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Biomedical subjects

M Arora

Publications and source records attributed to M Arora.

At least 37 records · Page 2Linked to original sources

Resolution of enantiomers of DL-amino acids on silica gel plates impregnated with optically pure (-)-quinine.

TLC resolution of enantiomers from racemic amino acids was achieved on silica gel plates impregnated with optically pure (-)-quinine. The successful solvent systems were butanol-chloroform-acetic acid (3:7:5, v/v) for DL-methionine; 6:8:4, v/v for alanine; 10:1:4; v/v for threonine; and ethyl acetate-carbon tetrachloride-propionic acid (10.5:6.5:3.5, v/v) for valine. Minimum detection limits were found to be different for each of the amino acid, ranging between 0.9 and 3.7 microg. The effects of concentration of impregnating reagent, temperature and pH on resolution of enantiomers have been studied in details.

Acetates↗

Pulmonary function tests in beta thalassemia.

To study pulmonary function tests (PFT) in multiple transfusion recipient thalassemics, PFTs were done for 30 thalassemics and 20 matched controls. Confirmed cases of thalassemia on regular transfusion therapy were the subject of study. Apart from history and physical examination of the thalassemics, serum ferritin estimation and spirometry were done. Parameters studied included lung volumes--functional residual capacity (FRC), forced vital capacity (FVC), residual volume (RV) and total lung capacity (TLC); and flow rates--forced expiratory volume in one second (FEV1), forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC), peak expiratory flow 25-75 (PEF 25-75%) and peak expiratory flow rate (PEFR). Single breath carbon monoxide diffusing capacity (DLco) and arterial blood gas (ABG) were also analysed. The mean height and weight of thalassemics were below that of age matched controls. A restrictive abnormality in PFT was found in 86.6% cases. These patients were found to have a decrease in all the lung volumes namely FVC, FRC, RV and TLC with a proportional decrease in the flow rates, FEV1, PEF 25-75% and PEF with a normal (> 0.75) FEV1/FVC ratio. DLco was decreased in all the patients with restrictive lung disease and fall in DLco showed a good correlation (r = 0.7, P < .001) with the severity of restrictive disease suggesting that some intrapulmonary pathology is likely to be responsible for the restrictive pattern. None of the cases had an obstructive or mixed pattern of pulmonary dysfunction. No correlation was found between severity of restrictive disease and the serum ferritin levels. A negative correlation with degree of hepatosplenomegaly was found. No correlation was found between severity of the defect and age, number of blood transfusions received and hemoglobin at the time of doing the test. To conclude, restrictive lung disease is the predominant abnormality in multi-transfused thalassemics, which is probably due to pulmonary parenchymal pathology. The abnormality of PFTs is not directly related to iron overload.

Adolescent↗

Azygos vein anomaly: the best predictor of a long gap in esophageal atresia and tracheoesophageal fistula.

The gap between the pouches has a direct bearing on the tension at the anastomosis that ultimately determines the anastomotic leak in esophageal atresia with or without tracheoesophageal fistula (EA-TEF). Long-gap EA has been reported to be associated with aortic-arch anomalies and 13 pairs of ribs. Our observation that EA-TEF with an azygos-vein anomaly (AVA) invariably had a long gap led us to retrospectively analyze our data. The mean gaps (+/- SD) in the groups with 13 pairs of ribs (n = 6), right-sided aortic arch (n = 16), and AVA (n = 9) were 1.25 +/- 0.27, 2.18 +/- 0.98, and 3.16 +/- 0.16 cm, respectively. There was no statistically significant difference in the gap in patients who had 13 pairs of ribs compared with controls who had 12 pairs of ribs. The gap was highest in the AVA group and was statistically significant (P < 0.001) compared with patients with a normal azygos vein. In addition, the AVA group had a significant increase in mortality (P < 0.05) compared to the groups with a normal azygos vein; although there was no statistically significant difference in other factors: birth weight, time between delivery and surgery, cardiac anomalies, anorectal malformations, renal malformations, and chest infection in the AVA group and controls. An extra pair of ribs is not associated with a long gap, and an AVA per se is an independent predictor of a long gap and mortality in EA-TEF.

Abnormalities, Multiple↗

Prescribing conventional antipsychotics at two Veterans Administration hospitals: are there geographical differences?

The medical records of 110 patients receiving conventional antipsychotics at two geographically distinct Veterans Administration hospitals (Syracuse, New York, and Omaha, Nebraska) were reviewed. The most common reasons for continuation of conventional antipsychotics were good response and patient or physician choice. Frequently, physicians did not discuss the reasons for continuing conventional antipsychotics or the availability of alternative therapies with their patients. Geographic differences in physicians' prescribing practices of conventional antipsychotics were apparent.

