Inhaled nitric oxide during emergency neonatal transportation

ABSTRACT Inhaled nitric oxide is currently being investigated as a selective pulmonary vasodilator for neonates with persistent pulmonary hypertension. The use of continuous inhaled nitric oxide during emergency transportation of three critically ill neonates with meconium aspiration and pulmonary hypertension is described. The successful application of this technique may allow safer transportation of neonates who require high level intensive care including ongoing nitric oxide, high frequency ventilation and/or extracorporeal life support. Regionally based nitric oxide-equipped retrieval teams may relieve the pressure on smaller neonatal intensive care units to provide inhaled nitric oxide therapy and allow centralization of nitric oxide resources, thus facilitating development of expertise and the completion of meaningful research programs with substantial recruitment.     

Health care and its costs for children with perinatally acquired HIV infection

Objective : To describe survival patterns, use of health services and related costs for Australian children with perinatally acquired human immunodeficiency virus (HIV) infection.
Methodology : A retrospective cross-sectional survey was made of 20 children with HIV infection (91% of those diagnosed) and 13 children with maternal antibodies who subsequently seroreverted, treated at 10 medical centres. Details of disease progression and use of health services were obtained from hospital medical records. Monthly costs for three phases of infection were estimated by linking service usage rates with estimates of the unit cost of each service. The average lifetime cost was estimated by combining monthly costs and phase duration estimates from the literature.
Results : Patterns of disease progression were similar to those reported internationally, with a median survival of 8 years. Use, of health services increased with severity of illness. Mean monthly costs were $120 per month (1992 Australian dollars) for children with maternal antibodies who subsequently seroreverted, $320 per month for children with HIV infection but no acquired immunodeficiency syndrome (AIDS)-defining illness, and $1830 per month for children with AIDS. The present value of total lifetime cost for a child with HIV infection was $48174,46% of which was for treatment of AIDS.
Discussion : The mean lifetime cost for a perinatally infected child was just over half that for a man with HIV in Australia. Health service usage and costs were lower for Australian than American children with HIV.     

Molecular analysis of PKU in Ireland

Classical phenylketonuria (PKU: McKusick No. 261600) is caused by mutations occurring at the phenylalanine hydroxylase (PAH) locus on chromosome 12 and has a prevalence in Ireland of 1 in 4500. We examined 304 independent alleles from 350 patients for the presence of six mutations and have characterized VNTR alleles within the minisatellite region 3' to the PAH gene in patients carrying the most prevalent mutation. R408W was the most common mutation found, with a relative frequency of 42%. All other mutations had relative frequencies of <10%. VNTR analysis showed that the R408W mutation is associated with the VNTR-8 allele in the Irish population, indicating that R408W is associated with RFLP haplotype 1. This differs from that reported from eastern Europe where R408W is associated with RFLP haplotype 2/VNTR-3; an observation which has led several groups to propose a Balto-Slavic origin for this mutation. These results support the hypothesis of a second, independent founding event for the R408W mutation on an RFLP haplotype 1 VNTR-8 chromsome background in the Irish/Celtic population.     

A new method for evaluating antitussives in cats using an electrode-cannula.

An emplaced laryngo-tracheal electrode-cannula was employed to induce and to measure cough in cats anesthetized with either sodium pentobarbital or Dial--urethane. Carbetapentane citrate, codeine sulfate and dextromethorphan hydrobromide were tested for antitussive action by this method. Relative antitussive potency obtained in order of decreasing effectiveness was dextromethorphan hydrobromide, codeine sulfate and carbetapentane citrate.     

Cell type selective accumulation of mercaptoundecahydro-<Emphasis Type="Italic">closo</Emphasis>-dodecaborate (BSH) in glioblastoma multiforme

Summary ¶Background. Boron uptake in glioblastoma tissue for boron neutron capture therapy is of great importance for the clinical outcome of the treatment. Methods. The cell type specific distribution of mercaptoundecahydro-closo-dodecaborate (BSH) in glioblastoma multiforme tissue sections of seven patients having received BSH prior to surgery was investigated by light and fluorescence microscopy. Findings. With use of specific antibodies against different tumour specific epitopes and BSH, BSH was found predominantly (approx. 90%) in the cytoplasm of GFAP-positive cells of all but two patients. The latter were younger (33 and 38 years versus 46–71 (mean 60) years). There was no correlation between BSH uptake and expression of EGFR, p53, CD44 and Ki-67. Interpretation. GFAP-positive cells appear to be the primary cell type for BSH uptake in primary glioblastoma, and an important cell type for localisation of BSH in secondary glioblastoma. The molecular basis and the selective uptake mechanism require further work. If a correlation between histologically distinct patterns and clinical outcome for patients undergoing boron neutron capture therapy could be derived, prognostic factors for the treatment could be developed.Published online October 20, 2003     

