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Biomedical subjects

J Clemens

Publications and source records attributed to J Clemens.

At least 55 records · Page 3Linked to original sources

Infant breastfeeding and the risk of childhood lymphoma and leukaemia.

BACKGROUND: A protective effect of breastfeeding on childhood lymphoma has been indicated but supportive evidence is limited. METHOD: Data from a population-based case-control study of childhood cancer in Shanghai, including 82 lymphoma cases and 159 acute leukaemia cases and their age- and sex-matched community controls, were analysed. RESULTS: After adjustment for potentially confounding variables, a slight, although non-significant, reduction in risk of lymphoma was observed among children who were breastfed as infants versus those who were not (odds ratio [OR] = 0.69; 95% CI: 0.3-1.7). The reduction was somewhat greater for children who had been breastfed longer and appeared to pertain primarily to Hodgkin's disease and to cases diagnosed before the age of 6 years. As expected, there was no reduction in risk of acute leukaemia associated with breastfeeding. CONCLUSIONS: Although providing neither strong support for nor refuting the study hypothesis, these data suggest that if breastfeeding does reduce the risk of lymphoma, its protective effect among Chinese children is likely modest in magnitude and concentrated in certain subgroups defined by length of breastfeeding, age at diagnosis and histological subtype of cancer.

Acute Disease↗

Impact of infection by Helicobacter pylori on the risk and severity of endemic cholera.

To evaluate the relationship between Helicobacter pylori infection and the subsequent risk and severity of endemic Vibrio cholerae O1 diarrhea among rural Bangladeshis, 285 children and adults with cholera (cases) and 881 contemporaneously selected community controls were studied. Cases and controls were contrasted for H. pylori infection, as manifested by serum IgG anti-H. pylori antibodies. Although the overall risk of cholera was not significantly increased among H. pylori-infected subjects, the risk of cholera of life-threatening severity was significantly elevated (relative risk [RR] = 1.61; 95% confidence interval [CI] = 1.07-2.42). A significant increase in the risk of severe cholera was seen in subjects who lacked natural serum vibriocidal antibodies (RR = 2.88; 95% CI = 1.28-6.48) but not in those with such antibodies. Thus, H. pylori infection was associated with a significant increase in the risk of life-threatening cholera, but only among persons lacking natural vibriocidal immunity.

Adolescent↗

Maternal smoking, alcohol drinking, caffeine consumption, and fetal growth: results from a prospective study.

In a prospective study of 712 pregnancies, we examined associations between maternal smoking, alcohol, and caffeine consumption and fetal growth. We interviewed patients at entry into care [12.9 +/- 4.3 (standard deviation) weeks], and at 28 and 36 weeks of gestation. We found the expected reductions in adjusted birthweight among women who smoked throughout pregnancy: 168 gm [95% confidence limits (CL) = -326, -10] for low/moderate amounts (< or = 15 cigarettes per day); 288 gm (95% CL = -491, -84) for heavy smoking (> 15 cigarettes per day). We also found a decrease in birthweight (-179 gm; 95% CL = -364, 7) among smokers who reported quiting early in pregnancy. First trimester alcohol consumption (average: four drinks per week) was associated with a 155-gm reduction in fetal growth (95% CL = -324, 15), even after adjustment for number of cigarettes smoked. The association, observed with all types of alcohol consumption, was stronger among smokers (-270 gm) but was also present in nonsmokers (-115 gm). Caffeine consumption showed no relation to fetal growth, even among heavy consumers, although they were relatively few. This study implicates heavy maternal smoking at any point in pregnancy, including solely in the early months, and possibly moderate alcohol drinking as causes of low birthweight.

Adult↗

Diagnostic X-ray and ultrasound exposure and risk of childhood cancer.

