Microsatellite instability is correlated with lymph node-positive breast cancer.

We analyzed 81 cases of primary breast carcinoma and 7 cases of fibroadenoma for microsatellite instability at eight loci. Twenty-seven cases (33.3%) manifested aberrant microsatellite alleles: 7 (8.6%) at one locus and 20 (24.7%) at two or more loci [tumors with replication error-positive (RER+) phenotype]. No evidence of microsatellite instability was observed in fibroadenomas. We investigated correlations between RER+ phenotype and clinicopathological characteristics of the carcinomas. The RER+ phenotype was statistically associated with large tumor diameter; of 19 RER+ tumors with measured size, 16 were > 2 cm, compared to 28 of 58 tumors with no evidence of microsatellite instability or with shifts in allele sizes limited to one locus (P

Microsatellite instability and pathological aspects of breast cancer.

Genomic instability plays a key role in hereditary nonpolyposis colorectal cancer and in a significant sub-set of non-hereditary colorectal tumors. Recent evidence suggests that microsatellite instability also occurs in various sub-sets of common, non-hereditary forms of extra-colorectal carcinoma. To investigate the role of microsatellite instability in breast cancer, and to correlate this type of alteration with clinico-pathological characteristics, including tumor proliferative activity, we analyzed the status of 8 different microsatellite loci in 28 cases of primary mammary carcinoma. For this purpose, microsatellite banding patterns were compared in paired breast-cancer/peripheral-blood DNA samples. Microsatellite instability was observed in 6/28 (21%) of the cases. Four of the 6 tumors had low proliferative activity, one had high proliferative activity, and in one case proliferative activity values were not available. All chromosomal loci investigated demonstrated microsatellite instability in one or more representative tumors of the series. Shifts in length larger than 2 bp were the most frequent change. Microsatellite instability significantly correlated with the lobular histotype, and with lymph-node involvement. A trend was also observed associating microsatellite instability and large tumor size.

XbaI polymorphism of the apolipoprotein B gene in patients with hyperlipidemia and echo-Doppler evidence of arterial lesions.

This study was designed to assess whether the XbaI restriction fragment length polymorphism (RFLP) for apolipoprotein B (apo B) gene could be related with a genetic predisposition to develop hyperlipidemia and atherosclerosis. Relationships between XbaI RFLP and serum cholesterol were evaluated by comparing hyperlipidemic patients with healthy controls. Statistical analysis (chi-square test) showed no significant difference in either genotype distribution or allele frequencies. Hyperlipidemic patients were then divided according to triglycerides, either above or below 200 mg/dl and XbaI genotype frequencies were measured. No significant differences in genotype distribution or allele frequencies were found. The hyperlipidemic patients were tested for the presence of arterial disease by echo-Doppler and angina questionnaire. The XbaI genotype frequencies were determined in patients with arterial disease and compared to those without evidence of disease. No significant differences were found between the two groups.

Addition of chlorthalidone to slow-release nifedipine in the treatment of arterial hypertension: a controlled study versus placebo.

The use of calcium antagonists and diuretics in combination for treatment of hypertension is controversial. In a single-blind study 16 patients (8 men, 8 women, age range 39 to 62 years) with primary hypertension of mild to moderate degree were given slow-release nifedipine 20 mg twice daily for 6 weeks, thereafter either chlorthalidone 25 mg (Group A) or placebo (group B) daily was randomly added for a further 6-week period. Blood pressure (BP), heart rate, plasma renin activity (PRA), aldosterone, and 24 hour urinary electrolytes were evaluated. Nifedipine decreased supine BP from 159/92 +/- 16/8 to 151/89 +/- 10/6 mmHg in group A and from 162/94 +/- 20/12 to 145/85 +/- 14/6 mmHg in group B. A further fall to 139/84 +/- 7/6 mmHg (p less than .05) was observed after addition of chlorthalidone. PRA significantly increased with combined treatment compared to baseline (3.3 +/- 0.8 to 9.9 +/- 3.3 ng/ml/hr; p less than 0.05). A slight reduction of 24-hour urinary calcium was observed after the addition of chlorthalidone. These data indicate that the combination of nifedipine and chlorthalidone might be beneficial in the treatment of arterial hypertension.

Adrenergic system and carbohydrate metabolism. Effects of beta-receptor blockade on insulin secretion and peripheral insulin sensitivity in normoglycaemic patients.

