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PCT
Terms modified by PCT Selected AbstractsEffects of Continuous Positive Airway Pressure Therapy on Right Ventricular Function Assessment by Tissue Doppler Imaging in Patients with Obstructive Sleep Apnea SyndromeECHOCARDIOGRAPHY, Issue 10 2008Nihal Akar Bayram M.D. Objectives: The effects of continuous positive airway pressure (CPAP) therapy on right ventricular (RV) function in patients with obstructive sleep apnea syndrome (OSAS) has not been previously studied by tissue Doppler imaging (TDI). The aim of this study was to assess RV function using TDI in patients with OSAS before and after CPAP therapy. Methods: Twenty-eight patients with newly diagnosed OSAS in the absence of any confounding factors and 18 controls were included in this study. The peak systolic velocity (S,m), early (E,m) and late (A,m) diastolic myocardial peak velocities at tricuspid lateral annulus, isovolumic acceleration (IVA), myocardial precontraction time (PCT,m), myocardial contraction time (CT,m), and myocardial relaxation time (RT,m) were measured. All echocardiographic parameters were calculated 6 months after CPAP therapy. Results: The RV diastolic parameters such as E,m velocity and E,m-to-A,m ratio were significantly lower, RT,m was significantly prolonged, A,m velocity was similar in patients with OSAS compared to controls; and the RV systolic parameters such as IVA and CT,m were significantly lower and S,m was similar in patients with OSAS compared to controls. At the end of the treatment, 20 of 28 patients were compliant with CPAP therapy. E,m velocity, E,m-to-A,m ratio, IVA, and CT,m increased, PCT,m, PCT,m-to-CT,m ratio, and RT,m decreased significantly after therapy, whereas S,m velocity and A,m velocity did not change after CPAP treatment in the compliant patients. Conclusion: OSAS is associated with RV systolic and diastolic dysfunction, and 6 months of CPAP therapy improves the RV systolic and diastolic dysfunction. [source] Cationic Conjugated Polyelectrolytes with Molecular Spacers for Efficient Fluorescence Energy Transfer to Dye-Labeled DNA,ADVANCED FUNCTIONAL MATERIALS, Issue 2 2007Y. Woo Abstract Two water-soluble conjugated polyelectrolytes, poly(9,9,-bis(6- N,N,N -trimethylammoniumhexyl)fluorene- alt -1,4-(2,5-bis(6- N,N,N -trimethylammoniumhexyloxy))phenylene) tetrabromide (P1i) and poly((10,10,-bis(6- N,N,N -trimethylammoniumhexyl)-10H-spiro(anthracene-9,9,-fluorene))- alt -1,4-(2,5-bis(6- N,N,N -trimethylammoniumhexyloxy))phenylene) tetrabromide (P2i) are synthesized, characterized, and used in fluorescence resonance energy transfer (FRET) experiments with fluorescein-labeled single-stranded DNA (ssDNA-Fl). P1i and P2i have nearly identical ,-conjugated backbones, as determined by cyclic voltammetry and UV-vis spectroscopy. The main structural difference is the presence of an anthracenyl substituent, orthogonal to the main chain in each of the P2i repeat units, which increases the average interchain separation in aggregated phases. It is possible to observe emission from ssDNA-Fl via FRET upon excitation of P2i. Fluorescein is not emissive within the ssDNA-Fl/P1i electrostatic complex, suggesting Fl emission quenching through photoinduced charge transfer (PCT). We propose that the presence of the anthracenyl "molecular bumper" in P2i increases the distance between optical partners, which decreases PCT more acutely relative to FRET. [source] Autonomy and modernisation: the management of change in an English primary care trustHEALTH & SOCIAL CARE IN THE COMMUNITY, Issue 3 2004Ruth McDonald BA MSc PhD Abstract Recent New Labour policy for the ,modernisation' of Government places a good deal of emphasis on decentralisation. This emphasis is particularly marked in relation to the organisation of primary care. However, like hospitals and other National Health Service institutions, primary care trusts (PCTs) are subject to a substantial raft of centrally established performance targets and indicators, including those which contribute to the public award of between zero and three performance ,stars'. This raises questions about the extent to which employees can exercise autonomy in the context of rigid top-down directives. This paper presents findings from a study using participant observation and interviews to examine the impact of a training course aimed ostensibly at increasing employee autonomy in an English PCT. The suggestion is that attempts to make employees more autonomous can be seen as a strategy for increasing central control based upon the internalisation by the employees of centrally promulgated values. The attraction of such strategies is that they may be potentially more effective and less costly than alternative strategies of direct control. However, the study suggests that the outcome of attempts by such methods as programmes to increase employee autonomy may be very different from those intended. [source] An Incenter Nocturnal Hemodialysis Program,Three Years ExperienceHEMODIALYSIS INTERNATIONAL, Issue 1 2003M. Gene Radford We report our experience