Hereditary hypertension caused by chimaeric gene duplications and ectopic expression of aldosterone synthase.

Patients with glucocorticoid-remediable aldosteronism (GRA) from 12 kindreds possess chimaeric gene duplications arising from unequal crossing-over, fusing regulatory sequences of steroid 11 beta-hydroxylase to coding sequences of aldosterone synthase. These chimaeric genes are specific for GRA and explain the biochemistry, physiology and genetics of this form of hypertension. Sites of crossing over range from intron 2 to intron 4. Most mutations have arisen independently from either sister or non-sister chromatid exchange between these genes, which are only 45 kilobases apart. The possibility of a susceptibility allele for GRA of Irish origin is suggested. These findings indicate the utility of a direct genetic test for this disorder.

The responses of professional groups to the use of Section 136 of the Mental Health Act (1983, as amended by the 2007 Act) in Gloucestershire.

BACKGROUND: Section 136 (S136) of the Mental Health Act (1983, as amended by the 2007 Act) empowers the police to detain those suspected of being mentally disordered in a public place and to convey them to a place of safety (POS) for further assessment. Gloucestershire has not had a specialist facility for S136 detentions and individuals were taken to the police cells or occasionally A&E departments for assessment. AIMS: This paper forms one part of three aspects under investigation. Two companion papers by the authors describe the use of S136 using anonymised audit data and the experiences of detainees. The objectives of this paper have been to assess the responses of the different professional groups involved in the process of S136. METHOD: An anonymous postal questionnaire was distributed to eight groups of professionals who were identified as having the potential to be involved in part of the process of a S136 detention. Results were collated and analysed, and formed the basis for a series of follow-up focus groups within groups to explore themes that warranted further investigation. RESULTS: An overall response rate of 59% was achieved. Seventy-four per cent of participants thought that there should be an alternative POS to the police station. A&E was thought to be an unsuitable alternative POS, with a psychiatric hospital being the first choice for 58%. CONCLUSIONS: There is a gap in the expectations of the different agencies involved in the S136 process, which have the potential to be divisive if interagency pathways and agreements are not in place.

The use of Section 136 (Mental Health Act 1983) in Gloucestershire.

The small number of published studies on the use of Section 136 (S136) of the Mental Health Act 1983 may reflect neither the current situation nor the true national picture as most of the research comes from large urban centres and was published before 1997. We studied the use of S136 between 2002 and 2006 in Gloucestershire, a rural English county with a population of approximately 585,000, by analysing data held by the police and local mental health services. On average 192 subjects (range 176-203) were detained each year under S136, equating to a population rate of 32.8 S136 detentions per 100,000 per year in Gloucestershire. In contrast to other published studies, ethnic minorities, particularly Afro-Caribbean males, were overrepresented only in a minor way. Of those individuals detained, about a third were admitted, a lower rate than in other studies. Acts or threats of self-harm were common (55%), but acts or threats of violence (28%) and evidence of intoxication (16%) were present in a minority, suggesting that detainees are more likely to pose a risk to themselves than others.

Cloning and characterization of a mouse gene with homology to the human von Hippel-Lindau disease tumor suppressor gene: implications for the potential organization of the human von Hippel-Lindau disease gene.

The human von Hippel-Lindau disease (VHL) gene has recently been identified and, based on the nucleotide sequence of a partial cDNA clone, has been predicted to encode a novel protein with as yet unknown functions [F. Latif et al., Science (Washington DC), 260: 1317-1320, 1993]. The length of the encoded protein and the characteristics of the cellular expressed protein are as yet unclear. Here we report the cloning and characterization of a mouse gene (mVHLh1) that is widely expressed in different mouse tissues and shares high homology with the human VHL gene. It predicts a protein 181 residues long (and/or 162 amino acids, considering a potential alternative start codon), which across a core region of approximately 140 residues displays a high degree of sequence identity (98%) to the predicted human VHL protein. High stringency DNA and RNA hybridization experiments and protein expression analyses indicate that this gene is the most highly VHL-related mouse gene, suggesting that it represents the mouse VHL gene homologue rather than a related gene sharing a conserved functional domain. These findings provide new insights into the potential organization of the VHL gene and nature of its encoded protein.

PA26, a novel target of the p53 tumor suppressor and member of the GADD family of DNA damage and growth arrest inducible genes.

Exposure of mammalian cells to hypoxia, radiation and certain chemotherapeutic agents promotes cell cycle arrest and/or apoptosis. Activation of p53 responsive genes is believed to play an important role in mediating such responses. In this study we identified a novel gene, PA26, which maps to chromosome 6q21 and encodes at least three transcript isoforms, of which two are differentially induced by genotoxic stress (UV, gamma-irradiation and cytotoxic drugs) in a p53-dependent manner. A functional p53-responsive element was identified in the second intron of the PA26 gene, in consistance with a mechanism of transcriptional induction of the PA26 gene by p53. No clues to its functions were revealed by sequence analysis, although pronounced negative regulation by serum factors argues for a potential role of PA26 in growth regulation. Immunological analysis suggests that PA26 protein(s) is localized to the cell nucleus. Our results suggest that the PA26 gene is a novel p53 target gene with properties common to the GADD family of growth arrest and DNA damage-inducible stress-response genes, and, thus, a potential novel regulator of cellular growth.

