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Biomedical subjects

B Charles

Publications and source records attributed to B Charles.

At least 19 recordsLinked to original sources

Chemical constituents of essential oils of muña, Bolivian plants traditionally used as pesticides, and their insecticidal properties against Chagas' disease vectors.

The composition of essential oils from two muña, Bolivian medicinal plants, derived from Minthostachys andina and Hedomea mandonianum, were analyzed by gas chromatography/mass spectrometry. Major differences were observed in their chemical composition. Pulegone was the major component of H. mandonianum oil (44.6%) and M. andina oil (25.5%); menthone and isomenthone were around 33% of these oils. Differences were also observed in their insecticidal activity against the Chagas' disease vector, Rhodnius neglectus or Triatoma infestans bugs exposed on impregnated oil filter papers. While M. andina oil showed 30%-50% of mortality in both triatomine species after a period of 1 week, H. mandonianum oil did not show any insecticidal activity. Nevertheless, both species had insecticidal activity (33.3% and 50%) when oils were topically applied. The significance of these results is discussed in relation to the variability of the chemical composition and their potential use in Chasgas' disease vector control.

Animals

Neonatal lipid utilization increases with injury severity: recombinant human growth hormone versus placebo.

Increased lipid oxidation has been observed in injured adult and pediatric patients who receive growth hormone (GH). In infants, whose bodies make fat more readily (de novo lipogenesis), this effect has not been tested. After surgery for necrotizing enterocolitis or gastroschisis, 22 neonates (average gestational age, 35 weeks; average postnatal age, 7 days) were provided basal protein-calorie parenteral repletion, and were prospectively randomized to receive either recombinant human GH (rhGH, 0.2 mg/kg/d) or placebo for 6 days. Injury severity was established by serial serum C-reactive protein (CRP) levels (high v low stress: CRP > or = 6.0 mg/dL v < 6.0 mg/dL). Indirect calorimetry was used to measure energy expenditure (MEE), respiratory quotient (RQ), net lipid oxidation (Fe), and lipid oxidative O2 consumption (VO2f). Among the GH+ group, MEE, Fe, and VO2f were significantly higher for the high-stress patients (MEE: 52.87 +/- 13.35 v 42.57 +/- 9.47 kcal/kg/d; P < .03: Fe; 18.32 +/- 27.74 v 0.81 +/- 13.47 kcal/kg/d; P < .02; VO2f: 7.21 +/- 9.86 v 0.01 +/- 7.42 L/d, P < .02), and RQnp was significantly lower in the high-stress patients (RQnp: 0.93 +/- 0.14 v 1.05 +/- 0.11; P < .02). In addition, Fe and RQnp were directly proportional to carbohydrate intake (CHO) in the high-stress patients (CHO to Fe: Pearson r = -.701; CHO to RQnp: Pearson r = .714; P < .05). Lipid oxidation was directly proportional to stress severity, was higher in the GH group (18.32 v 11.91 kcal/kg/d for the placebo group), and was depressed in response to increased CHO intake in all groups. Lipid is an important energy source in acutely injured, especially severely stressed neonates. Lipid substrate utilization is improved with GH supplementation during acute metabolic stress. In addition, excess carbohydrate delivery reduces the amount of lipid utilized for energy metabolism. An appropriately balanced, mixed-fuel formula should be used for caloric repletion in this infant population.

Double-Blind Method

Pharmacokinetics and bioavailability of flucloxacillin in elderly hospitalized patients.

