Birth weight, infant weight gain, and cause-specific mortality: the Hertfordshire Cohort Study

Low birth weight, a marker of adverse intrauterine circumstances, is known to be associated with a range of disease outcomes in later life, including coronary heart disease, hypertension, type 2 diabetes, and osteoporosis. However, it may also decrease the risk of other common conditions, most notably neoplastic disease. The authors describe the associations between birth weight, infant weight gain, and a range of mortality outcomes in the Hertfordshire Cohort. This study included 37,615 men and women born in Hertfordshire, United Kingdom, in 1911-1939; 7,916 had died by the end of 1999. For men, lower birth weight was associated with increased risk of mortality from circulatory disease (hazard ratio per standard deviation decrease in birth weight = 1.08, 95% confidence interval: 1.04, 1.11) and from accidental falls but with decreased risk of mortality from cancer (hazard ratio per standard deviation decrease in birth weight = 0.94, 95% confidence interval: 0.90, 0.98). For women, lower birth weight was associated with a significantly (p < 0.05) increased risk of mortality from circulatory and musculoskeletal disease, pneumonia, injury, and diabetes. Overall, a one-standard-deviation increase in birth weight reduced all-cause mortality risk by age 75 years by 0.86% for both men and women.     

Wenckebach atrioventricular block (Mobitz type I) in children and adolescents

Mobitz type I atrioventricular block in children, adolescents and young adults without overt heart disease or drug intoxication has been considered less significant than Mobitz type II block. In highly trained athletes and some nonathletes it has been presumed to be a benign manifestation of heightened vagal tone. Experience with 16 young patients, 6 female and 10 male, tends to alter the concept of benignity. Known onset of Wenckebach and varying first degree block was between 6 months and 17 years of age. Of eight patients followed up for 5 to 18 years, five have fixed complete heart block and three first degree block. Of eight followed up for 1 to 4 years, two have fixed complete heart block and the others varying first, second and third degree block. Two have required a pacemaker implant. On intracardiac electrography performed in seven patients, four manifested during sinus rhythm a Wenckebach response to atrial pacing at abnormally slow rates; in addition, the His bundle electrograms showed A-H delay in one patient, H-V delay in two patients and delay in both intervals in one patient. Of three patients studied during complete heart block all manifested A-H block and one also H-V prolongation. The occurrence of Wenckebach block in 7 of 16 children and adolescents before the development of fixed complete heart block suggests that such block is probably more common than heretofore recognized and may be a phase in the natural history of the development of idiopathic heart block. It often represents significant disease of the cardiac conduction system, which may be progressive, and it has a guarded prognosis.     

Species and strain differences in the expression of a novel glutamate-modulating cannabinoid receptor in the rodent hippocampus

A novel, non-CB1 cannabinoid receptor has been defined by the persistence of inhibition of glutamatergic EPSPs by the cannabinoid receptor agonist WIN55,212-2 in mice lacking the cloned CB1 receptor (CB1-/-) (Hajos et al., 2001). This novel receptor was also distinguished from CB1 by its sensitivity to the antagonist SR141716A and its insensitivity to the antagonist AM251 (Hajos & Freund, 2002). We have chosen to refer to this putative receptor as CBsc due to its identification on Schaffer collateral axon terminals in the hippocampus. We examined properties of CBsc receptors in Sprague Dawley (SD) rats and two strains of wild-type (WT) mice (C57BL/6J and CD1) used as backgrounds for two independent lines of CB1-/- mice (Ledent et al., 1999; Zimmer et al., 1999). The inhibition of synaptic glutamate release by WIN55,212-2 was observed in hippocampal slices from WT CD1 mice and SD rats but was absent in WT C57 mice. We also found that AM251 and SR141716A antagonized the effect of WIN55,212-2 in hippocampal slices from CD1 mice and SD rats demonstrating a lack of selectivity of these ligands for CB1 and CBsc receptors in these animals. The results indicate that the glutamate-modulating CBsc cannabinoid receptor is present in the hippocampi of CD1 mice and SD rats but not in C57BL/6J mice. Thus, we have identified animal models that may permit the study of cannabinoids independently of the novel CBsc receptor (C57CB1+/+), the CBsc receptor independently of the cloned CB1 receptor (CD1CB1-/-), or in the absence of both receptors (C57CB1-/-).     

Interventions to reduce mortality among patients treated in intensive care units

PURPOSE: Using sensitivity analysis to estimate the impact, in terms of patient lives, of the failure to use proven therapies known to reduce mortality in critically ill intensive care unit patients. MATERIALS AND METHODS: We identified high-impact interventions published in the last 5 years in the Journal of the American Medical Association or New England Journal of Medicine, extracted the absolute risk reduction associated with each intervention and gleaned the national incidence of each condition and the percent of the population not receiving the cited therapy from the literature. From this information, we calculated national estimates of the excess deaths from failure to use these therapies. RESULTS: With consistent and appropriate implementation of the 5 cited evidence-based interventions, we found a total of 167,819 lives could be saved per year, with a range of 137,670 to 197,965 lives saved per year. CONCLUSIONS: Mistakes of omission are common in the critical care setting and lead to significant preventable mortality. There is a significant gap between the discovery of effective interventions and their use in clinical practice. By viewing the delivery of healthcare as a science and increasing funding for health services research, we may be able to increase the use of effective therapies and, as a result, reduce patient mortality.     

Perductal electrolytic ablation of the porcine pancreas: A minimally invasive option-studies of morbidity and mortality

Background Pancreatic cancer has a dismal prognosis. Few patients are suitable for surgical resection, leaving the majority requiring symptom palliation. Current palliative techniques such as surgical bypass and endoscopic retrograde cholangiopancreatography (ERCP) are imperfect. A novel palliative therapy combining the symptom control of surgical bypass with the minimally invasive nature of ERCP is required.Methods Perductal electrolytic ablation of pancreatic tissue, in a porcine model, was performed. There were two survival groups of 2 weeks (n = 4) and 8 weeks (n = 4). Postoperatively, serum biochemistry, amylase and C-reactive protein (CRP) were assessed. Histological examination of the pancreas, lungs, and kidneys was performed to determine the presence of acute pancreatitis or systemic inflammatory response.Results An immediate transient increase in both amylase and CRP was seen. Although pancreatic histology demonstrated localised necrosis at the electrolytic site at 2 weeks, there was no evidence of generalized pancreatitis or a systemic inflammatory response at either 2 or 8 weeks.Conclusions This study suggests that, although there is localized pancreatic necrosis and transient hyperamylasemia, perductal pancreatic electrolytic ablation is safe, with neither generalized pancreatitis nor a systemic inflammatory response, in the medium and long term. Although performed in normal porcine pancreas, because of the absence of a large-animal model of pancreatic cancer, this study suggests that electrolytic pancreatic ablation is safe. This technique may have a role in the palliation of pancreatic cancer, especially if delivered via a minimally, invasive approach, and warrants further investigation.     

Haemorrhage from pancreatic pseudocysts presenting as upper gastrointestinal haemorrhage

Haemorrhage is a rare but frequently fatal complication of pancreatic pseudocysts. The high mortality associated with pancreatic haemorrhage makes prompt and aggressive management essential. Occasionally, haemorrhage may present atypically, leading to delay in its diagnosis and management. This report details a case of pancreatic haemorrhage presenting as an upper gastrointestinal bleed and discusses the subsequent management. When managing patients with pancreatic pseudocysts who present with the stigmata of upper gastrointestinal bleeding, the possibility that the bleeding originates from the pancreas must always be borne in mind.