with a program of long, slow, overnight hemodialysis (HD) performed 3 times a week in an existing dialysis facility. Beginning in April 1999, 14 chairs in one bay of our facility were replaced with beds, subdued lighting was installed, and machine alarms were decreased to minimum volume. Fresenius F60 dialyzers were selected with a QB of 220,300 ml/min and a QD of 400,500 ml/min. Patients dialyze for 7,8 hrs overnight. Staffing is with 1 nurse and 1 PCT for 10 patients. Standard dialysate is used, and heparin is dosed 100 U/kg at treatment initiation and again at mid-treatment. All access types are utilized. The program is open to all patients in our area. A total of 65 patients have participated, with a current census of 20 patients. Participants have tried nocturnal dialysis for a variety of reasons including work/school schedules, excessive interdialytic weight gains, inadequate dialysis (due to poor access function or large body mass), and hemodynamic instability with standard daytime HD. Blood pressure control has improved among the participants in the program, perhaps due to more gentle ultrafiltration and improvement in maintenance of dry weight. Among 31 patients who remained on nocturnal dialysis for over 6 months, 21 started the program on an average of 2.5 antihypertensive agents (AHA). After 6 months, 9 patients no longer needed AHA while 12 patients remain on an average of 1.3 AHA. URR also improved by an average of 4.35 among 13 patients who transferred from standard incenter HD to the nocturnal program. In all, 45 patients have left the program, for reasons which include insomnia/social (15), death (9), transfer to home HD (8), renal transplantation (6), noncompliance (3), moved away (2), and other (2). In conclusion, long overnight HD can be performed in an existing dialysis facility, providing patients with another HD option. Patients who may benefit from this modality include those with daytime jobs, patients with inadequate clearance on standard HD, patients with excessive interdialytic weight gains, and those who poorly tolerate standard HD. [source] Neoplastic development in plasma cellsIMMUNOLOGICAL REVIEWS, Issue 1 2003Michael Potter Summary:, An increasing number of model systems of plasma cell tumor (PCT) formation have been and are being developed. Discussed here are six models in mice and multiple myeloma (MM) in humans. Each model illustrates a unique set of biological factors. There are two general types of model systems: those that depend upon naturally arising mutagenic changes (pristane-induced PCTs, 5TMM, and MM) and those that are associated with oncogenes (Eµ-v-abl), growth factors [interleukin-6 (IL-6)], and anti-apoptotic factors (Bcl-xL/Bcl-2). PCTs develop in several special tissue microenvironments that provide essential cytokines (IL-6) and cell,cell interactions. In mice, the activation and deregulation of c-myc by chromosomal translocations is a major feature in many of the models. This mechanism is much less a factor in MM and the 5T model in mice. Genetically determined susceptibility is involved in many of the mouse models, but only a few genes have been implicated thus far. [source] Does chloroquine therapy of porphyria cutanea tarda influence liver pathology?INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 11 2009U Wollina MD Background, Porphyria cutanea tarda (PCT) is regularly associated with changes in liver tissue. On the other hand, systematic investigations are lacking on whether there is a correlation between the severity of liver damage and chloroquine treatment. Patients and methods, During a 20-year period, liver biopsies were obtained in 89 patients with PCT confirmed by biochemical analysis of urine and feces and low-dose chloroquine therapy. Seventeen patients with alcohol-induced liver disease were excluded. In 8 of 63 patients, only a single biopsy was available. Classification of liver damage was performed according to the Riedel score. Electron microscopy was available from 24 patients. In a second group of patients, the HFE status was investigated and Berlin blue stains of liver biopsies were performed. Results, There was no correlation between the duration of cutaneous symptoms and liver pathology. After 12 months chloroquine treatment, 45 patients (81%) disclosed an improvement of liver pathology, nine (16%) had no change, and a worsening was observed in one patient (3%). All patients achieved a complete clinical and biochemical remission. In 13 of 16 patients with a relapse, there was again a deterioration of liver damage. Patients with HFE mutations had a significant higher risk (P < 0.05) for hepatic siderosis. Conclusions, The severity of liver damage was not correlated with the disease duration. Chloroquine treatment resulted in PCT remission (clinical and biochemical) and in 81% to an improvement of liver morphology. [source] Mast cells and transforming growth factor-, expression: a possible relationship in the development of porphyria cutanea tarda skin lesionsINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 6 2008Glalcyara