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Biomedical subjects

S Patel

Publications and source records attributed to S Patel.

At least 487 records · Page 27Linked to original sources

Ventricle shunting in young H-Tx rats with inherited congenital hydrocephalus: a quantitative histological study of cortical grey matter.

Shunt surgery is the usual treatment for infantile hydrocephalus, but its precise effects on ventricles and cortex are not well understood. Infant H-Tx rats with inherited hydrocephalus, which have progressive enlargement of the lateral ventricles and thinned cerebral cortex, have been used to study the effect of ventriculosubcutaneous shunts by quantitative light microscopy. Two groups of rats received shunts at mean ages of 7 and 13 days after birth. The brains were processed for wax histology at either 14 or 21 days (n = 3 per group) together with age-matched control and unshunted (hydrocephalic) rats. Ventricle areas were measured and the volume calculated and the cortical layers in five cortical regions were measured. Shunting prevented further expansion of ventricles which were already enlarged at the time of operation, and resulted in volumes which were intermediate between those in control and unshunted rats. Cortical thinning was partially reversed by shunting and the thickness and number of discernible cortical laminae was improved. It is concluded that shunting was largely successful at preventing the pathological effects of hydrocephalus.

Age Factors↗

Use of doxorubicin and dacarbazine for the management of unresectable intra-abdominal desmoid tumors in Gardner's syndrome.

PURPOSE: The aim of this study was to describe the natural history and management of surgically unresectable intra-abdominal desmoid tumors in two patients with Gardner's syndrome from two unrelated families, where each had failed on conventional therapy. METHODS: Two patients with Gardner's syndrome were placed on a chemotherapy regimen which included doxorubicin (90 mg/m2) and dacarbazine (900 mg/m2) in divided doses over four days of continuous infusion. Their progress on chemotherapy was assessed by abdominal computerized tomography and laparoscopy. RESULTS: The computerized abdominal tomography scans proved difficult to interpret because of adhesions and matted small bowel resulting from the patients original colectomies. These findings made it difficult to differentiate postoperative changes from residual desmoid tumor. Second-look laparotomy in such patients was contraindicated as this may predispose to further desmoid production. Laparoscopy disclosed a complete response to this chemotherapy. Nevertheless, we had an iatrogenic small bowel perforation in one of these patients. Each patient showed a complete response to chemotherapy. CONCLUSION: Surgical resection remains the first-line treatment of intraabdominal desmoid tumors. However, doxorubicin/dacarbazine chemotherapy on a clinical trial basis may be indicated in patients whose intra-abdominal desmoid is unresectable, or who have failed to respond to treatment with hormones (tamoxifen, Toremifene), steroids (prednisone), and nonsteroidal anti-inflammatory agents (Clinoril; Merck & Co., Inc., West Point, PA).

Adult↗

Design of workcards for aircraft inspection.

The workcard is the primary document that controls an aircraft inspection task and serves as a major factor influencing inspection performance. The present study develops a methodology for design of workcards, based on the application of human factors knowledge to the analysis of aircraft inspection tasks. A taxonomy for design of usable documentation was developed using four basic categories: information readability, information context, information organization, and physical handling/environmental factors. Within the framework of this taxonomy two extreme representative conditions of aircraft inspection tasks, the A-check and the C-check, were analysed for usability. Issues for workcard redesign were identified within the taxonomy using data from user responses. These were then used to develop alternative design solutions offering improved usability. The increase in usability was measured using inspections of DC-9 aircraft, and proved significant. Not only does this study propose specific design solutions, it also provides a generic methodology that can be followed for design of quality documentation for other aircraft inspection tasks. This methodology is currently being extended for the design of usable information for automated workcards and hypermedia-based documentation.

Journal Article↗

Chylomicron retention disease: exclusion of apolipoprotein B gene defects and detection of mRNA editing in an affected family.

Chylomicron retention disease (CRD) is a rare autosomal recessive disorder characterized by the absence of post-prandial chylomicrons and apolipoprotein (apo) B-48 in sera from affected individuals. Apo B-100 is synthesized, and apo B-100-containing lipoproteins are present in sera. A crucial difference between the synthesis and secretion of apo B-containing lipoproteins from the liver and gut in man is the generation of apo B-48 by editing of apo B mRNA in the gut to create a premature stop-translation codon. In this study the hypothesis that CRD may represent an absence of editing of apo B mRNA in the gut was investigated. Two affected sisters were identified as having low cholesterol levels and an absence of post-prandial chylomicronemia. Segregation analysis in the family showed that the apo B locus is not the site of the defect. Using reverse transcription-polymerase chain reaction (RT-PCR), duodenal biopsy-mRNA from the affected sisters was isolated and analyzed. The apo B editing site was amplified after cDNA synthesis, and the products analyzed by the primer extension assay. The results show that editing of apo B mRNA is normal in patients with CRD. The data provides strong confirmation that the primary defect in CRD is not in the synthesis, or editing of apo B mRNA in the gut. More likely, the disease arises from a defect in a gene crucial to the assembly and/or secretion of the chylomicron particle.