In a population-based case-control study of 642 childhood cancer cases and the same number of matched controls in Shanghai, China, we evaluated the relationship between diagnostic X-ray (preconception, pre- and post-natal) and antenatal ultrasound exposure and the subsequent risk of developing three major types of childhood cancer (acute leukaemia, lymphoma and brain tumours) and all childhood neoplasms combined. Consistent with previous studies, prenatal X-ray exposure was found to be associated with an 80% increased risk of childhood cancers, although the estimation was based on 4% and 2% exposed cases and controls and was only marginally statistically significant (P = 0.08). Post-natal X-ray exposure was also linked with a small elevation in the risk of all cancers and the major categories of malignancies in children. Little evidence, however, was found to relate parental preconception X-ray exposure with the subsequent cancer risk in offspring, regardless of the exposure window and the anatomical site of X-ray exposures. This study adds further to the growing literature indicating that antenatal ultrasound exposure is probably not associated with an increased risk of childhood cancer.

Adolescent↗

Serum immunoreactive erythropoietin during the perioperative period.

BACKGROUND: Recombinant human erythropoietin is now available for clinical use. Therefore we sought to determine the frequency of anemia and low endogenous erythropoietin levels in patients undergoing elective, major general surgical procedures. METHODS: Serum immunoreactive erythropoietin levels were measured before operation and 1 and 5 days after operation in 84 patients (43 men and 41 women) with normal renal function. RESULTS: Twenty of the women (49%) and 27 of the men (63%) were anemic before operation. Nine of these anemic patients had inappropriately low serum erythropoietin levels for their degree of anemia. On postoperative day 1, 66% of the women and 88% of the men were anemic, but the mean serum erythropoietin level had not increased. On postoperative day 5, 80% of the women and all of the men were anemic, but 22% of the patients still had an inappropriately low serum erythropoietin level. Multiple regression analysis identified female gender and black ancestry as predictors of an inadequate erythropoietin response after operation. CONCLUSIONS: Diseases requiring operation are frequently associated with anemia that is in part caused by impaired erythropoietin production. Surgery also appears to contribute to suppression of erythropoietin production particularly in women and black persons.

Anemia↗

Identification and characterization of a nucleotide binding site of ovine prolactin with 2-azido-NAD.

Photoaffinity labeling of ovine prolactin with the NAD+ photoaffinity analog [alpha-32P]nicotinamide-2-azidoadenine dinucleotide has been used to identify an NADH/NADPH binding site. Specificity of nucleotide interaction was demonstrated by saturation and protection of labeling at physiologically relevant concentrations. Saturation of photoinsertion was observed at approximately 100 microM probe with an apparent Kd of approximately 25 microM. Protection of photoinsertion was observed with NAD+ and NADH. The photoinsertion was decreased by 75% and greater than 95%, respectively, upon addition of 200 microM of the above-mentioned compounds. The protection obtained with NADP+ and NADPH was of the same order, respectively. The adenine ring binding domain of NADH/NADPH binding site was identified by trypsin and chymotrypsin digestion of the photolabeled prolactin and purification of the photolabeled peptide by boronate affinity chromatography and immobilized Fe3+ affinity chromatography. The peptide was identified to be Ala22-Tyr28. These studies demonstrate that prolactin contains an NADH/NADPH binding site which may be significant in the mechanism of action of this hormone.

Affinity Labels↗

Vasectomy and prostate cancer risk: methodological review of the evidence.

Two recent studies have reported a significantly elevated risk of prostate cancer among vasectomized men. To assess whether the new results conflict with earlier studies that found no significant overall association, and, if so, whether such a conflict could have a methodological basis, we reviewed the six major epidemiological studies of this topic. Statistical analysis revealed significant (p < 0.01) heterogeneity among the associations in the six studies, attributable to one of the recent studies. Scrutiny of the studies for fulfillment of eight methodological standards for scientific validity revealed that no study completely fulfilled more than four standards, and that all studies were deficient in avoiding detection bias and obtaining accurate vasectomy histories. Our review indicates that the evidence on this topic is indeed conflicting, that the quality of the evidence does not resolve the conflict, and that future studies of this topic, designed to ensure scientific credibility of results, are needed.

Adult↗

The design and analysis of cholera vaccine trials: recent lessons from Bangladesh.

