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Biomedical subjects

N Varma

Publications and source records attributed to N Varma.

At least 19 recordsLinked to original sources
PubMed2006

An open-label study of darbepoetin alfa administered once monthly for the maintenance of haemoglobin concentrations in patients with chronic kidney disease not receiving dialysis.

OBJECTIVE: To demonstrate the efficacy and safety of once-monthly (QM) darbepoetin alfa administration in maintaining haemoglobin (Hb) 11.0-13.0 g dL(-1) in subjects with chronic kidney disease (CKD) not receiving dialysis and previously treated with darbepoetin alfa every other week (Q2W). SUBJECTS: This open-label study enrolled subjects > or =18 years of age who had glomerular filtration rate > or =15 and < or =60 mL min(-1)/1.73 m(2), had Hb 11.0-13.0 g dL(-1), and were receiving Q2W darbepoetin alfa. DESIGN: Subjects were switched to QM darbepoetin alfa therapy for 28 weeks; the QM dose was titrated to maintain Hb levels. Primary end-point: proportion of subjects maintaining Hb > or =11.0 g dL(-1) during the final 8 weeks of the study (evaluation phase). Secondary end-points: Hb concentration during evaluation, darbepoetin alfa dose during the study, adverse events, laboratory parameters, and blood pressure. RESULTS: The study enrolled 152 subjects (female 52%, white 64%). Mean Hb > or =11.0 g dL(-1) during evaluation was achieved by 76% of the 150 subjects who received at least one dose of darbepoetin alfa [95% confidence interval (CI): 68%, 83%]. Mean (SD) Hb during evaluation was 11.71 (0.92) g dL(-1). Eighty-five per cent of 129 subjects who completed the study (95% CI: 78%, 91%) had Hb > or =11.0 g dL(-1) during evaluation. The dose of darbepoetin alfa over the study period was median (95% CI) 124.4 mug (106.2, 140.0). Darbepoetin alpha administered QM was well tolerated in study subjects. CONCLUSION: Darbepoetin alpha administered QM maintained Hb in study subjects with CKD not receiving dialysis.

Administration, Oral↗
PubMed2005

Myelodysplastic syndrome with erythroid hypoplasia.

The incidence of myelodysplastic syndrome (MDS) with erythroid hypoplasia/aplasia is probably underestimated because in most patients it is mistaken for acquired pure red blood cell aplasia. This report describes three children who fulfilled the criteria for MDS with erythroid hypoplasia/aplasia. All these patients had transfusion dependent anaemia, reticulocytopenia, erythroid hypoplasia/aplasia, severe dysgranulopoiesis, and dysmegakaryopoiesis.

Blood Transfusion↗
PubMed2005

Change in tissue thromboplastin content of brain following trauma.

BACKGROUND: Tissue thromboplastin (TTP) is an integral membrane protein contributing to coagulopathy after trauma of brain, which is a rich source of TTP. AIMS: A study was undertaken to establish the TTP content of various areas of normal brain and estimate the changes in TTP activity of brain in response to varying degrees of trauma. MATERIALS AND METHODS: Samples from different areas of brain of ten cadavers were used as controls and they were compared with contused brain tissue obtained after surgery in 25 head injury (HI) patients of varying severity. RESULTS: In the study group, the TTP activity of the frontal, parietal, and temporal lobes after HI was significantly raised in contrast to that of the control group. The TTP activity was also significantly higher in the severe HI patients than those having moderate HI. The mode of injury and the time lapse after HI had no significant bearing on the TTP activity. Subjects above 40 years of age demonstrated a higher mean TTP activity after HI, though it was not statistically significant. CONCLUSION: The study provides quantitative data on TTP activity of normal brain and highlights the role of TTP in coagulopathy following HI through its increased activity after HI, more so in the severe HI group.

Adolescent↗
PubMed2005

Induction-intubation response--smokers vs non-smokers--.

