current biopsy using periodic acid methenamine silver (PAMS) stain demonstrated a large-sized bubbling appearance of the GBM; however, very weak immunoglobulin and complement deposition was observed in immunofluorescence studies. Routine electron microscopy demonstrated partial subendothelial expansion with electron-lucent materials, but no el...

Biocompatible characteristics of high-performance membranes.

Contributions to Nephrology — Mon, 29 Aug 2011 01:56:07 +0100

Authors: Uda S, Mizobuchi M, Akizawa T Abstract Interactions of blood with hemodialysis membranes induce activation of blood factors that may cause adverse clinical outcomes in hemodialysis patients. The biocompatibility of a hemodialysis membrane is determined by the change in blood factors induced by blood interactions, and it is important that these interactions are mild and well tolerated by dialysis patients. Bioincompatible membranes that activate the complement system and accelerate cytokine production by monocytes may lead to chronic inflammation, dialysis-related amyloidosis, malnutrition, and atherosclerosis. Contact activation by a bioincompatible membrane may also induce an anaphylactoid reaction via bradykinin production. Thus, high-performance membranes should have bo...

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Manifestations of transthyretin-related familial amyloidotic polyneuropathy: Long-term follow-up of Japanese patients after liver transplantation

Surgery Today — Sat, 27 Aug 2011 05:49:39 +0100

Conclusion Although LT is life-saving for patients with FAP, we observed progression of the ocular and cardiac symptoms of FAP in a significant number of these patients over the long term after LT. Content Type Journal ArticleCategory Original ArticlePages 1211-1218DOI 10.1007/s00595-010-4488-5Authors Yuki Ohya, Department of Transplantation and Pediatric Surgery, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556 JapanSadahisa Okamoto, Department of Neurology, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556 JapanMasayoshi Tasaki, Department of Diagnostic Medicine, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556 JapanMitsuharu Ueda, Department of Diagnostic Medicine, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556 JapanHirofumi Jono, Department of Di...

How to manage primary amyloidosis

Leukemia — Thu, 25 Aug 2011 23:00:00 +0100

Leukemia advance online publication, August 26, 2011. doi:10.1038/leu.2011.219 Author: M A Gertz (Source: Leukemia)

Pathogenic protein seeding in alzheimer's disease and other neurodegenerative disorders

Annals of Neurology — Wed, 24 Aug 2011 23:00:00 +0100

AbstractThe misfolding and aggregation of specific proteins is a seminal occurrence in a remarkable variety of neurodegenerative disorders. In Alzheimer's disease (the most prevalent cerebral proteopathy), the two principal aggregating proteins are β‐amyloid (Aβ) and tau. The abnormal assemblies formed by conformational variants of these proteins range in size from small oligomers to the characteristic lesions that are visible by optical microscopy, such as senile plaques and neurofibrillary tangles. Pathologic similarities with prion disease suggest that the formation and spread of these proteinaceous lesions might involve a common molecular mechanism – corruptive protein templating. Experimentally, cerebral β‐amyloidosis can be exogenously induced by exposure to dilute brain ext...

In vivo molecular imaging of peripheral amyloidosis using heparin-binding peptides [Medical Sciences]

Proceedings of the National Academy of Sciences — Mon, 22 Aug 2011 23:00:00 +0100

Heparan sulfate proteoglycans (HSPGs) are ubiquitous components of pathologic amyloid deposits in the organs of patients with disorders such as Alzheimer's disease or systemic light chain (AL) or reactive (AA) amyloidosis. Molecular imaging methods for early detection are limited and generally unavailable outside the United Kingdom. Therefore, there is an urgent need to develop novel, specific amyloidophilic radiotracers for imaging to assist in diagnosis, prognostication, and monitoring response to therapy. Amyloid-associated HSPG can be differentiated from HSPG found in surrounding healthy cells and tissues by the preferential binding of certain HS-reactive single chain variable fragments and therefore, represents a biomarker that can be targeted specifically with appropriate reagents. U...

Med Sci Monit 2011; 17(9):CR505-509 "Carpal tunnel syndrome in hemodialysis patients as a dialysis-related amyloidosis manifestation – incidence, risk factors and results of surgical treatment "

Medical Science Monitor — Mon, 22 Aug 2011 10:16:00 +0100

Conclusions: Surgical release procedure of the carpal tunnel gave good treatment results in patients with CTS. (Source: Medical Science Monitor)

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PEGylation enhances the therapeutic potential for insulin-like growth factor I in central nervous system disorders.

Growth Hormone and IGF Research — Sun, 21 Aug 2011 23:00:00 +0100

CONCLUSIONS: Our data generate the therapeutic potential for PEG-IGF-I to treat CNS disorders by systemic drug application, and in addition scientifically support its application in disorders of synaptic function and neuronal development. PMID: 21865068 [PubMed - as supplied by publisher] (Source: Growth Hormone and IGF Research)

Bortezomib and high dose melphalan conditioning for stem cell transplantation for AL amyloidosis: a pilot study.