The recent spread of cholera to Latin America, together with the persistent burden of this disease in Asia and Africa, have stimulated efforts to evaluate new cholera vaccines in field settings. Although the standard experimental paradigm for vaccine field trials is well established, the success of these trials will also depend on suitable consideration of the epidemiology of cholera and of cholera vaccination in the setting under study. Epidemiological studies done in Bangladesh emphasize the importance of appreciating the poorly predictable, multifocal occurrence of cholera in estimating a probable incidence of cholera for a field trial. They also underscore how the filtering effect of enrolling subjects into a prospective trial can dramatically reduce the available population for study, and can yield a study sample whose expected risk of cholera differs markedly from that for the source population. Finally, the data highlight the subtle effects that the mode of surveillance and the choice of an outcome definition can have upon protective efficacy, and emphasize the need for subgroup analyses that address the distinctive variations in vaccine protection that may occur in subjects differing in age and in ABO blood groups, and in subjects exposed to classical versus El Tor cholera.

ABO Blood-Group System↗

Passive immunotherapy in the treatment of advanced human immunodeficiency virus infection.

To evaluate the safety and efficacy of passive immunotherapy for advanced human immunodeficiency virus (HIV) infection, a randomized, double-blind, controlled trial of human anti-HIV hyperimmune plasma was conducted. Sixty-three subjects with stage IV HIV disease (AIDS) were randomized to received 250 mL of either HIV-immune plasma or HIV antibody-negative plasma every 4 weeks. Although nonsignificant trends toward improved survival and delayed occurrence of a new opportunistic infection were noted, no significant effects on absolute CD4 lymphocyte counts or quantitative HIV viremia were seen. The only notable toxicity was the allergenicity to be expected from infusing plasma products, usually manifesting as urticaria. Thus, results do not rule out the potential usefulness of passive immunization with different preparations, but did fail to demonstrate clinical benefit of the product studied.

Adult↗

Breast-feeding and the risk of life-threatening rotavirus diarrhea: prevention or postponement?

PURPOSE: To assess the relationship between breast-feeding and the risk of life-threatening rotavirus diarrhea among Bangladeshi infants and children younger than 24 months of age. DESIGN: Case-control study. SETTING: A rural Bangladesh community. PARTICIPANTS: One hundred two cases with clinically severe rotavirus diarrhea detected in a treatment center-based surveillance system during 1985 and 1986, and 2587 controls selected in three surveys of the same community during the same calendar interval. OUTCOMES: Cases and controls were compared for the frequency of antecedent breast-feeding patterns. RESULTS: Compared with other feeding modes, exclusive breast-feeding of infants was associated with significant protection against severe rotavirus diarrhea (relative risk (RR) = 0.10; 95% confidence interval [CI] = 0.03, 0.34). However, during the second year of life, the risk of this outcome was higher in breast-fed than in non-breast-fed children (RR = 2.85; 95% CI = 0.37, 21.71), and no overall protection was associated with breast-feeding during the first 2 years of life (RR = 2.61; 95% CI = 0.62, 11.02). CONCLUSIONS: Although exclusive breast-feeding appeared to protect infants against severe rotavirus diarrhea, breast-feeding per se conferred no overall protection during the first 2 years of life, suggesting that breast-feeding temporarily postponed rather than prevented this outcome. While not detracting from efforts to promote breast-feeding to alleviate the burden of diarrhea due to nonrotaviral enteropathogens, our findings cast doubt on whether such efforts will impact on the problem of severe rotavirus diarrhea.

Bangladesh↗

General pharmacology of loracarbef in animals.

