Two transthyretin variants (TTR Ala-49 and TTR Gln-89) in two Sicilian kindreds with hereditary amyloidosis.

We report the biochemical and molecular characterization of two new transthyretin (TTR) variants in two Italian families with hereditary amyloidosis. Both families presented neuropathy and cardiomyopathy but they differ in other clinical features. These TTR variants were previously detected by isoelectric focusing (IEF); one is a neutral TTR variant and the other one is basic. By protein and DNA analysis the neutral variant was found to have a substitution of an alanine for a threonine residue at position 49 (TTR Ala-49) of the polypeptide chain. The basic variant has a glutamine residue replacing glutamate at position 89 (TTR Gln-89).     

AL amyloidosis mimicking a preferentially autonomic chronic Guillain-Barré syndrome

Summary We report a case history of a patient whose diagnosis of AL amyloidosis remained elusive until postmortem examination. Exhaustive autonomic neuropathy mimicking a chronic Guillain-Barr'e syndrome dominated the clinical picture. The problems in establishing the definitive diagnosis of AL amyloidosis even in the face of strong clinical evidence are discussed.Abbreviations PNP peripheral neuropathy - AL AL-amyloidosis     

淀粉样变肾病研究进展

淀粉样变是由一组累及器官,在治疗和预后等方面大不相同的特定蛋白质的致病性错误折叠引起的疾病.淀粉样物质肾小球沉积表现主要为蛋白尿、明显的肾病综合征和不同程度的肾功能不全.然而,肾小管间质的累及占大部分,特别是一些遗传性类型载脂蛋白A-I淀粉样变性表现为进行性肾功能降低,但没有明显蛋白尿出现.研究表明,激光显微切割联合质谱分析(LMD/MS)的应用可以明确前体蛋白进而分型,对淀粉样变性肾病的组织病理学特征及不同分型的临床表现和治疗方法进行总结具有重要意义.     

Localized insulin-derived amyloidosis in patients with diabetes mellitus: a case report

Three patients with insulin dependent type 1 diabetes mellitus and one with insulin dependent type 2 diabetes mellitus developed localized amyloid tumors at their general insulin injection sites. All 4 patients (two women and two men) were treated with modern recombinant human insulin or insulin analogues. In addition, 1 patient had used both recombinant and animal insulin. The amyloid tumors were resected and examined histologically using Congo red staining and immunohistochemistry. Insulin was found to be the major component of the amyloid tumors in all four patients. These 4 cases were diagnosed recently within a relatively short period of time, which leads to the conjecture that local insulin-derived amyloid tumors remain principally a differential diagnosis of skin tumors in insulin-dependent diabetic patients.     

Secondary intestinal amyloidosis presenting intractable hematochezia: a case report and literature review

Amyloidosis is characterized by an extracellular deposition of insoluble fibrils. Amyloid deposition caused various clinical symptoms associated with affected organs. Secondary amyloidosis without renal involvement and chronic inflammatory conditions is rarely reported. We experienced a case of secondary intestinal amyloidosis presented with recurrent hematochezia and abdominal pain in a 54-year-old male. Sigmoidoscopy and abdominal computed tomography (CT) presented ischemic colitis and necrosis of whole colon. On microscopically, pinkish amorphous materials were infiltrated in the lamina propria and the thickened submucosal vessel walls in colon. The apple-green birefringence with polarized light on Congo red stain was demonstrated in the lamina propria and submucosal vessel walls. The deposits were positive for amyloid A and κ and negative for λ. The echocardiography and cardiac MRI findings showed infiltratives cardiomyopathy involving amyloidosis. Despite of conservative treatment, ischemic colitis and hemorrhage were aggravated and the patient expired.     

Visceral organ involvement and extracellular matrix changes in β2-microglobulin amyloidosis – a comparative study with systemic AA and AL amyloidosis

 Patterns of amyloid distribution and extracellular matrix changes in the heart and gastrointestinal tract were compared among β₂-microglobulin (B2M), AA (secondary), and AL (primary and multiple myeloma-associated) amyloidosis cases. B2M amyloid was found to be mainly distributed in the small arterioles, venules, endocardium and muscularis propria of these organs, the deposits characteristically forming subendothelial nodular lesions in the vessels. A marked increase of chondroitin sulfate (CS) was consistently detected in B2M amyloid. Heparan sulfate (HS) also showed an increase in amyloid deposits, but with less reactivity than CS in the small arterioles or venules. Basement membrane structures stained positively for laminin and collagen type IV were replaced by negative amyloid deposits. In the AL cases, the muscularis propria of the gastrointestinal tract was involved in amyloid deposits, as seen for the B2M type, but the vascular amyloid deposits were localized in the media and adventitia of larger vessels. Immunoreactivity for HS was more intense than that for CS, and no increase in laminin or collagen type IV was observed. In the AA cases, amyloid deposits were distributed in the capillaries, small arterioles, interstitium of the myocardium and mucosa. Immunoreactivity for laminin and collagen type IV was marked, and more intense than that for HS and CS. Although the existence of a direct relationship between increase in extracellular matrix material and amyloidogenesis remains to be proven, the observed variation in extracellular matrix changes in the background of each type of amyloidosis may indicate different binding sites of the amyloid precursor proteins, resulting in the specific histological features and distribution. Received: 23 August 1996 / Accepted: 9 January 1997     

