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Biomedical subjects

H H Keller

Publications and source records attributed to H H Keller.

At least 19 recordsLinked to original sources
PubMed2005

Validity and reliability of SCREEN II (Seniors in the community: risk evaluation for eating and nutrition, Version II).

BACKGROUND: Nutrition risk screening for community-living seniors is of great interest in the health arena. However, to be useful, nutrition risk indices need to be valid and reliable. The following three studies describe construct validation, test-retest and inter-rater reliability of SCREEN II. METHODS: Study (1) seniors were recruited from the general community and from a geriatrician's clinic to complete a nutritional assessment and SCREEN II. 193 older adults provided medical and nutritional history, 3 days of dietary recall and anthropometric measurements. A dietitian reviewed all information collected and ranked seniors on risk: 1 (low) to 10 (high risk). Receiver operating characteristic curves were completed. An abbreviated SCREEN II was developed through statistical analysis and expert ranking of the 17 items. Studies (2) and (3) seniors were recruited from the community to self-administer (n = 149) or be interviewed (n = 97) using SCREEN II twice within 2 weeks. For self-administration one index was completed via mail. Interviewer administration was completed via telephone with two interviewers. Intra-class correlations were calculated. RESULTS: (1) Total and abbreviated SCREEN II have increased sensitivity and specificity as compared to SCREEN I in identifying seniors at nutritional risk. (2) Test-retest reliability was adequate (intra-class correlation (ICC) = 0.83). (3) Inter-rater reliability was adequate (ICC = 0.83). CONCLUSIONS: SCREEN II appears to be a valid and reliable tool for the identification of risk for impaired nutritional states in community-living older adults, and is an improvement over SCREEN I.

Aged↗
PubMed2004

Nutrition and health-related quality of life in frail older adults.

BACKGROUND: Frail older adults are at risk for poor nutrition and frequently experience declining healthrelated quality of life (HR-QOL). The relationship between nutritional risk and HR-QOL although intuitive, has been rarely studied. OBJECTIVE: To determine the independent association of nutritional risk with HR-QOL in frail older adults. DESIGN: Cross-sectional survey. Data were collected by interviewer-administered questionnaire. Nutritional risk was measured by SCREEN (Seniors in the Community: Risk Evaluation for Eating and Nutrition) and HR-QOL by perceived health status and report of number of days in the past month where physical or mental health was not good, or where activities were limited. Frail (n=367) seniors were recruited from 23 community service providers. A wide variety of covariates were also measured. Multivariate modeling based on a conceptual model was used to identify factors associated with HR-QOL. RESULTS: Nutritional risk appears to be a significant and important factor associated with HR-QOL. Other significant covariates were: falls, social supports, social activity, health behaviours, pain and medication use. CONCLUSION: Nutritional risk as measured by SCREEN appears to be a significant covariate in explaining differences in HRQOL among frail older adults. Further work should determine if nutritional risk predicts changes in HR-QOL over time.

Age Factors↗
PubMed2003

Nutritional risk and time to death; predictive validity of SCREEN (Seniors in the Community Risk Evaluation for Eating and Nutrition).

BACKGROUND: Undernutrition in community-living seniors is common and has the potential to adversely influence health outcomes. Nutritional risk screening tools can help identify seniors at risk, but few have predicted health outcomes. METHODS: Seniors were recruited from 23 community service providers. The 8-item abbreviated version SCREEN (Seniors in the Community Risk Evaluation for Eating and Nutrition) was used to identify nutritional risk in 367 seniors; demographics, health, activities of daily living, and psychosocial variables were included in a baseline assessment. The seniors were followed-up by telephone for 18 months to determine the occurrence of health outcomes, including death. Cox regression was used to identify predictors of survival time. RESULTS: During the 18-month follow-up there were 27 deaths (approximately 7%). Using the abbreviated tool, nutritional risk was common (42.2%). This low rate of death limited the modeling to only a few key covariates, which were based on bivariate analyses. Nutritional risk was significantly associated with time to death. Gender was also associated with time to death, with men more likely to die sooner than women. Increasing age was also significantly associated with shorter survival times. CONCLUSIONS: Nutritional risk as measured by SCREEN was predictive of time to death. This simple tool may be useful for future epidemiological research on health outcomes of seniors. Further work should confirm these results, as the low event rate influenced the modeling strategy.

