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We retrieved a series of measurements made 35 years ago of the concentration of inorganic phosphate (P) in the serum from 56 cases of severe protein-energy malnutrition at the Tropical Metabolism Research Unit, Jamaica. There is no record of whether or not the cases were randomly selected. The samples were obtained within 4 days of admission and except in 3 cases there was no follow-up. The average age was 12 months. The children have been classified retrospectively from the notes as marasmus (11 cases), kwashiorkor (22 cases) and marasmic kwashiorkor (23 cases). In all 11 children died (fatality rate 20%), eight of them from the group with marasmic kwashiorkor. Weight-for-age, length-for-age and weight-for-length have been calculated as Z-scores. Nearly all serum phosphate concentrations were low (mean 1.41 mmol.l-1, SD 0.444, range 0.50-2.45) compared with the normal value at this age of about 2 mmol.l-1. The serum P was significantly less depressed in the marasmic children (P = 0.042), but there was no relation between serum P and any of the anthropometric measurements, nor with outcome (death or survival). There was, however, a significant relationship with the degree of oedema. Death was related to age--the children who died were younger (mean difference 3.8 months; P = 0.01; 95% confidence interval 0.23-6.43). It took about 3 weeks of feeding a milk-based diet for serum phosphate to reach normal levels. There have been few previous measurements of serum P in malnutrition.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects and interactions between pH and CitriC acid concentration on the inactivation of Listeria monocytogenes was determined using a three-strain mixture. Citric acid/sodium citrate combinations were added to brain heart infusion (BHI) broth to achieve concentrations of 0.1, 0.5, 1.0 and 2.0 M in conjunction with pH values of 4, 5, 6 and 7. The media were dispensed in 20-ml portions in dilution bottles, inoculated to approximately 10 8 CFU/ml, and incubated at 28°C. Survivor curves were generated using a linear model incorporating a lag term, and D-values and "time to 4-D inactivation" values were calculated. The results were compared against control cultures in which the pH was modified using hydrochloric acid (HCI). The rate of inactivation was dependent on both the pH and concentration of citric acid. Low levels of citric acid were protective, particularly at pH 5 and 6. At higher concentrations, a distinct anion effect was observed as compared to the HCl controls, with inactivation rates being correlated with the completely undissociated form of the acid. Comparison of the kinetic data with earlier results with lactic and acetic acids suggests that citric acid has both protective and bactericidal activity against L. monocytogenes , which involve different modes of action.

The autopsy records of 115 children with severe protein-energy malnutrition were reviewed. Sections of the lung histology showed evidence of bacterial pneumonia in 49% of cases. An additional 18% showed bronchitis, bronchiolitis or interstitial pneumonitis. Aspiration of gastric contents was evident in 10% of cases; 6% showed pulmonary oedema and congestion. In the remaining cases, no lung pathology was identified (17%). In 8 cases, rapid autopsy examination permitted fixation of lung tissue for electron microscopy. These included 4 cases of bronchopneumonia, one of which was associated with viral pneumonia. Another interstitial pneumonitis, probably of viral aetiology, was also studied. Both these virus-associated cases showed loss of type I pneumocytes and hyperplasia of type II pneumocytes. Another patient with herpes simplex hepatitis showed necrotic emboli in pulmonary capillaries with virions, as well as colonies of interstitial bacteria. One patient with acute pulmonary oedema displayed severe endothelial cell swelling on electron microscopy. In one case, there was no evidence of respiratory changes, apart from desquamation of type I pneumocytes. Useful information can be obtained on the fine structure of the lung, using samples taken soon after death.

