Genetic risk of knee osteoarthritis: a sibling study.

OBJECTIVES: To determine whether there is a genetic contribution to knee osteoarthritis (OA) as defined by structural change on plain radiographs. DESIGN: Sibling study. Comparison of knee OA prevalence in the community with knee OA prevalence among siblings of index cases with knee OA. SUBJECTS: 490 knee OA index cases listed for total knee replacement and 737 of their siblings aged >40 years, 1729 community subjects aged >40 years. MAIN OUTCOME MEASURE: Odds ratio for radiographic knee OA in siblings v community participants. RESULTS: The age, sex, and knee pain adjusted odds ratios in siblings were 2.9 (95% confidence interval 2.3 to 3.7) for tibiofemoral OA and 1.7 (1.4 to 2.2) for patellofemoral OA. This difference remained after adjustment for important environmental risk factors. The heritability estimate for knee OA was 0.62. CONCLUSIONS: Siblings are at increased risk of knee OA in comparison with the general population. This is likely to be due to genetic factors.

UK community prevalence of knee chondrocalcinosis: evidence that correlation with osteoarthritis is through a shared association with osteophyte.

OBJECTIVES: (1) To estimate the prevalence of chondrocalcinosis (CC) in the community and to characterise its compartmental distribution within the knee. (2) To investigate the associations between CC and individual radiographic features of osteoarthritis (OA) at the tibiofemoral joint (TFJ) and patellofemoral joint (PFJ). METHODS: From three community questionnaire studies investigating the prevalence of knee pain, standing anteroposterior and skyline radiographs were obtained on 1727 subjects (1084 women, 643 men; mean age 63.7; 999 (58%) with knee pain). A single observer recorded the presence and site of CC and graded osteophyte and joint space narrowing (JSN) using a line atlas. "OA" was globally defined as the presence of definite osteophyte and definite JSN. Minimum joint space width (JSW) was measured to 0.1 mm with a metered dial caliper RESULTS: (1) The crude prevalence of CC was 7.0% (95% confidence interval (CI) 5.8 to 8.2). This showed a strong association with age. The age adjusted odds ratio (aOR) for CC in women v men was 0.79 (95% CI 0.52 to 1.12). The age, sex, and knee pain standardised estimate for those aged >40 in Nottingham, UK was 4.5%. Patellofemoral CC was seen in only nine cases, all with tibiofemoral CC. (2) The age-sex aOR for the association between CC and OA was 2.08 at the PFJ (1.38 to 3.12) and 2.00 (1.11 to 3.60) at the TFJ. There was no association between measured JSW and CC at either the PFJ or TFJ. Both total osteophyte score and total number of sites with osteophyte were positively associated with CC; aOR for the upper quartile was 2.40 (1.48 to 3.90) and 1.94 (1.15 to 3.26), respectively. An association between CC and diuretic use was also demonstrated (aOR=2.07, 1.02 to 4.19). CONCLUSIONS: In this large UK community study the age, sex, and knee pain adjusted prevalence of CC was 4.5%. There was a strong age association, but no sex predisposition. Patellofemoral CC was uncommon. An association between OA and CC was confirmed, but this appears to operate through an association with osteophyte rather than JSN. The new association between CC and diuretic use might theoretically be explained by diuretic induced hypomagnesaemia.

Measures implemented to project personal privacy for an on-line national patient index: a case study.

Increasing use of electronic data storage and exchange is inevitable. Although of considerable benefit to all concerned, they pose a potential threat to personal privacy. Measures to protect personal privacy in national information networks are essential. These and related security issues require the highest priority in strategic planning because experience shows that poor handling of security is the single factor most likely to lead to rejection of a system. It is increasingly important to be able to identify individuals uniquely for health-related purposes, and implementation of an on-line master index is the approach that has been adopted in New Zealand to address this need. Such an index, however, contains personal information, the privacy of which must be respected. Substituting the unique identifier for all personal details in electronic messages can provide a degree of security as long as access to the index is controlled and usage is monitored. The article outlines the measures, technical and otherwise, implemented to manage security concerns successfully in that context.

Prevalence of atopic dermatitis in Leicester: a study of methodology and examination of possible ethnic variation.

A study was undertaken to investigate and compare various methods of estimating the prevalence of atopic dermatitis (AD), and to investigate a possible ethnic difference in our local community. Preschool children attending routine child health surveillance clinics and Social Services day nurseries were examined by a trained observer, and their parents were interviewed. In addition, general practice records from a health centre were scrutinized. Three hundred and twenty-two children aged 1-4 years were examined, and the point prevalence of AD was 14% [95% confidence interval (CI) 10-18]. There was no apparent ethnic difference in prevalence. Twenty-seven per cent (95% CI 22-32) of parents reported that their children had suffered from 'eczema' at some time. General practitioners' records contained a diagnosis of 'eczema' in 32% (95% CI 28-36) of 446 children aged 1-4 years. It is clear that methodology must be carefully standardized if comparisons are to be made between different studies. Accurate estimations of the prevalence of AD can probably only be obtained by examination of a population sample by a trained observer. However, the estimates obtained in this study are high, and would tend to support existing evidence that the prevalence of AD is rising.

