A standardised protocol for the validation of banking methodologies for arterial allografts.

The objective of this study was to design and test a protocol for the validation of banking methodologies for arterial allografts. A series of in vitro biomechanical and biological assessments were derived, and applied to paired fresh and banked femoral arteries. The ultimate tensile stress and strain, suture pullout stress and strain, expansion/rupture under hydrostatic pressure, histological structure and biocompatibility properties of disinfected and cryopreserved femoral arteries were compared to those of fresh controls. No significant differences were detected in any of the test criteria. This validation protocol provides an effective means of testing and validating banking protocols for arterial allografts.

Control of Culicoides sonorensis (Diptera: Ceratopogonidae) blood feeding on sheep with long-lasting repellent pesticides.

Culicoides sonorensis is the primary vector of bluetongue and epizootic hemorrhagic disease viruses in North America. Bluetongue disease is one of the most economically important arthropod-borne diseases of sheep in North America, because it causes significant morbidity and mortality and can lead to local quarantines and international trade restrictions. Long-lasting repellent pesticides could be applied to sheep as they are moved down from mountain pastures to protect them from biting midges until the 1st frost. We tested long-lasting pesticides on sheep as repellents against C. sonorensis. Both Python ear tags with 10% zeta-cypermethrin (9.8 g/tag) synergized with 20% piperonyl butoxide (PBO) and a 12-ml low-volume spray application of ready-to-use sheep insecticide (Y-TEX) with 2.5% permethrin and 2.5% PBO in an oil-based formulation were repellent to C. sonorensis for at least 3-5 wk after a single application.

Accumulation of factors influencing children's middle ear disease: risk factor modelling on a large population cohort.

STUDY OBJECTIVES: Data were analysed from a large national birth cohort to examine cumulative and interactive prediction from various risk factors for childhood middle ear disease, and to resolve conflicting evidence arising from small and incompletely controlled studies. The large sample size permitted appropriate covariate adjustment to give generality, and permit demographic breakdown of the risk factors. SETTING: A large multi-purpose longitudinal birth cohort study of all births in the UK in one week in 1970, with multiple questionnaire sweeps. PARTICIPANTS: Over 13,000 children were entered into the original cohort. Data on over 12,000 children were available at the five year follow up. MAIN OUTCOME MEASURES: For children at 5 years, parent reported data were available on health and social factors including data on two markers for middle ear disease: the occurrence of purulent (nonwax) ear discharge and suspected or confirmed hearing difficulty. MAIN RESULTS: In those children who had ever had reported hearing difficulty (suspected or confirmed), after control for socioeconomic status, three of the classic factors (male sex, mother's smoking habits since birth, and attending day care) were significantly more frequent. In those who had ever had ear discharge reported, only mother's smoking habit since birth was significantly more frequent. However, it showed an orderly dose response relation. In addition, a derived general child health score was found to be significantly associated with both the middle ear disease markers. Control for this variable in the analysis of those having reported hearing difficulty reduced the effect size of mother's smoking habit, but it remained statistically significant. For reported ear discharge, even after control for the general health score and social index, mother's smoking habits and day care attendance were both significant predictors. Mother's (but not father's) smoking habits and day care attendance were found to be significant risk factors for middle ear disease. Breast feeding effects were weak and did not generally survive statistical control. CONCLUSIONS: A child having all three risk factors (attends day care, a mother who smokes, and male sex) is 3.4 times more likely to have problems with hearing than a child who has none, based on cumulative risk. Further studies should focus on preventative risk modification and well specified intervention.

A self-administered questionnaire for detection of unrecognised coronary heart disease.

