The evolution of the doctor-patient relationship.

The doctor-patient relationship has undergone a transition throughout the ages. Prior to the last two decades, the relationship was predominantly between a patient seeking help and a doctor whose decisions were silently complied with by the patient. In this paternalistic model of the doctor-patient relationship, the doctor utilises his skills to choose the necessary interventions and treatments most likely to restore the patient's health or ameliorate his pain.

Enhanced feedback sensitivity to prednisolone in chronic fatigue syndrome.

Objective: Enhancement of negative feedback control of the HPA axis in patients with chronic fatigue syndrome (CFS) has been reported using the low dose dexamethasone suppression test. We have developed the use of prednisolone (5mg) as a more physiologically appropriate alternative to dexamethasone in the investigation of mild degrees of glucocorticoid resistance or supersensitivity. The objective of the study was to use this test to look for alterations in negative feedback control of the HPA axis in CFS patients.

Case-control genetic association study of fibulin-6 (FBLN6 or HMCN1) variants in age-related macular degeneration (AMD).

This article reports a well-powered age-related macular degeneration (AMD) case-control association study in the HMCN1 gene, showing that common variants do not account for a substantial proportion of AMD cases. Thus, the consistent linkage peak observed by several genome-wide linkage scans within the 1q32 region is unlikely to be attributed to polymorphisms at the HMCN1 locus. In addition, the analysis provides comprehensive data suggesting that low-frequency variants encoding possible functional amino acid polymorphisms in the HMCN1 gene may not contribute substantially to disease, although HMCN1 mutations may still confer disease susceptibility in a small subset of patients.

Immunogold labeling study of the distribution of GLUT-1 and GLUT-4 in cardiac tissue following stimulation by insulin or ischemia.

Whereas glucose transporter 1 (GLUT-1) is thought to be responsible for basal glucose uptake in cardiac myocytes, little is known about its relative distribution between the different plasma membranes and cell types in the heart. GLUT-4 translocates to the myocyte surface to increase glucose uptake in response to a number of stimuli. The mechanisms underlying ischemia- and insulin-mediated GLUT-4 translocation are known to be different, raising the possibility that the intracellular destinations of GLUT-4 following these stimuli also differ.

Specific targeting of cytosine methylation to DNA sequences in vivo.

Development of methods that will allow exogenous imposition of inheritable gene-specific methylation patterns has potential application in both therapeutics and in basic research. An ongoing approach is the use of targeted DNA methyltransferases, which consist of a fusion between gene-targeted zinc-finger proteins and prokaryotic DNA cytosine methyltransferases. These enzymes however have so far demonstrated significant and unacceptable levels of non-targeted methylation.

Role of innate immunity in cancer.

Recently, much progress has been made in the field of tumor immunology. Much of this work has focused on understanding and exploiting the innate immune response to tumor cells. A novel human receptor-ligand system that mediates natural killer (NK) and gammadelta T-cell killing of carcinoma cells has been identified, and the functions of an equivalent system in mice are beginning to be explored.

Pediatric liver disease.

Pediatric hepatology has advanced greatly over the past few years. Many more children with severe liver disease are now surviving into adulthood. There is a number of conditions not seen in adult practice that have been the focus of research efforts, and many of these efforts have borne fruit in the past year.

Pediatric liver disease.

Pediatric hepatology is no different than any other pediatric specialty. The prime objective is either to cure disease or to minimize its impact on the child. The result will be that children with chronic liver disease will become adults with chronic liver disease, and the long-term follow-up of pediatric liver disease will pass out of the hands of pediatricians.

Diagnosis of antiphospholipid syndrome.

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by recurrent vascular thrombosis and pregnancy losses. Laboratory diagnosis of APS relies on the demonstration of a positive anticardiolipin antibody test by an in-house or commercially available enzyme-linked immunosorbent assay, or on the presence of lupus anticoagulant by a coagulation-based test. Persistence of the positive results must be demonstrated, and other causes and underlying factors considered.

Analyses of variant human papillomavirus type-16 E5 proteins for their ability to induce mitogenesis of murine fibroblasts.

Background: Human papillomavirus type 16 (HPV-16) E5 protein co-operates with epidermal growth factor to stimulate mitogenesis of murine fibroblasts. Currently, little is known about which viral amino acids are involved in this process. Using sequence variants of HPV-16 E5 we have investigated their effects upon E5 transcription, cell-cycling and cell-growth of murine fibroblasts.

Urinary cortisol and cortisol metabolite excretion in chronic fatigue syndrome.

Objectives: Reduced basal hypothalamic-pituitary-adrenal (HPA) axis output in chronic fatigue syndrome (CFS) has been inferred from low cortisol levels in blood, saliva, and urine in some studies. Because > 95% of cortisol is metabolized before excretion, we assessed cortisol output by assay of both cortisol metabolites and free cortisol in 24-hour urine collections and also investigated sex differences in these between CFS and control groups.

