Biomedical subjects

V Gupta

Publications and source records attributed to V Gupta.

At least 145 records · Page 8Linked to original sources

PubMed1999

Efficacy of supratarsal dexamethasone versus triamcinolone injection in recalcitrant vernal keratoconjunctivitis.

PURPOSE: To compare the efficacy of supratarsal injection of short acting dexamethasone sodium phosphate versus intermediate acting triamcinolone acetonide as a new therapeutic modality for treating eyes with recalcitrant vernal keratoconjunctivitis (VKC). METHODS: The study was a prospective, randomized, double blind, case controlled trial, including 38 eyes of 19 patients with recalcitrant VKC. Except for two initial patients who received supratarsal injection of triamcinolone acetonide in both the eyes, one eye of each patient was randomly assigned to receive either 2 mg of dexamethasone sodium phosphate or 20 mg of triamcinolone acetonide. RESULTS: Both the drugs were equally effective with no statistically significant difference in the mean time of resolution of cobblestone papillae, limbal edema, shield ulcer, SPK and relief of symptoms. The recurrence rate of disease was, however, lower following triamcinolone acetonide injection. CONCLUSIONS: Supratarsal injection of corticosteroid is a cheap, effective and safe modality of treatment for managing eyes with recalcitrant VKC. Both short acting dexamethasone and intermediate acting triamcinolone acetonide are equally effective.

Adolescent↗

PubMed1999

Immunoglobulin motif DNA recognition and heterodimerization of the PEBP2/CBF Runt domain.

The polyomavirus enhancer binding protein 2 (PEBP2) or core binding factor (CBF) is a heterodimeric enhancer binding protein that is associated with genetic regulation of hematopoiesis and osteogenesis. Aberrant forms of PEBP2/CBF are implicated in the cause of the acute human leukemias and in a disorder of bone development known as cleidocranial dysplasia. The common denominator in the natural and mutant forms of this protein is a highly conserved domain of PEBP2/CBF alpha, termed the Runt domain (RD), which is responsible for both DNA binding and heterodimerization with the beta subunit of PEBP2/CBF. The three-dimensional structure of the RD bound to DNA has been determined to be an S-type immunoglobulin fold, establishing a structural relationship between the RD and the core DNA binding domains of NF-kappaB, NFAT1, p53 and the STAT proteins. NMR spectroscopy of a 43.6 kD RD-beta-DNA ternary complex identified the surface of the RD in contact with the beta subunit, suggesting a mechanism for the enhancement of RD DNA binding by beta. Analysis of leukemogenic mutants within the RD provides molecular insights into the role of this factor in leukemogenesis and cleidocranial dysplasia.

Cleidocranial Dysplasia↗

PubMed1999

Molecular insights into PEBP2/CBF beta-SMMHC associated acute leukemia revealed from the structure of PEBP2/CBF beta.

PEBP2/CBF is a heterodimeric transcription factor essential for genetic regulation of hematopoiesis and osteogenesis. DNA binding by PEBP2/CBF alpha is accomplished by a highly conserved DNA binding domain, the Runt domain (RD), whose structure adopts an S-type immunoglobulin fold when bound to DNA. The supplementary subunit beta enhances DNA binding by the RD in vitro, but its role in the control of gene expression has remained largely unknown in vivo. Chromosome 16 inversion creates a chimeric gene product fusing PEBP2/CBF beta to a portion of the smooth muscle myosin heavy chain (PEBP2/CBF beta-SMMHC) that is causally associated with the onset of acute myeloid leukemia in humans. The three-dimensional structure of PEBP2/CBF beta has been determined in solution and is shown to adopt a fold related to the beta-barrel oligomer binding motif. Direct analysis of a 43.6 kD ternary RD-beta-DNA complex identifies the likely surface of beta in contact with the RD. The structure of PEBP2/CBF beta enables a molecular understanding of the capacity of PEBP2/CBF beta-SMMHC to sequester PEBP2/CBF alpha in the cytoplasm and therefore provides a molecular basis for understanding leukemogenic transformation.

