Showing papers by "Leicester Royal Infirmary published in 2002"

Applications of diffusion-weighted and diffusion tensor MRI to white matter diseases - a review.

Abstract: This paper reviews the current applications of diffusion-weighted and diffusion tensor MRI in diseases of the brain white matter. The contribution that diffusion-weighted imaging has made to our understanding of white matter diseases is critically appraised. The quantitative nature of diffusion MRI is one of its major attractions; however, this is offset by the more advanced hardware required to collect diffusion-weighted images reliably, and the more complex processing to produce quantitative parametric diffusion images. With the now common availability of scanners equipped to perform echo-planar imaging, the acquisition of diffusion tensor images is sure to become more widespread and routine.

Azathioprine in severe adult atopic dermatitis: a double-blind, placebo-controlled, crossover trial.

Abstract: SummaryBackground There is a limited range of treatments for severe atopic dermatitis (AD). Azathioprine has often been used but there has been no randomized controlled trial of this drug to confirm its efficacy in AD. Objectives To establish or refute the efficacy of azathioprine in severe AD. To investigate the safety and tolerability of azathioprine in this patient population. Methods We performed a double-blind, randomized, placebo-controlled, crossover trial of azathioprine in adult patients with severe AD. Each treatment period was of 3 months' duration. Treatments were azathioprine 2·5 mg kg−1 day−1 and matched placebo. Disease activity was monitored using the SASSAD sign score. In addition, severity of pruritus, sleep disturbance and disruption of work/daytime activity were monitored using visual analogue scales. Adverse events were recorded and haematological and biochemical monitoring was performed. Results Thirty-seven subjects were enrolled, mean age 38 years (range 17–73). Sixteen were withdrawn, 12 during azathioprine treatment and four during placebo treatment. The SASSAD score fell by 26% during treatment with azathioprine vs. 3% on placebo (P < 0·01). Pruritus, sleep disturbance and disruption of work/daytime activity all improved significantly on active treatment but not on placebo. The difference in mean improvement between azathioprine and placebo was significant for disruption of work/daytime activity (P < 0·02) but not for pruritus or sleep disturbance. Gastrointestinal disturbances were reported by 14 patients during azathioprine treatment and four were withdrawn as a result of severe nausea and vomiting. Leukopenia was observed in two patients and deranged liver enzymes in eight during treatment with azathioprine. Conclusions Azathioprine is an effective and useful drug in severe AD although it is not always well-tolerated. Monitoring of the full blood count and liver enzymes is advisable during treatment.

Vitamin D and systemic cancer: is this relevant to malignant melanoma?

