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Biomedical subjects

J Mann

Publications and source records attributed to J Mann.

At least 55 records · Page 3Linked to original sources
PubMed2001

Air pollution and exacerbation of asthma in African-American children in Los Angeles.

Significant increases in asthma morbidity and mortality in the United States have occurred since the 1970s, particularly among African-Americans. Exposure to various environmental factors, including air pollutants and allergens, has been suggested as a partial explanation of these trends. To examine relations between several air pollutants and asthma exacerbation in African-Americans, we recruited a panel of 138 children in central Los Angeles. We recorded daily data on respiratory symptoms and medication use for 13 weeks and examined these data in conjunction with data on ozone (O3) nitrogen dioxide (NO2), particulate matter (PM10 and PM2.5), meteorological variables, pollens, and molds. Using generalized estimating equations, we found associations between respiratory symptom occurrence and several environmental factors. For example, new episodes of cough were associated with exposure to PM10 (OR = 1.25; 95% CI = 1.12-1.39; interquartile range [IQR] = 17 microg/m3, 24-hour average), PM2.5 (OR = 1.10; 95% CI = 1.03-1.18; IQR = 30 microg/m3, 12-hour average), NO2, and the molds Cladosporium and Alternaria, but not with exposure to O3 or pollen. The factors PM10 and O3 were associated with the use of extra asthma medication. For this population several bioaerosols and air pollutants had effects that may be clinically significant.

Adolescent↗
PubMed2001

A multicenter, randomized double-blind study of valsartan/hydrochlorothiazide combination versus amlodipine in patients with mild to moderate hypertension.

OBJECTIVE: To compare the antihypertensive efficacy and tolerability of a once-daily fixed valsartan/hydrochlorothiazide (HCTZ) combination and amlodipine in subjects with mild-to-moderate hypertension. SUBJECTS AND SETTING: In this multicentre, double-blind, randomized, comparative trial, 690 patients with sitting systolic blood pressure (BP) > or = 160 mmHg and sitting diastolic BP > or = 95 mmHg at the end of a 2-week placebo wash-out period were randomized to valsartan-based treatment (n = 342) or amlodipine (n = 348). METHODS: The patients received valsartan 80 mg o.d. or amlodipine 5 mg o.d for 4 weeks; in the case of an unsatisfactory blood pressure response, the treatments could be respectively changed to the fixed combination of valsartan 80 mg + HCTZ 12.5 mg o.d. or amlodipine 10 mg o.d. for a further 8 weeks. RESULTS: Both treatment approaches decreased systolic blood pressure and diastolic blood pressure to the same extent. The rate of responders to treatment at the end of fourth week (before up-titration) was 57.4% among the valsartan-treated patients and 61.9% among the amlodipine-treated patients (ns). At the end of the study, the rate of responders was not significantly different between the two groups (74.9 versus 72.1%). Valsartan-based treatment had a slightly lower incidence of adverse events (1.5 versus 5.5%; P = 0.006). CONCLUSIONS: The results of this trial demonstrate that the valsartan/hydrochlorothiazide combination and amlodipine are equally effective in lowering BP, and that the combination is better tolerated.

Adult↗
PubMed2001

Ongoing clinical trials in systemic hypertension.

Hypertension was identified as a cardiovascular risk factor in the late fifties and still remains a public health issue. The number of patients treated reaches only half of those diagnosed and, of those treated, half fail to reach target blood pressure. Furthermore, the number of antihypertensive drugs reaching the market has increased exponentially in the last few years, however, the impact on treatment and on attaining target blood pressure levels remains to be seen. The high percentage of treated patients who do not reach target blood pressure, combined with the high number of patients requiring more than one antihypertensive drug, have triggered a series of long-term morbidity and mortality trials comparing different therapeutic approaches ('new' pharmacological classes vs. 'old' pharmacological classes). These are described in this paper.

Antihypertensive Agents↗
PubMed2001

Pharmacokinetics and dosage recommendations for an oseltamivir oral suspension for the treatment of influenza in children.

