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Biomedical subjects

R Bhatia

Publications and source records attributed to R Bhatia.

At least 37 records · Page 2Linked to original sources
PubMed2003

Management of agitation and convulsions in hepatic encephalopathy.

Hepatic encephalopathy represents a reversible decrease in neurological function caused by liver disease. Overall incidence of seizures in hepatic encephalopathy varies between 2% and 33%. Non-convulsive status epilepticus may be particularly common in these patients. Psychiatric disturbances manifest as agitation, personality change, delusions, etc. Aims of seizure management include treatment of basic disease, correction of precipitant factors, imaging of head, and choice of a pharmacologically safe agent. It is important to consider non-convulsive status epilepticus and rule it out by an EEG. Absolute data for safety profile of drugs in liver disease is still not clear, as changes of pharmacokinetics make choice of drugs difficult. Free drug concentrations may be higher, making plasma concentration monitoring essential in such circumstances. A single seizure may not require therapy. However when started, antiepileptic drugs are usually discontinued early. Drugs with sedative effects are best avoided because of a risk of precipitating coma. Phenytoin and gabapentin are relatively preferred drugs; however, monitoring of drug levels is desirable. Management of agitation includes physical restraint and medication. Benzodiazepines are best avoided. Haloperidol is a safer choice in the presence of liver disease. Overall management of neuropsychiatric state aims at management of underlying pathology, the resolution of which leads to improvement in the clinical symptomatology.

Hepatic Encephalopathy↗
PubMed2002

Construction of green fluorescent protein (GFP)-marked strains of Bradyrhizobium for ecological studies.

AIM: To introduce the gfp gene encoding green fluorescent protein (GFP) into bradyrhizobia for their identification in nodules, soil and carrier-based inoculants. METHODS AND RESULTS: Bradyrhizobium sp. strains M29 and GN7, which nodulate mungbean (Vigna radiata), were conjugated with Escherichia coli S17-1 carrying plasmid EDS 15 (a suicide plasmid carrying a promoterless gfp gene fused with Tn5). The GFP-marked strain expressed the gfp gene from a Bradyrhizobium promoter and gave green fluorescence when observed under an epifluorescent microscope or u.v. transilluminater. All the GFP-marked strains were able to nodulate mungbean and fix nitrogen. The GFP-marked bradyrhizobia were recovered at a frequency of 90-100% and 16-63% from nodules formed under sterilized and unsterilized conditions, respectively. The GFP-marked bradyrhizobia were identified from soil and from charcoal-based inoculants on the basis of green fluorescence. CONCLUSIONS: The GFP-marked Bradyrhizobium was successfully identified on the basis of green fluorescence to study its competition and survival in the soil and in charcoal-based inoculants. SIGNIFICANCE AND IMPACT OF THE STUDY: Introduction of the gfp gene into Bradyrhizobium provides a simple, specific and cost-effective method of strain identification for ecological studies.

Bradyrhizobium↗
PubMed2002

Comparative study of "staples versus sutures" in skin closure following Dupuytren's surgery.

This prospective, randomized controlled trial assessed the use of staples for closure of the palmar skin following Dupuytren's surgery. Although staples were significantly quicker to insert than sutures, patients experienced significantly more pain on removal of staples. There was no difference in the cosmetic appearance of the wound in the two groups. We recommend use of staples for palmar wound closure following long procedures.

Adult↗
PubMed2002

Hypertrophic pachymeningitis: varied manifestations of a single disease entity.

Hypertrophic pachymeningitis is a unique clinical entity characterised by fibrosis and thickening of the duramater with resulting neurological dysfunction. Three cases of this entity are described. Presenting features were headaches and cranial neuropathies in two patients and predominantly cerebellar dysfunction in the third. One of the patients also had evidence of spinal involvement. Lower cranial nerves were chiefly involved in two patients whereas optic nerve was the predominantly affected nerve in one. Except for the presence of rheumatoid arthritis in one of the patients, we could not document clinical or biochemical evidence of any predisposing infective, inflammatory or infiltrative condition in the other two. All three patients had characteristic changes on imaging suggestive of thickened and enhancing duramater. Although variable steroid responsiveness was seen in all the three patients, tendency towards steroid dependence was evident. The clinical presentations, causes, radiological features, management options and differential diagnosis of this unique clinical syndrome have been discussed.