Abstract: 1,25-dihydroxyvitamin D3[1,25(OH)2D3] is a well-known potent regulator of cell growth and differentiation and there is recent evidence of an effect on cell death, tumour invasion and angiogenesis, which makes it a candidate agent for cancer regulation. The classical synthetic pathway of 1,25(OH)2D3 involves 25- and 1 alpha-hydroxylation of vitamin D3, in the liver and kidney, respectively, of absorbed or skin-synthesized vitamin D3. There is recent focus on the importance in growth control of local metabolism of 1,25(OH)2D3, which is a function of local tissue synthetic hydroxylases and particularly the principal catabolizing enzyme, 24-hydroxylase. The classical signalling pathway of 1,25(OH)2D3 employs the vitamin D nuclear receptor (VDR), which is a transcription factor for 1,25(OH)2D3 target genes. Effects of this pathway include inhibition of cellular growth and invasion. Cytoplasmic signalling pathways are increasingly being recognized, which similarly may regulate growth and differentiation but also apoptosis. 1,25(OH)2D3 has a major inhibitory effect on the G1/S checkpoint of the cell cycle by upregulating the cyclin dependent kinase inhibitors p27 and p21, and by inhibiting cyclin D1. Indirect mechanisms include upregulation of transforming growth factor-beta and downregulation of the epidermal growth factor receptor. 1,25(OH)2D3 may induce apoptosis either indirectly through effects on the insulin-like growth receptor and tumour necrosis factor-alpha or more directly via the Bcl-2 family system, the ceramide pathway, the death receptors (e.g. Fas) and the stress-activated protein kinase pathways (Jun N terminal kinase and p38). Inhibition of tumour invasion and metastasis potential has been demonstrated and mechanisms include inhibition of serine proteinases, metalloproteinases and angiogenesis. The lines of evidence for an effect of vitamin D3 in systemic cancer are the laboratory demonstration of relevant effects on cellular growth, differentiation, apoptosis, malignant cell invasion and metastasis; epidemiological findings of an association of the occurrence and outcome of cancers with derangements of vitamin D3/1,25(OH)2D3 and the association of functional polymorphisms of the VDR with the occurrence of certain cancers. In addition, vitamin D3 analogues are being developed as cancer chemotherapy agents. There is accumulating evidence that the vitamin D3/1,25(OH)2D3/VDR axis is similarly important in malignant melanoma (MM). MM cells express the VDR, and the antiproliferative and prodifferentiation effects of 1,25(OH)2D3 have been shown in cultured melanocytes, MM cells and MM xenografts. Recently, an inhibitory effect on the spread of MM cells has been demonstrated, low serum levels of 1,25(OH)2D3 have been reported in MM patients and the VDR polymorphisms have been shown to be associated with both the occurrence and outcome of MM. The relationship between solar irradiation and MM is more complex than for the systemic cancers. As in other cancers, there is evidence of a protective effect of vitamin D3 in MM, but ultraviolet radiation, which is a principal source of vitamin D3, is mutagenic. Further work is necessary on the influence of serum vitamin D3 levels on the occurrence and prognosis of MM, the effects of sun protection measures on serum vitamin D3 levels in temperate climates and epidemiological studies on geographical factors and skin type on the prognosis of MM. Meanwhile, it would seem mandatory to ensure an adequate vitamin D3 status if sun exposure were seriously curtailed, certainly in relation to carcinoma of breast, prostate and colon and probably also MM.

Isotropic resolution diffusion tensor imaging with whole brain acquisition in a clinically acceptable time.

Abstract: Our objective was to develop a diffusion tensor MR imaging pulse sequence that allows whole brain coverage with isotropic resolution within a clinically acceptable time. A single-shot, cardiac-gated MR pulse sequence, optimized for measuring the diffusion tensor in human brain, was developed to provide whole-brain coverage with isotropic (2.5 x 2.5 x 2.5 mm) spatial resolution, within a total imaging time of approximately 15 min. The diffusion tensor was computed for each voxel in the whole volume and the data processed for visualization in three orthogonal planes. Anisotropy data were further visualized using a maximum-intensity projection algorithm. Finally, reconstruction of fiber-tract trajectories i.e., "tractography" was performed. Images obtained with this pulse sequence provide clear delineation of individual white matter tracts, from the most superior cortical regions down to the cerebellum and brain stem. Because the data are acquired with isotropic resolution, they can be reformatted in any plane and the sequence can therefore be used, in general, for macroscopic neurological or psychiatric neuroimaging investigations. The 3D visualization afforded by maximum intensity projection imaging and tractography provided easy visualization of individual white matter fasciculi, which may be important sites of neuropathological degeneration or abnormal brain development. This study has shown that it is possible to obtain robust, high quality diffusion tensor MR data at 1.5 Tesla with isotropic resolution (2.5 x 2.5 x 2.5 mm) from the whole brain within a sufficiently short imaging time that it may be incorporated into clinical imaging protocols.

[Nphe1,Arg14,Lys15]nociceptin-NH2, a novel potent and selective antagonist of the nociceptin/orphanin FQ receptor.