Age Factors↗
PubMed2001

Construct validation and test-retest reliability of the seniors in the community: risk evaluation for eating and nutrition questionnaire.

BACKGROUND: We performed two studies. Study 1 was a construct validation of Seniors in the Community: Risk Evaluation for Eating and Nutrition (SCREEN), a 15-item questionnaire for assessing nutritional risk. In Study 2, we examined the test-retest reliability of SCREEN. METHODS: Study 1 was a cross-sectional study, and Study 2 was a cohort study. For Study 1, ten diverse community sites were used to recruit participants. A total of 128 older adults attended a clinic to provide medical and nutritional history and anthropometric measurements. A dietitian interviewed each participant. Dietitians used clinical judgment to rate the probability of nutritional risk from 1 (low risk) to 10 (high risk). Spearman's rho correlation and receiver operating characteristic curves were completed. An abbreviated SCREEN was developed through multiple linear regression analysis. In Study 2, SCREEN was randomly distributed to members of a seniors' recreation center where a self-selected sample (n = 124) completed two mailed SCREENs, 4 weeks apart. The test-retest reliability was estimated through paired correlations of total scores and individual items. RESULTS: In Study 1, total and abbreviated SCREEN scores were significantly associated with the dietitian nutritional risk rating (rho = -.47 and rho = -.60, respectively). Study 2 revealed that the test-retest reliability of SCREEN was adequate. CONCLUSIONS: SCREEN appears to be a valid and reliable tool for identifying community-dwelling older adults at risk for impaired nutritional states.

Aged↗
PubMed1999

A decade of doctoral research in nutrition.

OBJECTIVE: To describe North American dissertation research in human nutrition from 1986 through 1995. DESIGN: A census collection. SUBJECTS/SETTING: The unit of observation was the dissertation abstract submitted to Dissertation Abstracts International for the years 1986 through 1995. Only dissertations written in English with a human nutrition subject code (0570) that lead to a PhD, DrPH, EdD, or ScD at a North American university were included (N = 2,044). Abstracts were reviewed by 2 raters who extracted pertinent data on variables describing the dissertation research (e.g., topic of dissertation, type of sample). ANALYSES: Analyses were descriptive. RESULTS: The majority (n = 1,147) of doctoral dissertations were completed by female students. Male students were more likely to study in vitro samples than female students (11% vs 4%) and female students were more likely to study human subjects (64%). Male students tended to have male advisers, although overall male advisers appeared to predominate (34% men, 24% women, 42% unknown or missing). Topic areas for dissertation work reflected gender differences. Popular topics for dissertation research have changed over time; biochemical-, micronutrient-, and obesity-related research decreased and research in development of theoretical constructs and examination of dietary habits of selected groups increased. CONCLUSIONS: From 1986 through 1995 there was an increase in the proportion of female doctoral students. Female and male students varied in the type of sample studied, gender of advisers, age group of human subjects, and topics of their dissertations. Universities emphasized different topic areas and methodologies. There appears to have been an increase in areas of applied research (e.g., dietary habits) and a decrease in basic science topic areas (e.g., micronutrients) over the 10-year period examined.

Academic Dissertations as Topic↗
PubMed1995

Weight gain impacts morbidity and mortality in institutionalized older persons.

