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Biomedical subjects

V R Shah

Publications and source records attributed to V R Shah.

At least 19 recordsLinked to original sources
PubMed2006

Synthesis of bis-armed amino acid derivatives via the alkylation of ethyl isocyanoacetate and the Suzuki-Miyaura cross-coupling reaction.

Two synthetic routes to bis-armed-alpha-amino acid derivatives are described. The first route involves alkylation of dibromo derivatives with ethyl isocyanoacetate under phase-transfer catalysis (PTC) conditions. The second route uses a palladium-mediated Suzuki-Miyaura cross-coupling reaction between a DL-4-boronophenylalanine derivative and aromatic diiodo (or dibromo) compounds.

Acetates↗
PubMed2006

Embryonic stem cell derived and adult hematopoietic stem cell transplantation for tolerance induction in a renal allograft recipient:--a case report.

UNLABELLED: We generated an human embryonic stem cell (hESC) line to augment chimerism-associated tolerance. A 40-year-old African with chronic glomerulonephritis-chronic renal failure with 100% G6PD enzyme deficiency presented for renal transplantation with a 27-year-old, 6/6 HLA-matched sister as a willing donor. METHOD: We generated an hESC line from the donor's oocytes using long ovarian stimulation protocol simultaneously with tolerance induction protocol. A nuclear transfer (NT)-hESC line was derived by transferring a donor cumulus cell into an enucleated oocyte, subjected to electrical fusion, and cultured for 5 days. ESCs hatched from the blastocyst on day 6 were cocultured with her unmodified bone marrow for 2 days and suspended in Ringer's lactate. Five milliliters of suspension were collected for cell counting, viability, pluripotency, flow cytometry, and karyotyping. The remaining suspension was infused into the periphery of the recipient. Transplantation was performed 1 week later following a negative lymphocytotoxicity cross-match test using no immunosuppression. Peripheral blood chimerism (PBC) was studied using fluorescent in situ hybridization technique. Allograft biopsy was performed on day 7. RESULTS: NT-hESC CD34+ count was 7.6%, viability 100%, karyotyping normal, pluripotency markers: SSEA-1, SSEA-4, OCT-3/4, TRA-1/60:positive; 12% PBC was noted at 1 week after transplantation. Serum creatinine was 1.2 mg%, graft biopsy was unremarkable, and G6PD enzyme deficiency was corrected to 0% at 100 days posttransplant. Liver function tests and hematology profile were unremarkable for graft-versus-host disease. CONCLUSION: This is the first report of tolerance induction using NT-hESC-induced hematopoietic chimerism with synergistic use of adult bone marrow. It was safe and effective.

Adult↗
PubMed2005

Allogeneic hematopoietic stem-cell transplantation, mixed chimerism, and tolerance in living related donor renal allograft recipients.

