Foam cell nephropathy in heterozygous female with Fabry's disease

We describe the clinical and pathological characteristics of a 49 year-old heterozygous female carrier of Anderson-Fabry's disease. Light microscopy and ultrastructural study of a renal biopsy showed the presence of foam cell nephropathy and galactosylceramide deposits affecting podocytes, the parietal epithelium of Bowman's capsule and the distal tubular cells, endothelial cells and medullary interstitial elements. Retrospectively, the presence of storage disease was confirmed in a hysterectomy specimen obtained two years previously. Our observation shows that heterozygotes for this disorder can not only carry and transmit the disease but may also develop pathological deposits in various organs. A renal biopsy from these carriers allows precise identification of the disease, facilitates adequate genetic counseling and gives the option of enzyme replacement therapy in patients who have pathological deposits.     

New insights in cardiac structural changes in patients with Fabry's disease

BACKGROUND: Fabry's disease is an X-linked recessive genetic deficiency of the enzyme alpha-galactosidase leading to the pathologic intracellular deposition of neutral glycosphingolipids. Although cardiac involvement is frequent, there is controversy regarding the character of the associated left ventricular (LV) changes and the severity of valvular involvement. METHODS: Clinical evaluation (disease severity scaling, laboratory tests, and echocardiography) was performed in 13 hemizygous men (mean age 39 +/- 10 years) and 17 heterozygous women (mean age 35 +/- 19 years). RESULTS: LV hypertrophy (LVH) was frequent in subjects older than 30 years, more often in men (61%) than in women (18%, P <.001). The degree of LVH was independently associated with age and the logarithm of alpha-galactosidase activity (r(2) = 0.70, P <.001). The predominant LV geometric patterns were concentric LVH and remodeling, both present in 11 subjects (36%). Three patients had an asymmetric septal hypertrophy mimicking hypertrophic cardiomyopathy. In most subjects with LVH, the systolic function was normal and severe diastolic dysfunction (restrictive pattern) was not noted. Minor structural abnormalities of the mitral valve were found in 17 subjects (57%). The aortic valve was affected in 14 patients (47%). Valvular abnormalities were frequently accompanied by regurgitation of minor to mild degree. The presence of LVH or valvular changes was associated with increased disease severity. CONCLUSIONS: Echocardiographically detectable cardiac involvement is frequent with Fabry's disease, particularly in older subjects, and more pronounced in affected hemizygous men than in heterozygous women. LVH is frequently observed but usually not associated with significant systolic or restrictive diastolic dysfunction. Concentric LVH and remodeling appear to be the major manifestations of LV structural alteration. The frequently noted valvular abnormalities were not associated with a significant degree of regurgitation. Valvular and especially LV structural changes may serve as a useful marker of disease severity.     

Porphyria cutanea tarda-like skin changes in chronic hemodialysis patients

Porphyria cutanea tarda-like changes of the skin are described in two male patients undergoing chronic haemodialysis. The protoporphyrin values of the erythrocytes were somewhat higher than normal. Despite the same conditions of dialysis and the same medication in the subsequent two years of control no recidivations could be registered. The etiopathogenesis is not clarified.     

Evolution of changes in carbon monoxide transfer factor in men with chronic obstructive pulmonary disease

Progression of chronic obstructive pulmonary disease (COPD) has been studied predominantly by following change in forced expiratory volume in 1s (FEV1) which reflects both primary airway disease and associated alveolar disease. Carbon monoxide transfer (Tlco) (the product of the transfer coefficient Kco and alveolar volume Va) is the only simple, widely available test of alveolar function, but few studies have followed long-term changes in an individual. Seventeen middle-aged men with moderate chronic airflow obstruction (mean FEV1 56% of predicted values) were observed with yearly measurements of FEV1, Tlco and Kco over a mean of 18.9 yr. At the end of follow-up FEV1 had fallen to 29% of predicted values. Va, measured by single breath dilution, fell in each man. Kco at recruitment ranged from 41% to 110% predicted and remained >75% predicted in eight men at the end of follow-up supporting a phenotype of COPD with predominant airway disease and little emphysema. Fall in FEV1 was faster (2.03% predicted FEV1/yr) in seven men with low initial Kco<75% pred. than in men with initial Kco>75% pred. (1.14% predicted FEV1/yr, P=0.006). Repeated measurements of CO transfer in an individual should increase the present poor knowledge of the contribution of alveolar disease to the progression of chronic airflow obstruction.     