Liver specimens obtained immediately after death from eight severely malnourished children were examined by electron microscopy, and compared with seven liver biopsy specimens from children who had recovered from malnutrition. The liver cells from the fatal cases showed mitochondrial swelling, with coarse densities in the matrix, cholestasis, depletion of the endoplasmic reticulum and Golgi apparatus, diminished glycogen stores, prominent lipid deposits and focal cytoplasmic degradation. The nucleoli were enlarged. There was marked reduction in peroxisomes. In contrast, the biopsies from recovering children showed good cellular organisation, and a normal frequency of peroxisomes. Multiple factors, including sepsis, may lead to depletion of peroxisomes. Loss of peroxisomes may interrupt beta-oxidation of long-chain fatty acids and accentuate the accumulation of lipid. Moreover, a reduction in the concentration of catalase may remove one avenue for the detoxification of free radicals. As the concentration of other anti-oxidants, notably glutathione, is also reduced, free radical damage may occur, leading to lipid peroxidation of membranes, mitochondrial damage, pump failure and influx of water and electrolytes into the cell.

1. Cytokine production in vitro was assessed in 16 malnourished children, before and after nutritional recovery. 2. Tumour necrosis factor-alpha and interleukin-6 were measured in whole blood after lipopolysaccharide stimulation. 3. The total amount of both cytokines was significantly less after 24 h incubation among malnourished children when compared with the same children after nutritional rehabilitation. 4. Cytokine production in vitro is impaired in severely malnourished children.

Although malnourished children are stunted, their bone maturity is usually retarded to a comparable degree. This is seen in impoverished societies as well as in diseases such as coeliac disease, inflammatory bowel disease and hormonal deficiency. When these children are followed to adulthood they normally have some degree of spontaneous catch-up. With a change in environment, through adoption, emigration or with treatment of the disease there is usually definite catch-up growth, although it is often not to the NCHS standards. If puberty is delayed and/or growth continues into the early or mid twenties, then an acceptable final adult height is achieved. However, there may be a limitation imposed on an individual's maximum height by genetic imprinting in very early development. This may be the case where full catch-up appears to have taken place but is followed by an advanced puberty and early cessation of growth (Proos, Hofvander & Tuvemo, 1991a). The data from US slaves and cases of hormonal replacement, where treatment was initiated after age 18, each show that, if the circumstances of children in the Third World change, almost complete reversal of stunting is possible. The children can reach their own height potentials. Total reversal to affluent societal norms would probably require cross-generational catch-up. The most obvious reason why catch-up is not seen regularly is that an appropriate diet is not available over a sufficient period of time. We do not know the optimum ingredients for such a diet. Sulphur has been neglected as an essential nutrient; its economy should be examined in relation to skeletal growth in stunted populations.

Significant hormonal changes have been reported in childhood malnutrition, including high serum levels of growth hormone and cortisol, and low levels of circulating insulin. The ultrastructure of the endocrine pancreas in such patients has hitherto not been reported. A light microscopy survey of the pancreatic islets was carried out on 69 malnourished children dying from protein-energy malnutrition. In seven of these cases, a rapid autopsy protocol allowed tissues to be fixed for electron microscopy within 75 minutes of death. This paper presents the first ultrastructural observations on the Islets of Langerhans in childhood protein-energy malnutrition. In all cases, there was a variable degree of degeneration of all cell types with membrane damage, loss of ribosomes, vesiculation and mitochondrial swelling. In addition, the B-cells showed a high proportion of precursor granules compared to crystal forms, possibly accounting for low insulin serum levels reported by other workers. It is suggested that islet cell changes may be related to free radical damage secondary to depletion of glutathione and other antioxidants, as well as relative deficiencies of cysteine and zinc. In addition, the effects of agonal anoxia, and a short fixation delay after death must be considered.

Glutathione S-transferases (GSTs) are principally involved in detoxification. These enzymes can be induced by an increased flux of substrate, such as occurs during pro-oxidative stress or antioxidant deficiency. We tested the hypothesis that the postulated oxidative stress in severe malnutrition would result in induction of GSTs in erythrocytes. Erythrocyte GST activity towards 1-chloro-2,4-dinitrobenzene (CDNB) was measured in 271 malnourished children (22 undernourished; 92 marasmic; 82 kwashiorkor; 75 marasmic-kwashiorkor) and 48 healthy children. GST activity in the malnourished children was significantly higher than the control group (P < 0.01). The GST activity in the four classes of malnutrition did not differ. There was a weak relationship between GST activity and the height deficit, but not with the weight deficit, or the clinical features displayed by the children. The 11 children that died had a higher value than the survivors. There was no change in GST with anthropometric recovery. We conclude that erythrocyte GST has been induced in children with malnutrition. Induction of erythrocyte GST may be the result of exposure of the children to oxidative stress during the months prior to their presentation with severe malnutrition.