Binding Sites↗

PubMed1999

The effect of grapefruit juice on the time-dependent decline of artemether plasma levels in healthy subjects.

BACKGROUND: Artemether is a new and effective treatment for malaria, although relapse is a problem in monotherapy. These relapses could be related to a time-dependent decline in artemether plasma levels described in multiple-dose studies and probably caused by autoinduction. The aim of this study was to evaluate the effect of grapefruit juice on the decreasing bioavailability over time of artemether. METHODS: In a randomized, two-phase crossover study, eight healthy male subjects took 100 mg oral artemether with 350 mL water or with 350 mL double-strength fresh frozen grapefruit juice once daily for 5 days. On day 1 and day 5, 17 blood samples were collected over a period of 8 hours. RESULTS: The mean peak artemether plasma concentration (Cmax) and the mean area under the concentration-time curve (AUC) after the last dose at day 5 were about one third compared with day 1, without a change in the elimination half-life after intake with water (P = .006 for Cmax; P = .005 for AUC) and with grapefruit juice (P < .001 for Cmax and AUC). Grapefruit juice increased Cmax (P = .021) and AUC (P < .001) twofold on day 1 (P = .021) and day 5 (P = .05 for Cmax; P = .004 for AUC). Dihydroartemisinin, the active metabolite, showed a twofold increase in Cmax (P = .006) and AUC (P = .001) with grapefruit juice, without time-dependent changes of pharmacokinetic parameters. CONCLUSIONS: Grapefruit juice significantly increased the oral bioavailability of artemether but did not prevent the time-dependent reduction in bioavailability. It suggests that CYP3A4 in the gut wall is one of the metabolizing enzymes of artemether but seems to not be involved in the autoinduction process.

Administration, Oral↗

PubMed1999

Diagnostic efficacy of polymerase chain reaction in granulomatous uveitis.

SETTING: The granulomatous uveitis, multifocal choroiditis and periphlebitis have been suspected to be of tubercular origin but no definitive reports about detection of etiological agents have been documented in the literature. Conventional bacteriological methods are not generally helpful in diagnosing ocular tuberculosis due to difficulty with potential morbidity associated with obtaining the biopsy material from the eye. Thus, the diagnosis of ocular tuberculosis is most often presumptive. OBJECTIVE: We evaluated the role of polymerase chain reaction (PCR) for detection of Mycobacterium tuberculosis in the aqueous humor samples obtained from eyes with active uveitis. METHODS: Aqueous samples from 53 patients having cellular reaction in the anterior chamber along with any one or more of the following: 1) active vasculitis; 2) anterior vitreous cells; 3) snowball opacities; 4) snow banking in the pars plana; 5) retinochoroiditis were withdrawn by anterior chamber paracentesis and subjected to PCR. Seventeen samples from patients with definite clinical diagnoses other than tuberculosis formed a disease control group. Fifteen aqueous samples obtained from healthy subjects undergoing routine cataract surgery served as healthy controls. PCR was performed using primers capable of amplifying a 150 b.p. segment from a conserved repetitive sequence in the genome of M. tuberculosis. RESULTS: Twenty out of the 53 samples (37.7%) in the study group were positive where as only one sample out of 17 in the disease control group (5.7%) showed a weakly positive band. No sample from the healthy control group showed a positive PCR. CONCLUSION: Our study shows that PCR can be effectively used for the diagnosis of intraocular tuberculosis in the presence of uveitis.

Aqueous Humor↗

PubMed1999

Comparative efficacy and safety of nimesulide versus piroxicam in osteoarthritis with special reference to chondroprotection.

