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Biomedical subjects

S Mehta

Publications and source records attributed to S Mehta.

At least 91 records · Page 5Linked to original sources
PubMed1999

Porcine endotoxemic shock is associated with increased expired nitric oxide.

OBJECTIVES: Nitric oxide (NO) is believed to decrease systemic vascular resistance in sepsis, but the data are mainly from studies on rats and mice. We tested this hypothesis in pigs and also whether there is induction of the inducible form of nitric oxide synthase (iNOS). DESIGN: Animal study. SETTING: University center. SUBJECTS: Ten pigs. INTERVENTIONS: The pigs were anesthetized and mechanically ventilated. MEASUREMENTS AND MAIN RESULTS: Pulmonary and systemic hemodynamics were monitored and mixed expired NO was measured by chemiluminescence. Animals received 20 microg/kg of endotoxin over 2 hrs. We then infused 25 mg/kg of N(omega)-nitro-L-arginine methyl ester (L-NAME) over 10 mins, followed by 0.5 g/kg of L-arginine, the precursor of NO, for 30 mins more to reverse the effects of L-NAME. Five additional pigs were treated with 20 microg/kg of endotoxin for 2 hrs and followed for another hour. Plasma nitrite/nitrate was measured by Greiss reaction. The animals were then killed and tissues were sampled for iNOS by Western blot, and iNOS messenger RNA by reverse transcriptase polymerase chain reaction. After endotoxin infusion, arterial pressure (BP) initially increased, then decreased to 62+/-1 mm Hg from the baseline of 115+/-4 mm Hg (p<.001). Cardiac output initially decreased, then increased slightly from the baseline of 3.7+/-0.2 to 4.2 +/-0.3 L/min (p<.05). The BP pattern was mirrored by an increase in expired NO concentration from 6.4+/-0.8 to 10.4+/-1.4 parts per billion (p<.05) and increased rate of pulmonary NO excretion in expired gas (VeNO) from 71+/-10 to 146+/-24 pmol/kg/min (p<.05). Inhibition of NOS with L-NAME decreased expired NO concentration and VeNO and increased BP; however, cardiac output decreased. The vasoconstriction produced by L-NAME was partially reversed by L-arginine, and this also increased VeNO from 80+/-18 after L-NAME to 132+/-31 pmol/kg/min (p<.05). Plasma nitrite (n = 5) did not change and there was no iNOS by Western blot analysis in multiple tissues. However, there was a small increase in messenger RNA by reverse transcriptase polymerase chain reaction. CONCLUSIONS: The time course and pattern of changes in expired NO during endotoxemia followed the change in systemic hemodynamics, which supports a causal role for NO in sepsis. However, this is not due to a large production of NO by iNOS induction. The hemodynamic pattern, nitrite in blood, and changes in expired NO also differed markedly from those findings in rodent models and caution should be used in extrapolating from rodents to higher order animals.

Analysis of Variance↗
PubMed1999

Randomized trial of prolonged chloroquine therapy in advanced pulmonary sarcoidosis.

Sarcoidosis may cause severe ventilatory impairment requiring corticosteroid treatment. Chloroquine (CQ) can be an effective treatment for lung sarcoidosis with few side effects, but has not been accepted as standard therapy. We investigated the benefits of prolonged CQ therapy in 23 symptomatic patients with biopsy-proven pulmonary sarcoidosis (duration, >/= 2 yr). Patients were initially treated for 6 mo with CQ, 750 mg/d, tapering every 2 mo to 250 mg/d. Eighteen patients were then randomized to either a Maintenance group (CQ, 250 mg/d) or to an Observation group (no CQ). After the initial treatment, significant improvement was observed in symptoms, pulmonary function, angiotensin-converting enzyme, and lung gallium scan. Patients randomized to the Maintenance group showed a slower decline in pulmonary function (FEV1, 51.4 +/- 28.2 ml/yr [Maintenance] versus 196.3 +/- 33.4 ml/yr [Observation], p < 0.02) and had fewer relapses: 2 of 10 patients in the Maintenance group at 29.5 +/- 4.9 mo versus 6 of 8 patients in the Observation group at 15.5 +/- 2.9 mo. Adverse effects were seen mainly during high-CQ dosage. We conclude that CQ should be an important consideration for the treatment and maintenance of chronic pulmonary sarcoidosis.

Adult↗
PubMed1999

Painless left hemorrhagic pleural effusion: An unusual presentation of dissecting ascending aortic aneurysm.