Journal Article↗

Randomized clinical trial of thalidomide, cyclosporine, and prednisone versus cyclosporine and prednisone as initial therapy for chronic graft-versus-host disease.

Chronic graft-versus-host disease (CGVHD) is a major cause of morbidity following allogeneic bone marrow transplantation. Thalidomide is active in salvage therapy for high-risk or resistant CGVHD. In a prospective randomized trial, we tested initial therapy with thalidomide. Patients with extensive CGVHD were randomized to receive either cyclosporine and alternate-day prednisone (n = 27, no-thalidomide [no-thal] group) or cyclosporine, prednisone, and thalidomide (200-800 mg/day; n = 27, thal group). Although most patients responded, initial therapy with thalidomide did not improve control of CGVHD. Response rates were 83% versus 89% at 2 months (P = .7), 88% versus 84% at 6 months (P > .8) and 85% versus 73% at 1 year (P = .5) in the thal and no-thal groups, respectively. Multivariate analysis revealed related donor transplant (odds ratio [OR] = 11.3; P =.03) and de novo or quiescent onset of CGVHD (OR = 7.7; P =.04) to be significant predictors of good early response, whereas a platelet count of > or =100,000/microL was a significant predictor of good response (OR = 10.4; P =.04) at 1 year. Survival for the thal and no-thal groups was similar at 1 year (66% versus 74%) and 2 years (66% versus 54%, P = .85). Multivariate analysis revealed progressive onset CGVHD (relative risk [RR] = 4.2; P =.01), unrelated donor (RR = 5.7; P < .01), sex mismatch (RR = 7.9; P < .01), and platelet counts of <100,000/microL (RR = 3.8; P = .01) as significant predictors of poorer survival. These data suggest that despite a high response rate (79% response and 53% complete response) and encouraging survival rates (70% at 1 year and 60% at 2 years), thalidomide offers no clinical benefit when incorporated into initial therapy for CGVHD. The value of thalidomide as salvage therapy requires further study.

Bone Marrow Transplantation↗

Glutamate does not play a major role in controlling bone growth.

Bone cells express glutamate-gated Ca2+-permeable N-methyl-D-aspartate (NMDA) receptors and GLAST glutamate transporters. Blocking NMDA receptors has been reported to reduce the number of bone resorption pits produced by osteoclasts, and mechanical loading alters GLAST transporter expression, which should change the extracellular glutamate concentration and NMDA receptor activation. Thus, by analogy with the brain, glutamate is postulated to be an important intercellular messenger in bone, controlling bone formation and resorption. We found that activating or blocking NMDA receptors had no effect on bone formation by rat osteoblasts in culture. The number of resorption pits produced by osteoclasts was reduced by the NMDA receptor blocker MK-801 but not by another blocker AP-5, implying that this effect of MK-801 is unrelated to its glutamate-blocking action. By contrast, MK-801, AP-5, and NMDA had no consistent effect on the volume of pits. In mice with GLAST glutamate transporters knocked out, no differences were detected in mandible and long bone size, morphology, trabeculation, regions of muscle attachment, resorption lacunae, or areas of formation versus resorption of bone, compared with wild-type siblings. These data suggest that glutamate does not play a major role in controlling bone growth.

2-Amino-5-phosphonovalerate↗

Reversed patent ductus arteriosus in a dog.

A 5-year-old cocker spaniel with tachycardia, > 2 s capillary refill time, arrhythmia, split S2 heart sound, right ventricular enlargement, flattened interventricular septum, dilated pulmonary artery, and slight tricuspid valve insufficiency was diagnosed with reversed patent ductus arteriosus (right-to-left vs the more common left-to-right shunt). Two years later, the dog was still stable.

Animals↗

Ultrastaging of colorectal cancer by sentinel lymph node mapping technique--a multicenter trial.

Sentinel lymph node (SLN) mapping accurately diagnoses the status of nodal basin with >95% accuracy in melanoma and breast cancer. A multicenter trial for SLN mapping was performed on 203 patients with colorectal cancer to determine accuracy, upstaging, skip metastasis, and aberrant drainage. Lymphazurin 1% was injected subserosally around the tumor and 1-4 blue staining nodes were marked as SLNs for detailed histological analysis. SLN mapping was successful in 98% of patients with an average of 1.7 SLNs per patient. SLNs were negative in 63% of the patients and positive in 37% of the patients. Skip metastasis was seen in 8 of the patients. Occult micrometastasis was found in 14% of patients. In 5% of the patients, unusual lymphatic drainage lead to an alteration of the extent of lymphadenectomy. This multicenter trial proved that SLN mapping in patients with colorectal cancer is simple, cost effective, and upstages at least 14% of patients from AJCC stage I/II to stage III. These patients may then benefit from adjuvant chemotherapy.