The efficacy and tolerability profile of nimesulide was assessed in a double-blind, piroxicam-controlled trial in 49 patients with osteoarthritis of the knee joint. Nimesulide was administered orally as 100 mg twice daily, and piroxicam was administered as 20 mg orally in the morning and placebo in the evening. These patients were stratified into two groups: clinical assessment and magnetic resonance imaging evaluation of the knee. All patients were followed for 8 weeks with clinical assessment every 2 weeks; of these, 11 patients were selected for magnetic resonance imaging evaluation, and they were treated for 24 weeks. The principal efficacy parameters were improvement in osteoarthritis severity index, joint tenderness, swelling, and functional capacity of the patients. The final judgment of efficacy was made by the physician. Nimesulide improved all primary and secondary efficacy parameters with an activity comparable to piroxicam. Significant reduction in joint swelling and tenderness was observed as early as 2 weeks in the two treatment groups; however, a greater number of patients were relieved in nimesulide group. At 8 and 24 weeks, the number of patients with no joint swelling were 66.7% versus 50% and 80% versus 66.7% in the nimesulide and piroxicam groups (P <.05). Functional capacity at 8 weeks improved in 72.2% of nimesulide and 44.4% of piroxicam recipients. Mild adverse effects, mainly gastrointestinal, considered possibly related to treatment were recorded in 4 patients treated with nimesulide and in 12 patients treated with piroxicam. No significant change in the articulating cartilage of the tibiofemoral joint was observed over a 24-week period with either treatment. Nimesulide was as efficacious as piroxicam in reducing the inflammatory indices, and both drugs were equally well tolerated.

Adult↗

PubMed1999

Tuberculosis of the foot.

In 44 patients with tuberculosis of the foot we identified five radiological patterns of lesions; cystic, rheumatoid, subperiosteal, kissing and spina ventosa. Cystic destruction had the best outcome and rheumatoid the poorest. All the patients were cured after antituberculous treatment for 18 months, and none required surgery.

Adolescent↗

PubMed1999

Abortion: attitudes and perceptions of health professionals in Zimbabwe.

OBJECTIVE: To determine the attitudes of professional health workers (doctors, nurses, matrons, social workers and hospital administrators) to medically supervised abortion. DESIGN: Cross sectional study. SETTING: Randomly selected health institutions--urban as well as rural in the eight provinces of Zimbabwe. SUBJECTS: Males and females--age range 18 to 70 years. MAIN OUTCOME MEASURES: Perception of the problem of abortion by health professionals, their knowledge of the present abortion law and desire for change. RESULTS: The majority of doctors were supportive of medically supervised abortion (61.2%) while the nurses were divided 43.2% for and 42.0% against but 14.8% were undecided. The administrators and social workers were supportive. Of the doctors 75% felt that the present abortion law was restrictive and 55.6% supported change. All health professionals agreed that the majority of women who present for abortion treatment are single. The surprising finding was that it is knowledge of the dire complications of unsafe abortion that determines one's attitude to abortion rather than religion. CONCLUSION: By increasing single women's and adolescents' access to family planning services the incidence of unintended pregnancies which result in unsafe abortion with life threatening complications will be reduced. The present restrictive abortion laws which foster backstreet unsafe abortion need to be revised.

Abortion, Legal↗

PubMed1999

Development and implementation of guidelines for management of sedation and agitation in critically ill patients.

The article describes the development, implementation, and success of guidelines for pharmacological management of sedation and agitation in critically ill patients in a community hospital. Guidelines were developed with careful review of published literature and in cooperation with thought leaders in the institution. The primary focus of the guidelines was choice of medication and monitoring parameters and an educational campaign to ensure use of the guidelines. A prospective pharmacist intervention program was initiated for further enforcement of the guidelines. Implementation of these guidelines has resulted in a significant reduction in the cost of sedation and agitation (annual cost savings, > $40,000 per year).

Behavioral Symptoms↗

PubMed1999

School-based health centers in Louisiana: an introduction.

Up to 20% of students in America's public schools suffer from a chronic health condition. Working parents and the behavioral morbidities of the late 20th century put children at risk for poor physical health, poor mental health, and poor educational outcomes. Access to care is poor for adolescents in general and for the uninsured. School-Based Health Centers deliver primary mental and physical health care inside schools where the children are. They are run by interdisciplinary teams of professionals. They focus their efforts on primary care and prevention and collaborate with schools, parents, and the community to deliver this care.

Adolescent↗

PubMed1999

Community based study of reproductive tract infections among ever married women of reproductive age in a rural area of Haryana, India.