Lançoni MD Background, Porphyria cutanea tarda (PCT) is a metabolic disease characterized by vesicles and blisters in sun-exposed areas and scleroderma-like lesions in sun-exposed and non-sun-exposed areas. Mast cells participate in the pathogenesis of bullous diseases and diseases that show sclerosis, including PCT. Moreover, transforming growth factor-, (TGF-,) is the main cytokine in the development of tissue sclerosis. The correlation of mast cells and TGF-, with the lesions of PCT has not been examined, however. The possible role of mast cells and TGF-, (and the relationship between them) in the development of PCT lesions is discussed. Methods, To quantify mast cells and cells expressing TGF-, in skin samples from patients with PCT and controls, immunohistochemical studies were performed in tissue sections allied to morphometric analyses. Results, The numbers of mast cells and cells expressing TGF-, per square millimiter were increased in the PCT group relative to controls, and there was a direct and significant correlation between the mast cell number and cells expressing TGF-, in PCT. Conclusions, The results suggest that the increased number of mast cells and of cells expressing TGF-,, as well as their direct correlation, may contribute to the pathogenesis of the skin lesions in PCT. [source] Support staff in community pharmacy: who are they and what do they want?INTERNATIONAL JOURNAL OF PHARMACY PRACTICE, Issue 2 2008Dr. Ellen I Schafheutle research fellow Objective To collect information on different categories of support staff, their deployment in community pharmacy, their levels of experience and qualifications, and their opinions on a number of topical issues, such as training and regulation. Method Two ,snapshot' surveys, one of community pharmacists, another of support staff employed by them. Three focus groups with support staff. Setting The surveys were conducted in community pharmacies in two primary care trusts (PCTs) in England. Two focus groups were conducted in one of the PCTs with respondents who had taken part in the survey; a third took place in a third PCT during the design phase. Key findings Medicines counter assistants (MCAs) formed the largest category of support staff (56%); 21% were dispensing assistants (DAs); 17% were pharmacy technicians (PTs). All community pharmacies employed at least one (60%), and often more than one MCA, but 20% had no DAs and 40% operated without a PT. Nearly all (93%) support staff were women, and about one-third worked part-time. More mature (40+ years) staff commonly only held an MCA qualification and were often not keen on further training. Younger staff held higher qualifications and were interested in further training and career progression. The majority of all categories of staff showed high levels of job satisfaction and loyalty to their employer. Most held positive views towards the regulation of support staff. Poor salaries were identified as potential barriers to further training and regulation, and pharmacists identified problems recruiting support staff. Conclusion Many different categories of support staff are employed in community pharmacies, although some operated without DAs or a PT. Support staff were generally satisfied with their jobs, but increasing requirements for formal qualifications and regulation of support staff, if not accompanied by adequate recognition and remuneration, may worsen recruitment problems. [source] Subacute cutaneous lupus erythematosus with bullae associated with porphyria cutanea tardaJOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, Issue 3 2007Wiebke K. Peitsch Summary A 58-year-old patient presented with both annular and polycyclic as well as vesicular lesions. Histology revealed an interface dermatitis with focal hyperkeratosis and subepidermal blistering. Antinuclear antibodies were elevated (1 : 1280) and autoantibodies against Ro-SS-A were found. Based on these findings we made a diagnosis of subacute cutaneous lupus erythematosus (SCLE) with blister formation. Additionally, we diagnosed porphyria cutanea tarda (PCT) triggered by alcohol abuse. Treatment with systemic corti-costeroids and low-dose hydroxy-chloroquine led to rapid resolution of the skin changes. SCLE with blister formation is a rare cause of bullous skin eruptions and has to be distinguished from bullous autoimmune diseases as well as from bullous SLE. Recognition of concomitant PCT, which may be associated with all forms of LE, is especially important because of the therapeutic implications, since a reduced dosage of antimalarials is required. [source] A Power-Control Theory of Gender and ReligiosityJOURNAL FOR THE SCIENTIFIC STUDY OF RELIGION, Issue 2 2009Jessica L. Collett The fact that women are more religious than men is one of the most consistent findings in the sociology of religion. Miller and Stark (2002) propose that a gender difference in risk preference of physiological origin might explain this phenomenon. While acknowledging the utility of their risk-preference mechanism, we believe that their assumption regarding the genesis