Nafenopin, a hypolipidemic and non-genotoxic hepatocarcinogen increases intracellular calcium and transiently decreases intracellular pH in hepatocytes without generation of inositol phosphates

Addition of nafenopin (30-300 microM to 45Ca2+ preloaded cultured hepatocytes caused a rapid and concentration-dependent increase in 45Ca2+ efflux in a manner similar to vasopressin, as evidenced by the loss of radioactivity from the cells. In contrast to vasopressin, addition of nafenopin to [3H]inositol prelabelled hepatocytes in culture did not increase [3H]inositol phosphate production. When added simultaneously with vasopressin, nafenopin inhibited the vasopressin-stimulated [3H]inositol phosphate production. In hepatocyte suspensions isolated from rats treated for 1 week with a carcinogenic dose of nafenopin (1000 ppm in their daily food) the incorporation of [3H]inositol into the phosphoinositide fraction, particularly phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate, was much less than that in hepatocytes isolated from untreated rats. The vasopressin-stimulated [3H]inositol phosphate production was also decreased. Experiments with hepatocyte suspensions preloaded with Ca2+ or pH sensitive fluorescent indicators demonstrated that addition of nafenopin caused an increase in intracellular free Ca2+ and transient acidification of the cells. The increase in [Ca2+]i was decreased by only about 25% when extracellular calcium was removed indicating that nafenopin mainly mobilizes Ca2+ from intracellular stores. The recovery to basal pH was amiloride-sensitive indicating the importance of Na+/H+ exchange in pH recovery after intracellular acidification. Amiloride also inhibited DNA synthesis induced by nafenopin and by epidermal growth factor in cultured hepatocytes; but this effect occurred concomitantly with inhibition of basal DNA synthesis. We suggest that hepatic Ca2+ mobilization induced by nafenopin may play an important role in the mechanism by which nafenopin exerts its physiological as well as its tumour promotive activity upon chronic treatment with carcinogenic doses.     

Role of topical lignocaine during carotid endarterectomy.

Forty carotid endarterectomies were undertaken in 34 patients. Operations were prospectively randomized to periarterial application of either 1 per cent lignocaine (n = 19) or normal saline (n = 21), and detailed measurements taken of intraoperative pulse rate and blood pressure. Patients receiving lignocaine demonstrated a lower pulse rate, and lower systolic and mean blood pressures than those receiving placebo, with significance in relation to clamp application and shunt removal (P < 0.05). It was particularly noticeable that patients receiving lignocaine demonstrated less intraoperative variation in pulse rate and blood pressure. Topical lignocaine stabilizes pulse rate and blood pressure during carotid endarterectomy.     

Solid and papillary epithelial neoplasms of the pancreas: CT findings

Five female patients and one male patient with solid and papillary epithelial neoplasms of the pancreas were examined with computed tomography (CT). The mean age of the patients was 27 years (range, 13-46 years). All cases showed well-encapsulated, round or lobulated masses consisting of both cystic and solid areas. Cystic portions showed CT numbers that suggested hemorrhagic necrosis. There were no internal septations within the masses. In three tumors located in the head of the pancreas, dilatation of the biliary tree was absent or minimal, although the masses were large. Two tumors contained calcifications. One tumor demonstrated metastatic deposits in liver and lymph nodes. Metastatic masses appeared similar to the primary pancreatic mass. Solid and papillary neoplasm of the pancreas should be the primary diagnostic consideration when characteristic CT findings are detected in a young female patient.     

A quantitative study of body-related attitudes in patients with anorexia and bulimia nervosa.

The Ben-Tovim Walker Body Attitudes Questionnaire (BAQ) is a psychometrically sound self-report instrument for assessing women's attitudes towards their own bodies. The BAQ responses of a large sample of patients with eating disorders (ED) diagnosed in accordance with DSM-III-R criteria were compared with those from a normative population and from diverse groups of psychiatrically and physically ill patients. The ED group was distinct, and showed extreme responses in the area of weight and shape concerns. But a better discrimination between the ED and other populations was achieved using subscales that related to 'body disparagement' (an intense loathing of the body) and 'attractiveness', rather than to weight and shape concerns. ED patients may have a more pervasive disturbance in body-related attitudes than is currently widely accepted. Patients with anorexia and bulimia nervosa showed very similar attitudes despite the symptomatic differences between the groups.     

Interpreting hospital mortality data. The role of clinical risk adjustment

This study uses national Medicare data as well as data that were abstracted to calibrate the Medicare Mortality Predictor System to assess the usefulness of a risk adjustment system in interpreting hospital mortality rates. The majority of variation in annual hospital death rates for the four conditions studied (stroke, pneumonia, myocardial infarction, and congestive heart failure) is chance variability that results from the relatively small numbers of patients treated in most hospitals in a year. For hospitals in the highest and lowest quartiles of observed death rates, the difference between observed rates and those predicted by the Medicare Mortality Predictor System is not quite on third smaller than the difference between observed rates and unadjusted national rates. Risk adjustment methods do not show whether the unexplained difference in mortality rates results from differences in effectiveness of care or unmeasured differences in patient risk at the time of admission. Risk-adjusted mortality rates, therefore, should be supplemented by review of the actual care rendered before conclusions are drawn regarding effectiveness of care.     

Advanced primary breast cancer: assessment at mammography of response to induction chemotherapy

The response to induction chemotherapy is an important prognostic factor in patients with nonmetastatic, locally advanced breast carcinomas. Assessment at mammography of the response of 60 breast cancers in 59 women was performed between 1974 and 1986. Responses were excellent in 13 tumors, moderate in 34, and poor in 13 (excellent moderate = 78%). Assessment of response of discrete masses in a fatty breast was easiest; assessment of response of tumor areas that were poorly defined-such as a focal area of architectural distortion or mass in dense breast parenchyma-was more difficult. Of 17 patients with excellent pathologic responses-that is, minimal or no residual tumor-15 (88%) had complete responses (no residual tumor) as determined with mammography, physical examination, or both. Mammography provides information complementary to physical examination and is essential in the accurate assessment of the response to chemotherapy of locally advanced breast cancer.