Synthesis and Antitumour Activity of New Derivatives of Flavone-8-acetic Acid (FAA). Part 2: Ring-Substituted Derivatives

A range of 18 derivatives of flavone-8-acetic acid (FAA) with substituents on the 2-phenyl group have been prepared and their anti-tumour activity evaluated in vitro against a panel of human and murine tumour cell lines and in vivo against MAC 15A. There was no clear-cut relationship between in vitro and in vivo activity but the activity in each situation was found to be very sensitive to the precise substitution pattern with closely related isomers giving widely different activities. Some of the compounds, notably 10b,cj , and r , were active in vivo and these require further studies in order to evaluate their potential for development.     

Nociceptin (Orphanin FQ) abolishes gestational and ovarian sex steroid-induced antinociception and induces hyperalgesia

Nociceptin (Orphanin FQ) is a newly discovered endogenous heptadecapeptide substrate for the opioid-receptor-like 1 receptor, a G protein coupled receptor that bears striking amino acid sequence homology to opiate receptors. In rats, intrathecal (i.t.) administration of nociceptin is without effect on basal thresholds for responsiveness to electric foot shock. However, during either late gestation or its hormonal simulation, when nociceptive thresholds are elevated by approximately 70%, i.t. nociceptin substantially attenuates jump thresholds in a dose-dependent fashion. This hypoalgesic effect of nociceptin is not limited to attenuating the gestational or sex steroid-induced increment in pain thresholds. Following the highest i.t. dose of nociceptin employed (20 nmol), the gestational or sex steroid-induced increment in jump thresholds is not only abolished but a significant hyperalgesia is observed. These results underscore the importance of the hormonal milieu to nociceptin hypoalgesic sensitivity. The potential contribution of spinal nociceptive pathways that utilize nociceptin to the etiology of extraordinary painful pregnancy and labor should not be ignored.     

Doctoral Education in Nursing for Practitioner Knowledge and for Academic Knowledge: The University of Adelaide, Australia

Australian nursing has undergone rapid academization in the past 10 years and this radical change has tended to meld the somewhat different academic traditions of North America and Britain. The introduction of doctoral education in nursing in 1987 has led to a massive increase in scholarly activity and to the preparation of talented leaders. We concur with the view expressed by Henry (1997), "I am convinced that the problems we face in the nursing services would be much more creatively solved if the majority of our doctoral programs prepared young, energetic nurses, early in their career, for clinical practice, not for research and teaching" (p. 162).     

Acute cardiac and pulmonary arrest after infusion of vancomycin with subsequent desensitization

J Allergy Clin Immunol 1997;100:853-4.     

High-Risk Drinking across the Transition from High School to College

Alcohol use and related problems were studied from the senior year in high school to the first autumn in college for 366 heavy drinking students. Four risk factors-subject sex, family history of drinking problems, prior conduct problems, and type of college residence-were evaluated as predictors of: (1) differential changes in drinking rates, (2) differential changes in alcohol-related problems, and (3) alcohol dependence symptoms during the first college term. Results suggest that both dispositional and environmental factors are associated with changes in drinking rates and the existence of dependence symptoms. Increases in the frequency of drinking were specifically and strongly associated with residence in a fraternity (men) or sorority (women). Three risk factors were associated with increased quantity of drinking: male gender, residence in a fraternity or sorority, and a history of conduct problems. Prior conduct problems were also consistently associated with dependence symptoms during the first term in college. A family history of alcohol problems was not consistently related to changes in use rates or problems, although some analyses suggest interactive effects. Early interventions on college campuses should target individuals using additive risk profiles.     

Evidence for nitric oxide participation in down-regulation of CYP2B1/2 gene expression at the pretranslational level

Septic or inflammatory stimuli suppress drug metabolism by cytochrome P-450 in the liver, presumably at the pretranslational level. We have shown previously that nitric oxide is responsible at least in part for the inhibition by bacterial lipopolysaccharide of phenobarbital-induced CYP2B1/2 activity in vivo. This was attributed to the interaction of nitric oxide with heme in the active-center of cytochrome P450, leading to enzyme inactivation. Here, we report of nitric oxide with heme in the active-center of cytochrome P450, leading to enzyme inactivation. Here, we report that endogeneous nitric oxide also contributes to LPS-induced suppression of CYP2B1/2 in vivo by down-regulating the expression of CYP2B1/2 protein and mRNA.     