On an individual and a population basis, an increased incidence of coronary heart disease is associated with classical cardiovascular risk factors, but many cases occur in people not identified as at high risk. Conversely, many people at high statistical risk do not develop coronary disease. We used a questionnaire to identify unrecognised coronary heart disease in people attending large-scale health survey centres. Participants were required to report the presence and characteristics of any chest pain. Those returning responses consistent with myocardial ischaemia were offered treadmill exercise ECG tests. Over 18 months, 4070 questionnaires were returned. Of 475 respondents offered testing, 229 (198 male, 131 female) accepted. Thirty-two subjects (15 male, 17 female: a detection rate of 13.9 per cent of those assessed as likely on questionnaire, or 0.8 per cent of all respondents) had results consistent with significant coronary heart disease. Follow-up was available in 30 cases. There was no difference in classical risk-factor distribution (including multivariate risk percentiles: 42.4 (male) and 46.7 (female)) between those newly diagnosed with coronary heart disease and their community counterparts. More women than men were identified as suffering from unrecognised coronary heart disease, with a preponderance of younger women. Cost per case identified was A$1220. Screening by self-administered questionnaire is a useful and relatively cost-effective means of identifying unrecognised coronary heart disease.

Inequalities in prescribing of secondary preventative therapies for ischaemic heart disease in Ireland.

The study aim is to quantify the variation in prescribing rates of secondary preventative therapies for Ischaemic Heart Disease (IHD) across regions, age and gender. Patients receiving any prescriptions for a nitrate during a one year period (September 1999-August 2000) were considered using a national primary care prescribing database. Age-sex standardised prescribing rates of four secondary preventative therapies for IHD (Ace inhibitors, beta-blockers, aspirin, statins) were calculated for each region. Wide variations between regions were observed with significantly higher variability for Ace inhibitors compared with aspirin (F-ratio=22.8, p<0.001). Men were more likely to prescribed these therapies and the elderly were less likely (except Ace inhibitors). The study suggests that access to secondary preventative therapy is not equitable across regions, gender and age in Ireland. The wide variability may be due to uncertainty in prescribing secondary preventative therapies and/or variability in clinical need between regions.

Role of continuous positive airway pressure to the non-ventilated lung during one-lung ventilation with low tidal volumes.

INTRODUCTION: In multiple study populations large tidal volumes (8 - 12 ml/kg) have deleterious effects on lung function in multiple study populations. The accepted approach to hypoxemia during one-lung ventilation is the application of continuous positive airway pressure to the non-ventilated lung first, followed by application of positive end-expiratory pressure to the ventilated lung. To our knowledge the effectiveness of positive end-expiratory pressure or continuous positive airway pressure on maintaining PaO(2) with one-lung ventilation was not studied with smaller tidal volume (6ml/kg) ventilation. Our objective was to compare continuous positive airway pressure of 5 cm H(2)O or positive end-expiratory pressure of 5 cm H(2)O during small tidal volume one-lung ventilation. METHODS: Thirty patients undergoing elective, open thoracotomy with one-lung ventilation were randomized to continuous positive airway pressure or positive end-expiratory pressure and then crossed over to the other modality.  RESULTS: There was a statistically significant higher PaO(2) (141±81.6 vs 112±48.7, p = 0.047) with continuous positive airway pressure than positive end-expiratory pressure while on one-lung ventilation. Two patients desaturated requiring 100% O(2) with both positive end-expiratory pressure and continuous positive airway pressure. On two occasions the surgeon requested the continuous positive airway pressure be discontinued due to lung inflation. CONCLUSION: The use of continuous positive airway pressure of 5 cm H(2)O to the non-ventilated lung while using small tidal volumes for one-lung ventilation improved PaO(2) when compared with positive end-expiratory pressure of 5 cm H(2)O to the ventilated lung.

The utilization review program. Essential for hospital survival.

The survival of a health care institution in today's economic climate is dependent on, among other things, the efficiency of its utilization review program. The purpose of this article is to serve as a basic guideline for an institution to develop an adequate utilization review program. It emphasizes that a utilization review program is essential for the economic survival of any health care industry. The utilization review program should be an integrated organization with the support of administration, and the participation of staff physicians, physician advisors, review nurses, and important hospital departments, such as social service, laboratory, medical records, preplanning, and so forth. Following the format presented in this paper, an institution may easily develop a utilization review program. The ideas presented in this paper have been time-proven at our institution. There must be educational programs for physicians on the basics of managing patients according to the prospective payment system and the economic impact physicians can make on the hospital's economic status. These educational presentations must take place as often as necessary to reinforce policy and procedure, and to carry out effective patient management. The utilization review department, as well as the medical staff, must work in close harmony with administration to assist the facility in surviving trying economical times.

