LONG-TERM TREATMENT WITH A NEW NON-ERGOT LONG-ACTING DOPAMINE AGONIST, CV 205-502, IN WOMEN WITH HYPERPROLACTINAEMIA

Twenty-four hyperprolactinaemic women were treated for 6 months with the new, non-ergot, long-acting dopamine agonist, CV 205-502. The treatment resulted in normalization of PRL secretion in 17 of the 24 women at once-daily doses of 0.05 to 0.15 mg of the drug. Sixteen of these women as well as 4 of those who remained hyperprolactinaemic had regular menstrual bleeding. Five of the patients had previously discontinued bromocriptine therapy because of adverse effects but had no problems tolerating CV 205-502. Of three bromocriptine-resistant women, two responded partially while one also remained unresponsive to CV 205-502 treatment. Mild to moderate galactorrhoea was recorded at baseline in 19 of the 24 women. After 6 months' treatment mild galactorrhoea was still present in six patients, four of whom had attained normal PRL levels. Side-effects were mild and transient. CV 205-502 seems to be a valuable compound in the management of patients with hyperprolactinaemia.     

Fumes from the spleen

Human domination over nature is quite simply an illusion, a passing fancy by a naive species. It is an illusion that has cost us much, ensnared us in our own designs, given us a few boasts to make about our courage and genius, but all the same it is an illusion     

The effect of cisapride on oral and intravenous glucose tolerance in normal subjects

Cisapride is used widely for the treatment of diabetic gastroparesis. There is some evidence that cisapride may influence insulin secretion. The aim of this study was to evaluate the effect of cisapride on plasma concentrations of glucose, insulin and C-peptide in response to oral and intravenous glucose loads. Twelve normal subjects took cisapride and placebo, each for 10 days using a randomized, double-blind, crossover design. In each treatment phase, the plasma glucose, insulin and C-peptide response to intravenous (0.5 g/kg) and oral (75 g) glucose loads was evaluated on separate days. Gastric emptying of the oral glucose load was also measured. After the intravenous glucose load, plasma concentrations of C-peptide were higher (P < 0.01) on cisapride when compared with placebo (e.g. peak C-peptide 2.08 ± 0.25 nmol/L vs 1.78 ± 0.22 nmol/L, P < 0.01) while there was no significant difference in plasma glucose or insulin. Cisapride had no effect on the rate of gastric emptying of the oral glucose load. Mean plasma concentrations of insulin and C-peptide were higher after oral glucose on cisapride than placebo, but these differences were not significantly different. These observations indicate that cisapride may increase glucose-stimulated insulin secretion.     

Studies on Reproduction in Rats with Pirmenol, an Antiarrhythmic Agent

Studies on Reproduction in Rats with Pirmenol, an AntiarrhythmicAgent. ANDERSON, J. A., PETRERE, J. A., FITZGERALD, J. E., DELA IGLESIA, F. (1986). Fundam. Appl. Toxicol. 7, 221-227. Fertilityand perinatal-postnatal studies were performed in CD rats givenpirmenol, an antiarrhythmic agent, at dosages of 0, 25, 50,and 100 mg/kg. The drug was administered orally as diet admixturesin all studies. In the male fertility study, mature male ratswere treated for 61 days prior to mating with virgin, untreatedfemale rats. In the female fertility study, mature virgin femalerats were treated for 15 days prior to mating with untreatedpartners with treatment continuing throughout mating, pregnancy,parturition, and weaning of the litters. In both studies, one-halfof the dams in each group were killed on Day 21 of pregnancyand the remaining dams were allowed to deliver and wean theiroffspring and postnatal development was monitored. At weaning,two males and two females were arbitrarily selected from eachlitter, allowed to mature on unmedicated diet, and then matedwithin treatment groups to produce the F2 generation. In theperinatal-postnatal study, pregnant females were treated continuouslyfrom Day 15 of pregnancy until weaning of the litters on Day21 postbirth. No adverse effects on fertility, general reproductiveparameters, or offspring survival and development were evidentat doses employed in these studies.     