Complete bilateral transposition of femoral vessels: A rare case report

IntroductionAnomalies of the femoral vessels occur in only 0.02% of the population, most of them being asymptomatic. The study highlights the anomalies of femoral vessels in the femoral triangle and the importance of their recognition intra-operatively to prevent injuries.Materials & methodsHere we present a case of bilateral transposition of femoral vessels in the femoral triangle, which was detected during groin dissection in a case of carcinoma penis with inguinal lymph node metastasis.ObservationWe detected the anomalous transposition intra-operatively during groin dissection on the left side and the right sided anomaly postoperatively by CT angiography.ConclusionThe importance of this anomaly lies in procedures for which vascular access is need through the femoral vessels and groin surgeries like Trendelenburg operation for varicose veins where not appreciating these anomaly could lead to inadvertent vascular injury or bleeding.     

Plantar thermography is useful in the early diagnosis of diabetic neuropathy

OBJECTIVES:

This study evaluated plantar thermography sensitivity and specificity in diagnosing diabetic polyneuropathy using cardiac tests (heart rate variability) as a reference standard because autonomic small fibers are affected first by this disease.

METHODS:

Seventy-nine individuals between the ages of 19 and 79 years old (28 males) were evaluated and divided into three groups: control (n = 37), pre-diabetics (n = 13) and type 2 diabetics (n = 29). The plantar images were recorded at baseline and then minutes after a provocative maneuver (Cold Stress Test) using an infrared camera that is appropriate for clinical use. Two thermographic variables were studied: the thermal recovery index and the interdigital anisothermal technique. Heart rate variability was measured in a seven-test battery that included three spectral indexes (in the frequency domain) and four Ewing tests (the Valsalva maneuver, the orthostatic test, a deep breathing test, and the orthostatic hypotension test). Other classically recommended tests were applied, including electromyography (EMG), Michigan inventory, and a clinical interview that included a neurological physical examination.

RESULTS:

Among the diabetic patients, the interdigital anisothermal technique alone performed better than the thermal recovery index alone, with a better sensitivity (81.3%) and specificity (46.2%). For the pre-diabetic patients, the three tests performed equally well. None of the control subjects displayed abnormal interdigital anisothermal readouts or thermal recovery indices, which precluded the sensitivity estimation in this sample of subjects. However, the specificity (70.6%) was higher in this group.

CONCLUSION:

In this study, plantar thermography, which predominately considers the small and autonomic fibers that are commonly associated with a sub-clinical condition, proved useful in diagnosing diabetic neuropathy early. The interdigital anisothermal test, when used alone, performed best.     

Association light chain deposition disease (LCDD) and amyloidosis. One case

Up to now, light chain deposition disease (L.C.D.D.) and amyloidosis have been shown to occur in different individuals. A case of association is described in a 76 year old man with terminal renal failure and normal size kidneys. Percutaneous renal biopsy showed glomerular and peritubular fixation of labeled antikappa light chain serum. Stains for amyloidosis were positive in small vessels. Kappa free chains were found in both serum and urine and the bone marrow showed predominantly kappa-containing plasma cells. By electron microscopy both electron-dense granular deposits and amyloid like fibrils were found in the wall of arterioles and small arteries.     

Localized amyloidosis of the uterine cervix

Summary Localized amyloidosis of the uterine cervix was found in a 56-year-old woman. The firm enlarged cervix showed massive tumorous amyloid deposition. In the amyloid deposits there were foci of ossification and calcification. An infiltrate of multinucleated giant cells, histiocytes, lymphocytes, and plasma cells was seen adjacent to the amyloid deposits. Immunohistochemically, the amyloid reacted with antisera against A-lambda, amyloid protein of immunoglobulin lambda light chain origin. This indicated that the amyloid protein was of immunoglobulin origin in this rare case of localized amyloidosis of the uterine cervix.     

Genetically determined neuropathy (CMT 1A) accompanied by immune dysfunction: a case report

Peripheral Myelin Protein 22 (PMP22) is mostly expressed in Schwann cells where it is essential in the compaction of myelin. The duplication of the PMP22 gene results in a hereditary demyelinating neuropathy of the Charcot–Marie–Tooth type 1A (CMT1A). So far there are only a few case reports suggesting that dysimmune mechanisms may take part in the pathophysiology of this disease. We describe three siblings carrying the duplication of the PMP22 gene, with a significant reduction of serum immunoglobulin G levels in all three cases and sural nerve vasculitis in the two women, which supports the proposition, that immune dysfunction may accompany this disease in some cases.     

The sinoatrial node in familial amyloidosis with polyneuropathy

Summary The pathogenesis of disturbances of the initiation and conduction of the cardiac impulse in cardiac amyloidosis has been a matter of controversy. In this study, we have analyzed the histopathology of the sinoatrial node and the atrial myocardium in nine cases of familial amyloidosis with polyneuropathy. Our results indicate that in this disease, amyloid infiltration of the sinoatrial node and the atrial musculature per se may account for the electrophysiological disturbances of these regions.     