Haematologica — Sun, 21 Aug 2011 23:00:00 +0100

Authors: Sanchorawala V, Quillen K, Sloan JM, Andrea NT, Seldin DC Abstract Not applicable for letter to the editor. PMID: 21859734 [PubMed - as supplied by publisher] (Source: Haematologica)

Cutaneous signs of systemic disease

Clinics in Dermatology — Sat, 20 Aug 2011 15:44:23 +0100

Abstract: Commonly used dermatologic eponyms and characteristic skin signs are enormously helpful in guiding a diagnosis, even though they may not be pathonemonic. They include, on the nails, Aldrich-Mees' lines (syn.: Mees' lines), Beau's lines, Muehrcke's lines, Terry's nails, and half and half nails, often associated, respectively, with arsenic poisoning, acute stress or systemic illness, severe hypertension, liver disease and uremia, and, around the nails, Braverman's sign, associated with collagen-vascular disease. Elsewhere, one may see the Asboe-Hansen and Nikolsky's signs, indicative of the pemphigus group of diseases, Auspitz's sign, a classic finding in psoriasis, Borsieri's and Pasita's signs, seen in early scarlet fever, the butterfly rash, indicative of systemic lupus erythema...

In vivo imaging of astrocytosis in Alzheimer’s disease: an 11C-L-deuteriodeprenyl and PIB PET study

European Journal of Nuclear Medicine and Molecular Imaging — Fri, 19 Aug 2011 06:40:19 +0100

Conclusion Our conclusion is that DED may serve as an in vivo marker for astrocytosis in AD, providing a window into intermediate processes between amyloidosis and neuronal loss and a means of monitoring immunotherapy. Content Type Journal ArticleCategory Original ArticlePages 1-7DOI 10.1007/s00259-011-1895-9Authors Alexander Frizell Santillo, Geriatric Psychiatry, Department of Clinical Medicine, Lund University, c/o Cognitive Medicine, University Hospital, 221 85 Lund, SwedenJuan Pablo Gambini, Faculty of Medicine and Faculty of Science, University of the Republic, Montevideo, UruguayLars Lannfelt, Department of Public Health and Caring Sciences/Geriatrics, Uppsala University, Uppsala Science Park, 751 85 Uppsala, SwedenBengt Långström, Departments of Biochemistr...

Detection of cerebral microbleeds with quantitative susceptibility mapping in the ArcAbeta mouse model of cerebral amyloidosis

Journal of Cerebral Blood Flow — Tue, 16 Aug 2011 23:00:00 +0100

Authors: Jan Klohs, Andreas Deistung, Ferdinand Schweser, Joanes Grandjean, Marco Dominietto, Conny Waschkies, Roger M Nitsch, Irene Knuesel, Jürgen R Reichenbach & Markus Rudin (Source: Journal of Cerebral Blood Flow)

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Complementarily of urine analysis and serum free light chain assay for assessing response treatment response: Illustrated by three case examples.

International Journal of Clinical Chemistry — Mon, 15 Aug 2011 23:00:00 +0100

CONCLUSION: The results from these 3 cases suggest that as the FLC concentration drops, the serum FLC results may become more ambiguous. These results are consistent with guidelines cautioning about conclusions drawn from the serum FLC assay alone. Although more study is needed, the examples presented here illustrate that traditional urine IFE appear to adds important information regarding potential complete remissions and remains an important complementary assay to the serum FLC assay. PMID: 21864518 [PubMed - as supplied by publisher] (Source: International Journal of Clinical Chemistry)

d-Ribose glycates β(2)-microglobulin to form aggregates with high cytotoxicity through a ROS-mediated pathway.

Chemico-Biological Interactions — Mon, 15 Aug 2011 23:00:00 +0100

Authors: Kong FL, Cheng W, Chen J, Liang Y Abstract β(2)-Microglobulin (β(2)M) modified with advanced glycation end products (AGEs) is a major component of the amyloid deposits in hemodialysis-associated amyloidosis (HAA). However, the effect of glycation on the misfolding and aggregation of β(2)M has not been studied so far. Here we examine the molecular mechanism of aggregate formation of HAA-related ribosylated β(2)M in vitro. We find that the glycating agent d-ribose interacts with human β(2)M to generate AGEs that form aggregates in a time-dependent manner. Ribosylated β(2)M molecules are highly oligomerized compared with unglycated β(2)M, and have granular morphology. Furthermore, such ribosylated β(2)M aggregates show significant cytotoxicity to both human SH-SY5Y ne...

Influence of Janus Kinase Inhibition on Interleukin 6-mediated Induction of Acute-phase Serum Amyloid A in Rheumatoid Synovium.

J Rheumatol — Sun, 14 Aug 2011 23:00:00 +0100

CONCLUSION: Our data indicated that CP690,550 blocked IL-6-induced JAK2/STAT3 activation, as well as the induction of A-SAA. Inhibition of IL-6-mediated proinflammatory signaling pathways by CP690,550 may represent a new antiinflammatory therapeutic strategy for RA and AA amyloidosis. PMID: 21844139 [PubMed - as supplied by publisher] (Source: J Rheumatol)

Lenalidomide-induced purpuric eruption: A new adverse cutaneous reaction

Journal of the American Academy of Dermatology — Fri, 12 Aug 2011 16:59:45 +0100

We report a purpuric drug eruption in a patient with primary systemic amyloidosis receiving lenalidomide therapy. (Source: Journal of the American Academy of Dermatology)