Francis D. Moore

Factors associated with cardiac mortality in developed countries with particular reference to the consumption of wine.

Deaths from ischaemic heart-disease in 18 developed countries are not strongly associated with health-service factors such as doctor and nurse density. There is a negative association with gross national product per capita and a positive but inconsistent association with saturated and monounsaturated fat intake. The principal finding is a strong and specific negative association between ischaemic heart-disease deaths and alcohol consumption. This is shown to be wholly attributable to wine consumption.

Long-term Assessment of a Multidisciplinary Approach to Thyroid Nodule Diagnostic Evaluation

The diagnostic evaluation of patients with thyroid nodules is imprecise. Despite the benefits of fine‐needle aspiration (FNA), most patients who are referred for surgery because of abnormal cytology prove to have benign disease. Recent technologic and procedural advances suggest that this shortcoming can be mitigated, although few data confirm this benefit in unselected patients.

THE MEASUREMENT OF TOTAL BODY WATER IN THE HUMAN SUBJECT BY DEUTERIUM OXIDE DILUTION: WITH A CONSIDERATION OF THE DYNAMICS OF DEUTERIUM DISTRIBUTION

The interpretation of fluctuations in body weight and changes in the state of hydration requires a knowledge of the total amount of water in the organism. This investigation has been directed towards the perfection of a method for measurement of the total body water in the human subject. The increasing availability and lowered cost of both stable and radioactive isotopes has made possible study of the total amount of liquid and solid

Identification of the target self-antigens in reperfusion injury

Reperfusion injury (RI), a potential life-threatening disorder, represents an acute inflammatory response after periods of ischemia resulting from myocardial infarction, stroke, surgery, or trauma. The recent identification of a monoclonal natural IgM that initiates RI led to the identification of nonmuscle myosin heavy chain type II A and C as the self-targets in two different tissues. These results identify a novel pathway in which the innate response to a highly conserved self-antigen expressed as a result of hypoxic stress results in tissue destruction.

Necrotizing pancreatitis: Contemporary analysis of 99 consecutive cases

ObjectiveTo analyze the impact of a conservative strategy of management in patients with necrotizing pancreatitis, reserving intervention for patients with documented infection or the late complications of organized necrosis. Summary Background DataThe role of surgery in patients with sterile pancreatic necrosis remains controversial. Although a conservative approach is being increasingly used, few studies have evaluated this strategy when applied to the entire spectrum of patients with necrotizing pancreatitis. MethodsThe authors reviewed 1,110 consecutive patients with acute pancreatitis managed at Brigham and Women’s Hospital between January 1, 1995, and January 1, 2000, focusing on those with pancreatic necrosis documented by contrast-enhanced computed tomography. Fine-needle aspiration, the presence of extraintestinal gas on computed tomography, or both were used to identify infection. ResultsThere were 99 (9%) patients with necrotizing pancreatitis treated, with an overall death rate of 14%. In three patients with underlying medical problems, the decision was made initially not to intervene. Of the other 62 patients without documented infection, all but 3 were managed conservatively; this group’s death rate was 11%. Of these seven deaths, all were related to multiorgan failure. Five patients in this group eventually required surgery for organized necrosis, with no deaths. Of the 34 patients with infected necrosis, 31 underwent surgery and 3 underwent percutaneous drainage. Only four (12%) of these patients died, all of multiorgan failure. Of the total 11 patients who died, few if any would have been candidates for earlier surgical intervention. ConclusionsThese results suggest that conservative strategies can be applied successfully to manage most patients with necrotizing pancreatitis, although some will eventually require surgery for symptomatic organized necrosis. Few if any patients seem likely to benefit from a more aggressive strategy.

Health service "input" and mortality "output" in developed countries.

The relationship between age-specific mortality rates and some indices of health facilities and some environmental and dietary factors has been studied in 18 developed couuntries. The indices of health care are not negatively associated with mortality, and there is a marked positive association between the prevalence of doctors and mortality in the younger age groups. No explanation of this doctor anomaly has so far been found. Gross national product per head is the principal variable which shows a consistently strong negative association with mortality.

Experimental Whole-organ Transplantation of the Liver and of the Spleen°

THE RAPIDLY growing experience in experimental homotransplantation is largely based on observations of the skin, kidney, blood and bone marrow. These studies have been the pioneer ones for reasons that are clear historically: skin for its availability; kidney for its significance as a paired organ with a simple vascular pedicle, the biochemical product of which can easily be measured; blood for its circulatory support; and bone marrow for its use as a replacement tissue after hematopoietic destruction either in cancer

Somatic mitochondrial DNA (mtDNA) mutations in papillary thyroid carcinomas and differential mtDNA sequence variants in cases with thyroid tumours.