Tissue uptake of BSH in patients with glioblastoma in the EORTC 11961 phase I BNCT trial

Summary Purpose: The uptake of the boron compound Na₂B₁₂H₁₀-SH (BSH) in tumor and normal tissues was investigated in the frame of the EORTC phase I trial ‘Postoperative treatment of glioblastoma with BNCT at the Petten Irradiation Facility’ (protocol 11961). Methods and Materials: The boron concentration in blood, tumor, normal brain, dura, muscle, skin and bone was detected using inductively coupled plasma-atomic emission spectroscopy in 13 evaluable patients. In a first group of 10 patients 100 mg BSH/kg bodyweight (BW) were administered; a second group of 3 patients received 22.9 mg BSH/kg BW. The toxicity due to BSH was evaluated. Results: The average boron concentration in the tumor was 19.9 ± 9.1 ppm (1 standard deviation (SD)) in the high dose group and 9.8 ± 3.3 ppm in the low dose group, the tumor/blood ratios were 0.6 ± 0.2 and 0.9 ± 0.2, respectively. The highest boron uptake has been detected in the dura, very low uptake was found in the bone, the cerebro-spinal fluid and especially in the brain (brain/blood ratio 0.2 ± 0.02 and 0.4 ± 0.2). No toxicity was detected except flush-like symptoms in 2 cases during a BSH infusion at a much higher speed than prescribed. Conclusion: BSH proved to be safe for clinical application at a dose of 100 mg BSH/kg infused and at a dose rate of 1 mg/kg/min. The study underlines the importance of a further investigation of BSH uptake in order to obtain enough data for significant statistical analysis. The boron concentration in blood seems to be a quite reliable parameter to predict the boron concentration in other tissues.     

Tissue Uptake of BSH in Patients with Glioblastoma in the EORTC 11961 Phase I BNCT Trial

Purpose: The uptake of the boron compound Na₂B₁₂H₁₀-SH (BSH) in tumor and normal tissues was investigated in the frame of the EORTC phase I trial Postoperative treatment of glioblastoma with BNCT at the Petten Irradiation Facility (protocol 11961).Methods and Materials: The boron concentration in blood, tumor, normal brain, dura, muscle, skin and bone was detected using inductively coupled plasma-atomic emission spectroscopy in 13 evaluable patients. In a first group of 10 patients 100mg BSH/kg bodyweight (BW) were administered; a second group of 3 patients received 22.9mg BSH/kg BW. The toxicity due to BSH was evaluated.Results: The average boron concentration in the tumor was 19.9±9.1ppm (1 standard deviation (SD)) in the high dose group and 9.8±3.3ppm in the low dose group, the tumor/blood ratios were 0.6±0.2 and 0.9±0.2, respectively. The highest boron uptake has been detected in the dura, very low uptake was found in the bone, the cerebro-spinal fluid and especially in the brain (brain/blood ratio 0.2±0.02 and 0.4±0.2). No toxicity was detected except flush-like symptoms in 2 cases during a BSH infusion at a much higher speed than prescribed.Conclusion: BSH proved to be safe for clinical application at a dose of 100mg BSH/kg infused and at a dose rate of 1mg/kg/min. The study underlines the importance of a further investigation of BSH uptake in order to obtain enough data for significant statistical analysis. The boron concentration in blood seems to be a quite reliable parameter to predict the boron concentration in other tissues.     

Impaired detection of variable duration embedded tones in ectopic NZB/BINJ mice

Utilizing rodent models, prior research has demonstrated a significant association between focal neocortical malformations (i.e. induced microgyria, molecular layer ectopias), which are histologically similar to those observed in human dyslexic brains, and rate-specific auditory processing deficits as seen in language impaired populations. In the current study, we found that ectopic NZB/BINJ mice exhibit significant impairments in detecting a variable duration 5.6 kHz tone embedded in a 10.5 kHz continuous background, using both acoustic reflex modification and auditory event-related potentials (AERP). The current results add further support to the association between focal cortical malformations and impaired auditory processing, and the notion that these auditory effects may occur regardless of the cortical location of the anomaly.     

Trends in out-of-pocket spending by insured American workers, 1990-1997

This paper examines trends in out-of-pocket spending for insured workers from 1990 to 1997. Data are from the Consumer Expenditure Survey conducted by the U.S. Bureau of Labor Statistics. The survey collects detailed quarterly data on all consumer spending from logs kept each year by more than 10,000 households with job-based health insurance. During the study period, total out-of-pocket spending in constant dollars remained unchanged. Spending for medical expenses, drugs, and supplies declined by 23 percent, but this decline was offset by rising employee contributions for health insurance premiums. The shift to managed care, whose benefit structure requires less cost sharing, may have played a role in reducing out-of-pocket spending.