Mary Lawson

Linkage of the angiotensinogen gene to essential hypertension

BACKGROUND The renin-angiotensin system is a powerful pressor system with a major influence on salt and water homeostasis. Angiotensinogen (also called renin substrate) is a key component of this system; it is cleaved by renin to yield angiotensin I, which is then cleaved by angiotensin-converting enzyme to yield angiotensin II. The observation that plasma angiotensinogen levels correlate with blood pressure and track through families suggests that angiotensinogen may have a role in essential hypertension. We therefore investigated whether there is linkage between the angiotensinogen gene on chromosome 1q42-43 and essential hypertension. METHODS Samples of DNA from 63 white European families in which two or more members had essential hypertension were tested for linkage of the angiotensinogen gene to this disorder. Affected cousins, nephews, nieces, and half-siblings were included when possible. To test for linkage, we used as a marker a dinucleotide-repeat sequence flanking this gene, and we employed the affected-pedigree-member method of linkage analysis. Two molecular variants of the angiotensinogen gene, one encoding threonine instead of methionine at position 235 (M235T) and the other encoding methionine rather than threonine at position 174 (T174M), were also tested for possible association with essential hypertension. RESULTS We found significant linkage (t = 5.00, P < 0.001) and association (chi-square = 53.3, P < 0.001) of the angiotensinogen-gene locus to essential hypertension in the 63 multiplex families. This linkage was consistently maintained in the subgroup of subjects with diastolic pressure above 100 mm Hg and in the subgroups classified according to sex. It has been proposed previously that T174M and M235T are associated with essential hypertension. However, we found no association in our population between either polymorphism and this disorder. CONCLUSIONS This study provides strong and consistent support for the linkage to essential hypertension of regions within or close to the angiotensinogen gene. Precisely how mutations in this region may result in hypertension remains to be determined.

Linkage of the angiotensinogen gene locus to human essential hypertension in African Caribbeans.

The renin-angiotensin system regulates blood pressure and sodium balance. The angiotensinogen gene which encodes the key substrate within this system has been linked to essential hypertension in White Europeans. It has been suggested that people of West African ancestry may have a different genetic basis for hypertension. In this study we have tested whether there is linkage of the angiotensinogen gene to essential hypertension in African Caribbeans from St. Vincent and the Grenadines. DNA from 63 affected sibling pairs with hypertension was tested for linkage by analyzing whether there was excess allele sharing among siblings genotyped using an angiotensinogen dinucleotide repeat sequence. There was significant support for linkage (T = 3.07, P = 0.001) and association of this locus to hypertension (chi 2 = 50.2, 12 degrees of freedom, P << 0.001). A DNA polymorphism which alters methionine to threonine at position 235 (M235T) within the angiotensinogen peptide has been associated previously with hypertension. However, we found no association of this variant with hypertension in this study. These findings provide support for linkage and association of the angiotensinogen locus to hypertension in African Caribbeans and suggest some similarities in the genetic basis of essential hypertension in populations of different ethnicity.

Learning together: clinical skills teaching for medical and nursing students

Objective  To evaluate the feasibility and effectiveness of shared learning of clinical skills for medical and nursing students at the University of Manchester.

Meeting the challenge of prescribing and administering medicines safely: structured teaching and assessment for final year medical students

Objectives To promote safe prescribing and administration of medicines in the pre‐registration house officer (PRHO) year through a programme of structured teaching and assessment for final year medical students.

Developing an outcome-focused core curriculum

Background  Many UK medical schools have modified their curricula to meet the requirements of the General Medical Council and other external agencies. In particular, efforts have been focused on increasing integration and reducing factual overload through the definition of a core curriculum. Various approaches to curriculum change have been adopted in an attempt to meet such demands.