OBJECTIVE: Oseltamivir (Ro 64-0796) is an ester prodrug of the active metabolite Ro 64-0802 (oseltamivir carboxylate), a potent and selective inhibitor of the neuraminidase enzyme of influenza virus. In this study we report the pharmacokinetics of oseltamivir in healthy children volunteers (study 1) and in children with influenza (study 2). STUDY PARTICIPANTS AND METHODS: In study 1, an open-label, single dose study, serial plasma samples were obtained from a total of 18 healthy children (5 to 18 years) who were grouped by age (n = 6 per group) and received single oral doses of oseltamivir 2 mg/kg. In study 2, a randomised, placebo controlled phase III study in paediatric children (1 to 12 years) presenting with influenza symptoms, 199 pharmacokinetic sparse samples were obtained from 87 patients, and serial samples were obtained from 5 patients. Pooled data were compared with those from adult studies. RESULTS: Children (1 to 12 years) eliminated the active metabolite faster than both adolescents (13 to 18 years) and adults, resulting in lower exposure to the active drug. In these children, oseltamivir 2 mg/kg twice daily resulted in drug exposures within the range associated with tolerability and efficacy in adults administered approximately 1 mg/kg twice daily. Unit doses of oseltamivir 30, 45 and 60mg oral suspension are recommended twice daily in children weighing < or =15 kg (or < or =33 lb, aged 1 to 3 years), > 15 to 23 kg (or >33 to 51 lb, aged 4 to 7 years) and >23 to 40 kg (or >51 to 88 lb, aged 8 to 12 years), respectively. A 75 mg capsule may be a viable dosage formulation in children (e.g. over 8 years of age) who are able to swallow solid dosage forms. CONCLUSIONS: Young children cleared the active metabolite oseltamivir carboxylate at a faster rate than older children and adults. Convenient administration recommendations for the oseltamivir oral suspension in children are possible to maintain drug exposure within the target window.

Acetamides↗
PubMed2001

The comparative anticaries efficacy of a dentifrice containing 0.3% triclosan and 2.0% copolymer in a 0.243% sodium fluoride/silica base and a dentifrice containing 0.243% sodium fluoride/silica base: a two-year coronal caries clinical trial on adults in Israel.

The purpose of this two-year clinical study was to provide a comparison of the anticaries efficacy associated with two commercially available, American Dental Association-accepted dentifrices: Colgate Total Toothpaste, which contains 0.3% triclosan and 2% copolymer in a 0.243% sodium fluoride/silica base; and Crest Cavity Fighting Toothpaste with Fluoristat, which contains 0.243% sodium fluoride in a silica base. The study was conducted in harmony with the published 1988 American Dental Association guidelines for studies geared toward the comparison of fluoride dentifrices. The study employed a double-blind parallel-group design, and involved adults living in communities throughout Israel. Qualifying subjects were randomly assigned to the two treatment groups, with multiple subjects in the same household all assigned to the dentifrice randomly allocated to the first among them. Caries examinations were conducted in accordance with U.S. Food and Drug Administration guidelines for the clinical evaluation of drugs to prevent dental caries. Two calibrated examiners performed all of the measurements. After treatment assignment, study participants were instructed to brush their teeth at home with their assigned dentifrice at least twice daily. Brushing instructions were reinforced by indoctrination in proper oral hygiene techniques by dental professionals, supplemented by pamphlets supplied by the sponsor and yearly mailings to participants, emphasizing good oral hygiene and the need to ensure compliance with the study. Post-baseline examinations were performed after one year of product use, and again after two years of product use. Three-thousand, three-hundred and ninety-two (3,392) subjects completed this two-year study. For these subjects, the mean caries scores (DFS, decayed or filled surfaces) at baseline were 21.96 for the Colgate Total Toothpaste group, and 21.49 for the Crest Cavity Fighting Toothpaste with Fluoristat group. For caries increment after one year, the respective means were 1.37 for the Colgate Total Toothpaste group, and 1.56 for the Crest Cavity Fighting Toothpaste with Fluoristat group. After two years, the mean caries increments were 1.46 for the Colgate Total Toothpaste group, and 1.75 for the Crest Cavity Fighting Toothpaste with Fluoristat group. No statically significant difference was indicated between the treatment groups at baseline. However, for both the one-year and two-year increments, there was a statistically significant difference between treatment groups. Relative to the Crest Cavity Fighting Toothpaste with Fluoristat group, the Colgate Total Toothpaste group presented a 12.2% reduction in caries increment scores at one year, and a 16.6% reduction in caries increment scores at two years. In accordance with the procedures and standards provided by the published guidelines of the American Dental Association for the comparison of the anticaries efficacy of fluoride dentifrices, the results of this study support the conclusion that Colgate Total Toothpaste provides a superior level of coronal anticaries efficacy compared to Crest Cavity Fighting Toothpaste with Fluoristat.