The effects of pH and lactic acid or acetic acid concentration on Listeria monocytogenes inactivation were studied in brain heart infusion broth using a three strain mixture. Combinations of lactic acid/sodium lactate and acetic acid/sodium acetate were used to achieve concentrations of 0.1, 0.5, 1.0, and 2,0 M in conjunction with pH values of 4.0, 5.0, 6.0, and 7.0. Cultures adjusted with HCl to pH 3.0 to 7.0 in 0.5 pH unit intervals were used as 0.0 M controls. Each pH/concentration combination was inoculated to a level of 10 8 CFU/ml and incubated at 28°C for up to 60 d. Bacterial populations were determined periodically by plate counts. Inactivation was exponential after an initial lag period. Survivor curves (log# versus time) were fitted using a linear model that incorporated a lag period. The model was subsequently used to calculate D values and "time to a 4-D (99.99%) inactivation" (t 4-D ); t 4-D values were directly related to pH and inversely related to acid concentration. At acid/pH combinations that supported growth, the level of the organism increased slightly (2- to 10-fold) before declining. In the HCl-adjusted controls with pH's ≤5.5, the rate of inactivation was linearly related to pH. In the presence of the monocarboxylic acids, the duration of the lag period and the rate of inactivation were dependent on the pH, as well as the identity and concentration of acid. 4-D inactivation times were related to the level of undissociated lactic and acetic acids. That relationship was described by the equations, t 4-D = exp (-0.1773*LA 0.5 + 7.3482) and t 4-D = exp (-0.1468*AA 0.5 + 7.3905) for lactic and acetic acids, respectively, where LA and AA are mM of undissociated acid. These relationships were used in conjunction with the Henderson-Hasselback equation to develop a model for predicting the rate of inactivation as a function of pH and total organic acid concentration.

1. The responses of plasma levels of C-reactive protein and serum amyloid A were assessed in two groups of malnourished children. 2. Sixty-six severely malnourished children were studied at admission. Fifty of these had clinical and/or laboratory evidence of infection. C-reactive protein was not elevated in 23 (46%) and serum amyloid A was not raised in 29 (58%) of these 50 children. 3. Surviving children (n = 62) received two doses of diphtheria-pertussis-tetanus vaccine, to which the C-reactive protein and serum amyloid A responses were measured. The first was given early in recovery, the second after nutritional rehabilitation. Ten mildly malnourished children acted as controls, receiving a single dose of diphtheria-pertussis-tetanus vaccine. 4. The responses of both C-reactive protein and serum amyloid A to diphtheria-pertussis-tetanus vaccine were significantly less in early recovery than after nutritional recovery. The response of the mildly malnourished group was no different from that of the severely malnourished group in early recovery, but was less than their response on discharge. 5. The acute-phase protein response of malnourished children is impaired. This may have prognostic implications as the response plays a central role in promoting healing.

Pyridinoline (PYD) and deoxypyridinoline (DPD) are cross-linking aminoacids of collagen that are located mainly in bone and cartilage. When bone matrix is resorbed these cross-links are quantitatively excreted in the urine and therefore represent specific markers. We have measured the urinary excretion rate of PYD and DPD in 46 severely malnourished boys to assess their skeletal turnover and to relate this to their subsequent rate of growth. The children were aged 13 months (SD 6), and height-for-age was -3.6 (1.6) Z-score, and weight-for-height was -2.4 (0.8) Z-score. PYD excretion when malnourished and after "recovery" was 11.2 (4.6) nmol h-1m-2 and 32.2 (10.8) nmol h-1m-2 and DPD excretion was 2.6 (1.3) nmol h-1m-2 and 7.5 (3.0) nmol h-1m-2, respectively. The ratio of the two cross-links did not change with recovery. These data show that cartilage and bone turnover is much lower in the malnourished than in the recovered child. There was no difference in the degree of depression of turnover between the children with marasmus, marasmic-kwashiorkor, or kwashiorkor. The rate of height gain during recovery was significantly related to cross-link excretion, age, and weight-for-height on admission. These three factors accounted for 44% of the variance in the height velocity of the children. PYD and DPD excretion rate could be used to assess therapeutic interventions designed to alleviate stunting.