The introduction of large class problem-based learning into an undergraduate medical curriculum: an evaluation

When considering implementing integrated curriculum models, such as problem-based learning (PBL), concerns may be expressed about the need for increased staff resources required to deliver tutor-led small group PBL. Less staff intensive ways of supporting PBL need to be explored. We compared the outcomes of a PBL module conducted in a large class format within a lecture theatre with a module having the same defined learning outcomes delivered in small group PBL format, both supported by e-learning resources. The pre-existing 27 small groups within the whole class (n = 246) of first year students undertaking a cardiovascular basic science module at Sheffield undergraduate medical school, UK, were randomized to 22 groups undertaking the large class Integrated Learning Activity (ILA) and 5 groups to traditional small group facilitated PBL sessions. Outcome measures were: a pre–post knowledge based test, a student educational effectiveness questionnaire, and assessment of student group work and presentations. There seemed to be no significant differences in learning outcomes between the methods although it is recognized that students would prefer the small group teaching format. Within institutions where resources to support small group PBL are limited, the large group ILA format supported with e-learning techniques may be a useful alternative approach.

Consistency of teaching in parallel surgical firms: an audit of student experience at one medical school

Traditional clinical clerkships have been based on the apprenticeship model of learning, with opportunistic teaching by doctors on presenting patients. Students at King’s College School of Medicine, London had expressed concern that they were receiving inequitable experiences in different clerkships. This had become more apparent since the introduction of a school‐wide end‐of‐year skills assessment. We decided to assess the consistency of delivery of the surgical syllabus.

TEACHING AND LEARNING IN DAY SURGERY UNITS : A UK SURVEY

Recent increases in day case surgery offer new opportunities for medical student learning, whilst the reduction in surgical beds and length of hospital stays has reduced opportunities in traditional inpatient settings. To establish the extent and nature of undergraduate medical education in day surgery units in the UK, the authors undertook a postal questionnaire survey. Of the 227 units which replied, 45% are used for teaching. In 83% of these, students attend only single operating lists, and only 7% of units take students for more than 1 day per week. This suggests that students have very limited teaching in day surgery units. Diagnosis, common surgical procedures and rehabilitation are increasingly carried out in outpatient, day case and community settings. These may be missed by students unless educational programmes are responsive to trends in health care delivery. Day surgery units could play an increased role in medical education.

Absence of Linkage of the Epithelial Sodium Channel to Hypertension in Black Caribbeans

Hypertensives of African origin have low-renin, sodium-sensitive blood pressure and respond poorly to treatment with angiotensin converting enzyme inhibitors. The epithelial sodium channel may be important in the pathogenesis of essential hypertension in this population. This is supported by the identification of mutations within this channel, which lead to excess sodium reabsorption and hypertension in Liddles syndrome. In this study we tested whether there was linkage of the genes encoding the three subunits of the epithelial sodium channel to essential hypertension in 63 affected sibling pairs of West African origin from St. Vincent and the Grenadines. We found no support for linkage of the epithelial sodium channel to essential hypertension in this population. However, further studies will be needed in larger populations of African ancestry to exclude a contribution of the genes encoding the epithelial sodium channel to hypertension.

Problems presented by medical students seeking support: A possible intervention framework

Background: Academically bright and ambitious medical students must cope with a combination of curriculum, assessment, career choice, personal, family and social pressures. Many seek support, and some present complex problems that consume substantial resources. A few continue unresolved into postgraduate life and may affect future professional performance. Early intervention may be helpful in minimising the impact on both individual students and school resources. Aim: To develop a broad classification framework for personal problems presented by medical students to student support services. Methods: We report a study of more complex student problems presenting to student support services. A three stage iterative process, involving student support faculty from several international medical schools, discussed case scenarios based on pooled experience and developed a framework for categorising and considering management. Results: Seven profiles of student problems were developed, based on composites of unidentified cases drawn from participants’ experiences, reflecting: immaturity; learning skills; organisational skills; health or personal issues and poor insight. Broad characteristics and brief prognostic comments are provided for each profile. Discussion: While profiles may overlap and each student may have a unique set of issues, there appears to be similarities that allow some categorisation for management strategies and prognostic features in both undergraduate and postgraduate medical education. Further work is needed to develop ‘diagnostic’ assessments that might guide intervention. Conclusion: This classification may assist early intervention into personal problems presented by medical students to student support services.