Echocardiographic changes in patients with polycystic nephropathy]

We have studied with the echocardiography M-Mode, 2-D, Doppler three groups of 15 subjects for testing the presence of cardiac abnormalities probably related to primary collagen defect in patients with autosomal dominant polycystic kidney disease (ADPKD) The first group was made up of patients with ADPKD and normal renal function, the second of patients with ADPKD in hemodialysis (HD), the last one of patients in HD for other renal disease. In the first group we found no cardiovascular abnormalities while we found an increased incidence of valvular disease (p = 0.016) in patients with ADPKD in HD and an increased incidence in valvular disease (p = 0.016) and left atrial dilatation (p = 0.006) in patients in HD for different renal disease. When we estimated the cases on the ground of dialytic age uncorrelated with the initial renal disease, only the incidence of valvular calcifications was increased in patients on HD more than 3 years (p = 0.034). In our group of patients the echocardiographic abnormalities seem to be related more to uremic cardiomyopathy even if we cannot deny the existence of primary cardiac disease in patients with ADPKD.     

The usefulness of skin culture in the diagnosis of chronic meningococcaemia

Abstract. Texereau M, Roblot E', Dumars A, Grignon B, Becq-Giraudon B (Hbpital la Miktrie, Centre Hospitalier Universitaire, Poitiers, Cedex, France). The usefulness of skin culture in the diagnosis of chronic meningococcaemia (Case Report)
We deal with the second reported case of chronic meningococcaemia in which the culture of skin biopmeningococcaemia in which the culture of skin biopa history of recurrent fever and rash. Laboratory studies revealed an inflammatory syndrome. Serologic tests as well as blood culture tests were negative. The histological examination of skin lesions revealed a perivascular infiltrate in the dermis without any picture of leukocytoclastic vasculitis. A culture of skin specimen tested positive for Neisseria meningitidis (N. meningitidis). After a week of antibiotic treatment, the patient recovered with no recurrence of either fever or rash over a two year period.     

Tubular nephropathy in chronic polyarthritis

Disc electrophoresis and N-acetyl-beta-D-glucosaminidase (NAG) of urine are sensitive indicators of renal damage. In 28 from 50 patients with definite rheumatoid arthritis, a tubular proteinuria and a high urinary NAG-excretion and in 10 other patients one of these pathological parameters were detected. A positive correlation with disease activity was noted. Both methods are able to demonstrate a rheumatoid involvement of renal function.     

膜性肾病肾活检组织中nephrin和podocin表达改变及其意义

目的:检测膜性肾病(MN)患者肾活检组织中nephrin、podocin的表达和分布,分析MN蛋白尿与nephrin和podocin表达改变的关系,探讨肾小球足细胞裂孔隔膜蛋白nephrin和podocin在MN蛋白尿发生中的作用. 方法:选取2005年1月至2008年1月经肾穿刺活检病理确诊为II、III期MN的患者22例,其中肾病综合征组15例(MN-A组),非肾病综合征组7例(MN-B组),临床上排除系统性红斑狼疮、乙肝相关性肾病、糖尿病肾病以及肿瘤等继发性肾脏疾病;另取5例因肾脏肿瘤行一侧肾切除的远端相对正常肾脏组织作为对照(对照组).收集并分析患者的主要临床表现、内生肌酐清除率(Ccr)、尿常规、24h尿蛋白定量、血清白蛋白(Alb)、血脂等相关临床资料;按常规方法取肾组织制备3 μm厚石蜡切片,行HE、PAS、PASM、Masson染色普通光镜以及免疫组化(IgG、IgA、IgM、C3、C4、C1q)检查;各组肾组织行nephrin、podocin及IV型胶原α3链免疫荧光双套色染色,激光共聚焦显微镜下观察nephrin、podocin在两组MN及对照组肾组织中表达及分布的改变,以计算机图像分析系统进行半定量分析. 结果:22例MN病理分期分别为II期14例,III期8例;肾小球内免疫球蛋白及补体的沉积以IgG和C3为主,呈颗粒状沿毛细血管袢弥漫性分布.对照组肾组织免疫荧光染色可见nephrin和podocin沿肾小球毛细血管袢呈均匀连续线样分布;MN患者肾小球内nephrin与podocin表达皆明显减弱,免疫荧光强度降低,分布不均,部分区域有节段性缺失,部分由线状分布变成颗粒状分布,与对照组相比差异有统计学意义(P<0.05);MN-A组与MN-B组比较,MN-A组肾小球nephrin和podocin的平均表达量均低于MN-B组,差异有统计学意义(P<0.05),且尿蛋白量与nephrin或podocin表达呈负相关. 结论:MN患者肾小球内nephrin和podocin表达量均降低,分布形式亦发生改变,部分呈节段性缺失或不连续颗粒状分布,并与尿蛋白排泄量呈负相关,提示nephrin和podocin表达的减少及分布异常可能与蛋白尿发生及蛋白尿程度有关;但其损伤的始动因素仍需进一步探讨.     

