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Biomedical subjects

S Shah

Publications and source records attributed to S Shah.

At least 19 recordsLinked to original sources
PubMed1992

Perinatal cocaine exposure and functional brainstem development in the rat.

Rat pups exposed to cocaine via maternal intromission throughout gestation and lactation displayed significantly prolonged auditory brainstem response component latencies and interwave intervals. Longitudinal analysis revealed that this effect was most pronounced on the 22nd postnatal day. Increasing the rate of stimulation further impaired neurosensory transmission in the caudal auditory pathway. These results indicate that both axonal and synaptic events may be affected to some degree and the timing (age) of optimum cocaine influence suggests that delayed myelination may be involved. The corresponding retardation in general development of the cocaine exposed pups further implicates maternal, fetal and postnatal utilization of nutritional resources as the basis for this outcome.

Analysis of Variance↗
PubMed1992

Intranasal immunization with liposomes containing IL-2 enhances bacterial polysaccharide antigen-specific pulmonary secretory antibody response.

Secretory IgA (sIgA) present at mucosal surfaces such as the lungs and intestine plays an important role in resistance to infection occurring at these anatomic sites. Because IL-2 and IL-4 can augment B cell proliferation and Ig production, we investigated possible adjuvant effects of these cytokines on bacterial polysaccharide-specific pulmonary sIgA generation. As shown in previous studies, intranasal immunization with liposomes containing bacterial polysaccharide from Aerobacter levanicum and Pseudomonas aeruginosa resulted in increased numbers of bacterial polysaccharide-specific pulmonary plasma cells and sIgA titers, compared with those found in unimmunized mice. Inclusion of IL-2, but not IL-4, into the intranasally administered liposomes further increased titers of bacterial polysaccharide specific sIgA and pulmonary plasma cells. Intranasal vaccination with liposomes containing bacterial polysaccharide and 10 micrograms/kg IL-2 increased bacterial polysaccharide-specific pulmonary plasma cell numbers by more than 80-fold compared with the response in mice immunized with liposomes containing bacterial polysaccharide, but without IL-2. The percentage of pulmonary plasma cells producing antibody to polysaccharide from A. levanicum rose from 0.14% in mice intranasally immunized with liposomes containing only polysaccharide to 4.1% in animals vaccinated with liposomes containing polysaccharide and IL-2. Intranasal immunization with liposomes containing P. aeruginosa polysaccharide and IL-2 significantly reduced mortality from P. aeruginosa pneumonia. These results demonstrate that IL-2 has potent adjuvant effects on bacterial Ag-specific sIgA production in the lungs when included in intranasally administered liposomes.

Adjuvants, Immunologic↗
PubMed1992

Proton uptake accompanies formation of the ternary complex of citrate synthase, oxaloacetate, and the transition-state analog inhibitor, carboxymethyl-CoA. Evidence that a neutral enol is the activated form of acetyl-CoA in the citrate synthase reaction.

Citrate synthase complexes with the transition-state analog inhibitor, carboxymethyl-CoA (CM-CoA), are believed to mimic those with the activated form of acetyl-CoA. The X-ray structure [Karpusas, M., Branchaud, B., & Remington, S.J. (1990) Biochemistry 29, 2213] of the ternary complex of the enzyme, oxaloacetate, and CMCoA has been used as the basis for a proposal that a neutral enol of acetyl-CoA is that activated form. Since the inhibitor carboxyl has a pKa of 3.90, analogy with an enolic acetyl-CoA intermediate leads to the prediction that a proton should be taken up from solution upon formation of the analog complex so that the transition-state analog carboxyl is protonated when bound. We have obtained evidence in solution for this proposal by comparing the isoelectric points and the pH dependence of the dissociation constants of the ternary complexes of the pig heart enzyme with the neutral ground-state analog inhibitor, acetonyl-CoA (KCoA), and the anionic transition-state analog inhibitor (CMCoA) and by studying the NMR spectra of the transition-state analog complexes of allosteric (Escherichia coli) and nonallosteric (pig heart) enzymes. The pH dependence of the dissociation constant of the ground-state analog indicates no proton uptake, while that for the transition-state analog indicates that 0.55 +/- 0.04 proton is taken up when the analog binds to the citrate synthase-oxaloacetate binary complex. The overall charges of ternary complexes of the pig heart enzyme with the transition-state and ground-state analog inhibitors are the same, as monitored by their isoelectric points.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetyl Coenzyme A↗
PubMed1992

n-butyrate reduces the expression of beta-galactoside alpha 2,6-sialyltransferase in Hep G2 cells.

n-Butyrate, a short chain fatty acid that is produced by colonic bacterial fermentation, is detectable in portal blood and induces differentiation in various human neoplastic cell lines. Earlier reports indicated approximately 20-fold induction in vitro by n-butyrate of the sialyltransferase that catalyzes terminal glycosylation of GM3 ganglioside in HeLa and colon cancer cells. We previously isolated a 1.3-kilobase cDNA for a human beta-galactoside alpha 2,6-sialyltransferase, for which N-linked glycoproteins are the acceptors. We report here that treatment of Hep G2 cells with 5 mM n-butyrate for 24 h reduced beta-galactoside alpha 2,6-sialyltransferase mRNA levels by approximately 90%. Reductions in mRNA level were followed by approximately 75 and approximately 90% reductions, respectively, in specific beta-galactoside alpha 2,6-sialyltransferase enzyme activity after treatment for 24 and 36 h with 5 mM n-butyrate. However, in contrast with earlier reports of enhanced ganglioside synthesis in response to n-butyrate treatment, incubation of Hep G2 cells with n-butyrate did not alter the ganglioside pattern as assessed by thin layer chromatography of lipids extracted from treated cells. Nuclear run-on reactions indicated that the rate of transcription of beta-galactoside, alpha 2,6-sialyltransferase was not altered by treatment with 5 mM n-butyrate for 24 h, but the effects of this treatment on cytoplasmic levels of beta-galactoside alpha 2,6-sialyltransferase mRNA were largely negated by co-treatment with actinomycin D or cycloheximide. Therefore, our results show that n-butyrate reduces expression of mature beta-galactoside alpha 2,6-sialyltransferase mRNA by post-transcriptional mechanisms.

