Gastrointestinal stromal tumor in ileal neobladder

Abstract  Gastrointestinal stromal tumor (GIST) is a recently described mesenchymal tumor that can develop in any portion of the gastrointestinal tract. The occurrence of a GIST in the urinary tract is rare, but GIST can present as tumor of the urinary tract or invade the urinary tract. This is the first reported case of GIST in the ileal neobladder, which presented as a submucosal tumor. The patient underwent an open exploration and partial resection of the neobladder pouch.     

Chemically distinct rat olivocochlear neurons.

We have produced a neurochemical map of the cell bodies of origin of the cochlear efferent terminals in rat by combining glutamic acid decarboxylase (GAD), choline acetyltransferase (ChAT), or calcitonin gene-related peptide (CGRP) immunocytochemistry with retrograde transport of horseradish peroxidase. The locations of cochlear efferent cell bodies are in general agreement with the medial and lateral systems described by White and Warr (J. Comp. Neurol. 219:203-214, 1983) with some minor modifications. The lateral system consists of at least two pools of chemically distinct neurons located within the lateral superior olive (LSO) ipsilateral to the injected cochlea. One pool immunostains with an antibody to GAD while the other immunostains with antibodies to ChAT and to CGRP. The medial efferent system consists of periolivary neurons that are almost exclusively large and ChAT-positive but CGRP-negative. They are located both ipsilateral and contralateral to the cochlea they project to. There are a few GAD-positive small neurons in the medioventral and rostral periolivary regions that project ipsilaterally, but these may prove tobe ectopic neurons. The ipsilateral lateroventral periolivary region (LVPO) contains some efferent neurons, all of which are ChAT-positive but CGRP-negative. Additional cochlear efferent neurons, some of which are ChAT-positive and others GAD-positive, are present within and immediately dorsal to the fiber capsule surrounding the medial limb, and to a lesser extent the lateral limb, of the ipsilateral LSO. Not all GAD-positive or ChAT-positive olivary cells project to the cochlea. We have complemented the results in the brainstem by demonstrating two immunocytochemically distinct populations of efferent terminals in the cochlea simultaneously, one CGRP-positive and the other GAD-positive. Approximately equal numbers of boutons immunoreactive for both markers are present beneath inner hair cells throughout the entire length of the cochlea. Surprisingly high numbers of GAD-positive and CGRP-positive boutons are also present on outer hair cells, with each class having its spatially and morphologically distinct features. The lack of CGRP-positive periolivary cells that are retrogradely labeled by cochlear injections of HRP suggests that the lateral olivocochlear system sends projections to outer hair cells. Our results raise questions about species differences in the organization of targets of the lateral and medial olivocochlear systems.     

Grip and pinch strength among selected adult occupational groups

A survey of 402 normal subjects (203 men, 199 women) was conducted to assist in distinguishing potential differences in norms of hand strength. Norm data had previously been collected from mixed occupational groups, but in the present study it was hypothesised that people involved in heavy manual work on a daily basis might possess greater hand strength than others. The volunteers were adults working in industry and agriculture; they were subdivided into occupational categories. Measurements of grip, key and palmar pinch using the Jamar dynamometer and B and L pinch gauge were collected, using the protocol described by Mathiowetz. Volunteers also rated their individual hand strength job requirements subjectively. Mean values were established with regard to age, sex, dominance, occupational group and subjective rating. Significant differences were found with regard to age and sex but not to dominance; there was no evidence of differences between occupational groups or between subjective rating and individual scoring, i.e. volunteers who perceived their job as requiring a high degree of strength did not achieve higher test measurements than others. A high interrater reliability was demonstrated when comparing these follow-up measurements with the original data. It was concluded that, for clinical and rehabilitative purposes, therapists can interpret assessment of outcome most accurately by comparing patients' results with the existing norm data.     

Studies on the In-vitro Percutaneous Penetration of Indomethacin from Gel Systems in Hairless Mice

The influence of co-solvents on the in-vitro percutaneous penetration of indomethacin from gel systems was studied using a simplex lattice experimental design. Gel formulations were prepared by gelling the vehicle mixture of water, either alcohol or isopropanol and either propylene glycol or PEG 400 with 1% w/w Carbomer 940. Hairless mouse skin was employed as the barrier in a Franz-type diffusion cell. The penetration rates at steady state for seven formulations were fitted to a polynomial equation based on this simple lattice method and a three-dimensional plot was constructed. The formulation having the maximal penetration rate was determined to be the vehicle with a solvent ratio of water: alcohol: propylene glycol equal to 15:33:52, and which possessed a solubility parameter of 15 and a drug solubility of around 10 mg mL^?1. When the solubility parameter of the vehicle was > 15, the drug solubility increased. However, the penetration rate decreased with an increasing solubility parameter. For those vehicles with a solubility parameter < 15, both the drug solubility and the penetration rate decreased with a decrease in the solubility parameter. There was shown to be an approximately 20-fold increase in the relative enhancement factor when using both alcohol and isopropanol, but only a threefold increase for both propylene glycol and PEG 400, when compared with water.     