The Effects of Inhalation of Organic Chemical Air Contaminants on Murine Lung Host Defenses

The Effects of Inhalation of Organic Chemical Air Contaminantson Murine Lung Host Defenses. ARANYI, C., O'SHEA, W. J., GRAHAM,J. A., AND MILLER, F. J. (1986). Fundam. Appl. Toxicol. 6,713–720.The potential health hazards of exposure to threshold limitvalue (TLV) concentrations of acetaldehyde, acrolein, propyleneoxide, chloroform, methyl chloroform, carbon tetrachioride,allyl chloride, methylene chloride, ethylene trichloride, perchloroethylene,benzene, phenol, monochlorobenzene, and benzyl chloride, compoundswhich may be present in the ambient or work room atmospherewere investigated. The effects of single and multiple 3-hr inhalationexposures were evaluated in mice by monitoring changes in theirsusceptibility to experimentally induced streptococcus aerosolinfection and pulmonary bactericidal activity to inhaled Klebsiellapneumoniae. When significant changes in these parameters werefound, further exposures were performed at reduced vapor concentrationsuntil the no-measurable-effect level was reached. Multiple exposureson 5 consecutive days were then performed at this concentration.Significant increases in susceptibility to respiratory streptococcusinfection were observed after single 3-hr exposure to TLV concentrationsof methylene chloride, perchloroethylene, and ethylene trichloride.For methylene chloride and perchioroethylene, these exposureconditions also resulted in significantly decreased pulmonarybactericidal activity.     

Study of Pacemaker and Implantable Cardioverter Defibrillator Triggering by Electronic Article Surveillance Devices (SPICED TEAS)

The magnetic fields emitted by electronic article surveillance (EAS) systems (shoplifting gates) are a source of interference for implanted medical devices. In the Study of Pacemaker and Implantable Cardioverter Defibrillator Triggering by Electronic Article Surveillance Devices (SPICED TEAS), 25 adult volunteers with ICDs and 50 with pacemakers were exposed to the fields of six different EAS systems. These EAS systems used three modes of operation: magnetic audio frequency, swept radio frequency, and acoustomagnetic technology. No ICD exhibited interference mimicking sensing of tachyarrhythmias with any EAS system. Pacemakers interacted variably, depending on the type of EAS system. Swept radiofrequency systems produced no interaction with any implanted medical device. One magnetic audio frequency system interacted with 2 of 50 pacemakers. The acoustomagnetic system interacted with 48 of 50 pacemakers. Interactions included asynchronous pacing, atrial oversensing (producing "EAS induced tachycardia" in the ventricle), ventricular oversensing (with pacemaker inhibition), and paced beats resulting from the direct induction of current in the pacemaker ("EAS induced pacing"). These interactions produced symptoms in some patients ( palpitations, presyncopel only while patients were in the EAS field. No pacemaker was reprogrammed. We conclude that high energy, pulsed low frequency EAS systems such as acoustomagnetic systems interfere with most pacemakers. Pacemaker patients should be advised to minimize exposure to the fields of such systems to prevent the possibility of serious clinical events.     

KALLIKREINS AND KININS IN INFLAMMATORY-LIKE EVENTS IN THE REPRODUCTIVE TRACT

The normal reproductive events of proliferation of the endometrial lining of the uterus during the menstrual cycle and ovulation have been likened to inflammatory-like events. The kallikrein-kinin system is involved in inflammatory processes in many tissues. In this review, we identify which components of the kallikrein-kinin system — the enzyme, tissue kallikrein; the substrate, low molecular weight kininogen and the effector receptor for the generated bradykinin peptide, the B2 receptor — have been identified in the uterus and ovary and their known involvement in the function of these organs. All three components have been localized to the glandular epithelial cells of the human endometrium. Tissue kallikrein gene expression is elevated midcycle when estrogens levels are also rising. This is also a time of extensive endometrial proliferation and tissue remodelling in preparation for embryo implantation, an event which is likened to other inflammatory processes. Similarly, tissue kallikrein gene expression was elevated following the estrogen surge at proestrous in the rat uterus, suggesting tissue kallikrein gene expression may be regulated by estrogens. Tissue kallikrein enzyme activity and gene expression has been demonstrated in the rat ovary and shown to be variously altered at the time of ovulation. Bradykinin has also been implicated in the expulsion of the ovum at the time of ovulation. These findings show that various components of the kallikrein-kinin system are present in the uterus and ovary. Further studies are required to more fully delineate their role in reproductive function.     

