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Biomedical subjects

R Shah

Publications and source records attributed to R Shah.

At least 73 records · Page 4Linked to original sources
PubMed1999

Stable transfection of rat preporinsulin II gene into rat hematopoietic stem cells via recombinant adeno-associated virus.

We investigated the ability of recombinant adeno-associated virus (rAAV), to mediate the transfer of rat preproinsulin II (rI2) gene into rat hematopoietic stem cells in vitro and expression of rI2 following intra-venous (i.v.) injection of infected stem cells into syngeneic rats. The pLP-1 recombinant plasmid containing rI2 was engineered as follows: rI2 with RSV-promoter was released from pBC 12BI (ATCC), purified, and inserted into BamH1 site of rAAV vector plasmid pWP-19. Plasmid pLP-1, together with pAAV¿AD (Somatix Corp.), was used to co-transfect cell line 293 (ATCC). The rAAV genome was rescued using helper adenovirus and packaged into mature rAAV virions (vLP-1). Bone-marrow from female Wistar-Furth rats was enriched for stem cells by using plastic adherence and negative selection with monoclonal anti-rat CD3 and CD45RA to deplete T and B cells. The remaining cells were exposed to vLP-1 (moi=50:1) for 2 hours. Transfection was confirmed by PCR of neomycin resistance gene (neoR) after 8 days in culture. For in vivo studies, ten million exposed stem cells were injected i.v. into syngeneic rats (n=3). The results represent 3 identical experiments. Expression of neoR and rI2 was analyzed by RT-PCR. At week 1, neoR and rI2 were expressed in liver, spleen, thymus, peripheral blood lymphocytes and bone marrow. At week 2, neoR was expressed in spleen and brain, while at week 6, thymus, lymph nodes, bone-marrow, liver, spleen, and brain expressed neoR. rI2 was not detected after week 1. In summary, we showed that rAAV was efficient for transferring neoR and rI2 into rat hematopoietic stem cells.

Animals↗
PubMed1999

Hospitalization for mental illness in adolescents: risk groups and impact on the health care system.

PURPOSE: To determine the extent and cost of hospitalizations for mental illness among adolescents and to identify differences in acute care hospital use by gender and between racial/ethnic groups. METHODS: Analysis of discharge data for adolescents, 10 to 19 years of age (n = 27,595), with a principal diagnosis of mental illness from acute care hospitals in California in 1994. Relative risks (RRs) were calculated by race/ethnicity and gender and stratified by race/ethnicity and payment source. RESULTS: Mental illness accounted for 14.8% of hospitalizations in this age group; the mean length of stay was 10.9 days. Total charges exceeded $300 million. Overall, adolescent boys had a slightly lower risk of hospitalization for mental illness than did adolescent girls (RR = 0.90, 95% confidence interval [CI] = 0.87, 0.92) but a higher risk for certain diagnoses. Overall, nonwhite adolescents had a lower risk of hospitalization for mental illness than did white adolescents: African-Americans (RR = 0.77, 95% CI = 0.74, 0.81), Latinos (RR = 0.32, 95% CI = 0.31, 0.33), and Asians/others (RR = 0.27, 95% CI = 0.26, 0.29). These differences remained significant after stratification by payment source. CONCLUSIONS: The risk of hospitalization for mental illness among adolescents varies by specific mental illness and by race/ethnicity. In light of the significant human and financial costs associated with hospitalization for mental illness, further research into the determinants of illness and the options for care is warranted.

Adolescent↗
PubMed1999

Vaccination against Leishmania major in a CBA mouse model of infection: role of adjuvants and mechanism of protection.

Gp63 is a major surface protein of Leishmania promastigotes. Its protective efficacy has been tested in several experimental models using different mouse strains, gp63 forms, adjuvants and routes of immunization, giving rise to conflicting results. This investigation was designed to determine whether these discrepancies could be ascribed to differing experimental procedures, and to compare gp63-induced protection with that achieved using live promastigotes. Preliminary experiments demonstrated that gp63 was an extremely potent immunogen compared to a standard antigen (ovalbumin). Protection against Leishmania major infection afforded by gp63 inoculation was studied in CBA mice. Injection of gp63 in saline, or of CFA, BCG, and C. parvum without antigen, induced significant protection. When gp63 and adjuvants were combined, results differed depending on the site of vaccination relative to that of the challenge infection. Vaccination with gp63 plus adjuvants in the tail (i.e. close to the site of infection) led to a stronger reduction of lesion size than the basal level of protection elicited by adjuvants alone, except in the case of CFA. Surprisingly however, when the antigen was injected at a distance from the site of infection (immunization in the hind foot pads, infection in the rump), the protective effect of gp63 was decreased by the adjuvants. Finally, vaccination at either site using live parasites (radioattenuated or virulent promastigotes) resulted in most instances in better protection than achieved by any protocol using gp63 and adjuvants. While anti-gp63 T cells proliferated in vitro in response to L. major-infected bone marrow-derived macrophages, they were unable to activate macrophages for parasite killing. This is in contrast with lymphocytes from mice immunized with live parasites, which both proliferated and stimulated significant killing of the microorganisms within 48 h.

