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Biomedical subjects

M Manandhar

Publications and source records attributed to M Manandhar.

10 recordsLinked to original sources
PubMed2002

The association between nutritional status and handgrip strength in older Rwandan refugees.

OBJECTIVES: To investigate the association between nutritional status and handgrip strength in older Rwandan refugees. DESIGN: Cross-sectional study. SETTING: Rwandan refugee camp located in Karagwe district in the north-west of Tanzania. The study was carried out in the post-emergency phase. The response rate was 85%. SUBJECTS: A total of 413 men and 415 women aged 50-92 y participated in the study. METHODS: Weight, height, mid-upper-arm circumference (MUAC) and triceps skinfold were obtained using standard techniques. For people with visible kyphosis, height was estimated from armspan using regression equations developed from non-kyphotic subjects within the sample. Handgrip was measured using a mechanical handgrip dynamometer. Information regarding physical activity and health status was obtained by interview and clinical screening. RESULTS: Handgrip strength (kg) was significantly higher in men than in women (30.3+/-6.7 vs 22.3+/-5.1), and significantly lower in each older age group in both sexes. Handgrip strength was positively correlated to BMI (body mass index) and AMA (arm muscle area). The relative risk of impaired handgrip strength in individuals with poor nutritional status (BMI<18.5 kg/m(2)) compared with those of adequate nutritional status was 1.75. After controlling for potential confounders (sex, age and height), BMI remained a significant contributor to the variation in handgrip strength. CONCLUSION: Poor nutritional status is associated with poor handgrip strength independent of sex, age and height, in this refugee population. This may indicate that underweight older people are likely to have more difficulties in functioning independently in the community. Research is needed to investigate if improving nutritional status can lead to better functional ability. SPONSORSHIP: Department for International Development (UK) and HelpAge International.

Aged↗
PubMed1998

The nutritional status of older Rwandan refugees.

OBJECTIVE: To assess the nutritional status of older people in an unstable situation. DESIGN: Anthropometric and socioeconomic data were collected cross-sectionally. Body mass index (BMI), arm muscle area (AMA) and arm fat area (AFA) were calculated to evaluate nutritional status. For 41 subjects with kyphosis, height was estimated from arm span using sex-specific regression equations from the non-kyphotic group. SETTING: The study was carried out in the post-emergency phase in a Rwandan refugee camp in Karagwe district, north-west Tanzania. SUBJECTS: Measurements were obtained from 413 men and 415 women aged 50-92 years. RESULTS: The prevalence of undernutrition (BMI < 18. 5) was 19.5% in men and 13.1% in women and was higher above age 60 years in both sexes: in men the prevalences were 23.2% and 15.0% (P < 0.05) and in women 15.1% and 10.9% for the older and younger age groups respectively. AMA, which is important in relation to the ability to remain active and independent, was also significantly lower in older age groups. No difference was found in AFA. The proportion with low BMI was much higher in the group with kyphosis. CONCLUSIONS: Even in this population of older Rwandans who managed to reach the camp and survive in exile for more than a year, undernutrition does occur and is more prevalent at an advanced age. The higher prevalence of undernutrition in kyphotic people illustrates the importance of including this group in nutritional status assessments.

Age Distribution↗
PubMed1996

The SH3-domain protein Bem1 coordinates mitogen-activated protein kinase cascade activation with cell cycle control in Saccharomyces cerevisiae.

The mating mitogen-activated protein kinase (MAPK) cascade has three major outputs prior to fusion: transcriptional activation of many genes, cell cycle arrest in the G1 phase, and polarized growth. Bem1 localizes near the cortical actin cytoskeleton and is essential for polarized growth during mating. Here we show that Bem1 is required for efficient signal transduction and coordinates MAPK cascade activation with G1 arrest and mating. bem1delta null mutants are defective in G1 arrest and transcriptional activation in response to mating pheromone. Bem1 protein stimulates Fus3 (MAPK) activity and associates with Ste5, the tethering protein essential for activation of the MAPK kinase kinase Ste11. Bem1-Ste5 complexes also contain Ste11, Ste7 (MAPK kinase), and Fus3, suggesting that Ste5 localizes the MAPK cascade to Bem1. Strikingly, Bem1 also copurifies with Far1, a Fus3 substrate required for G1 arrest and proper polarized growth during mating. These and other results suggest that Bem1 may cross-link the Ste5-MAPK cascade complex to upstream activators and specific downstream substrates at the shmoo tip, thus enabling efficient circuitry for G1 arrest and mating.

Adaptor Proteins, Signal Transducing↗
PubMed1988

Methotrexate: assessment of in vivo clastogenicity and carcinogenicity.

The genotoxic and oncogenic potentials of methotrexate were studied in Sprague-Dawley rats. The rats received 0.1, 0.2, or 0.4 mg/kg of methotrexate as dietary admixtures on a 5 days on, 9 days off, regimen for 23 months. In the females of the high-dose group, there was a significant increase in mortality starting at 18 months. Significant increases in the number of rats with focal pulmonary interstitial fibrosis were seen in both sexes at the high-dose level. At the mid- and high-dose levels of both sexes, there was a significantly increased number of rats with myeloid and erythroid bone marrow hypoplasia. There was no evidence of either early onset or increased incidence of any tumor type in the treatment groups. Therefore, it is concluded that methotrexate does not have oncogenic potential. Also, at terminal sacrifice, bone marrow cells were harvested from selected animals on the last day of the 5-day dosing cycle and cytogenetic evaluation was performed. No significant increase in chromosomal aberrations was seen in any dose group relative to the control group. This observation further substantiates the absence of oncogenic potential due to methotrexate in rats.