OBJECTIVE: To determine if a significant weight change in previously undernourished older persons is associated with mortality and morbidity. DESIGN: Retrospective survey. SETTING: A chronic care hospital in Canada. SUBJECTS: Follow-up survey from an original data set (Time 1) on 88 previously diagnosed undernourished and 60 adequately nourished. Average age was 78 years; average length of residence was 40 months. Of the 148 subjects, 120 were male. MEASUREMENTS: Average time to follow-up (Time 2) was 319 days from Time 1. Data was collected on weight change, reported incidence of infection, use of antibiotics, number of falls, and admissions to acute centers, as well as incidence and cause of death. Three-day diet intake records were available on 15% of subjects within 1 month of Time 2. Five nutritional groups existed within this follow-up population: those previously undernourished who gained at least 5% of Time 1 weight (Group 1), those undernourished who lost at least 5% of Time 1 weight (Group 2), those undernourished who maintained their weight (Group 3), those adequately nourished who lost at least 5% of original weight (Group 4), and those who remained adequately nourished (Group 5). RESULTS: Forty-one of the 148 patients died; this was significantly associated with nutrition group (X2 = 11.23, P = 0.02), with fewer deaths in Groups 1, 3, and 5. As well, primary diagnosis (x2 = 32.6, P = 0.001), length of residence (X2 = 25.6, P = 0.01), and time to death (X2 = 26.4, P = 0.009) were significantly associated with nutrition group. Diet intake records indicated an improvement in energy and protein intake in Group 1 during the follow-up. Energy and protein change, whether increased or decreased from the original study, was significantly associated with nutrition group. Total number of feeding impairments and presence of dysphagia were significantly associated with nutrition group. Other morbidity events were not significantly associated with nutrition group, but trends suggest a positive effect of weight gain on incidence of falls, incidence of more than two infections, and incidence of recurring infections. CONCLUSIONS: A weight increase of at least 5% of body weight in previously undernourished patients is associated with a decreased incidence of death and may reduce morbidity events. Feeding impairments may affect ability of patients to gain weight, but dysphagia is associated with weight increase. Other nonnutritional variables of diagnosis, number of medications, and declining medical status also affect mortality and morbidity outcomes.

Accidental Falls↗
PubMed1993

Malnutrition in institutionalized elderly: how and why?

OBJECTIVE: To determine the prevalence of undernutrition and overnutrition in long-term care elderly patients and the functional, behavioral, environmental, nutritional, and medical variables associated with this prevalence. DESIGN: Cross-sectional, observational. SETTING: Long-term care hospital in Canada. SUBJECTS: Two hundred elderly patients (n = 166 male), average age 78.5 years. MEASUREMENTS: Assessment of nutritional status and presence of specific behavioral, medical, environmental, and functional characteristics known to impact on nutritional status. Nutritional status was determined by weight, % weight loss, BMI, skinfolds, arm circumference, area measurements, and % body fat. Multiple regression analyses were performed to identify the factors associated specifically with undernutrition and overnutrition in this population. RESULTS: Severe undernutrition was present in 18% (n = 36) and severe overnutrition in 10% (n = 20). Mild/moderate undernutrition was present in 27.5% (n = 55) and mild/moderate overnutrition in 18% (n = 36). Overnutrition was positively associated with primary diagnosis and number of medications and negatively associated with poor appetite, number of feeding impairments, protein intake, and mental state. Undernutrition was positively associated with dysphagia, slow eating, low protein intake, poor appetite, presence of a feeding tube, and age and negatively associated with primary diagnosis. CONCLUSIONS: Undernutrition exists at a level that is high (45.5%) but not unusual for this type of institutional setting. Behavioral, environmental, and disease-related factors greatly influence nutritional status. Undernutrition appears to be affected by nutritional factors more than overnutrition. Efforts should be directed toward influencing some of these factors to decrease undernutrition in the institutionalized elderly.

Aged↗
PubMed1990

From moclobemide to Ro 19-6327 and Ro 41-1049: the development of a new class of reversible, selective MAO-A and MAO-B inhibitors.

This study describes the serendipitous discovery of moclobemide, a short-acting MAO-A inhibitor which is in an advanced stage of clinical development as an antidepressant. The short duration of action of this MAO inhibitor containing a morpholine ring moiety is due to the complete reversibility (probably by metabolism of the inhibitory molecular species) of MAO-A inhibition. Since moclobemide is much more effective in vivo than expected from its in vitro activity, investigations to identify a possible metabolite(s) more active as MAO-A inhibitor than the parent compound were carried out. The study of the MAO inhibitory characteristics of several known and putative moclobemide metabolites did not allow the identification of a potent MAO-A inhibitor but led to the discovery of Ro 16-6491, a potent MAO-B inhibitor of novel chemical structure. Systematic chemical modification of the aromatic ring system of Ro 16-6491 finally provided Ro 19-6327 and Ro 41-1049 which are highly selective and reversible inhibitors of MAO-B and MAO-A, respectively. Tritiated derivatives of Ro 19-6327 and Ro 41-1049 were used in binding studies to elucidate their mechanisms of action and to study their cellular distribution by quantitative enzyme radioautography.