Adult↗

Congenital diaphragmatic hernia.

Over the last two decades there has been a constant improvement in the understanding of the pathophysiology of Congenital Diaphragmatic Hernia (CDH) and its management. However, the ideal treatment remains elusive. The earlier management strategy of immediate surgery is replaced by the principle of physiological stabilisation and delayed surgery. Conventional mechanical ventilatory techniques, with high pressures and hyperventilation to reverse ductal shunting and cause alkalinization, are being questioned because of the risks of barotrauma and consequent broncho-pulmonary dysplasia. It has also been shown that paralysis with pancuronium bromide for patients on conventional mechanical ventilation results in increased incidence of sensorineural hearing loss in childhood survivors of CDH. With the introduction of the concept of permissive hypercapnia and high frequency oscillation ventilation, the complications of pulmonary barotrauma are circumvented. Although ECMO therapy is invasive, yet has improved survival by about 15% independently, especially in critically ill infants who have the predictive mortality rate of more than 80%. Further insights into the pathophysiology of CDH and the introduction of less invasive therapeutic techniques in the form of high frequency oscillation ventilation, inhalation nitric oxide, surfactant, and perfluorocarbon liquid ventilation may even make the need for ECMO redundant.

Extracorporeal Membrane Oxygenation↗

Silent bowel perforation and transanal prolapse of a ventriculoperitoneal shunt.

A 2-year-old hydrocephalic child presenting with ventriculitis following intestinal perforation by a ventriculoperitoneal (VP) shunt is reported. The peritoneal end of the shunt had extruded through the anus without causing any abdominal signs. Removal of the shunt, external ventriculostomy, and antibiotics were effective treatment.

Cerebral Ventricles↗

Technical details of sentinel lymph node mapping in colorectal cancer and its impact on staging.

BACKGROUND: Sentinel lymph node (SLN) mapping for melanoma and breast cancer has greatly enhanced the identification of micrometastases in many patients, thereby upstaging a subset of these patients. The purpose of this study was to see if SLN mapping technique could be used to identify SLNs in colorectal cancer and to assess its impact on pathological staging and treatment. METHODS: At the time of surgery, 1 ml of Lymphazurin 1% was injected subserosally around the tumor without injecting into the lumen. The first to fourth blue nodes identified were considered the SLNs, which have the highest probability to contain metastases. A standard oncological resection of the bowel was then performed. Multilevel microsections of the SLNs, including a detailed pathological examination of the entire specimen, was performed. RESULTS: SLN was successfully identified in 85 (98.8%) of 86 patients. In 85 patients, there were 1,367 (16 per patient) lymph nodes examined, of which 140 (1.6 per patient) were identified as SLNs. In 53 (95%) of 56, of whom the SLNs were without metastases (negative), all other non-SLNs also were negative. In 29 (34% of 85) patients, SLNs were positive for metastases; in 14 of the 29 patients, other non-SLNs also were positive in addition to the SLNs. In the other 15 of the 29 patients (18% of 85 patients), SLNs were the only site of metastases, and all other non-SLNs were negative. In 7 patients (8.2% of 85 patients), micrometastases were identified only in 1 or 2 of the 10 sections of a single SLN. In five of seven patients, such micrometastases were detected by hematoxylin and eosin staining and immunohistochemistry; in the other two patients, it was detected only by immunohistochemistry. In patients with negative SLNs, the rate of occurrence of micrometastases in non-SLNs was 5 (0.4%) of 1,184 lymph nodes. CONCLUSIONS: SLN mapping can be performed easily in colorectal cancer patients, with an accuracy of more than 95%. The identification of submicroscopic lymph node metastases by this technique may have upstaged these patients (18%) from stage I/II to stage III disease, who may then benefit from further adjuvant chemotherapy.

Chemotherapy, Adjuvant↗

Expression of complement regulatory proteins in diffuse proliferative glomerulonephritis.