Should medical students be selected only from recent school-leavers who have studied science?

This study was undertaken to investigate the apparently widespread belief that in order to be successful at medical school, aspiring candidates must have a sound academic background based predominantly on the study of the natural sciences, be school-leavers aged about 18 (in the non-college educational environments such as Australia or the United Kingdom) and preferably be men. The demographic background and prior academic achievement of individual students entering the University of Newcastle Medical School between 1978 and 1989 has been reviewed and compared with their progress in medical studies. The data show that in the Newcastle medical school environment there is no significant correlation between outcome and previous study of any of the natural sciences. However, significant correlations between outcome and performance in the humanities in general, and English in particular, were found. In this regard a weak background in these subjects correlated with an increased tendency not to complete the medical course. There were no significant correlations found between outcome and age at entry, sex or levels of prior academic achievement (within the top 10% achievement band studied). In summary, the study offers no support for the current selection criteria dominating medical school admissions processes.

The objective structured interview for medical student selection.

An objective structured interview is an integral part of the process of selecting and admitting applicants to study medicine at this university. During the nine years (to the end of 1986) that the interview has been used 1600 candidates were interviewed out of roughly 13,000 applicants, and from these, 584 students were admitted to the course. Analysis of the interview data was carried out based on two aspects of student progress: graduation with honours and failure to complete the course of study. The interview as a whole, and especially some of the subscales, appears to identify students who may fail to complete the course: it may also help to predict which students are likely to graduate with honours.

The subcellular distribution of a membrane-bound calmodulin-stimulated protein kinase.

Incubation of subcellular fractions isolated from rat cerebral cortex with [gamma-32P]ATP results in the phosphorylation of a number of proteins including two with apparent molecular weights of approximately 50,000 and 60,000 daltons. These phosphoproteins were shown to be the autophosphorylated subunits of a calmodulin-stimulated protein kinase by a number of physicochemical criteria, including their mobility on non-equilibrium pH gradient electrophoresis, their phosphopeptide profiles and phosphorylation characteristics. When a crude membrane fraction obtained following osmotic lysis of a P2 fraction was labeled and subsequently fractionated on sucrose density gradients, approximately 80% of the autophosphorylated kinase was associated with fractions enriched in synaptic plasma membranes. Other substrates of calmodulin kinase(s) were similarly distributed. Detergent extraction of synaptic plasma membranes to produce synaptic junctions and post-synaptic densities indicated that the majority of the autophosphorylated kinase was solubilized, apparently as a holoenzyme. The major post synaptic density protein (mPSDp) was not readily extracted by detergents and was largely unlabeled under the conditions used for phosphorylation, and yet this protein is structurally closely related to the kinase subunit. It is possible that this lack of labeling is due to the mPSDp being attached to the PSD in a different way or being present there in a different isoenzymic form from that of the readily autophosphorylated enzyme subunit. Thus, the data suggest that, in vitro at least, a number of pools of calmodulin kinase exist in neuronal membranes.

Problem solving in undergraduate medical students.

In recent years the systematic development of the skill of clinical reasoning has come to assume a high priority as an explicit aim of medical education. Clinical reasoning, it is contended, is the application of general reasoning and problem-solving skills to the specific knowledge base of medicine. The results presented in this paper constitute a preliminary study designed to investigate the ability of first-year medical undergraduates to solve abstract problems using a simple nonmedical knowledge base. Further studies are being carried out and will continue to extend this into the specific medical knowledge base area. The potential implications for medical education and the development of clinical reasoning are discussed.

The preclinical course of study: help or hindrance?

The conventional structure of undergraduate medical education makes the implicit assumption that a "sound basis" in the understanding of the basic science disciplines is an essential prerequisite for starting clinical studies. It further assumes that the context within which the facts are presented is appropriate to this purpose and that demonstration of basic science knowledge is sufficient for the commencement of clinical studies. The precise structure of the preclinical phase of the medical course varies slightly from medical college to medical college but in general remains not unlike that described by Abraham Flexner more than 70 years ago, with the exception that it now packs many more facts and details into a similar space. The time has come to question the assumptions and to review the objectives of studying the basic medical sciences and the competencies that a student needs in order to progress to clinical studies. The author in this article reviews the available data and concludes that there is a substantial need for reform of the aims, content, and context of the learning in medical school preceding the clinical years.

Toward independent learning: curricular design for assisting students to learn how to learn.

It must be acknowledged that a university course in medicine cannot hope to present its students with everything they need to know in order to practice a lifetime's career in the profession. Even were the course years longer, increasing the content of factual knowledge would not equip the graduate for the practice of medicine. In part this is due to the fact that medical knowledge is continually changing or being reevaluated; in addition, facts alone cannot be correlated with practical application, and the process of how to use the facts is an essential part of the study and practice of medicine. It is essential, therefore, that an undergraduate medical course, among other things, teach the students to take responsibility for and to be able to structure their own learning. If the process of continual active learning is fostered during undergraduate days, it may readily be continued by the graduate alone in the absence of his teachers. The curriculum at the new medical school at Newcastle, New South Wales, Australia, is being developed with this priority in view. This paper describes some of the principles underpinning this philosophy and how such principles are being applied.