Abstract: 1. Nociceptin/orphanin FQ (N/OFQ) modulates several biological functions by activating a specific G-protein coupled receptor (NOP). Few molecules are available that selectively activate or block the NOP receptor. Here we describe the in vitro and in vivo pharmacological profile of a novel NOP receptor ligand, [Nphe(1),Arg(14),Lys(15)]N/OFQ-NH(2) (UFP-101). 2. UFP-101 binds to the human recombinant NOP receptor expressed in Chinese hamster ovary (CHO) cells with high affinity (pK(i) 10.2) and shows more than 3000 fold selectivity over classical opioid receptors. UFP-101 competitively antagonizes the effects of N/OFQ on GTPgamma(35)S binding in CHO(hNOP) cell membranes (pA(2) 9.1) and on cyclic AMP accumulation in CHO(hNOP) cells (pA(2) 7.1), being per se inactive at concentrations up to 10 microM. 3. In isolated peripheral tissues of mice, rats and guinea-pigs, and in rat cerebral cortex synaptosomes preloaded with [(3)H]-5-HT, UFP-101 competitively antagonized the effects of N/OFQ with pA(2) values in the range of 7.3 - 7.7. In the same preparations, the peptide was inactive alone and did not modify the effects of classical opioid receptor agonists. 4. UFP-101 is also active in vivo where it prevented the depressant action on locomotor activity and the pronociceptive effect induced by 1 nmol N/OFQ i.c.v. in the mouse. In the tail withdrawal assay, UFP-101 at 10 nmol produces per se a robust and long lasting antinociceptive effect. 5. UFP-101 is a novel, potent and selective NOP receptor antagonist which appears to be a useful tool for future investigations of the N/OFQ-NOP receptor system.

A pilot randomized trial comparing CD34-selected versus unmanipulated hemopoietic stem cell transplantation for severe, refractory rheumatoid arthritis.

Abstract: Objective. Evidence from animal studies, case reports, and phase I studies suggests that hemopoietic stem cell transplantation (HSCT) can be effective in the treatment of rheumatoid arthritis (RA). It is unclear, however, if depletion of T cells in the stem cell product infused after high-dose chemotherapy is beneficial in prolonging responses by reducing the number of infused autoreactive T cells. This pilot multicenter, randomized trial was undertaken to obtain feasibility data on whether CD34 selection (as a form of T cell depletion) of an autologous stem cell graft is of benefit in the HSCT procedure in patients with severe, refractory RA. Methods. Thirty-three patients with severe RA who had been treated unsuccessfully with methotrexate and at least 1 other disease-modifying agent were enrolled in the trial. The patients received high-dose immunosuppressive treatment with 200 mg/kg cyclophosphamide followed by an infusion of autologous stem cells that were CD34 selected or unmanipulated. Safety, efficacy (based on American College of Rheumatology [ACR] response criteria), and time to recurrence of disease were assessed on a monthly basis for up to 12 months. Results. All patients were living at the end of the study, with no major unexpected toxicities. Overall, on an intent-to-treat basis, ACR 20% response (ACR20) was achieved in 70% of the patients. An ACR70 response was attained in 27.7% of the 18 patients who had received CD34-selected cells and 53.3% of the 15 who had received unmanipulated cells (P = 0.20). The median time to disease recurrence was 147 days in the CD34-selected cell group and 201 days in the unmanipulated cell group (P = 0.28). There was no relationship between CD4 lymphopenia and response, but 72% of rheumatoid factor (RF)-positive patients had an increase in RF titer prior to recurrence of disease. Conclusion. HSCT can be performed safely in patients with RA, and initial results indicate significant responses in patients with severe, treatment-resistant disease. Similar outcomes were observed in patients undergoing HSCT with unmanipulated cells and those receiving CD34-selected cells. Larger studies are needed to confirm these findings.