Immunosuppression increases the susceptibility to infection and changes the inflammatory response in children with severe protein-energy malnutrition. In this 5-year prospective study bacteremia was documented in 16% of 336 severely malnourished children, 2 to 34 months of age, who were hospitalized consecutively in the Tropical Metabolism Research Unit, Kingston, Jamaica. The 53 children had 60 episodes of nosocomial and community-acquired bacteremia with 69 blood isolates. Community-acquired bacteremia accounted for 72% (43 of 60) of bacteremic episodes. Thirty-five percent (24 of 69) of the strains were coagulase-negative staphylococci, 19% (13 of 69) were Staphylococcus aureus and 11% (8 of 69) were Streptococcus Group D. Seventeen episodes of coagulase-negative staphylococcal bacteremia were acquired in the community and 7 were nosocomial. These patients were more likely to have pneumonic consolidation than children with all other bacteremias combined (P < 0.02, Fisher's exact test). The bacteremia-related case fatality rate was 8% (5 of 60). Polymicrobial and Gram-negative septicemia were independent positive predictive factors for mortality when compared with single-agent and Gram-positive sepsis (P < 0.02). This 71% (49 of 69) prevalence of Gram-positive organisms suggests a change in the epidemiology from the predominant Gram-negative etiologies (76%) described in previous reports.

During recovery from severe wasting, malnourished children gain weight at greatly accelerated rates. To determine if additional zinc added to their basal therapeutic diets increased the retention of lean tissue and stimulated protein metabolism, we studied three groups of children taking either the basal diet alone or the basal diet supplemented with either 76 mumol (5 mg) or 153 mumol (10 mg) Zn/kg diet. The zinc-supplemented children gained similar weight and consumed the same amount of diet as the unsupplemented children. Zinc supplementation resulted in a greater net absorption of nitrogen and a higher rate of protein turnover, as estimated from urinary ammonia 15N enrichment after oral [15N]glycine. We conclude that additional zinc affected the composition of newly synthesized tissue and intermediary nitrogen metabolism.

Histological sections of pancreas and liver from 65 cases of children dying from childhood malnutrition were reviewed. The extent of pancreatic atrophy and fibrosis was compared with fatty change in the liver. Pancreatic atrophy was common, and often associated with severe fatty change in the liver, but also occurred in marasmic children with scanty liver fat. Pancreatic fibrosis, when present, was only of mild degree. Among 16 patients with marasmus, fibrosis was only seen in one pancreas. Fibrosis was recorded in 8/25 cases of kwashiorkor, and in 7/24 cases diagnosed as marasmic-kwashiorkor. Electron microscopy of the pancreas was performed in seven cases, using tissue collected at immediate autopsy. Atrophy and variable amounts of degranulation of acinar cells were seen. There was often disorganization of the endoplasmic reticulum with intracisternal sequestration. Mitochondrial swelling was consistent with terminal anoxia. Centro-acinar cells were prominent. Some acini were dilated and contained fibrillar material. These findings support the pioneer paper by Blackburn and Vinijchaikul (1969) and underline the importance of pancreatic atrophy in the pathology of protein-energy malnutrition.

We report a case of herpes simplex hepatitis in a child with edematous malnutrition. Electron microscopy showed virus in parenchymal cells, with pulmonary embolization of necrotic, infected hepatic cell fragments. Systemic dissemination of herpes simplex may be related both to the profound immunoincompetence associated with kwashiorkor and to a reduction in the circulating and fixed polyanions that normally inhibit viral attachment to cells.