of this difference is a premature concession to biology. Returning to Miller's original paper on gender, risk, and religiosity, we draw on power-control theory (PCT), developed in the work of John Hagan and colleagues, to introduce a plausible socialization account for these differences. We evaluate these claims using data from the General Social Survey. Women raised by high-socioeconomic status (SES) mothers are less religious than women raised by low-education mothers, but mother's SES has little effect on men's chances of being irreligious and father's SES has a negligible effect on the gender difference in religiosity. [source] Modulation of the inflammatory response to cardiopulmonary bypass by dopexamine and epidural anesthesiaACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 10 2002F. Bach Background: Cardiopulmonary bypass (CPB) induces a systemic inflammatory reaction. Microcirculation-dependent alteration of the gut mucosal barrier with subsequent translocation of endotoxins is a postulated mechanism for this inflammatory response. This study was designed to elucidate whether two different approaches to modulate splanchnic perfusion may influence systemic inflammation to CPB. Methods: We examined 40 patients scheduled for elective coronary bypass surgery in a prospective, randomized study. One group (DPX) received dopexamine (1 µg · kg,1 · min,1) continuously after induction of anesthesia until 18 h after CPB. The control group (CON) received equal volumes of NaCl 0.9% in a time-matched fashion. In a third group (EPI) a continuous epidural infusion of bupivacaine 0.25% [(body height (cm) , 100) · 10,1=ml·h,1] was administered for the whole study period. Procalcitonin (PCT), tumor necrosis factor (TNF-,), soluble TNF receptor, human soluble intercellular adhesion molecule-1, C-reactive protein (CRP) and leukocyte count were measured as parameters of inflammation. Results: All parameters significantly increased following CPB. Increases of PCT, TNF-, and leukocyte count were significantly attenuated in the DPX and EPI groups at different time points. However, neither splanchnic blood flow nor oxygen delivery and consumption were different when compared with the CON-group. Conclusion: These results do suggest that mechanisms other than an improved splanchnic blood flow by DPX and EPI treatment have to be considered for the anti-inflammatory effects. [source] Determination of corneal volume from anterior topography and topographic pachymetry: application to healthy and keratoconic eyesOPHTHALMIC AND PHYSIOLOGICAL OPTICS, Issue 6 2009Alejandro Cerviño Abstract Purpose:, To describe a method to measure corneal volume from topography and pachymetry, and test its clinical use on a sample of healthy human subjects and a case of circumscribed posterior keratoconus. Methods:, Corneal curvature (PCT 200® corneal topography system; Optopol Technology SA, Zawiercie, Poland) and ultrasonic topographic pachometry on 25 points (Ophthasonic® A-Scan/Pachometer III; Teknar Inc., St Louis, MO, USA) were measured on each of 12 young healthy corneas and one cornea suffering from circumscribed posterior keratoconus. Topography and pachymetry data were used to calculate the coordinates for the corresponding points on the posterior surface of the cornea. TableCurve 3D software (Systat Software Inc., Chicago, IL, USA) was used to fit a surface to those points measured. Integration of the surface fitted to the data points, corresponding to the anterior and posterior corneal surfaces, was used to calculate the volume underneath each of them. Subtraction of volumes underneath anterior and posterior surfaces, taking into account an axial offset equal to the central corneal thickness, rendered corneal volume for the central 6 mm of the cornea. Results:, Central corneal thickness ranged from 520 to 630 ,m for the healthy corneas. Corneal volumes for this sample analyzed averaged 18.66 ± 1.15 mm3 (range 17.25,20.53 mm3). For the posterior keratoconic cornea, the affected area was located at about 1.5,2 mm from the corneal center on the 135° hemimeridian of the right eye, observed through topographic pachymetry. Calculated corneal volume for the central 6 mm was 16.072 mm3, noticeably lower than those found in the sample without pathology, but within the range for corneas presenting with keratoconus. Conclusions:, Corneal volume is a useful parameter for characterising dystrophic corneas and can aid in the detection of rare anomalies which are hardly detected with corneal topography and/or central corneal thickness evaluation. A potentially useful measure of corneal volume can be calculated from anterior corneal topography and topographic pachymetry data. Values obtained are in good agreement with previous studies using corneal tomography techniques. The methodology has been shown to have potential for retrospective analysis of data, or where no access is available to tomographical techniques. [source] Brain competition policy as a new paradigm of regional policy: A European perspectivePAPERS IN REGIONAL SCIENCE, Issue 2 2010Christian