Effects of oral and transdermal 17beta-estradiol with cyclical oral norethindrone acetate on insulin sensitivity, secretion, and elimination in postmenopausal women.

Few studies have examined the effects of 17beta-estradiol on parameters of insulin and glucose metabolism. We studied 42 healthy, untreated postmenopausal women seeking relief from menopausal symptoms. They were randomized to receive either oral 17beta-estradiol 2 mg daily combined with sequential oral norethindrone acetate (NETA) 1 mg daily from days 12 to 22, or transdermal 17beta-estradiol 0.05 mg daily combined with sequential oral NETA 1 mg daily from days 17 to 28. Intravenous glucose tolerance tests (IVGTTs) were performed at baseline and after 46 weeks (estrogen-alone phase) and 48 weeks (combined phase) of completed therapy. Mathematical modeling analysis of plasma glucose, insulin, and C-peptide concentration profiles provided measures of insulin resistance, secretion, and elimination. Both types of therapy were associated with a decrease in fasting insulin and glucose levels. Insulin sensitivity was increased by oral estradiol during the estrogen-alone phase but was reversed by the addition of NETA. Transdermal estradiol did not affect insulin sensitivity. Hepatic insulin uptake and insulin secretion were increased with both types of treatment. The oral regimen of estradiol therapy was favorable to both insulin elimination and sensitivity. Transdermal estradiol therapy had relatively few effects on insulin metabolism.

Selective estrogen receptor modulators: Women's panacea for the next millennium?

The purpose of this review is to assimilate relevant experimental and clinical information available on selective estrogen receptor modulators with respect to their potential use as agents to improve women's health in the postmenopausal years. In addition, the mechanisms of action of these drugs are outlined. Selective estrogen receptor modulators represent an exciting group of antiestrogens that possess agonist action on bone, lipids, and lipoproteins and antagonistic action in the endometrium and breast. Thus in theory these drugs may preserve bone density and reduce the risk of osteoporotic fracture and coronary heart disease at the same time that they lower the incidences of breast and endometrial neoplasms. Short-term data with the use of raloxifene suggest that bone is preserved and lipid profiles are less atherogenic. Long-term studies are needed to determine whether raloxifene or other selective estrogen receptor modulators are associated with any decrease in the risk of breast or endometrial cancer.

Radiographic evaluation of elbow joints before and after surgery in dogs with possible fragmented medial coronoid process.

OBJECTIVE: To determine the usefulness of 5 radiographic projections of the elbow joint for identification of fragmented coronoid process (FCP) and associated secondary degenerative changes in dogs. DESIGN: Longitudinal clinical study. ANIMALS: 19 dogs suspected of having FCP (7 dogs, 1 elbow joint; 12 dogs, both elbow joints). PROCEDURE: 5 radiographic projections were obtained before and after surgery for all elbow joints on which exploratory arthrotomy was performed because of suspected FCP. Radiographs obtained before surgery were compared with radiographs obtained after surgery and radiographs taken of the excised fragments. Each projection was evalated for its utility in definitively identifying FCP and 7 specific degenerative changes. Interevaluator agreement, use of each radiographic projection for definitively identifying a feature, and ability of the 4 evaluators to definitively identify a feature were analyzed. RESULTS: The craniolateral-caudomedial oblique (Cr15L-CdMO) projection had a significantly higher sensitivity for definitively identifying FCP, compared with the other 4 projections. Interevaluator and kappa agreement for the 5 projections did not differ significantly among the 7 degenerative changes evaluated. The radiographic projection with the highest sensitivity and specificity for detection of a particular degenerative change varied by feature. CLINICAL IMPLICATIONS: Of the 5 radiographic projections evaluated, the Cr15L-CdMO projection provided the highest sensitivity and was the best projection to use for definitively identifying FCP. The craniocaudal, Cr15L-CdMO, and mediolateral projections most reliably allowed for identification of secondary degenerative changes.

Patient acceptability of and tolerance to a placebo intravaginal ring in hysterectomized women: a pilot study.

OBJECTIVE: To assess the tolerance to and patient acceptability of a placebo intravaginal ring in hysterectomized, postmenopausal women over a 28-day period. DESIGN: Open, single-center. SETTING: University hospital specialist menopause clinic. PARTICIPANTS: A total of 24 healthy postmenopausal women attending menopause clinics at King's College Hospital and the Amarant Centre, London. MAIN OUTCOME MEASURES: Discomfort, ring expulsions, bowel, urinary and sexual difficulties associated with the ring and women's overall views on this method. RESULTS: The major problems with use of the intravaginal ring were patient discomfort, involuntary ring expulsion and sexual partner discomfort. These were experienced by 13, 11 and seven women and their partners, respectively, and resulted in premature discontinuation by three women who suffered discomfort and two women who experienced recurrent involuntary ring expulsion. CONCLUSIONS: Two-thirds of the patients found the intravaginal ring acceptable, one-third did not.