The pharmacokinetics and oral bioavailability of flucloxacillin were studied in five female and two male patients (age 68-87 yr) who had been hospitalized for orthopedic surgeries. A single dose of intravenous or oral flucloxacillin sodium (500 mg) was administered in random order on different occasions separated by at least 2 days. Blood and urine samples were taken up to 24 hours after drug administration and levels of flucloxacillin and 5-hydroxymethylflucloxacillin (5-HMF), a major metabolite, were measured by high-performance liquid chromatography. Flucloxacillin elimination, but not oral absorption, was reduced in the elderly, compared with data from young healthy subjects reported elsewhere. Total clearance, renal clearance, and volume of distribution were 0.083 +/- 0.013 L/kg/hr, 0.038 +/- 0.01 L/kg/hr, and 0.184 +/- 0.034 L/kg, respectively. Regression of flucloxacillin renal clearance (Clr) on estimated creatine clearance (CLcr) gave the relationship: Clr = 0.755 (CLcr) + 10.6 (r = 0.91; P = 0.004). Terminal half-lives for flucloxacillin and 5-HMF were 2.21 +/- 0.51 hr and 3.0 +/- 0.75 hr, respectively after intravenous administration. Flucloxacillin was absorbed rapidly after oral administration with a mean absorption time of 0.95 +/- 0.34 hr, and time to reach peak concentration of 1.20 +/- 0.29 hr. The absolute bioavailability of flucloxacillin from capsules was 54.4 +/- 18.8%.

Administration, Oral

Stratification of injury severity using energy expenditure response in surgical infants.

AIM OF STUDY: Injury severity stratification has important clinical outcome significance and can influence nutritional management. Although surgery alone has been shown not to increase measured energy expenditure (MEE) substantially, large increases in MEE can result from severe underlying acute illness, which frequently necessitates surgery (like sepsis or intense inflammation). The authors hypothesized that the magnitude and duration of the MEE response to surgery associated with a severe preoperative acute injury would exceed that of surgery in which no substantial preoperative stress was present, thus representing an index of overall injury severity in surgical infants. METHODS: MEE (kcal/kg/d) was determined on postoperative days (POD) 2, 5, and 8 in 12 infants (average age, 47 days) after two separate injury insults (at least 8 days apart). In each patient, one operation resulted in a peak serum C-reactive protein (CRP) concentration of less than 6.5 mg/dL (low stress), and the second operation, preoperatively associated with sepsis or a major inflammatory insult, resulted in a peak CRP of more than 6.5 mg/dL (high stress). Data were paired so that each child served as his or her own control. The initial basal protein-calorie delivery was similar in both groups. MAIN RESULTS: The mean peak CRP values were 14.1 +/- 10.7 mg/dL (high stress) and 4.1 +/- 2.3 mg/dL (low stress) and returned to normal levels earlier (before POD 8) after injury insult in the low-stress group. Analysis of energy expenditure on POD 2 demonstrated significantly elevated mean MEE values in the high-stress group (58.0 +/- 12.2 kcal/kg/d v 39.4 +/- 9.5 kcal/kg/d in the low-stress group; P = .0001). In contrast, analysis of POD 8 energy expenditure showed significantly lower mean MEE values in the high-stress group (50.7 +/- 12.0 kcal/kg/d) v (66.4 +/- 15.1 kcal/kg/d in the low-stress group; P = .0118) group. CONCLUSION: The early (POD 2) hypermetabolic response to injury as determined by MEE effectively differentiated the two stress groups. This finding suggests that acute underlying illness is an important determinant of postoperative MEE. Furthermore, in the low-stress group, serial CRP levels returned to normal earlier, associated with significantly greater late (POD 8) MEE values. Because MEE is directly proportional to growth rate in healthy infants, and growth is retarded during acute metabolic stress, these findings suggest that increased energy is utilized for growth recovery following the earlier resolution of the acute injury response in the low-stress group. These data indicate that serial postoperative MEE can be used to stratify injury severity and may be an effective parameter to monitor the return of normal growth metabolism in surgical infants.

Analysis of Variance

Early postoperative alterations in infant energy use increase the risk of overfeeding.

