Increased adhesion molecule expression in serosal fibroblasts isolated from patients with inflammatory bowel disease is secondary to inflammation

OBJECTIVE: To examine the expression of adhesion molecules by serosal and dermal fibroblasts in patients with inflammatory bowel disease. SUMMARY BACKGROUND DATA: The pathophysiologic process that leads to stricture formation in Crohn's disease (CD) is unknown. Serosal fibroblasts in these patients have an enhanced ability to contract collagen. This property may be reflected in fibroblast adhesion molecule expression, which in turn may be constitutive or secondary to the inflammatory process in patients with CD. METHODS: Fibroblasts were isolated from inflamed and macroscopically normal serosa of patients with CD or ulcerative colitis (UC) and from normal serosa of patients with colon cancer. Dermal fibroblasts were also isolated from the wound edge. Cell surface and whole cell expression of ICAM-1 were evaluated by flow cytometry and Western blot analysis, respectively. NFkappaB was measured by mobility shift assay in parallel experiments. Interleukin 1beta was added to the culture medium. RESULTS: Expression of ICAM-1 and NFkappaB, increased in patients with both CD and UC, was unaltered by interleukin 1beta. The whole cell concentration of ICAM-1 was greater in patients with CD than in patients with UC. Dermal fibroblasts did not display these features. CONCLUSIONS: Patients with inflammatory bowel disease display enhanced ICAM-1 expression in serosal fibroblasts but not dermal fibroblasts, indicating a secondary response to inflammation.     

Phase II trial of Paclitaxel and Dacarbazine with filgrastim administration in advanced malignant melanoma

A Phase II trial was conducted in patients with advanced malignant melanoma with intravenous Paclitaxel and Dacarbazine (DTIC). The initial starting dose for Paclitaxel was 135 mg/m² followed by DTIC 800 mg/m². Due to the lack of myelosuppression and other toxicities, the starting dose for Paclitaxel was escalated to 250 mg/m² and the dose for DTIC escalated to l000 mg/m². Twenty-five patients were enrolled in this study. Among the 25 patients assessable for response, three patients had a partial response with a response rate of 12% (CI 3-31%) and one patient had stable disease. Three additional patients showed evidence of anti-tumor activity with minor responses. For patients who had no prior chemotherapy or biochemotherapy, the response rate was 20%. Toxicity was generally tolerable and included mainly neurotoxicity from Paclitaxel. At the doses and schedule used, the combination of Paclitaxel and DTIC did not appear to increase the response rate compared to each agent used singly.     

Urinary albumin excretion rate and puberty in non-diabetic children and adolescents

Slightly elevated urinary albumin excretion rate (microalbuminuria) is a marker of early diabetic nephropathy, but it is unclear if the established definition of microalbuminuria (20–200 μg/min) is correct for children and adolescents. We investigated the albumin excretion rate, albumin/creatinine ratio and urinary albumin concentration in 150 healthy schoolchildren and adolescents to (a) obtain a reference value for albumin excretion rate, (b) relate albumin excretion to pubertal stages and (c) evaluate albumin/creatinine ratio and morning albumin concentration as screening methods for elevatcd albumin excretion rate. Albumin concentration was measured by immunoturbidimetry in timed overnight urine samples. The albumin excretion showed a skewed distribution (geometric mean 3.2 μg/min, 95 percentile 15.1 μg/min). In girls, a peak in the albumin excretion rate was found at the pubertal stage 4 (Tanner) and in boys at stage 5. Albumin/creatinine ratio of 2.5 mg/mmol as a scrccning level for elevatcd albumin cxcrction (15 μg/min) showed a high positivc (0.88) and negative (0.99) predictive value.     

Adenocarcinoma metastatic to a growth-hormone-secreting pituitary adenoma: case report.

Although the pituitary gland is known to harbor metastatic deposits, it is a rare occurrence for a metastatic deposit to appear in a pituitary adenoma. A case is presented of an adenocarcinoma metastatic in an acromegalic patient with a pituitary adenoma. This report adds to the literature of the unusual phenomenon of neoplasm-to-neoplasm metastasis.     

Studies of marginal zinc deprivation in rhesus monkeys. V. Fetal and infant skeletal effects

Skeletal maturation was evaluated in newborn and infant rhesus monkeys that had been subjected to a marginally zinc-deficient diet (4 ppm zinc) from conception through 12 months of postnatal life. Serial radiographic assessment of skeletal development was performed and compared to both ad libitum and pair-fed controls. Radiographs were obtained at birth and at 1, 3, 9, and 12 months of age. In each age group a maturation indicator was selected to identify individuals with abnormal skeletal maturation defined on the basis of presence of epiphyseal ossification centers. Animals were compared only within a given sex group. Additionally, to evaluate endochondral bone mineralization, the appearance of the zone of provisional calcification on the metaphyseal side of the growth plate and the width of the growth plate were assessed. A marginal level of zinc deprivation during gestation and during the 1st yr of life was found to be associated with significantly delayed skeletal maturation and defective mineralization. This abnormality of bone mineralization has many features similar to human rachitic syndromes and suggests that zinc plays an important role in endochondral bone formation.