Pathological case of the month. Cholesterol granuloma as a cause of fever of unknown origin.
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Biomedical subjects
Publications and source records attributed to S Lew.
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The leukocyte integrin receptor, alpha 4 beta 7, and the mucosal addressin cell adhesion molecule-1 (MAdCAM-1) are postulated to be important in regulating lymphocyte trafficking to normal intestine. Here we provide the first description of MAdCAM-1 expression in inflamed intestine. Using mouse models of experimentally induced colitis, we show a concordant increase in MAdCAM-1 expression associated with increased cellular infiltrates in areas of intestinal inflammation. To understand more of the molecular nature of the interactions between MAdCAM-1 and its leukocyte ligand, the alpha 4 beta 7 integrin receptor, we have analyzed the structural and functional properties of chimeric recombinant MAdCAM-1 proteins in vitro. Using site-directed mutagenesis and molecular modeling, we demarcate the alpha 4 beta 7 binding motif as three linear residues within the C-D loop in the first domain of MAdCAM-1. Mutation of residue L40, D41, or T42 in the first domain completely abrogates alpha 4 beta 7+ cell binding and cellular activation. Mutagenesis of other residues in the first domain do not impact these functions. We have modeled peptides based on the predicted structure of the alpha 4 beta 7 integrin binding motif on MAdCAM-1 and are able to show specific and selective blocking of cell binding. These observations suggest that the amino acid residues LDT on MAdCAM-1 play a role in the interaction with alpha 4 beta 7 in cell adherence and cell activation.
OBJECTIVES: The incidence of AIDS is increasing at a higher rate among homosexual Asian and Pacific Islanders (API) than white homosexual men in the United States. The number of homosexual API men engaging in unsafe sex is increasing at an alarming rate. HIV risk reduction is urgently needed in this population. SUBJECTS AND METHODS: We developed and evaluated culturally appropriate brief group counseling with 329 self-identified homosexual API recruited in San Francisco between 1992 and 1994. Participants were randomized into a single, 3-h skills training group or a wait-list control group. The intervention consisted of four components: (1) development of positive self-identity and social support, (2) safer sex education, (3) eroticizing safer sex, and (4) negotiating safer sex. Data were collected at baseline and 3 months after the intervention. RESULTS: Significant reductions in number of sexual partners were observed among all treatment subjects, regardless of ethnicity (P = 0.003). Treatment decreased the number of partners reported at 3-month follow-up by 46% [95% confidence interval (CI), 28-77]. Chinese and Filipino men further benefited from the intervention: treatment subjects from these two ethnic groups reduced unprotected anal intercourse at follow-up by more than half when compared to their counterparts (odds ratio = 0.41; 95% CI, 0.19-0.89; P = 0.024). CONCLUSIONS: We demonstrated the efficacy of brief group counseling in reducing HIV risk among homosexual API. Cities with significant API populations should adopt culturally tailored skills training as part of HIV prevention strategies for this group of homosexual men.
Chronic graft versus host disease (cGVHD) across minor histocompatibility barriers is associated with the development of cutaneous fibrosis, disappearance of mast cells and immunosuppression. The idea, which has been the basis of our previous and present studies, is that fibroblasts are not only a target for modulation in cGVHD, but also have effector roles in this condition. In the present study we investigated the production of prostaglandin E2 (PGE2) and of collagen by cultured dermal fibroblasts obtained from cGVHD and control mice. Early in the development of the disease (Day 8) cGVHD fibroblasts generated constitutively more PGE2 (3-fold) than did control fibroblasts. Thereafter, PGE2 production declined to near normal levels by Day 20 post cGVHD induction. On the other hand, at this time point cGVHD fibroblasts displayed an enhanced synthesis of collagen as compared to the control fibroblasts and to earlier time points. Therefore, PGE2 synthesis appears to inversely correlate with collagen synthesis by cGVHD fibroblasts. We propose that fibroblasts may contribute to the development of immunosuppression, which characterizes the early phase of cGVHD.
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In an attempt to reduce the number of breast biopsies done for benign breast disease in patients with breast lumps, we evaluated prospectively the sensitivity and specificity of the combination of three diagnostic modalities: clinical examination, mammography, and fine-needle aspiration cytologic examination (FNA). A total of 234 patients with a breast mass had a physical examination, a mammogram, and FNA, and were listed as malignant/suspicious or benign. All patients underwent a subsequent biopsy: 110 were found to have breast cancer, and 124 had a benign lesion. The sensitivity and specificity of the individual tests were as follows: 89% and 73%, respectively, for mammographic examination; 93% and 97% for FNA cytologic examination; and 89% and 60% for physical examination. For the combined triad of tests, the sensitivity was 100% and specificity 57%. All patients who had breast cancer had positive findings for malignancy in one or more of the diagnostic tests, i.e., 100% sensitively. All patients who had negative findings for malignancy in all three diagnostic tests had benign lesions, i.e., a negative predictive value of 100%. We conclude that breast masses can be diagnosed with a high degree of accuracy by combined physical, mammographic, and fine-needle aspiration cytologic examination. Patients in whom physical examination, mammography, and FNA were negative for malignancy can be safely observed, obviating the need for an open biopsy.
We present the first case of ovarian endometrioid carcinoma and endometriosis in a postmenopausal patient who was treated with tamoxifen for breast cancer. The association with prolonged unopposed estrogen-like stimulation with tamoxifen as a possible factor in the development of ovarian endometrioid carcinoma is discussed.
