Kamala Krishnaswamy

Development and testing of a quantitative food frequency questionnaire for use in Kerala, India

OBJECTIVE To develop and test a food frequency questionnaire (FFQ) for use in rural areas of Kerala, India. DESIGN Based on food use and market surveys of the study area, a quantitative 81-item interviewer-administered FFQ was developed. A validation study was conducted consisting of 24-h diet recalls (24HR) administered on 8 days randomly selected over an entire year and two administrations of the FFQ, one at the beginning of the 1-year period and the other at the end. FFQ and 24HR-derived nutrient scores were compared using correlation and regression analyses and by examining differences in the nutrient scores. SETTING Rural villages in Ernakulum district, Kerala, South India. SUBJECTS In each of 30 households, the male head of household and female food preparer were enrolled. RESULTS Pearson (parametric) correlation coefficients (r(p)) averaged about 0.50 in comparing nutrient scores derived from the 24HR with those from the first FFQ and about 0.55 in comparing the second FFQ. On average, Spearman correlation coefficients (r(s)) were slightly lower than the r(p) in comparing the scores derived from the first FFQ, but virtually identical for the second FFQ. Regression analyses indicated better agreement in the comparison of the 24HR-derived scores with the first FFQ than the second FFQ. Difference scores, however, tended to be larger in comparing the first FFQ scores with the 24HR. CONCLUSIONS This FFQ produces results broadly comparable to those used in Europe and North America, indicating its suitability for comparing exposures within a study population in reference to health-related endpoints.

GENU VALGUM AND OSTEOPOROSIS IN AN AREA OF ENDEMIC FLUOROSIS

Twenty-four male patients with genuvalgum deformity drawn from an area of endemic fluorosis in Andhra Pradesh, India, were investigated clinically, radiologically, and biochemically. All had evidence of spinal osteosclerosis along with extensive osteoporotic changes in the bones of the extremities. Levels of serum calcium, phosphorus, and alkaline-phosphatase activity were normal. It is concluded that deficiency of several nutrients may modify and aggravate the toxic effects of chronic fluoride intoxication. Hormones may play a part in the causation of the syndrome.

Validation of hemoglobin estimation using hemocue

Objective : This piece of work is an attempt to compare Hemocue and Cyanmethemoglobin methods for hemoglobin estimation.Methods : In 100 apparently healthy children of 1–6 years of age, Hb was estimated using Hemocue and cyanmethemoglobin methods from finger prick blood sample. The results, obtained by the two methods were compared using appropriate statistical methods.Results : Mean ±SD values for hemoglobin (g/dl) were 9.33 ±2.719 by Hemocue and 8.14 ±2.448 by cyanmethemoglobin method. When assessed by Hemocue method the proportion of children with anemia was 66% while it was 88% with cyanmethemoglobin method. The sensitivity of Hemocuc method was 0.75 and specificity 1.0 considering cyanmethemoglobin method as gold standard. The corresponding values by cyanmethemoglobin method for a given Hemocue value fell within the Mean difference ±2 SD with correlation coefficient being r = 0.922. Despite the good association, the two methods agreed, the magnitude of difference being -1.19 g/dl (CI: -1.40 to —0.98) thus suggesting an overestimate of hemocue values ranging from 10 to 15%. A correction factor was arrived for converting Hb values obtained by Hemocue method to arrive at the expected value by the reference method, this factor being 0.389 + 0.831 Hb (Hemocue).Conclusion : As there are limitations expressed for both the methods in accurately estimating Hb, it is difficult to decide whether one is an overestimate or the other an underestimate. By virtue of the principle involved in estimating Hb, cyanmethemoglobin method may be taken as an indirect indicator of iron status. However, it is not clear whether such a principle is involved in estimating Hb by Hemocue. Therefore, these two methods need to be further validated against a sensitive and specific indicator for iron status like circulating transferrin receptor to decide which of the methods can be used to accurately determine the prevalence of iron deficiency anemia in the community

Undernutrition and tetracycline half life

The plasma half life of tetracycline hydrochloride was determined in groups of well-nourished and undernourished subjects employing two dosage schedules and two routes of administration, namely oral and parenteral. Protein binding of the drug was estimated and relative volume distribution was calculated. The results indicated that in undernourished subjects, the half life of tetracycline hydrochloride, protein binding and relative volume distribution were all significantly low as compared to well-nourished subjects. The elimination rate was considerably higher in the undernourished groups, which accounted for the shorter half life. These data suggest that to maintain adequate serum concentrations of the drug in undernourished subjects, tetracycline needs to be given at more frequent intervals.