Central Nervous System Diseases↗
PubMed2002

Tetanus.

Tetanus is a potentially life threatening disease affecting nearly 50,000 to 1 million people world wide every year. Four major clinical forms of tetanus are described i.e. generalized, cephalic, localized and neonatal. Neonatal tetanus is particularly common in developing countries, due to unhygienic child birth practices, social taboos and improper immunization of pregnant mothers. Management of this disorder involves a team approach and aims at eradicating focus of infection, neutralizing the toxin, controlling spasms and dysautonomia and providing adequate ventilatory and supportive care. Metronidazole may be the preferred antibiotic although penicillin is still used frequently. Adequate wound debridement is necessary to prevent spore germination. Spasms are usually managed by sedatives like diazepam and neuromuscular blocking agents. Magnesium sulphate is an attractive substitute and may be tried if ventilatory facilities are unavailable. Use of baclofen is potentially advantageous but cannot be routinely prescribed. Dysautonomia is difficult to manage and requires therapy with benzodiazepines, morphine, magnesium sulphate, adrenergic blockers and recently tried baclofen therapy. Supportive care including ventilatory assistance are highly essential for successful outcome of the patients. It is imperative that complications are diagnosed early and managed appropriately. Immunization is extremely effective and is the key to prevention. Adequate steps and measures should be taken to increase awareness of this potentially preventable disease.

Diagnosis, Differential↗
PubMed2002

Naegleria meningitis: a rare survival.

Acute amebic meningoencephalitis caused by free-living amebae naegleria fowleri is extremely rare and uniformly fatal with only seven survivals reported till date. An interesting case of naegleria meningitis diagnosed by wet mount cytology of cerebrospinal fluid (CSF) and treated with amphoterecin B, rifampicin and ornidazole with complete recovery is presented. In cases of suspected pyogenic meningitis, if CSF staining, antigen detection or culture is negative for bacteria, a wet mount cytology of CSF for naegleria is suggested. Early treatment with amphoterecin B and rifampicin may improve survival.

Adult↗
PubMed2001

Solid cancers after bone marrow transplantation.

PURPOSE: To evaluate the incidence and associated risk factors of solid cancers after bone marrow transplantation (BMT). PATIENTS AND METHODS: We analyzed 2,129 patients who had undergone BMT for hematologic malignancies at the City of Hope National Medical Center between 1976 and 1998. A retrospective cohort and nested case-control study design were used to evaluate the role of pretransplantation therapeutic exposures and transplant conditioning regimens. RESULTS: Twenty-nine patients developed solid cancers after BMT, which represents a two-fold increase in risk compared with a comparable normal population. The estimated cumulative probability (+/- SE) for development of a solid cancer was 6.1% +/- 1.6% at 10 years. The risk was significantly elevated for liver cancer (standardized incidence ratio [SIR], 27.7; 95% confidence interval [CI], 1.9 to 57.3), cancer of the oral cavity (SIR, 17.4; 95% CI, 6.3 to 34.1), and cervical cancer (SIR, 13.3; 95% CI, 3.5 to 29.6). Each of the two patients with liver cancer had a history of chronic hepatitis C infection. All six patients with squamous cell carcinoma of the skin had chronic graft-versus-host disease. The risk was significantly higher for survivors who were younger than 34 years of age at time of BMT (SIR, 5.3; 95% CI, 2.7 to 8.6). Cancers of the thyroid gland, liver, and oral cavity occurred primarily among patients who received total-body irradiation. CONCLUSION: The risk of radiation-associated solid tumor development after BMT is likely to increase with longer follow-up. This underscores the importance of close monitoring of patients who undergo BMT.

Adolescent↗
PubMed2001

Abnormal growth factor modulation of beta1-integrin-mediated adhesion in chronic myelogenous leukaemia haematopoietic progenitors.