BACKGROUND AND OBJECTIVES: Tobacco smoking has been established to be a hazardous activity. Changing social attitude is bringing a decline in tobacco consumption but a significant proportion of patients presenting for surgery still continues to smoke, putting themselves at risk of perioperative complications. We evaluated induction-intubation response in 40 male patients (ASA-I) divided into two groups of 20, each consisting of smokers and non-smokers. METHODS: All patients received standard premedication and general anesthesia. Heart rate, blood pressure and rate-pressure product were measured prior to induction, just before intubation and at 1, 3, 5 and 10 minutes after intubation. Continuous electrocardiography (EKG lead II) monitoring was done. Carboxyhemoglobin and total hemoglobin were estimated at the time of securing venous access. Arterial blood gases were analysed 5 minutes before and after the tracheal intubation. RESULTS: Incidence of arrhythymias (30%) was higher in smokers compared to non-smokers (10%). Mean carboxyhemoglobin (COHb) level in smokers was 3.81 +/- 2.17 gdL(-1) as compared to 2.95 +/- 1.33 gdL(-1) in non-smokers. Four patients who continued to smoke till the day of surgery had higher COHb levels (8.2, 5.9, 6, 8.8 gdL(-1)). PaO2 and PaCO2 levels were comparable in both groups. CONCLUSIONS: During induction-intubation period, heart rate; systolic, diastolic and mean arterial pressure and rate-pressure product showed more pronounced fluctuations in smokers than in non-smokers (p < 0.05).

Adult↗
PubMed2004

Visceral leishmaniasis in a non-endemic area of India.

The study included 57 patients with visceral leishmaniasis. The average duration of symptoms was 3.8 +/- 3.55 months and pancytopenia was the commonest haematological abnormality. The parasite load directly correlated with the degree of anaemia at presentation (P=0.03). Splenic regression took 9.58 +/- 4.5 days and haematological parameters recovered in 14.5 +/- 9.07 days. There were five deaths over the five-year study duration. Leishmaniasis was not the first diagnosis in 14 patients, of whom eight were residents of non-endemic regions. Diagnosis was achieved in 13.5 days in these patients, compared to 4.5 days in patients where leishmaniasis was suspected at the outset.

Adult↗
PubMed2001

Metabotropic glutamate receptors drive the endocannabinoid system in hippocampus.

Endocannabinoids are key intercellular signaling molecules in the brain, but the physiological regulation of the endocannabinoid system is not understood. We used the retrograde signal process called depolarization-induced suppression of inhibition (DSI) to study the regulation of this system. DSI is produced when an endocannabinoid released from pyramidal cells suppresses IPSCs by activating CB1R cannabinoid receptors located on inhibitory interneurons. We now report that activation of group I metabotropic glutamate receptors (mGluRs) enhances DSI and that this effect is blocked by antagonists of both mGluRs and of CB1R. We also found that DSI is absent in CB1R knock-out (CB1R(-/-)) mice, and, strikingly, that mGluR agonists have no effect on IPSCs in these mice. We conclude that group I mGluR-induced enhancement of DSI, and suppression of IPSCs, is actually mediated by endocannabinoids. This surprising result opens up new approaches to the investigation of cannabinoid actions in the brain.

Animals↗
PubMed2001

Left ventricular diastolic dysfunction during demand ischemia: rigor underlies increased stiffness without calcium-mediated tension. Amelioration by glycolytic substrate.

OBJECTIVES: The goal of this study was to determine the subcellular mechanism(s) underlying increased left ventricular (LV) diastolic chamber stiffness (DCS) during angina (demand ischemia). BACKGROUND: Increased DCS may result from increased diastolic myocyte calcium concentration and/or rigor. Therefore, we assessed the effects of direct alterations of both calcium-activated tension and high-energy phosphates on increased DCS. METHODS: Demand ischemia was reproduced in isolated, isovolumic, red-cell perfused rabbit hearts by imposing low-flow ischemia and pacing tachycardia. This resulted in increased DCS. Interventions were performed after LV end-diastolic pressure had increased approximately 7 mm Hg. Initially, to determine the effects of altered calcium concentration or myofilament calcium responsiveness, hearts received either: 1) 5 or 14 mmol/L calcium chloride; 2) 8 mmol/L egtazic acid; 3) 5 mmol/L butane-dione-monoxime (BDM); or 4) 50 mmol/L ammonium chloride (NH4Cl). Then, to assess the contribution of decreased high-energy phosphate supply, hearts received 5) glucose (25 mmol/L) and insulin (400 microU/ml). RESULTS: 1) Calcium chloride, 5 and 14 mmol/L, increased LV systolic pressure by 42% and 70%, respectively (p < 0.001), indicating increased calcium-activated tension, but did not further increase DCS, implying intact diastolic calcium resequestration. 2) Egtazic acid reduced LV systolic pressure by 30% (p < 0.001), indicating reduced intracellular calcium, but failed to reduce increased DCS. 3) Butane-dione-monoxime and NH4Cl chloride affected contractile function (i.e., a calcium-driven force) but did not alter increased DCS. 4) Glucose and insulin, which increase high-energy phosphates during ischemia, reduced increased DCS by 50% (p < 0.001). CONCLUSIONS: Increased DCS during demand ischemia was insensitive to maneuvers altering intracellular calcium concentration or myofilament calcium-responsiveness, that is, evidence against an etiology of calcium-activated tension. In contrast, increased glycolytic substrate ameliorated increased DCS, supporting a primary mechanism of rigor-bond formation.

