Importance of light smoking and inhalation habits on risk of myocardial infarction and all cause mortality. A 22 year follow up of 12 149 men and women in The Copenhagen City Heart Study

STUDY OBJECTIVE: To determine risk of myocardial infarction (MI) and all cause mortality associated with light smoking and inhalation habits in men and women. DESIGN: Prospective cohort study with follow up of MI and all cause mortality through record linkage. SETTING: The Copenhagen City Heart Study, a cardiovascular study based on a sample of the general population established in 1976. PARTICIPANTS: 6505 women and 5644 men followed up until 1998 for first MI and for death from all causes. Main results: During follow up 476 women and 872 men suffered a MI whereas 2305 women and 2883 men died. After adjusting for major cardiovascular risk factors there was a dose-response relation between smoking with and without inhaling and both MI and all cause mortality. Among inhaling smokers significantly increased risks were found in women at a consumption of only 3-5 grams of tobacco per day with relative risks (RR) of MI and all cause mortality of 2.14 (95% CI 1.11 to 4.13) and 1.86 (95% CI 1.37 to 2.51), respectively. In men increased risks were seen when smoking 6-9 grams per day with RR of MI and all cause mortality of 2.10 (95% CI 1.40 to 3.14) and 1.76 (95% CI 1.39 to 2.23), respectively. Risks were also increased in non-inhaling smokers, although in men only significantly so for all cause mortality. After adjusting for inhalation and quantity smoked, cigarette smokers had a higher risk of all cause mortality (RR 1.16 (95% CI 1.07 to 1.26)) but not of MI (RR 1.11 (95% CI 0.95 to 1.30)). The RR associated with smoking were significantly higher in women than in men for both MI and all cause mortality. CONCLUSIONS: Smoking as little as 3-5 grams of tobacco per day or not inhaling the smoke was shown to carry a significantly increased risk of developing MI and of all cause mortality with higher RR found in women than in men. The study emphasises the importance of recognising that even very limited tobacco consumption has detrimental health effects.     

Outcome after extended follow-up in a prospective study of operable breast cancer: key factors and a prognostic index

In 1990, 215 patients with operable breast cancer were entered into a prospective study of the prognostic significance of five biochemical markers and 15 other factors (pathological/chronological/patient). After a median follow-up of 6.6 years, there were 77 recurrences and 77 deaths (59 breast cancer-related). By univariate analysis, patient outcome related significantly to 13 factors. By multivariate analysis, the most important of nine independent factors were: number of nodes involved, steroid receptors (for oestrogen or progestogen), age, clinical or pathological tumour size and grade. Receptors and grade exerted their influence only in the first 3 years. Progestogen receptors (immunohistochemical) and oestrogen receptors (biochemical) were of similar prognostic significance. The two receptors were correlated (r=+0.50, P=0.001) and displaced each other from the analytical model but some evidence for the additivity of their prognostic values was seen when their levels were discordant.     

The time from diagnostic excision biopsy to wide local excision for primary cutaneous malignant melanoma may not affect patient survival

BACKGROUND: The surgical management of primary cutaneous malignant melanoma usually involves an excision biopsy of the suspected lesion followed by wide local excision. No study has addressed whether a delay between these two surgical procedures influences patient outcome. OBJECTIVES: To determine if the surgical interval (SI) between the diagnostic excision biopsy and wide local excision for primary cutaneous malignant melanoma affects recurrence or survival outcome. METHODS: A cohort of 986 patients who had a diagnostic excision biopsy followed by wide local excision was identified from those registered on a specialist database that records the clinicopathological features, surgical treatment and follow-up information of all patients with malignant melanoma in Scotland. The cohort was divided into five arbitrary groups determined by the length of the SI as follows:< or =14 days, 15-28 days, 29-42 days, 43-91 days and > or = 92 days. Overall survival, disease-free survival and recurrence-free interval between the groups were compared univariately and multivariately. RESULTS: The mean age at excision biopsy was 47.4 years and the median period of follow-up was 5 years (range 27 days to 20.7 years). The median SI was 30 days (range 1-468 days). The SI was: (i)< or =14 days for 130 (13%); (ii) 15-28 days for 320 (33%); (iii) 29-42 days for 262 (27%); (iv) 43-91 days for 251 (25%); and (v) > or = 92 days for 23 (2%) patients. The latter group was older, had thinner melanomas, a higher percentage of lesions on the head and neck, fewer superficial spreading malignant melanomas and ulceration present less often compared with patients treated earlier. Univariately, there was no significant difference in overall survival (P = 0.60) or disease-free survival (P = 0.24) between the groups. Although there was a statistically significant difference in the percentage of recurrence-free patients between the groups (P = 0.011), the better recurrence-free rates occurred in the 29-42 and 43-91 day groups. After adjusting for age, sex, tumour thickness, site, histology, ulceration and mitotic activity using Cox's proportional hazards model, there was no statistically significant difference in overall survival, disease-free survival and recurrence-free percentages between the surgical groups (P = 0.88, P = 0.44 and P = 0.084, respectively). CONCLUSIONS: There was no evidence that survival outcome or recurrence was related to the time interval between the diagnostic excision biopsy and wide local excision of melanoma.     

Emergency medical care in rural America

The delivery of high-quality emergency care in a rural setting requires a conceptual framework quite different from that required in urban and suburban environments, given that available resources are limited in the rural setting. The intermittent and episodic nature of seriously ill and injured patients who present to rural emergency departments makes it difficult to plan, staff, and equip in order to provide emergency medical care at the same level seen at higher volume urban or suburban institutions. The objective of this article is to describe the distinctive nature and widely unrecognized features of emergency medicine in rural and remote areas, with a focus on clinical, workforce, and economic issues. We present recommendations for a shift in thinking and a call to action on behalf of all emergency medicine professionals that are based on a realistic assessment of the current status of emergency medicine and that are needed to develop and sustain high-quality emergency medical care in rural America.     