Apolipoprotein B-48↗

Cervical metastases of occult origin: the impact of combined modality therapy.

BACKGROUND: We have updated our experience with metastatic carcinoma to the neck of occult origin to assess whether increasing use of adjunctive radiation therapy has had a significant impact. METHODS: This retrospective review of 115 patients treated between 1977 and 1990 includes 73 (63%) with squamous cell carcinoma. These 73 patients were analyzed for survival, control of disease in the neck, and incidence of subsequent primary tumors. RESULTS: There has been no change in the proportion of patients with advanced neck disease (N2/N3 = 52; 71%) when compared to our last report. Surgery included comprehensive neck dissection in 59 (81%) and adjunctive radiotherapy was employed in 54 (83% of surgically treated patients). Primary carcinomas within the head and neck were identified subsequently in 9 (12%) patients, including 4 of 11 (36%) who did not have adjunctive radiotherapy and 5 of 54 (9%) who did (P = 0.038). Control of the treated neck (54/73; 74%) has improved significantly (P = 0.005) when compared to our earlier experience (37/74; 50%), and this was most apparent in those with extensive neck disease. However, cumulative survival at 5 years (45%) was not significantly different from that previously reported. CONCLUSION: Our data support the increased use of adjunctive radiation therapy for metastatic squamous cell carcinoma in the neck of occult origin. Control of neck disease has improved and the likelihood that a primary will be identified has been reduced, but there has been no improvement in survival when compared to historical controls.

Adult↗

Selective non-peptide ligands for an accommodating peptide receptor. Imidazobenzodiazepines as potent cholecystokinin type B receptor antagonists.

A series of imidazobenzodiazepines, non-peptide antagonists of the peptide hormone cholecystokinin (CCK), are described. Derived by chemical modification of the benzodiazepine ring system embedded within the CCK-B antagonist L-365,260, these compounds display CCK-B/CCK-A selectivity and some analogs have receptor binding affinities in the subnanomolar range. This group of novel imidazobenzodiazepines, among which N-[(2S,4R)-methyl-6-phenyl-2,4-dihydro-1H-imidazo[1,2- alpha][1,4]benzodiazepin-4-yl]-N'-[3-methylphenyl]-urea (12) is the principal compound, expands the structural diversity of the collection of non-peptide CCK-B antagonists and will be useful in further delineating the function of CCK in the central nervous system.

Animals↗

The relationship of age, gender, handedness, and sidedness to the size of the corpus callosum.

OBJECTIVES: We correlated the area and size of the corpus callosum, as measured by MR imaging, with the individual's handedness, sidedness, age, and gender. MATERIALS AND METHODS: A total of 117 patients (59 male, 58 female) aged 15-75 years were selected for this study. This included 12 persons who were either left-handed or ambidextrous. Each patient was tested extensively to determine handedness and sidedness. Callosal areas and thickness were measured and correlated with brain size. RESULTS: The body of the corpus callosum decreases in size with age and is larger in right-handed persons. The cross-sectional areas of the genu, splenium, and corpus callosum, overall, do not vary significantly with respect to age, gender, sidedness, or handedness. CONCLUSIONS: The size of the corpus callosum consistently decreases with age. Otherwise, few statistical differences in callosal size relate to gender, sidedness, or handedness.

Adolescent↗

An enzyme-linked immunosorbent assay (ELISA) for quantitation of adducts of granulocyte-macrophage colony stimulating factor (GM-CSF) and human serum albumin (HSA) in stressed solution mixtures.