Angina Pectoris↗
PubMed2001

Hyposplenism in alcoholic cirrhosis, facts or artifacts? A comparative analysis with non-alcoholic cirrhosis and extrahepatic portal venous obstruction.

BACKGROUND AND AIMS: Hyposplenism has been described in patients with alcoholic cirrhosis (AC). However, no data are available regarding hyposplenism in patients with non-alcoholic cirrhosis (NAC) and other forms of portal hypertension such as extrahepatic portal venous obstruction (EHPVO). The aim is to study the splenic functions in patients with AC, NAC, and EHPVO. METHODS: Splenic functions were assessed consecutively in 22 patients with AC, 21 with NAC, and 23 with EHPVO. The tests included pitted red blood cells (RBC; %) and Howell-Jolly bodies in the peripheral smear. Pitted RBCs > 2% with or without the presence of Howell-Jolly bodies were taken as indicators of hyposplenism. The splenic function in each group was compared with age-matched controls. RESULTS: Hyposplenism was found in 10 (45.45%) patients with AC, six (28.57%) with NAC and one (4.34%) with EHPVO. The mean pitted RBCs were significantly increased in patients with AC (mean 4.93 +/- 1.36% vs control 1.22 +/- 0.17%, P < 0.05), but not so with NAC (2.01 +/- 0.69%) and EHPVO (mean 0.99 +/- 0.1% vs control 0.66 +/- 0.1%, P > 0.05). Howell-Jolly bodies were seen in only four patients. The mean pitted RBCs were significantly higher among patients who were actively consuming alcohol (9.14 +/- 3.35%) compared to those who abstained at least for more than 24 weeks (2.0 +/- 1.3%, P < 0.05). CONCLUSION: Hyposplenism is more common in AC patients, particularly those who are actively consuming alcohol compared with those who abstain. Patients with NAC have a lower incidence of hyposplenism, while in EHPVO patients, it is uncommon.

Adult↗
PubMed2001

Central venous access resulting in selective failure of ICD defibrillation capacity.

In a patient with a defibrillator system incorporating a lead with integrated bipolar sensing, physical contact between a guidewire (inserted for venous access) and the right ventricular defibrillation coil created sensing artefacts that triggered an inappropriate discharge. The presence of the guidewire in the heart during the discharge resulted in an electrical short with irreversible damage to the generator and rendered it incapable of delivering further high voltage therapy.

Artifacts↗
PubMed2000

Lack of direct role for calcium in ischemic diastolic dysfunction in isolated hearts.

BACKGROUND: Ischemia is characterized by an increase in intracellular calcium and occurrence of diastolic dysfunction. We investigated whether the myocyte calcium level is an important direct determinant of ischemic diastolic dysfunction. METHODS AND RESULTS: We exposed isolated, perfused isovolumic (balloon in left ventricle) rat and rabbit hearts to low-flow ischemia and increased extracellular calcium (from 1.5 to 16 mmol/L) for brief periods. Intracellular calcium was measured by aequorin. Low-flow ischemia resulted in a 270% increase (P:<0.05) in diastolic intracellular calcium, a 50% (P:<0.05) calcium transient amplitude decrease, and a 52% (P:<0.05) slowing of calcium transient decline. Diastolic pressure increased by 6+/-2 mm Hg (P:<0.05), and rate of systolic pressure decay decreased by 65% (P:<0.05). Experimentally increasing extracellular calcium doubled both intracellular diastolic calcium and calcium transient amplitude, concomitant with a developed pressure increase; however, there was no increase in ischemic diastolic pressure, slowing of the calcium transient decay, or further slowing of systolic pressure decay. Similarly, after 45 minutes of low-flow ischemia, after diastolic pressure had increased from 8.5+/-0.6 to 19.7+/-3.5 mm Hg (P:<0.001), intracoronary high-molar calcium chloride infusion increased systolic pressure from 36+/-4 to 63+/-11 mm Hg (P:<0.001), indicating an increase in intracellular calcium, but it decreased diastolic pressure from 19. 7+/-3.5 to 17.5+/-3.7 mm Hg (P:<0.01). Conversely, EGTA infusion decreased systolic pressure, indicating a decrease in intracellular calcium, but did not decrease diastolic pressure. CONCLUSIONS: When calcium availability was experimentally altered during ischemia, there was no alteration in left ventricular diastolic pressure, suggesting that ischemic diastolic dysfunction is not directly mediated by a calcium activated tension.