Abnormal progenitor circulation and extramedullary haematopoiesis are characteristic features of chronic myelogenous leukaemia (CML). Growth factor (GF) and beta1-integrin interactions play an important role in regulation of progenitor trafficking to and from the marrow space. CML progenitors demonstrate abnormal beta1-integrin-mediated adhesion to fibronectin (FN). In the present study we investigated whether GF modulation of beta1-integrin-mediated adhesion and migration was altered in CML progenitors. Culture with low concentrations of GF enhanced normal progenitor adhesion to FN compared with no GF, but failed to enhance CML progenitor adhesion to FN. Similarly, high concentrations of selected GF rapidly enhanced beta1-integrin-mediated adhesion of normal progenitors to FN through a phosphotidylinositol-3 (PI-3) kinase-dependent mechanism, but failed to increase CML progenitor adhesion. Exposure to a BCR-ABL tyrosine kinase inhibitor restored GF modulation of CML progenitor adhesion. CML colony-forming cells (CFC) demonstrated increased migration across FN-coated transwells compared with normal CFC in the absence of GF. The addition of stem cell factor resulted in enhanced migration of CML and normal CFC on FN. In conclusion, GF stimulation failed to enhance integrin-mediated adhesion but enhanced migration in CML progenitors on FN. BCR-ABL induced abnormalities in GF-integrin interactions could contribute to abnormal circulation and microenvironmental localization of CML progenitors.

Androstadienes↗
PubMed2001

Amyloid beta protein forms ion channels: implications for Alzheimer's disease pathophysiology.

Amyloid beta protein (AbetaP) is the major constituent of senile plaques associated with Alzheimer's disease (AD). However, its mechanistic role in AD pathogenesis is poorly understood. Globular and nonfibrillar AbetaPs are continuously released during normal metabolism. Using techniques of atomic force microscopy, laser confocal microscopy, electrical recording, and biochemical assays, we have examined the molecular conformations of reconstituted globular AbetaPs as well as their real-time and acute effects on neuritic degeneration. Atomic force microscopy (AFM) of AbetaP1-42 shows globular structures that do not form fibers in physiological-buffered solution for up to 8 h of continuous imaging. AFM of AbetaP1-42 reconstituted in a planar lipid bilayer reveals multimeric channel-like structures. Consistent with these AFM resolved channel-like structures, biochemical analysis demonstrates that predominantly monomeric AbetaPs in solution form stable tetramers and hexamers after incorporation into lipid membranes. Electrophysiological recordings demonstrate the presence of multiple single channel currents of different sizes. At the cellular level, AbetaP1-42 allows calcium uptake and induces neuritic abnormality in a dose- and time-dependent fashion. At physiological nanomolar concentrations, rapid neuritic degeneration was observed within minutes; at micromolar concentrations, neuronal death was observed within 3-4 h. These effects are prevented by zinc (an AbetaP channel blocker) and by the removal of extracellular calcium, but are not prevented by antagonists of putative AbetaP cell surface receptors. Thus, AbetaP channels may provide a direct pathway for calcium-dependent AbetaP toxicity in AD.

Alzheimer Disease↗
PubMed2001

Expression of HoxA5 in the heart is upregulated during thyroxin-induced metamorphosis of the Mexican axolotl (Ambystoma mexicanum).

Widespread external and internal changes in body morphology have long been known to be hallmarks of the process of metamorphosis. However, more subtle changes, particularly at the molecular level, are only now beginning to be understood. A number of transcription factors have recently been shown to alter expression either in levels of message or in isoforms expressed. In this article, we describe a dramatic increase in the expression of the homeobox gene HoxA5 in the heart and aorta of the Mexican axolotl Ambystoma mexicanum during the process of thyroxin-induced metamorphosis. Immunohistochemical analysis with anti-HoxA5 antibody in thyroxin-induced metamorphosing animals showed a pattern of expression of HoxA5 comparable to that in spontaneously metamorphosing animals. Further, by in situ hybridization, we were able to show significant qualitative differences in the expression of this gene within the heart. Maximum HoxA5 expression occurred at the midpoint of metamorphosis in the myocardium, whereas the hearts of completely metamorphosed animals had the highest levels of expression in the epicardium and endocardium. In the aorta, smooth-muscle cells of the tunica media as well as cells of the tunica adventitia had an increase in expression of HoxA5 with thyroxin-induced metamorphosis. HoxA5 expression significantly changed in cells of the aorta and ventricle with treatment by thyroid hormone. HoxA5, a positive regulator of p53, may be involved with the apoptotic pathway in heart remodeling during amphibian metamorphosis.