Adult↗
PubMed2000

The effect of group housing on feeding patterns and social behaviour of previously individually housed growing pigs.

Group housed pigs make less frequent feeder visits of longer duration, and eat at a faster rate than pigs housed individually. They also have lower growth rates which may be due to elevated stress levels resulting from changes in the concentrations of hormones, such as cortisol and adrenaline associated with aggression and social stress. The aim of this experiment was to investigate the effects of grouping on feeding pattern, time budgeting and the social behaviour of pigs kept as individuals from weaning until grouping. In total, 12 Large WhitexLandrace male pigs (four pigs per block) mean (+/-S.E.) start weight 22.5+/-0.7kg were housed individually for 3 weeks (Period 1) after which in two replicates (Blocks 1 and 3), pigs were combined into a group of four (Period 2) before being returned to individual housing for a further 3 weeks (Period 3). In Block 2, the four pigs remained as individuals across periods but were moved between pens at the end of Periods 1 and 2 to account for any pen effects. Feeding pattern and food intake were recorded throughout and pigs were weighed three times a week. Video recordings and live behavioural observations were made to record time budgets and social behaviour. Grouped pigs made less visits to the feeder in Period 2 than when they were housed individually in Periods 1 (P<0.001) and 3 (P<0.01). Visit duration was longer in Period 2 than in Periods 1 (P<0.01) and 3 (P<0.05). Food intake and weight gain were greater in Period 3 than in Periods 1 and 2 (P<0.001 and P<0.01, respectively). There were no significant effects of moving pigs between pens in Block 2 on feeding behaviour and timebudgets. In Period 2, grouped pigs slept more (P<0.01) and spent less time feeding (P<0.01) and rooting (P<0.01) than in Periods 1 and 3. The frequency of aggression decreased over time from mixing (P<0.001). Possible explanations for the changes in feeding behaviour when pigs are moved from individual to group housing are competition, group cohesion, or that the high frequency of feeder visits when the pigs are housed individually is a consequence of a lack of social stimulation. Of these different possibilities, the results suggest that group cohesion is most likely to have been causal in the observed changes in feeding behaviour.

Journal Article↗
PubMed2000

[The HOPE Study. What does it contribute to general practice?].

The HOPE study investigated the hypothesis that inhibition of the RAS with the ACE inhibitor, ramipril, prevents cardiovascular events in patients with a high cardiovascular risk. The primary endpoint of the double-blind, placebo-controlled study was the combination of myocardial infarction, stroke and cardiovascular death. The result was a significant reduction in the number of myocardial infarctions (9.9 vs. 12.2%), cardiovascular deaths (6.1 vs. 8.1%), strokes (3.4 vs. 4.9%) and revascularizations (16.0 vs. 18.6%) under the ACE inhibitor. The cough rate was raised (by 5%). The cardio- and nephroprotective benefits of ramipril were largely independent of the reduction in blood pressure achieved by the ACE inhibitor. The effects of rampipril in terms of micro- and macrovascular complications benefitted in particular type 2 diabetics with additional cardiovascular risk factors, so that this group should not be denied ramipril. The level of albumin excretion in the urine is directly coupled with the rate of cardiovascular events.

Aged↗
PubMed2000

A novel inhibitor of human telomerase derived from 10H-indolo[3,2-b]quinoline.

The bis-dimethylaminoethyl derivative of quindoline (10H-indolo[3,2-b]quinoline), an alkaloid from the West African shrub Cryptolepis sanguinolenta, has been synthesised. This has been shown to have modest cytotoxicity, as well as inhibitory activity against the telomerase enzyme. It is hypothesised that the latter activity is due to stabilisation of an intermediate guanine-quadruplex complex, in accordance with computer modelling.

Aminoquinolines↗
PubMed2000

Human carbonyl reductase overexpression in the heart advances the development of doxorubicin-induced cardiotoxicity in transgenic mice.