OBJECTIVE: We designed a prospective, randomized, and controlled clinical trial to evaluate the efficacy and safety of achieving a mixed chimerism-associated tolerance protocol for recipients of living related donor (LRD) renal allografts. PATIENTS AND METHODS: Sixty-six consecutive patients were divided into two equal groups of 33 patients with end-stage renal disease. They were enrolled for transplantation after negative lymphocytotoxicity cross-matching (LCM). Both groups (treated [Tn] and control [Cn]) showed similar clinical and laboratory parameters and donor HLA match profiles. The Tn group underwent thymic transplantation of donor renal tissue, two donor-specific transfusions, low-intensity conditioning, and high-dose hematopoietic stem-cell transplantation (HSCT) before renal transplantation. The conditioning regimen included low-dose, target-specific irradiation (to abdominal and inguinal lymph nodes, bone marrow [BM] from thoracolumbar vertebrae and part of the pelvis on alternate days, 100 rad x 4), anti-T-cell antibodies (1.5 mg/kg body weight [BW]), cyclophosphamide (10 mg/kg BW x 2 consecutive days), and cyclosporine (CyA; >3 mg/kg BW/d). Unfractionated HSCT procured from the donor marrow was administered into the BM, portal and peripheral circulations, within 24 hours of achieving CD 4+/CD 8+ T-cell count less than 10% of normal. This infusion was supplemented with a dose of peripherally mobilized stem cells (mean total dose of 20 x 10(8) cells/kg recipient BW) administered peripherally. Renal transplantation was performed after negative LCM. Donor-specific cytotoxic antibodies were eliminated with intravenous immunoglobulins and plasmapheresis before renal transplantation. Mixed chimerism was evaluated before and after transplantation at monthly intervals in patients with donors of opposite gender by the FISH technique. Both groups received CyA and prednisolone for immunosuppression; Cn subjects also received mycophenolate mofetil/azathioprine. Rejection was treated with standard treatment. Immunosuppression was withdrawn 6 months after renal transplantation for patients with consistently positive chimerism. Clinical tolerance was defined as stable allograft function for more than 100 days without immunosuppression and confirmed by allograft biopsy. RESULTS: Over a mean follow-up of 210 days, all Tn patients showed stable allograft function with mean serum creatinines (SCr) of 1.20 mg/dL, no rejection/CMV infections/graft or patient loss. A low-level donor-specific cytotoxic antibody was observed in all Tn patients. The CyA toxicity was noted in 10 (30.3%) patients. Persistent mixed hematopoietic chimerism was seen in all 21 patients irrespective of donor-recipient HLA matching (mean 0.5% before and 1 +/- 0.3% after transplantation). All four patients on drug withdrawal have shown donor-specific tolerance at a mean follow-up of 129.8 days. Other Tn patients are in the process of being weaned off immunosuppression. Mean SCr of controls was 1.45 mg/dL over a mean follow-up of 216 days. Acute rejection was observed in 17 (51.5%) patients; no CMV infection/patient loss was noted and one (3.03%) graft was lost in controls. No patient was lost in controls. No graft-versus-host disease was observed in Tn patients. CONCLUSION: We have achieved mixed hematopoietic chimerism-associated tolerance with high-dose HSCT, intrathymic donor renal tissue transplantation, and minimal conditioning without any adverse effects.

Adolescent↗
PubMed2002

Central pontine myelinolysis: sequele of hyponatremia during transcervical resection of endometrium.

Transcervical resection of endometrium is an alternative to hysterectomy for women with menorrhagia. The procedure involves the use of cutting loop diathermy to resect the endometrium while the uterine cavity is irrigated with 1.5% glycine which can absorb consequent fluid and electrolyte shifts. Severe hyponatremia leading to central pontine myelinolysis is an extremely rare complication of this procedure. We report a case of a young female undergoing transcervical resection of endometrium for menorrhagia, who developed central pontine myelinolysis but made a complete recovery after three months.

Adult↗
PubMed2001

Oxidative stress status: possible guideline for clinical management of critically ill patients.

BACKGROUND: Critical care medicine has developed in the last few years into a separate scientific discipline and studies related to the outcome after intensive care usually suggest a long hospital stay that becomes cost prohibitive. The majority of problems (death) amongst critically ill patients requiring critical care involve sepsis, inflammation, tissue damage-oxidative stress, oxygen tension PO2, lipid peroxidation. The present investigation involves monitoring of serum levels of MDA, SOD as a possible guideline for severity of clinical situations in critically ill patients. METHODS: Fifty critically ill heterogeneous patients requiring intensive care in the ICU of IKDRC were selected as subjects with ages varying from 17 to 75 years. Serum levels of MDA (ng/ml), SOD (U/ml) were determined right from admission to discharge due to improvement / DAMA / death. MDA and SOD were estimated according to the methods of Buege and Aust et al. (1978), Nandi and Chatterji (1988). RESULTS: Critically ill patients irrespective of the disease process indicated significantly very high serum levels of MDA and low levels of SOD at the time of admission (13.28+/-4.26 ng/ml, 3.80+/-2.60 U/ml, respectively) according to the severity of the prevalent clinical situation. The pattern of serum levels of MDA and SOD according to subsequent clinical performance did indicate a decreasing trend of MDA (oxidant) and fluctuating trend of SOD (antioxidant enzyme except in those who inevitably succumbed to death in spite of adequate clinical management. CONCLUSIONS: The results of the present study have amply revealed the utility and relevance of monitoring oxidative stress in critically ill patients as biochemical markers, cost-effectiveness and role in decision making (withdrawal/continuation of different support modalities) as deemed fit.

