Intravenous diltiazem versus nitroglycerin for silent and symptomatic myocardial ischemia in unstable angina pectoris

For 18 patients consecutively admitted to the coronary care unit for unstable angina, 48-hour electrocardiographic Holter monitoring was performed after they were randomly assigned in a single-blind fashion to 1 of 2 treatment groups. The first group was treated with acetylsalicylic acid (ASA) and intravenous nitroglycerin, the second with ASA and intravenous diltiazem. All of the patients treated with nitroglycerin still had ischemic episodes after 48 hours (33% were symptomatic), in contrast with 11% of the diltiazem group (11% asymptomatic). Maximal ST-segment depressions of symptomatic and asymptomatic episodes were significantly different; and no significant increases in heart rate were observed either during the 15 seconds before ischemia began or during the ischemic episode. During the 48 hours, the diltiazem group had significantly fewer ischemic episodes (17) than did the nitroglycerin group (145). We concluded that "on-line" ST-segment observation is of prime importance for monitoring unstable angina; that the majority of the ischemic episodes associated with unstable angina are silent; and that intravenous diltiazem could be an effective pretreatment for patients who must undergo mechanical or surgical therapy.     

The CEC behaviour of several synthetic peptides related to the activin βA–βD subunits

Abstract: The resolution of several structurally related synthetic peptides, derived from the loop 3 region of the activin β_A–β_D subunits, has been studied using capillary electrochromatography (CEC) with Hypersil n‐octadecylsilica as the sorbent. The results confirm that the CEC migration of these peptides can be varied in a charge‐state‐specific manner as the properties of the background electrolyte, such as pH, salt concentration and content of organic modifier, or temperature are systematically changed. Acidic peptides followed similar trends in retention behaviour, which was distinctly different to that shown by more basic peptides. The CEC separation of these peptides with the Hypersil n‐octadecyl‐silica involved distinguishable contributions from both electrophoretic mobility and chromatographic retention. Temperature effects were reflected as variations in both the electro‐osmotic flow and the electrophoretic mobility of the peptides. When the separation forces acting on the peptides were synergistic with the electro‐osmotic flow, as, for example, with the positively charged peptides at a particular pH and buffer electrolyte composition, their retention coefficient, κ_cec, decreased with increasing capillary temperature, whereas when the separation forces worked in opposite directions, as for example with negatively charged peptides, their κ_cec values increased slightly with increasing temperature. Moreover, when the content of organic modifier, acetonitrile, was sufficiently high, e.g. > 40% (v/v) and nonpolar interactions with the Hypersil n‐octadecyl‐silica sorbent were suppressed, mixtures of both the basic and acidic synthetic peptides could be baseline resolved under isocratic conditions by exploiting the mutual processes of electrophoretic mobility and electrostatic interaction. A linear relationship between the ln κ_cec values and the volume fractions, ψ, of the organic modifier over a limited range of ψ‐values, was established for the negatively charged peptides under these isocratic conditions. These findings thus provide useful guidelines in a more general context for the resolution and analysis of structurally related synthetic peptides using CEC methods.     

Phase II study of pemetrexed in breast cancer patients pretreated with anthracyclines.

BACKGROUND: To assess antitumor activity and toxicity of pemetrexed in metastatic breast cancer (MBC) patients previously treated with anthracyclines. PATIENTS AND METHODS: Seventy-seven MBC patients from 12 European institutions were entered into the study. Seventy-two patients were considered evaluable for response and toxicity. Forty-two patients were classified as anthracycline-failure (relapse >30 days after completion of a prior anthracycline regimen) and 30 as anthracycline-refractory (progression within 30 days after anthracycline therapy). Pemetrexed 600 mg/m(2) was administered intravenously every 3 weeks until progressive disease or unacceptable toxicity. RESULTS: There were three complete and 12 partial responders [response rate 21% (95% confidence interval 12%)]. Response rates in the anthracycline-failure and anthracycline-refractory groups were 24% and 17%, respectively. A subset of 31 patients pretreated with anthracyclines and taxanes had a response rate of 26%. Median duration of response and median survival were 5.5 and 10.7 months, respectively (13 months in the failure group and 5.7 months for refractory). Grade 3/4 toxicities included neutropenia and thrombocytopenia in 56% and 19% of patients, respectively. Nine patients (12%) experienced neutropenic fever. Grade 3/4 non-hematological toxicities included skin rash (10%), nausea (12%), fatigue (10%) and stomatitis (5%). CONCLUSION: Our trial demonstrates pemetrexed to be active in breast cancer, with manageable toxicity. Activity of pemetrexed did not appear to be adversely affected by prior taxane, 5-fluorouracil or endocrine treatments.     

Proliferative lesions of oviduct and uterus in CD-1 mice exposed prenatally to tamoxifen

Tamoxifen (TAM) is widely used as adjuvant breast cancer therapy after surgery and as a chemopreventive agent in women of child-bearing age. However, TAM therapy has been shown to result in an increased incidence of endometrial carcinoma in women. The present study was designed to investigate the effects of TAM (5 mg/kg and 7.5 mg/kg body wt) given i.g. to pregnant CD-1 mice (1x/day, days 12 through 18 of gestation) on their female offspring. Progressive proliferative hyperplasia of the oviduct was frequently seen in TAM-exposed offspring, reaching 100% incidence by 52 weeks in both treatment groups. These females also developed progressive proliferative uterine lesions, including moderate/severe cystic endometrial hyperplasia (34-50%) and polypoid adenomas (27-30%) between 53 and 78 weeks. Deciduomas (15%) occurred at young ages (12 and 24 weeks) while leiomyomas (14%), a malignant leiomyosarcoma, and ovarian granulosa cell tumors (14%), were found between 72 and 78 weeks. Our findings thus suggest a strong association between transplacental TAM and reproductive tract abnormalities in female CD-1 mice.      

Hypoglycémie hyperinsulinémique persistante du nouveau-né et du nourrisson

Persistent hyperinsulinemic hypoglycaemia of infancy (PHHI) is the most frequent cause of hypoglycaemia in infancy. Clinical presentation is heterogeneous, with variable onset of hypoglycaemia and response to diazoxide, and presence of sporadic or familial forms. Underlying histopathological lesions can be focal or diffuse. Focal lesions are characterised by focal hyperplasia of pancreatic islet-like cells, whereas diffuse lesions implicate the whole pancreas. The distinction between the two forms is important because surgical treatment and genetic counselling are radically different. Focal lesions correspond to somatic defects which are totally cured by limited pancreatic resection, whereas diffuse lesions require a subtotal pancreatectomy exposing to high risk of diabetes mellitus. Diffuse lesions are due to functional abnormalities involving several genes and different transmission forms. Recessively inherited PHHI have been attributed to homozygote mutations for the beta-cell sulfonylurea receptor (SUR1) or the inward-rectifying potassium-channel (Kir6.2) genes. Dominantly inherited PHHI can implicate the glucokinase gene, particularly when PHHI is associated with diabetes, the glutamate dehydrogenase gene when hyperammonaemia is associated, or another locus.