Effect of the calcium antagonist nifedipine on intraocular pressure in normal subjects.

We studied the effects of nifedipine, a calcium antagonist, given intravenously and orally, on intraocular pressure in six normal volunteers. Nifedipine had no effect on intraocular pressure. Nifedipine is not contraindicated for the treatment of cardiovascular disease in glaucomatous patients and may have theoretical advantages in this situation, which are discussed.     

What has trust got to do with it? Cardiac risk reduction and family physicians' discussions of evidence-based recommendations

The management of patients through the use of evidence-based medicine has become the 'mantra' of medicine within many Western countries. Evidence-based medicine is aimed at providing the best objective, scientific care to all patients, and reducing as far as possible patients' risks of disease and complications from disease. Based on family physicians' discussions of the use of evidence-based recommendations for two cardiac diseases, this paper explores how subjectively-based trust enters into family physicians' decision to use evidence-based medicine. In addition, we show how trust influences physicians' work of recommending evidence-based medicine to patients, and physicians' perceptions of why patients follow recommendations aimed at risk reduction. We conclude that although much of the current discussion about evidence-based medicine assumes a 'rational' model of physician behaviour based on the application of the 'best objective scientific' results, subjectively-based perceptions of trust influence physician practices, and point to the need to understand the power of relational issues in influencing physician practices even when utilizing evidence-based knowledge.     

International multicenter pilot study of the first comprehensive self-completed nonmotor symptoms questionnaire for Parkinson's disease: the NMSQuest study.

Nonmotor symptoms (NMS) of Parkinson's disease (PD) are not well recognized in clinical practice, either in primary or in secondary care, and are frequently missed during routine consultations. There is no single instrument (questionnaire or scale) that enables a comprehensive assessment of the range of NMS in PD both for the identification of problems and for the measurement of outcome. Against this background, a multidisciplinary group of experts, including patient group representatives, has developed an NMS screening questionnaire comprising 30 items. This instrument does not provide an overall score of disability and is not a graded or rating instrument. Instead, it is a screening tool designed to draw attention to the presence of NMS and initiate further investigation. In this article, we present the results from an international pilot study assessing feasibility, validity, and acceptability of a nonmotor questionnaire (NMSQuest). Data from 123 PD patients and 96 controls were analyzed. NMS were highly significantly more prevalent in PD compared to controls (PD NMS, median = 9.0, mean = 9.5 vs. control NMS, median = 5.5, mean = 4.0; Mann-Whitney, Kruskal-Wallis, and t test, P < 0.0001), with PD patients reporting at least 10 different NMS on average per patient. In PD, NMS were highly significantly more prevalent across all disease stages and the number of symptoms correlated significantly with advancing disease and duration of disease. Furthermore, frequently, problems such as diplopia, dribbling, apathy, blues, taste and smell problems were never previously disclosed to the health professionals.     

General practitioners'' views on continuing medical education.

BACKGROUND. The 1990 contract for general practitioners altered the provision of continuing medical education. AIM. This study set out to examine doctors' experiences of postgraduate education before and after the contract and their preferences for the provision of postgraduate education. METHOD. In 1991 a structured questionnaire was sent to 1959 doctors registered on the database held by the west of Scotland postgraduate office. RESULTS. An 82% response rate was obtained. Eighty eight questionnaires had to be excluded. Of 1523 respondents, 74% were entitled to study leave under the terms of their practice agreement, an increase of 15% since the introduction of the contract. When attending courses 11% reported that they always employed a locum (32% occasionally). Those who did so were more likely to be general practitioners in rural areas than in urban or mixed areas. Almost all respondents (1485, 98%) had participated in postgraduate education since April 1990. Lectures remained popular (47% of respondents indicated it was their preferred or most preferred choice) while distance learning and practice based learning were least preferred. Evening meetings and afternoon meetings were the most popular, and Wednesday and Thursday were reported to be the most suitable days for educational meetings. CONCLUSION. Organizing education for a large number of people is difficult, but individuals' preferences and difficulties have emerged which must be taken into account when doing so. In terms of attendance, postgraduate education seems to have been a success although its value in influencing quality of care is more doubtful. Perhaps the development of personal education plans may make learning more useful and relevant.     

Selections from current literature: treatment of hypertension.

