THE INTERACTION BETWEEN ENALAPRILAT AND SELECTED α-ADRENOCEPTOR ANTAGONISTS IN ISOLATED RAT TAIL ARTERIES

1. Isolated perfused rat tail artery preparations were used to investigate the effects of the angiotensin converting enzyme inhibitor enalaprilat on the actions of a series of α-adrenoceptor antagonists. The agonist used was phenylephrine. 2. Enalaprilat (1 μmol/L) potentiated the competitive α₁-adrenoceptor antagonist actions of phentolamine (10–100 nmol/L) and yohimbine (0.3–3.0 μmol/L) as well as the non-competitive antagonist action of phenoxybenzamine (50–100 pmol/L). 3. The competitive α₁-adrenoceptor antagonist action of prazosin (1–10 nmol/L) was not affected by enalaprilat. 4. For the competitive α₁-adrenoceptor antagonists, including prazosin, there appeared to be an inverse relationship between antagonist potency and the extent of potentiation by enalaprilat. 5. The results support the hypothesis and angiotensin II modulates vascular smooth muscle α₁-adrenoceptor function.     

Contact angles of substances used for internal tamponade in retinal detachment surgery

In order to ascertain the tamponade effect of air and silicone oil we examined the contact angles subtended by ex vivo human retina, Teflon and Perspex to find a suitable experimental material which would mimic the surface properties of the retina at a three-phase interface. Using the captive bubble technique to measure the contact angle, it was found that air subtended a larger contact angle (38.8°) with the retina than did silicone oil (18.2°). On coating the Perspex surface with protein (PCP), it was observed that the surface properties were modified such that PCP subtended contact angles with air (43.0°) and silicone oil (16.4°) similar to those subtended by ex vivo human retina. Using PCP as an experimental material that mimics ex vivo human retina, spherical chambers were employed in order to examine qualitatively and to quantify the arc of contact obtained with air and silicone oil. It was found that air gave a greater arc of contact for the same percentage fill than silicone oil.     

Modulation of Ca2+ levels in keratinocytes by all-trans retinoic acid.

Human epidermal keratinocytes, that have been growth-arrested by removal of epidermal growth factor from the culture medium, are stimulated to proliferate by all-trans retinoic acid (RA). The same treatment inhibits the onset of differentiated features and reduces cell-substrate adhesion. In the present study we show that the same treatment results in a decrease in total cell-associated Ca2+ as measured by changes in the amount of 45Ca2+ bound to cells at equilibrium following RA treatment and by a decrease in intracellular free Ca2+ levels as measured with the Ca(2+)-sensitive dye, Indo-1. The alterations in Ca2+ levels were evident within an hour after RA treatment, were in the range of 30-35% and occurred over the same RA concentration range that stimulated proliferation (i.e., 0.25-1.0 micrograms/ml). When the extracellular Ca2+ concentration was elevated from the normal level of 0.15-1.4 mM, intracellular free Ca2+ increased by a factor of 2 while total cell-associated Ca2+ increased approximately 6-fold. Even under conditions of high extracellular Ca2+, RA was able to reduce cell-associated and intracellular free Ca2+. These data indicate that RA has the capacity to lower Ca2+ levels in keratinocytes concomitantly with its effects on biological behavior.     

The role of office hysteroscopy in in vitro fertilization.

Twenty-eight patients participated prospectively in a study to evaluate the impact of hysteroscopically detected uterine and cervical anomalies on the success rate of ET in an IVF-ET program. All participants had a normal intrauterine cavity by standard HSG. All the patients had a diagnostic office hysteroscopy under paracervical block before commencing COH. Because our IVF program does not include hysteroscopy as a requirement before undergoing IVF and because the significance of mild intrauterine abnormalities is not yet known, the hysteroscopic findings were not relayed to the personnel involved in the IVF-ET procedure. Sixteen patients (group I) had a normal hysteroscopic evaluation. Twelve patients (group II) had abnormal hysteroscopic findings including small uterine septa, small submucous fibroids, uterine hypoplasia and cervical ridges. Although no difference in patients or cycle characteristics was present, there was a significant difference in the clinical PR between patients in groups I and II. In conclusion, in an IVF-ET program patients with normal hysterography but abnormal hysteroscopic findings had a significantly lower clinical PR, demonstrating the importance of performing hysteroscopy before IVF-ET.     

