Serum-ionized calcium in mexican protein-energy malnourished children.

BACKGROUND: Hypocalcemia occurring in children with severe primary protein-energy malnutrition (PEM) has previously been shown to merely reflect a reduction in the protein-bound fraction of serum calcium. On the other hand, ultrafilterable, i.e., nonprotein bound calcium (Ca(U)), remains unaffected. The aim of the present investigation was to test the hypothesis that in infantile PEM, ionized calcium, which represents the major and physiologically most important component of Ca(U), is also kept within a normal concentration, whatever the total serum calcium levels. METHODS: Three milliliters of peripheral venous blood were obtained on admission and periodically afterward from 18 fasting marasmic infants and 6 children with the edematous form of PEM (kwashiorkor). Ionized calcium was determined in 125 microL aliquots of blood serum with ion-selective electrodes. The measurement of related elements and molecules was carried out with customary laboratory procedures. RESULTS: On admission, as well as during the ensuing stages of nutritional recovery, ionized serum calcium exhibited a normal concentration, with the exception of two initial samples. Total calcium, total protein, albumin, and inorganic phosphate concentrations were decreased in a variable degree according to the clinical type, ascending to normal levels during recovery. CONCLUSIONS: Ionized calcium serum concentration remains within normal limits in severe infantile PEM.

[Bayesian prediction of chloramphenicol blood levels in children with sepsis and malnutrition]. / Predicción bayesiana de las concentraciones séricas de cloranfenicol en niños con sepsis y desnutrición.

OBJECTIVE: To validate the population pharmacokinetic parameters of chloramphenicol in pediatric patients with sepsis and malnutrition (PPSM) using a bayesian forecasting program. DESIGN: Retrospective evaluation of predictive performance of a bayesian program in PPSM. SETTING: Tertiary care center. PATIENTS: Fifteen MPSP and ten NMPSP that receiving treatment with chloramphenicol. METHODS AND MAIN RESULTS: In the first part of the study, the medical records of 10 MPSP and 10 NMPSP who had received treatment with chloramphenicol were reviewed. The population pharmacokinetic parameter values for each group were estimated using a nonparametric expectation maximization algorithm (NPEM). In the second part, data gathered from five other MPSP receiving chloramphenicol were entered into a bayesian program. Chloramphenicol pharmacokinetic values for each of these five patients were estimated, first using the values of NMPSP as a priori distribution and then repeating the analysis using the MPSP values. The bayesian serum chloramphenicol concentrations predicted for each population model were compared with the actual peaks and troughs. The specific model for MPSP permitted forecasting the peak and trough serum chloramphenicol concentrations with less bias and a better precision compared with the NMPSP population model. CONCLUSIONS: These data indicate that chloramphenicol pharmacokinetics in PPSM can be predicted with minimal bias and good precision using a bayesian forecasting program, allowing a better control of the chloramphenicol serum concentrations. In addition, the limited number of samples required by the bayesian method may represent an important economical benefit for the patient.

Patterns of muscle and fat mass repair during recovery from advanced infantile protein-energy malnutrition.

OBJECTIVE: This paper shows the pattern of body composition within the frame three-compartment model repair during recovery from advanced infantile protein-energy malnutrition. DESIGN: Body composition was assessed in 26 severely malnourished male infants aged 1-7 months at the time of their admission at Instituto Nacional de Pediatria in Mexico City and through the initial process of nutritional recovery (NR), by means of radiological, anthropometrical procedures and 24-h creatinine excretion at fortnightly intervals. Throughout of NR period all children were fed with milk formula (13-14% protein, 40% carbohydrates and the remainder fat). RESULTS: There was high frequencies of children's intakes were above the median (160 kCa1/k/d), but in last period their intakes were close to child normal requirements. Repletion of weight-for-height deficit was complete in all children. Leg-muscle roentgenographic area showed significantly increment in size only the first 15 days (P < 0.05). The leg-fat area showed size increments in all 15-day intervals (P < 0.05 or P < 0.01). The leg-bone area did not show any change during NR. Body Weight as well as arm and arm-fat-free areas and calculated total muscle and fat body mass augmented significantly during nutritional rehabilitation (P < 0.01). However, the ratio of muscle to body mass increased only during the first month of NR (P < 0.05), while absolute and relative fat mass did so during the whole observation period (P < 0.05). The remainder of body organ mass (EOM) did not suffer any change during all NR period. CONCLUSIONS: This dysrythmic repair of body compartments might offer explanation of certain features of psychomotor performance of infants recovering from severe protein-energy malnutrition.

