A comparison of clinical variables that predict adverse outcome in term infants with severe respiratory failure randomised to a policy of extracorporeal membrane oxygenation or to conventional neonatal intensive care

OBJECTIVE: To identify clinical variables predicting adverse outcome in a group of infants with severe respiratory failure who were randomized either to referral for extra-corporeal membrane oxygenation (ECMO) or to conventional neonatal intensive care within the United Kingdom. METHODS: Adverse outcome was defined by death or disability by four years of age. Receiver operator characteristic (ROC) plots were constructed for variables with continuous data and relative risk (RR) with 95% confidence intervals (CI) calculated for binominal data. RESULTS: Of variables measurable at trial entry, congenital diaphragmatic hernia and lower birthweight was also associated with increased mortality and morbidity. Seizures or supplementary oxygen at discharge were markers of disease course, which predicted a poorer outcome amongst survivors. These variables behaved similarly in the two trial groups. Those infants in the ECMO group with an episode of sepsis, established full sucking feeds after 14 days of age or a hospital stay over 30 days were at increased risk of disability. CONCLUSIONS: This study has identified clinical variables that predict adverse outcome for term infants with severe respiratory failure. The results may assist clinicians caring for these babies, when counseling their families and in the development of guidelines for neonatal ECMO.     

The age-related changes in the incidence of 'natural' anti-sperm antibodies suggest they are not auto-/isoantibodies

PROBLEM: Establishing the age-dependent patterns of sperm antibody levels among normal humans. METHODS OF STUDY: Sera samples from 498 healthy subjects aged 0-97 years - 246 males and 252 females - were tested by the gelatin agglutination test of Kibrick, tray agglutination test of Friberg, sperm immobilization test of Isojima and enzyme-linked immunosorbent assay (ELISA). RESULTS: We found a significant increase in the level of sperm agglutinins after 40 years, which decreased after 88 years. The antibodies detected by ELISA were the highest among prepubertal subjects and also declined with aging. No age-dependent changes were established for the sperm immobilizins. With few exceptions, there were no significant differences between male and female sera, as well as between sera of newborn and their mothers. CONCLUSIONS: These data are similar to those established for the age-dependent changes of antibodies towards exogenous antigens, suggesting that the 'naturally occurring' antibodies against human spermatozoa are not auto-/isoantibodies.     

Oxidative stress and neuronal adaptation in Alzheimer disease: the role of SAPK pathways

Recent evidence indicates that oxidative stress occurs early in the progression of Alzheimer disease, significantly before the development of the hallmark pathologies, namely neurofibrillary tangles and senile plaques. The interaction of abnormal mitochondria, redox transition metals, and oxidative stress response elements contributes to the generation of reactive oxygen species in diseased neurons. Oxidative damage to major cellular molecules is seen in a number of disease states that are either acute or chronic and it is apparent that without eliciting compensations that restore redox balance, cells will rapidly succumb to death. Indeed, although oxidative stress is a prominent feature in Alzheimer disease, few vulnerable neurons show clear signs of apoptosis, suggesting that the level of oxidative stress does not significantly exceed neuronal oxidative defenses. In light of this observation, we propose that neurons in Alzheimer disease are exposed to low, but chronic, levels of oxidative stress that lead neurons to elicit adaptive responses such as the activation of stress-activated protein kinase pathways.     

"New century,new challenges"

The recently published report ‘New Century, New Challenges’from the Heads of Departments of General Practice and PrimaryCare sets out a vision for the development of academic generalpractice in the UK.¹ It reviews the substantial challenges nowfacing the academic departments and shows clearly how more investmentis essential if general practice and primary care services topatients are to be improved under the Government’s NHSPlan.² In 2001, there were 31 academic departments of general practiceand primary care in the UK compared with 24 departments in 1986.In the period since 1986, the number of professors of generalpractice increased from 16 to 66, and the proportion of non-clinical     

Impact of metals on the biodegradation of organic pollutants

Forty percent of hazardous waste sites in the United States are co-contaminated with organic and metal pollutants. Data from both aerobic and anaerobic systems demonstrate that biodegradation of the organic component can be reduced by metal toxicity. Metal bioavailability, determined primarily by medium composition/soil type and pH, governs the extent to which metals affect biodegradation. Failure to consider bioavailability rather than total metal likely accounts for much of the enormous variability among reports of inhibitory concentrations of metals. Metals appear to affect organic biodegradation through impacting both the physiology and ecology of organic degrading microorganisms. Recent approaches to increasing organic biodegradation in the presence of metals involve reduction of metal bioavailability and include the use of metal-resistant bacteria, treatment additives, and clay minerals. The addition of divalent cations and adjustment of pH are additional strategies currently under investigation.     

The cancer technology appraisal programme of the UK's National Institute for Clinical Excellence

The National Institute for Clinical Excellence (NICE) was established to ensure faster and more equitable uptake of new technologies by the NHS, through the provision of guidance on clinical and cost-effectiveness. The treatment of cancer is one of the UK government's priority areas and a range of guidance products have been developed by NICE to support implementation of national plans for managing patients with cancer in England and Wales. In its first 3 years, NICE's main activity was the "Technology Appraisals Programme" and it has created considerable interest and some controversy. 15 (out of a total of 56) technology appraisals related to oncology have been completed and another four are in preparation. The open, transparent, and inclusive approach NICE has adopted in reaching its decisions highlights the difficult ethical issues that need to be addressed in seeking to balance individual desires with public-health requirements. In this review we describe the process of appraising technologies, and address the recent criticism of the appraisal programme with regard to treatment of patients with cancer.     

A comparison of methods for gene dosage analysis in HMSN type 1

A number of different approaches are used in diagnostic laboratories to detect the 1.5 Mb duplication at 17p11.2 seen in approximately 70% of patients with hereditary motor and sensory neuropathy type 1 (HMSN1). Here we compare the methods used in UK diagnostic laboratories to detect the duplication. Samples referred to participating centres for HMSN testing were collected, randomised, and distributed for testing. One hundred samples were examined using five different methods; each method was tested by two independent laboratories. Identical results were obtained from all laboratories for 44 samples. The remaining samples were classified as duplication positive or duplication negative on the basis of the same result by two or more methods. A total of 95 samples were classified by more than one method, two were withdrawn from the study as the same result was not obtained by two methods, and three are thought to have a duplication smaller than 1.5 Mb. Seven of 49 duplications were not detected by methods used to detect the common junction fragment and the use of microsatellites failed to yield a result in four of 95 samples. Sequence tagged site (STS) dosage analysis was found to be the most sensitive of the methods tested, although this method was found to be the most likely to require repeat analysis. Eight samples gave discordant results between the two laboratories testing by the same method. Upon retesting, reasons for the initial incorrect result included processing and typographical errors.