The effects of 3 weeks of treatment with the beta-receptor blocking agent propranolol and a placebo on glucose tolerance, insulin secretion and peripheral insulin sensitivity have been evaluated in 7 normoglycaemic hypertensive patients by an oral glucose tolerance test and the insulin clamp technique. Significant changes in systolic and diastolic blood pressure and heart rate were observed at the end of propranolol treatment, but there were no associated changes in glucose tolerance, insulin secretion or peripheral insulin sensitivity. No difference was observed in glucagon, growth hormone and free fatty acids between propranolol and placebo treatment. The results support the view that the hypothetical pancreatic glucoreceptor, at least in non-acute studies, is not affected by beta blockade. In addition, there was no effect on tissue sensitivity to insulin.

Changing the Mediterranean diet: effects on blood lipids.

A study was carried out on 48 healthy middle-age men and women habitually subsisting on a "Mediterranean type" diet in a rural area of southern Italy. Their freely chosen natural diet was modified for a period of 42 days by partially substituting animal fats for olive oil. Currently available foods were used, and the subjects maintained their habitual lifestyle. Dietary fat content changed from 33 to 37% of total energy and the polyunsaturated to saturated fatty acid ratio changed from 0.48 to 0.22. The base-line serum total cholesterol of men increased during the dietary intervention period from 214 +/- 30 mg/dl (mean and SD) to 245 +/- 33 mg (+15%). Low-density lipoprotein cholesterol increased 19%, while high-density lipoprotein cholesterol remained unmodified. Women, while exhibiting a similar trend in serum total cholesterol (+16%), showed also a 19% increase in their high-density lipoprotein cholesterol (p less than 0.001). Apoprotein B increased in parallel with low-density lipoprotein cholesterol in both sexes. The results of the study confirm the impact of the dietary factor on blood lipids. They also provide additional evidence on the response of high-density lipoprotein cholesterol to diet in free-living populations.

Separate influence of dietary carbohydrate and fibre on the metabolic control in diabetes.

To clarify the separate influences of digestible carbohydrate and of dietary fibre on blood glucose control and serum lipoproteins, 14 diabetic patients (six Type 1 and eight Type 2) were submitted to three weight-maintaining diets for 10 days each: (1) low carbohydrate/low fibre diet with 42% carbohydrate and 20 g fibre; (2) high carbohydrate/low fibre diet (carbohydrate 53%, fibre 16 g); (3) high carbohydrate/ high fibre diet (carbohydrate 53%, fibre 54 g). In comparison with the low carbohydrate/low fibre diet, the 2-h post-prandial blood glucose and the daily blood glucose profile decreased significantly on the high carbohydrate/high fibre diet, without significant changes during the high carbohydrate/low fibre diet. The diet-induced modifications of blood glucose control were similar in both types of diabetic patients (two-way analysis of variance: F = 5.86, p less than 0.02 for dietary treatment and F = 2.09, NS for type of diabetes). Total and low-density lipoprotein cholesterol were also decreased after the high carbohydrate/high fibre diet in comparison with the low carbohydrate/low fibre diet (p less than 0.001 for both), while they were not significantly modified after the high carbohydrate/low fibre diet. Again the modifications of low density lipoprotein cholesterol induced by diet were similar in both types of diabetic patients (F = 10.02, p less than 0.005 for dietary treatment and F = 0.14 for type of diabetes, NS). High-density lipoprotein cholesterol was lower after the two test diets than after the low carbohydrate/low fibre diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of oral mesoglycan on plasma lipoprotein concentration and on lipoprotein lipase activity in primary hyperlipoproteinemia.

Mesoglycan extracted from calf aorta was orally administered (96 mg/day) to 15 patients with primary hyperlipoproteinemia: 4 type IIA, 4 type IIB, 6 type IV and one type V. In the seven hypertriglyceridemic patients the drug after two months of treatment reduced total and VLDL-triglyceride from 701 mg/dl to 423 mg/dl (p less than 0.025) and from 562 mg/dl to 377 mg/dl (p less than 0.025) respectively and increased lipoprotein lipase activity from 19.7 mumol/l/min to 27.8 mumol/l/min (p less than 0.05). No change was observed in the group with type IIA-IIB hyperlipoproteinemia.

Effect of oxprenolol and metoprolol on serum lipid concentration.

The aim of the present study was to evaluate whether a reduction in HDL-cholesterol is peculiar to non cardioselective beta blockers or whether it is also produced by cardioselective beta 1-blockers. 16 patients with primary arterial hypertension on a balanced isocaloric diet were given oxprenolol 120 to 240 mg/day or metoprolol 100 to 200 mg/day in a random cross-over study. No significant change was observed after either treatment in fasting blood glucose, serum total cholesterol and triglycerides. HDL-cholesterol concentration was significantly decreased on metoprolol, from 41 to 36 mg/dl (p less than 0.05), while oxprenolol did not affect it at all. The difference might depend on intrinsic sympathomimetic activity which is possessed by oxprenolol and which metoprolol lacks.