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Biomedical subjects

C Berry

Publications and source records attributed to C Berry.

At least 163 records · Page 9Linked to original sources

Chloroquine treatment of severe malaria in children. Pharmacokinetics, toxicity, and new dosage recommendations.

Although empirical regimens of parenteral chloroquine have been used extensively to treat severe malaria for 40 years, recent recommendations state that parenteral chloroquine should no longer be used because of potential toxicity. We studied prospectively the pharmacokinetics and toxicity of seven chloroquine regimens in 58 Gambian children with severe chloroquine-sensitive falciparum malaria. In all regimens the total cumulative dose was 25 mg of chloroquine base per kilogram of body weight. Chloroquine was rapidly absorbed after either intramuscular or subcutaneous administration (5 mg of base per kilogram every 12 hours), producing high peak blood concentrations but transient hypotension in 5 of 18 patients (28 percent). Intermittent intravenous infusion (5 mg of base per kilogram over 4 hours, repeated every 12 hours) also produced wide fluctuations in chloroquine levels, suggesting incomplete distribution from a small central compartment. Continuous infusion (0.83 mg of base per kilogram per hour for 30 hours) and smaller, more frequent intramuscular or subcutaneous injections of chloroquine (3.5 mg of base per kilogram every 6 hours) produced smoother blood-concentration profiles with lower early peak levels and no adverse cardiovascular or neurologic effects. Chloroquine given by nasogastric tube (initial dose, 10 mg of base per kilogram) was absorbed well, even in comatose children. We conclude that simple alterations in dosage and frequency of administration can give parenteral chloroquine an acceptable therapeutic ratio and reinstate it as the treatment of choice for severe malaria in areas where chloroquine resistance is not a major problem.

Animals↗

Ultrastructural studies as a method of prenatal diagnosis of neuronal ceroid-lipofuscinosis.

Ultrastructural studies of uncultured amniotic fluid cells obtained by genetic amniocentesis at 16 wk of gestation demonstrated 3 major cell types. Membrane bound curvilinear cytosomes were observed in about 30% of a subpopulation of dark, elongated cells. These are considered typical of the inclusions of the late infantile variant of neuronal ceroid-lipofuscinosis. This technique was used to monitor 6 at-risk pregnancies of which 2 were identified as affected. We have followed 6 of the 7 fetuses through to delivery with confirmation of our findings by skin biopsy in 4 and with clinical observations of a fifth child. There are major problems involved in the use of uncultured amniotic fluid cells for prenatal diagnosis. In addition to a great deal of heterogeneity of cell type, there is a considerable amount of tissue debris and a very high proportion of nonviable cells. We have examined chorionic villus tissues of 3 fetuses known to have inborn errors of lysosomal metabolism without finding any evidence of storage material. This is taken as an indication that the mutant gene(s) is not expressed in these tissues at this early stage of pregnancy. Notwithstanding these limitations, the usefulness of this technique in monitoring at-risk pregnancies has to be determined.

Amniocentesis↗

Antenatal origin of neurologic damage in newborn infants. I. Preterm infants.

Currently, the diagnosis of white matter necrosis may be performed with echoencephalography when cysts are observed in the white matter adjacent to the lateral ventricles. One hundred twenty-seven infants with a gestational age less than 36 weeks (mean [+/- SE] gestational age = 31 +/- 3.2 weeks) were studied in the neonatal period with echoencephalography to determine the incidence of white matter necrosis and the perinatal variables associated with this complication. Twenty-three infants (18.3%) had white matter necrosis. Thirteen (10.3%) had cysts by day 3 (11 on day 1), indicating that the onset of white matter necrosis occurred antenatally. The incidence of antenatal white matter necrosis was inversely related to birth weight and was more frequent in infants weighing less than 1000 gm (19%). Stepwise logistic regression analysis of 31 antenatal variables showed that placental vascular anastomoses in multiple pregnancies, funisitis, and purulent amniotic fluid were the only complications associated with antenatal white matter necrosis. Follow-up neurologic evaluations were abnormal in four of six patients with antenatal white matter necrosis. The findings in this study focus attention on prenatal, rather than intrapartum and postnatal, factors as causative agents of neurologic morbidity and emphasize the importance of early and sequential evaluation of neonatal brain structures.

Cerebral Hemorrhage↗

Influence of starches of low digestibility on the rat caecal microflora.

1. Male Sprague-Dawley rats were fed on either a purified, fibre-free diet or a diet in which half the maize starch was replaced with uncooked amylomaize or potato starch (equivalent to 100 or 200 g amylase-resistant starch (ARS)/kg diet respectively). Changes in short-chain fatty acids (SCFA), pH, ammonia and a number of bacterial variables in caecal contents were then assessed. 2. Both ARS supplements decreased caecal content pH by approximately 1-2 units, with an associated reduction in ammonia concentration. Potato starch significantly decreased the concentration of SCFA in the hindgut, while amylomaize supplementation increased propionic and butyric acids but decreased the occurrence of minor, branched-chain fatty acids. 3. Caecal bacterial biotransformation activities (beta-glucosidase (EC 3.2.1.21), beta-glucuronidase (EC 3.2.1.31), reduction of p-nitrobenzoic acid, apparent ammonia formation) were consistently decreased by both ARS sources. 4. The results demonstrate that amylase-resistant carbohydrate altered toxicologically important functions in the large-intestinal flora of the rat.