Subintimal Angioplasty of Isolated Infragenicular Vessels in Lower Limb Ischemia: Long-term Results

Abstract: Purpose:To assess the outcome of subintimal angioplasty in treating isolated infragenicular arterial disease in patients with severe lower limb ischemia.Methods:A retrospective study reviewed 67 consecutive patients (39 men; mean age 76 years, range 41–96) who underwent infragenicular subintimal angioplasty between March 1997 and May 2000 for ischemia in 70 limbs. The median length of occlusion was 6 cm (range 1–10) in the below-knee popliteal arteries, 4 cm (range 1–4) in the tibioperoneal trunk, 21 cm(range 1–35) in the anterior tibial artery, 10 (1–30) in the posterior tibial artery, and 5 (range 1–20) in the peroneal artery.Results:The technical and clinical success rates were 86% and 80%, respectively. In the 10 (14%) patients with a technical failure, 3 underwent successful bypass, 4 had an amputation, 1 had a lumbar sympathectomy, and 2 were treated conservatively. Of the 4 (6%) limbs that did not achieve clinical success, 2 patients required femorodistal bypass and their ulcers improved; in the ot...

Anti-E-selectin is ineffective in the treatment of psoriasis: a randomized trial.

Abstract: SummaryBackground Skin-homing, memory T lymphocytes play an important role in the pathogenesis of psoriasis by interacting with the vascular addressin, E-selectin and trafficking into lesional skin Thus an attractive option for targeted therapy of the disease would be blockade of skin-homing T cells with an antibody directed at E-selectin Objective We performed a multicentre, randomized, placebo-controlled trial to investigate the clinical efficacy and side-effect profile of a humanized monoclonal antibody to E-selectin, CDP850, in the treatment of moderate to severe chronic plaque psoriasis Methods Patients with moderate/severe chronic plaque psoriasis were selected for study Nine male subjects (mean age 37 years, range 25–47) were given 20 mg kg−1 CDP850 intravenously as a single dose and four subjects (three males, one female; mean age 40 years, range 23–50) received placebo infusion Clinical response to treatment was assessed using the psoriasis area and severity index (PASI) Skin biopsies were taken for immunohistochemical analysis at the baseline, pretreatment, visit and also at day 2 and weeks 1 and 4 postinfusion Results The treatment was well-tolerated with a minimal side-effect profile Plasma E-selectin levels were significantly decreased in those subjects who received CDP850 compared with those who had placebo for the entire study period At the end of study (8 weeks postinfusion), there was no significant reduction in PASI from baseline for either the CDP850 or placebo-treated groups Immunohistochemical analysis of biopsies taken from lesional psoriatic skin showed that 2 days after dosing with CDP850, staining for E-selectin was decreased, although not absent, on dermal vascular endothelial cells when compared with baseline (P < 0·01) This decrease in E-selectin expression was maintained 4 weeks after infusion (P < 0·05) It was not, however, accompanied by a significant reduction in numbers of neutrophils or lymphocytes in the dermis There was a statistically significant increase in CD1a-positive epidermal Langerhans cells compared with pre-dose levels at week 1 (P < 0·05) Conclusions This clinicopathological study shows that anti-E-selectin (CDP850), although a well-tolerated, logical and safe therapy, does not appear to possess a therapeutic role in the treatment of chronic plaque psoriasis

A randomized control trial of the effect of negotiated telephone support on glycaemic control in young people with Type 1 diabetes.

Abstract: Aim: To evaluate changes in self-efficacy for self-management in young people with Type 1 diabetes participating in a 'Negotiated Telephone Support' (NTS) intervention developed using the principles of problem solving and social learning theory. Methods: One-year RCT with 79 young people (male 39; mean age ± sd 16.5 ± 3.2 years, duration 6.7 ± 4.4 years, HbA1c 8.6 ± 1.5%) randomized into: Group 1 (control group), continued routine management, n = 28; Group 2, continued routine management with NTS, n = 25; Group 3, annual clinic with NTS, n = 26. Outcome measures: HbA1c, self-efficacy, barriers to adherence, problem solving, and diabetes knowledge. Results: There were no differences between the groups at baseline. Participants in Groups 2 and 3 received an average of 16 telephone calls/year (range 5–19), median duration 9 min (2–30), with a median interval of 3 weeks (1–24) between calls. Significant correlations were found between age and average length of call (r = 0.44, P Conclusions: NTS is an effective medium to deliver a simple theory-based psychological intervention to enhance self-efficacy for diabetes self-management. Reduced clinic attendance, combined with NTS, did not result in a deterioration of HbA1c. Intensive personal support needs to be combined with intensive diabetes therapy to improve glycaemic control in this age group.

