Calcium modulators of the anellated dihydropyridine type. Synthesis and pharmacologic action

The anellated dihydropyridines 4a-l can be gained by Hantzsch-like synthesis from 5,5-dimethylcyclohexanedione (1), the aromatic aldehydes 2a-l and methyl-beta-aminocrotonate (3). Cyclisation of the side chains with bromosuccinimide or pyridiniumbromideperbromide leads to the octahydrofuro[3,4-b]chinoline-diones 4m-p. Structures of type 4 are characterized by the spectroscopic data. Positive inotropic effects, caused by calcium agonism, are exerted by the tested substances at the isolated, electrically stimulated left guinea pig atrium, 4j being the most potent with an intrinsic activity of 0.79, compared with ethyl 4-[2-(difluoromethoxy)phenyl]-1, 4,5,7-tetrahydro-2-methyl-5-oxo-furo[3,4-b]pyridine-3-carboxylate. BaCl2-induced contractions at the guinea pig ileum are suppressed dose-dependently.     

Case series: Combined spinal epidural anesthesia for Cesarean delivery andex utero intrapartum treatment procedure

PURPOSE: To report the use of regional anesthesia and iv nitroglycerin to provide anesthesia and uterine relaxation for three Cesarean deliveries (CD) involving ex utero intrapartum treatment (EXIT) of potentially life-threatening airway obstruction in the newborn. CLINICAL FEATURES: Case 1--a 36-yr-old woman at 38 weeks' gestation was scheduled for an elective CD for fetal skeletal dysplasia and micrognathia. Case 2--a 34-yr-old woman at 35 weeks gestation had a fetal ultrasound revealing fixed neck flexion and micrognathia consistent with fetal arthrogryposis. Case 3--a 27-yr-old woman presented at 38 weeks gestation for CD for severe fetal micrognathia, with mandibular growth below the fifth percentile. For each case, a combined spinal epidural anesthetic was performed with 0.75% bupivacaine, fentanyl and morphine intrathecally followed by placement of a multiorifice epidural catheter. Prior to uterine incision patients received a loading dose followed by an iv infusion of nitroglycerin. Uterine relaxation was sufficient in all cases for delivery of the fetus, and allowed for evaluation by direct laryngoscopy and intubation while maintaining fetal-placental circulation. The surgical procedures were completed without incident. CONCLUSIONS: Anesthesia and uterine relaxation for CD and EXIT procedures can be safely provided with regional anesthesia and iv nitroglycerin.     

Development of a new Adolescent Patient-Provider Interaction Scale (APPIS) for youth at risk for STDs/HIV

PurposeAlthough an adult model of patient-provider mutual exchange of information has been proposed, there is no guiding model for adolescents or measurement methodology. Our purpose was to develop a new scale of patient-provider interaction for adolescents accessing reproductive health care and at risk for sexually transmitted diseases (STDs) and human immunodeficiency virus (HIV), and assess the reliability and validity of the scale.MethodsThe Adolescent Patient-Provider Interaction Scale (APPIS) was developed from the Roter and Hall theory of doctor-patient relationships, previously validated adolescent satisfaction and communication scales, and focus group and individual elicitation interviews. To assess construct validity, the new nine-item APPIS was compared with the satisfaction scale used by the Young Adult Health Care Survey (YAHCS), and Kahn’s Provider Communication Scale. Pearson correlation coefficients were used to examine convergence across scales, and factor analysis of the APPIS was performed.ResultsThe study recruited 192 African American girls aged 17.9 ± 1.7 years (range 15–21 years) from three sites: a county STD clinic (n = 51), urban adolescent clinic (n = 99), and a family planning clinic (n = 42). Most participants (85%) rated their overall health care highly (≥ 7 on a 10-point scale); 49% felt that both the provider and patient were “in charge” of the visit, and 88% “strongly agreed” or “agreed” that there was an equal “exchange of information” during the visit. The APPIS showed good internal consistency (Cronbach alpha = .75), and moderate convergence with the six-item YAHCS scale (r = .57, p < .001) and seven-item Kahn scale (r = .48, p < .001). Three factors emerged from exploratory factor analyses, supporting our conceptualization of patient-provider interaction as being multi-dimensional.ConclusionsA new theory-based scale of adolescent patient-provider interaction compares favorably with previous scales of health care satisfaction and communication. The new APPIS may be useful for evaluating approaches to improve health care outcomes for adolescents at-risk for STDs and HIV.     

Syndrome of inappropriate secretion of arginine vasopressin in patients with cancer of the head and neck.