The rate of exposure to geohelminth infection of children living in 2 institutions in Jamaica, West Indies, was estimated from the product of their rates of ingestion of soil and the density of parasite eggs in the environment. The estimated mean rate of egg ingestion was 9-20 Ascaris lumbricoides eggs and 6-60 Trichuris trichiura eggs per year, although the distribution was highly overdispersed so that some individuals had an estimated annual exposure of several hundred eggs. The estimated individual rates of exposure correlated significantly with the observed worm burdens in children at one of the homes, but not at the other. It is suggested that the susceptibility of the children and the distribution of infective stages in the environment may be important in determining the relationship between exposure and the rate of acquisition of infection.

A new classification of essential nutrients is proposed based on whether the major response to a deficiency is either (a) specific defects which lead to loss of particular functions and characteristic clinical signs and symptoms or (b) a primary cessation of growth. Diagnosis of deficiency of the nutrients which give rise to growth failure (nitrogen, essential amino acids, potassium, sodium, phosphorus, sulphur, zinc, magnesium) is particularly difficult because of the nature of the response and the lack of a body store. The implications of the differences in the types of deficiency are explored in relation to assessment of the likelihood that widespread deficiency exists. Poverty is particularly likely to be associated with unrecognised deficiency of these "growth" nutrients because of the monotony of the diet. This will lead to slow growth. There is probably a difference in the nutrient requirements for longitudinal and ponderal growth. Of the growth nutrients sulphur is likely to be required in much higher amounts for skeletal growth than soft tissue growth.

In a study of the pathogenesis of the oedema of kwashiorkor the ultrastructure of the kidneys from 6 children was examined shortly after they died from oedematous malnutrition. There was a generalised effacement of the glomerular epithelial cells onto the basement membrane. The filtration slits that remained were narrowed. The picture was similar to that seen in minimal-change nephrotic syndrome--but none of the children had albuminuria. The degree of effacement was statistically related to treatment with gentamicin. The findings suggest that there is a defect in the anionic charge of the glomerular basement membrane in oedematous malnutrition, that the membrane charge is more easily neutralised by cations such as gentamicin, and that, because proteinuria is not a feature of oedematous malnutrition, the proteinuria in other conditions associated with glomerular epithelial cell effacement (eg, minimal-change nephrotic syndrome) is due to something more complex than simple loss of charge.

The effect of a controlled stress (DPT inoculation) on the hormonal control of glucose homeostasis was investigated in children nutritionally rehabilitated from severe malnutrition. The age range of the 15 children studied was 6-26 months. Plasma insulin (INS), growth hormone (GH) and interleukin-1 (IL-1) were measured by radioimmunoassay; plasma glucose (GLU) by a glucose oxidase method; and red cell insulin binding (%SB) was determined, using A-14 monoiodinated insulin. Measurements were made on two occasions: (T-0) at 10 a.m., 12 hr before DPT inoculation, and (T-36) 36 hr. after inoculation. On both occasions, 4 hr post-prandial blood samples were used, and the mean body temperature (T) on the day of the test was determined. Red cell insulin binding (%SB) was significantly higher at T-36 than at T-0 (16.8 +/- 1.7 vs 12.1 +/- 1.2 (14), p = 0.005). (Results were expressed as mean +/- SEM, numbers of paired observations in parentheses). The higher %SB after DPT was accompanied by an increase in the number of receptor sites (S) (29.05 +/- 6.5 vs 15.6 +/- 2.5 (14), p = 0.025). However, insulin receptor affinity (K x 10(9) M-1) was decreased (0.7 +/- 0.1 vs 1.5 +/- 0.3 (14), p = 0.008). There were no significant differences in the plasma levels of insulin, glucose and interleukin-1, but plasma growth hormone (microU/ml) was increased after DPT, (18.0 +/- 3.0 vs. 11.5 +/- 1.2 (13), p = 0.04). Body temperature (degree C) was also significantly increased after DPT, (99.6 +/- 0.4 vs. 98.3 +/- 0.2 (14), p = 0.006).(ABSTRACT TRUNCATED AT 250 WORDS)