Adolescent↗
PubMed1999

A man with inflamed ears.

A 23-year-old man presented with fever, dyspnea, nonproductive cough, left eye redness, reduced vision, and bilateral ear pain and tenderness. The symptoms had begun two days earlier, eight days after he was discharged from the hospital with a presumptive diagnosis of Still's disease. He was first seen a month before the current admission for complaints of fever (as high as 39.4 degrees C), nonproductive cough, and asymmetric arthritis. The workup at that time included arthrocentesis of the right knee. Analysis of the joint fluid showed 7,500 white blood cells/mm3 and no crystals. A gram stain and culture of the fluid were negative. HIV and hepatitis tests, bone marrow biopsy and culture, transesophageal echocardiography, abdominal computed tomography, radionuclide bone scanning, and rheumatologic tests failed to identify the problem. The development of an evanescent macular pink rash on day 15 suggested the possibility of Still's disease. Treatment with prednisone (40 mg po qd) was initiated, and the patient was discharged on day 19.

Adult↗
PubMed1999

Effect of renal transplantation (surgical stress) on serum levels of oxidants and reducing system.

BACKGROUND: This study attempts to understand the correlation (if any) between surgical stress of renal transplantation and serum levels of pro-oxidant/antioxidants. METHODS: Twenty-four ESRD patients having undergone transplant surgery followed from day-1 to day-10 postsurgery were investigated for serum levels of MDA, SOD, Vit. C and E. The drug regimen received was immunosuppressant, H2 blockers and antihypertensives as per the situation. RESULTS: The typical observations indicated elevated serum levels of MDA from preoperative stage reaching peak value 24 hrs after surgery followed by a steady fall and achieving minima on the 10th day. As regards antioxidants enzyme SOD, Vit. C, Vit. E were low from pretransplant day reaching minima 24 hours postoperatively and returning to normal from 7th day. CONCLUSIONS: The present investigation has amply shown a typical imbalance between pro-oxidant/antioxidants from pretransplant day up to 24 hrs and there after returning to normal level from 7th day suggestive to desired recovery and surgical stress not a limiting factor in way of health progress renal transplant. Dietary intake of Vit. C and E in mega doses can be a good therapeutic measure.

Adult↗
PubMed1998

Sensitive liquid chromatographic-mass spectrometric assay for the simultaneous quantitation of nefazodone and its metabolites hydroxynefazodone m-chlorophenylpiperazine and triazole-dione in human plasma using single-ion monitoring.

