Familial hyperaldosteronism

Primary aldosteronism (PAL) may be as much as ten times more common than has been traditionally thought, with most patients normokalemic. The study of familial varieties has facilitated a fuller appreciation of the nature and diversity of its clinical, biochemical, morphological and molecular aspects. In familial hyperaldosteronism type I (FH-I), glucocorticoid-remediable PAL is caused by inheritance of an ACTH-regulated, hybrid CYP11B1/CYP11B2 gene. Genetic testing has greatly facilitated diagnosis. Hypertension severity varies widely, demonstrating relationships with gender, affected parent's gender, urinary kallikrein level, degree of biochemical disturbance and hybrid gene crossover point position. Analyses of aldosterone/PRA/cortisol 'day-curves' have revealed that (1) the hybrid gene dominates over wild type CYP11B2 in terms of aldosterone regulation and (2) correction of hypertension in FH-I requires only partial suppression of ACTH, and much smaller glucocorticoid doses than those previously recommended. Familial hyperaldosteronism type II is not glucocorticoid-remediable, and is clinically, biochemically and morphologically indistinguishable from apparently sporadic PAL. In one informative family available for linkage analysis, FH-II does not segregate with either the CYP11B2, AT1 or MEN1 genes, but a genome-wide search has revealed linkage with a locus in chromosome 7. As has already occurred in FH-I, elucidation of causative mutations is likely to facilitate earlier detection of PAL and other curable or specifically treatable forms of hypertension. (C) 2001 Elsevier Science Ltd. All rights reserved.

Identifying trajectories of adolescent smoking: An application of latent growth mixture modeling

The goal of the current study was to identify discrete longitudinal patterns of change in adolescent smoking using latent growth mixture modeling. Five distinct longitudinal patterns were identified. A group of early rapid escalators was characterized by early escalation (at age 13) that rapidly increased to heavy smoking. A pattern characterized by occasional puffing up until age 15, at which time smoking escalated to moderate levels was also identified (late moderate escalators). Another group included adolescents who, after age 15, began to escalate slowly in their smoking to light (0.5 cigarettes per month) levels (late slow escalators). Finally, a group of stable light smokers (those who smoked 1-2 cigarettes per month) and a group of stable puffers (those. who smoked only a few puffs per month) were also identified. The stable puffer group was the largest group and represented 25% of smokers.

Haptic information stabilizes and destabilizes coordination dynamics

Goal-directed, coordinated movements in humans emerge from a variety of constraints that range from 'high-level' cognitive strategies based oil perception of the task to 'low-level' neuromuscular-skeletal factors such as differential contributions to coordination from flexor and extensor muscles. There has been a tendency in the literature to dichotomize these sources of constraint, favouring one or the other rather than recognizing and understanding their mutual interplay. In this experiment, subjects were required to coordinate rhythmic flexion and extension movements with an auditory metronome, the rate of which was systematically increased. When subjects started in extension on the beat of the metronome, there was a small tendency to switch to flexion at higher rates, but not vice versa. When subjects: were asked to contact a physical stop, the location of which was either coincident with or counterphase to the auditor) stimulus, two effects occurred. When haptic contact was coincident with sound, coordination was stabilized for both flexion and extension. When haptic contact was counterphase to the metronome, coordination was actually destabilized, with transitions occurring from both extension to flexion on the beat and from flexion to extension on the beat. These results reveal the complementary nature of strategic and neuromuscular factors in sensorimotor coordination. They also suggest the presence of a multimodal neural integration process-which is parametrizable by rate and context - in which intentional movement, touch and sound are bound into a single, coherent unit.

Telemedicine and clinical genetics: establishing a successful service

There is a surprising lack of published experience on the use of videoconferencing in clinical genetics. Patients were randomly allocated to either a telegenetic (cases) or face-to-face (control) conventional clinic. The telegenetic consultation was done by videoconferencing, using ISDN lines at 384 kbit/s. Evaluation by the doctor and counsellor took place immediately after each appointment. The patient was asked to evaluate the appointment by telephone questionnaire about four weeks after the event. Forty-two patients were invited to participate and 33 (79%) returned their consent forms. Four patients declined to participate and were seen in ordinary face-to-face clinics. Preliminary results showed that the assessment of the telegenetics consultations by doctors, counsellors and patients was very favourable, and they responded positively when asked if they would be happy to use telemedicine in the future. For use in selected consultations, videoconferencing does appear to fulfil a useful role in clinical genetics.