Diagnosis and classification of amyloidosis by an immuno-histological method

Following the recent classification of amyloidosis by the amyloid proteins involved, we decided to approach its tissue diagnosis and chemical classification by an immunohistological method. Post-mortem tissue specimens from various organs of patients with primary and secondary amyloidosis were examined by the immunoperoxidase technique with specific antibodies against proteins AL and AA which respectively characterize primary and secondary amyloidosis. The major advantage of this technique is that it can be applied to formalin fixed, paraffin embedded tissues. The immunoperoxidase technique proved to be extremely sensitive for the detection of amyloid deposits. Moreover, the deposited proteins could be clearly characterized as AL or AA by the specific anti-sera. We therefore believe that the immunooperoxidase technique is extremely useful for the early tissue diagnosis and chemical classification of amyloidosis.     

一个遗传性玻璃体淀粉样变性家系TTR基因的突变检测

目的 对1个遗传性玻璃体淀粉样变性家系进行致病基因分析.方法 采集该家系4个成员(包括临床确诊患者3例,无症状者1例)的外周静脉血,提取基因组DNA.PCR方法扩增TTR基因的4个外显子,产物直接测序进行基因突变检测,同时选择150名无亲缘关系的正常对照.结果 该家系的4例受检者中均检测到TTR基因第3外显子第103位密码子发生了G＞C(Gly103Arg)杂合突变,而150名正常对照中未发现相同的突变.结论 TTR基因Gly103Arg杂合突变可能与该家系遗传性玻璃体淀粉样变性的发病有关.     

中国南方人股骨干形态特征及其对股骨外翻角的影响

目的　基于中国南方人群股骨外翻角（femoral valgus angle,FVA）和股骨弯曲角（femoral bending angel,FBA）的定量分析,探究下肢旋转体位改变对不同形态股骨的FVA测量值的影响,提高膝关节置换手术的安全性。 方法　收集我院75位（113侧）无膝关节骨性关节炎患者的下肢全长CTA扫描数据。通过三维重建和定位,测量FBA和FVA。根据FBA分为4组：严重内翻畸形组：FBA＞4°;轻度内翻畸形组：1°＜FBA≤4°;无畸形组：-1°≤FBA＜1°;外翻畸形组：FBA≤-1°,对比各组的FVA,确定FBA与FVA之间的相关性。应用三维模拟技术,以股骨后髁连线与X轴平行时作为股骨中立位,每10°为一个档位,调节股骨轴向旋转角度从内旋20°至外旋40°,记录FBA与FVA测量值,并作相关统计分析。 结果　总体FVA平均值为（5.3±1.4）°,4组FVA分别为（7.2±1.1）°,（3.4±0.8）°,（5.6±0.87）°及（4.7±1.0）°,各组间存在统计学差异（P<0.05）;FBA与FVA存在显著相关性（R2＝0.6,P<0.001）。下肢从内旋20°至外旋40°,各组的FVA呈增大趋势,各组间无统计学差异（P>0.05）。 结论　股骨干形态存在内翻或外翻畸形时,直接影响股骨外翻角的大小。股骨外翻角的测量需综合考虑股骨干形态及下肢旋转体位的影响。     

股骨颈骨折患者并发股骨头坏死的预后相关影响因素

创伤引发的股骨颈骨折是临床上常见的骨科疾病之一,而其后续发生的以股骨头缺血坏死为代表的并发症是导致患者出现下肢运动功能障碍的主要原因之一。目前对于创伤后股骨颈骨折具体的损伤及修复机制仍不甚明了,因此研究股骨颈骨折后患者身体的各项指标及临床上针对的治疗措施对预后产生的影响,可为预测股骨颈骨折患者未来的预后打好基础,并为采取相应的干预手段提供思路。目前主要认为创伤后股骨颈血供不足和相关炎性重建反应是创伤性股骨头坏死的主要作用机制,而作用于相关机制的因素则被认为是其可能的危险因素。本文整理了近年来对于股骨颈骨折后续发生坏死相关影响因素的报道。学界主要认为受伤原因、Garden分型等骨折分型方式、内固定方式及复位质量等因素被认为是导致预后不良的可能危险因素。     

Skin deposits in hereditary cystatin C amyloidosis

Summary Clinically normal skin from 47 individuals aged 9–70 years was investigated. Cystatin C amyloid deposits were found in various locations of the skin by light and/or electron microscopy, in all 12 patients with a clinical history of hereditary cystatin C amyloidosis (HCCA). Six asymptomatic individuals, who had the Alu 1 restriction fragment length polymorphism (RFLP) marker reported to cosegregate with the disease, also had cystatin C amyloid deposits in the skin. Three asymptomatic individuals (age 17–46) belonging to the HCCA families were without amyloid in the skin but had Alu 1 RFLP marker. Skin from 12 individuals who served as controls and skin from 14 close relatives of the patients was negative for amyloid. Punch biopsy of the skin is a simple procedure which is of value for the diagnosis of HCCA, even before the appearance of clinical symptoms. This method might also be of use in following progression of the disease.