Adjuvants, Immunologic↗
PubMed1999

Phenomenology of gasoline intoxication and withdrawal symptoms among adolescents in India: a case series.

Inhalant withdrawal symptoms have previously been described but not well documented. This case-series describes the sociodemographic and clinical characteristics of nine children and adolescents with gasoline abuse. Gasoline inhalation was the drug of choice in our patients. The mean age was 13.6 years and all the subjects belonged to low socioeconomic status. Most of the subjects used daily and all subjects reported alcohol abuse in the father. All subjects reported a syndrome of intoxication as described in previous reports. All subjects also reported a withdrawal syndrome including irritability, psychomotor retardation, anhedonia, dry mouth, sleep disturbances, craving, and increased lacrimation.

Adolescent↗
PubMed1999

Post-hysteroscopic ablation reaction: a histopathologic study of the effects of electrosurgical ablation.

Ablation of the endometrium is now an established treatment modality for dysfunctional uterine bleeding (DUB). There have been few reports of the inflammatory and healing reaction within the endomyometrium subsequent to this therapy, and its identifying characteristics. The morphologic reaction after electrosurgical ablation in particular has received scant attention. In this retrospective study, 19 women were identified who had undergone both an endometrial ablation using electrosurgical rollerball ablation and a subsequent endometrial sampling or hysterectomy. The average age of the patients was 47 years (range, 28 to 60). Fifteen patients had been ablated for DUB, while four had been ablated immediately after a resection that later revealed atypical hyperplasia. Histopathologic specimens were examined from 1 to 48 months postablation. The six specimens examined at 3 months or less after ablation all exhibited necrotic myometrium, and in five of these six cases, a florid foreign body and granulomatous reaction to necrotic myometrium and spicules of thermally damaged myometrium. A variable degree of acute inflammation was evident in all six cases and was exclusively present in one case. The remaining 13 cases were examined at > 3 months posttreatment. Necrotic myometrium was no longer evident, but a persistent granulomatous, a foreign-body reaction, or both was detected in 5 of 12 cases up to 16 months postablation. In most cases (9 of 12), there was striking endometrial scarring. The morphologic response of the endometrium after electrosurgical endometrial ablation is similar to that reported previously for both resection and laser ablation. Post-hysteroscopic ablative reaction should be recognized and distinguished from other causes of granulomatous endometritis.

Adult↗
PubMed1999

Cardiovascular autonomic neuropathy in HIV infected patients.

OBJECTIVE: To evaluate the presence and extent of autonomic dysfunction in HIV infected individuals of one ethnic group. DESIGN: Prospective, age-sex matched study. METHODS: 25 patients (seven asymptomatic (HIV), eight AIDS related complex (ARC), 10 AIDS) and 25 controls were recruited from patients and staff at the Aga Khan Hospital, Nairobi. Autonomic function was assessed by measurement of pulse rate variability on standing, rest, deep breathing, Valsalva manoeuvre, isometric exercise, cold face test, and mental stress. Blood pressure was measured during standing, supine resting, and on Valsalva manoeuvre. CD4 count was correlated with number of abnormal test results. RESULTS: 21 patients had at least one abnormal test of autonomic function compared with one control (p < 0.0001). There were significant differences between AIDS patients and controls for supine heart rate (p < 0.001), Valsalva ratio (p = 0.05), and cold face test (p = 0.05), and almost significant results for mental stress (p = 0.051). Evidence of autonomic hypersensitivity was found in response to exercise and/or mental stress in some patients with HIV or ARC. No difference was found in blood pressure measurements. Abnormalities in autonomic function occurred at all CD4 counts and all patients with four abnormal tests of heart rate variation had a CD4 count less than 300 x 10(6)/l. CONCLUSIONS: There is evidence of substantial autonomic dysfunction in AIDS patients compared with controls and mild abnormalities in the majority of HIV infected patients studied irrespective of CD4 count. Autonomic hypersensitivity may precede loss of function in some cases.