Doxorubicinol (dxol) is the major metabolite formed in the hearts of cancer patients being treated with the widely used chemotherapeutic agent, doxorubicin (dox). The well-documented cardiomyopathy associated with dox treatment has been studied in vitro and ex vivo providing evidence that the C-13 hydroxy metabolite, dxol, might play a key role in the development of dox-induced cardiotoxicity. In this report, we have developed transgenic mice with heart-specific expression of human carbonyl reductase (HCBR), an enzyme that metabolizes dox to dxol. Dox was rapidly converted to dxol in the hearts of the transgenic expressers, which led to advanced development of both acute and chronic cardiotoxicity. Acute cardiotoxicity was evident by a 60% increase in serum creatine kinase activity and a 5-fold increase in cardiac damage measured by electron microscopy. Myofibril degeneration was the major damage observed in acute dox toxicity. Electrocardiograph telemetry, survival data, and electron microscopy were monitored during chronic dox-induced cardiotoxicity. HCBR expressers developed cardiotoxicity 6-7 weeks before the nonexpressers. The HCBR expressers survived for 5 weeks compared with 12 weeks for the controls. Electrocardiograph profiles and necropsies showed the cause of death to be the development of cardiomyopathies leading to congestive heart failure. Levels of dxol were four times higher in the HCBR expresser hearts than in the nonexpressers. Electron microscopy data showed swelling and major structural damage of the mitochondria in the HCBR expressers. These data demonstrate that the C-13 hydroxy metabolite of dox advances the development of dox-induced cardiotoxicity in an in vivo system and suggest that heart carbonyl reductase activity may contribute to dox-induced cardiotoxicity in humans.

Alcohol Oxidoreductases↗
PubMed2000

Glycaemic index of New Zealand foods.

AIM: To determine the glycaemic index values to a range of foods that are unique to New Zealand, and those that are grown and/or manufactured locally. METHODS: We determined the glycaemic index of 28 carbohydrate foods in both healthy subjects and those with type 2 diabetes. Venous blood samples were collected over two to three hours, and the incremental area under the blood glucose curve was used to calculate glycaemic index values. RESULTS AND CONCLUSIONS: This study has identified the glycaemic index values for a range of New Zealand foods which will be clinically useful in the nutritional management of individuals with diabetes mellitus. People with diabetes are recommended to choose foods with a low glycaemic index which is associated with optimal blood glucose control and lipid levels.

Adult↗
PubMed2000

Identification of new heterocyclic nitrogen compounds from glucose-lysine and xylose-lysine maillard model systems.

Aqueous sugar (glucose or xylose)-lysine model systems were heated at 80 degrees C for 6 h with the pH maintained at a predetermined value (3, 4, or 5). Selected compounds were isolated by combinations of solvent extraction and semipreparative HPLC, prior to identification by NMR and mass spectrometry. Two compounds were identified from the pH 5 glucose system and were identified as epsilon-[2-formyl-5-(hydroxymethyl)pyrrole-1-yl]-L-norleucine (pyrraline) and the new compound, 1-(5-carboxy-5-aminopentyl)-2-formyl-3-(1,2,3-trihydroxypropyl)pyrrole. A third compound was partially characterized. 2-Acetyl-5-hydroxymethyl-5,6-dihydro-4H-pyridinone was identified in the pH 3 xylose system, and the new compound, 8-furan-2-yl-methyl-5-hydroxymethyl-5,6-dihydro-indolizine-1,7-dione, was identified in the pH 4 xylose system. 2-Furfurylidene-4-hydroxy-5-methyl-3(2H)-furanone was identified in both xylose systems. Mechanisms of formation are proposed for the novel compounds.

Chromatography, High Pressure Liquid↗
PubMed2000

Dental anxiety among Israeli dental students: a 4-year longitudinal study.