Behaviour and cognitive outcomes from middle ear disease.

OBJECTIVES: To resolve controversies over associations between a history of middle ear disease and psychosocial or cognitive/educational outcomes. DESIGN: Multipurpose longitudinal birth cohort study. Original cohort comprised all UK births between 5 and 11 April 1970; data were available for approximately 12,000 children at 5 years old and 9000 children at 10 years old. METHODS: For 5 year old children, parent reported data were available on health, social, and behavioural factors, including data on two validated markers of middle ear disease. Cognitive tests were administered at 5 and 10 years of age, and behavioural problems rated at 10 years by the child's teacher. RESULTS: After adjustment for social background and maternal malaise, the developmental sequelae of middle ear disease remained significant even at 10 years. The largest effects were observed in behaviour problems and language test data at age 5, but effect sizes were modest overall. IMPLICATIONS: These results provide an epidemiological basis for policies that aim to minimise the sequelae of middle ear disease by awareness in parents and preschool teachers, early referral, and intervention for more serious or persistent cases.

Under-prescribing of cardiovascular therapies for diabetes in primary care.

OBJECTIVE: To determine the extent to which cardiovascular therapies are prescribed in primary care for those with diabetes, compared with those without diabetes. METHODS: Population study of patients with and without diabetes identified using a national primary care prescribing database. All patients receiving a prescription for any diabetes therapy, including insulin and oral hypoglycaemic drugs, or diagnostic test kit for glucose ( n=8523) and those receiving no such therapies ( n=145,756) during a 1-year period (September 1999-August 2000) in the Eastern Regional Health Authority of Ireland were identified. In addition, a sub-set of patients receiving a nitrate prescription, a marker for ischaemic heart disease (IHD), were also identified ( n=14,826). Odds ratios and 95% confidence intervals for prescribing of cardiovascular therapies between those with diabetes and those without, adjusted for age and gender, were calculated using logistic regression. RESULTS: The proportion of those (and 95% CES) with diabetes and IHD prescribed secondary preventative therapies was 37.3% (35.0, 39.6) for statins, 55.3% (53.0, 57.6) for angiotension converting enzyme inhibitors, 34.7% (32.5, 36.9) for beta blockers, 73.3% (71.2, 75.4) for aspirin, 4.4% (3.4, 5.4) for angiotensin-II antagonists and 2.5% (1.8, 3.2) for fibrates. The adjusted odds ratios for prescribing in those with diabetes compared with those without are 1.44 (1.30, 1.61) for statins, 3.09 (2.79, 3.42) for angiotension converting enzyme inhibitors, 0.82 (0.74, 0.91) for beta blockers, 1.23 (1.09, 1.38) for aspirin, 1.47 (1.13, 1.87) for angiotensin-II receptor blockers and 4.23 (2.88, 6.14) for lipid-lowering fibrates. CONCLUSION: The greater rate of prescribing of cardiovascular therapies in those with diabetes relative to those without is not unexpected given the higher risk of coronary heart disease in those with diabetes. However, the proportion of patients with diabetes, particularly those with established IHD, prescribed cardiovascular therapies is considerably below that recommended in local and international guidelines.

Behaviour and developmental effects of otitis media with effusion into the teens.

OBJECTIVE: To examine whether behavioural or cognitive sequelae of otitis media with effusion (OME) continue into late childhood and the early teens (11-18 years). SETTING: Data from a large multipurpose birth cohort study: the Dunedin multidisciplinary health and development study. PARTICIPANTS: Around 1000 children from the study. The main independent variable of interest was otological status of the child up to age 9. MAIN OUTCOME MEASURES: Parent and teacher rated behaviour problems, including antisocial, neurotic, hyperactive, and inattentive behaviours, and tests of academic achievement including intelligence quotient (IQ), reading, and spelling were available in a high proportion of the cohort at ages 11 to 18 years. RESULTS: After adjustments for covariates such as socioeconomic status, hyperactive and inattentive behaviour problems were evident as late as 15 years, and lower IQ associated with OME remained significant to 13 years. The largest effects were observed for deficits in reading ability between 11 and 18 years. CONCLUSIONS: No previous study considering behaviour problems as an outcome has followed children long enough to determine whether some of the early sequelae of OME are still present in the early to late teens. Some developmental sequelae of OME, particularly deficits in reading ability, can persist into late childhood and the early teens.

