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Biomedical subjects

A Robbins

Publications and source records attributed to A Robbins.

At least 37 records · Page 2Linked to original sources
PubMed1996

Antiprogestins: mechanism of action and contraceptive potential.

Antiprogestins are characterized by substitutions at the 11 beta and 17 alpha positions of the steroid ring system and bind strongly to both progesterone and glucocorticoid receptors. Although they function predominantly as antiprogestins and antiglucocorticoids, on occasion they display progestin agonistic and even antiestrogenic properties. The most common clinical use of the antiprogestin mifepristone is to induce a medical abortion in the early stages of pregnancy. Progesterone maintains the endometrium, transforming it from a proliferative to a secretory state. It also facilitates the luteinizing hormone surge, which initiates ovulation. As a consequence, antiprogestins may also have contraceptive potential. Although antiprogestins do delay ovulation, this effect is inconsistent unless high doses are given, and under these circumstances, the antiprogestin effect is associated with unopposed estrogen action on the endometrium. Very low doses of antiprogestins do not affect hormonal secretion or ovulation or alter bleeding patterns, but they do have contraceptive potential by inducing profound alterations in endometrial morphology. Mifepristone is also a very effective and safe postcoital agent. This new class of pharmacological agents has numerous other gynecological and obstetrical indications, such as endometriosis, uterine myoma, and expulsion of the fetus in the case of fetal death in utero. Antiprogestins may also be used in the treatment of steroid-dependent tumors. There are also therapeutic implications consequent to their antiglucocorticoid properties.

Abortifacient Agents, Steroidal↗
PubMed1996

Public perceptions of brain tumours in Scotland: the need for access to appropriate information.

The aim of the study was to evaluate knowledge and perceptions of brain tumours in a heterogeneous, highly educated group of adults living in Edinburgh. Two hundred and forty four respondents answered a questionnaire about the causes, effects and treatments of brain tumours. There were misconceptions about several clinical and biological aspects of intracranial tumours although most respondents were aware of the bleak prognosis associated with many neoplasms. These results, from the intellectual elite of Scotland's capital, suggest that access to information about brain tumours should be readily available. Five leaflets, covering various aspects of brain tumours, that are available through the recently established Scottish charity Brain Tumour Action seem well formulated to address areas of concern and misconception.

Adult↗
PubMed1995

Infusions of diazepam and allopregnanolone into the midbrain central gray facilitate open-field behavior and sexual receptivity in female rats.

We have previously shown that blocking GABAA receptors with bicuculline in the dorsal and lateral quadrants of the rostral two-thirds of the midbrain central gray (MCG) in rats reduces the lordosis quotient (LQ) and proceptive behaviors without increasing the defensive index (McCarthy, Pfaff, and Schwartz-Giblin, 1991b), indicating that tonic release of endogenous GABA in the MCG has a primary facilitatory effect on reproductive behaviors. The present study tests whether two modulators of the GABAA-benzodiazepine-receptor complex, diazepam and the progesterone metabolite, allopregnanolone, facilitate female receptivity as well as open-field behavior. Ovariectomized estradiol benzoate (EB)-treated rats were bilaterally infused in the MCG with vehicle, diazepam, or allopregnanolone and tested 20 min after diazepam and 12 min after allopregnanolone. Animals were tested once each for both receptive or open-field behavior with testing sessions being at least 1 week apart in a crossover design between vehicle and one of the two drugs. Both diazepam and allopregnanolone significantly increased the lordosis quotient in a dose-dependent manner, the lowest effective dose tested being 100 and 250 ng, respectively. In the open-field test, infusion of diazepam (100 ng) in EB-treated rats significantly increased the ratio of central squares entered to total squares entered (C/T) without a change in total activity. Rats without EB elicited comparable C/T ratios when tested with five times as much diazepam. Diazepam infusions at more dorsal sites in the midbrain and in overlying cortex were without effect on C/T ratios in EB-treated rats. Allopregnanolone (500 ng) infusions in MCG of EB-treated rats did not alter C/T ratios compared to animals without EB. Our results are consistent with diazepam and allopregnanolone acting through the GABAA receptors of the MCG to enhance female sexual receptivity and with estradiol potentiating the effect of diazepam in the MCG to increase open-field behavior.

Animals↗
PubMed1994

Evaluating generalist education programs: a conceptual framework. Generalist program evaluation working group.

This paper provides and applies a conceptual framework and a list of guiding principles for evaluation of generalist education programs. Programs are systematic efforts to achieve specified objectives. Evaluations gather data in order to improve or appraise programs and have a continuum of purposes and methods. Descriptive evaluations characterize the structures, processes, and outcomes of programs; research evaluations definitively assess the effectiveness of a program in terms of outcomes. Intermediate outcomes are changes in knowledge, attitudes, and skills of program participants; conclusive outcomes reflect the quality of performance of graduates in actual clinical situations. Outcomes are affected by inputs--the qualities of students entering the program. Guiding principles of program evaluation ensure that data gathered are useful. The authors illustrate the guiding principles with an actual pilot study that determined that expert pediatricians, general internists, and family practitioners could agree on key generalist competencies and that explores evaluation design based on these competencies. Finally, they consider the implications of undertaking generalist education evaluation.

