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Biomedical subjects

S Shah

Publications and source records attributed to S Shah.

At least 343 records · Page 19Linked to original sources
PubMed1992

Colonoscopic study of 50 patients with colonic tuberculosis.

Fifty patients with colonic tuberculosis are reported in whom a colonoscopic diagnosis confirmed by histological examination was possible in 40. Bacteriological studies did not increase the diagnostic yield. Abdominal pain was the most common symptom (90%) and an abdominal mass the most common abnormal physical finding (58%). A nodular mucosa with areas of ulceration was the usual colonoscopic finding. Ileocaecal disease was found in 16, ileocaecal and contiguous ascending colon disease in 14, segmental colonic tuberculosis in 13, ileocaecal disease and non-confluent involvement of another part of the colon in five, and pancolitis in two patients. This report emphasises that colonoscopy is a useful procedure for diagnosing colonic tuberculosis and that segmental colonic tuberculosis is not uncommon.

Biopsy↗
PubMed1992

Clinical experience of clozapine-induced neutropenia in the UK. Laboratory investigation using liquid culture systems and immunofluorocytometry.

An incidence of drug-induced neutropenia of 2.5% has been found in the first 1000 patients to be treated with clozapine in the UK. The majority of affected patients experienced mild neutropenia (n = 22) with only 3 patients developing agranulocytosis. Data collected from these 25 patients suggest that the mechanism of neutropenia may be multifactorial. Laboratory investigation using liquid culture systems and immunofluorocytometry has identified clozapine and its major metabolite N-desmethyl clozapine as exhibiting toxic effects against myeloid maturation and myeloid mitotic compartments, respectively. Increased susceptibility to the toxic effects of clozapine was shown in 1 patient who had previously developed clozapine-associated neutropenia. No clinical or laboratory evidence of drug-induced antineutrophil or antimyeloid precursor antibodies was found.

Bone Marrow↗
PubMed1992

Thyroid dysfunction in multi-transfused iron loaded thalassemia patients.

Seventy-two transfusion-dependent iron loaded thalassemia patients were investigated for thyroid dysfunction by estimating circulating thyroid hormones (T4 and T3) and basal thyroid stimulating hormone (TSH). They were also evaluated for their liver function (biochemically) and iron overload by estimating serum ferritin. Thyroid failure (hypothyroidism) was documented in 14 patients (19.4%). In all, 3 groups were seen, i.e. Group 1: Normal T4, T3, TSH (58 patients: 80.6%); Group 2: Compensated hypothyroidism characterized by normal T4, T3 and raised TSH (9 patients: 12.5%); Group 3: Decompensated hypothyroidism characterized by decreased T4 and increased TSH (5 patients: 6.9%). Interestingly, impaired thyroid function could not be correlated with age, amount of blood transfused, liver dysfunction or degree of iron overload. It is postulated that an inter-play between chronic hypoxia, liver dysfunction and iron overload may be responsible for the thyroid damage.

Body Height↗
PubMed1992

Moisture transfer from stopper to product and resulting stability implications.

Since the stability of a freeze-dried product is often sensitive to the level of moisture, control of residual moisture by attention to the secondary drying phase of the freeze-drying process is of considerable importance. However, several reports in the literature as well as our own experience suggest that low residual moisture immediately after manufacture does not ensure low moisture throughout the shelf life of the product. Equilibration of the product with moisture in the stopper can lead to significant increases in product water content. This research is a study of the kinetic and equilibrium aspects of moisture transfer from stopper to product at 5 degrees C, 25 degrees C, and 40 degrees C for two amorphous materials: vancomycin (highly hygroscopic) and lactose (moderately hygroscopic). Stoppers are 13 mm butyl rubber (#1816, West Co.) slotted freeze-drying stoppers which were studied: (a) "U"-with no treatment; (b) "SV1"-steam-sterilized followed by 1 hr vacuum drying; and (c) "SV8"-steam sterilized followed by 8 hrs vacuum drying. No evidence was found for moisture transmission through the stopper. Rather, the product moisture content increases with time and reaches an apparent equilibrium value characteristic of the product, amount of product, and stopper treatment method ("SV1" much greater than "U" greater than "SV1"). As a first approximation, the rate of approach to "equilibrium" depends only on temperature (t1/2 approximately 10 months at 5 degrees C to approximately 4 days at 40 degrees C) with the "equilibrium" water content being independent of temperature. The "equilibrium" moisture content increases as the dose decreases and is larger for vancomycin than for lactose. The "equilibrium" moisture contents range from 5.0% (25 mg vancomycin, "SV1" stoppers) to 0.68% (100 mg lactose, "SV8" stoppers).