AIDS-Related Complex↗
PubMed1999

Analysis of the costs of surgery for Hirschsprung's disease: one-stage laparoscopic pull-through versus two-stage Duhamel procedure.

The purpose of this report is to evaluate the cost-effectiveness of a single-stage laparoscopic pull-through for Hirschsprung's disease compared to the traditional two-stage Duhamel procedure. In this series of 33 children, the length of hospitalization (2.5 +/- 3.5 vs 10.6 +/- 3.9, p < 0.01), cost (19,088 +/- 13,075 vs 34,110 +/- 19,443, p < 0.05), and complications were all significantly less with the laparoscopic assisted pull-through compared to the more traditional open approach.

Child↗
PubMed1999

Oesophagogastrectomy in the elderly high risk patients: role of effective regional analgesia and early mobilisation.

BACKGROUND: Oesophagogastrectomy is the best available treatment for patients with carcinoma of the oesophagus or cardia. However, surgical resection may lead to increased mortality, morbidity and longer hospital stays in elderly (aged over 70 years) high risk patients. METHODS: To assess the impact of balanced pre-emptive and postoperative analgesia combined with early mobilisation in elderly patients undergoing oesophagogastrectomy we consecutively studied 52 patients (30 male, 22 female) of 75+/-4.2 years of age (mean+/-SD). Pre-emptive analgesia was by pre-incisional percutaneous paravertebral block combined with an opiate and a nonsteroidal anti-inflammatory drug (NSAID) premedication. Postoperative maintenance analgesia was by NSAID and continuous extrapleural intercostal nerve block. Following surgery all but three patients were returned to the ward. RESULTS: The hospital mortality rate was 7.6%. Morbidity caused by cardiovascular (27%), respiratory (23%) and cerebrovascular (19%) complications occurred in 19 patients, with two patients requiring ventilatory support. The mean hospital stay for the survivors was 10 days (range 8 to 30 days). All the survivors had their swallowing restored to normal and returned to their accustomed environment. CONCLUSIONS: These data suggests that surgical treatment can be achieved in the elderly high risk patients with acceptable mortality and morbidity. This is achieved by early mobilisation enabled by balanced pre-emptive and postoperative analgesia.

Aged↗
PubMed1999

Post-thoracotomy spirometric lung function: the effect of analgesia. A review.

BACKGROUND: The effects of postthoracotomy pain management on pulmonary function has been assessed. METHODS: All English language publications involving prospective, randomised, controlled studies of patients undergoing postero-lateral thoracotomy incisions where perioperative spirometry had been studied were included. The mean postoperative percentage preservation of preoperative lung function was recorded or determined for each analgesic regimen. RESULTS: 55 studies were reviewed with a total of 1762 patients. The most effective analgesic method in terms of preservation of spirometric function was paravertebral analgesia, patients having approximately 75% of their preoperative values in the first 48 hours after surgery. Most other techniques e.g. intercostal nerve blocks, epidural local anaesthetics or local anaesthetic-opiate combinations produced approximately a 55% preservation by 48 hours. Interpleural analgesia was the least effective, with a mean of 35% preservation by 48 hours, less even than TENS or cryoanalgesia. CONCLUSIONS: A thoracotomy potentially produces a marked reduction in postoperative pulmonary function and the choice of pain management has major implications. Attenuation of postthoracotomy pulmonary dysfunction by effective analgesia should be provided for all patients undergoing chest surgery. Simply providing effective analgesia on its own without regard to pulmonary function is inadequate. Spirometric monitoring should be standard in all thoracic units and is essential for objective comparisons of the efficacy of different methods of pain management.

Analgesia↗
PubMed1999

Spontaneous down-regulation of Fas-associated phosphatase-1 may contribute to excessive apoptosis in myelodysplastic marrows.