The genetic epidemiology of irrational fears and phobias in men

BACKGROUND: Much of our knowledge of the role of genetic factors in the etiology of phobias comes from one population-based sample of female twins. We examined the sources of individual differences in the risks for phobias and their associated irrational fears in male twins. METHODS: In personal interviews with both members of 1198 male-male twin pairs (707 monozygotic [MZ] and 491 dizygotic [DZ]) ascertained from a population-based registry, we assessed the lifetime history of agoraphobia and social, animal, situational, and blood/injury phobias as well as their associated irrational fears. Twin resemblance was assessed by means of probandwise concordance, odds ratios, tetrachoric correlations, and univariate and multivariate biometrical model fitting. RESULTS: The suggestive results obtained by analysis of phobias only were supported by analyzing both fears and phobias. All 5 phobia subtypes aggregate within twin-pairs. This aggregation is due largely or solely to genetic factors with heritability of liabilities ranging from 25% to 37%. Multivariate analysis revealed a common genetic factor, genetic factors specific to each subtype, and a common familial-environmental factor. CONCLUSIONS: In male subjects, genetic risk factors, which are partially common across all subtypes and partially subtype specific, play a moderate role in the etiology of phobias and their associated irrational fears. Family environment probably has an impact on risk for agoraphobia and social phobia. The genetic liability to blood/injury phobias is not distinct from those of the more typical phobias.     

Safe technique for removal of extensive renal cell tumors

We describe our technique for excision of a renal tumor that extended to the right atrium and was adherent to the inferior vena cava within the liver. The surgical procedure was performed using cardiopulmonary bypass with deep hypothermic circulatory arrest and retrograde cerebral perfusion to extend the safe period of cerebral ischemia.     

Parenting and adult mood, anxiety and substance use disorders in female twins: an epidemiological, multi-informant, retrospective study

BACKGROUND: Although parenting has long been considered an important risk factor for subsequent psychopathology, most investigations of this question have studied a single informant, clinical populations, one or a few disorders and did not consider relevant covariates. METHODS: Three dimensions of parenting (coldness, protectiveness and authoritarianism) were measured by combining the retrospective reports from adult female twins, their co-twins, and their mothers and fathers. We assessed by personal interview, lifetime history in the twins of eight common psychiatric and substance abuse disorders and a range of predictors of parenting. Analyses were performed using logistic regression. RESULTS: Examined individually, high levels of coldness and authoritarianism were modestly but significantly associated with increased risk for nearly all disorders, while the impact of protectiveness was more variable. These associations declined modestly when putative predictors of parenting were added as covariates. Maternal and paternal parenting were equally associated with outcomes in adult daughters. When coldness, protectiveness and authoritarianism were examined together, nearly all significant associations were seen solely with coldness. Few significant interactions were found between maternal and paternal parenting or between coldness, protectiveness and authoritarianism. The shared experience of these three dimensions of parenting predicts a quite small correlation in liability to these disorders in dizygotic twin pairs (e.g. r < 0.04). CONCLUSION: In women, parenting behaviour, especially levels of coldness, is probably causally related to risk for a broad range of adult psychiatric disorders. The impact of parenting on substance use disorders may be largely mediated through their co-morbidity with major depression, phobias and generalized anxiety disorder. In general population samples, the association of poor parenting with psychiatric illness is modest, largely non-specific and explains little of the observed aggregation of these disorders in families.     

Evaluation of attempted prevention of unexpected infant death in very high-risk infants by planned health care

Three hundred and ninety-six babies born in Sheffield between 1982 and 1990 identified as being at "very high risk" of unexpected infant death by means of a scoring system, received an intensive programme of health care including a case discussion between a paediatrician, the GP and the health visitor held in the family doctor's surgery, weekly visits from the health visitor and informal hospital admission. Significantly fewer sudden unexpected infant deaths occurred in this group than were expected by logistic regression anlysis or occurred in the best available control group with comparable scores ( p = 0.024). Problems in evaluation include identification of an adequate control population, ethical difficulties in introducing a controlled study when the programme is already perceived as effective, and the calculation of "expected death rates". The results of this study indicate that very energetic programmes of intervention may prevent some deaths in vulnerable infants.     

Tumor induction by the c-Myc target genes rcl and lactate dehydrogenase A

The characterization of c-Myc target genes, such as rcl and lactate dehydrogenase A (LDH-A), is critical for understanding the mechanisms of c-Myc-induced cell transformation and tumorigenesis. We have previously demonstrated that Rcl induces anchorage-independent growth in Ratla fibroblasts and that LDH-A is required for cell transformation by c-Myc. In this study, we report that Rcl and LDH-A act synergistically to induce anchorage-independent growth. Cells expressing both Rcl and LDH-A form tumors after s.c. injection into nude mice, although neither Rcl or LDH-A overexpression alone induces tumorigenesis. The inability of Rcl and LDH-A to fully recapitulate c-Myc activity, however, indicates that other c-Myc target genes participate in tumorigenesis. In addition, cells that coexpress Rcl and vascular endothelial growth factor are more comparable with c-Myc overexpressing cells in their ability to form tumors in nude mice. These findings confirm Rcl and LDH-A as critical components of the cell transformation program induced by c-Myc and suggest that Rcl is tumorigenic in cells that are provided with a permissive metabolic milieu.