Duration of action of antispasmodic agents: novel use of a mouse model as an in vivo pharmacological assay.

OBJECTIVE: Radial arteries are increasingly used as conduits for coronary artery bypass grafts, but perioperative graft vasospasm remains a concern. In vitro testing has demonstrated the efficacy of phenoxybenzamine and verapamil/nitroglycerin as topical antispasmodic agents, but their duration of action in vivo is unknown. Using an in vivo mouse model, we measured their duration of action in functioning vascular grafts, and compared this to their in vitro duration of action in ungrafted vascular segments. METHODS: Two millimetre mouse aortic segments (C57/BL6) were incubated with phenoxybenzamine, verapamil/nitroglycerin, or buffer (controls) for 15 min in organ chambers. Isometric tension responses to phenylephrine and prostaglandin F2alpha were measured at 0, 2, 6 and 12 h post-incubation. In parallel, 36 murine infrarenal aortic interposition grafts (2 mm) were performed. Twelve grafts were pre-treated (15 min) with phenoxybenzamine, 12 with verapamil/nitroglycerin and 12 remained untreated (controls). Isometric tension responses to the same agonists were measured in grafts harvested 2, 6, 13 and 23 h after surgery. RESULTS: Phenoxybenzamine prevented alpha-adrenergic vasoconstriction for up to 16 h in vivo (grafts), and 12h in vitro (ungrafted segments). Verapamil/nitroglycerin was effective for at least 2 h in vitro, but did not prevent vasoconstriction after 2 h in vivo. CONCLUSIONS: The mouse model appears to be a useful technique for assessing the pharmacological properties of antispasmodic agents in vivo. Phenoxybenzamine has an extended action in arterial grafts in vivo. Verapamil/nitroglycerin is short-lived in vivo but lasts longer in vitro. Measurements of antispasmodic duration of action in vitro should be interpreted with caution.     

Dispelling myths: a study of PMS and relationship satisfaction

For more than 50 years, professional literature has linked premenstrual tension (PMS) with psychoemotional symptoms, without addressing how women's roles and development may be related to PMS. This article's research examines aspects of a relationship that exemplify three reported psychoemotional concerns present in PMS women: marital-, sexual- and family-relationship satisfaction. Twenty-six PMS clients of a nurse practitioner and 26 non-PMS women completed three questionnaires about relationship satisfaction. Statistically, PMS subjects reported significantly more dissatisfaction with marital and sexual relationships. No effects linked to age were found. Results are explained within the context of women's development and roles, and implications are discussed for clinicians who provide health care to clients with PMS.     

Hot beverages and oesophageal cancer in southern Brazil: a case-control study

There is a cluster of high-incidence areas of oesophageal cancer in south-eastern South America, including Southern Brazil, Uruguay and parts of Argentina. The present case-control study investigated the hypothesis that this may be due to the drinking of maté, a traditional beverage drunk at a very high temperature, and also studied the role of other known risk factors such as alcohol and tobacco. Cases (171) and age- and sex-matched controls (342) were recruited from hospitals in the State of Rio Grande do Sul in Southern Brazil. The crude odds ratio for daily maté drinkers was 1.92 relative to those drinking less frequently than daily (p = 0.006). Other risk factors included the drinking of cachaça (a sugar cane spirit), smoking, rural residence, low fruit consumption and high intake of meats. After adjustment for these variables through conditional logistic regression, the odds ratio associated with daily maté drinking was reduced to 1.47 (90% CI = 0.87 - 2.50). Although the study failed to provide evidence of a strong association between maté and oesophageal cancer, the cluster of high rates could be explained by relative risks of the magnitude observed. This is due to the fact that approximately 70% of adult males and 50% of females are daily drinkers. In addition, this study revealed that alcohol, tobacco smoking and rural residence are the main risk factors for oesophageal cancer in this population and the fruit consumption confers some degree of protection.     