Antigens, CD↗
PubMed1992

Late results of suprarenal Greenfield vena cava filter placement.

Placement of the Greenfield filter above the renal veins was necessary in 71 (9%) of 821 total patients in the filter registries of two institutions. The status of 60 patients (85%) could be verified, with follow-up data ranging from 18 months to 16 years (average, 53 months). Of 24 deaths (34%), none was from recurrent embolism or renal failure; death was most commonly associated with a malignant neoplasm. The recurrent embolism rate was 4%, identical to the infrarenal experience. Duplex evaluation of the filters in 22 patients, representing the majority (61%) of living patients, showed that all the filters were patent. Sixteen patients (41%) had lower-extremity edema that predated filter insertion, and in no patient did the results of noninvasive venous studies worsen. Filter fracture (two patients) or distal migration (two patients) had no clinical sequelae, and there was no evidence of renal dysfunction. For thrombus extending to the level of the renal veins or within them and for pregnant patients or women of childbearing age, suprarenal placement of the Greenfield filter is safe and effective, with no filter obstruction seen in follow-up extending to 16 years.

Adolescent↗
PubMed1992

Early evidence of beneficial effects of chordal preservation in mitral valve replacement on left ventricular dimensions.

Earlier authors have shown the improved left ventricular (LV) function after chordae-preserving mitral valve replacement (MVR) in follow-up studies. Seventy-nine consecutive patients undergoing MVR were studied preoperatively and pre-discharge with M-mode and two-dimensional Color Doppler echocardiography for early LV morphometric changes. Conventional MVR was performed in 42 patients (Group 1) and the posterior leaflet-chordae-papillary muscle complex was preserved in 37 patients (Group 2). Both cohorts were similar in age, sex, preoperative NYHA class and valve pathology. Four St. Jude bioprostheses, 9 Medtronic and 66 Sorin prostheses were implanted. The intraoperative and perioperative management protocol was uniform for both groups. The median left atrial dimension in both groups decreased to better physiological levels (53 to 46 mm in group 1, 52.5 to 46 mm in group 2). The median LV enddiastolic dimension increased from 47 to 48 mm in group 1 while it decreased from 56.5 to 49 min in group 2. The median LV endsystolic dimension remained unchanged in group 1 but decreased in group 2 (37.6 to 36 mm). Echocardiographic documentation of such early changes in the LV dimensions after modified MVR indicates that the beneficial effects of chordal preservation become evident early in the postoperative period and may explain the improved perioperative LV function after modified MVR compared to conventional MVR.

Adolescent↗
PubMed1992

In-vitro activity of RP 59500, a new semisynthetic streptogramin antibiotic, against gram-positive bacteria.

A study of the in-vitro activity of RP 59500, a semisynthetic derivative of pristinamycin, against a range of Gram-positive bacteria including erythromycin-resistant strains was undertaken. MICs were determined by plate dilution in IsoSensitest agar and MBCs by velvet pad replication. RP 59500 was found to have in-vitro activity almost identical to that of its parent compound, pristinamycin. Sixty methicillin-resistant Staphylococcus aureus (MRSA) and 60 methicillin-sensitive S. aureus (MSSA) were found to be sensitive to RP 59500, with MICs of 0.13-1 mg/L. All the MSSA and most MRSA showed an MBC less than 2 mg/L. Erythromycin-resistant S. aureus (62) were as sensitive to RP 59500 as were erythromycin-sensitive strains (58). RP 59500 was more active against MRSA than fusidate, vancomycin, amikacin, ciprofloxacin, imipenem or erythromycin. Forty strains of coagulase-negative staphylococci (11 were erythromycin-resistant) showed MICs of 0.25-1 mg/L, and RP 59500 was more active than methicillin, erythromycin, imipenem, cefotaxime or vancomycin. Sixty strains of streptococci (20 pneumococci and 40 of groups A, B, C, or G) and 20 enterococci were inhibited by 0.13-1 mg/L and 0.25-4 mg/L, respectively. Gram-positive bacilli (five each of diphtheroids, lactobacilli, Listeria monocytogenes and Bacillus spp., and 19 Clostridium spp.) were also sensitive, with MICs of between 0.06 and 4 mg/L. All 279 strains tested were judged to be sensitive to RP 59500, which was bactericidal and showed a small inoculum effect. The activity against MRSA, and against erythromycin-resistant strains of all species was particularly interesting.

Erythromycin↗
PubMed1992

The power of the N-test of haplotype concordance.

The N-test of haplotype concordance among siblings affected by some disease under investigation is used to decide whether there is a disease susceptibility gene linked to a marker locus or chromosomal region. The use of this test and appropriate modifications of it is briefly reviewed. The power of the ordinary N-test is then derived as a function of several parameters. The sample size needed to attain a given power is then derived. Some of the parameters are specified and the required sample sizes are given in tables for different values of the main unknown parameters.

Algorithms↗
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↗