We used a computer-assisted morphometry approach to analyze quantitatively the process of cytoplasmic granule formation in mouse pancreatic acinar cells stimulated with pilocarpine to induce secretion. Our findings suggest that each condensing vacuole/immature granule of pancreatic acinar cells is formed by the progressive aggregation of 106 to 128 "unit progranules" of narrowly fixed volume, define a range of 7.7 to 9.2 for the factor of volume condensation between the largest immature granules and the mature unit granule, and predict that the formation of a single mature unit granule by the aggregation and fusion of unit progranules involves a net reduction of at least 95% in the amount of membrane surface area associated with these structures.
Extension of Wilms' tumor into the renal vein and vena cava complicates the operative treatment of a small but significant number of patients. Two children presented with Wilms' tumor and intracaval tumor extension. After biopsy, both children were given chemotherapy. In one case the tumor completely disappeared from the vena cava, and in the other the tumor regressed substantially, and proximal control became possible at the level of the infrahepatic vena cava. Both children then had an uneventful nephrectomy that was greatly simplified. We conclude that preoperative chemotherapy can induce resolution of intravascular tumor, and may be a useful option in cases of extension of Wilms' tumor into the vena cava.
Urea kinetic modeling depends critically on the parameters of the model used. When urea is removed during hemodialysis, the kinetic model is quite complex. This experiment describes for the first time the use of injected stable isotope-labeled urea to define kinetics in ESRD patients and compares the magnitude of the two urea compartments in these patients with those of control subjects. Such an experimental approach provides the kinetic data in the most direct manner. A gas chromatograph/mass spectrometer-based assay provided quantitation to as little as 0.2 mol% excess urea. The rapidly equilibrating fraction of the two urea compartments is quantified as 41.2% in ESRD patients and 33.4% in controls (P = 0.24). The rest is in a more slowly equilibrating pool. The urea clearances between these two compartments were near 1 L/min for both sets of subjects. The elimination of urea was due to the metabolic removal of the 15N label in both groups of subjects as well as renal elimination in the controls. The nearly threefold larger clearance (Cl) of labeled urea removal in controls (Cl = 74.6 mL/min) than in ESRD patients (Cl = 25.4 mL/min; P = 0.015) shows the extent to which renal clearance is more important than metabolism. These direct analyses of the fractional volumes and intercompartmental clearances for urea agree closely with previous measurements during high-efficiency hemodialysis and indicate that ESRD patients do not differ significantly from control subjects in these parameters.
We describe a rare case of ectopic placental tissue, presenting as a vaginal tumor during normal intra-uterine pregnancy. Its clinicopathological features, and its possible relation to placental site trophoblastic tumors are discussed. To the best of our knowledge, this is the first case to be reported in the English literature of such a lesion occurring at this site.
Ectopic gastric mucosa in the small bowel not associated with Meckel's diverticulum, is rare. Most of the few cases found in the literature are symptomatic and complicated. We report a case of a three month-old baby, the youngest patient reported thus far. He had ectopic gastric mucosa in a polypoid lesion of the mid-ileum, which caused ileo-ileal intussusception.
A blue naevus of the prostate in an 80-year-old patient is presented, including electronmicroscopical examination and the demonstration of S-100 protein positivity. Cells expressing S-100 protein were sought in prostates of infants, young adults and elderly patients with hyperplasia and carcinoma. Positive staining was found in stromal cells, but the number diminished with age and disease. These findings could explain the rarity of blue naevus and the virtual absence of primary malignant melanoma in the prostate.
A 5 1/2-year-old Sephardic Jewish girl, born of consanguineous parents, is described. She has short stature, microcephaly, conductive hearing loss, skin mastocytosis and microtia. Since this constellation of findings has not been reported previously, we think that these findings represent a new congenital malformation, most probably of genetic etiology.
A retrospective study of eight patients who had suffered from malignant melanoma in the anorectal region was carried out. The initial presentation, histological findings, treatment, and survival are described. Mean survival was 18 months; however, one patient survived 147 months after initial diagnosis. An inverse correlation was noted between depth of tumor penetration and the number of giant multinucleated cells. No correlation was found between survival and histological findings or therapy regimen.
We report a case of an elderly female with a history of long-standing urinary tract infection, who developed sudden macroscopic hematuria. A renal clear-cell carcinoma with diffuse pyelonephritis and malakoplakia was discovered at nephrectomy. This is the first neoplasia of the kidney associated with malakoplakia ever published.
The cases of five patients (7 knees) who had villous lipomatous proliferation of the synovial tissue (lipoma arborescens) are reported. The longest duration of symptoms was thirty years. Six of the seven knees were treated by synovectomy. The length of follow-up ranged from two to eleven years, and six knees were followed for five years or more. The patients who were treated by synovectomy had complete healing of the synovial lesion, but the osteoarthritis tended to progress, especially in patients who had long-standing symptoms. Because of the clinical, macroscopic, and microscopic features of this rare disease, we suggest discarding the name lipoma arborescens, which implies that the lesion is a neoplasm, and using the more descriptive term of villous lipomatous proliferation of the synovial membrane.
A 36-year-old woman required laparotomy early in the puerperium after a normal delivery because of the presence of a large abdominal cyst. At laparotomy, a large mucinous cystadenoma was found attached to the root of the ileal mesentery; the ovaries were normal. This is the third case of mesenteric cyst published in association with pregnancy, but the first with a mucinous pattern. Pathologic aspects, possible complications, and treatment are discussed.