Aortic dissection is a catastrophic event that is commonly associated with severe pain, massive hemorrhage, and high mortality. In this report, we present the case of a 31-year-old man who presented with painless, hemorrhagic left pleural effusion. Further investigation revealed a 9-cm dissecting ascending aortic aneurysm that was thought to be due to a congenitally bicuspid aortic valve. We suggest that ascending aortic aneurysm be included in the differential diagnosis of hemorrhagic pleural effusion, even in the absence of the classic features of aortic dissection, such as chest pain, advanced age, or history of hypertension.

Adult↗
PubMed1999

Immunosuppressive activity in buffalo placenta.

Immunosuppressive activity in buffalo placenta was evaluated by measuring proliferation of lymphocytes in presence of phytohaemagglutinin (PHA) alone or PHA plus placental proteins. The immunosuppressive activity was dose-dependent over the protein concentration range of 10-50 micrograms/ml. Proteins from both cotyledon and non-cotyledon portions of placenta exhibited immunosuppressive activity. Fractions obtained with 0-40, 40-60 and 60-80% saturated ammonium sulphate exhibited 70, 73 and 75% suppression, respectively. PBS-soluble placental proteins were resolved on G-100 column into three peaks that exhibited 69 (peak 1), 55 (peak 2) and 73% (peak 3) suppression. Exogenously added interleukin-1 (IL-1) failed to reverse the suppression caused by buffalo placental proteins.

Animals↗
PubMed1999

Inflammatory bowel disease in children: Indian perspective.

The magnitude of inflammatory bowel disease in childhood in India is largely unknown. At the Pediatric Gastroenterology section of PGIMER, Chandigarh, 15 out of 294 children (5%) admitted for colonic disorders were diagnosed to have ulcerative colitis. Diagnosis is suspected on the basis of clinical presentation and established by sigmoidoscopy, rectal biopsy and double contrast barium enema. Widely prevalent bacillary dysentery, acute amoebic colitis and antibiotic induced colitis need to be kept in differential diagnosis of acute presentation of ulcerative colitis. Chronic or recurrent colitis needs to be differentiated from tuberculous colitis. Inflammatory bowel disease deserves clinical suspicion in all unusual cases of colitis which do not respond to treatment of common infective agents.

Adolescent↗
PubMed1998

Repression of enzymes of the pentose phosphate pathway by glucose in fission yeast.

We examine here the effect of carbon sources on the synthesis of the shunt pathway enzymes in the fission yeast Schizosaccharomyces pombe growing on a mixture of ethanol and glycerol. Delta-gluconolactone induces practically every one of these enzymes. Glucose in contrast tends to attenuate the synthesis of the majority of them. RNA analysis confirms that their induction and repression reflect changes in the levels of their transcripts.

Enzyme Induction↗
PubMed1998

Activation of the Jak2-Stat5 signaling pathway in Nb2 lymphoma cells by an anti-apoptotic agent, aurintricarboxylic acid.

Biological effects of many hormones and cytokines are mediated through receptor-associated Jak tyrosine kinases and cytoplasmic Stat transcription factors, including critical physiological processes such as immunity, reproduction, and cell growth and differentiation. Pharmaceuticals that control Jak-Stat pathways are therefore of considerable interest. Here we demonstrate that a single Jak-Stat pathway can be activated by aurintricarboxylic acid (ATA), a negatively charged triphenylmethane derivative (475 Da) with anti-apoptotic properties. In prolactin (PRL)-dependent Nb2 lymphocytes, ATA sustained cell growth in the absence of hormone and mimicked rapid PRL-induced tyrosine phosphorylation of Jak2 and activation of Stat5a and Stat5b with tyrosine phosphorylation, heterodimerization, DNA binding, and induction of the Stat5-regulated pim-1 protooncogene. ATA also mimicked PRL activation of serine kinases ERK1 and ERK2. However, unlike PRL, ATA did not regulate Stat1 or Stat3. ATA also did not affect Jak3, which is activated in these cells by interleukin-2 family cytokines. Although the mechanism and specificity by which ATA activates Jak2, Stat5, and ERKs in Nb2 cells are still unclear, the present study demonstrates that certain hormone or cytokine effects on Jak-Stat pathways can be discretely imitated by a low molecular weight, non-peptide pharmaceutical. The results are also consistent with Stat5 involvement in lymphocyte growth and survival.

Apoptosis↗
PubMed1998

What do parents know about lead poisoning? The Chicago Lead Knowledge Test. Pediatric Practice Research Group.