Antitumor activity of patulin and structural analogs.

A comparison between the cytotoxicity and the antitumor activity of patulin and five structural analogs (isopatulin, dehydroisopatulin, dimethylisopatulin, trimethylisopatulin and isopropylisopatulin) has been established. In vitro assays using L 1210 and P 388 cells showed that the structure of the pyranic ring as well as the nature of the substituents influenced the observed activities. Among the five structural analogs of patulin assayed in vivo against Ehrlich carcinoma, L 1210 and P 388 leukemias, dehydroisopatulin was the only one to be active on all 3 types of tumors at a dose of 100 mg.kg-1.d-1. The ratio between the LD50 in mice and the active dose was 5 while with patulin it was 10. It can be assumed that the lactone function is not solely responsible for the activity of patulin and its structural analogs.     

Rural Hospital Inpatient Surgical Volume: Cutting-edge Service or Operating on the Margin?

Surgical services are an important part of modern health care, but providing them to isolated rural citizens is especially difficult. Public policy initiatives could influence the supply, training, and distribution of surgeons, much as they have for rural primary care providers. However, so little is known about the proper distribution of surgeons, their contribution to rural health care, and the safety of rural surgery that policy cannot be shaped with confidence. This study examined the volume and complexity of inpatient surgery in rural Washington state as a first step toward a better understanding of the current status of rural surgical services. Information about rural surgical providers was obtained through telephone interviews with administrators at Washington's 42 rural hospitals. The Washington State Department of Health's Commission Hospital Abstract Recording System (CHARS) data provided a count of the annual surgical admissions at rural hospitals. Diagnosis-related group (DRG) weights were used to measure complexity of rural surgical cases. Surgical volume varied greatly among hospitals, even among those with a similar mix of surgical providers. Many hospitals provided a limited set of basic surgical services, while some performed more complex procedures. None of these rural hospitals could be considered high volume when compared to volumes at Seattle hospitals or to research reference criteria that have assessed volume-outcome relationships for surgical procedures. Several hospitals had very low volumes for some complex procedures, raising a question about the safety of performing them. The leaders of small rural hospitals must recognize not only the fiscal and service benefits of surgical services--and these are considerable--but also the potentially adverse effect of low surgical volume on patient outcomes. Policies that encourage the proper training and distribution of surgeons, the retention of basic rural surgical services, and the rational regionalization of complex surgery are likely to enhance the convenience and safety of surgery for rural citizens.     

Geographic Benefit from Decentralized Medical Education: Student and Preceptor Practice Patterns

The performance of area health education center (AHEC)-stimulated programs and decentralized education for medicine is not well understood. The Statewide Education Activities for Rural Colorado's Health (SEARCH)/AHEC project at the University of Colorado School of Medicine was examined to determine if the program had an effect on the practice location of its graduates. Practice location and specialty of graduates of the University of Colorado School of Medicine (UCSOM) classes 1980-1985 were compared for students who had participated in decentralized SEARCH/AHEC experiences versus students who had not. The majority of the graduates were practicing out of state in 1990. Non-Colorado doctors were more often practicing in rural (non-metropolitan statistical area [MSA]) counties and in towns of fewer than 2,500, 5,000 and 10,000 residents, respectively. In addition, of the 251 active patient care physicians practicing in Colorado communities of fewer than 10,000 in non-MSA counties in 1986, those who precepted UCSOM students on SEARCH rotations were more likely to have remained in their same practice location in 1992 (77.8% versus 62.1% for those who had not precepted students). This analysis of both student and preceptor practice patterns documents the value of decentralized medical education in addressing the geographic and specialty maldistribution of physicians. These results have important policy implications for funding medical education programs.