Electrical stimulation therapy in the treatment of cigarette smoking.

In this study electrical stimulation therapy (EST) is explored as a possible new treatment for smoking cessation within a randomized controlled trial. The investigation follows reports of several authors that electrical stimulation applied to specific acupuncture points is effective in treating a variety of drug dependencies, including cigarette smoking. Three key features of treatment (electrical stimulation, frequency modulation, and electrode placement), were investigated in a 2 x 2 x 2 factorial design, resulting in eight treatment combinations. Out of 265 smokers recruited into the trial 216 completed the one-week treatment. Outcome was assessed in terms of complete abstinence from smoking and symptomatic relief of withdrawal symptoms. Smokers receiving active electrical stimulation obtained higher abstinence rates than those in the inactive groups although the difference did not achieve statistical significance (all active vs. all placebo groups: lambda 1,1(2) = 0.50, p > 0.10, 95% confidence interval = -8.04 to +17.44%; most effective vs. least effective group: lambda 1,1(2) = 3.11, p = 0.08, CI0.95 = -2.2 to +48.8%). The efficacy of electrical stimulation therapy for smoking is not supported.

Is there a menopausal metabolic syndrome?

Estradiol-17 beta has beneficial effects on a range of metabolic risk factors for coronary heart disease and the decline in estrogen concentrations at the menopause would be expected to have adverse effects. Review of the literature on effects of the menopause and of estradiol-17 beta provides evidence for the following changes occurring at or after the menopause: increased total cholesterol and triglycerides; decreased high density lipoprotein (HDL) and HDL subfraction 2; increased low density lipoprotein, particularly in the small, dense subfraction; increased lipoprotein (a); increased insulin resistance; decreased insulin secretion; decreased insulin elimination; increased android fat distribution; impaired vascular function; increased factor VII and fibrinogen, and reduced sex-hormone binding globulin. Many of these changes will themselves have adverse effects on other metabolic risk factors. This complex of inter-correlated adverse changes in metabolic risk factors justifies identification of a distinct menopausal metabolic syndrome which originates in estrogen deficiency and which could contribute to the increased risk of coronary heart disease seen in postmenopausal women. Estrogen replacement can diminish the expression of this syndrome.

Arthrography of the equine shoulder joint.

Techniques and normal radiographic anatomy for positive and double contrast shoulder arthrography in horses were evaluated. General anaesthesia was used for most radiographic projections of the shoulder. The mediolateral projection provided the most information during arthrography, although the supinated mediolateral view occasionally allowed better definition of the cartilage surfaces on the medial aspects of the humeral head. The craniocaudal mediolateral oblique and caudocranial projections provided limited additional information. Water soluble non-ionic contrast agents, such as metrizamide and iohexol, were suitable for shoulder arthrography; iohexol resulted in less synovitis and lameness. Arthrography in cases of osteochondrosis and osteochondritis dissecans allowed better evaluation of cartilage attachment to subchondral bone, better evaluation of the length and depth of cartilage lesions and more accurately defined the site and shape of osteocartilaginous free bodies. Cartilage thickening without detachment from the subchondral bone could only be determined by arthrography. Although these thick cartilage regions may later dissect from the subchondral bone, most cases where the cartilage was firmly adherent were not candidates for surgical debridement and carried a favourable prognosis. The determination of a free flap by arthrography indicated the need for surgery. Extensive humeral and glenoid cavity lesions were better defined by arthrography, allowing a rational decision between surgical debridement or euthanasia. Using arthrography, evaluation of the size and patency of the communicating canal to a subchondral cystic defect better separated cases with long, narrow and poorly patent canals for conservative rather than surgical therapy.

Congenital cranioventral abdominal wall, caudal sternal, diaphragmatic, pericardial, and intracardiac defects in cocker spaniel littermates.

Five littermate Cocker Spaniels were born with concomitant pericardial, diaphragmatic, caudal sternal, and cranioventral abdominal wall defects. Three of the 5 pups had ventricular septal defects. A sixth pup with a cranioventral abdominal wall defect died 4 days after birth. No history of teratogen exposure was reported, and none of the pups from previous litters of the dam was affected. Each pup underwent successful surgical correction (without median sternotomy) of the diaphragmatic and cranial abdominal wall defects when they were 10 to 12 weeks old. The ventricular septal defects were not corrected. In 2 of 3 pups with ventricular septal defects, thoracic radiography 6 months after surgery revealed moderate generalized cardiomegaly. All pups were healthy one year after surgery.