AIM OF STUDY: Energy needs in infants are decreased after surgery because of growth inhibition (resulting from catabolic stress metabolism), decreased insensible losses, and inactivity. Using standardized formulas that account for growth, activity, and insensible losses during this stress period can lead to overfeeding in excess of 200% of the actual measured requirement. Overfeeding during this acute injury period can result in increased CO2 production from lipogenesis. This study determined the effects of a reduced rate of mixed caloric repletion on infant energy use during the early postoperative period. METHODS: C-reactive protein (CRP), oxygen consumption (VO2), carbon dioxide production (VCO2), measured energy expenditure (MEE), and total urinary nitrogen (TUN) were measured serially in seven infants (average age, 78 days) during the first 72 hours after abdominal or thoracic surgery. Nonprotein respiratory quotient (RQnp), and values for oxidation of carbohydrate (Ce) and fat (Fe) were calculated. Injury severity was stratified based on serum CRP concentrations of > or = 6.0 mg/dL (high stress) or < 6.0 mg/dL (low stress). Recovery from acute stress was analyzed by comparing studies in which CRP had decreased to < or = 2.0 mg/dL (resolving stress group) with those in which CRP values were greater than 2.0 mg/dL (acute stress group). RESULTS: Average total caloric intake (64.56 +/- 18.51 kcal/kg/d; approximately 50% of predicted energy requirement) exceeded average MEE (42.90 +/- 9.98 kcal/kg/d) by approximately 50%. Average TUN was 0.18 +/- 0.07 g/kg/d (high stress 0.2 +/- 0.05 versus low stress 0.16 +/- 0.09 g/kg/d). Average RQnp was 1.05 +/- 0.13 and average Ce was 37.28 +/- 16.86 kcal/kg/d. The average calculated Fe was 0.0 +/- 12.27 kcal/kg/d, reflecting approximately equal amounts of fat oxidized compared with fat generated from excess glucose (lipogenesis). When individual studies were analyzed at a CRP cutpoint of 2.0 mg/dL, overfeeding (RQ > 1.0) was significantly less likely in the resolving (2/6 studies, 33.4%) versus acute stress (9/13 studies, 69.2%, Z test P < .001) group. Five of seven (5/7) patients (9/19 individual studies) had negative Fe values (average -9.89 +/- 10.02) reflecting net lipogenesis. The RQnp for these nine studies was 1.14 +/- 0.11 versus 0.97 +/- 0.09 for the remaining 10, and this difference was significant (P < .01). A significant correlation existed between carbohydrate intake and VCO2 (Pearson r = .6951, P < .01). In addition, there was a good correlation between carbohydrate intake and VCO2 (Pearson r = .6591, P < .01). The coefficient of variation for MEE was 8.0% (low stress) versus 30.2% (high stress). CONCLUSION: Lipogenesis with increased CO2 production is substantial, even at reduced caloric delivery rates that exceeded MEE by only 50%, during the early postoperative acute metabolic stress period in infants. These data suggest that caloric requirements during stress are likely equal to or only minimally in excess of actual MEE. Intersubject variability, especially in more severely stressed infants, underscores the importance of serial measurements of energy expenditure to enable precise caloric delivery and avoid overfeeding. In the absence of calorimetric measurement, the data suggest that PBMR (predicted basal metabolic rate) should be used to estimate caloric delivery until CRP values are < or = 2.0 mg/dL.

Abdomen

Simultaneous high-performance liquid chromatographic determination of 6 beta-hydroxycortisol and cortisol in urine with fluorescence detection and its application for estimating hepatic drug-metabolizing enzyme induction.

