Biomedical subjects

V Dhar

Publications and source records attributed to V Dhar.

At least 19 recordsLinked to original sources

PubMed2006

Effect of frequent dosing of an oral proton pump inhibitor on intragastric pH.

BACKGROUND: Treatment with a continuous i.v. proton pump inhibitor is presumed to promote clot formation and stability by sustaining intragastric pH > or = 6. AIM: We postulated that very frequent oral dosing of proton pump inhibitors should simulate i.v. infusion and achieve similar pH control. METHODS: Twenty healthy volunteers were stratified by Helicobacter pylori status (10 positive; 10 negative) and had determination of CYP2C19 status. After an overnight fast, an intragastric pH probe was placed. Subjects received 120 mg of lansoprazole at 8 am and 30 mg every 3 h until 8 pm. Intragastric pH was measured over 24 h, and lansoprazole plasma concentrations were determined at five time points. RESULTS: Intragastric pH was > or = 6 for 41% (95% CI: 30-53%) of the 15-h period from 8 am-11 pm and 46% (95% CI: 35-56%) of the 24-h period (8-8 am). The mean proportion of patients with pH > or = 6 was not significantly different in H. pylori-positive vs. negative patients. Only 25% of subjects sustained pH > or = 6 for at least 60% of the 15-h period, and 35% had a sustained pH > or = 6 for at least 60% of the 24-h period. CONCLUSIONS: A dose of 120 mg of oral lansoprazole followed by standard 30 mg doses of lansoprazole every 3 h did not reliably sustain pH at the desired level of 6.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed2001

Evidence suggesting that high intake of fluoride provokes nephrolithiasis in tribal populations.

The present study was designed to evaluate the role of fluoride in urolithiasis in humans. Two areas were selected for this purpose, a fluoride endemic area (EA) and a fluoride non-endemic area (NEA). The prevalence of uroliathiasis was 4.6 times higher in EA than in NEA. Furthermore, the prevalence was almost double in subjects with fluorosis than without fluorosis in the endemic area. No relationship was observed between urolithiasis and the duration of fluorosis. The fluoride levels in drinking water ranged from 3.5 to 4.9 ppm in EA and subjects from this area excreted more fluoride. A comparison of normal subjects (NS) from EA and NEA revealed that endemic subjects tend to have slightly higher mean serum thiobarbituric acid reactive substance (TBAR) levels and excrete more oxalate and fluoride than their non-endemic counterparts. The urinary stone formers (SF) from the two areas showed a similar tendency, though again the difference was not significant. Citrate excretion in SF was almost normal in the EA, but NEA SF had significantly lower excretion levels. Urinary stones from endemic patients had higher fluoride, oxalate and calcium levels than those from non-endemic patients. In vitro studies suggested that fluoride did not influence the heterogonous mineralization of calcium oxalate. In conclusion, the data suggest that fluoride in vivo may behave as a mild promoter of urinary stone formation by (a) excretion of insoluble calcium fluoride, (b) increasing oxalate excretion and (c) mildly increasing the oxidative burden.

Adult↗

PubMed1999

Comparative analysis of tensile bond strength of two new fissure sealants using invasive and non-invasive techniques.

In this era of preventive dentistry, a galore of dental materials used for prevention of dental diseases is available. Since the last few decades efforts are being directed towards prevention of dental caries which is one of the major dental diseases tormenting mankind. The rationale of using a fissure sealant is that when it is applied on the caries prone fissures, it penetrates these pits and fissures and seals them from the oral environment. One of the main problems usually encountered is retention of the sealant material. This study was undertaken with the aim to evaluate the tensile bond strength of two new fissure sealants using invasive and non-invasive techniques. The results substantiated the use of invasive techniques over non-invasive techniques and resin sealants over glass ionomer sealants.

Adhesiveness↗

PubMed1998

Autopsy in a neonatal intensive care unit: utilization patterns and associations of clinicopathologic discordances.