A community based study was carried out to estimate the load of reproductive tract infections (RTIs) among ever married rural women aged 15-44 years and utilisation of a mobile village based treatment facility by them, during 1997. Complete household survey was done in 10 randomly selected villages of Mahindergarh district in Haryana, India. A total of 2325 women were interviewed by auxiliary nurse midwives and were invited for medical examination in a health camp set-up in their village. Sixty-one percent (1415/2325) women reported symptoms of RTIs. Only 35% (812/2325) had their per-speculum examination done. Out of those examined, 32% (263/812) had vaginitis, 21% (175/812) had cervicits, and 19% (156/812) had pelvic inflammatory disease. Vaginal smear of those having discharge revealed that 48% (231/476) had bacterial vaginosis, 0.8% (4/476) had fungal infection 9% (44/496) had trichomonal infection and none was found to be having gonococcal infection. Tests for chlamydial infection could not be performed as the cost was not affordable. Eighty-nine percent of women who reported symptoms of RTIs had not consulted anyone for their problem prior to our village based camp. Only 42% symptomatic and 24% asymptomatics availed the services even in the village based camps. Study revealed high load of reproductive tract infections and low utilisation of treatment facility. In-depth studies are required to understand for high RTI morbidity load and low treatment seeking rate so as to design an appropriate RTI control programme.

Adolescent↗

PubMed1998

Effects of Boswellia serrata gum resin in patients with bronchial asthma: results of a double-blind, placebo-controlled, 6-week clinical study.

The gum resin of Boswellia serrata, known in Indian Ayurvedic system of medicine as Salai guggal, contains boswellic acids, which have been shown to inhibit leukotriene biosynthesis. In a double-blind, placebo-controlled study forty patients, 23 males and 17 females in the age range of 18 - 75 years having mean duration of illness, bronchial asthma, of 9.58 +/- 6.07 years were treated with a preparation of gum resin of 300 mg thrice daily for a period of 6 weeks. 70% of patients showed improvement of disease as evident by disappearance of physical symptoms and signs such as dyspnoea, rhonchi, number of attacks, increase in FEV subset1, FVC and PEFR as well as decrease in eosinophilic count and ESR. In the control group of 40 patients 16 males and 24 females in the age range of 14-58 years with mean of 32.95 +/- 12.68 were treated with lactose 300 mg thrice daily for 6 weeks. Only 27% of patients in the control group showed improvement. The data show a definite role of gum resin of Boswellia serrata in the treatment of bronchial asthma.

Adolescent↗

PubMed1998

Measurement and control of interface strength of RF magnetron-sputtered Ca-PO coating on Ti-6Al-4V substrates using a laser spallation technique.

In previous studies, an RF magnetron sputter technique was developed for the production of thin calcium phosphate coating. Several deposition parameters were found to influence the growth rate and the stoichiometry of the coatings. For instance, deposition with additional oxygen pressure decreased the Ca to P ratio of the coatings to 1.67. For application of these coatings on actual Ti implants, it is important to know their adhesive tensile strength with the implant surface and how it varies with the deposition parameters. Motivated by these goals, the aim of this study was to measure the adhesive tensile strength of these coatings with Ti substrates and to study its variation with the deposition parameters. Since most mechanical characterization methods are incapable of providing a direct measure of the interface's fundamental strength, a novel laser spallation experiment was used to accomplish this task. In this experiment, a compressive stress pulse is generated on the back side of a substrate by impinging a 3-ns long Nd:YAG laser pulse. The stress pulse propagates through the substrate and is reflected into a tensile stress wave from the free surface of the coating deposited on its front surface. The returning tensile pulse pries off the coating if its amplitude is high enough. The peak interface tensile stress is computed by using the optically recorded free surface displacement of the coating. Because interface decohesion is accomplished at a strain rate of almost 10(7) s-1, all inelastic processes essentially are suppressed and the measured value essentially is the intrinsic tensile strength of the interface. Tensile strength values in the range of 500-900 MPa were recorded for the interfaces between sputter-deposited calcium-phosphate coatings and Ti substrates. To confirm the locus of failure, the spalled spots were examined using SEM and EDS. The variation in the measured values was related to the changes in the deposition conditions.