A sensitive, selective, accurate, precise and reproducible high-performance liquid chromatographic-mass spectrometric (LC-MS) assay was developed and validated for the simultaneous determination of nefazodone (NEF), hydroxynefazodone (OH-NEF), m-chlorophenylpiperazine (mCPP), and triazole-dione (Dione) in human plasma using trazodone (TRZ) as the internal standard (I.S.). The method involved simultaneous protein precipitation with acetonitrile and liquid-liquid extraction with methylene chloride, after which the organic layer was evaporated to dryness. The residue was reconstituted in 25% acetonitrile in 10 mM ammonium formate (pH 4.0), and an aliquot was injected onto a BDS Hypersil C18 column at a flow-rate of 0.3 ml/min. The mobile phase comprising of 10 mM ammonium formate (pH 4) and acetonitrile in 55:45 (v/v) was used in an isocratic condition. The mass spectrometer was programmed to admit the protonated molecules at m/z 197.0 (mCPP), 372.0 (I.S.) 470.4 (NEF), 458.1 (Dione), and 486.2 (OH-NEF). Standard curves were linear (r2 > or = 0.995) over the concentration range of 4-1000 ng/ml for Dione and 2-500 ng/ml for other analytes. The lowest standard concentrations were the lower limit of quantitation for each analyte. The mean predicted quality control (QC) concentrations for all analytes deviated less than -12.1% from the corresponding nominal values; the intra-assay and inter-assay precision of the assay for all analytes were within 7.0% relative standard deviation. All analytes including I.S. were stable in the injection solvent at room temperature for at least 24 h. The extraction recovery of the various analytes ranged from 67.3 to 86.5%. The validated assay was applied to a pharmacokinetic study of nefazodone.

Antidepressive Agents, Second-Generation↗
PubMed1998

High-performance liquid chromatographic-electrochemical assay for the quantitation of BMS-181885 in monkey plasma.

A high-performance liquid chromatographic-electrochemical assay was developed and validated for the quantitation of BMS-181885 (I), an anti-migraine agent, in monkey plasma. The assay involved a solid-phase extraction of I and BMY-46317 (internal standard; I.S.) on a 1-ml cyano cartridge using the automatic solid-phase extraction cartridge (ASPEC) system. Immediately following the conditioning of the cyano column (3 ml of methanol and 2 ml of 1% glacial acetic acid), plasma (0.25 ml) was loaded on to the column. The column was then washed with a 3 ml of 0.1 M ammonium acetate buffer (pH 6). The final elution of the analytes was performed using 2 ml of methanol. The eluate was then evaporated to dryness (gentle stream of nitrogen at 40 degrees C) and the residue was dissolved in the mobile phase and injected on to a YMC basic column (15 cm x 4.6 mm; 5 microm particle size) at a flow-rate of 1 ml/min. A mixture of 0.1 M ammonium acetate at pH 6-acetonitrile-methanol (70:20:10, v/v) was used as the mobile phase. Standard curves, with a lower limit of quantitation of 2 ng/ml of I were linear (r2> or =0.998; range: 2-50 ng/ml). Based on the analysis of the quality control (QC) samples, the assay was both accurate and precise. The stability of I was established following freeze-thaw cycles and storage at or below -20 degrees C. The extraction recovery of I from monkey plasma was about 82%. The validated assay method was applied to determine the pharmacokinetics of I in monkeys following a single 1 mg/kg intravenous dose.

Animals↗
PubMed1998

Pharmacokinetic assessment of the sites of first-pass metabolism of BMS-181101, an antidepressant agent, in rats.

The relative contribution of the gut and the liver to the first-pass metabolism of BMS-181101 (3-[3-[4-(5-methoxy-4-pyrimidinyl)-1-piperazinyl]propyl]-5-fluoro-1H-ind ole dihydrochloride), a potential antidepressant agent, has been evaluated in rats. Nine male Sprague-Dawley rats were divided into three groups of three and each rat received a single 20 mg kg(-1) dose of [14C]BMS-181101 via a 30 min constant-rate intravenous infusion, a 30-min constant-rate intraportal infusion or oral gavage. Serial blood samples were collected for 8 h after dosing and plasma was analysed for unchanged BMS-181101 and total radioactivity. Extraction ratios for BMS-181101 by the gut and liver were calculated on the basis of ratios of the area under the plasma BMS-181101 concentration-time curve. The gut had a high intrinsic capacity for metabolizing BMS-181101-extraction ratios were 93% and 10% for the gut and liver, respectively. After oral administration BMS-181101 is sequentially exposed to the gut then the liver. As a result, the contribution of the gut to the overall first-pass effect (ca. 93%) was significantly greater than that of the liver (ca. 0.7%). The estimated total first-pass effect of 94% for BMS-181101 in rats is in excellent agreement with the observed absolute oral bioavailability of 6%. These results clearly illustrate the importance of metabolic activity in the gut for orally administered BMS-181101.