A follow-up study of breast and other cancers in families of an unselected series of breast cancer patients.

The cancer experience among relatives of an unselected cohort of 402 breast cancer patients was previously reported. Cases and their first degree relatives were flagged at the National Health Service Central Register for continuous notification of cancer registrations and deaths. More than 10 years of follow-up data have been analysed to update cancer risks overall and to estimate breast cancer risk in relatives prospectively according to family history at the time of breast cancer diagnosis in the index case. Significant excesses of breast cancer (RR 2.24, P<0.0001), prostate cancer (RR 1.71, P=0.039) and bone sarcoma (RR 6.564, P=0.042) overall and soft tissue sarcoma in mothers only (RR 15.44, P=0.001) were found. There was no excess of any other cancer, including ovarian. High breast cancer risk in relatives was associated with young age at diagnosis in the index (index <40 years at diagnosis, RR in relatives 3.76, P=0.004). Prospective risk of breast cancer was higher in relatives of index patients who had an affected first degree relative at the time of their diagnosis (no family history, RR 1.87, P=0.012; with a family history, RR 3.72, P=0.015). These prospective risk estimates are valuable in advising relatives of newly diagnosed breast cancer patients.

Quantitative trait loci affecting dengue midgut infection barriers in an advanced intercross line of Aedes aegypti.

Quantitative trait loci (QTL) affecting the ability of the Aedes aegypti midgut to become infected with Dengue 2 virus (DEN2) were mapped in the F5 generation of an advanced intercross line (AIL). A strain of Ae. aegypti previously selected for DEN2 susceptibility was crossed to a new strain selected for refractoriness to midgut infection. In P1 and F1 parents and 147 F5 offspring, genotypes at forty-four cDNA loci were analysed. A new sex linked QTL and a second QTL on chromosome II with genotypes subject to balancing selection were detected that condition midgut susceptibility. Alleles at these QTL contributed additively in determining susceptibility and accounted for approximately 24% of the phenotypic variance. Markers associated with a midgut escape barrier were inconsistently supported.

Immunity to onchocerciasis: cells from putatively immune individuals produce enhanced levels of interleukin-5, gamma interferon, and granulocyte-macrophage colony-stimulating factor in response to Onchocerca volvulus larval and male worm antigens.

Antigen-specific interleukin-5 (IL-5), gamma interferon (IFN-gamma), and granulocyte-macrophage colony-stimulating factor (GM-CSF) responses in individuals living in an area of hyperendemicity for onchocerciasis in Cameroon were examined. The responses against antigens prepared from Onchocerca volvulus third-stage larvae (L3), molting L3 (mL3), and crude extract from adult males (M-OvAg) were compared to the responses against antigens from adult female worms and skin microfilariae. Cytokine responses for the putatively immune individuals (PI) and the infected individuals (INF) were compared. A differential cytokine profile of IL-5 (Th2 phenotype) and IFN-gamma (Th1 phenotype) was found in these individuals in response to the antigens. In both the PI and the INF, Th2 responses against all the antigens tested were dominant. However, in the PI group as a whole, there was an enhanced Th2 response against the larval antigens and the adult male and adult female antigens, and a Th1 response in a subgroup of the PI (27 to 54.5%) against L3, mL3, and M-OvAg antigens was present. While the PI produced significantly higher levels of GM-CSF against L3, mL3, and M-OvAg antigens than the INF, there was no difference in the GM-CSF responses of the groups against the other antigens. The present study indicated that, in comparison to the INF, the PI have distinct larva-specific and adult male-specific cytokine responses, thus supporting the premise that immunological studies of the PI would lead to the identification of immune mechanisms and the target genes that play a role in protective immunity.