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Biomedical subjects

R Lakshman

Publications and source records attributed to R Lakshman.

At least 19 recordsLinked to original sources
PubMed2005

Postmortem diagnosis of chronic granulomatous disease: how worthwhile is it?

A previously healthy 11 year old boy died unexpectedly after a rapid course of progressive pneumonia. Postmortem microbiology and histopathology suggested an underlying diagnosis of chronic granulomatous disease. This was confirmed by neutrophil oxidative burst and gene mutation analysis of other family members, one of whom benefited from early bone marrow transplantation.

Burkholderia Infections↗
PubMed2003

Pneumococcal nasopharyngeal carriage in children following heptavalent pneumococcal conjugate vaccination in infancy.

AIMS: To ascertain whether the reduction in nasopharyngeal carriage of vaccine serotypes induced by pneumococcal conjugate vaccine (PnCV) administered to infants persists beyond the age of 2 years. METHODS: Non-randomised, unblinded controlled study of 2-5 year old children who had received three doses of heptavalent PnCV (7VPnCV) in infancy and 23-valent pneumococcal polysaccharide vaccine at 13 months, and unimmunised controls. Nasopharyngeal swabs were taken in summer (150 vaccinated subjects, 126 controls) and winter (143 vaccinated subjects, 188 controls). The swabs were cultured and serotyped for Streptococcus pneumoniae. RESULTS: Carriage rates (vaccinated subjects: 24.7% and 43.4%; controls: 27.0% and 41.0%, in summer and winter respectively) and carriage of vaccine serotypes (subjects: 10.0% and 30.0%; controls: 13.5% and 31.5%, in summer and winter respectively) were similar in the two groups. CONCLUSIONS: Effects of vaccination in infancy on rates of nasal carriage of pneumococcus and serotype replacement in children living in a largely unvaccinated population are no longer evident by 2-5 years of age.

Anti-Bacterial Agents↗
PubMed2001

Alcohol biomarkers: clinical significance and biochemical basis.

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Raj Lakshman and Mikihiro Tsutsumi. The presentations were (1) Sialic acid index of apolipoprotein J: A new marker for chronic alcohol consumption, by P. Ghosh and M. R. Lakshman; (2) Microheterogeneity of serum glycoproteins in alcoholics, by M. Tsutsumi and S. Takase; (3) Probing protein-ethanol adducts with combinatorial peptide libraries displayed by filamentous phage, by H. Anni, O. Nikolaeva, and Y. Israel Y; (4) Carbohydrate-deficient transferrin as a marker for heavy alcohol use: What have we learned; Where do we go from here, by R. F. Anton; (5) Sensitivity and specificity of carbohydrate-deficient transferrin in drinking experiments and different patient groups, by O. M. Lesch; (6), Transferrin variants interfere with the measurement of carbohydrate-deficient transferrin, by A. Helender, G. Eriksson, and J-O. Jeppson; and (7) Chronic ethanol on protein trafficking in liver, by P. Marmillot, M. N. Rao, and M. R. Lakshman.

Alcoholism↗
PubMed2001

Primary and booster mucosal immune responses to meningococcal group A and C conjugate and polysaccharide vaccines administered to university students in the United Kingdom.

Meningococcal group A+C capsular polysaccharide (PS) conjugate vaccines may prime for serum immunoglobulin G (IgG) memory responses to meningococcal capsular PS. It is not known whether these vaccines induce immunological memory at the mucosal level, which may be important in reducing nasopharyngeal carriage. Mucosal immune responses to meningococcal conjugate and PS vaccines in young adults were investigated. Healthy university students were randomized to receive either a groups A+C meningococcal conjugate vaccine (MACconj, n = 100) or a group A+C meningococcal PS vaccine (MACPS, n = 95). One year after the primary immunization, both groups were randomized again to receive a MACconj or a MACPS booster vaccination. Saliva samples were collected before and 1 month after the primary and booster vaccinations. Anti-meningococcal A (MenA) and C (MenC) PS IgA and IgG antibody levels were measured by a standard enzyme-linked immunosorbent assay. After the primary vaccination, salivary MenA and MenC IgG and MenA IgA concentrations were significantly increased after immunization with both MACconj and MACPS vaccines, but the salivary Men C IgA level was increased only after MACPS vaccine (P < 0.01). IgA responses to both serogroups were greater for MACPS than MACconj vaccine (P < 0.05), whereas no significant differences were seen for IgG responses. MenA IgG titers were higher after the MACPS booster in MACconj-primed subjects than after the MACPS primary vaccination, suggesting the presence of IgG memory. Antibody responses to a dose of either MACPS or MACconj were not significantly reduced in those previously given MACPS compared to the primary responses to those vaccines. Meningococcal A+C conjugate and PS vaccines induce significant mucosal responses in young adults. MACconj priming may induce IgG memory at the mucosal level, which is likely to be a reflection of an anamnestic serum IgG response. No evidence of mucosal hyporesponsiveness was observed after MACPS priming in this study.