Renal lesions in patients with Fabry's disease

Kidney involvement is one of the main manifestations of Fabry's disease. In the absence of enzyme replacement therapy, hemizygous males and some heterozygous females progress to end stage renal failure. In hemizygous males, diffuse glycolipid accumulation is observed in all glomerular and vascular cells whereas distal tubular cells are focally involved. In heterozygous females, the glycolipid storage is irregular in glomeruli and vessels, some cells being massively involved, others being normal. In both sexes, degenerative changes occur, linked to the necrosis of overloaded mesangial and vascular smooth muscle cells. Their progression leads to unspecific arteriopathy and glomerulosclerosis not prone to reverse under enzymotherapy. Kidney biopsy is useful for confirming the diagnosis if clinical presentation of Fabry's disease is atypical. Moreover, histological analysis of renal tissue allows to assess the severity of degenerative changes and to evaluate the beneficial impact of enzyme replacement therapy.     

慢性砷中毒患者皮肤过度角化的切除和病理改变

对１０２例皮损病人手术局限切除皮肤过度角化痛点、溃疡点，不但病灶清除，疼痛消失，局部功能恢复，而且预防恶变。其治愈率达８７．２％，总有效率达９６％。指出尽早、彻底地切除病灶组织是保证手术成功的关键。４４例手术组织病理显示：皮肤角化层增厚，棘层肥厚和表皮乳头样增生为主要病理变化，表皮下纤维增生次之，纤维间质粘液变性，炎症细胞浸润，组织萎缩均有存在。核异质现象和癌细胞的检出率各占６．８１％和４．５４％。     

Hypothalamo-pituitary gonadal axis in men with chronic hepatitis

BACKGROUND/AIMS: Hypothalamo-pituitary function of male patients with chronic active hepatitis was evaluated. The effects of interferon alpha therapy on hypothalamo-pituitary-gonadal axis were also investigated. METHODOLOGY: Twenty patients with chronic B and C hepatitis, and 10 healthy subjects were studied. Before and after treatment with IFN alpha, basal levels of FSH, and LH were obtained and all groups were evaluated with LH-RH stimulation test. RESULTS: Baseline hormone levels and FSH and LH responses to LH-RH stimulation test were similar in patients and controls. It was notable that the LH response was considerably greater than that of FSH and pretreatment FSH results in patients with HCV infection appeared earlier than those of patients with HBV infection. Following IFN alpha treatment, the results of LH-RH stimulation test were similar to those of controls but there were a delayed LH and FSH response to LH-RH stimulation test. CONCLUSIONS: Hypothalamic and/or gonadal hypogonadism is correlated with the degree of liver damage in cirrhosis. In patients with chronic hepatitis, which is characterized by lesser degree of liver damage than cirrhosis, HPG axis is not affected. IFN alpha, still in use for treatment of hepatitis, did not have any effect on HPG axis although it has many side effects.     

Streptococcal lymphadenitis in homosexual men with chronic lymphadenopathy

Lymphadenopathy is an important clinical problem in homosexual men. Over a period of 10 months, three homosexual patients were treated for chronic lymphadenopathy and spontaneous lymphadenitis of the inguinal lymph nodes. All patients presented with fever, chills, and rapidly enlarging inguinal masses. In each case, cultures showed group A beta-hemolytic streptococci. None of the patients had an obvious portal of entry for infection, and all had responses to penicillin and surgical drainage. Streptococcal lymphadenitis should be considered in any homosexual man with chronic lymphadenopathy in whom rapidly enlarging inguinal nodes develop.     

Radiological changes in men and women with ankylosing spondylitis.

The radiographic changes of ankylosing spondylitis were studied in 50 females and 82 males. There was a tendency for the males to have more severe arthritic changes in the sacroiliac joints than the females, but the difference did not reach statistical significance. Males significantly more often had radiological involvement of the lumbar spine. More restricted lumbar mobility, total spinal flexion, and chest expansion were found in males with x-ray changes in the lumbar spine than in males without such features. No such significant difference could be found in females. These findings may indicate a less severe disease as judged roentgenologically in females than in males. The correlations between restriction of chest and spinal mobility and x-ray changes were stronger in males.