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Biomedical subjects

M Kumar

Publications and source records attributed to M Kumar.

At least 109 records · Page 6Linked to original sources

Administration of oral acyclovir suppressive therapy after neonatal herpes simplex virus disease limited to the skin, eyes and mouth: results of a phase I/II trial.

BACKGROUND: Neonatal herpes simplex virus (HSV) infections limited to the skin, eyes and mouth (SEM) can result in neurologic impairment. A direct correlation exists between the development of neurologic deficits and the frequency of cutaneous HSV recurrences. Thus, the National Institutes of Allergy and Infectious Diseases Collaborative Antiviral Study Group conducted a Phase I/II trial of oral acyclovir therapy for the suppression of cutaneous recurrences after SEM disease in 26 neonates. METHODS: Infants < or = 1 month of age with virologically confirmed HSV-2 SEM disease were eligible for enrollment. Suppressive oral acyclovir therapy (300 mg/m2/dose given either twice daily or three times per day) was administered for 6 months. RESULTS: Twelve (46%) of the 26 infants developed neutropenia (< 1000 cells/mm3) while receiving acyclovir. Thirteen (81%) of the 16 infants who received drug 3 times per day experienced no recurrences of skin lesions while receiving therapy. In comparison, a previous Collaborative Antiviral Study Group study found that only 54% of infants have no cutaneous recurrences in the 6 months after resolution of neonatal HSV disease if oral acyclovir suppressive therapy is not initiated. In one infant, HSV DNA was detected in the cerebrospinal fluid during a cutaneous recurrence, and an acyclovir-resistant HSV mutant was isolated from another patient during the course of the study. CONCLUSIONS: Administration of oral acyclovir can prevent cutaneous recurrences of HSV after neonatal SEM disease. The effect of such therapy on neurologic outcome must be assessed in a larger, Phase III study. As such, additional investigation is necessary before routine use of suppressive therapy in this population can be recommended.

Acyclovir

Frequency and factors influencing portal hypertensive gastropathy and duodenopathy in cirrhotic portal hypertension.

Portal hypertensive gastropathy and duodenopathy are distinct clinical and endoscopic entities. Data on factors influencing the development of these lesions are still emerging. Data on portal hypertensive duodenopathy are scarce. We prospectively studied 230 patients with liver cirrhosis and oesophageal varices attending the liver clinic of the Sanjay Gandhi Post Graduate Institute of Medical Sciences. One hundred and forty-two patients had no history of upper gastrointestinal bleeding, while the remainder had bled in the past. Endoscopic appearances were recorded before starting patients on a sclerotherapy programme. Forty-four patients were re-evaluated after variceal eradication. The frequency of portal hypertensive gastropathy (PHG) and duodenopathy (PHD) was 61 and 14%, respectively. Mild PHG was present in 85% and was severe in the rest. Portal hypertensive duodenopathy was mild in 50%, while in the other half it was severe. There was no relationship of PHG and PHD to: (i) a history of upper gastrointestinal bleed; (ii) size of oesophageal varices; (iii) aetiology of liver cirrhosis; or (iv) liver function status as assessed by Child Pugh's scores (P = NS for all). The prevalence of PHG was higher in those patients with oesophagogastric varices (74 of 107; 69%) compared with patients with oesophageal varices alone (68 of 123; 55%; P < 0.05). However, no such increase in frequency of PHD was noted in patients with oesophagogastric varices. Sclerotherapy increased the frequency of PHG. Twenty-four patients had PHG before starting sclerotherapy, while it was noted in 33 patients 1-3 months after variceal eradication (P < 0.05). In contrast, there was no increase in the prevalence of portal hypertensive duodenopathy after sclerotherapy (P = NS). There was no correlation between endoscopic and histological changes of PHG and PHD. In conclusion, PHG is quite frequent in patients with cirrhosis and its frequency increases with the presence of oesophagogastric varices and after sclerotherapy. However, the frequency of PHD is low and is not affected by the factors studied.

Adult

Bereavement is associated with time-dependent decrements in cellular immune function in asymptomatic human immunodeficiency virus type 1-seropositive homosexual men.

Seventy-nine human immunodeficiency virus type 1 (HIV-1)-seropositive homosexual men participating in a longitudinal study of HIV-1 infection were assessed twice, 6 months apart, to investigate associations between bereavement and cellular immune function. Subjects were assessed by using a theory-driven model comprising life stressors, social support and coping style, and control variables. Natural killer cell cytotoxicity was decreased among the bereaved at both times. Lymphocyte proliferative response to phytohemagglutinin was decreased among the bereaved at the second time point but not at the first. These functional immune decrements are associated with increased neuroendocrine responses of the sympathetic adrenomeduallary system as well as the limbic-hypothalamic-pituitary-adrenal axis. Implications for differential neuroendocrine responses over time are discussed. Active coping style was independently and positively related to both immune measures. The results imply that a bereavement support group intervention merits investigation for an effect on immunological measures and clinical progression of HIV-1 infection as well as grief resolution.

