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Biomedical subjects

A Shankar

Publications and source records attributed to A Shankar.

At least 37 records · Page 2Linked to original sources
PubMed2000

Influence of age and HLA type on interferon-gamma (IFN-gamma) responses to a naturally occurring polymorphic epitope of Plasmodium falciparum liver stage antigen-1 (LSA-1).

Antigenic polymorphism and HLA restriction may limit the immunogenicity of a subunit vaccine against liver-stage Plasmodium falciparum. We examined 59 clinical isolates and five laboratory clones of P. falciparum for polymorphism in the N- and C-terminal regions of LSA-1, evaluated binding of the corresponding peptides to selected HLA class I alleles, and measured IFN-gamma responses in residents of a malaria-endemic area of Papua New Guinea where HLA-A*1101, -24, -B13, and -B40 are the most common class I alleles. LSA-1 polymorphism was limited to a single non-synonymous mutation encoding serine (S), proline (P), or threonine (T) at amino acid 85. Nine-mer 84-92 peptides with S, T, or P at the primary anchor position bound differentially to HLA-A11, -A2, and -B7. IFN-gamma ELISPOT responses increased with age in malaria-exposed subjects: 14-16% and 30-36% of 2-5- and 6-54-year-olds, respectively, had > or =10 IFN-gamma-secreting cells/106 peripheral blood mononuclear cells when stimulated with at least one peptide variant (P<0.05). IFN-gamma responses to all three peptides were also greater for older than younger individuals. No children < 3 years old had lymphocytes that responded to all three 84-92 peptides, whereas 45% of adults (mean age 48 years) had aggregated IFN-gamma responses. These data support the notion that age-related cumulative exposure to P. falciparum increases the frequency of IFN-gamma responses to polymorphic epitopes of liver-stage antigens such as LSA-1.

Adolescent↗
PubMed2000

Therapeutic effects of oral zinc in acute and persistent diarrhea in children in developing countries: pooled analysis of randomized controlled trials.

BACKGROUND: Zinc deficiency is prevalent in children in developing countries. Supplemental zinc provides therapeutic benefits in diarrhea. OBJECTIVE: We sought to measure the effect of supplemental zinc given with oral rehydration therapy during recovery from acute or persistent diarrhea. DESIGN: We conducted pooled analyses including all available published and unpublished randomized controlled trials of the effects of supplementary oral zinc in children aged <5 y with acute or persistent diarrhea. We used Cox survival regression analysis to evaluate the overall effect of zinc on continuation of diarrhea and possible differential effects in subgroups divided by sex, age, weight-for-height, and initial plasma zinc concentration. Dichotomous outcomes were analyzed by logistic regression. To assess the effects of excluding studies without original data from the pooled analyses, effect-size was estimated for all studies by using random-effects models. RESULTS: Zinc-supplemented children had a 15% lower probability of continuing diarrhea on a given day (95% CI: 5%, 24%) in the acute-diarrhea trials and a 24% lower probability of continuing diarrhea (95% CI: 9%, 37%) and a 42% lower rate of treatment failure or death (95% CI: 10%, 63%) in the persistent-diarrhea trials. In none of the subgroup analyses were the 2 subgroups of each pair significantly different from each other; however, in persistent diarrhea there tended to be a greater effect in subjects aged <12 mo, who were male, or who had wasting or lower baseline plasma zinc concentrations. CONCLUSION: Zinc supplementation reduces the duration and severity of acute and persistent diarrhea.

Acute Disease↗
PubMed1999

Regional endocardial mapping of spontaneous and induced atrial fibrillation in patients with heart disease and refractory atrial fibrillation.