Biological Products↗
PubMed1992

Assessment of gall bladder dynamics, cholecystokinin release and the development of gallstones during octreotide therapy for acromegaly.

The development of gallstones is a well recognized complication of therapy with the long-acting somatostatin analogue, octreotide in patients with acromegaly. A group of nine acromegalic patients was treated with octreotide at doses of 300-600 micrograms daily for 8 months and the changes in fasting and post-prandial cholecystokinin release, and gall bladder motor function (determined by a radiosotopic technique) were assessed at regular intervals. In addition the development of any gallstones was determined by serial ultrasonography. Fasting cholecystokinin levels showed no significant change over 6 months, whereas the post-prandial levels demonstrated a significant decrease (p less than 0.01) during therapy, yet remained significantly higher than fasting levels. Twenty-four hours after commencing therapy gall bladder ejection fraction was decreased by 57 +/- 23 per cent and gall bladder ejection rate decreased by 63 +/- 19 per cent compared to the pretreatment values, whereas after 6 months' therapy a marked reduction in gall bladder ejection fraction (greater than 35 per cent) and gall bladder ejection rate (greater than 40 per cent) persisted in only four of nine patients. Three of these four patients with persistently impaired gall bladder motor function were subsequently shown to have developed either gallstones or biliary sludge during the course of therapy. We conclude that treatment with octreotide is associated with an impaired post-prandial release of cholecystokinin in all acromegalic patients, but gallstones only develop in those patients who, in addition, have evidence of a persistently impaired gall bladder motor response to cholecystokinin.

Acromegaly↗
PubMed1991

Improved detection of hypotension by automated noninvasive blood pressure monitoring.

This study was undertaken to determine whether the use of automated noninvasive blood pressure monitoring altered the frequency of detection of intraoperative hypotension. We retrospectively reviewed 1,861 anesthetic records from a period in 1987, when blood pressure was obtained manually by auscultation. We compared the records from 1987 with 1,716 anesthetic records from 1989, when automated blood pressure monitors were used universally. The incidences of hypotension requiring vasopressor therapy were determined during the two periods and compared using Student's two-tailed t test. The data revealed that the incidence of detected hypotension increased from 2.4 to 5.2% with the use of automated blood pressure monitors (P less than 0.00002). We conclude that at our hospital the use of automated noninvasive blood pressure monitors increases the incidence of detection of intraoperative hypotension as compared with the use of manual blood pressure measurement.

Anesthesia↗
PubMed1991

Screening for vertebral osteoporosis using individual risk factors. The Multicentre Vertebral Fracture Study Group.

Osteoporosis is a major cause of ill health in postmenopausal women. Several risk factors for osteoporosis have been identified, and they have been widely recommended as a means of identifying subgroups of postmenopausal women who might benefit from prophylaxis and therapy. Evidence to support this use of risk factors is currently lacking, however. We have constructed and evaluated a profile of putative risk factors as a means of identifying women attending general practitioners who have sustained vertebral fractures. The overall prevalence of vertebral fractures in the 1012 women (mean age 64.4 years) studied was 7.8%. Women who had sustained vertebral fractures in this population were significantly (p less than 0.05) older and shorter than those without fractures. They reported a significantly (p less than 0.05) earlier menopause, lower parity and a greater prevalence of hyperthyroidism. However, the best screening instrument devised was not sufficiently predictive to warrant widespread use.