In this study, we examined the role of Fas-signaling in the apoptotic pathway in myelodysplastic syndromes (MDS). Ficoll-separated mononuclear cells from 18 bone marrow aspirate specimens obtained from 17 MDS patients, 4 normal healthy donors, and 3 acute myeloid leukemia patients transformed from MDS (t-AML) were studied for mRNA expression of Fas-L, Fas, and the effectors of their signaling, Caspase 1 and Caspase 3, using reverse transcriptase polymerase chain reaction. Fas-L, Fas, and Caspase 1 were detectable in all of the samples in the three groups. Caspase 3 was detectable both in MDS and t-AML specimens but was negligible in normal cells. The apoptotic index (AI%) determined by in situ end labeling of fragmented DNA in 4-hour cultures of mononuclear cells was significantly higher in MDS cells compared to normal or t-AML cells (mean +/- SEM: 2.3% +/- 0.4% in MDS, n = 10 vs. 0.6% +/- 0.2%, n = 4, P = 0.014 in normal cells, and 0.2% +/- 0.2%, n = 3, P = 0.007 in t-AML cells). Treatment of MDS cells with anti-Fas-L antibody suppressed apoptosis (AI%: 2.1% +/- 0.6% in untreated vs. 1.37% +/- 0.5% in treated, n = 6, P = 0.02), indicating functional participation of Fas-signaling in MDS. Further, it was found that Fas-L, Fas, and Caspase 1 mRNA expression remained unchanged in 4 hours. Caspase 3 expression appeared in normal cells after 4 hours and was present at both 0 and 4 hours in MDS and t-AML cells. In contrast to persistent expression in normal and t-AML cells, cells from the 5 MDS patients studied consistently showed significantly lowered or undetectable expression of a negative regulator of Fas, called Fas-associated phosphatase-1 (Fap-1) after 4 hours. Thus, the high AI% in MDS corresponds to a rapid decline in Fap-1. Furthermore, in tumor necrosis factor alpha (TNF-alpha) treated HL60 promyelocytic cells, a definite periodicity in the expression of different mRNAs was observed with upregulation of TNF-alpha itself at 30 minutes, increased expression of Fas and the appearance of Fas-L after 2 hours, and a decrease in Fap-1 expression after 8 hours. These results suggest that TNF-alpha not only induces the effectors of Fas-signaling but also may downregulate the inhibitor. We conclude that a spontaneous and rapid down-regulation of Fap-1, possibly induced by TNF-alpha, a cytokine shown to be present in excess in MDS marrows, may underlie the increased apoptotic death of hematopoietic cells in these patients. Interference with Fap-1 turnover may provide a new therapeutic modality for MDS.

Apoptosis↗
PubMed1999

Lateralization of cortical function in swallowing: a functional MR imaging study.

BACKGROUND AND PURPOSE: While functional MR imaging and other techniques have contributed to our knowledge of functional brain localization, these methods have not been extensively applied to the complex and incompletely understood task of swallowing. We used functional MR imaging to investigate motor cortex activity during swallowing in healthy human adults. METHODS: Eight subjects were imaged on a 1.5-T MR system using blood oxygen level-dependent contrast mechanisms. Subjects performed three swallowing tasks and a finger-tapping task. Areas of activation in the cortex and subcortical areas were tabulated, and a laterality index, defined as LI = [sigmas left - sigmas right]/[sigmas left + sigmas right] x 100, was computed for the three tasks. RESULTS: Activation was observed in the primary motor and sensory cortices, motor processing and association areas, and subcortical sites. This activity was dominant for one hemisphere with left hemispheric dominance more prevalent among the subjects. Right hemispheric dominance, however, showed stronger lateralization than the left hemisphere. CONCLUSION: Our data indicate that specific sites in the motor cortex and other cortical and subcortical areas are activated with swallowing tasks and that hemispheric dominance is a feature of swallowing under these conditions. In addition, we demonstrate the utility of functional MR imaging in the study of the cortical representation of swallowing and suggest a role for functional MR imaging in the diagnosis of dysphagia of cerebral origin.

Adult↗
PubMed1998

Newly described form of X-linked arthrogryposis maps to the long arm of the human X chromosome.

Arthrogryposis is a heterogeneous birth defect characterized by limitation of movement at multiple joints. One in 3,000 infants is born with arthrogryposis, and at least a third of these cases have a genetic cause. Four distinct types of X-linked arthrogryposis have been reported, and a severe lethal form recently was mapped to Xpll.3-qll.2. We now report an extended family affected with a novel variant of X-linked arthrogryposis that involves only the lower limbs. Linkage analysis with polymorphic DNA markers maps the disease locus in this unique family to the long arm of the human X chromosome between DXS1220 and DXS1205 in Xq23-27.