Opiate control of spontaneous locomotor activity in a urodele amphibian

An intraperitoneal injection of the preferential opiate receptor agonist (+/-) bremazocine HCl given to male rough-skinned newts acutely and dose-dependently reduced their spontaneous locomotor activity. Inversely, and contrary to the situation generally observed in other vertebrates, administration of the opiate receptor antagonist naloxone HCl dose-dependently and acutely stimulated locomotion. Given at a behaviorally active dosage, naloxone counteracted the inhibitory effect of bremazocine on locomotion. The behavioral influence of the two substances was observed using two different sampling techniques (continuous recording for 3 minutes: repeated instantaneous sampling for 60 minutes). These data are discussed in view of our current knowledge on the opiate regulation of locomotor activity in vertebrates.     

Nonvoluntary sexual activity among adolescents

Data from the 1987 round of the National Survey of Children indicate that seven percent of Americans aged 18-22 have experienced at least one episode of nonvoluntary sexual intercourse. Women were more likely than men to report having had such an experience, with just under half of all nonvoluntary experiences among women occurring before the age of 14. Multiple classification analysis reveals that white women who had lived apart from their parents before age 16, those who had been brought up in poverty, those who had had a physical, emotional or mental limitation when they were young, those whose parents had been heavy drinkers, those whose parents had used illegal drugs and those whose parents had smoked cigarettes when they themselves were teenagers were at significantly greater risk for experiencing sexual abuse. Six percent of young white women with no risk factors, nine percent of those with one, 26 percent of those with two, and 68 percent of those with three or more had been sexually abused before or during adolescence.     

Digital mucoid cyst excision by using the bilobed flap technique and arthroplastic resection

There are a number of proposed causes and treatment approaches for digital mucoid cysts. The described treatment outcomes for this cyst have been variable, with the highest success rate reported with complete excision and single-lobe skin flap closure. This report describes a bilobed flap reconstruction in conjunction with resection of the head of the middle phalanx. A retrospective review was undertaken to evaluate the recurrence rate, complications, and patient satisfaction with this combined procedure. Fifteen patients with an average follow-up of 4.6 years were evaluated. There were no recurrences, flap failures, or other major complications. The use of this flap allows for greater exposure than traditional semi-elliptical incisions while allowing the wide excisional defects to be closed primarily.     

Systemic activation of integrin alphaVbeta3 in donors with spontaneous intracerebral hemorrhage is associated with subsequent development of vasculopathy in the heart transplant recipient.

BACKGROUND: Recipients of hearts from donors with spontaneous intracerebral hemorrhage (ICH) are at increased risk of allograft vasculopathy compared with trauma donors. We have recently shown that the vitronectin receptor (integrin alpha(V)beta3) is upregulated in transplant vasculopathy. We hypothesized that donor ICH is associated with systemic activation of alpha(V)beta3 in the donor before transplantation. METHODS: We evaluated mRNA expressions of alpha(V)beta3 (TaqMan PCR) in endomyocardial biopsy samples at 1-week post-transplant in 20 recipients from ICH donors and 20 recipients from trauma donors. To investigate whether systemic activation of alpha(V)beta3 was present in the donor before transplantation, alpha(V)beta3 expression was also evaluated in the corresponding donor spleen lymphocytes. All patients underwent serial coronary intravascular ultrasound to evaluate for coronary vasculopathy. The baseline characteristics were similar except for increased donor age in the ICH Group. RESULTS: The ICH Group showed significant increased mRNA expression of alpha(V)beta3 in the heart biopsy samples (3.8-fold, p = 0.012) and in the corresponding donor spleen lymphocytes (3.5-fold, p = 0.014) compared with the Trauma Group. At 1 year, the ICH Group also showed increased progression of coronary vasculopathy. Multivariate regression analysis found that donor lymphocytic alpha(V)beta3 mRNA expression was independently associated with increased risk of vasculopathy (odds ratio, 1.9; 95% CI, 1.21-3.98, p = 0.03). CONCLUSIONS: Our report demonstrates the presence of systemic activation of alpha(V)beta3 in donors with spontaneous intracerebral hemorrhage and its association with the subsequent development of allograft vasculopathy in the recipient.