Aged↗
PubMed1991

Stroke rehabilitation: Australian patient profile and functional outcome.

A prospective, multi-institutional, population based study identified 1274 non-surgical stroke admissions to all hospitals in a major Australian city during 1984. The demographic and diagnostic profile and the nature of functional recovery of all 258 first stroke survivors who were referred for inpatient rehabilitation are presented. The median duration of rehabilitation stay was 49 days. The mean functional independence score, as measured on a modified Barthel Index at admission was 44, compared with 78 on discharge, a mean improvement of 34. Stair climbing had the lowest mean value on admission (12), while bowel control had the lowest residual deficit on discharge (95). The stroke study group was representative of the unimpaired aged population in all respects except ethnicity, where differences are attributed to age. The variables identified as significant are; side and severity of paralysis, age and sex, marital status and ethnicity. Stroke rehabilitation outcome was not influenced by etiology, site of lesion, arterial distribution, occupation or education.

Activities of Daily Living↗
PubMed1991

Study of the mechanisms of flux enhancement through hairless mouse skin by pulsed DC iontophoresis.

Enhanced iontophoretic transport using pulsed DC is usually explained by citing the observed decrease in skin resistance caused by an increase in AC pulse frequency at very small currents. Alternately, it has been suggested that the "on-to-off" nature of pulsed DC imparts an "impact energy" to the fluid, thereby increasing transport. This report provides a test of these mechanisms for enhanced delivery via pulsed iontophoresis. The DC resistance of hairless mouse skin during continuous and pulsed DC iontophoresis is measured as a function of time for selected pulse frequencies and duty cycles using current densities ranging from 0.1 to 1.0 mA/cm2. As a test of the impact energy mechanism, the iontophoretic transport of 14C-glucose measured with pulsed DC is compared with similar data obtained previously using continuous DC. It is suggested that pulsed current can yield lower resistance and enhanced drug delivery provided that (a) the "steady-state" current during the "on" phase of the pulse is very small and (b) the frequency is low enough to allow depolarization of the skin during the "off" phase of the pulse. The glucose transport results suggest that the "impact energy" concept does not apply to iontophoresis.

Animals↗
PubMed1991

Clean intermittent self-catheterisation for quadriplegic patients--a five year follow-up.

We present the findings of clean intermittent self-catheterisation (CISC) as a long term method of bladder management for 36 quadriplegic spinal cord injured patients, primarily at C6/C7 level, who were taught CISC between 1983 and 1987. Success in CISC was assessed by a mail survey, a telephone interview, and current sterile urine status. Twenty nine (81%) of 36 patients continued to use CISC after a mean discharge period of 2.9 years (p less than 0.001) with high levels of acceptance. Rao's V discriminant analysis showed success in CISC was affected by the interval between injury and initial self-catheterisation (Canonical Correlation Co-efficient = 1.34). Results of urinalysis for patients continuing CISC were obtained for 18 (62%) patients, 16 (88%) of whom had sterile urine. Implications of these and other findings along with reasons for cessation of CISC are discussed.

Activities of Daily Living↗
PubMed1991

Characterization and generation of Escherichia coli adenylate cyclase deletion mutants.

Escherichia coli delta cya-283 is a 75-bp in-frame deletion overlapping the 5' end of delta cya-854; delta cya-201 is a 41-bp frameshift deletion overlapping the 3' end of delta cya-854. Sequence repeats were found at the boundaries of delta cya-283 and delta cya-201, suggesting a mechanism for deletion formation. Recombinant DNA procedures were used to construct a strain in which the total cya structural gene in the chromosome was replaced by the kanamycin resistance gene.