The Effect of Malnutrition on the Pharmacokinetics of Phenylbutazone

SummaryThe pharmacokinetics of Phenylbutazone were studied after a single oral dose of 6mg/kg bodyweighl in 35 adult male subjects with differing nutritional status.The elimination half-life was significantly shorter and plasma clearance accelerated in undernourished patients who had significant weight deficit and low serum albumin concentration. Plasma protein binding was only 86% compared with 95 to 96% in normal subjects (smokers and non-smokers). The apparent volume of distribution was also higher in undernourished patients. Significant correlations were observed between serum albumin, protein binding and bodyweight.Multiple regression analysis of the data indicated that altered drug protein binding partially contributed towards variation in half-life and clearance; and the plasma albumin concentration significantly influenced the amount of drug bound in plasma.The results indicate that nutritional status is one of the important environmental variables that can alter drug kinetics and disposition in man. Further studies, including measurement of steady-stale plasma concentrations of various other drugs, are necessary to elucidate drug kinetics in malnourished subjects.

Glutathione S-transferase Mu (GST Mu) deficiency and DNA adducts in lymphocytes of smokers

The effect of smoking on DNA adduct formation in lymphocytes was analysed in individuals with low (deficient) and high (non-deficient) glutathione S-transferase (class Mu) activity. DNA adduct levels in lymphocytes were determined by the highly sensitive nuclease P1-enhanced 32P-postlabeling assay. The lymphocyte DNA adducts/10(8) nucleotides of smokers deficient in glutathione S-transferase Mu activity (n = 12) were significantly higher than those of smokers non-deficient (n = 9) in glutathione S-transferase Mu activity. The DNA adduct levels of the lymphocytes inversely correlated with glutathione S-transferase Mu activity. A correlation was found between DNA adduct levels and daily cigarette consumption. Results of the present study suggest that individuals deficient in glutathione S-transferase Mu activity may be at greater risk of DNA damage.

Drug metabolism and pharmacokinetics in malnutrition

Malnutrition is one of the major public-health problems of the Third World and several million people are underfed and suffer from deficiencies of essential nutrients. Drugs, though not an answer to the problem of malnutrition, do play an essential role in various health projects. However, nutrient-drug interactions, particularly in humans, have attracted very little attention. Only recently have data accumulated to indicate that under-nutrition and malnutrition have great potential for altering drug metabolism and disposition, which may have direct clinical relevance. The pathophysiological changes encountered in both macro- and micro-nutrient deficiencies are such that they can interfere with pharmacokinetic and pharmacodynamic processes in the body which may result in altered drug response. Studies in laboratory animals and in malnourished human subjects indicate that dietary factors and nutritional status considerably influence absorption, plasma protein binding, distribution, biotransformation and excretion of drugs. Therapeutic response and toxicity are therefore likely to be altered. Data obtained show that the doses and dosage regime in the under-nourished or malnourished depend on three factors, namely environment, patient and the drug concerned. A wide variety of environmental factors, operating at different levels, and their interaction with the complex problem of malnutrition, of varying types and severity, need to be considered and evaluated properly in the under-nourished population.

Effect of food on bioavailability of chloroquine

SummaryThe bioavailability of chloroquine in 7 healthy adult male volunteers was assessed with and without a standard breakfast. Chloroquine (600 mg base) was administered orally and timed blood samples were obtained for determination of plasma concentrations. The results suggest that the AUC and peak plasma levels were significantly higher when chloroquine was administered together with food, although the rate of absorption was not different. It appears, therefore, that food facilitates chloroquine absorption and the extent of absorption is significantly modified. Hence administration of chloroquine together with food appears to be an advisable clinical practice.

Failure to produce atherosclerosis in Macaca radiata on a high-methionine, high-fat, pyridoxine-deficient diet.

Accelerated atherosclerotic lesions are observed in genetic defects characterised by marked homocystinaemia as a result of low levels of cystathionine synthase, a pyridoxal phosphate-dependent enzyme. Attempts were therefore made to induce atherosclerosis in Macaca radiata, maintained on a high-protein, high-methionine and high-fat diet by inducing pyridoxine deficiency with deoxypyridoxine. Pyridoxine deficient monkeys failed to show any biochemical or pathological evidence of atherosclerosis, despite a significant decrease in the activity of hepatic cystathionine synthase.

Chloroquine kinetics in the undernourished

SummaryThe plasma and whole blood kinetics of chloroquine was studied in 7 normal and 8 undernourished subjects following a single oral dose of 600 mg. The terminal half-lives were similar in both groups. The AUC was also similar in the 2 groups, even though a higher dose per kg body weight was administered to the undernourished. This was probably because of faster clearance in this group. Chloroquine uptake by erythrocytes, its main site of action in malaria, was also comparable in the two groups. The plasma concentration of chloroquine over a period of time was found to be similar in 4 normal and 4 undernourished subjects following administration of 1.5 g of the drug in divided doses. The undernourished appear, therefore, to handle chloroquine in such a way that they do not suffer a greater risk of toxicity than normals.