The Baby Hearts Study - a case-control methodology with data linkage to evaluate risk and protective factors for congenital heart disease.

INTRODUCTION: The Baby Hearts study aimed to investigate risk and protective factors for congenital heart disease (CHD), and to investigate the health behaviours of a representative sample of pregnant women in Northern Ireland. OBJECTIVES: We describe and evaluate the population-based case-control design enhanced with data linkage to administrative health data. METHODS: Cases (mothers of babies with CHD, n=286) were recruited following diagnosis prenatally or postnatally. Controls (mothers of babies without CHD, n=966) were recruited at 18-22 weeks gestation, from all women attending each maternity unit during a designated month. Hybrid data collection methods were used, including a self-administered iPad/postal questionnaire, and linkage to maternity and prescription records. RESULTS: Refusal rates were low (8%). iPad questionnaire completion at clinic or home visit had high acceptability whereas postal questionnaires were poorly returned leading to a further 9-10% loss of eligible cases/controls. In total, 61% of eligible cases and 68% of eligible controls were recruited, closely representative of the Northern Ireland population, with no evidence of selection bias. Of those recruited, 97% gave consent for linkage to medical records. Thirty-three percent of women had an unplanned pregnancy and 76% suspected they were pregnant by 5 weeks gestation, with no significant differences between cases and controls. There was considerable discordance between self-report, maternity and prescription records regarding medications obtained/taken in the first trimester, but no evidence of differences between cases and controls that would indicate substantial recall bias. Although there was high concordance between self-report and maternity records regarding folic acid supplementation, cases had significantly lower concordance than controls. CONCLUSIONS: Our results suggest hybrid data collection approaches are a useful way forward for aetiological studies to reduce responder burden and address and estimate recall bias, and that the Baby Hearts study protocol is suitable for replication in other populations, modified to the local context.

Psychological problems in children with hemiplegia: a European multicentre survey.

OBJECTIVE: To describe the prevalence and determinants of psychological problems in European children with hemiplegia. DESIGN: Cross-sectional survey. SETTING: Home visits in nine European regions by research associates who administered standard questionnaires to parents. PATIENTS: 279 children with hemiplegia aged 8-12 years were recruited from population-based case registers. OUTCOME MEASURE: Strengths and Difficulties Questionnaire comprising emotion, conduct, hyperactivity, peer problems and prosocial domains. An "impact score" (IS) measures the social and psychological impact of the child's difficulties. RESULTS: Children with hemiplegia had higher mean scores on the total difficulties score (TDS) compared with a normative sample (p<0.001). 48% and 57% of children, respectively, had borderline-abnormal TDS and IS. Significant, independent associations were observed between intellectual impairment and an increased risk for hyperactivity (odds ratio; OR 8.4, 95% CI 3.4 to 20.8), peer problems (OR 3.1, 95% CI 1.7 to 5.5), psychological and social impact (OR 3.0, 95% CI 1.6 to 5.6) when children with an intellectual quotient (IQ) <50 were compared with those with an IQ >70. Boys had an increased risk for conduct (OR 2.1, 95% CI 1.2 to 3.7) and hyperactivity disorders (OR 2.5, 95% CI 1.4 to 4.6). Poor self-esteem was associated with an increased risk for peer problems (OR 5.8, 95% CI 2.5 to 13.4) and poor prosocial skills (OR 7.5, 95% CI 2.4 to 23.2) compared with those with high self-esteem. Other determinants of psychological adjustment were impaired communication, severe pain and living with a single parent. CONCLUSIONS: Many of the psychological problems identified are amenable to treatment. Special attention should be given to those at highest risk of developing psychological difficulties.

Self-perception in overweight and obese children: a cross-sectional study.

AIM: The aim of this study was to examine the relationship between obesity and self-esteem in children in relation to specific domains of their self-perception, and further to explore the extent to which this may vary by gender and economic circumstances. METHOD: A total of 211 children aged 8-9 years drawn from both advantaged and disadvantaged areas of Belfast completed the Harter Self-Perception Profile for Children and measures of body mass index were obtained. RESULTS: Overweight, impoverished children had significantly reduced social acceptance and physical competence scores. Boys had significantly lower scores than girls in the behavioural conduct domain. Girls had significantly lower scores than boys for the athletic competence. CONCLUSION: These results suggest that risk factors of increased weight and impoverished backgrounds have a combined negative effect, placing some children at increased risk of having lower self-perceptions in some, but not all domains. Health interventions for childhood obesity should consider the likelihood of specific relationships between physical and psychosocial factors.

A phase II trial of 6-hydroxymethylacylfulvene (MGI-114, irofulven) in patients with advanced non-small cell cancer previously treated with chemotherapy.