Alloys↗

PubMed1998

Deletion of transmembrane domain 12 of CDR1, a multidrug transporter from Candida albicans, leads to altered drug specificity: expression of a yeast multidrug transporter in baculovirus expression system.

Cdr1p, an ATP-binding cassette transporter from the pathogenic yeast Candida albicans, confers resistance to several unrelated drugs including anti-Candida drugs (Prasad et al., 1995b). We demonstrate that the deletion of 237 bp (79 aa) from the 3' end of CDR1 (which encompasses the transmembrane domain (TM) 12 of the putative transporter) did not result in the total loss of its ability to efflux cytotoxic agents. While the expression of deltaCDR1 in yeast resulted in impaired sensitivity to drugs like cycloheximide, anisomycin, sulfomethuron methyl and antifungal nystatin, its ability to confer resistance remained unaltered to drugs such as o-phenanthroline, 4-nitroquinoline-N-oxide, cerulenin, azoles, oligomycin, erythromycin, and benomyl. Similar to human MDR1p. Cdr1p might also have localized drug binding sites in TM 12, but that might not be the case for all the drugs. The TM 12 deletion also did not lead to any significant impairment in NTPase activities. Both ATPase and UTPase activities of complete Cdr1p and deltaCdr1p were not significantly altered, as was the case with respect to their ability to efflux Rh123 and steroid hormone like [3H]-beta-estradiol. To further dissect the functionality of Cdr1p, its truncated version was overexpressed in a baculovirus-insect cell expression system. The synthesis of deltaCdr1p in Sf9 cells was temporally regulated as a function of the baculovirus polyhedrin gene promoter. The Sf9 derived deltaCdr1p was approximately 130 kDa, which was lower than the expected size, probably due to the differences in glycosylation. This, however, did not affect the functionality of deltaCdr1p. The deletion of TM 12 did not affect the targeting of the protein and deltaCdr1p was exclusively localized in plasma membrane of Sf9 cells as detected by immunofluorescence. The expression of deltaCdr1p in the baculovirus-insect expression system generated a high drug-stimulated plasma membrane-bound ATPase activity which was not demonstrable when deltaCdr1p was expressed in yeast.

ATP-Binding Cassette Transporters↗

PubMed1998

In-frame elimination of exon 10 in Cftrtm1Unc CF mice.

Cystic fibrosis (CF) is a severe autosomal-linked inherited disease in humans. Transgenic CF animals play a crucial role in the study of molecular mechanisms underlying disease pathology. In the present study, CFTR mRNA expression was examined in different tissues from one CF mouse model that contains a disruption in exon 10 sequence of the CF transmembrane conductance regulator (CFTR) gene. Multiple tissue samples were collected from new-born normal (+/+), homozygous (-/-), and heterozygous (+/-) mice and compared for their CFTR mRNA expression. Total RNA samples were prepared from eight different tissues (nasal mucosa, trachea, lung, colon, intestine, pancreas, liver, gonads, and brain) and then analyzed by reverse transcription polymerase chain reaction (RT-PCR) amplification. A 329-bp fragment comprising exon 9 through exon 11 of the CFTR gene was amplified from all tissues of the normal mouse. In contrast, a 137-bp fragment was observed in tissue samples from homozygous CF mice. Both the 329-bp and 137-bp fragments were detected in samples from heterozygous mice. Direct sequencing analysis of the amplified fragments showed an exon 9-exon 11 splice junction, indicating that the entire exon 10 sequence was eliminated from homozygous CF mice. RT-PCR analysis of the 3' end of CFTR mRNA showed the presence of a 682-bp, exon 20-24 fragment in -/- and +/- mice. These results demonstrate that an alternately spliced CFTR mRNA is produced in this CF 'knock-out' mouse. A semi-quantitative comparison of the wild-type and exon 10 minus CFTR (CFTR-E10) mRNA in heterozygote animals indicated that less (but a detectable amount) mutant CFTR mRNA was present in all organs tested. There was, however, a significant reduction of CFTR-E10 mRNA in the liver and the pancreas. Since the deletion of exon 10 is in-frame, the significance of the CFTR-E10 mRNA in terms of CFTR protein and function requires further analysis.