Adolescent↗
PubMed2001

Safety of a new conjugate meningococcal C vaccine in infants.

BACKGROUND: Group C conjugate meningococcal vaccines (Men C) were introduced into the UK primary immunisation schedule in November 1999. There has been extensive professional and public interest in their efficacy and safety. AIM: To determine the occurrence of at least one uncommon adverse event in infants related to the administration of the Chiron Men C vaccine. METHODS: A total of 2796 infants aged approximately 2 months were recruited into the study from areas in and around Sheffield and from Scotland. They were vaccinated with the Chiron Men C vaccine at 2, 3, and 4 months along with routine immunisations. Data on adverse events occurring one month after each dose were collected actively and prospectively and reviewed for possible relation to the vaccine. RESULTS: There were no deaths. There were no serious adverse events considered definitely or probably caused by the vaccine. Four infants developed serious adverse events (hypotonia, screaming syndrome, maculopapular rash, and agitation, respectively) that were considered possibly related to the vaccine. All recovered completely. Adverse events were seen in 1804 children but were considered possibly related to the vaccine in only 49 (1.8%). On subsequent immunisation there were no recurrences of adverse events considered to be possibly related to the vaccine.

Female↗
PubMed2001

Neutrophil disorders and their management.

Neutrophil disorders are an uncommon yet important cause of morbidity and mortality in infants and children. This article is an overview of these conditions, with emphasis on clinical recognition, rational investigation, and treatment. A comprehensive list of references is provided for further reading.

Chemotaxis, Leukocyte↗
PubMed1999

Long-term ethanol exposure alters the sialylation index of plasma apolipoprotein J (Apo J) in rats.

We have previously shown that chronic ethanol treatment impairs the glycosylation of proteins in the rat liver. Changes in the microheterogeneity of transferrin, a N-sialoprotein under chronic alcohol consumption are well established. Apolipoprotein J, another N-glycoprotein, is a normal component of plasma high-density lipoproteins in the rat and human. Apo J is also highly sialylated and, thus, may be vulnerable to the deleterious actions of ethanol. Therefore, to understand the specific nature of alterations of Apo J sialylation as a consequence of chronic ethanol treatment, we have determined: (1) the sialylation index of Apo J (moles sialic acid per mole Apo J protein) in rats administered ethanol for 4, 6, and 8 weeks and a gradual withdrawal and a follow-up abstinence for 1, 2, and 4 weeks; and (2) enzymatic activities of hepatic sialyltransferase and plasma sialidase during the same periods of alcohol treatment and abstinence in rats. Although no significant differences in the Apo J sialylation index between rats of the control and ethanol groups were found at the 4th week of alcohol treatment, a highly significant loss of 24% (p < 0.001) and 44% (p < 0.001) was found after 6 and 8 weeks, respectively, of alcohol feeding of these animals. Furthermore, a significant recovery of 38% (p < 0.001), 78% (p < 0.001), 84% (p < 0.001) and 96% (p < 0.001) in the sialylation index of Apo J were found, respectively, during withdrawal and 1, 2, and 4 weeks of subsequent alcohol abstinence in these animals. These changes in the sialic acid content of Apo J were accompanied by a similar pattern of changes in the enzyme activities of hepatic sialyltransferase and plasma sialidase in animals undergoing chronic ethanol treatment, withdrawal, and abstinence periods. The analysis of the sialylation index of Apo J seems to be a simple and feasible method to use to evaluate the extent of ethanol exposure.

Alcohol Drinking↗
PubMed1998

Prevention and Treatment of Hypertension Study (PATHS): effects of an alcohol treatment program on blood pressure.