Red cell insulin binding was studied in 13 Jamaican children (age range 4-24 months), while malnourished (MAL), during early recovery (GI), late recovery (GII), and after anthropometric recovery (REC). The rate of weight gain (RW), the energy intake (EN), and the protein intake (PR) were monitored at each phase of the study. Four-hour fasting blood samples were used, and the insulin binding characteristics were investigated in the physiological range of insulin concentrations (16.7-1670 pM). Analyses of variance were used to examine differences in the variables measured at the four phases. Red cell-specific insulin binding (SB) was lower in MAL than in GI (P less than 0.001) and in (GII) (P = 0.026). SB in REC and MAL were not significantly different. Insulin receptor affinity (K) was also lower in MAL than in GI (P less than 0.001). GII (P = 0.001), and REC (P = 0.012). The insulin receptor number (S) appeared to be high in malnutrition and to decrease as recovery progressed; however the decrease was not significant. Children with fever demonstrated high insulin binding. Plasma insulin (IN) rose during recovery, and was significantly higher in GII than in MAL (P = 0.01). There was no difference in plasma glucose (G) at any phase of the study. The interrelationships among the variables measured were investigated longitudinally using multiple regression analyses, SB was positively associated with S (P = 0.032), EN (P = 0.029), and PR (P = 0.0076). S was negatively associated with K (P less than 0.001). The associations of S and K with PR were positive and approached significance (P = 0.09 and P = 0.07 respectively). RW was positively associated with PR (P less than 0.001), and with EN (P = 0.001). There were no significant relationships between G and any of the other variables longitudinally. However, correlations of the variables within phases demonstrated that in MAL, G was negatively associated with SB (P less than 0.05) and with K (P less than 0.05); but in REC, G was positively associated with SB (P less than 0.05). These results demonstrated that in severe malnutrition, the red cell insulin receptor affinity was low. During catch-up growth when protein and energy intakes were increased, both insulin receptor affinity and specific insulin binding were also increased. The negative relationship between insulin binding and plasma glucose during malnutrition may be related to carbohydrate intolerance.

The Trichuris Dysentery Syndrome (Ramsey, 1962) is an insidious, chronic condition which has clinical features similar to Crohn's ileocolitis and ulcerative colitis, diseases similarly associated with growth retardation. The attained heights and weights of 19 children at the time of diagnosis of intens, -2.4 Standard Deviation (Z) scores from the Tanner-Whitehouse median with weight, adjusted for height-age, -1.3 Z. We present data on the growth velocities of 11 of the children in the half-year following worm expulsion by mebendazole. These children returned to their home environments without food supplementation or close follow-up, but showed an average height velocity of +5.5 Z and weight velocity (for height-age) of +2.4 Z. Of 8 children with unequivocal height spurts only 3 had any weight spurt. We suggest that the pattern of catch-up growth points to the existence of some specific link between allergy or inflammation in the lower intestinal tract and suppression of linear growth, rather than to stunting due to general deprivation and undernutrition.

Stool specimens from 90% of the population of 2 marginal communities in Coatzacoalcos, Mexico, were examined by the Kato-Katz technique for the estimation of eggs per gram of faeces (epg). Average epg values for Ascaris lumbricoides and Trichuris trichiura were calculated for each family in the community, based on the arithmetic mean epg of family members for each parasite. 39 families were classified as either lightly or heavily infected with A. lumbricoides and infected members were treated with mebendazole. A. lumbricoides expelled following treatment were collected from the children 2-10 years of age, and reinfection was monitored monthly for 6 months. At the end of the reinfection interval, a final stool specimen was collected from all family members and those infected were treated. Again, A. lumbricoides expelled by the children 2-10 years of age were collected. There was a significant correlation between the number of A. lumbricoides expelled by the children at the first and second treatments as well as in epg values before the first and second treatments for both A. lumbricoides and T. trichiura in children (2-10 years) and adults (greater than 19 years). At the family level, there were significant correlations between the values of family mean epg before each treatment for both A. lumbricoides and T. trichiura.

Zinc supplementation of children who were just completing a period of rapid "catch-up" growth during recovery from severe malnutrition was found to stimulate sodium transport in their leucocytes. These results suggest that zinc status should be studied in the large number of serious illnesses, now known or thought to be associated with impaired sodium transport.

An adult (21 year old) male is described who developed Reye's syndrome in association with dengue type 1 infection.

