Inhibitors of cholesterol biosynthesis. 2. 1,3,5-trisubstituted [2-(tetrahydro-4-hydroxy-2-oxopyran-6-yl)ethyl]pyrazoles

A series of 1,3,5-trisubstituted pyrazole mevalonolactones were prepared and evaluated for their ability to inhibit the enzyme HMG-CoA reductase in vitro. Since previous studies suggested that the 5-(4-fluorophenyl) and 3-(1-methylethyl) substituents afforded optimum potency, attention was focused on variations in position 1 of the pyrazole ring. Biological evaluation of analogues bearing a variety of 1-substituents suggested that, although most substituents were tolerated, none afforded an advantage over phenyl, which exhibited potency comparable to that of compactin in vitro.     

The developing mouse thyroid: embryonic vessel contacts and parenchymal growth pattern during specification, budding, migration, and lobulation.

Normal mouse thyroid development has been revised to identify critical morphogenetic events. The early thyroid primordium associates with the aortic sac endothelium at the time of specification and budding. The vascular contact is lost after the thyroid buds from the pharyngeal endoderm, but is resumed before the gland divides to form two lobes. Lateral expansion of parenchyma takes place along the course of the third pharyngeal arch arteries. Thyroid precursor cells expressing Titf1/Nkx2.1 do not proliferate until the migration stage, implicating that progenitors likely are recruited from outside the thyroid placode. Early lobulation involves engulfment of the entire ultimobranchial bodies by the growing midline thyroid. At the same time, proliferation of the ultimobranchial body epithelium is silenced preceding the differentiation of C cells. Before folliculogenesis, thyroid lobe enlargement is reminiscent of a budding-branching-like growth pattern. It is suggested that thyroid inductive signals arise from embryonic vessels, and that this provides ideas to conceptually new pathogenetic mechanisms of thyroid dysgenesis.     

Users' subjective evaluation of electronic vision enhancement systems

The aims of this study were (1) to elicit the users' responses to four electronic head-mounted devices (Jordy, Flipperport, Maxport and NuVision) and (2) to correlate users' opinion with performance. Ten patients with early onset macular disease (EOMD) and 10 with age-related macular disease (AMD) used these electronic vision enhancement systems (EVESs) for a variety of visual tasks. A questionnaire designed in-house and a modified VF-14 were used to evaluate the responses. Following initial experience of the devices in the laboratory, every patient took home two of the four devices for 1 week each. Responses were re-evaluated after this period of home loan. No single EVES stood out as the strong preference for all aspects evaluated. In the laboratory-based appraisal, Flipperport typically received the best overall ratings and highest score for image quality and ability to magnify, but after home loan there was no significant difference between devices. Comfort of device, although important, was not predictive of rating once magnification had been taken into account. For actual performance, a threshold effect was seen whereby ratings increased as reading speed improved up to 60 words per minute. Newly diagnosed patients responded most positively to EVESs, but otherwise users' opinion could not be predicted by age, gender, diagnosis or previous CCTV experience. User feedback is essential in our quest to understand the benefits and shortcoming of EVESs. Such information should help guide both prescribing and future development of low vision devices.     

Violent and nonviolent methods of suicide: different patterns may be found in men and women with severe depression.

The objective of this study was to investigate violent and nonviolent suicidal acts in men and women with severe depression. The records of 98 suicide victims, who had been admitted to the Department of Psychiatry, Lund University Hospital, Sweden between 1956 and 1969, were evaluated and the subjects were monitored up to 1998. The female group displayed a significant linear trend for nonviolent completed suicide after one suicide attempt, and even more significantly, after repeated attempts. A switch from only nonviolent suicide attempts to completed violent suicide was significantly more common in men than in women. These different progressions may contribute to the expected finding that men used violent methods for completed suicide more often than women.     

Experiences of pain and distress in hip fracture patients

The aims were to investigate: (1) experiences of physical pain in elderly patients with hip fracture; (2) if background variables, confusion, experiences of pain and distress and interventions aimed at reducing pain and distress, functional ability, pain in the ambulance, and type of fracture varied between patients with more intense physical pain and patients with less intense physical pain. The sample included 49 patients, 70 years or older, with hip fracture. Structured instruments were used to interview and observe the patients on four occasions during the hospital stay. The patients’ experiences of physical pain decreased during the hospital stay. Physical pain at rest was lower than pain with movement. Patients who scored physical pain as more intense (group B) during the visit to the hospital had significantly more unfavourable experiences in the sensory, emotional, and existential dimensions the day before discharge from the hospital compared with the patients who scored pain as less intense (group A). The patients in group B perceived the interventions as less favourable than group A. Furthermore, group B had more intense physical pain in the ambulance than the patients in the other group. More patients in group B than in group A had additional health problems.     

Compliance with ambulatory saliva sampling in the Chicago Health, Aging, and Social Relations Study and associations with social support

Background: Noncompliance with instructed saliva sampling times in ambulatory settings can compromise resulting cortisol findings.Purpose and Methods: Here, the impact of noncompliance on the cortisol awakening response (CAR), an established marker for hypothalamic-pituitary-adrenal axis activity, was examined over 3 sampling days in middle- and older-age participants in the Chicago Health, Aging, and Social Relations Study.Results: Noncompliant participants had a significantly lower cortisol rise after awakening (assessed by an awakening sample and a 30-min after awakening sample) on 2 of the 3 sampling days (Day 1, ns; Days 2 & 3, ps<.02). Furthermore, social support measured by the Interpersonal Support Evaluation List correlated negatively with the number of “noncompliant” samples (r=−.19, p<.05), indicating that participants reporting more social support had more “compliant” samples.Conclusion: The results confirm that nonadherence to saliva sampling in ambulatory settings can exert a significant impact on the resulting CAR. Furthermore, the data raise the idea that the extent of nonadherence might be systematically associated with psychosocial factors like social support. For future studies on the relationship between CAR and psychological factors, we therefore recommend controlling for saliva sampling adherence because noncompliance might be systematically associated with the phenomenon being investigated. Funding was provided by the National Institute of Aging Grant No. PO1 AG18911 and the John Templeton Foundation. Brigitte M. Kudielka was supported by grants from the German Research Foundation (DFG grant KU 1401/3-1 and KU 140/4-1).     

Department of law and ethics

The January 7, 1988 issue of The New England Journal of Medicine has two interesting articles concerning what might generally be termed euthanasia. The article titled Initiating and Withdrawing Life Support represents a consensus among members of the Stanford University Medical Center Committee on Ethics. Its main authors have written a fine example of applied ethics (1).     

Can we understand partnerships in general practice? A pilot study

BACKGROUND: Partnerships have been investigated in different professions,but other than identifying problems, little work has been carriedout on general practice. OBJECTIVE: The aim of this present study was to develop methods for studyingpartnerships in general practice. METHOD: A tripartite methodological approach was used, with questionnairesadapted from other instruments in use in other professions,followed by an individual interview with each partner, and non-participantobservation at a partnership meeting. Results for one case-studypartnership are given. RESULTS: There were no major differences between the partners on alldimensions measured; the minor differences indicated by theresults of the questionnaires were corroborated by the partnerinterviews and observations. CONCLUSIONS: We conclude that the use of such techniques could provide supportto partnerships going through significant periods of change. Keywords. General practice, interview, observation, partnerships, questionnaire.