A new dosing regimen for metronidazole in malnourished children.

The use of metronidazole for the treatment of intestinal parasitosis has increased markedly, particularly in developing countries, where the association of malnutrition and parasitosis is very common. Since biotransformation of metronidazole is significantly affected by severe malnutrition, and undesirable effects of the drug seem to be related to its plasma concentration, it was decided to carry out a study to establish a dosing-regimen of metronidazole in severely malnourished children. A single dose of 30 mg/kg body weight, and computer simulation of a steady-state was studied in 10 malnourished and in 10 patients undergoing nutritional rehabilitation. Due to ethical considerations (refusal of parents to allow a second dose of metronidazole) acute malnourished children and rehabilitated patients are 2 distinct groups. The results indicate that a predicted drug cumulation would occur in malnourished children with the ordinary dosage regimen (30 mg/kg/day). Based on the clearance data, daily maintenance doses for pediatric patients with severe malnutrition should be 12.0 mg/kg/day, corresponding to a 60% reduction of the common dose calculated to achieve and maintain a plasma concentration of 6.0 micrograms/ml of metronidazole. The study illustrates the need for pharmacokinetic data to establish the individual dose of a drug particularly under conditions that alter biotransformation processes.

Pharmacokinetics of metronidazole in severely malnourished and nutritionally rehabilitated children.

A comparison of the pharmacokinetics of oral metronidazole, after a single dose of 30 mg/kg body weight, was done in two groups of subjects: group I consisted of 10 severely malnourished children, aged 4 to 43 months; group II consisted of 10 children, aged 3 to 25 months, who were studied after nutritional rehabilitation. The biologic half-life of elimination was significantly longer (p less than 0.01) in severely malnourished children (median, 10.21 hours; range, 4.89 to 22.93 hours) than in rehabilitated children (median, 5.09 hours; range, 2.61 to 8.75 hours). Metabolic clearance of metronidazole was significantly lower in group I (p less than 0.01; median, 0.077 L/kg/hr; range, 0.033 to 0.192 L/kg/hr) than in nutritionally rehabilitated children (median, 0.166 L/kg/hr; range, 0.105 to 0.300 L/kg/hr). Volume of distribution was not different between groups I and II, although both showed higher values than the values reported for children who were not malnourished. These findings suggest that the dose of metronidazole should be reduced in malnourished children, and the therapeutic regimen should be individualized for each patient.

Biotin deficiency in protein-energy malnutrition.

Several of the clinical and biochemical manifestations of biotin deficiency also occur in severe protein-energy malnutrition (PEM). Average plasma biotin concentrations were lower in 16 malnourished children (10 with marasmus, 3 with kwashiorkor and 3 with marasmic kwashiorkor) than in 31 controls. Lymphocyte mitochondrial carboxylase activities were studied in 11 controls and in 10 patients with PEM; on the average, they were lower in the patients. Their activation indices (the ratio of enzyme activity in cells incubated with biotin to activity in cells incubated without the vitamin) were higher in PEM. All these differences were statistically significant. None of these parameters were age-dependent in a range between 3 and 72 months. Carboxylase activities and plasma biotin levels increased to normal during nutritional recovery in two malnourished patients who were further studied. These results suggest that there is biotin deficiency in severe PEM. Urinary biotin concentrations, expressed per g of creatinine, were higher in the patients than in the controls; this may have been caused by increased renal clearance or by the reduced creatinine excretion which occurs in malnourished individuals. It will be important in future studies to determine the relative contribution of biotin deficiency to the malnourished phenotype.