Loracarbef ((6R, 7S)-7-[(R)-2-amino-2-phenyl-acetamido]-3-chloro-8-oxo-1- azabicyclo [4.2.0]oct-2-ene-2-carboxylic acid, monohydrate, LY 163892, CAS 121961-22-6) is a carbacephem antibiotic targeted for use in the treatment of infectious disease. The potential pharmacological effects of this agent were examined on cardiovascular, respiratory, gastrointestinal, central nervous and autonomic nervous systems. Also examined were local anesthetic activity, effects on platelet aggregation, circulating blood glucose, primary antibody production, renal function, blood coagulation, ocular irritation, and the acute inflammatory response. Doses of 100, 1000, and 2000 mg/kg given by the oral route were selected for most in vivo studies. Concentrations up to 3 x 10(-3) mol/l were used in vitro. Loracarbef was essentially inactive in the tests of central and autonomic nervous system function, platelet aggregation, renal function, blood hemolysis, primary antibody production, blood coagulation, and ocular irritation. It had no local anesthetic activity. At high oral or intravenous doses, representing significant multiples of the therapeutic dose, loracarbef caused changes in gastrointestinal (decrease in gastric acid production and gastric fluid volume; increased biliary output), cardiovascular (increased mean pressure, cardiac output, heart rate, and femoral flow), blood glucose (increased glucose levels), and anti-inflammatory tests (suppressed acute inflammatory response). In summary, loracarbef exhibited minimal activity in these pharmacodynamic studies. These results indicate loracarbef has a low potential to produce adverse effects at therapeutic doses.

Anesthetics, Local↗

Safety and immunogenicity of single-dose live oral cholera vaccine CVD 103-HgR in 5-9-year-old Indonesian children.

Oral vaccines offer great promise as public-health measures to prevent disease in less-developed countries. CVD 103-HgR, a genetically engineered, attenuated, Vibrio cholerae O1 strain has proved effective in industrialised countries. We have assessed the safety, immunogenicity, and excretion of this live cholera vaccine in children in north Jakarta, Indonesia. 412 children aged 5-9 years received single doses of 5 x 10(6), 5 x 10(7), 5 x 10(8), 5 x 10(9), or 1 x 10(10) colony forming units (CFU) of CVD 103-HgR or placebo (5 x 10(8) inactivated Escherichia coli K-12) with buffer. All doses were well tolerated. The 5 x 10(8) CFU dose, which is highly immunogenic in subjects in industrialised countries (greater than 90% seroconversion), elicited seroconversions of vibriocidal antibody in only 16% of Indonesian children. By contrast, a single 5 x 10(9) CFU dose of vaccine resulted in high rates (75% and 87%) of seroconversion with two different batches of vaccine. A batch prepared with a centrifugation step gave significantly higher geometric mean titres (16-fold increase over baseline) than did a batch in which there was a filtration step between fermentation and lyophilisation (10-fold increase over baseline). At a 5 x 10(9) CFU dose, CVD 103-HgR is well tolerated and highly immunogenic in Indonesian children and should therefore be further investigated for use as a one-dose live oral cholera vaccine in developing countries.

Administration, Oral↗

An oral B subunit: whole cell vaccine against cholera.

During the last decade there has been a rapid progress in the development of new, much improved vaccines against cholera. These vaccines, which are given orally to stimulate the gut mucosal immune system, are based on either a combination of purified cholera toxin B (binding) subunit and killed cholera vibrios of Inaba and Ogawa serotypes and El Tor and classical biotypes (B subunit-whole cell vaccine, B-WC) or on a live attenuated mutant strain of Vibrio cholerae producing the B subunit (CVD 103-HgR). The safety of the oral B-WC cholera vaccine and the immunogenicity and protective efficacy of this vaccine against both cholera and diarrhoea caused by enterotoxigenic Escherichia coli have been extensively documented, e.g. in a large randomized, placebo-controlled field trial in 90,000 persons living in a cholera endemic area. The potential for inexpensive large-scale manufacturing of the B-WC vaccine has recently been much facilitated by the introduction of recombinant DNA technology for production of the B subunit component. This now gives promise that this vaccine could become a useful, cost-effective tool in future strategies to control cholera both in endemic situations and in relation to acute epidemic outbreaks.

Administration, Oral↗

Cholera vaccines.

The currently licensed parenteral cholera vaccine has not been a useful public health tool in the control of cholera. Building on the knowledge that primary infection offers significant protection against reinfection and that mucosal immunity mediates this protection, several oral cholera vaccines have been developed. These vaccine candidates or future candidates derived using the techniques of molecular biology will no doubt contribute to the control of cholera.

Cholera↗