Animals↗
PubMed1990

[Surgery of the eyelid edge--references for general practice].

a) Punctum plasty (eversion of the lacrimal point): This simple method results in a permanently enlarged punctum. A 4-0 silk suture is passed through the vertical part of the canaliculus and the conjunctiva, drawing them together very tightly. The thread falls out after 4-6 weeks. b) Management of trichiasis: Electrolysis of misdirected lashes leads to contraction and renewed misdirection. This disadvantage is avoided by excising the lashes with a 1 mm trephine. The trephine must follow the direction of the lash exactly, so that a complete cylinder including the hair and root can be removed. The resulting small defect heals quickly without contraction.

Dacryocystorhinostomy↗
PubMed1990

Short-lasting and reversible inhibition of monoamine oxidase-A by moclobemide.

In ex vivo experiments, the time course of monoamine oxidase-A (MAO-A) inhibition after 10 mg/kg oral moclobemide was virtually the same for whole rat brains and liver: the onset was rapid, the maximum effect was obtained in 15 min, and the duration of action was short (about 16 h) compared with several days for the irreversible MAO inhibitors. The time course of MAO-B inhibition was peculiar: almost complete inhibition was obtained in the time only between the first and second hours, whereas in the whole brain, or various brain areas, maximum MAO-B inhibition (40%) did not occur until 2 h after drug administration. Inhibition in other peripheral organs, such as kidney and small intestine, was of even shorter duration (3 h). After even marked MAO-A inhibition in the liver by moclobemide, the activity recovered within about 4 h when the homogenate was dialysed against water or buffer at 37 degrees C. This rapid recovery is temperature-dependent and does not occur at 18 degrees C. The substance causing the marked inhibition of MAO-A activity when moclobemide is given is probably itself inactivated by the enzyme (reversibility by metabolism). It is expected that more insight into the mechanism of action of moclobemide will be obtained from the use of highly purified preparations of the MAO-A isoenzyme.

Animals↗
PubMed1989

[Comparison of the new MAO-A inhibitors moclobemide, brofaromine and toloxatone with tranylcypromine in an animal experiment: significance for clinical practice].

The rat studies presented in this manuscript show that the new non-hydrazine compounds moclobemide, brofaromine and toloxatone have a profile typical of monoamine oxidase-A (MAO-A) inhibitors. These inhibitors are short-acting (16-24 h), reversible, non-hepatotoxic and have only low liability to potentiate tyramine pressor effects (cheese-effect). The present results in rats and the clinical trials provide evidence that moclobemide is an orally active MAO-A inhibitor which, due to its remarkably low tyramine potentiating pressor effects and to its lack of anticholinergic activity, has a very attractive pharmacological profile. In contrast to moclobemide, tranylcypromine is an irreversible and mixed MAO-A and MAO-B inhibitor with long-lasting effects. This hydrazine derivative is not devoid of hepatotoxic effects and markedly potentiates tyramine pressor effects. Moclobemide, being a particularly safe MAO-A inhibitor, seems to be an effective new compound for the therapy of exogenous and endogenous depressive states.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1989

Preclinical profiles of the novel reversible MAO-A inhibitors, moclobemide and brofaromine, in comparison with irreversible MAO inhibitors.

Acceptance into clinical practice of monoamine oxidase (MAO) antidepressants requires unequivocal evidence that novel, non-hepatotoxic and reversible MAO-A inhibitors carry little or no risk of inducing severe hypertensive crises (cheese effect). This study summarizes the most relevant preclinical aspects which differentiate the novel reversible MAO-A inhibitors moclobemide and brofaromine, from previous irreversible MAO inhibitors of the old generation, particularly phenelzine and tranylcypromine. Moclobemide and brofaromine bear no chemical relation to irreversible inhibitors such as hydrazine derivatives (phenelzine) or aminocyclopropyl derivatives (tranylcypromine). Experiments in rats show that moclobemide and brofaromine increase the level of serotonin (5-hydroxytryptamine) and decrease that of 3,4-dihydroxyphenylacetic acid for only 16-24 hours. In vitro, moclobemide and brofaromine behave as mechanism-based, enzyme-activated inhibitors since their intrinsic inhibitory activity increases with the duration of their interaction with the enzyme in tissue homogenates. In contrast to irreversible monoamine oxidase inhibitors, which are much more potent in vitro than in vivo, moclobemide has the characteristic to be virtually equipotent in vitro and in vivo. MAO-A inhibition induced by moclobemide in the rat in vivo was rapidly reversed by simply incubating liver homogenates at 37 degrees C in the absence of the inhibitor, indicating a rapid metabolic inactivation of moclobemide in vitro. This reversibility is a distinctive feature of moclobemide, when compared with brofaromine or irreversible MAO inhibitors. Hepatotoxicity is not an inherent property of MAO inhibitors indeed, moclobemide or brofaromine, due to their chemical structures, cannot be converted into isopropyl hydrazine, the hepatotoxic metabolite of iproniazid suspected to induce liver necrosis. Results from preclinical and clinical investigations demonstrate that moclobemide and brofaromine, in contrast to tranylcypromine and phenelzine, very weakly potentiate the pressor effects of orally administered tyramine. In conclusion, the reversible MAO-A inhibitors moclobemide and brofaromine, due to their well-documented safety characteristics, to their lack of anticholinergic-effects and to their good tolerability, will provide innovative tools for clarifying the role of MAO-A inhibitors in the treatment of endogenous and atypical depressive states.

