Fibrillary renal deposits and nephritis.

Fibrillary renal deposits and nephritis. The authors have studied 8 patients whose glomeruli contain abundant fibrils in their mesangial matrix and basement membranes. Although the location of these fibrils is very similar to that of amyloid, they are about twice the size of amyloid fibrils, averaging 20 nm in width, and fail to react as amyloid does with special stains. Immunofluorescence-microscopic studies are usually positive with antiserums to IgG, often IgM, and in some cases IgA, and also kappa and lambda light chains, C3, and C4. The fibrils are associated with diffuse mesangial widening and increased mesangial matrix strands. Although peripheral glomerular capillary walls appear to be spared initially, their eventual involvement leads to glomerular capillary collapse and glomerular obsolescence. Crescent formation occurred in 5 cases, focally in 3 and diffusely in 2. Tubular basement membrane involvement was seen in 1 case. These patients exhibit hematuria, and proteinuria, and often hypertension and renal insufficiency. Proteinuria was in the nephrotic range in 3 patients in whom involvement of glomerular capillary basement membranes was extensive. Unless electron microscopy is applied to renal biopsies, these cases may be considered to represent mesangiocapillary or rapidly progressive glomerulonephritis, or amyloidosis. The nature of these fibrils is as yet not determined. It is likely that they have been called "atypical amyloidosis" in the past.     

Insular carcinoma of thyroid--a case report

Insular carcinoma of thyroid (ICT) is a rare tumor, which accounts for 4-6% of thyroid malignancies. ICT arising from follicular cells of thyroid shows a characteristic insular growth pattern characterized by solid nests of tumor cells separated by vessels. A 52-year-old female presented with a huge swelling in midline of the neck with retrosternal extension. The patient was euthyroid. Near total thyroidectomy was done. Grossly, the tumour was involving both the lobes and isthmus of thyroid. Microscopic examination revealed features of insular carcinoma. On immunohistochemistry, tumour cells were positive for thyroglobulin and negative for calcitonin.     

TPA (12-O-tetradecanoyl-phorbol-13-acetate) activation and differentiation of human peripheral B lymphocytes

The effect of the tumour-promoting phorbol ester TPA (12-O-tetradecanoyl-phorbol-13-acetate) on normal human peripheral blood and tonsil B lymphocytes was investigated. A strong DNA-synthesis response with the maximum at day 4 was detected. This response was, however, inhibited by increasing concentrations of serum in the medium. The membrane Ig expression was changed with a rapid decrease in IgD expression and a slower decrease in IgM and IgG expression. TPA-induced Ig secretion was detected in 12 out of 22 tested donors and the response was found to be independent of T cells and macrophages. The expression of four monoclonal antibody-detected B cell activation and differentiation markers, B1, B2, LB1 and BB1, was followed. The results indicate activation and differentiation of the B cells.     

Gelatinous transformation of bone marrow: a study of 43 cases

Gelatinous marrow transformation (GMT) is an uncommon and poorly recognized condition characterized by deposition of seromucinous gelatinous material in the bone marrow stroma. Forty-three cases of GMT were studied in a period of 4 years. There was male preponderance. Fourteen cases were in pediatric age group (less than 12 years). Majority of patients had a preceding history of anorexia, malnutrition and chronic debility. All the patients had anemia. Bone marrow biopsy revealed focal or diffuse GMT. Bone marrow aspirate showed metachromatic dense mucoid material with a few entrapped hematopoietic cells on Giemsa staining. The gelatinous material stained with alcian blue at pH 2.5.     

Case report: glomus tumor of the colon

Glomus tumors are tumors of pericytic origin and are usually found in the distal extremities. Glomus tumors have rarely been reported in viscera. The authors report a glomus tumor of the colon that caused rectal bleeding in a 40-yr-old man and was biopsied and excised endoscopically. The histology and immunohistochemical profile of the tumor are described and the literature on visceral glomus tumors is reviewed.     

Autonomic nerve function in children and adolescents with insulin-dependent diabetes mellitus.

Autonomic nerve function was assessed in 67 insulin-dependent diabetic children and adolescents and in 30 control subjects of the same age. The heart rate and blood pressure reactions to a deep breathing test (E/I ratio) and a tilt table test (acceleration and brake indices) were used. The E/I ratio, 1.54 +/- 0.21, and the acceleration index, 25 +/- 7.7, in the diabetic children were not significantly different from those of the control children, 1.51 +/- 0.16 and 24 +/- 7.5, respectively. Neither was any difference observed between the mean brake index values; 24.3 +/- 14.6 vs 23.5 +/- 7.5. However, the variance of the brake index in diabetic children was significantly higher than in control children (P less than 0.005). The brake index was negatively correlated to age in the healthy control children (r = -0.48, P less than 0.1). The acceleration index, but not the E/I ratio, also tended to be age related (r = -0.32, P less than 0.01 NS). No correlation was observed between sex, glycaemic control or duration of diabetes and the autonomic nerve function. Neither were severe hypoglycaemic episodes in diabetic children related to the autonomic nerve function. It is concluded that autonomic neuropathy is uncommon in diabetic children and adolescents and that age-related index values should be used when autonomic nerve function is evaluated in children of different ages.     