Ammonia↗

Pharmacokinetics of rimantadine hydrochloride in patients with chronic liver disease.

Six patients with chronic liver disease and six sex-, age (+/- 5 years)-, and weight (+/- 5 kg)-matched healthy control subjects received a single dose of two 100 mg tablets rimantadine HCl. Eight additional patients with chronic liver disease who were not matched to healthy subjects received a single dose of two 100 mg tablets of rimantadine HCl. Blood and urine samples were collected and rimantadine concentrations were determined by a GCMS method. The values for maximum plasma concentration, AUC, elimination half-life, and renal clearance were not significantly different between patients and control subjects, independent of the statistical analyses (parametric and nonparametric) used. The mean apparent elimination half-life, volume of distribution, and total clearance in the matched patients with liver disease were 32 hours, 24 L/kg, and 676 ml/min, respectively. Renal clearance and the amount excreted in the urine unchanged were 63 ml/min and 10%, respectively. In conclusion, rimantadine pharmacokinetics were not appreciably altered in patients with less severe chronic liver disease.

Adamantane↗

Identification, cloning and sequence analysis of the Bacillus sphaericus 1593 41.9 kD larvicidal toxin gene.

A number of strains of the widespread aerobic soil bacterium, Bacillus sphaericus, possess crystalline inclusions of a toxin lethal to a variety of insect (larvae) which are vectors of major tropical diseases. Partial amino acid sequence data from one strain, B. sphaericus 2362 have permitted us to design oligonucleotide probes for identifying the toxin gene in the closely related B. sphaericus 1593. The gene was found to be contained within an EcoRI-HindIII fragment and was cloned in its entirety in the bacterial plasmid pUC12. The DNA sequence was determined together with the upstream and downstream controlling elements, and a sequence of 370 amino acids was deduced for the toxin protein. This is the first reported sequence of a B. sphaericus toxin gene and will facilitate further work in characterizing the genes from other strains of different virulence and host range. The data do not support the suggestion that the toxin is derived by proteolysis of a protoxin precursor.

Amino Acid Sequence↗

Diminished atherosclerotic arterial calcifications in asthma. A possible role for elevated endogenous heparin-like material.

Twenty-seven patients beyond the age of 50 were radiographically compared with age- and sex-matched controls for the degree of calcified atherosclerotic plaque formation in the aorta and its major pelvic branches. Significantly less calcification was present in the aorta, iliac and hypogastric arteries of the asthmatics (P = 0.01). Previous studies in other asthmatic patients have shown elevated endogenous heparin-like material to be present in their plasma. It is speculated that diminished atherosclerosis in asthmatic patients might be a consequence of elevated circulating endogenous heparin-like material.

Aged↗

Continuous-wave Doppler velocities and gradients across fixed tunnel obstructions: studies in vitro and in vivo.

The simplified Bernoulli relationship appears to be quite accurate for predicting gradients across discrete valvular obstructions. Controversy exists about how accurately it predicts the severity of disease in longer segment obstructions. In this study we constructed a pulsatile model of subvalvular pulmonary stensosis in vitro to study nine custom-made subvalvular tunnels 2, 4, and 7 mm in length with flow cross sections of 0.5 to 1.5 cm2 and with the stenotic segment proximal to a nonstenotic bioprosthetic valve, and a pulsatile model in vitro of a 16 mm long tunnel-like ventricular septal defect (VSD) of varying cross-sectional area (0.20 to 0.64 cm2). We also compared the observations in vitro with those in an open-chest dog preparation with a tunnel-like interventricular communication. In the subpulmonic stenosis model, for each individual tunnel, 10 instantaneous peak gradients between 15 to 105 mm Hg were available. The pressure gradients across the tunnel alone, measured in the subvalvular area, were consistently higher than the measured gradients across the tunnel plus valve, suggesting some relaminarization of flow (i.e., a decrease in velocity) and pressure recovery (i.e., an increase in pressure) distal to the obstruction. Continuous-wave Doppler velocities across the 4 and 7 mm tunnels for the highest gradients were slightly lower than for the 2 mm tunnel at the same gradients, and it was only for the 0.5 cm2 cross section, 4 and 7 mm tunnels that there was a suggestion of minor viscous energy loss. For all the subvalvular tunnels studied, the Bernoulli relationship accurately predicted the results of the pressure drop across the tunnel only, while the gradient across tunnel plus valve was consistently lower. For the VSD tunnel model in vitro, the Doppler-derived gradients were approximately 40% higher than the measured gradients. The findings for the subvalvular and VSD tunnels in vitro and similar findings in the open-chest dogs with VSD suggest that relaminarization of flow and recovery of pressure occurred distal to the tunnel orifice, whereas continuous-wave Doppler findings correlate with the highest instantaneous gradients measured in the lowest pressure areas at the vena contracta of the tunnel.