Animals↗
PubMed1989

Pre-clinical pharmacology of moclobemide. A review of published studies.

The novel antidepressant, moclobemide, is a reversible inhibitor of monoamine oxidase (MAO) preferentially of monoamine oxidise-A (MAO-A); it emerged for study out of a series of lipid-lowering agents. In spite of its weak MAO-A inhibition in vitro, moclobemide is a potent inhibitor of MAO-A, in vivo; its in vivo activity is of short duration, in contrast to the extremely long-lasting inhibition, e.g. by tranylcypromine. Moclobemide only slightly potentiates the pressor effect of oral tyramine in freely moving rats, again in contrast to tranylcypromine; it is not anti-cholinergic and is free of hepatotoxicity. Published evidence on the preclinical pharmacology is reviewed.

Animals↗
PubMed1989

Neurochemical profile of moclobemide, a short-acting and reversible inhibitor of monoamine oxidase type A.

Moclobemide belongs to a new generation of short-acting, reversible, monoamine oxidase (MAO) inhibitors. In vitro (rat brain homogenates) moclobemide inhibits MAO-A selectively with lower potency than many of the reference MAO inhibitors. However, when measured ex vivo in the rat, the potency of moclobemide is similar to that of reference compounds. In vivo the drug induces a dose-dependent, short-lasting (8-16 hr) and preferential inhibition of MAO-A in the brain and both MAO-A and MAO-B inhibition in extracerebral organs (liver, small intestine and kidney). In the extracerebral tissues of the rat moclobemide induces marked peripheral MAO-B inhibition due to rapid and extensive biotransformation of its morpholine ring. The active molecular species is probably the metabolite Ro 16-6491. The moderate MAO-B inhibition measured after moclobemide intake in human platelets indicates that only minor amounts of Ro 16-6491 are formed in humans. Virtually all metabolites of moclobemide so far identified have been tested in vitro and ex vivo in the rat and proved to be either equipotent or, mostly, less effective than moclobemide as MAO-A inhibitors. In liver homogenates of moclobemide-treated rats MAO-A activity recovers during dialysis or simple incubation at 37 degrees C, suggesting a biodegradation of moclobemide and/or the moclobemide-derived active metabolite(s) by MAO itself or a slow dissociation of the active inhibitory species from the enzyme. Similar to other MAO-A inhibitors, moclobemide induces an increase in the rat brain levels of 5-hydroxytryptamine, norepinephrine and dopamine and a concomitant decrease of their deaminated metabolites. These effects are of short duration (8-16 hr) and parallel the time course of MAO-A inhibition. Moclobemide administered subchronically down-regulates beta adrenoceptors as shown by binding experiments with brain cortical membranes using dihydroalprenolol as ligand. In vitro MAO inhibition by moclobemide is specific in that the compound does not affect other amine oxidases or monoamine uptake mechanisms; furthermore, it does not interact with various neurotransmitter or drug receptor sites. In conclusion, a large body of preclinical evidence characterizes moclobemide as a short-acting and reversible MAO-inhibitor. The neurochemical profile of moclobemide indicates clearly that this nonhydrazine nonhepatotoxic MAO-A inhibitor represents a novel and safe drug for treatment of affective disorders.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