Differential effects of right unilateral and bilateral ECT on heart rate

In a series of 11 melancholic patients who received both right unilateral and bilateral ECT during a single course of treatment, mean and minimum postictal heart rates were greater after bilateral ECT. Greater catecholamine release during bilateral ECT is the most likely explanation for these effects. These differences complement other evidence that bilateral ECT has a more pronounced physiological impact than unilateral ECT.     

Delayed osteotomy but not fracture healing in pediatric osteogenesis imperfecta patients receiving pamidronate.

This study evaluated factors influencing fracture (n = 197) and osteotomy (n = 200) healing in children with moderate to severe OI. Pamidronate treatment was associated with delayed healing after osteotomy, but not after fracture. The data suggest that both pamidronate and mechanical factors influence bone healing in this cohort. INTRODUCTION: Intravenous pamidronate is widely used to treat children with moderate to severe osteogenesis imperfecta (OI). However, the effect of this treatment on bone healing is not well characterized. We therefore retrospectively analyzed the healing of lower limb fractures and osteotomies in children with moderate to severe OI, both before and after the start of pamidronate treatment. MATERIALS AND METHODS: Bone healing was evaluated on standard radiographs after 197 lower limb fractures (132 femur and 65 tibia) in 82 patients (age at fracture, 0.0-19.9 years) and 200 intramedullary rodding procedures in 79 patients (age at surgery, 1.2-19.8 years). Delayed healing was diagnosed when a fracture or osteotomy line was at least partially visible 12 months after the event. RESULTS: Delayed fracture healing was observed more frequently during than before pamidronate treatment. However, the effect of pamidronate was no longer significant when age differences were taken into account (odds ratio [OR], 1.76; 95% CI, 0.61-5.10). Better mobility status was a strong independent predictor of delayed healing after fractures that occurred during pamidronate treatment. After osteotomies, delayed healing was more frequent when pamidronate had been started before surgery (OR, 7.29; 95% CI, 2.62-20.3), and this effect persisted after adjustment for multiple confounders. During pamidronate treatment, older age (OR per year of age, 1.25; 95% CI, 1.06-1.47) and osteotomy of the tibia (OR, 3.51; 95% CI, 1.57-7.82) were independent predictors of delayed healing. CONCLUSIONS: This study suggests that pamidronate therapy is associated with delayed healing of osteotomy sites after intramedullary rodding procedures. Better mobility status, but not pamidronate treatment, seems to be predictive of delayed healing after fractures.     

Mothers' and children's intakes of vitamin A in rural Bangladesh.

The vitamin A intake of 370 mothers and 183 children 3-27 mo of age in rural Bangladesh was ascertained monthly from January to July in 1986. For mothers, dark green leafy vegetables and fruits were the main sources of vitamin A. Vitamin A from vegetables, the single most important source, did not show consistent associations with wealth or with the other socioeconomic indicators. In May and June, fruits provided wealthier (and more educated) mothers with significantly higher vitamin A intakes than poor mothers, whereas in January the poorer mothers had higher intakes. When breast milk was included, average intakes for children came close to 100% of the recommended dietary allowance; the only other significant source of vitamin A for children was seasonally available mangoes. Fourteen children who had stopped breast-feeding by the end of the study were at very high risk of vitamin A deficiency when fruits were not plentiful.     

Modulation of ion transport in cultured rabbit tracheal epithelium by lipoxygenase metabolites.

Lipoxygenase metabolites influence ion movement and fluid balance in the airways. We studied the effects of nordihydroguaiaretic acid (NDGA), a general inhibitor of the lipoxygenase pathway, on Na+ and Cl- secretion in cultured tracheal epithelial cells from adult rabbits through short-circuit current (Isc) and radioactive tracer flux experiments. NDGA inhibition of leukotriene release in freshly isolated rabbit tracheal epithelial cells was assayed by a 3H peptidyl-leukotriene radioimmunoassay. 3 microM NDGA resulted in a 91% reduction of leukotriene release. In unstimulated cultures, Cl- secretion (furosemide-inhibited fraction of Isc) was 11.1 +/- 2.8 muamp/cm2 (n = 10) and was unchanged in the presence of NDGA (n = 10). Epinephrine-stimulated Cl- secretion increased Isc by 12.2 +/- 2 muamp/cm2 (n = 10). This stimulation was unchanged by pretreatment with NDGA (n = 10), suggesting that inhibition of the lipoxygenase pathway did not affect Cl- secretion. In unstimulated cultures, Na+ absorption (amiloride-inhibited portion of Isc) was 10.7 +/- 3.3. muamp/cm2 (n = 10) and was reduced by 79% in the presence of NDGA (n = 10), suggesting that inhibition of the lipoxygenase pathway was associated with inhibition of Na+ absorption. Radioactive tracer flux experiments supported these findings. Exogenous LTD4 (n = 7) and LTC4 (n = 7) were added to cells pretreated with NDGA, and Na+ absorption was restored to 76% and 70% of control, respectively. In addition, LTD4 (n = 4) and LTC4 (n = 4) were added to cells without prior inhibition of the lipoxygenase pathway to NDGA and resulted in an increase in Cl- secretion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of the costs of compliance with nutrition education messages to improve the diets of Bangladeshi breastfeeding mothers and weaning-age children

Local market prices in rural Bangladesh were used to compute the costs of filling the nutrient gaps between actual intakes and safe nutrient requirements, and the costs of compliance with nutrition messages, for 78 lactating mothers and 61 weaning-age breastfed children. (The gap is the difference between the requirement and the amount of nutrient consumed.) To fill the mother's energy gap of approximately 1050 kcal (4393 kJ) would cost an additional 21% of the daily wage, or almost double the value of food she was presently eating. Given social reality, these costs would probably be much greater, as the mother would also need to increase the allocation of food to other household members. The weaning-age children's energy gap could theoretically be closed for less than one-third of the cost of improving the mothers' diets, or about 8% of the daily wage. The increase in food intake equivalent to 2% of the daily wage actually achieved through nutrition education resulted in a significant improvement in child weight gain, though not ideal. These findings suggest that, in the absence of programs which reduce economic barriers, it is economically feasible for families to close the nutrient gaps for weaning-age breastfed children in Bangladesh, but not for lactating women. Thus, education to improve women's diets should be incorporated into programs that make these improvements affordable, whereas education to improve weaning-age children's diets can be implemented with or without other program supports.     