Adult↗
PubMed1994

Introduction: vaccine technologies and public health. Why a critical review now?

Since Jenner's time, there have always been enthusiasts and skeptics about the role of vaccines in the prevention of disease. This introduction explains why, at this time, it is crucial to assess the historical role vaccines have played in limiting damage caused by infectious diseases, the role they can play in the future, and the technologies that are best suited to achieving optimal gains for public health and development worldwide.

Child Welfare↗
PubMed1994

The global capacity for manufacturing vaccines. Prospects for competition and collaboration among producers in the next decade.

Can the world respond to the demands of the Children's Vaccine Initiative (CVI) to produce large quantities of affordable vaccines that have never been manufactured previously? Vaccines for the world's birth cohort of 150 million will continue to be produced in the countries that use the greatest part of the global vaccine supply. Thus, the CVI will rely on increased self sufficiency in vaccine production in the developing world and "shared development" of new and improved vaccines. The CVI's goal is to direct product development to meet the needs of immunization programs, but it must not neglect production. Thus, from the start, investment at the front end of the development and production sequence requires attention to the ultimate production capacity.

Child Welfare↗
PubMed1994

National health care reform minus public health: a formula for failure.

Universal access to medical services will not address all important health needs. Impending health care reform, guided by public health strategies, could achieve many previously unattainable health goals. However, such a public health role seems unlikely. Public health reaches beyond the current popular notion of prevention focused on individual lifestyle, yet attention to public health authority has waned. The history of immunization, a personal health service effective only within a public health strategy, illustrates the dilemma. Britain required 40 years of National Health Service before it invoked a public health strategy to assure effective immunization. Reformed health care must perform certain functions systematically that in the past were optional for medical practitioners or left to health departments by default. Reformers must rebuild public health authority in states, to assure that medical services we will pay for under health care reform accomplish functions critical to the health of the public.

Health Care Reform↗
PubMed1993

Overall signal sequence hydrophobicity determines the in vivo translocation efficiency of a herpesvirus glycoprotein.

We have described three mutant strains of Pseudorabies virus that contain mutations in the signal sequence coding region of a nonessential envelope glycoprotein, gIII. The alterations disrupt, truncate, or eliminate the hydrophobic core domain of the signal sequence. Each mutant was assayed for its ability to promote the translocation of gIII across the endoplasmic reticulum membrane and the subsequent localization of the mature form of the glycoprotein to the infected cell surface or the virus envelope. Our results confirm and extend findings in other systems that the overall hydrophobicity of the signal sequence core region is a major determinant of translocation efficiency. We were unable to correlate simply the length of the core or the average hydrophobicity of core residues with export efficiency. Because our work involved the use of infectious virus mutants, we were able to identify a virus defect associated with a complete block in gIII export. This defect will facilitate a pseudo-reversion analysis of gIII signal sequence function.

Amino Acid Sequence↗
PubMed1993

Functional differences between afferent fibers in the hypogastric and pelvic nerves innervating female reproductive organs in the rat.

1. The uterus, cervix, and vaginal canal are innervated by afferent fibers in the hypogastric and pelvic nerves. Four studies compared the innervation territory and sensitivity to peripheral stimuli of the two sets of fibers in adult virgin rats. 2. Innervation territory was studied anatomically by injecting different fluorescent dyes into different parts of the reproductive, lower urinary, and lower digestive tracts and examining retrogradely labeled neurons in dorsal root ganglia. It was also studied electrophysiologically in anesthetized rats by summing potentials evoked in branches of the two nerves by electrical stimulation of different parts of the reproductive tract. 3. In both studies sensory innervation of the reproductive tract shifted from the pelvic to the hypogastric nerve (i.e., shifted entry into the spinal cord from the L6-S1 to the T13-L3 dorsal root ganglia, respectively) as the dye or stimulating electrode shifted from the vaginal entrance to the uterine horns, with fibers from both nerves densely innervating the cervix region (i.e., entering the spinal cord through both sets of ganglia). The anatomic results suggested that the regions innervated by fibers in one nerve might also be innervated by a small component of normally quiescent fibers in the other nerve. 4. Response sensitivity was studied electrophysiologically by simultaneously recording multiunit activity in branches of the hypogastric and pelvic nerves in two ways. First, in intact, anesthetized rats, activity was recorded during mechanical stimulation of the reproductive tract (distension of the vagina and uterus, probing the cervix). Second, in an in vitro organ preparation of the uterus and vagina, activity was recorded during chemical stimulation through the uterine artery with bradykinin, serotonin, NaCN, CO2, and KCl. 5. Pelvic nerve fibers were markedly more sensitive than hypogastric nerve fibers to uterine and cervical mechanostimulation. Similarly, pelvic nerve fibers were more likely to respond or responded more vigorously than hypogastric nerve fibers to all chemical stimuli (except KCl). 6. These results provide strong evidence that afferent fibers in the pelvic and hypogastric nerves of nulliparous adult rats subserve different functions in reproduction and sensation. Pelvic nerve fibers seem closely tied to sensory and behavioral processes associated with mating and conception, whereas hypogastric fibers seem closely tied to pregnancy and nociception, with fibers in both nerves serving functions during parturition.