OBJECTIVES: To examine the extent of parental knowledge about lead poisoning and its prevention and to determine characteristics associated with accurate lead knowledge. SETTING: Twenty-three pediatric practices and 1 family practice in Chicago, Ill, and its suburbs. METHODS: A 24-question test regarding lead poisoning and its prevention (Chicago Lead Knowledge Test) was developed based on lead specialists' review and parental test-retest reliability. One point was assigned for each correct response. It was self-administered by a sample of 2225 parents of 0- to 6-year-old children visiting study practices. A 1-way analysis of variance (ANOVA) was used to determine the association of demographic descriptors with test scores. RESULTS: Respondents had a mean age of 33 years. Ninety percent were mothers, 49% were college graduates, and 80% were home owners. Fifteen percent lived in homes built before 1950, of which 36% were remodeled or renovated during the last 6 months. Respondents' youngest children were 80% white, 10% Hispanic, 5% African American, and 5% other. Ten percent received Medicaid and 86% had other medical insurance. Thirty-four percent recalled receipt of lead information from a health care provider, and 2.4% had had a child with a blood lead level of 0.48 micromol/L (10 microg/dL) or higher. The mean Chicago Lead Knowledge Test score was 12.2 (SD, 3.7). Questions related to lead exposure were more often answered correctly than those related to prevention and diet. In the ANOVA model, those who recalled receipt of lead information from a health care provider, college graduates, respondents aged 30 years or older, Hispanic respondents, and those living in homes built before 1950 had higher scores (all ANOVA P< or =.001). CONCLUSIONS: Parents do not have much knowledge of ways to prevent childhood lead poisoning. Information from a health care provider can aid parental knowledge. The Chicago Lead Knowledge Test is a new self-administered tool to help evaluate lead education programs.

Adult↗
PubMed1998

Primary alpha-sarcoglycan deficiency responsive to immunosuppression over three years.

An 8-year-old girl developed weakness over 2 years and an elevated creatine kinase. The biopsy was most consistent with an active dystrophy with many inflammatory cells present. A trial of immunosuppression was started. In the first 2 months of treatment with prednisone, she had functionally and quantitatively significant improvement in her proximal strength. Over 3 years of treatment she maintained stable strength. Subsequent genetic studies showed that she had primary alpha-sarcoglycan deficiency. The timing and the degree of benefit in strength were similar to that seen in boys with Duchenne muscular dystrophy who are treated with prednisone.

Amino Acid Substitution↗
PubMed1998

Patterns of angiotensin-converting enzyme inhibitor prescriptions, educational interventions, and outcomes among hospitalized patients with heart failure.

BACKGROUND: Among hospitalized patients with heart failure, we describe characteristics associated with prescription of angiotensin-converting enzyme (ACE) inhibitors in the doses recommended by clinical practice guidelines. We also describe the impact of ACE inhibitor prescriptions, increases in ACE inhibitor dose, and nonpharmacologic educational interventions on readmission-free survival rates. HYPOTHESIS: We hypothesize that care by a cardiologist physician and higher mean arterial blood pressure on admission are associated with receipt of optimal ACE inhibitor doses. We hypothesize that receipt of an ACE inhibitor at discharge and an increase in ACE inhibitor dose during hospitalization are associated with superior readmission-free survival. METHODS: Between January 1, 1992, and December 31, 1993, medical records were reviewed for consecutively hospitalized patients with a principal diagnosis of heart failure at an academic medical center. Documented instructions and medications prescribed at discharge were abstracted. Deaths and readmissions through December 31, 1994, were identified with the National Death Index and the study institution's administrative data base, respectively. RESULTS: During 1992 and 1993, 387 patients were discharged alive from hospitalization for heart failure. Among patients discharged on enalapril or captopril, 18% received doses recommended by heart failure clinical practice guidelines. Patients discharged on a recommended ACE inhibitor dose were more likely to be African-American and had lower sodium levels and higher mean arterial pressures than patients discharged on lower ACE inhibitor doses. In survival analyses, an increase in ACE inhibitor dose was associated with improved readmission-free survival, independent of left ventricular systolic function type. Receipt of an ACE inhibitor at discharge was also associated with superior readmission-free survival, while nonpharmacologic educational instructions were not associated with improved outcomes. CONCLUSION: Interventions are needed to improve the frequency with which ACE inhibitors are prescribed at recommended doses to hospitalized patients with heart failure. We conclude that among these patients, receipt of an ACE inhibitor at discharge and an increase in ACE inhibitor dose during hospitalization are each associated with measurable effects on readmission-free survival, while provision of educational instructions as currently practiced is not associated with better outcomes.

Aged↗
PubMed1998

An evidenced-based clinical pathway for acute appendicitis decreases hospital duration and cost.