Animals↗

PubMed1998

Expression of CDR1, a multidrug resistance gene of Candida albicans: transcriptional activation by heat shock, drugs and human steroid hormones.

We have examined the expression of CDR1 (Candida drug resistance gene) in different stress conditions. There was a significant but transient enhancement of CDR1 expression associated with elevated temperatures. Most noteworthy transcriptional activation was observed with miconazole and vinblastine. Interestingly, beta-estradiol and progesterone were also able to enhance CDR1 expression. Elevated levels of CDR1 and CDR2 (a homologue of CDR1) mRNA were found in some azole-resistant clinical isolates of C. albicans. CaMDR1 (benomyl-resistant) expression, however, did not differ among all the resistant isolates. Our results confirm the existence of multiple mechanisms of azole resistance in C. albicans.

Antifungal Agents↗

PubMed1998

Characterisation of human steroid hormone transport mediated by Cdr1p, a multidrug transporter of Candida albicans, belonging to the ATP binding cassette super family.

Cdr1p, a multidrug transporter from a pathogenic yeast Candida albicans, confers resistance to several unrelated drugs including anti-Candida drugs. We demonstrate that Cdr1p can specifically transport human steroid hormones namely beta-estradiol and corticosterone. Saccharomyces cerevisiae transformant S-12, harbouring the CDR1 gene, accumulated about 3-fold less [3H] beta-estradiol and about 2-fold less [3H]corticosterone than the non-transformed strain. When CDR1 was expressed in AD strain (AD-CDR1) which had seven ATP binding cassette (ABC) superfamily of putative transporter genes disrupted, the net accumulation of these hormones as compared to S-12 was significantly lower. Efflux of beta-estradiol and corticosterone was inhibited by a 100-fold higher (200 nM) concentration of beta-estradiol, corticosterone, ergosterol or dexamethasone, but progesterone which could not be transported by Cdr1p did not affect the efflux and thus accumulation. Interestingly, some of the drugs viz. cycloheximide, chloramphenicol, fluconazole and o-phenanthroline, to which CDR1 confers resistance, could also prevent efflux and enhance accumulation to some extent. In conclusion, we show that human steroid hormones could be the substrates for Cdr1p and the energy dependent transport mediated by it is specific for estradiol and corticosterone.

ATP-Binding Cassette Transporters↗

PubMed1998

Primary stenting of de novo lesions in small coronary arteries: a prospective, pilot study.

Technical advancement and new anti-thrombotic regimens have recently shown so much improvement in the results of coronary stenting that the conventional contra-indication for stenting in small coronary arteries (<3 mm) needs to be revised. We undertook a prospective pilot study of elective Palmaz-Schatz stenting in de novo lesions located in coronary arteries of less than 3 mm diameter. Fifty consecutive patients (63 +/- 9 years) with stable (n = 38) and unstable angina (n = 12) were included. Philips-DCI quantitative coronary analysis was used to measure reference diameter, minimal lumen diameter and percent diameter stenosis before PTCA, after stenting and at 6-month angiographic follow-up study. All measurements were performed after intracoronary injection of nitroglycerin (300 microg). All patients received ticlopidine (250 mg/day) and aspirin (100 mg/day). The mean lesion length was 9 +/- 3 mm. The balloon size used for stent delivery was 2.75 mm in 30 patients and 2.5 mm in 20 patients and the mean balloon inflation pressure used for stent deployment was 12 +/- 2 atm. All stents were deployed successfully. In-hospital complications occurred in two patients, diagonal branch occlusion at day 2 requiring emergency PTCA in one and a hematoma at the femoral puncture site requiring surgery in the other. Major adverse cardiac event (MACE) rate remained 2% (nonfatal infarct in one). Follow-up angiography (n = 46, 92%) at 6 +/- 3 months showed a 30% restenosis rate. Target vessel revascularization (TVR) rate was 13%. We conclude that elective stenting in small coronary arteries is feasible and involves an acceptable risk of restenosis.

Angina Pectoris↗