HPLC analyses of GM-CSF in solution mixtures containing both GM-CSF and HSA showed losses of GM-CSF which could not be accounted for using conventional electrophoretic and/or RP-HPLC techniques. Further investigation of these mixtures by immunoblotting and by immunoaffinity chromatography demonstrated the presence of high molecular weight (> 67,000 GM-CSF related species. No such species was detectable in solutions of GM-CSF alone. This experiment pointed to the formation of an adduct between GM-CSF and HSA in the solution mixtures. To probe further the hypothesis of a GM-CSF/HSA adduct, an immunologically based test was conceived which could react only with this type of hybrid molecule. A sandwich enzyme-linked immunosorbent assay (ELISA) was developed using two antibodies, anti-GM-CSF (capture antibody) and anti-HSA (detection antibody), as part of the quantitation of GM-CSF/HSA adducts. After confirming its existence by ELISA, a GM-CSF/HSA adduct was isolated from the solution mixture containing both GM-CSF and HSA. This isolate served as a primary reference standard in the ELISA assay. The immunoassay has a subnanogram sensitivity and is highly specific for GM-CSF/HSA adducts in the presence of either free GM-CSF or free HSA. As a verification, conjugates of GM-CSF/HSA were synthesized using a cross-linking reagent. These covalent conjugates reacted positively in the ELISA and are employed as a convenient alternative reference standard.

Chromatography, Affinity↗

Male pseudohermaphroditism caused by mutations of testicular 17 beta-hydroxysteroid dehydrogenase 3.

Defects in the conversion of androstenedione to testosterone in the fetal testes by the enzyme 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) give rise to genetic males with female external genitalia. We have used expression cloning to isolate cDNAs encoding a microsomal 17 beta-HSD type 3 isozyme that shares 23% sequence identity with other 17 beta-HSD enzymes, uses NADPh as a cofactor, and is expressed predominantly in the testes. The 17 beta HSD3 gene on chromosome 9q22 contains 11 exons. Four substitution and two splice junction mutations were identified in the 17 beta HSD3 genes of five unrelated male pseudohermaphrodites. The substitution mutations severely compromised the activity of the 17 beta-HSD type 3 isozyme.

17-Hydroxysteroid Dehydrogenases↗

Biochemical effects of manufactured gas plant residue following ingestion by B6C3F1 mice.

The toxic potential of manufactured gas plant residue (MGP) given in the diet to male and female B6C3F1 mice was evaluated. In addition, the bioavailability of chemical components of MGP were also investigated by monitoring polycyclic aromatic hydrocarbon (PAH) metabolites in urine and DNA adduct formation in forestomach and lung tissue. Basal gel diets containing 0.05, 0.25, 0.50% MGP or 0.005% benzo[a]pyrene (BaP) were fed to animals for 94 and 185 d. Mice readily consumed adulterated diets without any evidence of acute toxicity. The total amount of MGP and BaP consumed by mice ranged from 118 to 2604 mg and from 12 to 29 mg, respectively. Male mice fed a control or BaP diet and female mice fed a 0.05% MGP diet had the highest body weight gains. Male and female mice fed a 0.50% MGP diet had the lowest body weight gains. The bioavailability of chemical components of MGP was evaluated by monitoring the urinary excretion of PAH metabolites by male mice fed a 0.25% MGP diet. 1-Hydroxypyrene was determined by high-performance liquid chromatography analysis to be the major fluorescent metabolite excreted by mice throughout the 185 d of diet administration. At necropsy, no chemical-related gross lesions were detected. In addition, no treatment-related microscopic lesions were evident in tissues obtained from animals fed a 0.50% MGP- or BaP-adulterated diet. The 32P-postlabeling assay was used to evaluate MGP- and BaP-induced DNA adduct formation in lung and forestomach tissue. The level of DNA adducts formed from the chemical components of MGP paralleled the amount of material ingested by animals. Lung DNA adduct levels were considerably higher than forestomach levels when mice ingested a 0.25% or 0.50% MGP diet. These studies demonstrate that the continuous ingestion of MGP or BaP for 185 d does not result in acute toxicity or chemical-related lesions at doses up to 0.50% MGP or 0.005% BaP.

Administration, Oral↗

Comparative analysis of neovascularization in primary cutaneous melanoma and Spitz nevus.