Regionalization of perinatal care in Europe.

This review describes European health policies related to the place of birth of very preterm babies, and the organizational context in which these policies were enacted using data from two European studies. It also compiles available information on the place of birth of very preterm babies from the published literature. In Europe, there is significant diversity in approaches to the provision of intensive care services for the small proportion of pregnant women and babies that need it, both in terms of health policies and the supply and characteristics of maternity and neonatal units. These diverse models in countries with similar levels of development and medical technology could offer an opportunity to understand how different organizational characteristics affect access to care, health outcomes and resource use.     

Safety of aerosolized INS 365 in patients with mild to moderate cystic fibrosis: results of a phase I multi-center study

Cystic fibrosis (CF) is characterized by defective cystic fibrosis transmembrane regulator (CFTR) expression and function, associated with abnormal ion transport and mucociliary clearance, and clinical lung disease. Triphosphate nucleotides such as uridine-5'-triphosphate (UTP) and INS 365, may be useful for CF through actions, mediated via P2Y(2) extracellular receptors, on chloride and liquid secretion, and ciliary beat frequency. INS 365 may offer chemical stability advantages over UTP. In a randomized, double-blind, multicenter phase I study, we studied the safety and maximally tolerated dose of escalating, single doses of aerosolized INS 365, in adult and pediatric patients with mild to moderate CF lung disease (FEV(1) > or = 45% predicted). In four successive dose cohorts of adult patients (n = 12 per cohort, age > or = 18 years) and four successive pediatric dose cohorts (n = 12 per cohort, age 5-12 years), patients were randomized 3:1 active/placebo (0.9% saline) to evaluate doses of 20, 40, 80, and 100 mg INS 365 delivered by nebulizer (Pari Star ). Sputum was collected pre- and post-dosing to obtain preliminary results on clinical efficacy. After each dose cohort, a Data Safety Monitoring Committee (DSMC) reviewed the data. Forty-eight adult and 36 pediatric patients completed the protocol (up to 100 mg for adults, 80 mg for pediatric patients). The predominant adverse events were cough, wheezing, chest tightness, and a decrease in FEV(1) (occurring in 8/48 adults, and 5/36 pediatric patients), which occurred predominantly in the 80-mg and 100-mg dose cohorts. Though a few adult patients had a tendency to increase sputum production, there was little consistent effect noted on sputum production in this acute, single-dose study. The data suggest that aerosolized INS 365 is safe when delivered at single doses of up to 40 mg in adults and children with CF, but that higher doses are unlikely to be tolerated.     

Repeated adeno-associated virus serotype 2 aerosol-mediated cystic fibrosis transmembrane regulator gene transfer to the lungs of patients with cystic fibrosis: a multicenter, double-blind, placebo-controlled trial

STUDY OBJECTIVES: The primary objective was to determine the safety and tolerability of repeated doses of aerosolized adeno-associated serotype 2 vector containing cystic fibrosis transmembrane conductance regulator (CFTR) complementary DNA (cDNA) [tgAAVCF], an adeno-associated virus (AAV) vector encoding the complete human CFTR cDNA. Secondary objectives included evaluation of pulmonary function assessed by spirometry, lung abnormalities by high-resolution CT (HRCT), airway cytokines, vector shedding, serum neutralizing antibody to AAV serotype 2 (AAV2), and gene transfer and expression in a subset of subjects undergoing bronchoscopy with bronchial brushings. DESIGN: Randomized, double-blind, placebo-controlled, phase II trial. SETTING: Eight cystic fibrosis (CF) centers in the United States. SUBJECTS: CF patients with mild lung disease, defined as FEV(1) > or =60% predicted. INTERVENTIONS: Subjects were randomized to inhale three aerosolized doses of 1 x 10(13) deoxyribonuclease-resistant particles of tgAAVCF or matching placebo at 30-day intervals using the Pari LC Plus nebulizer (PARI; Richmond, VA). Measurements and results: Of 42 subjects randomized, 20 subjects received at least one dose of tgAAVCF and 17 subjects received placebo. No difference in the pattern of adverse events or laboratory abnormalities was noted between the two treatment groups. Improvements in induced-sputum interleukin-8 (p = 0.03) and FEV(1) (p = 0.04) were observed at day 14 and day 30, respectively, in the group receiving tgAAVCF when compared to those receiving placebo. No significant differences in HRCT scans were noted. Vector shedding in sputum was observed at low levels up to 90 days after the third dose of vector. All subjects receiving tgAAVCF exhibited an increase (by at least fourfold) in serum AAV2-neutralizing antibodies and detectable levels in BAL fluid from five of six treated subjects undergoing BAL. Gene transfer but not gene expression was detected in a subset of six tgAAVCF subjects who underwent bronchoscopy. CONCLUSIONS: Repeat doses of aerosolized tgAAVCF were safe and well tolerated, and resulted in encouraging trends in improvement in pulmonary function in patients with CF and mild lung disease.