This study assessed the expression of complement receptor 1 (CR1), decay accelerating factor (DAF) and membrane inhibitor of reactive lysis (CD59) on the erythrocytes and glomerulus of diffuse proliferative glomerulonephritis (DPGN) of systemic lupus erythematosus (SLE) patients using flow cytometry and immunofluorescence techniques to elucidate their role in the pathogenesis of DPGN. Expression of CR1 on the erythrocytes and glomerulus of DPGN patients was reduced compared with expression in normal subjects. However, expression of DAF and CD59 was increased on both erythrocytes and glomerulus of DPGN patients, suggesting the generation of a protective response against complement-mediated injury.

Adolescent↗

The yeast pheromone-responsive G alpha protein stimulates recovery from chronic pheromone treatment by two mechanisms that are activated at distinct levels of stimulus.

The pheromone response of Saccharomyces cerevisiae is mediated by a receptor-coupled heterotrimeric G protein. The beta gamma subunit of the G protein stimulates a PAK/MAP kinase cascade that leads to cellular changes preparatory to mating, while the pheromone-responsive G alpha protein, Gpa1, antagonizes the G beta gamma-induced signal. In its inactive conformation, Gpa1 sequesters G beta gamma and tethers it to the receptor. In its active conformation, Gpa1 stimulates adaptive mechanisms that downregulate the mating signal, but which are independent of alpha-beta gamma binding. To elucidate these potentially novel signaling functions of G alpha in yeast, epistasis analyses were performed using N388D, a hyperadaptive mutant form of Gpa1, and null alleles of various loci that have been implicated in adaptation. The results of these experiments indicate the existence of signaling thresholds that affect the yeast mating reaction. At low pheromone concentration, the Regulator of G Protein Signaling (RGS) homologue and putative guanosine triphosphatase (GTPase) activating protein, Sst2, appears to stimulate sequestration of G beta gamma by Gpa1. Throughout the range of pheromone concentrations sufficient to cause cell cycle arrest, Gpa1 stimulates adaptive mechanisms that are partially dependent on Msg5 and Mpt5. Gpa1-mediated adaptation appears to be independent of Afr1, Akr1, and the carboxy-terminus of the pheromone receptor.

Acyltransferases↗

Lipid peroxide levels in chronic renal failure.

To determine presence of oxidant stress in chronic renal failure and to evaluate the efficacy of vitamin E in its amelioration, we studied 34 patients (Group I, age 32.4 +/- 11 years, M:F 3:1) and 10 healthy controls (Group II, age 27.4 +/- 5 years, M:F 4:1). The difference in baseline values of lipid peroxide (nmol/ml) was statistically significant (Group I 4.19 +/- 1.69, Group II 1.87 +/- 1.39, p = 0.004). Values of vitamin E (mg/l) were also significantly lower in Group I as compared to Group II (12.18 +/- 4.27 vs. 19.32 +/- 2.03, p = 0.003). Serum lipid peroxide values decreased significantly after supplementation with 400 mg/day of vitamin E for six weeks in Group I (4.19 +/- 1.69 to 3.21 +/- 1.13, p = 0.053) but not in Group II (1.87 +/- 1.39 to 1.03 +/- 0.87). Levels of vitamin E increased in both the groups (Group I: 12.18 +/- 4.27 to 16.01 +/- 5.13, Group II: 19.32 +/- 2.03 to 23.21 +/- 1.94, p < 0.005). No significant difference was observed in values of serum creatinine and urea before and after intervention.

Adult↗

Complement-regulatory protein expression and activation of complement cascade on erythrocytes from patients with rheumatoid arthritis (RA).

It has been previously reported that the expression of the complement receptor, CR1, on erythrocytes is reduced in patients with RA and that the reduced expression of CR1 is related to disease activity. In this study we investigate the role of other regulatory proteins, i.e. decay-accelerating factor (DAF) and CD59 (membrane inhibitor of reactive lysis), in the pathogenesis of RA by checking the expression of DAF and CD59 on erythrocytes of RA patients to establish whether reduced expression of DAF and CD59 on erythrocytes could be related to increased ability of erythrocytes to activate complement in RA. Flow cytometry was used to measure the expression of DAF and CD59 on erythrocytes from RA patients as well as the deposition of C3 fragments occurring in vivo or after in vitro complement activation. Significantly reduced expression of DAF and CD59 was observed on erythrocytes of RA patients. A significant inverse relationship was observed between DAF expression and in vitro complement activation, whereas no significant relationship between CD59 and complement activation was observed. Finally, we demonstrated an inverse relationship between CH50 activity and DAF expression. Thus, determination of DAF on erythrocytes can emerge as an additional tool in the assessment of extent of complement activation in RA.

Adolescent↗