Method: We calculated total urinary cortisol metabolites (TCM) and cortisol metabolite ratios from individual steroid data in 40 patients (20 males and 20 females) with CFS who were free of medication or comorbid psychiatric disorder likely to influence the HPA axis.

Cognitive behavioural therapy in addition to antispasmodic therapy for irritable bowel syndrome in primary care: randomised controlled trial.

Objectives: To determine whether cognitive behavioural therapy (CBT) in addition to antispasmodic treatment offers a cost-effective benefit to primary care patients with irritable bowel syndrome (IBS) and to identify predictors of outcome.

Design: This was a randomised controlled trial in primary care of the addition of CBT to standard general practice management of IBS, using the antispasmodic agent mebeverine hydrochloride. The study set out to compare the addition of a standardised package of IBS-specific CBT to treatment with mebeverine hydrochloride.

Morbidity in expatriates--a prospective cohort study.

Background: Expatriates comprise an important, but rarely studied subset of international travellers. This study was performed to assess the incidence of health events in an expatriate group and to evaluate factors affecting this incidence.

Methods: A cohort of 2020 Foreign and Commonwealth Office (FCO) staff and partners living abroad were followed-up over 1 year.

Validation of a non-mercury digital auscultatory device with manual pressure registration (PMS Mandaus).

Objective: To assess the clinical accuracy of a non-mercury digital auscultatory device (PMS Mandaus) with manual pressure registration in an adult population.

Methods: The accuracy of the device was assessed by predefined criteria (European Society of Hypertension protocol) in 33 study participants recruited from among patients and staff in a teaching hospital. A series of same-arm sequential blood pressure measurements were taken: first, two observers taking simultaneous mercury readings, followed by a reading with the device.

Effect of areca nut on salivary copper concentration in chronic chewers.

The chewing of areca nut is associated with the development of oral submucous fibrosis (OSF), a condition predominantly encountered in Asians indulging in the habit. The pathogenesis of this condition is however, unclear, though several mechanisms have been proposed. Copper has previously been implicated as a possible aetiological factor.

The implications of a growing evidence base for drug use in elderly patients. Part 4. Vitamin D and bisphosphonates for fractures and osteoporosis.

Fractures are common in elderly subjects, disabling and occasionally fatal. Their incidence increases exponentially with age, with the commonest affected sites being the wrist, vertebrae, hip and humerus. Of these, hip fractures are the most relevant in terms of morbidity and financial cost.

Exercising in the cold inhibits growth hormone secretion by reducing the rise in core body temperature.

Objective: Ambient temperature alters exercise induced GH secretion. It is unknown whether temperature affects GH secretion at exercise intensities above the anaerobic threshold when other factors may override the relationship seen at lower intensities.

Design: Cross-over study of ambient temperature on exercise induced GH in swimmers and rowers.

Sleep-related problems of Parkinson's disease.

Objective: To define the epidemiology, characteristics and aetiology of nocturnal symptoms and sleep disorders in patients with Parkinson's disease (PD) and evaluate the available methods for their diagnosis and management.

Methods: A review of the English-language literature pertaining to sleep disturbances associated with PD, using the Medline database and bibliographies in relevant articles.

Results: Sleep-related problems specific to PD may occur early and even predate the diagnosis of the disease but are generally more frequent and more severe in patients with advanced PD.

The effect of noninvasive ventilation on ALS patients and their caregivers.

Background: Noninvasive ventilation (NIV) reduces mortality and improves some aspects of quality of life (QoL) in ALS. However, concerns remain that progressive disability may negate these benefits and unnecessarily burden caregivers.

Methods: Thirty-nine patients requiring NIV were offered treatment.

Cancer and laterality: a study of the five major paired organs (UK).

Objective: The human body displays marked asymmetry: paired organs differ bilaterally exerting effects upon cancer incidence and progression. However the factors involved remain contentious. In this large study involving over a quarter of a million cancer patients, we examine the epidemiological correlates of cancer laterality including incidence, stage at diagnosis and survival in the five major paired organs: the breasts, lungs, kidneys, testes and ovaries.

Thromboprophylaxis in major abdominal surgery for cancer.

Aims: To review the epidemiology and pathogenesis of venous thromboembolism (VTE) in surgical cancer patients, in addition to the use of thromboprophylaxis in major abdominal surgery, such as low-molecular-weight heparin (LMWH) and fondaparinux.

Methods: Systematic review of the literature, focussing on risk factors for VTE, parenteral methods of thromboprophylaxis, approaches to prolonged prophylaxis, and effects on patient survival.

Findings: Patients with cancer undergoing abdominal surgery are at substantially higher risk for VTE than patients without cancer.