Experimental study of large-volume microwave ablation in the liver.

Abstract: Background: Microwave coagulation therapy is useful in the destruction of small, irresectable liver tumours of primary and secondary origin. Unfortunately, the small lesion size produced by currently available equipment makes it difficult and time consuming completely to ablate lesions larger than 3 cm in diameter. A microwave system capable of producing large-volume ablations in very short periods of time has been developed. Using a large-animal model the ability of the equipment to produce large-volume lesions in a safe, predictable and dose-dependent manner was tested. Methods: Fourteen large white pigs were anaesthetized and underwent multiple microwave treatments. The animals were killed at different timepoints to investigate lesion size and evolution. Results: The microwave system was able to generate large-volume ablations of up to 6·5 cm in diameter in a controlled and dose-dependent manner. Conclusion: This novel microwave system allows the ablation of large volumes of liver tissue in a short period of time. The ability to produce lesions reproducibly and safely highlights the potential of this system in the future treatment of irresectable liver tumours. © 2002 British Journal of Surgery Society Ltd

Matrix metalloproteinases and atherosclerotic plaque instability.

Abstract: Background: There is growing interest in the role of matrix metalloproteinases in atherosclerosis. Excessive tissue remodelling and increased matrix metalloproteinase activity have been demonstrated during atherosclerotic plaque disruption, a frequent predeterminant of ischaemic cardiac events and stroke. These enzymes represent a potential target for therapeutic intervention to modify vascular pathology. Methods: The core of this review is derived from a Medline database literature search. Results: There is convincing evidence of increased matrix metalloproteinase activity during acute plaque disruption. Evidence for an imbalance promoting increased matrix degradation is less well documented. However, studies of matrix metalloproteinase inhibition in models of vascular disease suggest a potential therapeutic benefit. Conclusion: In vivo studies of matrix metalloproteinase inhibition are required to study the potential for reversal or deceleration of the excessive tissue remodelling that accompanies acute plaque disruption. © 2002 British Journal of Surgery Society Ltd

Examination of insulin injection sites: an unexpected finding of localized amyloidosis.

Abstract: A 34-year-old man with a 17-year history of Type 1 diabetes mellitus attended an annual review clinic in December 1999 and complained of a lump on his right thigh. His diabetic control was moderate (HbA 1c 8.3%), and he displayed no long-term complications of diabetes. A firm well-defined 7-cm mass clinically distinct to adjacent areas of lipohypertrophy was found in the anterior aspect of his right thigh, an area that represented his current insulin injection site. Numerous smaller lesions of similar consistency were noted at other regular injection sites in his upper limbs and the contra-lateral thigh. No other clinical abnormalities were present and routine biochemical tests were unremarkable. Surgical excision was performed at a later date under general anaesthesia, revealing that the lesion was composed entirely of a waxy grey material. Histological examination showed the majority of the tissue to be amorphous acellular eosinophilic material possessing a mild chronic inflammatory cell infiltrate. The acellular matrix, when stained with Congo red and viewed through cross-polarized light, demonstrated the classical apple-green birefringent properties of amyloid (Fig. 1). This finding was corroborated by the appearance of non-branching fibrils on transmission electron microscopy. The association between the unusual and apparently localized soft tissue amyloid deposits and the insulin injection sites was considered and investigated further. Although parenteral drug abuse may occasionally result in reactive systemic (AA) amyloidosis by virtue of producing

Determination of gestational age after the 24th week of gestation from fetal kidney length measurements