The Induction Profile of Three Orally Active Imidazopyridine-Containing Cardiotonic Agents in Rat Hepatic Microsomes

The Induction Profile of Three Orally Active Imidazopyridine-ContainingCardiotonic Agents in Rat Hepatic Microsomes. BERNSTEIN, J.R, AND FRANKLIN, R. B., (1986). Fundam Appl. Toxicol. 7, 26-32.The induction of hepatic cytochrome P-450-linked monooxygenaseshas been studied after the twice daily, oral administrationof two imidazo[4,5-c]pyridine-containing compounds and one imidazo[4,5-6]pyridine-containingdrug. The compounds were administered by the oral route, atdifferent doses, for 6 days after which time hepatic microsomeswere prepared. In vitro biochemical assays revealed that allthree compounds increased the O-deethylation of 7-ethoxyresorufinin a dose-dependent manner while not significantly affectingeither the 0-de- alkylation of 7-ethoxycoumarin or the levelsof NADPH-cytochrome c reductase. Ethylmorphine- N-demethylationwas decreased after dosing with the imidazo[4,5-b]pyridine-containingdrug. Levels of cytochrome(s) P-450 and liver-to-body weightratios were not significantly altered. The imidazo[4,5-c]pyndine-containingcompound was more potent in terms of the induction of 7-ethoxyresorufinthan either of the imidazo[4,5-c]pyridine-containing compoundsbut was approximately fourfold less active in this regard than3-methylcholanthrene. No induction of cy- tochrome-.P-450-linkedmonooxygenase activities was evident at a twice daily dose of5 mg/kg for 6 days for all three compounds tested, constitutinga no-effect level. The imidazo[4.5-c]pyridine-1 containing compoundsexhibited modified Type II difference spectra when added toa suspension of rat hepatic microsomes. The imidazo[4,5-6]pyridine-containingcompound has previously been reported to be (i) a rapid andpotent inducer of monooxygenase activity and (ii) have a TypeII difference Spectrum.(c) 1986 Society of Toxicology     

The DIET Study: Long-term Outcomes of a Cognitive-behavioral Weight-control Intervention in Independent-living Elders

Objective to describe the long-term outcomes of a cognitive-behavioral weight-control intervention implemented in a community-based sample of independent-living, older adults.Design A quasi-experimental design was used to compare an intervention community with a wait-listed control community. Comparisons between the communities were made at 40 weeks (J Am Diet Assoc. 1994;94:37-42). The controlled trial ended at 40 weeks; then both communities received 2 years of intervention. Two-year data from both communities were combined and are presented in this article. Three-year outcome data from the initial intervention community were available and are also presented.Subjects A total of 247 overweight (>4.5 kg of age-adjusted weight), older (mean AGE=71 years) adults in 2 independent-living retirement communities participated in the study.Intervention The Dietary Intervention: Evaluation of Technology (DIET) study consisted of an intensive 10-week psychoeducational approach focused on lifestyle change, followed by a less intensive 2-year phase focusing on relapse prevention and maintenance of lifestyle changes.Outcome measures Physiologic and behavioral variables were analyzed at baseline and at 2 years after baseline. This article reports the combined 2-year outcome data from both retirement communities. Results of an additional follow-up 1 year after intervention was withdrawn are reported for the initial intervention community.Statistical analysis A within-subjects repeated measures analysis of variance design was used to test for significant changes in weight and lipid values over time.Results At 2 years, 70% of those who started the intervention remained actively enrolled. This group showed significant decreases in body mass index (−1.2, P<.001) and glucose level (−0.80 mmol/L, P<.001). Although high-density lipoprotein cholesterol (HDL-C) levels had increased at 40 weeks after baseline, this was not maintained at 2 years. At the 3-year follow-up, changes in body mass index and glucose level were maintained.Applications/conclusions The purpose of this article was to describe the long-term outcomes of a community-based weight-reduction intervention for older adults. The findings may be of interest to clinicians who design community or worksite weight-reduction programs. Although the intervention was designed to be a low-intensity program, attrition over the length of the study was still problematic. Nevertheless, our follow-up study indicates that this intervention was efficacious in maintaining reductions in weight and glucose levels for overweight older adults for 3 years. J Am Diet Assoc. 1998;98:1276–1281.