Lysine α-ketoglutarate reductase, but not saccharopine dehydrogenase, is subject to substrate inhibition in pig liver

The activity of lysine α-ketoglutarate reductase (LKR), the initial enzyme in the principal pathway of lysine catabolism, is a primary determinant of whole-body lysine status. Past research indicated that LKR activity was predominantly hepatic; recent in vivo data suggest that other tissues can also catabolize lysine. The hypothesis of this investigation was that lysine catabolism takes place in extrahepatic tissues in pigs and that the enzymes involved may be subject to inhibition or activation. Using mitochondria from various tissues of market-age pigs, the activities of LKR and saccharopine dehydrogenase were measured. Liver mitochondria had the highest LKR activity, and the enzyme was subject to substrate inhibition. Mitochondria from the muscle, kidney, heart, and intestinal epithelial cells all had measurable LKR activity. The LKR activity was significantly inhibited by a variety of compounds including saccharopine, α-aminoadipate, α-ketoadipate, 5-hydroxy-l-lysine, and several metals. Oxidation of ¹⁴C-lysine to ¹⁴CO₂ was demonstrated in mitochondria isolated from the liver, muscle, and intestinal epithelial cells. Western blotting confirmed the presence of the α-aminoadipate δ-semialdehyde synthase protein in some extrahepatic tissues. These data show a significant capacity for lysine degradation in these extrahepatic tissues, most notably in cells of the intestine and muscle. These tissues should be considered important contributors to whole-body lysine catabolism.     

Emergencies in continuous dialysis patients: diagnosis and management

The number of patients undergoing long-term hemodialysis and peritoneal dialysis is growing in the United States. To provide adequate emergent care to these patients emergency physicians must understand the alterations in normal physiologies present in these patients and how this may affect care. Cardiovascular disease and infection (especially Staphylococcus aureus sepsis) are the leading causes of death among dialysis patients. These patients are also subject to a significantly higher incidence of life-threatening electrolyte disturbances, particularly hyperkalemia and hypercalcemia, than the general population. Suicide, cardiac tamponade, intracranial hemorrhage, bleeding disorders, and bowel infarction are also much more frequent. The inability of dialysis patients to excrete drugs, metabolites, toxins, and fluids significantly alters their responses to common emergencies and should directly influence their care. Failure to recognize these differences in physiology may result in the use of standard forms of emergency therapy that may compound, rather than treat, the underlying disorder. Although most dialysis patients who come into an emergency department have conditions that can, and should, be managed by their nephrologist, the presence of a life threatening emergency requires prompt, appropriate therapy by the emergency physician.     

Uptake of screening for breast cancer in South Lancashire

Study objective: To describe and explain variation among general practices in the uptake of screening for breast cancer.Design: Analysis of the variation in uptake of screening by general practice. Uptake rates are calculated and related to a social deprivation score created for each practice, and to the presence of at least one female general practitioner.Setting: South Lancashire Health Authority, England.Patients: All women aged 50–64 y registered with Lancashire Family Health Services Authority and resident in South Lancashire in 1988–1995.Main results: Variation in the uptake of screening for breast cancer during Round 1 of the national programme is explained partly by a deprivation score for each practice and by the presence of at least one female general practitioner. In Round 2 the deprivation index continues to explain variation, but the effect of a female GP has diminished. The number of hours worked by practice nurses has no effect on uptake of breast screening.Conclusions: Variation in the uptake of breast cancer screening is closely related to social deprivation. Results suggest that the presence of a female general practitioner has a beneficial effect on uptake.     

Spatial clustering of amyotrophic lateral sclerosis in Finland at place of birth and place of death

Previous evidence for spatial clustering of amyotrophic lateral sclerosis is inconclusive. Studies that have identified apparent clusters have often been based on a small number of cases, which means the results may have occurred by chance processes. Also, most studies have used the geographic location at the time of death as the basis for cluster detection, rather than exploring clusters at other points in the life cycle. In this study, the authors examine 1,000 cases of amyotrophic lateral sclerosis distributed throughout Finland who died between June 1985 and December 1995. Using a spatial-scan statistic, the authors examine whether there are significant clusters of the disease at both time of birth and time of death. Two significant, neighboring clusters were identified in southeast and south-central Finland at the time of death. A single significant cluster was identified in southeast Finland at the time of birth, closely matching one of the clusters identified at the time of death. These results are based on a large sample of cases, and they provide convincing evidence of spatial clustering of this condition. The results demonstrate also that, if the cluster analysis is conducted at different stages of the cases' life cycle, different conclusions about where potential risk factors may exist might result.     

Respiratory health effects of industrial air pollution: a study in east Lancashire, UK.