Effects of once-daily benazepril therapy on exercise tolerance and manifestations of chronic congestive heart failure. The Benazepril Heart Failure Study Group.

The effects of the long-acting angiotensin-converting enzyme inhibitor benazepril hydrochloride on exercise tolerance and signs and symptoms of congestive heart failure (CHF) were evaluated in a double-blind, multicenter, placebo-controlled clinical trial. Patients with chronic New York Heart Association class II to IV symptoms of CHF and an ejection fraction by radionuclide scanning of less than or equal to 35% were randomized in a 2:1 ratio to treatment with ascending doses of oral benazepril (n = 114) or placebo (n = 58) once daily, while continuing to receive background therapy with digoxin and diuretics. After randomization, patients were evaluated clinically every 2 weeks during a 12-week, double-blind treatment period. Maximal exercise tolerance was measured before and at specified time points after randomization by graded treadmill exercise testing. At week 12, mean exercise time increased 95 +/- 12 (SEM) seconds in the group receiving benazepril, whereas the increase was 37 +/- 18 seconds in the group receiving placebo (p less than 0.01 for the difference between the groups). There was also greater improvement in overall clinical status and in the signs and symptoms of CHF in benazepril-treated patients than in control subjects. There were 3 deaths in placebo-treated patients and none in benazepril-treated patients (p less than 0.05); the overall incidence of adverse effects was identical in the 2 groups. Benazepril is a well-tolerated angiotensin-converting enzyme inhibitor that provides clinically important improvement in exercise tolerance and in signs and symptoms when given once daily to patients with CHF receiving background therapy with digoxin and a diuretic.

Recurrence of acoustic neurilemoma as a malignant spindle-cell neoplasm. Case report.

A 75-year-old man presented with a right cerebellopontine angle tumor 11 months after complete macroscopic resection of a right acoustic neurilemoma. Histological examination of the recurrent tumor showed a malignant spindle-cell neoplasm with positive staining for S-100 protein. The patient had no stigmata of von Recklinghausen's disease. It is proposed that this recurrence represents progression from a benign to a malignant acoustic nerve-sheath tumor, an event that is extremely rare outside the clinicopathological context of neurofibromatosis.

Degradation and inactivation of antitumor drugs.

Chemical methods for the degradation of 11 antineoplastic drugs [etoposide, teniposide, bleomycin, mitomycin C, cisplatin, cis-dichloro-trans-dihydroxy-bis(isopropylamine) platinum IV (CHIP), cyclophosphamide, ifosfamide, carmustine, lomustine, and methotrexate] were investigated. The success of the degradation procedures was assessed by HPLC and degree of biological inactivation by mutagenicity assays. The most widely applicable procedure was oxidation with potassium permanganate or 5.25% sodium hypochlorite solution (bleach). Oxidation completely degraded and inactivated etoposide, teniposide, bleomycin, mitomycin C, and methotrexate. In addition, oxidation followed by nucleophilic substitution resulted in the complete degradation and inactivation of cyclophosphamide and ifosfamide. Although carmustine and lomustine were chemically degraded by treatment with acidic potassium permanganate, the resulting reaction mixtures remained mutagenic. Therefore, this procedure cannot be recommended. The platinum-containing compounds, cisplatin and CHIP, were rendered nonmutagenic by reaction with sodium diethyldithiocarbamate. These easily performed, relatively safe procedures can be used to prevent exposure to mutagenic wastes and spills in the hospital setting.

A randomized, double-blind, parallel group comparison of disopyramide phosphate and quinidine in patients with cardiac arrhythmias.

This report summarizes the results of a randomized, double-blind, parallel group, multicenter study which compared the antiarrhythmic activity and safety of oral disopyramide phosphate and oral quinidine sulfate. A total of 124 outpatients, whose pretreatment rates of ventricular and/or supraventricular arrhythmias were documented by ambulatory ECG recordings, were randomly assigned to receive either oral disopyramide or oral quinidine for the eight-week course of the study. Every two weeks, ten-hour ambulatory ECG recordings were obtained from each patient and blood was drawn to determine serum concentrations of assigned drug.

Early surgery for posterior circulation aneurysms following subarachnoid haemorrhage.