Ambystoma↗
PubMed2001

Estimation of health benefits from a local living wage ordinance.

OBJECTIVES: This study estimated the magnitude of health improvements resulting from a proposed living wage ordinance in San Francisco. METHODS: Published observational models of the relationship of income to health were applied to predict improvements in health outcomes associated with proposed wage increases in San Francisco. RESULTS: With adoption of a living wage of $11.00 per hour, we predict decreases in premature death from all causes for adults aged 24 to 44 years working full-time in families whose current annual income is $20,000 (for men, relative hazard [RH] = 0.94, 95% confidence interval [CI] = 0.92, 0.97; for women, RH = 0.96, 95% CI = 0.95, 0.98). Improvements in subjectively rated health and reductions in the number of days sick in bed, in limitations of work and activities of daily living, and in depressive symptoms were also predicted, as were increases in daily alcohol consumption. For the offspring of full-time workers currently earning $20,000, a living wage predicts an increase of 0.25 years (95% CI = 0.20, 0.30) of completed education, increased odds of completing high school (odds ratio = 1.34, 95% CI = 1.20, 1.49), and a reduced risk of early childbirth (RH = 0.78, 95% CI = 0.69, 0.86). CONCLUSIONS: A living wage in San Francisco is associated with substantial health improvement.

Absenteeism↗
PubMed2001

Epidemiological characteristics of rabies in Delhi and surrounding areas, 1998.

OBJECTIVE: To describe the epidemiological characteristics of rabies in Delhi in 1998. METHODS: Analysis of the records of hydrophobia cases admitted to the Infectious Diseases Hospital, Delhi (IDH) in 1998. RESULTS: About 46 percent (99/215) of the hydrophobia cases admitted to the IDH in 1998 belonged to Delhi. The remaining came from the adjoining states, both urban and rural areas. In Delhi residents, overall hospitalization rate was 0.81 per 100,000 population. It was significantly higher in 5-14 year old than in other age groups and in males than in females (p <0.0009). Cases occurred round the year. Almost 96 percent cases (206/215) gave history of animal exposure, 13 days to 10 years (median 60 days) before hospitalization. Majority (195/206) had class III exposure. Animals involved were stray dog (193/206 = 90 percent), pet dog, cat, jackal, mongoose, monkey and fox. Most of cases were never vaccinated (78 percent) or inadequately vaccinated (22 percent); only 1 percent each received appropriate wound treatment, or rabies immunoglobulin. CONCLUSIONS: Rabies is a major public health problem in Delhi. Its incidence is significantly higher in 5-14 year old children than in other age groups. The results indicate the need to educate the community and health care workers about the importance of immediate and adequate post-exposure treatment and to start an effective control program for dogs, the principal vector of rabies.

Adolescent↗
PubMed2001

Vertebral artery dissection due to indirect neck trauma : an underrecognised entity.

Vertebral artery dissection is an important cause of brain stem stroke, especially in the young. Dissections of carotid and vertebral arteries in neck account for about 20% of strokes in young compared with 2.5% in the elderly. Three patients of vertebral artery dissection related to indirect neck trauma are described. The first patient developed the symptoms while dancing, the second after a trivial fall and the third while he was on a dental chair. None of them had a direct severe neck trauma or concomitant risk factor like hypertension, connective tissue disease or migraine. Clinical symptomatology was similar in all the patients and included occipito-nuchal pain, headache and brain stem dysfunction chiefly in the posterior inferior cerebellar artery (PICA) territory. One of the patients also had associated ischaemic myelopathy. MRA and DSA confirmed dissection in all with a predominant steno-occlusive picture. Cases of so called trivial neck movement/torsion related dissection have been described previously but have not received any major importance. Usually classified as 'spontaneous' or 'traumatic', there is a possible ambiguity in literature about appropriate terminology. We emphasise that a history of such subtle precipitating events be taken while diagnosing young patients with brain stem strokes, to recognise this clinical entity. Although mechanisms are not absolutely clear, yet there seems to be an important relationship between arterial dissection and neck movements or minor trauma.

Adult↗
PubMed2000

Drug solubilization in lung surfactant.