STUDY OBJECTIVE: To determine whether there was a higher incidence of respiratory ill health in children living near to a cement works than in those from a different area, and if so whether the higher incidence was due to the use of a hazardous waste-derived fuel at the works. STUDY DESIGN: A sample of the population of children living near the cement works (the study area) was compared with a sample of children living between 9 and 19 km away from the site (the control area). SETTING: The cement works is located on the north eastern edge of a small rural town in east Lancashire. METHODS: Data were collected via the use of a health questionnaire. This was distributed through selected primary schools to families who had one or more children of primary school age (5-11 years). MAIN RESULTS: The study and control populations were comparable in terms of response rates, gender, and socioeconomic indicators. There was no significant difference in the incidence of asthma (as diagnosed by a general practitioner) between the two areas when adjustment for hayfever was made. The incidence of sore throat was significantly higher in the case area, a difference not explained by other factors. For two other non-specific indicators of respiratory health (blocked nose and sore eyes) there was a significantly higher incidence in the study area, although hayfever and mould were also significant influences. CONCLUSIONS: The results indicated that certain non-specific health indicators were more common in the children living near a cement works. This excess may be due to exposure to emissions from the site. However, it is not possible to draw firm conclusions because there are no epidemiological data predating the use of the hazardous waste derived fuel.     

Secrets and lies: Breastfeeding and professional paid work

This paper explores the conflict between health advice and organisational practice regarding breastfeeding. It focuses on the group of mothers with the highest rates of both breastfeeding initiation and of continuous employment following maternity leave: specifically, educated mothers in managerial and/or professional occupations. In this context, the paper investigates, through in-depth interviews, the embodied experiences of 20 heterosexual UK mothers, qualified to degree level, who returned to professional employment within 1 year of childbirth. The paper observes that mothers who attempted to combine breastfeeding with paid work did so with difficulty because the material activity of breastfeeding was 'taboo' within the workplace. Thus, the requirement to conform to organisational expectations regarding 'suitable' embodied behaviour contradicted health advice about what was 'best' for infant children. In order to comply with workplace requirements, mothers in the study were obliged either to cease breastfeeding or to conceal breastfeeding activities. In the light of mothers' experiences, the paper suggests that breastfeeding duration rates among professionally employed mothers can only be improved if negative attitudes about maternal bodies and employment are challenged and if employers, as well as mothers, are the focus of health initiatives aimed at promoting breastfeeding.     

Can physical trauma cause breast cancer?

The objective of this study is to explore the effect of lifestyle on the risk of invasive breast carcinoma in women aged 50-65 years. A case-control study using a questionnaire and a semi-structured interview. Cases (n = 67) and controls (n = 134) were closely matched on known risk factors for breast cancer including age, family history, age at menarche, parity, age at first birth and menopausal status. Controls were chosen from a pool of 5600 women who attended for breast screening and filled in a questionnaire giving details to allow matching with cases. The study took place at the North Lancashire Breast Screening Service. Women were aged 50-65 years and presented with breast cancer or attended for breast screening.Women with breast carcinoma were more likely to report physical trauma to the breast in the previous 5 years than were the controls (odds ratio (OR) 3.3, 95% confidence interval (CI) 1.3-10.8, P < 0.0001). There were no significant differences in a wide range of other lifestyle indicators including factors relevant to social class, education, residence, smoking and alcohol consumption. In conclusion, recall bias is an unlikely explanation for these results in view of the nature and severity of physical trauma. Models of epithelial cell generation indicate that a causal link between physical trauma and cancer is plausible. A latent interval between cancer onset and presentation of under 5 years is also plausible. The most likely explanation of the findings is that physical trauma can cause breast cancer.     

Immunization against whooping cough in Salford: a spatial analysis

The decline in pertussis (whooping cough) immunization in the 1970s is related to public concern about the safety of the vaccine. The debates about its safety and effectiveness and the impact of vaccination on notifications are reviewed. A study is made of spatial variations in vaccine uptake within the metropolitan district of Salford, Greater Manchester, using data available at ward level. Salford as a whole has one of the lowest rates of uptake in the North Western Regional Authority, which itself has the lowest uptake in the country. Variations from ward to ward are noted and an attempt is made to account for these using Poisson regression. Both the number of children being immunized against pertussis and the number receiving diphtheria and tetanus vaccine (but foregoing the pertussis component) are used as dependent variables. Of the explanatory variables social class proves a useful predictor. However, the analysis is an ecological one and further work is called for at the scale of individual clinics in order to investigate health worker and parental attitudes and the accessibility constraints felt by those responsible for bringing children to clinics.