A retrospective analysis of 32 patients with posterior circulation aneurysms operated on within three days of subarachnoid haemorrhage is presented. The cases were treated at two Australian neurosurgery units over a five year period (1988-1992), both units having a policy of treating patients of all grades and all ages with early surgery. No patients suffered rebleeding. Five patients developed clinical vasopasm. Twenty-four patients (75%) had a good outcome (Glasgow Outcome Score 1-2), three had a poor outcome (GOS 3), and five died (16%). Of the five deaths, three presented as Hunt and Hess grade V. The results are considered in detail and the literature regarding the timing of surgery for posterior circulation aneurysms is reviewed.

The preventability of death in road traffic fatalities with head injury in Victoria, Australia. The Consultative Committee on Road Traffic Fatalities.

Since 1992 the Consultative Committee on Road Traffic Fatalities in Victoria (CCRTF) has examined the medical management of patients who died following motor vehicle accidents. Three hundred and fifty-five fatalities with head injury occurring between 1 July, 1992 and 31 December 1997 were assessed by the CCRTF. They represented 79% of the total 449 fatalities examined by the Committee. Following examination of the complete medical records and multidisciplinary discussion, the Committee considered 237 (67%) of the 355 neurotrauma deaths to be non-preventable, 105 (30%) potentially preventable and 13 (4%) preventable. The present analysis excludes the non-preventable deaths in order to focus on preventable factors. Problems identified in the 118 patients pre-hospital included: no intubation; prolonged scene time; and no intravenous access; in 139 emergency room attendances: inappropriate reception including delay in arrival of a consultant, no neurosurgical consultation, no CT scan of the head, inadequate blood gases and oxygen monitoring, inadequate fluid resuscitation, delayed respiratory resuscitation and delayed dispatch to the operating room; in 111 operating room visits: no ICP monitoring, inadequate fluid administration and inappropriate anaesthetic technique; and in 90 intensive care unit admissions: no ICP monitoring. Overall, 1745 individual problems in the various areas of care were identified, of which 1104 (63%) were judged to have contributed to death. Improved delivery and quality of trauma care could reduce the identified problems in emergency services and clinical management. Basic principles of trauma management remain the most important means of reducing morbidity and death following road trauma. The leadership role of the neurosurgeon in neurotrauma care is emphasised.

Lessons learned from the development of a distance-learning programme.

The development of an effective educational programme, i.e. one that not only delivers education but which also fosters change, requires both educational skills and subject expertise from the producers. This paper looks at the key lessons learned when developing a distance-learning programme. These seven key lessons, which focus heavily on needs assessment as well as team working and the need to consider a multiprofessional approach, offer practical advice to those in the medical and dental professions wishing to produce their own educational programmes.

Fetal abuse.

The possible occurrence of fetal abuse in expectant mothers has received little attention in either clinical practice or in research. Five cases with reported fetal abuse are presented. Each case suffered from depression and four of the five women had unplanned pregnancies and had considered a termination of pregnancy. Other possible factors associated with fetal abuse included: denial of the pregnancy, ambivalence towards the pregnancy, previous postpartum depression, and relationship difficulties. Enquiry of possible fetal abuse in pregnant women should be made, particularly if a depressive illness is demonstrated. The relationship between fetal abuse and subsequent child abuse remains unclear.

"On Track"--an educational resource to support dental SHO training.

This paper describes the development, implementation and evaluation of an educational resource, "On Track", designed to support dental SHOs throughout their time in post, thereby helping them gain optimum benefit from this important stage in their early postgraduate training. The need for such a resource was highlighted by a previous study undertaken by the paper's key authors with SHOs and their trainers in a UK dental school. Among several areas of change identified by both trainers and trainees were the needs to develop the SHO experience into more than an apprenticeship by improving the trainer/trainee relationship, and to encourage trainee-centred learning and self-appraisal. The key aims of "On Track" were therefore to define the outcomes of SHO training, to facilitate the relationship between SHO and educational supervisor (trainer), and to encourage the SHO in reflective learning and self-appraisal."On Track" was subject to developmental testing with both trainers and trainees to ensure that it could achieve these aims and the resultant resource is described, along with its implementation and evaluation. "On Track" met with mixed success and the reasons behind this and conclusions drawn for the introduction of any future similar resources are outlined.

Experience with dental implant patients at Riyadh Armed Forces Hospital.

Full text is available as a scanned copy of the original print version.

Benchmarking and supplier networking--best practice approaches.

This article examines the approach adopted by a health service to benchmark outside the health industry and to network with its own suppliers in its quest for best practice. The Maryborough District Health Service was selected for funding under the Commonwealth Government's Best Practice in the Health Sector Program. This rural health service is setting a fine example of how generic benchmarking can be used to increase efficiency and improve outcomes in an environment of change, increasing demands, and contracting resources. The organisation has networked with its suppliers with a view to ensuring that, as a customer, it has access to the best quality goods and services. The objective is to improve the services and quality of patient care provided by the health service and to minimise its cost structures.