PURPOSE: To test the efficacy and safety of the novel antitumor agent MGI-114 (NSC 683863) in patients with advanced non-small cell lung cancer (NSCLC) previously treated with chemotherapy. METHODS: A two-stage accrual design was used to ensure detection of a true response rate of at least 20% with a type I error of .04. Eligible patients received 11 mg/m2 daily for five consecutive days. Cycles were repeated every 28 days. RESULTS: Fifteen patients received a total of 34 cycles of MGI-114. All patients had a performance status of 0 or 1. Eleven patients had previously received carboplatin and paclitaxel +/- radiation. Two patients had received cisplatin and CPT-11, one patient had received weekly paclitaxel, and one patient had received carboplatin and docetaxel. None of the first 15 patients enrolled experienced objective tumor response, and the study was closed. Forty percent of patients developed > or = grade 2 thrombocytopenia. Grade 3 nausea and > or = grade 2 vomiting were observed in 40% and 47% of patients respectively. Thirty-three percent of patients experienced > or = grade 2 fatigue. CONCLUSIONS: MGI-114, at this dose and schedule, does not have significant activity as second line therapy for patients with advanced NSCLC.

Selecting respirators for control of worker exposure to infectious aerosols.

A method for selecting respirators for protection in infectious aerosol environments was developed, building on a procedure used to choose respiratory protection for environments containing nonbiological contaminants. Modifications in the traditional respirator selection method are proposed for situations where information on occupational exposure limits, toxicity, and airborne concentrations is absent. Toxicity is determined from risk rankings proposed by a variety of organizations. The nature of the activity allows assessment of source generation, which is combined with room volume and airflow to obtain a ranking of airborne concentration. Finally, concentration and toxicity ranks determine a minimum assigned protection factor, which corresponds to a respirator class. Case studies are presented to illustrate the proposed decision logic. For each situation, the procedure yielded choices that were both protective and reasonable. These results suggest that the procedure will be applicable to a variety of settings for a range of infectious organisms.

Improved methods for generation, sampling, and recovery of biological aerosols in filter challenge tests.

In preparation for filter efficiency tests and sampler comparison studies, methods of biological aerosol generation, sampling, and filter recovery were modified from previous studies. Methods described include (1) techniques for generating aerosols that reduced nuisance particles to negligible levels and increased the cell culturability of Mycobacterium abscessus by 30%, (2) sampling techniques that lowered the detectable range of biological particle size from 0.65 to 0.45 micron and reduced the sampling flow from the chamber from 28.3 to 1.5 L/min, and (3) development of methods to remove culturable organisms from respirator filter media. These methods were developed for filter challenge tests with M. abscessus and were applied to two other bacteria. They may also have application to a wider variety of organisms and bioaerosol assessments.

Collection of three bacterial aerosols by respirator and surgical mask filters under varying conditions of flow and relative humidity.

A variety of respirator filters and surgical masks were challenged with three aerosolized bacteria: Mycobacterium abscessus (M.a.) (a rod), Staphylococcus epidermidis (S.e.) (a sphere), and Bacillus subtilis (B.s.) (a rod). Tests were conducted at two flow rates (45 and 85 l./min) and two humidity levels (30 and 70%). Aerosols were measured with a total-particle, direct-reading, spectrometer and a viable particle cascade impactor. Measurements up- and downstream of the filter or mask were used in determining aerosol penetration; respirator or surgical mask fit was not evaluated. Bioaerosol penetration measured with two aerosol sampling instruments was found to correlate. Additionally, bioaerosol test parameters were evaluated with respect to their effect on penetration. Increasing flow resulted in increased penetration of all organisms while an increase in relative humidity did not exert a consistent effect on all organisms. Of the respirators approved by the National Institute for Occupational Safety and Health (NIOSH), filter efficiency was as expected with dust/mist respirators having the lowest and HEPA filters the highest efficiency. Surgical masks were the least efficient of all filters tested; these are not certified by NIOSH. Bioaerosol penetration was compared to that of a polystyrene latex sphere (PSL) aerosol. Penetration of the test aerosols was predicted on the basis of particle aerodynamic diameter and was expected to be in this order: PSL > M.a. > S.e. = B.s. The PSL aerosol was the most penetrating, as predicted. However, results showed that B.s. was more penetrating than S.e. The aerodynamic diameter may not be the best parameter for predicting aerosol penetration of non-spherical particles in these filters.

The amiloride resistance gene, car1, of Schizosaccharomyces pombe.