The relative affinity of glucocorticosteroids for lung surfactant was determined for the purpose of identifying chemopreventive agents with a high therapeutic index for lung cancer. The aqueous solubility and the extent of solubilization in Survanta, a native extract of bovine lung, of budesonide, triamcinolone acetonide, dexamethasone, and flunisolide were determined as a function of temperature by a dialysis technique. The aqueous solubilites at 37 degrees C were 19.6, 35.8, 104 and 120 microg/ml for the above listed compounds, respectively. The temperature dependence of the solubilities was modest consistent with the hydrophobic properties of the steroids. The amount of drug in solution was significantly enhanced in the presence of Survanta with solubilization ratios of 0. 019, 0.023, 0.014, and 0.02 microg drug dissolved per microg of Survanta phospholipid, respectively. In addition, the extent of solubilization also generally increased with temperature, although the phase transition of the surfactant lipid appeared to complicate the functional relation between temperature and solubilization. These results show that there is enhanced solubilization of glucocortosteroids by lung surfactant which is secreted by the cancer susceptible type II cells of the lung.

Animals↗
PubMed2000

Predictors of therapy-related leukemia and myelodysplasia following autologous transplantation for lymphoma: an assessment of risk factors.

We analyzed data on 612 patients who had undergone high-dose chemoradiotherapy (HDT) with autologous stem cell rescue for Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) at the City of Hope National Medical Center, to evaluate the incidence of therapy-related myelodysplasia (t-MDS) or therapy-related acute myeloid leukemia (t-AML) and associated risk factors. A retrospective cohort and a nested case-control study design were used to evaluate the role of pretransplant therapeutic exposures and transplant conditioning regimens. Twenty-two patients developed morphologic evidence of t-MDS/t-AML. The estimated cumulative probability of developing morphologic t-MDS/t-AML was 8.6% +/- 2.1% at 6 years. Multivariate analysis of the entire cohort revealed stem cell priming with VP-16 (RR = 7.7, P = 0.002) to be independently associated with an increased risk of t-MDS/t-AML. The influence of pretransplant therapy on subsequent t-MDS/t-AML risk was determined by a case-control study. Multivariate analysis revealed an association between pretransplant radiation and the risk of t-MDS/t-AML, but failed to reveal any association with pretransplant chemotherapy or conditioning regimens. However, patients who had been primed with VP-16 for stem cell mobilization were at a 12. 3-fold increased risk of developing t-AML with 11q23/21q22 abnormalities (P = 0.006). Patients undergoing HDT with stem cell rescue are at an increased risk of t-MDS/t-AML, especially those receiving priming with VP-16 for peripheral stem cell collection. (Blood. 2000;95:1588-1593)

Adolescent↗
PubMed2000

Chronic myelogenous leukemia primitive hematopoietic progenitors demonstrate increased sensitivity to growth factor-induced proliferation and maturation.

We investigated whether primary chronic myelogenous leukemia (CML) hematopoietic progenitors demonstrated altered proliferation and maturation in response to growth factor (GF) stimulation. The effect of GF stimulation on proliferation and expansion of committed and primitive progenitors (colony forming cells [CFC]) was evaluated. Culture of CML and normal CD34(+) cells with different GF for 7 days resulted in similar expansion of committed progenitors (CFC). In contrast, GF culture conditions that expanded normal primitive progenitors (week-6 long-term culture-initiating cells (LTC-IC)] led to depletion of CML LTC-IC numbers. GF culture also resulted in increased depletion of week-10 extended LTC-IC, which represent an even more primitive progenitor population, from CML compared with normal CD34(+) cells. CML CD34(+) cells enter into cycle more quickly than normal CD34(+) cells and CML CFC expansion was accelerated compared to normal CFC. Evaluation of primitive progenitor proliferation using PKH-26 and single-cell LTC-IC analysis demonstrated that the majority of CML LTC-IC remaining after GF culture originated from divided CD34(+) cells, whereas GF-cultured normal LTC-IC were derived mainly from undivided cells. Depletion of CML primitive progenitor numbers in association with increased proliferation suggests increased sensitivity to GF-induced maturation. These studies indicate that CML primitive progenitors have enhanced sensitivity to GF-induced cell division and maturation. Altered GF responsiveness may contribute to abnormal expansion of malignant myeloid cells in CML. These findings may also be applied toward the development of novel approaches to select benign stem cells in CML.

Antigens, CD34↗