Administration, Oral↗
PubMed1996

High-performance liquid chromatographic analysis of 2'-fluoro-2',3'-dideoxyadenosine and 2'-fluoro-2',3'-dideoxyinosine in dog plasma and urine.

A high-performance liquid chromatographic assay was developed and validated for a simulataneous determination of 2'-fluoro-2' 3'-dideoxyadenosine (FddA) and its metabolite, 2'-fluoro-2',3'-dideoxyinosine (Fddl) in dog plasma and urine. In vitro, FddA and Fddl exhibit activity against human immunodeficiency virus (HIV). A solid phase extraction was applied to extract FddA, Fddl, and the internal standard (IS; 3',5'-anhydrothymidine) from the biomatrices. The processed samples were chromatographed using a C8 column coupled with a mobile phase consisting of monobasic phosphate, dibasic phosphate, ethylene glycol monomethyl ether, and water. Detection was performed at 257 nm. The nominal retention times were 9, 14, and 26 min for Fddl, IS, and FddA, respectively. The lower limits of quantitation were 0.1 and 2.0 micrograms/mL in plasma and urine, respectively, for both analytes. The accuracy of the assay deviated < or = 10% from the nominal concentrations, and the precision was < or = 14% coefficient of variation. In either matrix, both analytes were stable for at least three freeze-thaw cycles and in the injection media for at least 54 h. The extraction recoveries of the analytes were greater than 80%. The application of this assay was demonstrated in a preliminary pharmacokinetic study of FddA and Fddl in dogs. Two male dogs per dose level received a 100, 250, or 500 mg/kg oral dose of FddA once daily for 14 days. The early appearance of Fddl in plasma (0.25 h; the first sampling time) and greater plasma levels of Fddl than FddA (> 50-fold of Cmax), suggested that the conversion of FddA to Fddl was rapid and extensive. Renal excretion appeared to be the major route of elimination of Fddl.

Administration, Oral↗
PubMed1992

Oral absolute bioavailability and intravenous dose-proportionality of cefprozil in humans.

The absolute bioavailability (F) and dose proportionality of cefprozil were investigated in a parallel design study with an embedded two-way crossover leg. Twenty-four healthy male subjects divided into 3 dosing groups received a single 250-, 500-, or 1000-mg dose of cefprozil by a 30-minute intravenous infusion. Subjects assigned to the 500-mg dose group also received a 500-mg oral dose of cefprozil in crossover manner with a wash-out period of 7 days between each treatment. Cefprozil consists of cis and trans isomers in an approximate 90:10 ratio. Serial blood and urine samples were collected and analyzed for the concentrations of the cis and trans isomers of the cephalosporin using high-pressure liquid chromatographic assay with UV detection methods. After the 250-, 500-, and 1000-mg intravenous administration of cefprozil, the peak concentrations were 13.2, 26.0, and 48.5 micrograms/mL, and area under the plasma concentration versus time profiles were 17.2, 31.4, and 58.1 micrograms.hour/mL, respectively, for the cis isomer increasing in a dose proportional manner. Total body clearance, renal clearance, and volume of distribution at steady state, adjusted for body weight, were not significantly different among all groups. Mean residence time, elimination half-life, and urinary recovery were invariant with the dose. Based on the plasma and urine data, the estimates of F were 89% and 94% for the cis isomer, respectively. The plasma concentrations of the trans isomer were about 1/10th of the cis isomer, and all parameters were similar to those observed for the cis isomer. In summary, cefprozil exhibits linear pharmacokinetics and is essentially completely absorbed after oral administration.

Adult↗
PubMed1992

Excretion of cefprozil into human breast milk.