Somatic mutations in mtDNA have recently been identified in colorectal tumours. Studies of oncocytic tumours have led to hypotheses which propose that defects in oxidative phosphorylation may result in a compensatory increase in mitochondrial replication and/or gene expression. Mutational analysis of mtDNA in thyroid neoplasia, which is characterised by increased numbers of mitochondria and is also one of the most common sites of oncocytic tumours. has been limited to date. Using the recently developed technique of two-dimensional gene scanning, we have successfully examined 21 cases of thyroid tumours, six cases of non-neoplastic thyroid pathology, 30 population controls, nine foetal thyroid tissues and nine foetal tissues of non-thyroid origin, either kidney or liver. We have identified three different somatic mutations (23%) in papillary thyroid carcinomas. In addition, we have found significant differential distributions of mtDNA sequence variants between thyroid carcinomas and controls. Interestingly, these variants appear to be more frequent in the genes which encode complex I of the mitochondrial electron transport chain compared to normal population controls. These findings suggest first, that somatic mtDNA mutations may be involved in thyroid tumorigenesis and second, that the accumulation of certain non-somatic variants may be related to tumour progression in the thyroid.

The effects of complement activation during cardiopulmonary bypass. Attenuation by hypothermia, heparin, and hemodilution.

Complement activation was examined prospectively in 100 car-diopulmonary bypass (CPB) patients. Plasma C3a desArg (C3a) increased (cannulation: 234 ± 33 ng/mL; 20 minutes on CPB: 622 ± 51; 2 hours after CPB: 1143 ± 109, p < 0.0001). C3a at 2 hours was higher in the 13 patients requiring mechanical ventilation for longer than 1 day (1023 ± 274) than in the 67 without respiratory complication (568 ± 45, p < 0.004). Five more patients were studied for neutrophil activation to confirm that a biologic effect of complement activation occurs during CPB; in these five patients C3a increased to 317% of baseline after 10 minutes on CPB with a corresponding rise in neutrophil cell surface receptors for the complement opsonin C3b (as measured by indirect immunofluorescence) to 168% (p < 0.05). Both increases were sustained at 30 minutes. Temperature, dilution, and heparin were studied as variables relevant to CPB. Exposure of normal neutrophils to C5a in vitro caused an increase in C3b receptors which was dependent on temperature (0 specific fluorescence at 0 C, 30 at 25 C, 180 at 30 C, and 275 at 37 C). Generation of C3a and C5a in normal serum by zymosan was also temperature-dependent (ng/mL C5a generated: 0.7 at 25 C, 200 at 30 C, and 897 at 37 C; ng/mL C3a generated: 546 at 25 C, 10872 at 30 C, and 65,667 at 37 C). Serum dilution to 33% decreased ng/mL C5a generated in the same system from 200 to 76 with no effect on C3a. Addition of heparin to 20 U/mL decreased ng/mL C3a generated from 10872 to 913 and C5a from 200 to 8. Thus, hypothermia, dilution, and heparin protect CPB patients from complement activation by reducing both generation of C3a/C5a and the subsequent cellular response of neutrophil activation.

Is severity of necrotizing pancreatitis increased in extended necrosis and infected necrosis

Introduction We previously reported that organ failure occurs in 50% of patients with necrotizing pancreatitis, that extended pancreatic necrosis (greater than 50% necrosis) is not associated with an increased prevalence of organ failure or infected necrosis, and that the prevalence of organ failure is similar in sterile necrosis and infected necrosis. Aims To analyze these relations in a larger group of patients and to evaluate other factors that might have prognostic significance. Methodology We reviewed 1,110 consecutive cases of acute pancreatitis between January 1, 1995, and January 1, 2000. Necrosis was documented by contrast-enhanced CT. A p value less than 0.05 was considered significant. Results Ninety-nine patients (9%) had necrotizing pancreatitis; 52% had organ failure. Patients with extended pancreatic necrosis did not have increased prevalence of organ failure or infected necrosis but did have an increased need for intubation and an increased mortality rate associated with multiple organ failure. Patients with infected necrosis did not have an increased prevalence of organ failure but did have a marginally increased prevalence of multiple organ failure and increased need for intubation. Overall mortality was 14% and was markedly increased among patients with organ failure at admission (47%) and among patients who had multiple organ failure during the hospitalization (49%). Conclusion Although severity of necrotizing pancreatitis was somewhat increased in extended pancreatic necrosis and infected necrosis, mortality was more strongly linked to organ failure at admission and multiple organ failure during hospitalization.