Endothelin 1 mediates ex vivo coronary vasoconstriction caused by exogenous and endogenous cytokines

Treatment of rats with cytokines has been associated with an increase in the circulating levels of endothelin 1 (ET-1). Here we show that administration of tumor necrosis factor alpha (TNF-alpha; 4 micrograms.kg-1) to anesthetized rats caused within 15 min a strong elevation in the circulating levels of ET-1. This was associated with a striking coronary vasoconstriction in hearts from these animals when they were removed and perfused in vitro by the Langendorff technique. This vasoconstriction was largely overcome by treatment with either the endothelin type A (ETA) receptor antagonist FR 139317 or antibody against ET-1. Furthermore, it was mimicked by in vivo exposure to exogenous ET-1. Endogenously produced TNF-alpha may also cause such a coronary vasoconstriction, for treatment with interleukin 2 (600 micrograms.kg-1) produced an increase in coronary perfusion pressure that correlated with the increases in circulating TNF-alpha. This coronary vasoconstriction was substantially reversed by treatment either with antibody against TNF-alpha or with FR 139317. We suggest, therefore, that cytokine-driven changes in the production of ET-1 are key events in the development of vascular pathologies.     

The Smoking Consequences Questionnaire-Adult: Measurement of smoking outcome expectancies of experienced smokers.

The original Smoking Consequences Questionnaire (SCQ; T. H. Brandon & T. B. Baker, 1991) measured college students' outcome expectancies for cigarette smoking. A version (SCQ-Adult) was needed for assessing expectancies in more typical, older, nicotine-dependent smokers. Two separate versions of the SCQ were developed and compared. Tests of construct validity provided greater support for the version comprising probability items over the version comprising subjective expected utility items. As expected, principal components analyses revealed a greater number of factors than the original SCQ suggesting that expectancies become more specific with smoking experience. All scales showed good reliability. Over the course of smoking cessation treatment, expectancies became less positive, especially for abstaining participants. Other validity tests also tended to be consistent with research on alcohol expectancies and with contemporary models of drug outcome expectancies. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Anti-macrophage monoclonal antibody D-11 in the diagnosis of histiocytic tumors

Anti-macrophage monoclonal antibody (Mab) D-11 was tested in surgical material and biopsies of non-epithelial tumors and tumor-like lesions from 181 patients in order to assess possibility of using this Mab for diagnosis of histiocytic tumors, malignant fibrous histiocytoma in particular. The study was performed in parallel on cryostat sections and smears by immuno-peroxidase method. It is established that D-11 reacts positively with both histiocytic tumors and tumors of other genesis this being a limiting factor in differential diagnosis of histiocytic tumors. However, taking into consideration 100% of positive results with histiocytic tumors only, this antibody can be used for exclusion of tumors studied from the group of histiocytomas in cases of negative reaction.     

Comparison of the efficacy and safety of once-daily versus twice-daily formulations of diltiazem in the treatment of systemic hypertension. The Canadian Multicenter Diltiazem-CD Hypertension Trial Group

The efficacy and safety of optimally titrated once-daily (CD) and twice-daily (SR) diltiazem were compared in 111 patients with mild to moderate systemic hypertension [seated diastolic blood pressure (DBP) > or = 95 mmHg and < or = 114 mmHg] in a multicenter, randomized, double-blind, placebo run-in, parallel-group trial. Following a 4 week washout and placebo-controlled run-in period, patients were randomized to receive diltiazem CD 180 mg and matching placebo (n = 54), or diltiazem SR 90 mg bid (n = 57). Total daily doses were titrated from 180 mg to 360 mg to achieve a goal of seated DBP < 90 mmHg during a 6 week titration period. The patients continued to receive their optimal dose for a 6 week follow-up period. Ninety-six (96) patients (diltiazem CD: 47, diltiazem SR: 49) completed the study protocol, with 60% of the diltiazem CD and 55% of the diltiazem SR patients achieving the goal of seated DBP of < 90 mmHg (p = 0.685). Although significant decreases occurred in seated and standing measurements of diastolic and systolic BP and heart rate with treatment in both groups, there were no significant differences between treatment groups. Both medications were well tolerated, with a similar frequency of adverse effects [diltiazem CD: 24/54 (37%) patients; diltiazem SR: 24/57 (42.1%) patients] with the most frequently reported adverse effects being headache and edema.     

Efficacy and toxicity of radiation in preparative regimens for pediatric stem cell transplantation. I: Clinical applications and therapeutic effects

Here, we review the role of total body irradiation in the treatment of children with bone marrow transplantation, as well as alternative sources of stem cells. We were unable to demonstrate any clear superiority of TBI-containing preparative regimens, but we were able to find a few definitive reports of significantly enhanced toxicity or important variations in control of the underlying primary diseases, in comparing TBI-based regimens, with those containing only chemotherapy.     

Human papillomavirus investigation of patients with cervical intraepithelial neoplasia 3, some of whom progressed to invasive cancer

Unstable expansion of the CTG repeats in the 3' untranslated region encoding a member of the protein kinase family in the q13.3 band on chromosome 19 is a mutation specific for myotonic dystrophy. To examine the correlation between clinical expression and CTG trinucleotide repeat length, we carried out Southern blot analysis in a family with myotonic dystrophy. In this pedigree, the expanded CTG repeats were transmitted maternally. The mother had three female children. The mother had about 200 CTG repeats, and the number of repeats for each child was about 800, 1500 and 1600 in birth order. The mother and the patient with 800 repeats were unaware of muscle weakness or myotonia. Symptoms were present from age 3 years in the patient with 1500 repeats and from birth in the one with 1600 repeats. Although the mother menstruated regularly, the patients with 800 and 1500 repeats both menstruated irregularly, and the one with 1600 repeats has never menstruated. The age of onset and severity of the disease were correlated with the size of the expanded repeats. Endocrinological studies revealed that the basal levels of the gonadotropins, PRL and E2 were within normal range, and a pituitary response to LHRH was observed. These data suggest that the amenorrhea and menstrual irregularities were caused by a suprahypophyseal dysfunction. When expanded CTG repeats are transmitted maternally, abnormal products resulting from the metabolic disturbance in the affected mother may harm the fetus in utero. A heterozygous fetus, who has more CTG repeats, may be unable to metabolize the pathologic products sufficiently and therefore may become more severely affected. This may explain the exclusive maternal transmission of congenital myotonic dystrophy.