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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

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

A multi-user real time inventorying system for radioactive materials: a networking approach.

A computerized system for radioisotope management and real time inventory coordinated across a large organization is reported. It handles hundreds of individual users and their separate inventory records. Use of highly efficient computer network and database technologies makes it possible to accept, maintain, and furnish all records related to receipt, usage, and disposal of the radioactive materials for the users separately and collectively. The system's central processor is an HP-9000/800 G60 RISC server and users from across the organization use their personal computers to login to this server using the TCP/IP networking protocol, which makes distributed use of the system possible. Radioisotope decay is automatically calculated by the program, so that it can make the up-to-date radioisotope inventory data of an entire institution available immediately. The system is specifically designed to allow use by large numbers of users (about 300) and accommodates high volumes of data input and retrieval without compromising simplicity and accuracy. Overall, it is an example of a true multi-user, on-line, relational database information system that makes the functioning of a radiation safety department efficient.

Computer Communication Networks↗

The ankle brachial index independently predicts walking velocity and walking endurance in peripheral arterial disease.

OBJECTIVES: Maintaining function among older men and women is an important public health goal as the population lives longer with chronic disease. We report the relationships between lower extremity peripheral arterial disease (PAD), PAD severity, and PAD-related symptoms with walking velocity and endurance among men and women aged 55 and older. DESIGN: A cross-sectional design. SETTING: An academic medical center. PARTICIPANTS: Participants with PAD were men and women aged 55 and older identified from a blood flow laboratory or a general medicine practice (n = 158). Randomly selected controls without PAD were identified from the general medicine practice (n = 70). MEASUREMENTS: PAD was diagnosed and quantified using the ankle brachial index (ABI). Subjects were categorized according to whether they had severe PAD (ABI <0.40), mild to moderate PAD (ABI 0.40 to <0.90), or no PAD (ABI 0.90 to <1.50). Walking endurance was assessed with the 6-minute walk. Usual walking velocity and maximal walking velocity were assessed with "usual" and "maximal" paced 4-meter walks, respectively. RESULTS: Average distances achieved in the 6-minute walk were 1569+/-390 feet for subjects with ABI 0.90-1.50, 1192+/-368 feet for subjects with ABI 0.40 to <0.90, and 942+/-334 feet for subjects with ABI < 0.40 (trend P value < .001). Walking velocities for both the usual and maximal paced 4-meter walks were slowest among subjects with ABI < 0.40 and fastest among subjects with ABI 0.90 to <1.50. Subjects with PAD who had pain at rest had slower walking velocity and poorer walking endurance than other subjects with PAD. In multiple linear regression analyses that included subjects with PAD only, ABI level was an independent predictor of 6-minute walk performance (regression coefficient = 159 ft/0.40 ABI units, P = .011), usual paced 4-meter walk (regression coefficient = .095 meters/sec/0.40 ABI units, P = .031), and maximal paced 4-meter walk (regression coefficient = .120 meters/sec/0.40 ABI units, P = .050) adjusting for age, sex, race, leg symptoms, and comorbid diseases known to affect functioning. Pain at rest was associated independently with the maximally paced 4-meter walk (-0.201 meters/sec, P = .024), but not with the other walks. CONCLUSION: ABI level has a measurable and independent association with walking endurance and both usual and maximal walking velocity. These data suggest that PAD may impair lower extremity function by diminishing function of both Type I ("slow twitch") and Type II ("fast twitch") muscle fibers. Because walking velocity has important prognostic implications for functioning, these data also suggest that ABI may be used to identify patients at increased risk of mobility loss.

Aged↗

Endogenous pulmonary nitric oxide in the regulation of airway microvascular leak.

Endogenous nitric oxide (NO) is an important modulator of airway function, but its role in the regulation of airway microvascular leak (AMVL) remains unclear. Thus we assessed the effects of NO synthase (NOS) inhibition on expired NO (ENO) levels and on AMVL measured by the Evans blue dye technique in guinea pigs. In control unsensitized animals, systemic NG-nitro-L-arginine methyl ester (L-NAME) reduced ENO by 70 +/- 8% (P < 0.01) and reduced AMVL by 92 +/- 1 and 44 +/- 17% (P < 0.05 for both) in the extrapulmonary and intrapulmonary airways, respectively. In animals sensitized and challenged with intratracheal antigen, markedly increased levels of AMVL and ENO were similarly attenuated by L-NAME. In contrast, aminoguanidine, a relatively selective type II NOS inhibitor, reduced ENO in both antigen-sensitized and control unsensitized animals by 39 +/- 3% (P < 0.01) but had no effect on AMVL. These data indicate that endogenous pulmonary NO contributes to both basal and antigen-stimulated levels of AMVL in guinea pigs and that this NO-dependent activity does not appear to be derived from type II NOS.

Animals↗

A calcaneal fracture with extrusion of the posterior facet.