We performed simultaneous catheter mapping of right and left atrial regions at onset and during sustenance of spontaneous atrial fibrillation (AF) in patients with ischemic and/or hypertensive heart disease. Seventeen patients with structural heart disease had spontaneous and electrically induced AF episodes mapped from their onset simultaneously in multiple right and left atrial regions. Atrial premature complexes (APCs) that initiated spontaneous AF had coupling intervals ranging from 260 to 400 ms (mean 332 +/- 61), most commonly arising from the lateral right atrium (31%), right atrioventricular junction (13%), atrial septum (6%), superior left atrium (25%), or inferior left atrium (25%). APC morphology on surface electrocardiograms did not correlate with origin in specific atrial regions. The earliest regions of atrial activation for the first AF cycle were the lateral right atrium (n = 5), superior left atrium (n = 4), distal or mid coronary sinus (n = 4), atrial septum (n = 2), and right atrioventricular junction at the His bundle location (n = 2). Spontaneous AF at onset usually showed discrete but irregular electrograms at virtually all right and left atrial sites mapped, with a reproducible region of AF initiation in all 8 patients with multiple events. The region of earliest atrial activation at spontaneous AF onset was in close proximity to the APC origin in 15 of 16 patients (94%), and 39 of 40 episodes (97%) mapped. Stable patterns of right and left atrial activation were observed at AF onset in 14 patients. Induced AF elicited with right atrial stimulation demonstrated different sites of earliest regional atrial activation at onset compared with spontaneous AF events in 4 of 8 patients. However, discrete intracardiac electrograms were also present in induced AF in all of the mapped atrial regions. Furthermore, the site of extrastimulus delivery in induced AF was also found to be in close proximity to the earliest region of atrial activation for the first AF beat. We conclude that spontaneous AF is initiated by APCs arising in different right or left atrial regions in patients with structural heart disease and the initial region of atrial activation in AF is in proximity to the region of APC origin. Organized and repetitive electrical activation is frequently observed in both right and left atria at AF onset. Although electrically induced AF may have different activation patterns than spontaneous AF at onset in many patients, both types of AF demonstrate organization and earliest atrial activation in proximity to the initiating APC.

Aged↗
PubMed1999

Prevention of diarrhea and pneumonia by zinc supplementation in children in developing countries: pooled analysis of randomized controlled trials. Zinc Investigators' Collaborative Group.

OBJECTIVES: This study assessed the effects of zinc supplementation in the prevention of diarrhea and pneumonia with the use of a pooled analysis of randomized controlled trials in children in developing countries. STUDY DESIGN: Trials included were those that provided oral supplements containing at least one half of the United States Recommended Daily Allowance (RDA) of zinc in children <5 years old and evaluated the prevention of serious infectious morbidity through household visits. Analysis included 7 "continuous" trials providing 1 to 2 RDA of elemental zinc 5 to 7 times per week throughout the period of morbidity surveillance and 3 "short-course" trials providing 2 to 4 RDA daily for 2 weeks followed by 2 to 3 months of morbidity surveillance. The effects on diarrhea and pneumonia were analyzed overall and in subgroups defined by age, baseline plasma zinc concentration, nutritional status, and sex. The analysis used random effects hierarchical models to calculate odds ratios (OR) and 95% CIs. RESULTS: For the zinc-supplemented children compared with the control group in the continuous trials, the pooled ORs for diarrheal incidence and prevalence were 0.82 (95% CI 0.72 to 0.93) and 0.75 (95% CI 0.63 to 0.88), respectively. Zinc-supplemented children had an OR of 0.59 (95% CI 0.41 to 0.83) for pneumonia. No significant differences were seen in the effects of the zinc supplement between the subgroups examined for either diarrhea or pneumonia. In the short-course trials the OR for the effects of zinc on diarrheal incidence (OR 0.89, 95% CI 0.62 to 1.28) and prevalence (OR 0.66, 95% CI 0.52 to 0.83) and pneumonia incidence (OR 0.74, 95% CI 0.40 to 1.37) were similar to those in the continuous trials. CONCLUSIONS: Zinc supplementation in children in developing countries is associated with substantial reductions in the rates of diarrhea and pneumonia, the 2 leading causes of death in these settings.

Child↗
PubMed1999

Noradrenaline improves the tumour to normal blood flow ratio and drug delivery in a model of liver metastases.

