Cigarette smoking and benign breast disease.

The association between cigarette smoking and the occurrence of benign breast disease was assessed in a hospital-based case-control study conducted in Connecticut during 1979-81. Current smokers, but not former smokers, were at reduced risk for all benign breast diseases. The odds ratios associated with current smoking were 0.7 (95% confidence intervals = 0.6, 0.9) for fibrocystic breast disease, 0.6 (95% confidence intervals = 0.5, 0.9) for fibroadenoma, 0.6 (95% confidence intervals = 0.4, 1.0) for fibrocystic breast disease concomitant with fibroadenoma, and 0.6 (95% confidence intervals = 0.5, 0.9) for other benign breast disease. Adjustments for potentially confounding variables, including indices of medical care utilisation, affected these odds ratios only slightly. There was no convincing evidence of an association, either negative or positive, between current cigarette smoking and the degree of epithelial atypia of the fibrocystic lesions. However, the negative association between fibrocystic disease and current cigarette smoking was strongest for atypical lobular hyperplasia, which in turn has been associated with a particularly elevated risk of subsequent breast cancer.     

Frequency of Abnormal Sphincter of Oddi Manometry Compared with the Clinical Suspicion of Sphincter of Oddi Dysfunction

Patients with pancreaticobiliary pain or idiopathic pancreatitis have been classified as having definitive (type I), presumptive (type II), or possible (type III) sphincter of Oddi dysfunction (SOD) based on clinical, laboratory, and ERCP data. This study was undertaken to determine the frequency of abnormal sphincter of Oddi manometry (SOM) when patients are classified by this system. Two hundred and thirteen patients with pancreaticobiliary pain were evaluated clinically; SOM, ERCP, and ductal contrast drainage time tests were performed. For biliary types I, II, and III, the frequency of abnormal SOM was 85.7%, 55.1%, and 28.1%, respectively. Similarly, for pancreatic types I, II, and III, an elevated basal sphincter pressure occurred in 92.3%, 58.2%, and 35.1%, respectively. When patients with an abnormal basal sphincter pressure were characterized by the magnitude of the elevation, the manometric profiles were similar for types I, II, and III. These data suggest that elevated sphincter pressure occurs more frequently in type III patients than previously reported, and supports consideration of SOM when evaluating and treating type II and type III patients.     

Incomplete antigenic cross-reactivity between platelets and megakaryocytes: relevance to ITP

Immune thrombocytopenias are usually associated with normal or increased numbers of megakaryocytes in the marrow. Therefore, the mechanism(s) responsible for the destruction of circulating platelets may not affect megakaryocytes in the same way. One of the possibilities which could account for the differential effect on the cells would be the development of antibodies to components of platelet membranes which are not exposed on the surface of all megakaryocytes. To investigate this possibility, a rabbit antiserum specific for mouse platelets was tested against fresh and cultured mouse megakaryocytes by indirect immunofluorescence. This antiserum cross-reacted with 46% of fresh murine megakaryocytes and 54% of cultured megakaryocytes. Phase- contrast microscopy revealed the reacting megakaryocytes to be fully granulated with irregular contours and in the process of releasing platelets. Nonreactive megakaryocytes demonstrated smooth contours and lacked morphological evidence of thrombocytopoiesis. Electron microscopy showed that only in megakaryocytes (MK) with an irregular contour had the demarcation membrane system (DMS) reached continuity with the plasma membrane. Ultrastructural analysis of megakaryocytes from patients with ITP showed approximately 25% to 50% of megakaryocytes without evidence of injury, whereas 50% to 75% had extensive damage. In undamaged cells, platelet territories had not yet reached the peripheral zone. The DMS of damaged megakaryocytes opened to the exterior elaborating platelets. The observations suggested that some platelet antibodies react only with megakaryocytes which have reached the stage of thrombocytopoiesis. Relevant target antigens may not be exposed on all megakaryocytes before cytoplasmic fragmentation occurs.     