Harnessing the potential of dystrophin‐related proteins for ameliorating Duchenne’s muscular dystrophy

Duchenne’s muscular dystrophy (DMD) is a fatal disease caused by mutations in the DMD gene that lead to quantitative and qualitative disturbances in dystrophin expression. Dystrophin is a member of the spectrin superfamily of proteins. Dystrophin itself is closely related to three proteins that constitute a family of dystrophin‐related proteins (DRPs): the chromosome 6‐encoded DRP or utrophin, the chromosome‐X encoded, DRP2 and the chromosome‐18 encoded, dystrobrevin. These proteins share sequence similarity and functional motifs with dystrophin. Current attempts at somatic gene therapy of DMD face numerous technical problems. An alternative strategy for DMD therapy, that circumvents many of these problems, has arisen from the demonstration that the DRP utrophin can functionally substitute for the missing dystrophin and its overexpression can rescue dystrophin‐deficient muscle. Currently, a promising avenue of research consists of identifying molecules that would increase the expression of utrophin and the delivery of these molecules to dystrophin‐deficient tissues as a means of DMD therapy. In this review, we will focus on DRPs from the perspective of strategies and issues related to upregulating utrophin expression for DMD therapy. Additionally, we will address the techniques used for anatomical, biochemical and physiological evaluation of the potential benefits of this and other forms of DMD therapy in dystrophin‐deficient animal models.     

Prophylactic mastectomy: pathologic findings in high-risk patients

BACKGROUND: According to recently published data, prophylactic mastectomy (PM) appears to prevent about 90% of the expected malignant neoplasms in women with a family history of breast cancer. OBJECTIVES: To identify the frequency of high-risk lesions in PM specimens and to determine occurrence of any new primary breast cancer following PM. DESIGN: We performed a retrospective study of women undergoing unilateral or bilateral PM. Medical charts and pathologic findings of 35 patients who underwent bilateral mastectomies at University Hospital, Syracuse, NY, from 1989 to 1996 were reviewed. Patients with biopsy-proven bilateral breast cancer were excluded. Patients were divided into 3 groups: (A) positive family history and no known breast cancer (n = 9), (B) positive family history and contralateral neoplasia (n = 13), and (C) negative family history and contralateral neoplasia (n = 13). These findings were compared with those found in reduction mammoplasty specimens from 10 women at standard risk of breast cancer. RESULTS: The mean age of the control group of women undergoing reduction mammoplasty was 38 years. The pathologic specimens demonstrated no significant pathologic findings in 9 and fibrocystic change in 1. In group A, the mean number of affected relatives was 3.1, and the mean age was 38 years. Two of these 9 women had atypical duct hyperplasia and 1 had atypical lobular hyperplasia in their breasts (ie, 33% with high-risk pathologic findings). Of the 13 group B women (mean age, 46.6 years; mean of 2.5 affected relatives and unilateral breast cancer), the contralateral PM specimen contained duct carcinoma in situ in one and invasive ductal cancer in a second (15% with occult malignant neoplasms). In 13 group C patients (mean age, 47.1 years), 3 (23.1%) of the contralateral PM specimens displayed atypical duct hyperplasia or atypical lobular hyperplasia. At a mean follow-up of 4.8 years, there have been no new breast malignant neoplasms in these 45 women. CONCLUSIONS: The occurrence of unilateral cancer in patients with family history of breast cancer is associated with a 15.4% probability of simultaneous occult malignant neoplasms in the contralateral breast. Patients with a strong family history but no evidence of breast cancer have a substantially similar rate of proliferative disease in their PM specimens as those women who have unilateral cancer but no significant family history.     

Caregiver perceptions of psychotropic medication in residential facilities

Direct caregivers (designated as "psychopaedic nurses" in New Zealand) in two public residential facilities were surveyed regarding their perceptions, opinions, and knowledge of psychotropic drugs. Of 276 individuals contacted, 227 (82%) returned usable questionnaires. The results indicated that unit supervisors (charge nurses) and unit doctors were perceived as wielding most influence on decisions regarding psychotropic drugs, whereas caregivers based outside residential units were seen as having little influence. Aggressive/destructive behavior and, to a smaller extent, self-injurious behavior were seen as the most likely problem behaviors to lead to medication use. Subjective measures were generally favored for assessing drug effects although, in a hypothetical "ideal" situation, nurses gave increasing priority to more objective indices. Endorsement of behavior modification as an alternative to pharmacotherapy was generally high. A large majority of these caregivers (85%) expressed dissatisfaction with their training concerning psychotropic drugs. Finally, data were presented on drug topics about which respondents wanted to learn more and about changes they wished to see instated in their facilities. Our principal conclusion was that these data indicate a need for more education on a variety of social, pharmacological, and behavioral issues as they relate to medication use.