The three papers reviewed for this issue deal with unrelated aspects of hypertension, illustrating the broad range of questions that still exist about optimal diagnosis and management. Physicians have for years been unsure about the efficacy, safety, and impact on morbidity of treating ISH. The result of these concerns has been that many, if not most patients with ISH never received treatment. The SHEP data are a powerful argument for routine treatment of ISH, which would represent a new standard of care for this condition. Only clinical experience and future trials will indicate whether treatment of ISH in the general population will be accompanied by the low incidence of side effects and morbidity observed in the more highly selected population of the SHEP trial. The study of Zeller et al. adds to the evidence that less is more, or at least the same, when it comes to treatment of hypertensive urgencies. The practice of oral 'loading' doses was not shown to improve therapeutic results. It is still not completely clear what criteria physicians should use in making a decision about inpatient parenteral therapy versus outpatient oral therapy. In patients with evidence of acute onset and end-organ injury, it is probably prudent to admit. In the absence of these risk factors, institution of an outpatient oral antihypertensive regimen can probably be accomplished with safety and at dramatically lower cost. The study of Koren et al. demonstrated a marked additional risk when LVH was present in hypertensive patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Distribution of transforming growth factor-beta 1 in human astrocytomas.

We used immunohistochemical techniques to study the distribution of transforming growth factor-beta 1 (TGF-beta 1) and infiltrating lymphocytes and macrophages in human astrocytomas. Thirteen of 15 grade 4 astrocytomas (glioblastomas) showed staining with anti-TGF-beta 1 antibody, predominantly in proliferating endothelial complexes and surrounding small and medium-sized blood vessels. Brain tissue microscopically free of tumor cells (n = 8) and more differentiated astrocytomas of varying grade (1 to 3; n = 6) devoid of endothelial proliferation did not stain with anti-TGF-beta 1. Normal brain contained only rare lymphoreticular cells. The majority of astrocytomas studied, however, contained T lymphocytes and macrophages with smaller numbers of B lymphocytes. The lymphoreticular infiltrates were concentrated primarily in close proximity to blood vessels. Within an individual tumor perivascular regions staining for TGF-beta 1 never contained more than occasional T lymphocytes. Perivascular regions not staining for TGF-beta 1 frequently contained low to high numbers of T lymphocytes. The inverse relationship in the distribution of TGF-beta 1 and lymphocyte infiltrates is compatible with a functional relationship between this cytokine and an immune effector cell response to glioblastomas.     

Nitrates in the elderly. Pharmacological considerations.

Although a significant proportion of patients receiving nitrates are elderly, surprisingly little published work is available describing the pharmacokinetics and pharmacodynamics of these agents in elderly patients. The lack of pharmacokinetic data is related to the difficulty in assaying nitrates and there are at present no definitive data describing the effect of aging on their bioavailability or elimination. A common finding in old age is of decreased hepatic first-pass metabolism. This would affect isosorbide-2-mononitrate and isosorbide-5-mononitrate less than isosorbide dinitrate and nitroglycerin (glyceryl trinitrate). Venous responsiveness to nitrates does not appear to alter with age, so that pharmacodynamic properties would not be expected to alter. However, decreased baroreflex function causes an increased tendency for posturally related side effects to occur. Mechanisms of tolerance are likely to be unaltered but any possible alteration in quantitative aspects of tolerance has not been studied. Nitrate therapy in the elderly would benefit from systematic investigation. At the moment, therapy needs to be titrated to the individual patient, with care taken to avoid age-related side effects by careful initiation of therapy and appropriate reviews of each patient.     

Reversal of fulminant hepatic failure using an extracorporeal liver assist device.

Liver transplantation is currently the only effective therapy for patients with fulminant hepatic failure. The availability of an artificial liver could bridge these patients through the relatively brief crisis period and allow their own livers to regenerate, providing a more favorable outcome and sparing the trauma and expense of transplant. We have developed a device consisting of a highly differentiated human liver cell line cultured in a hollow fiber cartridge. This device is capable of supporting dogs with acetaminophen-induced fulminant hepatic failure for a period long enough for their own livers to resume function. Even though liver function tests such as albumin and prothrombin time became extremely abnormal during the course of the experiment, the dogs did not become encephalopathic. Two of the three treated animals recovered sufficient liver function after 42 to 48 hr of treatment that they could be disconnected from the device, and they survived the experiment. Histological results and serum ALT levels suggest that the device affected the course of the disease in two animals, allowing recovery of hepatocytes that would otherwise have lysed. In the third animal, regenerative nodules demonstrated that, even in the presence of severe liver injury, the device was capable of supporting total liver function.