A simple and sensitive high-performance liquid chromatographic method is described for the simultaneous determination of 6 beta-hydroxycortisol (6 beta-OHF) and cortisol (F) in urine. Urine (1 ml) containing fludrocortisone as the internal standard is extracted with ethyl acetate. The extract is washed successively with sodium hydroxide solution and water, and subsequently dried under a stream of nitrogen. The residue is redissolved in methanol. The 6 beta-OHF, F and fludrocortisone in the methanol solution are oxidized by cupric acetate and the resulting glyoxal compounds are converted into fluorescent derivatives with 1,2-diamino-4,5-methylenedioxybenzene (DMB). The DMB derivatives of the corticosteroids are separated within 70 min on a reversed-phase column, L-Column ODS, using stepwise elution with methanol-acetonitrile-0.5 M ammonium acetate and detected fluorimetrically at 350 nm (excitation) and 390 nm (emission). The lower limits of detection for 6 beta-OHF and F are 1.8 pmol (680 pg) and 2.4 pmol (950 pg)/ml urine (0.6 pmol and 0.8 pmol/100 microliters injection volume), respectively, at a signal-to-noise ratio of 3. This method can be applied to the determination of urinary 6 beta-OHF, and the ratio of 6 beta-OHF to F in humans and in rhesus monkeys treated orally with phenobarbital as a hepatic drug-metabolizing enzyme inducer.

Administration, Oral

Individualizing aminophylline doses in premature infants using bioelectrical impedance: a non-invasive approach.

The role of bioelectrical impedance (BI) in estimating the pharmacokinetics and, therefore, individualized doses, of aminophylline in preterm infants (gestational age 26-35 weeks) was assessed in a two-phase study. Multiple regression analysis in the first group of neonates (phase I, n = 19) identified resistance, reactance, weight and length as optimal predictors of distribution volume (adjusted R2 = 0.84, coefficient of variation (CV) = 10.17%), and length2/impedance and postconceptual age as predictors of clearance (adjusted R2 = 0.74, CV = 26.73%). Application of these models to an independent group (phase II, n = 20) generated doses which satisfactorily achieved target theophylline loading and steady-state (SS) 'peaks' of 10 micrograms/mL and SS 'troughs' of 7.7 +/- 0.6 micrograms/mL. A better understanding of specific criteria and limitations of the impedance technique in neonates is necessary in order to refine BI measurements.

Aminophylline

Pharmacokinetics of dexamethasone following single-dose intravenous administration to extremely low birth weight infants.

The single-dose pharmacokinetics of dexamethasone were studied in 7 extremely low birth weight infants of mean (+/- SD) gestational age 25.6 +/- 0.5 weeks suffering bronchopulmonary dysplasia. A mean peak dexamethasone concentration of 250.5 +/- 70.7 ng/ml was obtained following an intravenous bolus dose (0.369 +/- 0.04 mg/kg dexamethasone) of dexamethasone sodium phosphate. Dexamethasone was measured in plasma by HPLC. Mean clearance (0.143 +/- 0.028 litres/kg/h) was approximately half that reported previously in children and adults, while the half-life (9.26 +/- 3.34 h) was 2- to 3-fold longer than in these patients. The volume of distribution (1.9 +/- 0.483 litres/kg) was larger than reported in a previous study in adults, but was similar to that determined in pediatric and adult patients in another study.

Bronchopulmonary Dysplasia

Home health care in France.

Home health care in France has a long tradition, but is limited in its development. Since 1970 hospitals are by law permitted to extend services at home. Apart from this, patient associations are a driving force in the organization of home health care. There is a trend to more home health care, but this is hampered by splitting of responsibilities of local, departmental or central authorities. The hospital pharmacist is recommended to focus on his scientific and technical competence. Improved relations between community pharmacists and hospital pharmacists are advocated.

Aged

The effects of ingestion time of gliclazide in relationship to meals on plasma glucose, insulin and C-peptide levels.

The effect of altering the timing of gliclazide administration in relation to a meal was studied in ten type 2 (non-insulin dependent) chronically treated diabetics. Gliclazide was given 30 min before, at the start of and 30 min after breakfast or omitted altogether. Plasma gliclazide was present at greater than 2 mg/l throughout the study periods. Administration at 30 min after the meal significantly delayed the time to peak for plasma gliclazide. No significant difference was noted in plasma glucose, insulin or c-peptide patterns with any protocol. It is concluded that, in clinical practice, with chronically treated diabetics the timing of gliclazide ingestion in relation to meals is not critical.

Aged