OBJECTIVES: (1) To develop methods to describe autopsy utilization patterns in a neonatal intensive care unit. (2) To identify classes of patients likely to have clinicopathologic concordance or discordance. METHODS: Five hundred forty-five consecutive neonatal intensive care unit deaths (338 autopsied, rate 62%) in a regional tertiary/quaternary care neonatal intensive care unit for referred infants (65,000 annual births) were classified in six clinical diagnostic groups (anomalies, cardiac anomalies, hypoxic ischemic encephalopathy, prematurity and its complications, infections, and other) and rated in three levels of certainty of clinical diagnosis as "gold standard" certainty, almost complete certainty, and less certain than the latter. Clinicopathologic discordances were rated in three classes using clinical, pathologic, and multidisciplinary mortality conference records. The proportions of autopsied cases, cases with major discordances, and cases with no discordances were compared and analyzed in relation to diagnostic group and level of certainty. RESULTS: Performance of autopsy was associated with clinical diagnostic uncertainty (p = 0.008). Major discordances with implications for outcome (Class I) were found in 3%, and without implications for outcome (Class II) in 15% of cases; 42% of cases had no discordances. Major discordance rate varied inversely with the degree of diagnostic certainty (p = 0.000) and varied among clinical groups. CONCLUSIONS: (1) Autopsy was used most for cases with potential for high yields. (2) Clinicopathologic discordances were more frequent and important in certain clinical diagnostic groups (prematurity, other) and with high levels of diagnostic uncertainty. When the diagnostic "gold standard" is available during life, autopsy will provide little information.

Autopsy↗

PubMed1998

Neuroendocrine responses to inhibitors of steroid biosynthesis in patients with major depression resistant to antidepressant therapy.

OBJECTIVE: Patients with major depression frequently have high cortisol levels and resistance to dexamethasone. We sought to determine to what extent major depression might be influenced by inhibitors of steroid biosynthesis and to study the endocrine changes produced. METHOD: After drug washout, 20 treatment-resistant patients with major depression were given aminoglutethimide, metyrapone, and/or ketoconazole, along with a small dose of cortisol for 8 weeks. Hamilton Depression Rating Scale (HDRS) ratings, 8:00 AM cortisol dehydroepiandrosterone sulfate (DHAS), adrenocorticotropin (ACTH), and testosterone levels were followed weekly or oftener. A dexamethasone suppression test (DST) was conducted before and after treatment. RESULTS: Seventeen patients (85%) completed the course of treatment, and a significant mean drop (P < or = 0.0001) of 50% in the HDRS score occurred by 7 weeks of treatment. Cortisol levels fluctuated widely and were often still high after the patient had improved clinically. Dehydroepiandrosterone sulfate levels fell more uniformly and were found to be a useful indicator of compliance and, to some extent, efficacy with aminoglutethimide and ketoconazole therapy. The correlation between DHAS and HDRS (r = 0.94) was significant (P = 0.02). Testosterone levels in men fell with ketoconazole but returned promptly to normal at the end of treatment. Adrenocorticotropin levels were normal or elevated, depending on the assay used, and rose (P = 0.07; n = 13) in most subject during therapy. Of the 6 responders who had nonsuppressor DSTs before starting therapy, 5 had reverted to normal 1 to 2 weeks following cessation of therapy (P = 0.0006). CONCLUSIONS: Abnormal metabolism of adrenocortical steroids may perpetuate depression, and alterations of synthesis or metabolism of these steroids may lead to a remission.

Adult↗

PubMed1998

Bite mark analysis in child abuse.

The science of bite mark analysis is relatively new and potentially valuable. This science has been greatly used in identifying the suspects involved in crimes related to sex, child abuse, and altercations of various types. Child abuse is presenting a serious social problem with global dimensions, which is increasing at an alarming rate in all socioeconomic strata and all ethnic or racial communities. The aim of the present study was to assess these bite marks and analyze the effectiveness of a simple technique used in the department of pedodontics and preventive dentistry, College of Dental Surgery, Manipal.

Bites, Human↗

PubMed1998

Rationale and potential use of cytokines in the prevention and treatment of neonatal sepsis.

Despite advances in the use of newer antimicrobials and aggressive supportive care, sepsis and its sequalae remain a major source of morbidity and mortality in the neonate. The VLBW neonate is especially at high risk. We and others have demonstrated that neonatal MNC are deficient in their production of G-CSF and GM-CSF, which, in part, may explain the neonates propensity to develop neutropenia during times of sepsis. G-CSF and GM-CSF have been shown to both enhance neonatal neutrophil superoxide production in vitro and to increase circulating neutrophil numbers through expansion of the NSP in the BM in neonatal rats and humans. G-CSF is protective (if given with or before antibiotics) during experimental GBS in the neonatal rat and appears to be well tolerated (both short term and 2 years after its use) in the human neonate. In a phase II randomized pilot multicenter study, GM-CSF prophylaxis in the VLBW neonate was well tolerated during 4 weeks of administration and was noted to have significantly reduced the incidence of nosocomial infections. Future efficacy and safety studies in more neonates need to be completed and assessed before the routine pharmacologic use of G-CSF or GM-CSF is recommended to prevent and treat neonatal sepsis.