BACKGROUND: Vasopressors administered via the hepatic artery appear to increase drug delivery to colorectal liver metastases, but are limited by a short duration of action. This study measured their effect on blood flow and drug delivery during a prolonged infusion in a model of liver metastases. METHODS: In Hooded Lister rats with liver metastases, blood flow in tumour and adjacent normal liver was measured using laser Doppler flowmetry during a 30-min hepatic arterial infusion of endothelin 1, angiotensin II, vasopressin, N-nitro-L-arginine methyl ester (L-NAME), noradrenaline or saline (n = 6 per group). The same agents were co-administered with radiolabelled 5-fluorouracil (5-FU) (n = 6 per group) and uptake in the tumour and normal liver was measured. RESULTS: The mean(s.d.) duration of effect and resulting percentage changes in tumour to normal blood flow ratio of the vasopressors during this period were: noradrenaline, 2.9(0.4) min and 34(5) per cent (P < 0.05); angiotensin II, 4.2(0.2) min and 10(2) per cent (P < 0.05); vasopressin, 11.1(0.9) min and 7(2) per cent (P < 0.05); endothelin 1, 21.5(2.3) min and 14(5) per cent (P < 0.05); and L-NAME, 22.6(3.3) min and 2(1) per cent (P not significant). The mean(s.d.) uptake of radiolabelled 5-FU by the tumour in the groups studied was: saline, 5.1(3.2) x 10(5) c.p.m. per g tissue; angiotensin II, 5.1(1.4) x 10(5) c.p.m. per g; endothelin 1, 15.8(14.2) x 10(5) c.p.m. per g; L-NAME, 3.5(1.3) x 10(5) c.p.m. per g; and vasopressin, 6.8(3.5) x 10(5) c.p.m. per g. Significant improvements in 5-FU uptake only resulted from noradrenaline infusion (22.0(9.8) x 10(5) c.p.m. per g; P < 0.05). CONCLUSION: These findings suggest that hepatic arterially infused noradrenaline might be used to improve drug delivery to liver metastases.

Animals↗
PubMed1999

Colorectal cancer in adolescents.

Colorectal cancer, one of the most common malignancies among adults, is rare in adolescence. This low incidence coupled with non-specific symptoms and aggressive natural history leads to a poorer prognosis than in reported adult series. This article describes two cases of colorectal cancer in adolescents and reviews the literature regarding this rare condition. Earlier diagnosis and a greater understanding of the natural history may lead to improved treatment with concomitant improvements in survival.

Adenocarcinoma↗
PubMed1998

Treatment of colorectal cancer in patients aged over 75.

Colorectal cancer is a common malignancy which is occurring with increasing incidence in the elderly. As the age of the population increases so the importance of this malignancy will gradually increase. In addition a high proportion of elderly patients present with intestinal obstruction secondary to colorectal cancer and therefore the management of intestinal obstruction in the elderly becomes an important surgical consideration. This review discusses the management of colorectal cancer in patients over the age of 75 in both the elective and emergency situations with particular reference to screening, surgical management and the use of adjuvant therapy.

Age Factors↗
PubMed1998

Raised endothelin 1 levels in patients with colorectal liver metastases.

BACKGROUND: Endothelin 1 (ET-1), a vasoconstrictor peptide, has been implicated as a tumour growth stimulator and an angiogenesis factor. METHODS: To assess the involvement of ET-1 in colorectal cancer, immunoelectron microscopy for ET-1 was performed in colorectal liver metastases and normal liver (n = 6). ET-1 plasma levels were measured by radioimmunoassay in patients with colorectal cancer, with (n = 18) and without (n = 12) liver metastases, and in controls (n = 22). RESULTS: In normal liver, ET-1 was present in endothelial cells; in tumour, it was observed in endothelial cells, tumour cells and myofibroblasts. Mean(s.d.) plasma ET-1 levels were 2.75 (1.37) pg/ml in controls, 4.53(1.61) pg/ml in patients with colorectal liver metastases (P = 0.001) and 3.92(1.32) pg/ml in patients without metastases (P = 0.02). CONCLUSION: ET-1 was present in various cell types within colorectal liver metastases and raised levels were found in the plasma of patients with colorectal cancer. ET-1 may not only modulate tumour vascular tone but also act on tumour growth and angiogenesis, both locally and systemically.

Aged↗
PubMed1997

Donor lymphocyte infusion for childhood acute lymphoblastic leukaemia relapsing after bone marrow transplantation.