The point-of-referral barrier - a factor in the success of telehealth

A feasibility study was carried out to test the hypothesis that, for an effective telehealth service, a full-time coordinator is required to act as a single point of contact for consultation requests. By shifting the responsibility for telepaediatrics from the referrer to the provider, the telehealth process becomes equally (or more) attractive as the conventional alternative. Preliminary results showed that, within six months, telepaediatric activity increased to an average of 8 h per month. Not only did certain health services become more accessible to children and their families in remote areas of Queensland, but significant savings were also made. At least 12 patient transfers were avoided to and from the tertiary facility, with an estimated minimum saving of $18,000 to the health-care provider.

Rapid opiate detoxification and naltrexone treatment: past, present and future

This Article does not have an abstract

Some factors affecting diagnostic accuracy

Diagnosis involves a complex and overlapping series of steps, each of which may be a source of error and of variability between clinicians. This variation may involve the ability to elicit relevant information from the client or animal, in the accuracy, objectivity and completeness of relevant memory stores, and in psychological attributes including tolerance for uncertainty and willingness to engage in constructive self-criticism. The diagnostic acumen of an individual clinician may not be constant, varying with external and personal factors, with different clients and cases, and with the use made of tests. In relation to clients, variations may occur in the ability to gain their confidence, to ask appropriate questions and to evaluate accurately both verbal and nonverbal responses. Tests may introduce problems of accuracy, validity, sensitivity, specificity, interpretation and general appropriateness for the case. Continuing effectiveness as a diagnostician therefore requires constant attention to the maintenance of adequate and up-to-date skills and knowledge relating to the animals and their diseases and to tests, and of sensitive interpersonal skills.

Immune responses to ISCOM (R) formulations in animal and primate models

ISCOMs(R) are typically 40 nm cage-like structures comprising antigen, saponin, cholesterol and phospholipid. ISCOMs(R) have been shown to induce antibody responses and activate T helper cells and cyrolytic T lymphocytes in a number of animal species, including non-human primates. Recent clinical studies have demonstrated that ISCOMs(R) are also able to induce antibody and cellular immune responses in humans. This review describes the current understanding of the ability of ISCOMs(R) to induce immune responses and the mechanisms underlying this property. Recent progress in the characterisation and manufacture of ISCOMs(R) will also be discussed. (C) 2001 Elsevier Science Ltd. All rights reserved.

Repeated blood pressure measurements in a sample of Swedish twins: heritabilities and associations with polymorphisms in the renin-angiotensin-aldosterone system Iliadou, Anastasia, Lichtenstein, Paul, Morgenstern, Ralf, Forsberg, Lena, Svensson, Richard, de Faire, Ulf, Martin, Nicholas, Pedersen, Nancy

Background Twin and family studies have shown that genetic effects explain a relatively high amount of the phenotypic variation in blood pressure. However, many studies have not been able to replicate findings of association between specific polymorphisms and diastolic and systolic blood pressure. Methods In a structural equation-modelling framework the authors investigated longitudinal changes in repeated measures of blood pressures in a sample of 298 like-sexed twin pairs from the population-based Swedish Twin Registry. Also examined was the association between blood pressure and polymorphisms in the angiotensin-I converting enzyme and the angiotensin 11 receptor type 1 with the 'Fulker' test Both linkage and association were tested simultaneously revealing whether the polymorphism is a Quantitative Trait Locus (QTL) or in linkage disequilibrium with the QTL. Results Genetic influences explained up to 46% of the phenotypic variance in diastolic and 63% of the phenotypic variance in systolic blood pressure. Genetic influences were stable over time and contributed up to 78% of the phenotypic correlation in both diastolic and systolic blood pressure. Non-shared environmental effects were characterised by time specific influences and little transmission from one time point to the next. There was no significant linkage and association between the polymorphisms and blood pressure. Conclusions There is a considerable genetic stability in both diastolic and systolic blood pressure for a 6-year period of time in adult life. Non-shared environmental influences have a small long-term effect Although associations with the polymorphisms could not be replicated, results should be interpreted with caution due to power considerations. (C) 2002 Lippincott Williams Wilkins.