Prevalence of aneuploidy,overexpressed ER,and overexpressed EGFR in random breast aspirates of women at high and low risk for breast cancer

Summary Breast tissue biomarkers which accurately predict breast cancer development within a 10 year period in high risk women are needed but currently not available.We initiated this study to determine 1) the prevalence of one or more breast tissue abnormalities in a group of women at high risk for breast cancer, and 2) if the prevalence of biomarker abnormalities is greater in high risk than in low risk women. Eligible high risk women were those with a first degree relative with breast cancer, prior breast cancer, or precancerous mastopathy. Low risk women were those without these or other major identifiable risk factors. Ductal cells were obtained via random fine needle aspirations and cytologically classified. Biomarkers included DNA ploidy, estrogen receptor (ER), and epidermal growth factor receptor (EGFR).The prevalence of DNA aneuploidy was 30%, overexpression of ER 10%, and overexpression of EGFR 35%, in the 206 high risk women whose median 10 year Gail risk (projected probability) of developing breast cancer was 4.5%. The prevalence of aneuploidy and overexpressed EGFR was significantly higher in the high risk women than in the 25 low risk controls (p < 0.002), whose median 10 year Gail risk was 0.7%. The difference in the prevalence of ER overexpression between high and low risk groups was not statistically significant (p = 0.095). This may be due to the low prevalence of overexpressed ER and the small number of controls. A significant difference was noted in the prevalence of one or more abnormal biomarkers between the high risk and low risk women (p < 0.001).A large prospective trial is needed to determine if one or more of these biomarkers, is predictive of breast cancer development.     

Treatment of preeclampsia with prostaglandin A1

The vasodepressor prostaglandin A1 appeared to offer a major clinical potential solution in cases of severe pregnancy-induced hypertension. Thirty pregnant women with severe pregnancy-induced hypertension and a low Bishop score were studied in three equal groups. Group 1 received prostaglandin A1 infusions alone (0.5 microgram/kg/min for a maximum of 24 hours). Group 2 had received initial priming by prostaglandin E2 vaginal gel 6 hours before the onset of the prostaglandin A1 infusion, and group 3 was treated by conventional therapy and oxytocin induction. In the first two groups blood pressure was reduced to normotensive values, and labor was induced satisfactorily in 15 of the 20 cases, but four patients in group 1 were delivered within 24 hours after infusion. Group 2 offered the most favorable results because 80% were delivered during the infusion; thus the postinfusion rebound rise in blood pressure was avoided. Group 3 presented the least acceptable results, with the highest failure rate and an increased number of operative deliveries.     

The Syndrome of Hepatitis and Aplastic Anaemia

S ummary . Eighty-eight cases of severe pancytopcnia closely following the onset of apparently typical viral hepatitis have been described. We report two additional patients. Remarkable features of the syndrome are the rapid, high mortality (88%) and the fact that the age and sex distribution parallel that of hepatitis, not that of other wries of aplastic anaemia. Although viral damage to haematopoietic cells can be demonstrated in vitro , chromosonies in our patients were normal after short-term culture of peripheral lyrnpliocytes. Therapeutically, androgens may be of some benefit despite the high mortality. No adequate explanation for the association is available, but infectious hepatitis should be accepted as a potential cause of aplastic anacmia.     

Sarcopenia and Aging

Sarcopenia refers to the gradual decline in muscle mass and quality noted with advancing age. There is growing evidence linking sarcopenia to functional disability, falls, decreased bone density, glucose intolerance, and decreased heat and cold tolerance in older adults. Factors implicated in the etiology of sarcopenia include decreased physical activity, malnutrition, increased cytokine activity, oxidative stress, and abnormalities in growth hormone and sex steroid axes. At present, progressive resistance training is the best intervention shown to slow down or reverse this condition. Preliminary studies show that the utilization of several trophic factors, notably testosterone and DHEA, may have a salutary effect on muscle mass and/or strength in older adults. More research is needed, however, before drawing definite conclusion as to the clinical utility of these substances in the management of sarcopenia.     

In vitro effects of trace elements on blood clotting and platelet function. A--Iron, copper, and gold.

The present in vitro study of the effects of iron on the blood coagulation mechanism in rats showed that addition of ferrous sulphate to pooled rat plasma resulted in inhibition of blood coagulation, as shown by prolongation of the clotting parameters tested, an effect which was dose-dependent. In vitro addition of ferrous sulphate to rat PRP in doses of 2-5 mg/ml significantly decreased platelet aggregation in response to ADP, while collagen-induced aggregation was significantly diminished in presence of the higher doses of ferrous sulphate (4-5 mg/ml). Also, preincubation of ferrous sulphate with thrombin or with pure fibrinogen indicated that iron could produce decrease of thrombin activity as well as impairment of fibrinogen clottability. In vitro addition of copper sulphate (300-1000 micrograms/ml) elicited an anticoagulant effect, though thrombin time was markedly shortened with all tested concentrations of copper sulphate. Addition of copper sulphate to PRP produced inhibition of platelet aggregation in response to PRP produced inhibition of platelet aggregation in response to ADP and to collagen. Preincubation of copper sulphate with thrombin resulted in slight enhancement of thrombin activity followed by inhibition, while preincubation of copper sulphate with pure fibrinogen caused only minimal impairment of fibrinogen clottability. Also, addition of gold chloride in doses of 50-500 micrograms/ml to plasma in vitro produced a dose-dependent progressive prolongation of all clotting parameters tested, the effects reaching a maximum after 30 min. incubation. Further the in vitro addition of gold chloride to rat PRP resulted in marked inhibition of platelet aggregation in response to both ADP and collagen. In addition, preincubation of gold chloride with thrombin or with pure fibrinogen showed that gold exerted an antithrombin action and prolonged the fibrinogen clotting time indicating impaired fibrinogen clottability.     

A detailed examination of the in vivo and in vitro effects of ACTH on gonadotropin secretion in the adult rat

These studies were designed to: (1) determine the effects of continuous infusion of synthetic ACTH(1-24) on postcastration changes in serum and pituitary LH, FSH and prolactin in the male rat; (2) assess the effects of adrenalectomy on the gonadotropin and prolactin response to ACTH, and (3) test the hypothesis that ACTH may directly (not via adrenal factors) alter gonadotropin secretion at the brain and/or pituitary level. Adult male rats were either orchidectomized (ORX) or orchidectomized-adrenalectomized (ORX-ADX), and were treated continuously for 6 days with ACTH(1-24) (10 micrograms/day) or saline using an osmotic minipump. Animals were killed on day 6 following castration. ACTH treatment reduced serum LH and prolactin levels in ORX rats to mean values +/- SE of 204 +/- 25 and 37 +/- 3 ng/ml respectively, compared to 366 +/- 72 and 62 +/- 7 ng/ml in saline-treated ORX animals. Serum FSH concentrations were not altered by ACTH administration. Pituitary concentrations of LH and FSH, but not prolactin were enhanced by ACTH treatment. Adrenalectomy had no effect on serum and pituitary gonadotropin and prolactin levels, but abolished the effects of ACTH on these parameters. Central (intracerebroventricular) infusion of ACTH(1-24) (6 micrograms/day X 4 days) failed to alter the rise in serum LH in male rats following orchidectomy. Acute treatment with large doses of ACTH of perifused anterior pituitary glands from male rats and chronic treatment with ACTH of enzymatically dispersed anterior pituitary cells from female rats did not influence basal or GnRH-stimulated LH secretion.(ABSTRACT TRUNCATED AT 250 WORDS)