Spitz nevus is a well-known histologic simulator of malignant melanoma. Vascularity of human neoplasms has been associated with prognosis as well as propensity for metastasis. Were vascularity significantly different between melanoma and Spitz nevus, it could serve as a feature to distinguish between these two neoplasms. We evaluated the vascularity of a series of primary cutaneous melanomas ranging from thin superficial spreading to nodular lesions as well as superficial compound and nodular deep Spitz nevi by using light-microscopic evaluation of factor-VIII-stained sections. Vascularity was density graded and microvessels were counted per x200 and x400 field. Vascular density and microvessel counts were significantly different between melanomas of 2+ and 3+ vascularity compared with all types of Spitz nevi. Although nodular malignant melanomata tended to have a greater degree of vascularity than thin melanomas, there was a significant population of both of these subtypes having few or many vessels. We conclude that the number of microvessels per x200 and x400 field in areas of greatest vascularity is significantly less in Spitz nevus than in malignant melanoma. There is a subset of melanoma, however, in which the number of microvessels may be low. Nodular melanomata tended to have a greater number of vessels than did thin superficial spreading lesions. Evaluation of microvessel count may be of assistance when coupled with clinical and histologic findings in distinguishing between melanoma and Spitz nevus in selected cases.

Blood Vessels↗

Clinical evaluation of a portable ultrasonic and a standard optical pachometer.

The clinical performance of a portable ultrasonic pachometer was compared with a modified optical pachometer on a group of normal subjects. The mean central corneal thickness according to optical pachometry using the "edge-to-edge" method of optical doubling was 0.553 mm (SD = +/- 0.022). The mean central corneal thickness using the ultrasonic device was 0.506 mm (SD = +/- 0.039). The differences between the means was statistically significant (at 1% level of probability). Based on the light distribution within the corneal optical section viewed during optical pachometry a hypothesis is derived supporting the notion that optical pachometry tends to overestimate corneal thickness rather than ultrasonic pachometry underestimating corneal thickness.

Adolescent↗

Determining periodontal ligament (PDL) cell vitality from exarticulated teeth stored in saline or milk using fluorescein diacetate.

One of the key factors for obtaining a favourable long-term prognosis in avulsed teeth is maintenance of the vitality of the periodontal ligament (PDL) cells. Most studies which have examined PDL cell vitality have used neutral red or trypan blue as stains. However, these stains have certain inherent disadvantages. The purpose of this paper was to (i) evaluate the use of saline and milk as storage media for PDL cells and (ii) determine the value of using fluorescein diacetate (FDA) as a staining medium for vital PDL cells on the root surface of avulsed teeth. Thirty-two single-rooted premolars were utilized from patients aged 13 to 28 years. Following atraumatic extraction, the teeth in the experimental groups were air dried for 10 min and then placed in either milk or saline for 120 min. Both control and experimental teeth were subjected to trypsinization procedures, staining with FDA, and haemocytometer readings to determine the number of vital cells. There was no statistically significant difference in the number of viable cells on the root surfaces of teeth after 2 h of storage in either milk or in saline. Furthermore, staining with FDA provided an excellent method by which to determine PDL cell vitality.

Adolescent↗

Pharmacology of high-threshold calcium currents in GH4C1 pituitary cells and their regulation by activation of human D2 and D4 dopamine receptors.

1. The objective of this study was to characterize the pharmacology of calcium currents in GH4C1 pituitary cells and determine whether activation of heterologously expressed human dopamine receptors can regulate their function. Human D2(short), D3 and D4.2 receptor cDNA's were separately transfected into GH4C1 cells and whole cell calcium currents were recorded by use of nystatin-perforated patch clamp techniques. 2. High-threshold calcium currents were antagonized in a biphasic manner by the dihydropyridine, nisoldipine. The half-maximally effective concentration for each site was 0.2 nM (pIC50 = 9.78 +/- 0.21, n = 4) and 339 nM (pIC50 = 6.47 +/- 0.12, n = 4). The component of current inhibited by 10 nM nisoldipine was also blocked by omega-conotoxin GVIA (30 +/- 9% at 30 nM, n = 6) or by omega-agatoxin IVA (34 +/- 7% at 100 nM, n = 4). 3. Activation of either D2 or D4 receptors by dopamine (10 microM) or quinpirole (0.1 to 10 microM) reduced the peak calcium current by ca. 20% in the majority of cells studied. No inhibition was observed in control or D3 transfected GH4C1 cell lines. 4. The mobilisation of intracellular calcium by thyrotropin releasing hormone in hD4-GH4C1 cells was also studied using Fura-2 AM microspectrofluorimetry. Thyrotropin releasing hormone caused a concentration-dependent increase in calcium mobilisation with an EC50 of 7 nM. D4 receptor activation had no effect upon either basal or hormone-induced [Ca2+]i transients. 5. These results demonstrate that GH4C1 pituitary cells have at least two types of dihydropyridine sensitive high-threshold calcium currents and that like D2 receptors, human D4 receptors can also regulate calcium channel function.

Animals↗