Animals↗
PubMed2000

Increased diastolic chamber stiffness during demand ischemia: response to quick length change differentiates rigor-activated from calcium-activated tension.

BACKGROUND: Increased diastolic chamber stiffness (increased DCS) during angina (demand ischemia) has been postulated to be generated by increased diastolic myocyte calcium concentration. METHODS AND RESULTS: We reproduced demand ischemia in isolated isovolumically contracting red-cell-perfused rabbit hearts by imposing pacing tachycardia during global low coronary blood flow (32% of baseline). This increased lactate production without increasing oxygen consumption and resulted in increased DCS (isovolumic left ventricular end-diastolic pressure [LVEDP] increased 10 mm Hg, P<0. 001, n=38). To determine the mechanism of increased DCS, we assessed responses to a quick-stretch-release maneuver (QSR), in which the intraventricular balloon was rapidly inflated and deflated to achieve a 3% circumferential muscle fiber length change. QSR was first validated as an effective method of discriminating between calcium-driven and rigor-mediated increased DCS. QSR imposed during demand ischemia when DCS had increased (LVEDP pretachycardia versus posttachycardia, 15+/-1 versus 27+/-2 mm Hg, P<0.001, n=6) reduced DCS to pretachycardia values (LVEDP post-QSR, 15+/-1 mm Hg, P<0.001), ie, elicited a response characteristic of rigor, without any component of calcium-generated tension. CONCLUSIONS: A rigor force, possibly resulting from high-energy phosphate depletion and/or an increase in ADP, appears to be the primary mechanism underlying increased DCS in this model of global LV demand ischemia.

Animals↗
PubMed2000

Serum ferritin level as a marker of preterm labor.

OBJECTIVE: To compare the serum ferritin levels in women with preterm labor (PTL) or preterm premature rupture of membranes with those in normal gravid women. METHOD: The study group consisted of 50 consecutive subjects with preterm labor and 49 subjects with preterm premature rupture of membranes (PROM). The control group consisted of 50 subjects matched with the study group for hemoglobin (Hb) and gestation who did not have PTL or preterm PROM. Serum ferritin levels were assayed in both the groups. RESULTS: Mean serum ferritin levels in patients with preterm labor and preterm premature rupture of membranes were 23.24+/-12.13 ng/ml and 29.44+/-28.41 ng/ml, respectively. The mean serum ferritin in control subjects was 8.69+/-3.7 ng/ml. The difference was evaluated by Student's t-test and was found to be statistically significant. CONCLUSION: The serum ferritin level is significantly raised in pregnant women with preterm labor and preterm PROM.

Adult↗
PubMed2000

Expression of receptor-Ck and SREBP genes in mononuclear cells from acute leukemia patients.

We have recently shown that Receptor-Ck regulated genes, involved in cellular growth and death through a transcriptional factor (SREBP) which has affinity for sterol regulatory element (SRE) present in the promoter region of these genes. The present study revealed that blasts, derived from both ALL and AML patients, were unable to express SREBP gene product although they had the capacity to express Receptor-Ck gene product. These results which depict defective Receptor-Ck-dependent signalling are in conformity with our previous results which showed that lymphocytes from CML patients as well as other human leukemic cell lines are unable to express gene coding for Receptor-Ck leading again to a state of impaired Receptor-Ck-dependent signalling. On the basis of these results, we propose that deregulated Receptor-Ck-dependent signalling may have an important role in leukemogenesis.

Blast Crisis↗