Extracellular matrix formation by osteoblasts from patients with osteogenesis imperfecta.

Extracellular matrix proteins synthesized by bone cells isolated from 16 patients with different forms of osteogenesis imperfecta (OI) were analyzed in vitro. Specific components of the extracellular matrix by OI and age-matched cultures were investigated by steady-state radiolabeling followed by quantitation of label into specific proteins and comparison of OI cultures to those of age-matched controls. The in vitro proliferation of OI bone cells was found to be lower than that of control cells. In seven patients, abnormalities of the alpha 1(I) and/or alpha 2(I) chains of type I collagen were detected by gel electrophoresis. In two of these patients, the mutations in the COLIA1 and COLIA2 genes have been previously identified. Although the amount of total protein synthesized by the cells in culture was the same for OI bone cells and age-matched control cells, OI bone cells showed a significantly reduced synthesis of not only collagen but also other bone matrix glycoproteins. The synthesis of osteonectin (SPARC/BM40) and three proteoglycans [a large chondroitin sulfate proteoglycan, biglycan (PGI), and decorin (PGII)] was found to be decreased in OI cells. The reduction was most pronounced at the developmental age at which these macromolecules reach maximal levels during normal development.     

Osteogenesis imperfecta: A clinical study of the first ten years of life

Summary One hundred twenty-seven children with osteogenesis imperfecta (O.I.) were studied during the first 10 years of life. According to Sillence, 40 patients were assigned to type I, 39 to type III, and 48 to type IV O.I. Centiles for height, weight, and the annual number of fractures could be established for the different types of O.I. The development of the skeletal changes could be documented for the different forms of the disease. At birth, the skeletal changes were significantly more severe in type III than in type IV patients. During the first 10 years of life the number of fractures, extent of skeletal deformities, and growth retardation did not differ between types III and IV. Only fracture nonunion, dentinogenesis imperfecta, and congenital cardiac malformations were more frequent in type III than in type IV. Papillary calcifications of the kidney and kidney stones were diagnosed in 4 type III and 2 type IV patients. Hemihypertrophy of the body developed, in 2 type I patients. Although types III and IV patients suffered from severe short stature, serum insulin-like growth factor (IGF) I was in the normal range.     

TNF-alpha -308G>A polymorphism modulates cytokine serum concentrations and macrovascular complications in diabetic patients on aspirin.

BACKGROUND: Tumor necrosis factor (TNF)-alpha has pleiotropic effects in cytokine-mediated inflammation underlying atherogenesis. Activation of this inflammatory process is assumed to be different in diabetic and non-diabetic individuals. Previous studies in non-diabetic subjects showed no association between TNF-alpha -308G>A polymorphism and coronary artery disease. METHODS: Vascular complications and cytokine serum concentrations were assessed as a function of the TNF-alpha -308G>A polymorphism in 76 diabetic patients on low-dose aspirin. RESULTS: Of 76 adult diabetic patients, 18 (24%) carried the TNF-alpha -308A allele (17 AG, 1 AA) and 58 (76%) carried wild-type alleles (GG). Prevalence of macrovascular complications was 33% in TNF-alpha -308A allele carriers (AG+AA) and 78% in wild-type allele carriers (GG) (p<0.001). In contrast, prevalence of microvascular complications was 78% and 84%, respectively, and did not significantly differ between the study groups. TNF-alpha -308A allele carriers (AG+AA) compared to wild-type allele carriers (GG) had significantly lower median serum concentrations of hs-C-reactive protein (1.5 vs 2.9 mg/L, p=0.030), interleukin 1-beta (0.9 vs 1.2 ng/L, p=0.046), and interleukin-6 (3.6 vs 4.9 ng/L, p=0.023). In multiple regression analysis, the prevalence of macrovascular diabetic complications was significantly associated with TNF-alpha -308G>A polymorphism (p<0.001) and serum concentrations of HDL-cholesterol (p=0.007) while confounding effects of further variables were excluded. CONCLUSION: TNF-alpha -308G>A polymorphism modulates cytokine serum concentrations and macrovascular complications in diabetic patients on aspirin. Diabetic carriers of the TNF-alpha -308A allele might benefit more from a prophylaxis with low dose aspirin than non-carriers.