Four children with acute lymphoblastic leukaemia (ALL) who relapsed after allogeneic bone marrow transplantation (BMT) were treated with donor lymphocyte infusion (DLI) without prior conditioning. Three patients had previously received a non-T-cell-depleted matched sibling BMT and the fourth had a T-cell-depleted matched unrelated BMT. Two patients developed grade III-IV acute graft-versus-host-disease (GVHD) of the skin, which required intervention. Both are alive in complete haematological remission 7 and 10 months from DLI with chronic GVHD of the skin requiring immunosuppressive therapy. A third patient went into haematological remission 6 weeks after DLI, but with no clinical evidence of GVHD. His bone marrow remained in remission 11 months post-DLI despite the disease (ALL) relapsing in extramedullary sites. The fourth patient showed no clinical or haematological response to three consecutive doses of DLI given at 4-weekly intervals and died from progressive disease 11 months after relapse. These preliminary observations indicate that in constrast to experience in adult ALL, DLI may be effective in inducing sustained remission in children with ALL relapsing after BMT, and a response may occur even in the absence of clinical evidence of GVHD.

Adolescent↗
PubMed1995

Microvascular disease and anastomotic dehiscence in the colon.

Platelet-derived serotonin released in response to tissue manipulation during surgery may contribute to mesenteric arterial vasospasm leading to postoperative anastomotic leakage after colorectal resection. Organ bath experiments were used to demonstrate the efficacy of naftidrofuryl fumarate (NFT) to oppose serotonin-induced vasoconstriction of human mesenteric arteries. Cumulative dose-response curves were derived with and without NFT at 10(-9) and 10(-6) mol/l concentrations. The difference in maximal contractility between the three sets of curves (n = 8 for each) was significant (P < 0.0001). Sensitivity to serotonin in each of the three curves was measured by calculating the concentration for half-maximal response; differences were again significant (P < 0.0001). NFT reduced serotonin-induced contractility in a dose-dependent fashion in rings of human mesenteric arteries in vitro. This suggests a possible role for NFT in reducing mesenteric vasospasm in colorectal surgery.

Anastomosis, Surgical↗
PubMed1995

Restorative proctocolectomy for Chagasic megacolon.

Chagas' disease is endemic in South America, affecting several million people. Megacolon, the commonest intestinal manifestation, causes severe constipation and usually requires surgery. We report a case which was treated by restorative proctocolectomy. We believe this to be a useful new technique in the treatment of this condition.

Adult↗
PubMed1994

The effect of treating with anti-interleukin-1 receptor antibody on the course of experimental murine cutaneous leishmaniasis.

To assess the role of interleukin-1 (IL-1) in cutaneous leishmaniasis, Leishmania major-infected mice were treated with an anti-IL-1 receptor monoclonal antibody, LA-15.6. MoAb LA-15.6 prevents binding of IL-1 to both the T cell and B cell/macrophage forms of the IL-1 receptor. We found that treating with LA 15.6 inhibited the development of cutaneous lesions of L. major in both genetically-susceptible and resistant mice. Interestingly, this treatment had little or no effect on parasite numbers in the lesions or on the cytokines (interferon-gamma, interleukin-4) that the animals produced in response to infection with the parasite. These results suggest that although IL-1 plays a detrimental role in cutaneous leishmaniasis, it does not mediate this effect by altering the parasite-specific T cell response.

Animals↗
PubMed1993

Reversion to virulence in Leishmania major correlates with expression of surface lipophosphoglycan.

An attenuated clone of Leishmania major was produced by chemical mutagenesis with N-methyl-N'-nitro-N-nitrosoguanidine and was biochemically characterized to determine the reason(s) for its loss of virulence. We found that the degree of virulence of L. major did not correlate with either the level of expression of promastigote surface protease (PSP) or with the enzymatic activity of the molecule. In contrast, the levels of lipophosphoglycan (LPG) expressed by the attenuated clone were found to be at least 6-fold less than those of virulent L. major. When the attenuated L. major was injected into BALB/c mice and allowed to revert to virulence, the degree of reversion to virulence that the parasites underwent correlated directly with the amount and form (metacyclic) of LPG expressed by the parasites. Thus, these results further implicate LPG as an important Leishmania virulence factor.

Animals↗