Abstract: Objective To evaluate the application of kidney length measurement to the determination of gestational age between the 24th and 38th weeks and to compare its accuracy with that of other fetal biometric indices Study design Seventy-three women with singleton uncomplicated pregnancies underwent standard ultrasound fetal biometry and kidney length measurement every 2 weeks between 24 and 38 weeks' gestation These measurements were used to date the pregnancies relative to crown–rump length dating between 8 and 10 weeks' gestation Linear regression models for estimation of gestational age were derived from the biometric indices and kidney length In addition, stepwise regression models were constructed to determine the best model for determining gestational age between 24 and 38 weeks Comparisons were then made between the accuracy of these models in the determination of gestational age Results The best model for estimating gestational age in late pregnancy included the variables kidney length, biparietal diameter, head circumference, femur length and abdominal circumference This model accurately predicted gestational age with a standard error of ±848 days A model including kidney length, biparietal diameter, head circumference and femur length accurately predicted gestational age with a standard error of ±857 days These models were slightly more accurate than models derived from the biometric indices of biparietal diameter, head circumference and femur length (±987 days), biparietal diameter, head circumference, femur length and abdominal circumference (±945 days) and biparietal diameter and femur length (±99 days) Kidney length and femur length were the most accurate single parameters for predicting gestational age using simple linear regression models (±1029 and 1096 days, respectively); the abdominal circumference was the least accurate (±1454 days) Conclusion Kidney length is a more accurate method of determining gestational age than the fetal biometric indices of biparietal diameter, head circumference, femur length and abdominal circumference between 24 and 38 weeks' gestation When combined with biparietal diameter, head circumference and femur length, the precision of dating is improved by 2 days This measurement is easy to make and could therefore be easily incorporated into the model for dating pregnancies after 24 weeks of gestation, in particular when measurements of the biparietal diameter and head circumference are difficult Copyright © 2002 ISUOG

Effects of remifentanil and alfentanil on the cardiovascular responses to induction of anaesthesia and tracheal intubation in the elderly

Abstract: Background We compared the effects of remifentanil and alfentanil on arterial pressure and heart rate at induction of anaesthesia and tracheal intubation in 40 ASA I–III patients aged greater than 65 yr, in a randomized double-blind study. Methods Patients received either remifentanil 0.5 μg kg−1 over 30 s, followed by an infusion of 0.1 μg kg min−1 (group R) or alfentanil 10 μg kg−1 over 30 s, followed by an infusion of saline (group A). Anaesthesia was then induced with propofol, rocuronium, and 1% isoflurane with 66% nitrous oxide in oxygen. Results Systolic arterial pressure (SAP) and mean arterial pressure (MAP) decreased after the induction of anaesthesia (P Conclusions Remifentanil and alfentanil similarly attenuate the pressor response to laryngoscopy and intubation, but the incidence of hypotension confirms that both drugs should be used with caution in elderly patients.

Differential effects of cyclosporin and tacrolimus on the expression of fibrosis-associated genes in isolated glomeruli from renal transplants.

Abstract: Background Chronic allograft nephropathy is characterized by an excessive accumulation of extracellular matrix proteins leading to glomerular and interstitial fibrosis. The aim of this study was to determine the effects of two different immunosuppressive agents (cyclosporin and tacrolimus) on the expression of the genes controlling extracellular matrix deposition in renal transplant glomeruli. Methods Fifty-one renal transplant recipients were randomized to receive immunosuppression with either microemulsion cyclosporin or tacrolimus. Isolated glomeruli were plucked from protocol transplant biopsies performed 1 week, 3 months and 6 months after transplantation. Expression of the genes for collagen IVα2, collagen III, matrix metalloproteinase 2, tissue inhibitor of metalloproteinases (TIMP) 1 and TIMP-2, tenascin and transforming growth factor (TGF) β1 was studied by quantitative reverse transcriptase–polymerase chain reaction. Results The expression of messenger RNA (mRNA) for collagen III and TIMP-1 was significantly higher in patients receiving cyclosporin therapy than in those having tacrolimus (P < 0·01); this finding was accounted for by differences in the biopsy material at 1 week. A significant difference in collagen III, TIMP-1 and TIMP-2 mRNA expression was also detected between patients depending on the source of renal donor (cadaveric or living). There were no significant differences in the level of glomerular TGF-β1. Conclusion The data provide new in vivo evidence that tacrolimus may exert a less fibrogenic influence on transplant glomeruli than cyclosporin. © 2000 British Journal of Surgery Society Ltd