The excretion of cefprozil into breast milk in nine healthy, lactating female subjects was investigated. Each subject received a single 1,000-mg oral dose of cefprozil consisting of cis and trans isomers in an approximately 90:10 ratio. Serial blood, urine, and breast milk samples were collected and analyzed for the concentrations of the cis and trans isomers by a specific high-pressure liquid chromatography-UV assay. The mean pharmacokinetic parameters for both isomers were essentially the same. The mean peak concentrations in plasma for the cis isomer were 14.8 micrograms/ml, and the area under the concentration curve was 54.8 micrograms.h/ml. The mean values of elimination half-life, renal clearance, and urinary excretion for the cis isomer were 1.69 h, 164 ml/min, and 60%, respectively. The mean concentrations in milk of the cis isomer over a 24-h period ranged from 0.25 to 3.36 micrograms/ml, with the maximum concentration appearing at 6 h after dosing. The average maximum concentration in milk of the trans isomer was less than 0.26 micrograms/ml. The concentrations of the trans isomer in plasma and in breast milk were about 1/10 of those for the cis isomer. Less than 0.3% of the dose was excreted in breast milk for both isomers of cefprozil. Even if one assumes that the concentration of cefprozil in milk remains constant at 3.36 micrograms/ml (the highest concentration of cefprozil observed in breast milk), an infant ingesting an average of 800 ml of milk per day will be exposed to a maximum amount of about 3 mg of cefprozil per day. This value represents about 0.3% of the maternal dose. Low excretion of cefprozil in breast milk and the excellent safety profile of cefprozil suggest that this cephalosporin may be administered to nursing mothers when indicated.

Administration, Oral↗
PubMed1991

Simultaneous high-performance liquid chromatographic analysis of cefprozil diastereomers in a pharmacokinetic study.

Cefprozil, a new oral cephalosporin, consists of a 90:10 cis:trans isomer mixture. Sensitive, specific and reproducible high performance liquid chromatographic methods have been developed for the simultaneous quantification of the two stereoisomers of cefprozil in plasma and urine samples from human and rats. Cephalexin acted as the internal standard. Plasma protein was precipitated with acetonitrile and trichloracetic acid with subsequent extraction of acetonitrile. After vortexing and centrifuging, the aqueous phase was injected onto a reverse phase C8 column. Urine samples were acidified with sodium acetate buffer (pH 3.8) and then directly injected onto a reverse phase C18 column. The detector was set at 280 nm. These methods were applied to determine protein binding of both isomers in human and rat sera, and to perform a pharmacokinetic study in human. Results showed that both isomers bound moderately to serum proteins with no interference by the other isomer. The pharmacokinetic study in human indicated that cefprozil was well absorbed and the cis and trans isomers have similar pharmacokinetics.

Animals↗
PubMed1981

Occupational noise exposure and hearing levels.

A study was made at the Bhabha Atomic Research Center to measure the hearing levels of persons working in a noisy environment. Two different workplaces, central air-conditioning plant and glass flowing shops, where a number of persons were exposed to noise levels exceeding 85 dB(A) were chosen. The occupational exposure to noise was determined using a sound level meter, an octave band filter and a personal noise dose meter. The hearing levels of persons exposed to these high levels of noise and a control group not exposed to occupational noise were measured by means of a pure-tone audiometer in a specially-build booth. These persons, aged between 20 to 60 years, were divided into four age groups for the study. The low ambient noise levels in the booth were measured using correlation technique since such low signals cannot be detected by an ordinary sound level meter. The audiometric findings and the results of the noise level survey are discussed in this paper.

Adult↗
PubMed1979

Haemorrhagic cholecystitis.

Two cases of haemobilia due to haemorrhagic cholecystitis are presented; only 28 other cases have been described. As there are so many more dramatic causes and treatment for haemobilia it is important for the surgeon to recognize that a common operation will suffice for this rare condition. In both cases bacteria were grown from the bile and it is to be hoped that bile culture will be recorded more commonly in future in cases of this interesting condition.

Bacteria↗