Adenylyl Cyclases↗
PubMed1991

Characterization of Gardnerella vaginalis and G. vaginalis-like organisms from the reproductive tract of the mare.

Gardnerella vaginalis has been isolated from women with bacterial vaginosis, from the genital tracts of asymptomatic women, and from several other infected body sites in humans. However, until recently, it has not been isolated from any other animal species. Between June 1988 and October 1989, 31 isolates identified as G. vaginalis and 70 isolates identified as G. vaginalis-like organisms have been recovered from the genital tracts of 93 mares from Michigan and Ohio. Identification was based on biochemical reactions, hemolysis on media containing blood from various animal sources, and susceptibility to select antimicrobial agents. This report details the characterization of G. vaginalis and G. vaginalis-like organism isolates obtained from the reproductive tracts of these mares and compares the equine isolates with human isolates.

Abortion, Veterinary↗
PubMed1991

A novel metalloproteinase present in freshly isolated rat glomeruli.

We have utilized [3H] gelatin to document high activity of a metalloproteinase present in freshly isolated rat glomeruli. [3H] gelatin degradation by glomeruli was markedly inhibited by EDTA (10 mM: -89 +/- 2.3%) and o-phenanthroline (2 mM: -72 +/- 0.1%), inhibitors of metalloproteinases. No significant inhibition of [3H]gelatin degradation was observed with inhibitors of serine or cysteine proteinases. Most (greater than 80%) of the glomerular metalloproteinase (GLOMP) activity was associated with the pellet after centrifugation of sonicated glomeruli at 100,000 g for 90 min. The pH optimum for gelatin degradation by sonicated glomeruli was approximately pH 8.5. Sodium dodecyl sulfate substrate (gelatin)-polyacrylamide gel electrophoresis revealed a single major band of EDTA-inhibitable gelatin-degrading activity with a molecular mass of approximately 116-125 kDa. The GLOMP activity was not inhibited by tissue inhibitors of metalloproteinases, did not appear to be latent, and was not activated by organomercurial activators of several latent metalloproteinases. GLOMP activity was increased 3.4-fold after incubation with trypsin (20 micrograms/ml, 25 min, 22 degrees C). These data indicate that GLOMP is distinct from the previously described matrix metalloproteinases, as well as other metalloproteinases present in the kidney, including the gelatinase secreted by cultured mesangial cells, Meprin, and endopeptidase 24.11 (enkephalinase, EC 3.4.24.11).

Animals↗
PubMed1991

Class II major histocompatibility complex antigen expression on unstimulated and gamma-interferon stimulated monocytes from patients with multiple sclerosis, rheumatoid arthritis and normal controls.

HLA-DR, HLA-DQ, and HLA-DP antigen expression was assessed by immunofluorescent flow cytometry on monocytes from 19 patients with active multiple sclerosis (MS), 19 with inactive MS, 7 patients with early active rheumatoid arthritis (RA), and 19 normal controls. Percentage positivity and median channel fluorescence (MCF) were determined after separation of the monocytes (TO) and following 48 h culture with (T48 + IFN) and without (T48) recombinant gamma interferon (rIFN-gamma). The percentage positivity of the cells was normal at TO for all groups of patients for each of the HLA types but statistically significantly increased above normal, on monocytes from patients with inactive MS, after culture with rIFN-gamma. At TO, the MCF values for HLA-DQ, and HLA-DP were statistically significantly increased above normal on monocytes from patients with active MS indicating some pre-programming of the cells in vivo. After culture, when the carry-over from baseline TO values was eliminated, the increment in MCF for HLA-DR, on monocytes from patients with inactive MS, was statistically significantly lower than normal in the non-gamma-IFN cultures but was normal in the presence of rIFN-gamma. Conversely, the increment in MCF for HLA-DP on monocytes from patients with active MS was significantly lower than normal after culture with rIFN-gamma. Therefore, the stimulation required to increase antigen density on cells already expressing antigen may be different to that required to stimulate de novo expression on negative cells. Both systems appear to be abnormal in MS, possibly reflecting differences in disease activity, while only one system appears abnormal in RA.