Construct a Problem-based Course.

This article outlines the preparation of an integrated, problem-based course as followed by the Faculty of Medicine, University of Newcastle, New South Wales. The policy and philosophy of the school, and the cardiovascular system course unit will be outlined in subsequent issues of this journal (Neame 1981, Powis and Neame 1981). The keys to successful course construction are faculty emphasis on the tasks to be achieved rather than on the disciplines themselves, coherent statements of policy and objectives which staff view as at least as important as those of their own disciplines, and a willingness to communicate, negotiate and be flexible. Students at the end of their third year were considered to be at least as competent as those from conventional curricula and excelled in some areas. A recent unpublished survey of the full-time academic staff revealed a high level of commitment to the goals of the course and satisfaction with the procedures involved.

The cardiovascular system.

In the last issue of this journal an approach to the construction of integrated, multidisciplinary course units was described (Neame 1981). This approach is illustrated in relation to the cardiovascular system course unit developed for use early in the second year of the five-year curriculum at the Faculty of Medicine, The University of Newcastle, New South Wales.

The subdivision of beta-adrenoceptors in the cardiovascular system of the rat.

1 The antagonism by the beta-adrenoceptor blocking drugs, propranolol (non-selective) and practolol (beta-selective), of the cardiovascular actions of isoprenaline has been investigated in the rat. 2 All doses of practolol (0.1, 1 and 3 mg/kg) blocked the cardio-accelerator action of isoprenaline but only the largest dose blocked the vasodilator effect. 3 All doses of propranolol (0.01, 0.03 and 0.1 mg/kg) blocked the vasodilator effect of isoprenaline but only the largest dose diminished the tachycardia. 4 It is concluded that in the rat, as in other species, beta-adrenoceptors may be subdivided into beta 1 (cardiac) and beta 2 (peripheral vascular) types.

Responses of the cardiovascular system of the rat to alpha-and beta-adrenoceptor agonists.

1 The effects of intravenously infused phenylephrine and isoprenaline upon the cardiovascular system of the rat anaesthetized with pentobarbitone, have been investigated.2 Phenylephrine produces a dose-dependent rise in mean arterial blood pressure (MABP) that is due mainly to an increase in total peripheral vascular resistance (TPR), though at all doses tested cardiac output was invariably raised.3 The increase in cardiac output was due in each instance to an increase in stroke volume, heart rate being unchanged. This increase in cardiac output is probably brought about by effects of phenylephrine on the capacitance vessels rather than by an effect on the heart.4 Evidence is presented to show that the effects of phenylephrine are mediated largely by alpha-adrenoceptors, but that beta-adrenoceptors which affect TPR are also stimulated by the amine.5 Isoprenaline produces a dose-dependent fall in MABP that is due entirely to a fall in TPR since the cardiac output increases.6 Unlike phenylephrine, the increase in cardiac output obtained with isoprenaline was achieved by an increase in heart rate while stroke volume remained close to control values. It is contended that the augmented venous return required for the elevated cardiac output results in this case mainly from the isoprenaline-induced fall in TPR which enhances transfer of blood from arteries to the veins.7 Evidence is presented to show that the effects of isoprenaline are mediated mainly by beta-adrenoceptors.8 Under the present experimental conditions the adrenoceptor-mediated cardiovascular changes are little modified reflexly by the arterial baroreceptors.

Responses of the cardiovascular system of the rat to noradrenaline infusions and their modification by adrenoceptor blocking agents.

1 The effects of noradrenaline upon the cardiovascular system of the rat, anaesthetized with pentobarbitone, have been investigated.2 Noradrenaline produces a dose-dependent increase in mean arterial blood pressure (MABP) which is due entirely to an increase in cardiac output; total peripheral vascular resistance (TPR) remains unchanged.3 Following beta-adrenoceptor blockade the pressor response to infused noradrenaline is enhanced and is now due mainly to an increase in TPR; the increment in cardiac output is reduced.4 After alpha-adrenoceptor blockade the pressor response is greatly reduced; the residual increase in MABP is due solely to an increase in cardiac output.5 After ganglion blockade resting cardiac output and TPR both fall, resulting in a reduction in MABP. The pressor response to noradrenaline is enhanced and is now due to increases in both TPR and in cardiac output.6 The cardiovascular response of the anaesthetized rat to noradrenaline can be explained in terms of classical alpha- and beta-adrenoceptor stimulation by the amine; the unusual form of the response may be due to an effective predominance of beta-adrenoceptor-mediated effects in this species.7 It is suggested that the failure of exogenous noradrenaline to produce a rise in TPR results from a balance between the alpha-adrenoceptor-mediated increase and beta-adrenoceptor-mediated decrease in this variable. However, this proposed balance is lost if resting vasoconstrictor tone is reduced by ganglion blockade.