Improved vessel dilator for percutaneous catheterization

Three commercial vessel dilators and a dilator of an improved design were tested during percutaneous catheterization in 16 mongrel dogs to evaluate arterial damage produced with their use. The results indicate that, although all dilators often produce arterial damage, the improved design produced much less damage. In addition, lesions were less severe overall. The dilator has been safely and successfully used in patients for percutaneous vessel catheterization for the past 30 years at the authors' institution.     

Effect of nebulised recombinant DNase on neutrophil elastase load in cystic fibrosis.

BACKGROUND: DNA released by degenerating inflammatory neutrophils contributes to mucous plugging of airways in patients with cystic fibrosis. Neutrophil elastase, a major effector of tissue destruction in the lungs of patients with cystic fibrosis, is a highly cationic molecule which is bound and inhibited by negatively charged polyanions such as mucin and DNA in purulent sputum. Thus, the solubilisation of DNA in the airways by aerosolised recombinant DNase may remove a source of neutrophil elastase inhibition, effectively increasing elastase load. The aim of this study was to assess the effect of rhDNase therapy on neutrophil elastase load in patients with cystic fibrosis. METHODS: Blood and sputum were collected from 15 patients with cystic fibrosis before initiation of nebulised DNase therapy and at 12 weeks following therapy. The long term effects of continuous rhDNase administration were evaluated at 52 weeks for 11 of these patients. Plasma was analysed for neutrophil elastase, interleukin (IL)-8 and neutrophil elastase in complex with alpha 1-protease inhibitor (alpha 1PI). Sputum was assessed for neutrophil elastase, IL-8, and active elastase. At each visit spirometric measurements were carried out. RESULTS: Sputum elastase activity decreased at 12 weeks and was maintained at 52 weeks when a decline in total plasma elastase was also observed. Although, as expected, there was a correlation between plasma levels of total elastase and neutrophil elastase/alpha 1PI complex, the decrease in the levels of the complex at 52 weeks did not reach statistical significance. CONCLUSIONS: This study indicates that prolonged daily administration of rhDNase results in a reduction in elastase load in patients with cystic fibrosis.     

Increased height in diabetes mellitus corresponds to the predicted and the adult height

This study was conducted to analyse the effect of childhood-onset diabetes mellitus on adult height. The height at time of diagnosis of 35 children with insulin-dependent diabetes mellitus (IDDM) was compared with growth reference data. Predictions of the adult height were made at the time of diagnosis using the target height and the Tanner-Whitehouse II method. The adult height was compared with both the predicted values and the height of healthy adults. The height at time of diagnosis of the prepubertal children was increased compared with growth reference data, in contrast to pubertal children who had normal heights. Only the prepubertal boys were taller at time of diagnosis. The adult height of the prepubertal patients was taller than growth reference data. The mean adult height in all patients did not differ significantly from the predicted heights. In conclusion, the increased height at the start of IDDM in prepubertal children persists until adulthood.     

Effects of short-term hypoxia on platelet counts of mice

Recent studies have shown that long-term hypoxia causes decreased platelet counts in mice and short-term hypoxia increased platelet counts. In an attempt to explain the mechanism that increases platelet counts of mice after exposure to short-term hypoxia, we measured platelet counts, total circulating platelet counts (TCPC), total circulating platelet masses (TCPM), percentages of 35S incorporation, and platelet sizes. Platelet counts, as well as TCPC and TCPM of mice, increased after 1-3 days of hypoxia, but these values were decreased after 6-7 days of hypoxia. Although platelet counts were increased in hypoxic mice, the percentage 35S incorporation into platelets and platelet sizes did not show a concurrent increase. After 6 days of hypoxia, average platelet diameters began to increase as platelet counts decreased. Splenic release did not account for the increase in platelet counts of mice after short-term hypoxia. It seems possible, therefore, that megakaryocytes "shed" platelets into the circulation in response to hypoxia. The platelets that enter the circulation in response to short-term hypoxia are smaller and incorporate less 35S than platelets that are produced in response to acute thrombocytopenia.