The aims of the present study were (a) to evaluate students' estimation of their parents' dental anxiety; (b) to measure students' dental anxiety and to study their ranking of the most fear provoking stimuli in the dental situation during their pre-clinical and clinical years; (c) to investigate gender differences among students with regard to dental anxiety. 30 3rd-year students (15 male and 15 female) who completed a 4-section questionnaire which requested sociodemographic information, evaluation of parents' dental anxiety, dental anxiety scale (DAS) and dental fear scale (DFS), completed the DAS and DFS in their 5th and 6th years. Both male and female students estimated their mothers' dental anxiety as significantly higher than their fathers'. Female students ranked their parents higher than males. DAS scores were significantly higher among female students than among males in the 3rd year. However, DAS scores were reduced from the 3rd to the 6th year among the total class and significantly among females, while males' levels of anxiety remained within close range throughout the years. The dental anxiety scores of all students who experienced a dental procedure in the past were higher than the scores of the students who did not. The most fearful stimulus was 'feeling the needle'. Our findings may suggest that the change in the reported dental anxiety of the students during the years of dental studies in the present study may be explained by the increased professional education and clinical experience that the students acquire throughout their studies in the dental school. Being exposed to basic trivial dental procedures (such as local anaesthetic injection) may help students either to be habituated or to use rational coping strategies when dealing with personal dental experience.

Adaptation, Psychological↗
PubMed2000

Linkage heterogeneity for the IBD1 locus in Crohn's disease pedigrees by disease onset and severity.

BACKGROUND & AIMS: There is evidence for the IBD1 Crohn's disease (CD) susceptibility locus on chromosome 16 in several but not all populations studied. Genetic and phenotypic heterogeneity may underlie ability to replicate IBD1. We determined if age and severity stratification could identify a clinical subgroup at risk for IBD1. METHODS: Linkage analysis at microsatellites spanning chromosome 16 was performed in 2 groups of CD pedigrees: group 1, 57 pedigrees with at least one affected relative classified as having "severe" disease, by history of surgical resection or immunomodulator therapy, and with disease diagnosed before age 22; and group 2, 33 pedigrees with no history of early-onset, severe CD. RESULTS: Group 1 pedigrees demonstrated genomewide significant linkage evidence for the IBD1 locus (nonparametric multipoint logarithm of the odds [Mlod], 3.84; P = 1.3 x 10(-5)) with linkage evidence greater than all 90 pedigrees (Mlod, 2.12; P = 9.0 x 10(-4)). Group 2 pedigrees had near zero nonparametric 2-point and Mlod scores for the IBD1 region. Heterogeneity between groups 1 and 2 was significant (P = 0.002). CONCLUSIONS: Presence of early-onset, more severe CD identifies pedigrees at high risk for IBD1. These pedigrees will have more power to refine the IBD1 locus and identify the causative gene.

Adult↗
PubMed2000

Determinants of elevated urinary albumin in the 4,937 type 2 diabetic subjects recruited for the DIABHYCAR Study in Western Europe and North Africa.

OBJECTIVE: Whether ACE inhibition is useful for type 2 diabetic patients with micro- and macroalbuminuria remains unknown. The Non-Insulin-Dependent Diabetes, Hypertension, Microalbuminuria, Cardiovascular Events and Ramipril (DIABHYCAR) Study was set up to address this issue through a multicenter double-blind parallel placebo-controlled > or = 3-year trial in Europe and North Africa. In this article, we report the characteristics of the randomized patients. RESEARCH DESIGN AND METHODS: The main selection criteria were as follows: men or women aged > or = 50 years with type 2 diabetes treated with oral antidiabetic drugs, with or without hypertension, with a plasma creatinine level < 150 mumol/l, and with persistent micro- or macroalbuminuria, as assessed centrally by two successive urine samples containing a urinary albumin concentration > or = 20 mg/l. Patient characteristics were studied by comparing patients who were randomized to those who were not, taking their geographical origin into account. RESULTS: There were 25,455 patients screened for urinary albumin (20,296 from France, 918 from Germany, 1,019 from Northwest Europe, 969 from Central Europe, 959 from Mediterranean Europe, and 1,294 from North Africa). Of these patients, 4,937 were randomized. Compared with the nonrandomized patients, the randomized patients were older, more often men, more obese, had higher systolic/diastolic blood pressure and plasma glucose, smoked more tobacco, drank more alcohol, and had complications more frequently. Using a logistic regression analysis, all the above-mentioned items appeared as independent determinants for randomization into the study, with the exception of alcohol intake. The contribution of each item varied slightly from one geographical origin to another. CONCLUSIONS: The physical, biological, and behavioral characteristics create a poor renal and cardiovascular prognosis for the type 2 diabetic patients randomized to the DIABHYCAR Study because of micro- and macroalbuminuria. Testing the usefulness of ACE inhibition for the type 2 diabetic patients with microalbuminuria seems feasible through the DIABHYCAR Study.

Africa, Northern↗