Adaptation, Psychological

Isolation of an ftsZ homolog from the archaebacterium Halobacterium salinarium: implications for the evolution of FtsZ and tubulin.

We have isolated a homolog of the cell division gene ftsZ from the extremely halophilic archaebacterium Halobacterium salinarium. The predicted protein of 39 kDa is divergent relative to eubacterial homologs, with 32% identity to Escherichia coli FtsZ. No other eubacterial cell division gene homologs were found adjacent to H. salinarium ftsZ. Expression of the ftsZ gene region in H. salinarium induced significant morphological changes leading to the loss of rod shape. Phylogenetic analysis demonstrated that the H. salinarium FtsZ protein is more related to tubulins than are the FtsZ proteins of eubacteria, supporting the hypothesis that FtsZ may have evolved into eukaryotic tubulin.

Amino Acid Sequence

Massage therapy is associated with enhancement of the immune system's cytotoxic capacity.

Twenty-nine gay men (20 HIV+, 9 HIV-) received daily massages for one month. A subset of 11 of the HIV+ subjects served as a within subject control group (one month with and without massages). Major immune findings for the effects of the month of massage included a significant increase in Natural Killer Cell number, Natural Killer Cell Cytotoxicity, soluble CD8, and the cytotoxic subset of CD8 cells. There were no changes in HIV disease progression markers (CD4, CD4/CD8 ratio, Beta-2 microglobulin, neopterin). Major neuroendocrine findings, measured via 24 hour urines included a significant decrease in cortisol, and nonsignificant trends toward decrease of catecholamines. There were also significant decreases in anxiety and increases in relaxation which were significantly correlated with increases in NK cell number. Thus, there appears to be an increase in cytotoxic capacity associated with massage. Implications for HIV+ men as those with other illnesses, particularly cancer, are discussed.

Adult

Healing of chronic antral gastritis: effect of sucralfate and colloidal bismuth subcitrate.

BACKGROUND: Colloidal bismuth subcitrate (CBS) causes endoscopic and histological improvement in gastritis and eradication of Helicobacter pylori in patients with non-ulcer dyspepsia (NUD). The effect of sucralfate, a cytoprotective drug, on endoscopic and histologic gastritis and H pylori clearance is not clear. We studied the effect of CBS and sucralfate on these features in patients with NUD. METHODS: Sixty three patients with NUD and H pylori infection were randomized to receive one of the following for four weeks: (i) CBS (240 mg twice daily) (Group 1); (ii) placebo I, similar in size, color and shape to CBS (Group 2); (iii) sucralfate (2.0 g twice daily) (Group 3) and (iv) placebo II, similar to sucralfate (Group 4). Symptoms, endoscopic and histological findings and H pylori status were assessed before and after treatment. RESULTS: Similar symptomatic improvement was observed with each treatment, indicating a placebo effect. Significant endoscopic and histological improvement was observed with CBS only. CBS was better than sucralfate in inducing endoscopic and histological improvement. Clearance rate of H pylori was 46.6% with CBS, 16.6% with its placebo, 33.3% with sucralfate and 13.3% with its placebo. CONCLUSION: CBS is more effective than sucralfate in inducing endoscopic and histologic healing of H pylori-related gastritis among NUD patients.

Adult

Gastrointestinal bleeding in children.

We prospectively evaluated 139 consecutive children presenting to the Sanjay Gandhi Postgraduate Institute of Medical Sciences (Lucknow, India) with gastrointestinal (GI) bleeding from January 1991 to November 1994. Our aims were to find out whether the causes of GI bleeding in a developing country differed from developed countries and how the application of newer diagnostic techniques would help in the diagnosis of GI bleeding. Barium studies, endoscopy, technetium-99m-labelled (erythrocytes and pertechnetate) scans, selective abdominal angiography using a digital subtraction technique and rectal endoscopic ultrasonography were performed. Upper GI bleeding (n = 75) was variceal in 71 (95%) children (extrahepatic portal venous obstruction in 65, cirrhosis in six) and non-variceal in four (5%) cases (Henoch-Schonlein purpura, idiopathic thrombocytopenic purpura, drug-induced gastric erosions and pseudoaneurysm of the gastroduodenal artery due to idiopathic chronic calcific pancreatitis). Causes of lower GI bleeding (n = 64) were colitis (27 cases; 42%), colorectal polyps (26 cases; 41%), enteric fever (n = 3), solitary rectal ulcer (n = 3), portal hypertensive colopathy (n = 2), colonic arteriovenous malformation (n = 1) and internal haemorrhoids (n = 1). One patient remained undiagnosed. Angiography performed in four children was diagnostic in two. In one child with massive lower GI bleeding from portal colopathy, the bleeding site (caecum) was localized by intra-operative colonoscopy, while in the other child with portal colopathy, rectal endoscopic ultrasonography was performed to substantiate the diagnosis. We conclude that the causes of upper GI bleeding in children in developing countries are different from those in developed countries (variceal bleeding due to extrahepatic portal venous obstruction is the most common cause, while peptic ulcer is rare). However, the spectrum of lower GI bleeding is similar to that of developed countries. Application of newer diagnostic techniques is helpful and safe in the identification of the cause of GI bleeding in children.