This is a case report of a 19-year-old woman who sustained multiple fractures including a right calcaneal fracture with extrusion of the posterior facet. The medial soft-tissue injury led to a full thickness skin loss. Despite loss of subtalar motion and decreased toe movement, she is satisfied with her result. The importance of the soft-tissue injuries, especially to the skin and tendons, associated with severely displaced calcaneal fracture dislocations is emphasized by this case report.

Adult↗

Characterizing alterations in the pulmonary surfactant system in a rat model of Pseudomonas aeruginosa pneumonia.

Bacterial pneumonia remains a significant cause of patient morbidity and mortality worldwide. Pulmonary surfactant serves to maintain homeostasis in the lung through the maintenance of alveolar stability and the regulation of the alveolar immune response. The purpose of this study was to characterize the lung injury and associated surfactant alterations in a rat model of acute Pseudomonas aeruginosa pneumonia. Pneumonia was induced in male Sprague-Dawley rats via intratracheal injection of 0.2 ml, phosphate-buffered saline (PBS) containing P. aeruginosa (6x10(8) colony-forming units x mL(-1)). Control animals received 0.2 mL sterile PBS. Twenty-four hours after inoculation, the pneumonia group (PN) exhibited clinical signs of pneumonia including deficits in gas exchange, leukopenia and elevated arterial lactate levels. Morphological assessment confirmed the presence of pneumonia with airspaces filled with polymorphonuclear cells. Lung homogenate analysis demonstrated evidence of bacterial colonization of pneumonic lung tissue. Lung compliance was also significantly lower in the PN group. Lung lavage analysis of PN rats revealed the pooled surfactant levels to be lower and the surfactant function reduced compared to control rats. Surfactant composition was also found to be altered in PN rats. These results demonstrate that in Pseudomonas aeruginosa pneumonia, the pulmonary surfactant system is both poorly functioning and reduced in quantity. These alterations may contribute to the lung dysfunction characteristic of this disorder.

Acute Disease↗

Oxidative-hepatic injury of isoniazid-rifampicin in young rats subjected to protein and energy malnutrition.

The role of protein and energy malnutrition in the pathogenesis of isoniazid (INH)-rifampicin (RMP) induced hepatic injury was investigated. Status of oxidative/antioxidative profile was the mechanistic approach to enumerate the nature of injury. Weanling rats were fed with ad-libitum quantity of isocaloric diets containing 5% casein based proteins for the production protein and energy malnutrition. INH and RMP (50 mg/kg of each) were injected intraperitonially for a period of two weeks. Analysis of serum transaminases and histopathological observations revealed hepatic injury. Hepatic thiols and blood glutathione were decreased significantly in INH and RMP treated groups. Among antioxidative enzymes, hepatic superoxide dismutase, catalase, glutathione peroxidase and glutathione-S-transferases (against CDNB and DCNB substrates) showed significant decline of activities in INH and RMP treated groups. The activities of hepatic glutathione reductase, glutathione-S-transferase (against EA substrate) and lipid peroxidation observed significant elevation. A careful comparison of protein and energy restriction revealed a greater degree of oxidative-stress of INH-RMP in protein-restriction.

Animals↗

Regional changes in 5-HT1A but not in 5-HT2A receptors in mouse brain after Semliki Forest virus infection: radioligand binding and autoradiographic studies.

Dysfunction of brain 5-hydroxytryptaminergic systems has been associated with several neurological and psychiatric diseases which may have a viral aetiology. The effect of Semliki Forest virus (SFV) on 5-hydroxytryptamine (5-HT1A and 5-HT2A) receptors in mouse brain has been assessed by membrane homogenate binding and autoradiography. Adult mice were injected with saline or virus and brains removed 2, 6, 14, 22 and 35 days after infection. 5-HT1A and 5-HT2A receptors were characterised by saturation studies using [3H] 8-OH-DPAT and [3H] Ketanserin respectively. SFV infection increased 5-HT1A receptor numbers by up to 80% in the cortex on days 6, 14, and 22 but had no effect on Bmax in the midbrain, pons/medulla and the hypothalamus. SFV infection did not affect 5-HT2A receptor number in any of the brain regions studied and the affinity (Kd) of either ligand for 5-HT1A or 5-HT2A receptors was unaffected. Autoradiographic mapping of 5-HT1A receptors in SFV-infected brain showed substantially higher binding in nucleus accumbens, tenia tecta, septohippocampal nucleus, septum, medial and basolateral amygdaloid nucleus, anterioventral preoptic nucleus, hippocampus, interpeduncular nucleus, frontal, lateral orbital, and entorhinal cortex and claustrum on days 6 and 14. Elevated binding persisted in tenia tecta, frontal, lateral orbital, entorhinal cortex, and hippocampal formation to day 22. Autoradiography of 5-HT2A receptors using [3H] Ketanserin showed no difference in the binding in SFV-infected brains. A decrease in plasma corticosterone levels in SFV-infected mice was observed on post infection days 6 and 22. These results show SFV infection induces a regionally selective upregulation of 5-HT1A but not 5-HT2A receptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