Amiloride, an inhibitor of various sodium transporters, is toxic to Schizosaccharomyces pombe at low concentration in minimal but not in rich media. Amiloride-resistant mutants were isolated and shown to represent a new locus (car1 for changed amiloride resistance) on chromosome I. The car1 gene was cloned and sequenced. Sequence analysis revealed an open reading frame of 526 amino acids with a predicted molecular weight of 58,545 Da. It has 52% hydrophobic residues and belongs to the class of 12-transmembrane-domain transport proteins. Gene disruption of car1 results in increased amiloride resistance. car1 has sequence similarity to proteins from Candida associated with resistance to benomyl, methotrexate and cycloheximide. No single physiologically identifiable component of sodium transport appeared to be lost. We propose that car1 serves an uptake function, perhaps as a symport with an unknown substrate and this carrier may transport amiloride into the cell. Further, we suggest that amiloride toxicity at low concentrations is not due to its effect on sodium transport but, rather, depends on intracellular interference with an unknown biosynthetic pathway.

Gene amplification at a locus encoding a putative Na+/H+ antiporter confers sodium and lithium tolerance in fission yeast.

We have identified a new locus, sodium 2 (sod2) based on selection for increased LiCl tolerance in fission yeast, Schizosaccharomyces pombe. Tolerant strains have enhanced pH-dependent Na+ export capacity and sodium transport experiments suggest that the gene encodes an Na+/H+ antiport. The predicted sod2 gene product can be placed in the broad class of transporters which possess 12 hydrophobic transmembrane domains. The protein shows some sequence similarity to the human and bacterial Na+/H+ antiporters. Overexpression of sod2 increased Na+ export capacity and conferred sodium tolerance. Osmotolerance was not affected and sod2 cells were unaffected for growth in K+. In a sod2 disruption strain cells were incapable of exporting sodium. They were hypersensitive to Na+ or Li+ and could not grow under conditions that approximate pH7. The sod2 gene amplification could be selected stepwise and the degree of such amplification correlated with the level of Na+ or Li+ tolerance.

Transitional cell carcinoma of the bladder: patterns of recurrence after cystectomy as determined by CT.

CT scans have been recommended for examination of patients at risk for recurrent transitional cell carcinoma after cystectomy. For CT to be useful in this regard, the location and type of recurrences must be known, so that appropriate scans can be made. Therefore, we retrospectively studied CT scans in 27 postcystectomy patients with recurrent transitional cell carcinoma of the bladder to identify the type and location of the recurrent disease. Recurrence was documented by biopsy in 18 patients and by progression of disease shown on serial CT scans in nine patients. All 27 patients had pelvic CT, and 23 had concomitant abdominal CT. Tumor recurred at the cystectomy site in 10 (37%) of 27 patients, pelvic adenopathy was present in 18 (67%) of 27 patients, and retroperitoneal adenopathy was present in 13 (57%) of 23 patients. Tumor recurrence at the cystectomy site was associated with pelvic adenopathy in seven of 10 patients, and the cystectomy site was the solitary site of disease in the remaining three patients. Conversely, in 11 of 18 patients with pelvic adenopathy no recurrence was seen at the cystectomy site. Combined retroperitoneal and pelvic adenopathy was identified in 11 of 23 patients, but two patients had retroperitoneal lymphadenopathy as their only site of recurrence. Hepatic metastases were seen in seven (30%) of 23 patients; six of these seven patients had metastases elsewhere. In four of five patients in whom underestimation of recurrent disease occurred, the deep pelvis and/or deep perineal space were involved. Our results show that the pelvis is the most common site for recurrence. Cystectomy site or retroperitoneal nodal recurrences are usually accompanied by pelvic adenopathy, but the converse is not as common. Our findings of deep perineal and isolated abdominal recurrences indicate that proper protocol for CT follow-up of the postcystectomy patient should include abdominal scans and scans through the perineum.

Rhesus diploid rabies vaccine (adsorbed), a new rabies vaccine. Results of initial clinical studies of preexposure vaccination.

To meet the need for a safe, efficacious, and low-cost rabies vaccination program, the Michigan Department of Public Health developed a new rabies vaccine: rhesus diploid rabies vaccine, adsorbed (RDRV). Initial clinical studies were conducted in 534 volunteers using preexposure protocols consisting of two injections of RDRV given 1, 2, or 4 weeks apart. This new rabies vaccine induced an excellent rabies virus antibody response two to three weeks after vaccination: antibody levels were superior to those reported after duck embryo rabies vaccine and were similar to those reported with human diploid rabies vaccine. In addition, vaccination with RDRV was associated with an acceptable level of local and constitutional symptoms.

General anesthesia for newborn pigs.

A safe technique for the induction and maintenance of general anesthesia in newborn pigs was accomplished. After premedication with atropine sulphate, anesthesia was induced by giving a mixture of oxygen, nitrous oxide and 2.5% halothane introduced by face mask. An endotracheal tube was inserted, and anesthesia was maintained using 0.5--1% halothane. Recovery was prompt, and there were no postoperative complications related to anesthesia.