Animals↗

PubMed1997

Interleukin-1 alpha upregulates the expression of surfactant protein-A in rabbit lung explants.

Interleukin-1 (IL-1) is an important participant in infectious and inflammatory conditions. Interleukin-1 receptor antagonist (IL-1ra) prevents the effect of IL-1. We have shown that injection of interleukin-1 alpha (IL-1 alpha) into the amniotic fluid of pregnant rabbits stimulates the expression of surfactant protein-A (SP-A) in the lungs of the fetuses. We hypothesized that IL-1 alpha similarly enhances the expression of SP-A in rabbit lung explants in vitro. Explants obtained from 22-day fetal rabbit lungs were cultured in Waymouth's medium on a rotating platform in the presence or absence of IL-1 alpha (5.7-570 ng/ml) or IL-1ra (1-10 micrograms/ml). Dibutyryl cAMP (1 mM) served as a positive control. After 3 days in culture, the explants were harvested and Northern analysis of SP-A was performed using the 1.9-kb rabbit SP-A cDNA probe. IL-1 alpha and dibutyryl cAMP increased the expression of SP-A twofold, as judged by video densitometry. IL-1ra did not change SP-A expression as compared with controls, suggesting that endogenous IL-1 activity was not responsible for the basal level of SP-A expression in the explants. Dibutyryl cAMP increased the expression of SP-B mRNA, whereas IL-1 alpha had no effect on SP-B mRNA concentration. We conclude that inflammatory mediators interact with lung cells to alter synthesis of important components of the surfactant system.

Animals↗

PubMed1996

Impaired jun-NH2-terminal kinase activation by ultraviolet irradiation in fibroblasts of patients with Cockayne syndrome complementation group B.

c-jun-NH2 kinases (JNK) are among the UV-activated protein kinases that play an important role in cellular stress response via the phosphorylation of c-jun, ATF2, and p53. Activation of JNK by UV irradiation requires cooperation between membrane and nuclear components, including DNA lesions per se. The role of DNA lesions in JNK activation led us to explore the inducibility of these kinases in cells of repair-deficient patients. Analyses of primary fibroblast cell lines from patients with Cockayne Syndrome of complementation group B (CS-B) revealed poor JNK activation after UV irradiation in four of five cases when compared with three repair-proficient, normal human fibroblast cell lines. Impaired ability to activate JNK persisted at various time points and with different doses of UV irradiation and coincided with failure of in vitro damaged DNA to activate these kinases. In contrast to UV irradiation, other forms of stress, such as H2O2 or heat shock were capable of inducing JNK activation in CS-B cells. Interestingly, when UV irradiation was administered after osmotic shock, it led to JNK activation in CS-B cells, indicating that alternate signal transduction pathways that are activated in response to other forms of stress can potentiate JNK activation by UV irradiation. Unlike CS-B cells, those of other repair-deficient cells, including xeroderma pigmentosum of different complementation groups, revealed proper activation of JNK by UV irradiation. Together, our findings point to deficiency of JNK activation by UV irradiation in CS-B cells, a phenomenon which may be associated with impaired CS-B, the mutant repair gene in these patients.

Calcium-Calmodulin-Dependent Protein Kinases↗

PubMed1995

The psychotropic effects of inhibitors of steroid biosynthesis in depressed patients refractory to treatment.

Twenty patients, diagnosed as suffering from treatment-resistant major depression, were treated with one or more drugs that decrease corticosteroid biosynthesis. Nine were psychotic, 11 nonpsychotic. Seventeen completed the treatment (8 psychotic, 9 nonpsychotic); 13 responded (5 psychotic, 8 nonpsychotic; 11 responded completely (i.e., a drop in the Hamilton Depression Scale of at least 50%, to < or = 15), and 2 responded partially. The mean age of the responders (45.2 +/- 12.6 years) did not differ significantly from that of the nonresponders (48.7 +/- 12/3). Data were analyzed in the following categories; (1) the presence or absence of psychosis, (2) response or nonresponse to treatment, and (3) the drug(s) used (aminoglutethimide, ketoconazole, or a combination of either of these with metyrapone). The patients improved over time on the Hamilton Depression Scale independent of the medication used. Responders demonstrated improvement in mood, insomnia, anxiety, diurnal variation, paranoia and obsessive compulsiveness. Nonpsychotics responded better than psychotics.