OBJECTIVE: To determine whether blood pressure is reduced for at least 6 months with an intervention to lower alcohol intake in moderate to heavy drinkers with above optimal to slightly elevated diastolic blood pressure, and whether reduction of alcohol intake can be maintained for 2 years. DESIGN: A randomized controlled trial. METHODS: Six hundred forty-one outpatient veterans with an average intake of 3 or more alcoholic drinks per day in the 6 months before entry into the study and with diastolic blood pressure 80 to 99 mm Hg were randomly assigned to a cognitive-behavioral alcohol reduction intervention program or a control observation group for 15 to 24 months. The goal of the intervention was the lower of 2 or fewer drinks daily or a 50% reduction in intake. A subgroup with hypertension was defined as having a diastolic blood pressure of 90 to 99 mm Hg, or 80 to 99 mm Hg if recently taking medication for hypertension. RESULTS: Reduction in average weekly self-reported alcohol intake was significantly greater (P<.001) at every assessment from 3 to 24 months in the intervention group vs the control group: levels declined from 432 g/wk at baseline by 202 g/wk in the intervention group and from 445 g/wk by 78 g/wk in the control group in the first 6 months, with similar reductions after 24 months. The intervention group had a 1.2/0.7-mm Hg greater reduction in blood pressure than the control group (for each, P = .17 and P = .18) for the 6-month primary end point; for the hypertensive stratum the difference was 0.9/0.7 mm Hg (for each, P = .58 and P = .44). CONCLUSIONS: The 1.3 drinks per day average difference between changes in self-reported alcohol intake observed in this trial produced only small nonsignificant effects on blood pressure. The results from the Prevention and Treatment of Hypertension Study (PATHS) do not provide strong support for reducing alcohol consumption in nondependent moderate drinkers as a sole method for the prevention or treatment of hypertension.

Adult↗
PubMed1998

Effects of moderate intensity exercise on serum lipids in African-American men with severe systemic hypertension.

The prevalence of systemic hypertension and its cardiovascular consequences is higher in African-Americans than in whites. Low to moderate intensity aerobic exercise lowers blood pressure (BP) in African-American patients with severe hypertension. It is not known whether such exercise can improve lipid metabolism in these patients. Thirty-six African-American men with established essential hypertension, aged 35 to 76 years, were randomly assigned to an exercise (n = 17) or no exercise (n = 19) group. The exercise group exercised for 16 weeks, 3 times/week, at 60% to 80% of maximum heart rate. After 16 weeks, peak oxygen uptake in the exercise group improved (21+/-4 vs 23+/-3 ml/kg/min; p <0.001). Body weight did not change. Exercise intensity correlated with high-density lipoprotein (HDL) cholesterol changes from baseline to 16 weeks (r = 0.65; p <0.01) and was the strongest predictor of these changes (R2 = 0.4; p = 0.009). Lipoprotein-lipid changes in the 2 randomized groups did not differ significantly. A 10% increase in HDL cholesterol--42+/-19 versus 46+/-19 mg/dl; p = 0.003--noted in 10 patients who exercised > or = 75% of maximal heart rate suggested the existence of an exercise intensity threshold. Thus low to moderate intensity aerobic exercise may not be adequate to modify lipid profiles favorably in patients with severe hypertension. However, substantial changes in HDL cholesterol were noted in patients exercising at intensities > or = 75% of age-predicted maximum heart rate, suggesting an exercise-intensity threshold.

Adult↗
PubMed1995

Response to a second single antihypertensive agent used as monotherapy for hypertension after failure of the initial drug. Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents.

BACKGROUND: An important issue in clinical practice is how to treat patients whose blood pressure does not respond to the first antihypertensive drug selected. OBJECTIVE: To analyze the antihypertensive response of patients who had failed to achieve their diastolic blood pressure goal (< 90 mm Hg at the end of 8 to 12 weeks of titration) with one of six randomly allocated drugs or placebo to the random allocation of an alternate drug. METHODS: We initially randomized 1292 men with diastolic blood pressure of 95 to 109 mm Hg to treatment with hydrochlorothiazide, atenolol, captopril, clonidine hydrochloride, diltiazem hydrochloride (sustained release), prazosin hydrochloride, or placebo. Of 410 men in whom initial treatment failed, 352 qualified for randomization to the alternate drug. RESULTS: Of the 352 patients, 173 (49.1%) achieved their goal diastolic blood pressure, in 133 (37.8%) the alternate drug failed, and 46 (13.1%) left the study for various reasons. Overall response rates were as follows: diltiazem, 63%; clonidine, 59%; prazosin, 47%; hydrochlorothiazide, 46%; atenolol, 41%; and captopril, 37%. The best response rate for patients in whom hydrochlorothiazide failed was achieved with diltiazem (70%); after atenolol failure, clonidine (86%); after captopril failure, prazosin (54%); after clonidine failure, diltiazem (100%); after diltiazem failure, captopril (67%); and after prazosin failure, clonidine (53%). The combined response rate for patients initially randomized to an active treatment was 76.0%, which is similar to that achieved by the combination of two drugs in previous studies. CONCLUSIONS: We conclude that sequential single-drug therapy is a rational approach for treatment of hypertension in patients in whom initial drug therapy has failed.

Adult↗