Animals↗
PubMed1987

A guide for mutagenicity testing using the dominant lethal assay.

The dominant lethal assay has been used and continues to be used to provide information about the effects of chemicals on the gonadal cells of male animals. Guidelines for conducting this test are useful but as with any guideline scientists should avoid interpreting them as protocols. Thus this document is a general approach to dominant lethal testing and should be used in conjunction with other available protocols and procedures.

Animals↗
PubMed1987

Control of epidemic group A meningococcal meningitis in Nepal.

During the first six months of 1983, an epidemic of serogroup A meningococcal meningitis occurred in the Kathmandu valley of Nepal, resulting in 875 cases and 95 deaths. The annual attack rate was 103 cases per 100,000 population, with a peak attack rate occurring in April. Epidemic meningococcal disease had not been recognized previously in Nepal. Early in 1984, a review of hospital-based data on pyogenic meningitis in Kathmandu showed three times as many cases per month compared with the same period the previous year, suggesting that a recurrent epidemic was unfolding. Beginning in February 1984, a vaccination campaign directed at a high-risk target population of people aged 1-24 years was launched; over 329,000 doses of bivalent A/C meningococcal vaccine were given, achieving approximately 64% coverage of the target population. A dramatic decline in the number of new meningitis cases occurred coincident with the initiation of the mass vaccination campaign. This experience demonstrates that it is possible, with appropriate surveillance efforts, to detect an evolving epidemic of meningococcal disease early in its course and to institute control measures in advance of the expected epidemic peak.

Adolescent↗
PubMed1986

Genetic toxicology evaluation of the novel semi-synthetic antibiotic piperacillin.

Piperacillin (T-1220, Pipracil) a semi-synthetic antibiotic was evaluated in a battery of genetic toxicology assays. The assays employed were: the microbial assay, the host mediated assay, the microbial assay incorporating urine samples from mice dosed with piperacillin, the in vivo cytogenetic assay, and the dominant lethal assay. In all assays, piperacillin produced consistent negative results indicating that piperacillin does not have mutagenic potential.

Animals↗
PubMed1986

Genetic toxicology profile of the new antineoplastic drug mitoxantrone in the mammalian test systems.

As part of safety evaluation and drug development, 1,4-dihydroxy-5,8-bis[[2-[(2-hydroxyethyl) amino]-ethyl]amino]-9,10-anthracenedione dihydrochloride (mitoxantrone, NSC 301739, CL 232,315, Novantrone) was tested in the mammalian test systems to determine its mutagenic potential. Mitoxantrone produced significant clastogenic effect in bone marrow of rats treated for 5 days at greater than or equal to 0.5 mg/kg i.p. It produced apparent increases in DNA repair in the rat hepatocyte UDS (unscheduled DNA synthesis) test and increased SCEs (sister chromatid exchanges) in CHO cells and mutant frequencies in mouse lymphoma assay. In the cell transformation test using C3H/10T 1/2 cl 8 cells, mitoxantrone did not produce significant increases in type II or type III transformed foci. In the dominant lethal test in rats, mitoxantrone administered 2 mg/kg/d i.p. affected matings of treated males, however, total implantations as well as early deaths resulting from matings with surviving males were unaffected. These results show the potential of mitoxantrone to produce genetic activity in vitro and in the somatic cells in vivo but inability of the drug to cause morphological transformation in vitro or genotoxic effect in the germinal cells in vivo. The biological significance of findings such as above is uncertain. Examination of genetic end-points such as chromosomal assays in rodents on life time studies which are currently being completed will delineate the significance, if any, of these findings.

Animals↗
PubMed1985

Current status of bioassays in genetic toxicology--the dominant lethal assay. A report of the U.S. Environmental Protection Agency Gene-Tox Program.

The term dominant lethal may be defined as death of the heterozygote arising through multiple chromosomal breaks. The assay is generally conducted by treating male animals, usually mice or rats, acutely (1 dose), subacutely (5 doses), or over the entire period of spermatogenesis. Animals treated acutely or subacutely are mated at weekly intervals to females for a sufficient number of weeks to cover the period of spermatogenesis. Those treated for the entire spermatogenic cycle are mated for 1 or 2 successive weeks at the termination of treatment. Females usually are killed at 14 days of pregnancy and examined for the number of total implantations in the uterus, the number of implantations classified as early deaths, and, in some cases, the number of corpora lutea. The category of early death is the most significant index of dominant lethality. A total of 249 papers were reviewed and 140 chemicals were evaluated. Of the 140 chemicals, 65 were positive by the criteria used by the Work Group in evaluating each publication. The category of "positive" includes those responses of a borderline nature. 99 chemicals were declared negative. There is considerable overlap of chemicals in both categories, which accounts for the incongruity in the total number of chemicals tested and the number considered positive and negative. A total of 44 animal carcinogens have been tested in the dominant lethal assay, 26 of which were positive and 18 negative for a correlation of 59%. The role of the assay should be that of confirming positive results from lower tier chromosomal aberration-detecting systems (confirming in the sense of indicating the ability of the chemical to penetrate gonadal tissue and to produce cytogenetic damage). The dominant lethal assay should not be used as a risk assessment method.

Animals↗