Influence of dietary composition on gastric emptying and motility in dogs: potential involvement in acute gastric dilatation.

Gastric dilatation-volvulus is a dramatic and life-threatening disease of large-breed dogs. The cause is unknown, but ingestion of dry cereal-based food is frequently incriminated as a predisposing factor. The purpose of this study was to examine the effect of commercial diets on gastric motility and emptying in the dog. Four large-breed dogs were fed 3 different diets (diet A = canned meat-based; B = cereal-based with 77% added water; and C = dry cereal-based) in a randomized block design. Each experiment was done in triplicate. Motility was assessed, using 5 AgAgCl electrodes and 2 strain gauges sutured along the serosa of the stomach and proximal duodenum. Dogs were fed at the same time each day and the time to change from the fed to the fasted pattern of gastrointestinal motility (changeover) was measured. Gastric emptying was assessed by recording gastric radioactivity. After feeding a meal mixed with 99mTc-labeled resin, the log of activity was plotted against time, and the half-time of gastric emptying (t1/2 GE) was calculated. Mean (+/- SEM) times from feeding to changeover for the 3 diets were: diet A, 9.7 +/- 0.9; B, 10.5 +/- 0.4; and C, 11.0 +/- 0.8 hours. Diet had minimal influence on the half time of gastric emptying (diet A, 2.2 +/- 0.3; B, 2.6 +/- 0.4; and C, 2.9 +/- 0.3 hours; P greater than 0.05). The data indicate that gastric motility and emptying in healthy large-breed dogs were not affected by dietary composition. Because most large dogs are fed cereal-based food for reasons of cost and ease of use, these diets may have been wrongly incriminated as a predisposing factor in gastric dilatation-volvulus.

Occipito-atlanto-axial malformation with atlanto-axial subluxation in an ataxic calf.

Occipito-atlanto-axial malformation with atlanto-axial subluxation was diagnosed radiographically in a 4-day-old Holstein calf with a short neck, symmetric ataxia, and tetraparesis, indicative of a cervical spinal cord lesion. Necropsy confirmed the clinical diagnosis and revealed ribs on C-7, with partial fusion of C-7 and T-1. Histologic examination revealed focal degeneration of the spinal cord in the second cervical segment at the level of the atlanto-axial joint and extensive secondary neuronal fiber degeneration possibly caused by spinal cord trauma that occurred in utero.

Predicting undergraduates' intentions to drink.

Sex-linked differences in motivation to drink were studied with Fishbein's model of the relationship between attitudes and behavior. Fishbein's model was revised so that personal normative beliefs were seen as measuring ideal behavioral intentions (what the person intended given real-world constraints) rather than personal norms. A total of 101 college students (53 women) completed a questionnaire. Also, 10 additional students (five women) were interviewed to determine referents whose expectations were salient for the present sample. Both attitudes and social normative beliefs (SNB) correlated significantly with ideal behavioral intentions (IBI); IBI was able to be predicted from the weighted sum of attitudes and SNB. IBI correlated significantly with actual behavioral intentions and accounted for the majority of the variance in actual intentions to drink. Support for the revision of Fishbein's model was shown by the direct effect of attitude on women's intentions to drink. The lack of mediation of attitudes by IBI showed that IBI function differently from actual intentions. The revised model was shown to be very successful in predicting intentions to drink, and in exploring gender and cultural differences therein.

Neurotoxicologic effects of the nonionic contrast agent iopamidol on the leptomeninges of the dog.

The effect of iopamidol on the leptomeninges was tested and compared with that of metrizamide and normal saline solution in 18 dogs. Pathologic and clinical effects were evaluated at 24 hours and 14 days after cisternal injection of iopamidol, metrizamide, or normal saline solution. Pathologic changes were evaluated by microscopic examination of serial CSF samples and of sections of brain and spinal cord with the leptomeninges intact. Clinical changes were subjectively evaluated. Electromyograms and EEG were performed on each dog after physical and neurologic examination. There were no changes seen in neurologic status, electromyogram, or EEG in any of the dogs immediately after subarachnoid injection nor at 24 hours or 14 days later. Pathologic changes were limited to mild, moderate, or severe patchy hemorrhagic leptomeningitis seen at 24 hours after iopamidol or metrizamide was injected. The severity of changes were judged to be similar with both these agents. The CSF analysis and histologic evaluation of brain and spinal cord sections revealed a neutrophilic response to iopamidol and a mononuclear response to metrizamide. These findings indicate that iopamidol has minimal neurotoxicologic effect on the leptomeninges and therefore has merit as a myelographic agent.