1. Rates of total protein turnover, synthesis and breakdown were measured in five children before and after recovery from severe protein-energy malnutrition and while receiving 0.6 g of protein and 397 kJ day-1 kg-1. 2. Thes rates were calculated after giving doses of [15N]glycine every 2 h along with the feeds and measuring the rate of excretion of [15N]urea in urine. 3. Malnourished children had significantly lower rates of protein turnover, synthesis and breakdown than after they had recovered. 4. During recovery from protein-energy malnutrition, two children on a daily intake of 1.2 g of protein and 605 J/kg body weight, had rates of protein turnover, synthesis and breakdown that were twice as great as those found on admission and higher than after recovery. 5. On the study diet the malnourished children maintained their weight while the recovered children lost weight; the apparent nitrogen balance was more positive in the malnourished children. 6. In recovered children, the rate of protein synthesis was unchanged over a wide range of protein intake, whereas the rate of protein breakdown appeared to rise with a reduction in protein intake.

The Trichuris trichiura worm burdens of 23 children living in a Place-of-Safety in Kingston, Jamaica, were assessed by stool collection for more than five days after treatment with mebendazole. This procedure was repeated after a seven-month period of natural re-infection. For both collections the maximum rate of worm expulsion was achieved on the fourth day after starting treatment. The worm population distributions were overdispersed and well described by the negative binomial probability model (k = 0.29) in each case. For any one individual, the number of worms passed on the first expulsion was unrelated, absolutely or relatively, to the number passed on the second. These data suggest that: knowledge of the time dependency of helminth expulsion is essential for the accurate estimation of worm burdens by this method; populations of Trichuris are more highly aggregated than those of Ascaris and may thus be more susceptible to control by selective rather than random chemotherapy; and the inherent predisposition of hosts to infection may be of minor importance in determining the distribution of worms in the population-heavily infected hosts appear no more or less likely to acquire large worm burdens on subsequent exposures.

The most common form of pica, geophagy, has direct adverse nutritional effects and also exposes children to soil-borne infection. Existing methods for assessing geophagy are either inappropriate for field use (radiology) or unreliable (reporting). A new method is described, based on the measurement of soil-derived silica in stools. More than 90% of silica is excreted within one gut transit period of ingestion. The amount excreted is proportional to the amount ingested. Faecal levels of dietary silica (less than 2% dry wt stool) can be distinguished from levels due to geophagy (up to 25% dry wt stool). Studies in 2 children's homes in Jamaica showed that 33% and 66% of children were geophagous, ingesting up to 10 g soil day-1. The geophagy of less than 20% of the children accounted for greater than 60% of the total soil ingested. This overdispersion of exposure to soil-borne infection may contribute to the observed aggregation of geohelminth infection.

An ion-pairing reversed-phase HPLC assay employing amperometric detection has been developed for the determination of free minoxidil (MNX) in human serum. The drug is isolated from the serum and concentrated by solid phase extraction with a disposable cartridge column containing ethylsilane (C2) bonded phase packing material. The average absolute recovery from serum was 85%. The HPLC separation is performed on a Sperisorb-C(8) column, using n-octanesulphonic acid as the pairing ion. The method exhibits linear behaviour from 0.3 to 100 ng/ml for spiked serum samples. The average daily relative standard deviations of replicate samples at the 0.75 and 2.0 ng/ml levels were 9.6 and 6.4%, respectively. Utilizing a 1 ml sample the limit of detection (S/N > or = 3) was 0.3 ng/ml.

1. Whole-body protein turnover was measured in rats by constant infusion of 15N-labelled glycine, aspartate, valine and leucine and measuring the enrichment of hepatic and renal urea and ammonia nitrogen. 2. The values obtained with [15N]glycine were comparable with values reported with methods based on different assumptions. 3. [15N]Aspartate gave rise to an increased enrichment of urea and ammonia and hence to lower protein-turnover rates. 4. [15N]Valine and [15N]leucine gave low enrichments of nitrogenous end products and hence to high protein-turnover rates. 5. All 15N-labelled amino acids are not equally suitable for measuring whole-body protein turnover by the end-product method. The relative amounts of 15N going to the end products can be predicted from the known individual metabolism of aspartate and the branched-chain amino acids.