Animals↗
PubMed1992

Estrous cycle variation of afferent fibers supplying reproductive organs in the female rat.

Multi-unit afferent nerve activity was recorded from branches of the hypogastric and pelvic nerves in virgin female rats on different days of the estrous cycle. In each rat, the response of hypogastric nerve fibers to uterine distension and the response of pelvic nerve fibers to vaginal distension was tested. The minimal pressure necessary to evoke a response was highest in diestrus for both the hypogastric and pelvic nerve fibers. For the hypogastric nerve, the minimal necessary pressures were significantly lower during both proestrus and estrus, whereas for the pelvic nerve, the pressure was significantly lower only on the day of proestrus. These results suggest that the overall response sensitivity of afferent fibers in the pelvic and hypogastric nerves are differentially affected by hormonal variations occurring across the estrous cycle in a manner that would enhance reproduction.

Afferent Pathways↗
PubMed1992

Reticulospinal and reticuloreticular pathways for activating the lumbar back muscles in the rat.

These experiments tested hypotheses about the logic of reticulospinal and reticuloreticular controls over deep back muscles by examining descending efferent and contralateral projections of the sites within the medullary reticular formation (MRF) that evoke EMG responses in lumbar axial muscles upon electrical stimulation. In the first series of experiments, retrograde tracers were deposited at gigantocellular reticular nucleus (Gi) sites that excited the back muscles and in the contralateral lumbar spinal cord. The medullary reticular formation contralateral to the Gi stimulation/deposition site was examined for the presence of single- and double-labeled cells from these injections. Tracer depositions into Gi produced labeled cells in the contralateral Gi and Parvocellular reticular nucleus (PCRt) whereas the lumbar injections retrogradely labeled cells only in the ventral MRF, indicating that separate populations of medullary reticular cells project to the opposite MRF and the lumbar cord. In the second series of experiments the precise relationships between the location of neurons retrogradely labeled from lumbar spinal cord depositions of the retrograde trace, Fluoro-Gold (FG) and effective stimulation tracks through the MRF were examined. The results indicate that the Gi sites that are most effective for activation of the back muscles are dorsal to the location of retrogradely labeled lumbar reticulospinal cells. To verify that cell bodies and not fibers of passage were stimulated, crystals of the excitatory amino acid agonist, N-methyl-D-aspartate (NMDA) were deposited at effective stimulation sites in the Gi. NMDA decreased the ability of electrical stimulation to activate back muscles at 5 min postdeposition, indicating a local interaction of NMDA with cell bodies at the stimulation site. In the third series of experiments, electrical thresholds for EMG activation along a track through the MRF were compared to cells retrogradely labeled from FG deposited into the cervical spinal cord. In some experiments, Fast Blue was also deposited into the contralateral lumbar cord. Neurons at low threshold points on the electrode track were labeled following cervical depositions, indicating a direct projection to the cervical spinal cord. The lumbar depositions, again, labeled cells in MRF areas that were ventral to the locations of effective stimulation sites, primarily on the opposite side of the medulla. In addition, the lumbar depositions back-filled cells in the same cervical segments to which the Gi neurons project. These results suggest that one efferent projection from effective stimulation sites for back muscle activation is onto propriospinal neurons in the cervical cord, which in turn project to lumbar cord levels.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Challenging official health cost estimates: an alternative view that incorporates the behavioural and economic effects of policy changes.

Cost estimates of health care policy changes are extremely important. Historically, however, the US government has done a poor job in projecting the actual cost of new health care programmes. These projections have been inaccurate primarily because government forecasters use 'static' methods that fail to incorporate the change in people's behaviour as a direct result of a new policy. In contrast, 'dynamic' forecasts incorporate the behavioural effects of policy changes on individuals and the economy. Static and dynamic estimates can lead to different results for 4 areas of US health policy: (a) the Medicare Catastrophic Coverage Act; (b) mandated health benefits; (c) health insurance tax subsidies; and (d) national health insurance. Improving health care policy requires the adoption of dynamic estimation practices, periodic appraisals evaluating the accuracy of official estimates in relation to actual experience, and clear presentation of proposed policy changes and estimates to policymakers and the general public.

Financing, Government↗