Alleles↗
PubMed1998

Functional interactions between the holliday junction resolvase and the branch migration motor of Escherichia coli.

Homologous recombination generates genetic diversity and provides an important cellular pathway for the repair of double-stranded DNA breaks. Two key steps in this process are the branch migration of Holliday junctions followed by their resolution into mature recombination products. In E.coli, branch migration is catalysed by the RuvB protein, a hexameric DNA helicase that is loaded onto the junction by RuvA, whereas resolution is promoted by the RuvC endonuclease. Here we provide direct evidence for functional interactions between RuvB and RuvC that link these biochemically distinct processes. Using synthetic Holliday junctions, RuvB was found to stabilize the binding of RuvC to a junction and to stimulate its resolvase activity. Conversely, RuvC facilitated interactions between RuvB and the junction such that RuvBC complexes catalysed branch migration. The observed synergy between RuvB and RuvC provides new insight into the structure and function of a RuvABC complex that is capable of facilitating branch migration and resolution of Holliday junctions via a concerted enzymatic mechanism.

Bacterial Proteins↗
PubMed1998

Laparoscopic pyloromyotomy: a safer technique.

A modified technique of laparoscopic pyloromyotomy was used to treat infantile hypertrophic pyloric stenosis. Introducing a 5-mm periumbilical port for visualization, two stab wounds are made on either side laterally to directly insert 2.7-mm instruments for manipulation. From the left, the stomach is grasped - not the duodenum! From the right, an inexpensive disposable arthroscopy knife is used to incise the serosa and begin the myotomy, which is completed with a laparoscopic spreader until the muscle is separated sufficiently to relieve the obstruction. Twenty-nine children treated with laparoscopic pyloromyotomy were compared to 125 children treated with the conventional open Ramstedt pyloromyotomy. There were no statistically significant differences in the presentation or results between groups, suggesting that the laparoscopic technique is a safe and equal alternative.

Female↗
PubMed1998

Neck dissection with simultaneous carotid endarterectomy.

BACKGROUND: Patients with metastatic neck disease from upper aerodigestive tract carcinomas have an extensive history of tobacco and alcohol abuse. These patients are predisposed to develop atherosclerotic vascular disease. OBJECTIVE: An increased incidence and severity of carotid stenosis in patients receiving radiotherapy for head and neck cancers is known. Management of patients with severe carotid stenosis who require surgical treatment of their neck disease has not been described. The authors describe our experience with simultaneous carotid endarterectomy and neck dissection. STUDY DESIGN: Prospective data collection. METHODS: From 1991 to 1997 at West Virginia University Hospitals, Morgantown, West Virginia, and State University of New York (SUNY) at Buffalo, three patients with severe carotid stenosis required surgery for metastatic neck disease. Preoperative evaluation revealed a bilateral carotid stenosis greater than 90% in all patients. All patients underwent modified radical neck dissections and simultaneous carotid endarterectomies with saphenous vein grafting. Two patients, one undergoing partial pharyngectomy and laryngectomy and the other a laryngectomy and neck dissection, had coverage of the carotid artery with the myogenous component of a pectoral major graft. One patient had only a neck dissection. RESULTS: Two patients healed with no local morbidity, no neck recurrence, and a patent carotid artery by Doppler. No strokes were encountered. One patient died of a myocardial infarction. CONCLUSION: Severe carotid stenosis that requires revascularization may have endarterectomy performed simultaneously with treatment of head and neck primary with no increase in morbidity.

Aged↗
PubMed1998

Outcomes of cytomegalovirus retinitis following the use of ganciclovir implants.

PURPOSE: To determine the results and complications from the use of ganciclovir implants to treat patients with HIV infection and cytomegalovirus (CMV) retinitis. METHODS: The present study was a retrospective review of 87 consecutive ganciclovir implant surgeries performed in 60 patients over a 3 year period. RESULTS: Based on the results of the present study, ganciclovir implants are an efficacious therapy for CMV retinitis but are associated with significant postoperative complications, including retinal detachment (12.0%), vitreous haemorrhage (7.2%) and cataract formation (6.0%). In this series, all implanted eyes responded to treatment and the mean time to progression was 252 days. Only a small number of patients developed second eye involvement (n = 9) or clinically significant CMV infection of other organ systems (n = 5). CONCLUSIONS: This small retrospective study provides additional data confirming the effectiveness of ganciclovir implants and the complications from their use.

AIDS-Related Opportunistic Infections↗