A survey of 428 households in a shanty town in Coatzacoalcos, Mexico, revealed high prevalences of Ascaris lumbricoides and Trichuris trichiura. The data were analysed separately for A. lumbricoides and T. trichiura in order to investigate the spatial distribution of heavy infections through the town. Within each age class, those individuals with egg counts in the upper 20% of the range for that age were classified as "heavily infected". When the data were stratified by household size, it was found that the distribution of "heavily-infected" individuals was not random in the community. "Heavily-infected" individuals were found together in households; fewer household units had a single heavily-infected individual than would be expected by chance. Such a pattern could result either from genetic similarities among family members influencing their ability to mount an effective immunological response to infection, or focal transmission in the vicinity of the home, or both. This result may have important implications for the development of community control programmes.

The modified Kato technique has the advantages of reproducibility, simplicity and economy: the disadvantage is that it cannot be used in conjunction with traditional faecal preservatives. Sodium azide has been evaluated as a preservative for human faeces for subsequent Kato analysis. More than 400 faecal samples (from normal and malnourished children, and from mixed-age participants in a field survey of the Turks and Caicos Islands) were each mixed with 2-5 mg of sodium azide powder and stored in 2 or 4 ml autoanalyser cups at ambient tropical temperature. At intervals up to 30 weeks, aliquots were prepared for Kato analysis. Trichuris trichiura, Ascaris lumbricoides and Necator americanus eggs were well preserved without degenerative or developmental changes in morphology. Quantitative analyses of 18 samples indicated that the mean egg count/sample did not change significantly after storage for 1, 2, 4, 8, 12 and 16 weeks in preservative. The use of azide preservative extends the applications of the Kato technique to field and clinical studies in which delays may occur between specimen collection and examination. The direct costs of azide preservation are substantially lower than for traditional methods and the preserved specimens are more compact and resistant to leakage.

Whole-body protein synthesis was measured with [15N]glycine in malnourished and recovered infants and in obese patients. Comparisons were made: 1) between results obtained with single (S) and repeated (R) oral dosage of tracer; and 2) between urea and ammonia as end products. In the infants S and R gave similar values for the synthesis rate. With both methods of dosage, the values obtained with NH3 as end product were about two-thirds of those with urea. It is suggested that the cause of this result is that glycine contributes preferentially to the formation of urinary NH3. With NH3 as end product, a collection period of 12 h has been found to be suitable. With urea it is not possible to define an appropriate collection period. The combination of single dose of [15N]glycine with urinary NH3 as end product provides a simple method for measuring whole-body protein synthesis under clinical and field conditions. It can be repeated at short intervals and can give useful comparative information provided that conditions are carefully standardized. The reproducibility so far is +/- 13%.

1. The growth of muscle fibres was analysed by light microscopy in biopsies from subjects when malnourished, during nutritional rehabilitation, and after clinical recovery. 2. Muscle fibres from malnourished subjects were extremely atrophic (cross-sectional area, 110 micrometers2). The fibres doubled in size during the early period of rehabilitation. Growth of muscle fibres during later periods of rehabilitation occurred at a slower rate. 3. The absolute rates of change in fibre sizes differed considerably between subjects, but the rates of change relative to the rate of gain of total body-weight (expressed as % recovery or % expected weight-for height (Nelson, 1975)) were similar between subjects after the initial growth spurt. The pattern of recovery appeared to differ between older and younger subjects. 4. Fibre sizes correlated with body-weight but not with age in the malnourished subjects. A significant correlation between fibre areas and either weight or age was observed during rehabilitation and after clinical recovery. 5. Fibre sizes of clinically-recovered subjects (mean age, 13.8 months; weight, 8.7 kg) were only approximately 60% of that for a well-nourished 6-month-old control subject (6.4 kg). These results suggest that a longer period of time is required for fibres to reach their expected size. Therefore, when the child has regained body-weight to that of a normal child of the same height, his muscles have not yet recovered and his body composition is abnormal.