Adult↗
PubMed1991

Towards the design of heterovalent anti-malaria vaccines: a hybrid immunogen capable of eliciting immune responses to epitopes of circumsporozoite antigens from two different species of the malaria parasite, Plasmodium.

The peptide CS.T3, corresponding to residues 378-398 of the Plasmodium falciparum (Pf) circumsporozoite (CS) protein sequence (except with cysteines 384 and 389 replaced by alanines), has been found to be almost universally recognized by human and mouse T lymphocytes. When colinearly linked to the repetitive B-lymphocyte-specific epitope (Asn-Ala-Asn-Pro)n of Pf CS protein, CS.T3 induces T-helper activity for an anti-(Asn-Ala-Asn-Pro)n antibody response in mice of different haplotypes. We constructed a double-epitope peptide, CS.T3-R3, by co-linearly joining a truncated 18-mer form (IEKKIAKMEKASSVFNVV) of CS.T3 to three tandem repeats (R3) of a B-cell-specific epitope, QGPGAP, of Plasmodium yoelii (Py) CS protein, via a two-glycine spacer. Whereas CS.T3 and R3 did not induce specific antibodies, CS.T3-R3 elicited anti-CS.T3 and anti-R3 antibodies in different mouse strains. Some human anti-Pf sera from malaria-endemic areas contained high-titred anti-CS.T3 antibody IgG, indicating that parasite-derived CS.T3 contains a B-cell determinant which is maintained in the alanine-substituted synthetic CS.T3. Antibody absorption experiments showed that CS.T3-R3 contains no new B-cell-specific determinants other than R3 and CS.T3. That the Pf CS protein epitope, CS.T3, supports T-cell help for antibody responses against the Py CS protein repeat epitope, QGPGAP, implies the possible use of CS.T3 in anti-sporozoite multiple-epitope vaccines against different species of Plasmodium. Colinearly linking CS.T3 to R3, via a two-glycine spacer, appears to be a useful model by which different T- and B-cell-specific determinants can be jointed into a heterovalent immunogen while retaining their distinct immunological properties.

Animals↗
PubMed1991

Efficacy and safety of 1-2, dimethyl-3-hydroxypyrid-4-one (L1) as an oral iron chelator in patients of beta thalassaemia major with iron overload.

Twenty-four patients with beta thalassaemia major, aged 8-22 years (mean 15.3 +/- 8.1) were given 1-2, dimethyl-3-hydroxypyrid-4-one (L1) orally for a period of three months. The drug was given in the dose of 25 mg/Kg/day for the first week and gradually increased to 100 mg/Kg/day which was continued until 3 months. The mean urinary iron excretion was 5.73 +/- 3.648 mg/day on 25 mg/Kg/day of L1; 15.2 +/- 11.225 mg/day on 50 mg/Kg/day; 24.2 +/- 12.69 mg/day on 75 mg/Kg/day and 36.3 +/- 19.4 mg/day on 100 mg/Kg/day of L1. Serum ferritin estimated by ELISA before and 3 months after L1 therapy in 21 patients showed significant drop in levels, the mean drop being 964.3 +/- 844.4 (P less than 0.001). The only side-effects noted were transient gastrointestinal symptoms in 5 patients and skeletomuscular pain in 3 patients. Both these groups of symptoms were of transient nature. The efficacy of L1 appears to be excellent and equivalent to the standard iron chelation therapy available at present i.e. desferrioxamine. It appears to be free of major toxicity. L1 is also a specific chelator for iron as it does not deplete trace metals. L1 appears to be a cheap and effective oral alternative to desferrioxamine for treating iron overloading.

Adolescent↗