Adrenal Cortex Hormones↗

PubMed1994

Dissociation of bone mineral density from age-related decreases in insulin-like growth factor-I and its binding proteins in the male rat.

We evaluated the possibility that age-related decreases in circulating and/or bone-associated insulin-like growth factor-I (IGF-I) and its binding proteins (BPs) were associated with the development of osteopenia in 8-, 16-, and 24-month-old specific pathogen-free Brown Norway/Fischer 344 male rats. We measured bone mineral densities (BMD) of femurs by dual-energy x-ray absorptiometry. IGFs and IGFBPs were extracted from bone and separated by molecular exclusion HPLC before quantitation by specific radioligand assays. BMD did not change significantly between 8 and 24 months of age. IGF-I levels decreased by about 30% between 8 and 24 months in both serum and bone. Similarly, both circulating and bone-derived IGFBPs also declined (30% and 60%, respectively) with age. Thus, maintenance of femoral BMD throughout most of the adult rat life span was dissociated from the age-related decline in circulating and bone-associated IGF-I and IGFBPs.

Aging↗

PubMed1993

Streptococcal vulvovaginitis in girls.

Group A beta-hemolytic Streptococcus (GAHS) was isolated from 18% of swabs submitted to a district microbiology laboratory from girls with vulvovaginitis, a figure similar to that from a contemporary British study. This suggests that vulvovaginitis is more commonly associated with GAHS than reported previously. This could represent either an increase in frequency of the condition or better recognition of it.

Adolescent↗

PubMed1991

Interleukin 10: a novel stimulatory factor for mast cells and their progenitors.

We have characterized the mast cell stimulating activity of murine cytokine synthesis inhibitory factor, referred to as interleukin 10 (IL-10). It was found that IL-10 alone failed to support the growth of mast cell lines and mast cell progenitors. Nevertheless, it dramatically enhanced their growth when combined with IL-3 or IL-4. Moreover, IL-4 plus IL-10 supported the proliferation of mast cells as well as IL-3, suggesting that these two factors may provide a pathway for their development independent of IL-3. However, optimal mast cell growth was stimulated by the combination of IL-10, IL-4, and IL-3. This particular set of cytokines are coordinately produced by activated T cells and may constitute an effective network regulating early and late stages of mast cell development during certain immune responses.

Animals↗

PubMed1991

The premenstrual syndrome and its treatment.

The premenstrual syndrome has been described briefly and the literature relating to its pathophysiology and treatment have been reviewed. The great number of theories as to etiology and many different kinds of treatments attest to our ignorance of the exact nature of this problem. Although it is obvious that the hypothalamo-pituitary-ovarian axis must be involved, the exact mechanism whereby the symptoms come about remains elusive. Progestin in the presence of estrogen appears to be essential. Excess estrogen may aggravate the condition. The popular theory of progesterone deficiency has not been supported by double blind trials of progesterone in various forms versus placebo. Because of the important placebo effect in this condition, double blind trials are essential in the assessment of any form of treatment.

Female↗

PubMed1991

Role of EBNA-1 in arresting replication forks at the Epstein-Barr virus oriP family of tandem repeats.

The 20-member family of 30-bp tandem repeats located within the oriP region of Epstein-Barr virus (EBV) can act as a transcriptional enhancer in the presence of EBV nuclear antigen 1 (EBNA-1). A replication fork barrier and a termination site of plasmid replication in human B cells is also found within or near the EBV tandem repeats. Within each tandem repeat is a consensus binding sequence for the EBNA-1 protein that is required for extrachromosomal maintenance of oriP-containing plasmids. To investigate the factors that contribute to the arrest of replication forks and termination in the region of the family of repeats, we have used an in vitro replication system in which replication of EBV recombinant plasmids is initiated from the simian virus 40 (SV40) DNA replication origin in the presence of SV40 T antigen and soluble extracts prepared from human cells. The system can support bidirectional replication, initiating from the SV40 DNA origin with termination occurring in a region opposite the origin. Using two-dimensional agarose gel electrophoresis, we observed a barrier to replication forks in the presence of EBNA-1 in the region of the EBV repeats. Termination occurs at or near the tandem repeats in a manner similar to that observed in vivo (T.A. Gahn and C.L. Schildkraut, Cell 58:527-535, 1989). Reducing the number of repeats from 20 to 6 had little effect on the strength of the replication fork barrier. In the absence of EBNA-1, replication forks also arrested at the EBV repeats, but at a much lower efficiency. The addition of competitor DNA containing the EBV family of repeats can almost completely abolish the replication barrier produced in the presence of EBNA-1.