Animals↗

Prophylactic treatment of very premature infants with human surfactant.

We undertook a randomized, controlled trial to determine whether human surfactant administered endotracheally at birth to very premature infants (gestational age, 24 to 29 weeks) would prevent the respiratory distress syndrome or reduce its severity. Thirty-one treated infants (birth weight, 938 +/- 286 g) were compared in a blinded fashion with 29 control infants (birth weight, 964 +/- 174 g). The lecithin/sphingomyelin ratio was less than 2 in all infants, and phosphatidylglycerol was not present in amniotic fluid or tracheal fluids at birth, indicating a deficiency of surfactant in the lungs. The principal dependent variables were neonatal death, the incidence of bronchopulmonary dysplasia, and the infant's requirement for respiratory support (and its complications). The surfactant-treated group had significantly fewer deaths than the control group (16 percent vs. 52 percent, P less than 0.001), fewer cases of bronchopulmonary dysplasia (16 percent vs. 31 percent), and significantly fewer cases of pulmonary interstitial emphysema (P less than 0.001) and pneumothorax (P less than 0.02). Prophylactic treatment with human surfactant also substantially reduced the period of neonatal intensive care. We conclude that treatment with human surfactant offers promise for improving the survival of very premature infants with a surfactant deficiency and for reducing the pulmonary sequelae of the respiratory distress syndrome.

Amniotic Fluid↗

What's new in transplacental carcinogenesis?

The discovery that a non-steroidal oestrogen may cause malformations and neoplasia following transplacental administration in man has led to a considerable amount of experimental work on this type of carcinogenesis. In general, there are a number of features which suggest that this is unlikely to be a commonly occurring mode of carcinogenesis in man and the reasons for this are discussed and considered here together with some experimental justification for this position.

Animals↗

Mechanical vascular changes and hypertension: pathological consequences.

Arteries are more than simple conduits for blood, they are a functionally active part of the cardiovascular system. Their mechanical performance is preserved at different levels of blood pressure and adapts to progressive increases but this functional change is accompanied by wall changes (e.g. medial thickening, scleroprotein increase) which have pathological effects. The way in which these changes are brought about is discussed.

Aging↗

Kinetics of oxygen uptake and heart rate at onset of exercise in children.

Requirements for cellular homeostasis appear to be unchanged between childhood and maturity. We hypothesized, therefore, that the kinetics of O2 uptake (VO2) in the transition from rest to exercise would be the same in young children as in teenagers. To test this, VO2 and heart rate kinetics from rest to constant work rate (75% of the subject's anaerobic threshold) in 10 children (5 boys and 5 girls) aged 7-10 yr were compared with values found in 10 teenagers (5 boys and 5 girls) aged 15-18 yr. Gas exchange was measured breath to breath, and phases I and II of the transition and phase III (steady-state exercise) were evaluated from multiple transitions in each child. Phase I (the VO2 at 20 s of exercise expressed as percent rest-to-steady-state exercise VO2) was not significantly correlated with age or weight [mean value 42.5 +/- 8.9% (SD)] nor was the phase II time constant for VO2 [mean 27.3 +/- 4.7 (SD) s]. The older girls had significantly slower kinetics than the other children but were also found to be less fit. When the teenagers exercised at work rates well below 75% of their anaerobic threshold, phase I VO2 represented a higher proportion of the overall response, but the phase II kinetics were unchanged. The temporal coupling between the cellular production of mechanical work at the onset of exercise and the uptake of environmental O2 appears to be controlled throughout growth in children.

Adolescent↗

Evidence indicating that UDP-N-acetylglucosamine does not appear to stimulate hepatic microsomal UDP-glucuronosyltransferase by interaction with the catalytic unit of the enzyme.

The binding studies in this paper indicate that the catalytic unit(s) of microsomal UDP glucuronosyltransferase(s) is not accessible to N-ethylmaleimide or UDP-N-acetylglucosamine, when the enzyme is in its membrane environment. Thus a separate regulatory factor may exist within the endoplasmic reticulum membrane that mediates the stimulation of UDPglucuronosyltransferase(s) by UDP-N-acetylglucosamine. The possible role and the mode of interaction of the putative regulatory factor with the multiple forms of UDPglucuronosyltransferase are discussed.

Animals↗

Short-term interpersonal therapy (IPT) with the depressed elderly: case reports and discussion.

Interpersonal psychotherapy (IPT), a short-term treatment developed and tested for use with ambulatory depressed patients, has been successfully applied to elderly patients in a recent pilot study. Case reports of treated elderly patients are presented and the specific utility of IPT for this population is described. The potential of short-term psychotherapies for the treatment of the elderly is discussed and research directions are outlined.

Aged↗