The syndrome of inappropriate secretion of arginine vasopressin (AVP) known as the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is associated with a variety of malignant and nonmalignant diseases. Only 17 cases of SIADH have been reported in the literature in association with cancer isolated to the head and neck. A retrospective review of 1,436 patients with head and neck malignancy excluding skin cancer through The University of Iowa Tumor Registry revealed 60 patients with the diagnosis of either SIADH or hyposmolality. A chart review for each of these patients was then done to establish the diagnosis of SIADH through relevant laboratory values and by excluding other causes of hyposmolality and hyponatremia. In 43 of these patients (3%), SIADH was found to be associated only with the cancer of the head and neck. We conclude that the incidence of SIADH in patients with cancer of the head and neck is much higher than previously recognized. As elevated serum AVP levels may not be clinically apparent unless associated with excessive water ingestation, it is possible that an even higher percentage of patients may have increased serum AVP levels.     

Case report 720

A man presented with a mass in the left first metacarpal bone. Later, his chest radiograph showed extensive, bilateral, rounded opacities in both lungs with enlarged hilar lymph nodes, and he developed expanding lesions in the left radius, ulna, and metacarpal bones. The pulmonary lesions were treated with radiotherapy and cytotoxic agents, and the tumor mass in the first metacarpal was debulked. All biopsies showed similar features of a mixed tumor (pleomorphic adenoma) with metastatic or embolic pulmonary involvement; ultrastructural and immunocytochemical investigations supported this unique diagnosis. The patient remains well 15 years after the initial diagnosis. It is possible that the myoepithelial elements in this case had been displaced intraosseously during development. We are not aware of a similar case in the literature.     

The Domain of Hypertrophic Chondrocytes in Growth Plates Growing at Different Rates

In this study, we tested the hypotheses that (a) both the domain volume (volume of the cell and the matrix it has formed) and matrix volume of juxtametaphyseal hypertrophic chondrocytes in the growth plate is tightly controlled, and that (b) the domain volume of juxtametaphyseal hypertrophic chondrocytes is a strong determinant of the rate of bone length growth. We analyzed the rate of bone length growth (oxytetracycline labeling techniques) and nine stereologic and kinetic parameters related to the juxtametaphyseal chondrocytic domain in the proximal and distal radial and tibial growth plates of 21- and 35-day-old rats. The domain volume increased with increasing growth rates, independent of the location of the growth plate and the age of the animal. Within age groups, the matrix volume per cell increased with increasing growth rates, but an identical growth plate had the same matrix volume per cell in 21- and 35-day-old rats. The most suitable regression model (R ²= 0.992) to describe the rate of bone length growth included the mean volume of juxtametaphyseal hypertrophic chondrocytes and the mean rate of cell loss/cell proliferation. This relationship was independent of the location of the growth plate and the age of the animal. The data suggest that the domain volume of juxtametaphyseal hypertrophic chondrocytes, as well as the matrix volume produced per cell, may be tightly regulated. In addition, the volume of juxtametaphyseal hypertrophic chondrocytes and the rate of cell loss/rate of cell proliferation may play the most important role in the determination of the rate of bone length growth. Received: 2 December 1996 / Accepted: 24 March 1997     

Cardiac microcirculatory effects of beta-adrenergic blockade during sympathetic stimulation.

The effects of beta-adrenergic blockade on cardiac transcapillary exchange were examined at rest and during sympathetic stimulation. Multiple indicator dilution experiments were carried out in closed-chest anesthetized dogs at rest and during carotid occlusion, either under basal conditions or after beta-adrenergic blockade with alprenolol. beta-Adrenergic blockade at rest had no effect on coronary flow or transcapillary exchange in comparison with the control situation, but it abolished the increase in coronary flow and in the permeability/surface area product for labeled sucrose produced by carotid occlusion. High coronary resistance values in beta-blocked animals with carotid occlusion were associated with a high degree of heterogeneity in capillary transit times, but the overall relation between coronary flow and the capillary permeability/surface area product was unchanged. The findings indicate that beta-blockade increases coronary resistance during sympathetic stimulation and, simultaneously, decreases the coronary blood flow and capillary permeability/surface area product while increasing the heterogeneity of capillary transit times.     

Invasive ventilation in the emergency department: Part 2: Implications for patient safety

The use of mechanical ventilation in the Emergency Department requires adequate resources in order to maintain patient safety and avoid potential risks. Moreover, developments in technology require increased knowledge of mechanical ventilation techniques to address the complexity of decision-making involved. Organisational issues and system factors have the potential to negatively impact on the ability of the emergency service to provide optimum care to patients receiving mechanical ventilation. These issues include staffing and skill-mix, demand on emergency services, role-delineation, scope of practice, and current mechanisms for monitoring of quality and safety. Furthermore, in response to advances in ventilator technology, current education programs for both nursing and medical staff require review to ensure that they provide comprehensive information about the types of ventilation techniques now available and the relative risks and benefits associated with their application.This article is the second in a two-part series and explores the educational and organisational factors that impact upon safety and quality of care delivered to patients receiving mechanical ventilation in the emergency department. Recommendations for future policy development, curriculum review and reporting mechanisms to support further research in the application of mechanical ventilation in the emergency department are made.