Antigens, Viral↗

PubMed1991

Response to steroid suppression in major depression resistant to antidepressant therapy.

Because of the similarities in the psychiatric symptoms of Cushing's syndrome and those of major depression, and because the former generally remits when the hyperadrenalism is alleviated, an open clinical trial of the effect of steroid suppression in major depression was undertaken. Ten patients satisfying the DSM-III-R criteria for major depression, and classified as treatment-resistant, were included. Eight patients completed the study, which consisted of discontinuation of other psychotropic drugs and 2 months' treatment with one or more steroid suppressive agent (aminoglutethimide, ketoconazole and/or metyrapone). Six were classified as responders, and two as partial responders. In six, the improvement has been sustained for longer than 5 months after withdrawing the drugs. Side effects were mild to moderate. These results provide some evidence that steroids are involved in the maintenance of major depression, and that their suppression may lead to a readjustment of the hypothalamic-pituitary-adrenal axis with remission of the depression.

Adult↗

PubMed1990

Double-blind randomized crossover trial of luteal phase estrogens (Premarin) in the premenstrual syndrome (PMS).

Eleven patients with moderate to severe premenstrual syndrome were given Premarin during the latter half of the menstrual cycle for at least two cycles, and a placebo for at least two cycles. Mental and physical symptoms were monitored daily with a self-rating scale. Premarin was significantly less effective than placebo in relieving the severity of both mental (p less than 0.02) and physical (p less than 0.02) symptoms of PMS (combined data p less than 0.01). It is concluded that luteal phase Premarin is ineffective as a treatment for PMS, and may actually aggravate the symptoms.

Adult↗

PubMed1990

Production of cytokines by mouse B cells: B lymphomas and normal B cells produce interleukin 10.

We have examined a panel of murine Ly-1+ B lymphomas and purified normal murine peritoneal B cells separated into subsets on the basis of expression of the Ly-1 surface antigen, for their ability to produce cytokines. Where possible, we have used a combination of cytokine detection methods in order to compensate for differences in sensitivity and specificity, and the possibility of inhibitors masking an activity. All the lymphomas tested were shown to constitutively express TGF-beta and CSIF/IL-10. In addition, varying levels of IL-6, TNF-alpha and TNF-beta, and G-CSF, were demonstrable in most of the lymphomas, and variants of one lymphoma (CH12) additionally produced varying levels of IL-3, IL-4, and GM-CSF. FACS purified normal Ly-1+ and Ly-1- peritoneal B cells, were also shown to express RNA encoding CSIF/IL-10, IL-6, TNF-alpha and TNF-beta, and very low levels of G-CSF, following stimulation with LPS. These data were supported by the detection of IL-6 and CSIF/IL-10 in supernatants from LPS-stimulated Ly-1+ and Ly-1- B cells using specific immunoassays. None of the lymphomas or B cell preparations produced IL-1 alpha, IL-2, IL-5, IL-7, or IFN-gamma. The purity of our normal B cell populations was assessed by phenotypic analysis on the FACS and also by the disappearance of certain mRNA transcripts after purification, e.g. CD4, c-fms, GM-CSF, and IFN-gamma, most of which could be detected in LPS-stimulated total peritoneal cell populations. This suggested that our B cell purification method had reduced, to a level undetectable in our assays, contaminating T cells (CD4), macrophages (c-fms, GM-CSF), and NK cells (IFN-gamma). Absence of IL-3, IL-4, IL-5, and GM-CSF expression by LPS-stimulated Ly-1+ and Ly-1- B cells reduced the concern that contaminating peritoneal mast cells could account for the observed cytokine production. We therefore believe our data provide strong support for production of a subset of cytokines by LPS-stimulated normal B cells. Both the Ly-1+ B lymphomas and normal Ly-1+ and Ly-1- B cells appear capable of expressing IL-6, TNF-alpha, TNF-beta, and CSIF/IL-10.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