Child

Immunoproliferative small intestinal disease: a frequently missed diagnosis.

Immunoproliferative small intestinal disease (IPSID) is a poorly recognized cause of malabsorption syndrome in India. Clinicopathological features of five patients with IPSID seen over a two-year period are described. Our data suggest that IPSID is commonly misdiagnosed as intestinal tuberculosis due to lack of awareness and reluctance to obtain small bowel biopsies. Empirical institution of anti-tubercular chemotherapy not only leads to delayed diagnosis but also possibly alters the natural history of the disease, resulting in an intermediate phase of amelioration followed by a terminal phase of lymphomatous transformation. The disease is therefore usually diagnosed at an advanced stage and hence is associated with a relatively poor outcome.

Adult

Synthetic peptides related to laminin pentapeptide (YIGSR) fragment.

The synthetic laminin pentapeptide amide fragment (LF), Tyr-Ile-Gly-Ser-Arg-NH2 corresponding to a part of B1 chain of the glycoprotein, laminin, and six of its analogues having structural modifications at positions 1, 3 and 4 were synthesized by solid phase method employing mainly 9-fluorenylmethoxycarbonyl-amino acid trichlorophenyl esters as coupling agents and Merrifield resin as the solid support. Their biological activities were studied in vivo by lung tumor colonization assay and in vitro by cell adhesion assay. The activity of synthetic LF was found to correlate with the earlier reported results in both in vivo and in vitro assays. Among the analogues made, [Tyr4] LF and [Thr4]LF were found to inhibit the lung tumor colonies more efficiently than LF itself in the in vivo assay whereas [D- Ser4]LF exhibited almost the same inhibition as LF.

Animals

Neonatal cholestasis syndrome: an appraisal at a tertiary center.

OBJECTIVE: To know the magnitude, etiology and clinical profile, the efficacy of various investigations and the outcome in patients with neonatal cholestasis syndrome (NCS). DESIGN: Prospective evaluation of 60 consecutive infants with NCS (mean age 3.9 +/- 1.9 months; 49 males) over a period of 3.5 years. SETTING: Tertiary level referral gastroenterology center in North India. METHODS: Liver function tests, urine examination, serum antibodies against Cytomegalovirus (CMV), Rubella and Toxoplasma; abdominal ultrasonography, hepatobiliary scintigraphy and liver biopsy were done. In appropriate setting, laparotomy and surgical corrections were done for biliary tract disorders. RESULTS: NCS constituted 19% of pediatric liver diseases. Considerable delay in presentation was observed [mean delay, extrahepatic biliary atresia (EHBA) = 4 +/- 2.0 months, neonatal hepatitis (NH) = 2.2 +/- 1.3 months]. Thirty three (55%) infants had EHBA, 14 (23%) NH (4 CMV, 2 galactosemia, 1 urinary tract infection and 7 idiopathic), 2 (3%) paucity of intralobular bile ducts and 11 (18%) were of indeterminate etiology. Liver biopsy was the most accurate (96.4%) investigation in discriminating between EHBA and NH. Of the 18 operated infants with EHBA (portoenterostomy-15 and hepatico-jejunostomy-3), 10 were alive (mean follow up = 22.8 +/- 8.6 months) of which 4 were completely asymptomatic. CONCLUSIONS: (i) NCS is an important cause of liver disease in Indian children. (ii) It requires prompt referral, quick investigative approach and targeted management. (iii) Liver biopsy is highly accurate in differentiating EHBA and NH. (iv) infants with EHBA and compensated status of liver should undergo corrective surgery irrespective of age at presentation.

Biliary Atresia

Endoscopic, histologic and microbiologic evaluation of upper abdominal pain with special reference to Helicobacter pylori infection.