An investigation into the transference and survivability of human DNA following simulated manual strangulation with consideration of the problem of third party contamination

Abstract: Amplification was performed on human DNA material transferred during a model of manual strangulation. A total of 29 separate experiments were performed using a single male offender-female victim combination to observe whether DNA was transferred both from the offender's fingers to the victim's neck and vice versa and to consider the period of time after the event during which the material could potentially be recovered and amplified. DNA was amplified from either the victim's neck or the offender's fingers for at least 10 days after the contact although it is discussed whether this is potentially due to primary contact or a secondary/tertiary transfer event. The study highlights the problem of contamination of the offender's hands and victim's neck with third party DNA, the presence of which could have a significant outcome for both the investigating authority and the third party.

Hidden errors of aneroid sphygmomanometers.

Abstract: Background Measurement of blood pressure remains the most commonly performed screening test in medical practice. With the likely removal of mercury sphygmomanometers from the workplace alternative devices are required. Of these the aneroid sphygmomanometer is popular both in the community and hospital setting. We investigated the accuracy of all the aneroid and mercury sphygmomanometers during dynamic calibration within a tertiary referral maternity hospital. Methods We compared the accuracy of 39 aneroid and 36 mercury sphygmomanometers to a recently calibrated and serviced mercury sphygmomanometer (the accepted gold standard). All devices were in current clinical use. Using three blinded, trained observers, 30 different pressures were checked throughout the pressure range following British Hypertension Society protocol guidelines. Results Only 31 (86%) of the mercury devices and 36 (92%) of the aneroid devices were in adequate working condition and suitable for analysis. Significantly more aneroid devices had systematic errors of > 5 mmHg (19 versus 3%, P 10 mmHg out compared to only 10% of mercury devices (chi square programme). Conclusions Aneroid sphygmomanometers in apparent good working order are inaccurate compared to mercury devices. Some of these faults can only be detected during dynamic testing. To minimize the risk of erroneous blood pressure recording, aneroid devices should be regularly checked for accuracy using dynamic calibration methods as recommended in validation protocols.

Death certification: an audit of practice entering the 21st century

Abstract: Aims: Death certification, a legal duty of doctors, continues to be poorly performed despite Royal College recommendations and increased education at an undergraduate level. Therefore, the current performance of certifying doctors was audited within a large teaching hospital entering the new century. Methods: A total of 1000 completed certificate counterfoils were examined retrospectively for appropriateness of completion and the ability to construct a logical cause of death cascade. Results: Only 55% of certificates were completed to a minimally accepted standard, and many of these failed to provide relevant information to allow adequate ICD-10 coding. Nearly 10% were completed to a poor standard, being illogical or inappropriately completed. Conclusions: The results show no improvement in the state of certification. Possible interventions to improve outcomes are discussed; however, in light of a recent high profile legal case a current Home Office review of death certification may suggest the passing of statutory law to ensure accurate completion.

The epidemiology of influenza

Abstract: Influenza remains a globally important cause of febrile respiratory illness. Influenza virus activity in the community results in significant mortality, morbidity and economic disruption, particularly in those at high risk of developing complications, such as the elderly and those with underlying chronic medical conditions, including pulmonary disease and diabetes mellitus. The occurrence in Hong Kong in 1997 of avian influenza H5N1 in man, which resulted in six deaths, served to remind us of the importance of continuing surveillance and preparation for the next pandemic.