Analgesic profile of the sodium salt of pemedolac

Pemedolac Na, 1-ethyl-1,3,4,9-tetrahydro-4-(phenylmethyl)-pyrano [3,4-b] indole-1-acetic acid sodium salt, exhibited equipotent analgesic effects after oral, iv, and im administration, suggesting that it is well absorbed. In mouse writhing models, the ED₅₀ values ranged from 0.3 mg (0.81 μmol)/kg (vs. acetylcholine) to 4.3 mg (11.6 μmol)/kg (vs. paraphenylbenzoquinone [PBQ]). In the rat Randall-Selitto model, the ED₅₀ o the compound was approximately 0.001 mg (2.7 nmol)/kg, with a flat dose response curve. The peak effects lasted for 7–9 h, 10–18 h, and 5 h following oral, im, and iv injections, respectively. Intracerebroventricular (i.c.v.) injections of pemedolac Na inhibited the PBQ-induced writing in mice with an ED₅₀ of 43.5 μg (0.12 μmol)/mouse, and this effect was not antagonized by naloxone. It was inactive in the hot plate and tail flick tests, demonstrating that pemedolac Na does not act via an opiate mechanism. These results indicate that pemedolac Na is a viable parenteral and oral analgesic, typified by high analgesic potency, a rapid onset and long duration of action, and an extremely wide safety index. © Wiley-Liss, Inc.     

Use of suture-mediated vascular closure devices for the management of femoral vein access after transcatheter procedures.

Groin complications remain the most common complication of cardiac catheterization procedures. While the use of closure devices is increasing for arterial sheaths, venous sheaths tend to be removed and hemostasis achieved with manual compression. We report our experience using Perclose suture-mediated vascular closure device to achieve hemostasis and early mobility in patients who have had venous access as part of their procedure. There were a total of 42 patients (21 males; average age, 63.5 years) studied. The majority of the patients had 7 Fr sheaths (24), with access sites of sheaths up to 14 Fr being closed with this technique. Two patients developed complications at the access site: one patient requiring rehospitalization for intravenous antibiotics because of late access site infection, and one patient with deep venous thrombosis and pulmonary emboli. We conclude that the use of the Perclose suture-mediated closure device for closure of femoral venous access sites is feasible and should be considered especially in patients with larger venous sheaths and those at increased risk of groin complications.     

Organisational factors in relation to control of blood pressure: an observational study

BACKGROUND: Studies show that 60-75% of treated patients with hypertension in general practice, still do not reach the recommended blood pressure targets of <150/90 mmHg. AIM: To investigate aspects of hypertension management in relation to sociodemographic variables, antihypertensive drug treatment, and organisational factors in primary care. DESIGN OF STUDY: Observational study over 3 years. SETTING: Eight general practices in Tayside, UK. METHOD: Participants were 560 randomly selected patients aged 40-79 years receiving treatment for hypertension. The outcome measurement was blood pressure control, expressed in binary form based on the British Hypertension Society audit standard of <150/90 mmHg. RESULTS: Of 536 eligible patients, 261 (49%) were defined as having inadequate blood pressure control at the end of the study period. No significant associations were discovered with sex, age, deprivation score and comorbidity. In those patients with inadequate control, 30% had no modifications to their drug treatment during the study period. Blood pressure control at the end of the study period was not associated with number of antihypertensive drugs taken or number of antihypertensive drug modifications. The mean number of clinician contacts was 11 (standard deviation = 8), and mean continuity in primary care was high, although this was not associated with improved blood pressure control. A higher proportion of hypertension-related consultations were associated with increased odds of having inadequate blood pressure control. CONCLUSION: Achieving adequate blood pressure control continues to represent a substantial health problem in a significant proportion of the hypertensive population. Patient, physician and organisational elements play a role in ensuring effective delivery of hypertension care in the community.