OBJECTIVE: To study children with significant upper abdominal pain of unidentifiable etiology and evaluate: (a) the relationship of pain to inflammatory esophago-gastro-duodenal lesions and Helicobacter pylori (HP) infection, and (b) the response to specific therapy. DESIGN: Prospective study. SETTING: Pediatric section of a tertiary referral gastroenterology center. SUBJECTS: Thirty three consecutive children with significant upper abdominal pain [mean age 9.9 +/- 2.7, range 4-15 years; 20 males] were subjected to upper gastrointestinal tract endoscopy and antral mucosal biopsies obtained for rapid urease test (RUT), Gram's staining of impression/crush smears and culture for HP and histologic examination. Patients with HP gastritis were treated with triple therapy, colloidal bismuth subcitrate, amoxycillin and metronidazole, for two weeks. At 8 weeks from the initiation of therapy, patients were re-evaluated for symptoms and HP eradication by repeat endoscopy and antral biopsies. Patients with esophagitis, gastritis and duodenitis without HP infection were treated with ranitidine for 6 weeks. All the patients were followed up for 6 months. RESULTS: Histology revealed antral gastritis in 28/33 (85%) patients. HP infection was present in 12/28 (43%) patients with antral gastritis. Symptomatic improvement with triple therapy was observed in 10/12 (83%) patients with HP gastritis and eradication of HP in 5/7. Improvement on ranitidine therapy was observed in 12/16 (75%) patients with HP negative gastritis. On follow-up, no patient with initial improvement with therapy had relapse of symptoms. CONCLUSION: Symptomatic children with HP related gastritis should be treated with triple therapy and HP negative gastritis with H2-receptor antagonist.

Abdominal Pain

Serotonin uptake and its kinetics in platelets of women with Alzheimer's disease.

The uptake of serotonin (14C-5-hydroxytryptamine, 5HT) in platelets and its kinetic characteristics were investigated in a group of women (n = 20) with probable Alzheimer's Disease (mean age = 76.0, years, SD = 8.27, range = 63-88) and in healthy normal women (n = 18, mean age = 72.6 years, SD = 7.24, range = 61-84). Both the apparent affinity of binding of 5HT to the platelet membrane (Km) and the maximum velocity (Vmax) of the rate of transport of 14C-5HT into platelets were significantly higher in the Alzheimer's Disease group than in the normal comparison group. Initial velocity of 14C-5HT uptake not passive diffusion (nonspecific uptake of 14C-5HT at 4 degrees C) differed significantly in the two groups. Our findings suggest abnormalities in the kinetic mechanisms involved in the uptake of 14C-5HT by platelets in women with Alzheimer's Disease.

Aged

A methylnickel intermediate in a bimetallic mechanism of acetyl-coenzyme A synthesis by anaerobic bacteria.

Resonance Raman (RR) spectroscopy was used to identify a methylnickel adduct (upsilon Ni-C = 422 wave numbers) of carbon monoxide dehydrogenase (CODH) from Clostridium thermoaceticum. Formed at a nickel/iron-sulfur cluster on CODH called center A, the methylnickel species is the precursor of the methyl group of acetyl-coenzyme A in an anaerobic pathway of carbon monoxide or carbon dioxide fixation. Rapid kinetic and RR studies demonstrated that methylation of nickel occurs by heterolysis of the methyl-cobalt bond (upsilon Co-C = 429 wave numbers) of a methylated corrinoid/iron-sulfur protein. In combination with the earlier finding of an iron-carbonyl adduct at center A, detection of the methylnickel intermediate establishes a bimetallic mechanism for acetyl-coenzyme A synthesis.

Acetyl Coenzyme A

The effect of phosphorylation on the antigenic reactivity of p53 in cultured human keratinocytes.

The detection of p53 in human keratinocytes is dependent on the specific anti-p53 monoclonal antibody that is used. Differences in antibody recognition are postulated to be due to the masking or exposure of particular epitopes in different conformations of p53. This study addresses the role of phosphorylation on p53-epitope accessibility in human keratinocytes. Keratinocytes were treated with the phosphatase inhibitor, okadaic acid, to determine the effect of inhibiting cellular phosphatases on p53 phosphorylation and epitope recognition. These studies suggest there is a correlation between the level of p53 phosphorylation and the antigenic reactivity of certain p53 epitopes in human keratinocytes. We also examined the ability of the catalytic subunits of protein phosphatase 1 and 2A to dephosphorylate p53 derived from human keratinocytes in vitro. These data suggest that PP2A may be the phosphatase that acts on p53 in cultured human keratinocytes.

Antibodies, Monoclonal