BACKGROUND/PURPOSE: In the pediatric population, appendicitis remains the most common surgical emergency encountered. The purpose of this study was to determine the impact of an evidence-based clinical pathway for acute appendicitis on patient care as well as hospital and home care costs at the authors' pediatric institution. METHODS: A prospective evaluation was conducted of an appendicitis clinical pathway (June 1996 through November 1996) compared with historical control patients (June 1994 through November 1994) not cared for by the pathway. RESULTS: Data (average +/- SD) for 120 pathway (P) patients were compared with 122 control (C) patients. Age (11.5 +/- 3.6 years for C v 11.2 +/- 3.9 years for P), rates of negative appendectomy (12.3% for C v 9.2% for P) and perforation (26.2% for C v 18.3% for P) were similar. Pathway patients with nonperforated appendicitis were more often discharged from the hospital within 24 hours (48% for C v 67% for P; P = .014) with lower hospital costs ($4,095 +/- $1,280 for C v $3,638 +/- $1,633 for P; P = .001). Pathway patients with perforated appendicitis had shorter hospitalization (185.2 +/- 59 hours for C v 113 +/- 44 hours for P; P = .0001) and lower hospital costs ($11,175 +/- $3,893 for C v $7,823 +/- $2,366 for P; P = .0001). CONCLUSION: An evidence-based appendicitis pathway decreased duration of hospitalization and cost without adversely affecting diagnosis or therapy. Clinical pathways for surgical diagnoses may prove useful as a means to minimize costs without compromising patient care.

Acute Disease↗
PubMed1998

SAP90 binds and clusters kainate receptors causing incomplete desensitization.

The mechanism of kainate receptor targeting and clustering is still unresolved. Here, we demonstrate that members of the SAP90/PSD-95 family colocalize and associate with kainate receptors. SAP90 and SAP102 coimmunoprecipitate with both KA2 and GluR6, but only SAP97 coimmunoprecipitates with GluR6. Similar to NMDA receptors, GluR6 clustering is mediated by the interaction of its C-terminal amino acid sequence, ETMA, with the PDZ1 domain of SAP90. In contrast, the KA2 C-terminal region binds to, and is clustered by, the SH3 and GK domains of SAP90. Finally, we show that SAP90 coexpressed with GluR6 or GluR6/KA2 receptors alters receptor function by reducing desensitization. These studies suggest that the organization and electrophysiological properties of synaptic kainate receptors are modified by association with members of the SAP90/PSD-95 family.

Amino Acid Sequence↗
PubMed1998

Dynamic in vitro and in vivo performance of a permanent total artificial heart.

In vivo characterization studies were performed to compare the dynamic in vivo performance of the Penn State/3M Health Care electric total artificial heart to existing in vitro data. Fully implanted systems were utilized including the artificial heart, controller, backup batteries, compliance chamber, and transcutaneous energy transmission. Catheters were implanted to measure central venous pressure (CVP), left atrial pressure (LAP), right atrial pressure (RAP), pulmonary artery pressure (PAP), and aortic pressure (AoP). Cardiac output (CO) was determined from the implanted controller, and systemic vascular resistance (SVR) was calculated. Steady state data were collected for each animal along with data regarding the transient responses to changes in preload and afterload. Preload was manipulated through volume changes. Afterload changes were accomplished through vasoactive agents. Increased preload caused little change in cardiac output because the pump output was nearly maximum at baseline. LAP, AoP, and SVR increased with increasing RAP. Decreased preload caused a reduction in CO, LAP, and SVR. Afterload increase resulted in a slight decrease in flow and an increase in system power and SVR. Afterload reduction was accompanied by a decrease in preload and a concomitant reduction in flow. Overall, the system response was similar to the response observed in vitro.

Animals↗
PubMed1998

Pharmacokinetics of a degradable drug delivery system in bone.

Local delivery of antibiotics via a degradable carrier has the potential for high local antibiotic levels and avoids systemic toxicity. Intravenous access, renal function monitoring, and later surgical removal may not be required when degradable local delivery modalities are used. This study examined the in vivo elution of gentamicin from processed bovine collagen (Type I). Gentamicin impregnated collagen (3 mg/kg) was implanted into the femoral medullary canal of 45 adult white rabbits. The gentamicin was released into the bone and averaged greater than 600 micrograms/ml during the initial 48 hours. Local bone levels fell to 144.40 +/- 229.84 micrograms/ml at 5 days and were subsequently greater than or equal to 10.30 +/- 5.02 micrograms/ml through Day 28. Serum levels reached an average peak of 1.25 +/- 0.29 micrograms/ml 5 hours after implantation and fell below 1.0 microgram/ml at 12 hours after implantation. Serum levels subsequently averaged less than or equal to 0.63 +/- 0.09 microgram/ml through Day 28. Collagen impregnated with gentamicin proved to be an effective degradable carrier of gentamicin in the healthy rabbit; it provided local bone concentrations above the minimum inhibitory concentration of gentamicin and serum concentrations below levels associated with systemic toxicity as long as 28 days after implantation.

Animals↗