Reiner Brain competition policy; human capital; innovation; Europe Abstract The emerging knowledge economy has led to an increase of demand and locational competition for highly-skilled labour. Brain competition policy (BCP) is the reaction from national and regional policymakers. In short, BCP refers to the attraction, education and circulation of talent in and between regional and national economies. This new focus on human capital instead of physical capital indicates a paradigmatic shift in innovation policy and regional policy. While most of the contributions to this new policy approach come from the US, it can be demonstrated that different institutions in Europe prevent the simple copying of those strategies. The article contributes to the ongoing paradigmatic shift by conceptualizing a coherent framework for BCP from a European perspective. Abstract La emergente economía del conocimiento ha llevado a un aumento de la demanda y competencia en localización de mano de obra altamente especializada. Las políticas de competencia por talento (PCT) son la reacción nacional y regional de formuladores de políticas. En resumen, PCT se refiere a la atracción, educación y circulación de talento dentro de, y entre, economías regionales y nacionales. Este nuevo enfoque en cuanto a capital humano en lugar de capital físico indica un cambio paradigmático en políticas innovadoras y políticas regionales. Aunque la mayoría de aportes a este nuevo enfoque de políticas proviene de los EE.UU., se puede demostrar que las diferentes instituciones europeas impiden el copiar simplemente dichas estrategias. El artículo contribuye al cambio paradigmático continuo mediante la conceptualización de un marco coherente para PCT desde una perspectiva europea. [source] Overexpression of p53 protein and MDM2 in papillary carcinomas of the thyroid: Correlations with clinicopathologic featuresPATHOLOGY INTERNATIONAL, Issue 1 2001Satoshi Horie Expression of p53 protein and MDM2 was evaluated in paraffin-embedded tissue from 78 patients with papillary carcinomas of the thyroid (PCT), in order to elucidate the relationship between them and their correlations with some clinicopathologic features implicated in tumor progression. These proteins were expressed in nuclei of tumor cells, but not in non-tumor cells. Staining was defined as positive when 10% or more of tumor cells expressed these proteins. The number of cases positive for p53 protein was 21/78 (27%), and that positive for MDM2 was 26/78 (33%). Co-overexpression of p53 protein and MDM2 was observed in 12/78 cases (15%). A significant positive relationship was found between them (P < 0.01); p53-positive cases tended to be also positive for MDM2 and vice versa. Statistical analysis revealed that overexpression of p53 protein significantly correlated with large tumor size (P = 0.0271) and the presence of capsular invasion (P = 0.04). There were significant positive correlations between tumor size and intrathyroidal invasion and between tumor size and capsular invasion in PCT, suggesting that p53 protein overexpression is associated only with tumor progression (tumor size). However, we could not find any significant correlations between MDM2 expression and clinicopathologic features. Our findings suggest that overexpression of p53 protein and MDM2 in papillary carcinoma of the thyroid is associated with the progression of the tumors, and that p53 may be a marker of the progression of PCT. [source] Is procalcitonin useful to differentiate rejection from bacterial infection in the early post-operative period of liver transplantation in children?PEDIATRIC TRANSPLANTATION, Issue 8 2009Maria Cecília Mendonça Coelho Previous studies performed in adults who underwent liver or heart transplantation indicated that PCT plasmatic levels help to differentiate between rejection and infection. The objective of this study was to evaluate whether PCT has the same role in liver-transplanted children. Thirty-six patients were studied between the first and the thirtieth post-operative days, and PCT determinations were prospectively performed according to the clinical status of the patient. In the non-complicated patients, PCT measurements performed on the first and second post-operative days revealed a median value of 1.60 ng/mL (mean 5.68 ± 7.05; range 0.69,18.30). After the fourth day of transplantation, PCT plasma concentrations decreased to a median value of 0.21 ng/mL (mean 0.47 ± 0.59; range 0.05,2.00; normal values are less than 0.5 ng/mL). In infected patients, PCT plasma levels demonstrated a significant increase, differing from the patients with acute liver rejection whose levels were similar to those of non-complicated patients. In conclusion, we could demonstrate that in the early post-operative period of liver transplantation in children, measuring PCT plasmatic levels might be a useful tool for differentiation between bacterial infection and acute liver rejection. [source] Supramolecular selectivity of poly(ethylene oxide) in semi-crystalline polymer nanocompositesPOLYMER INTERNATIONAL, Issue 12 2007Li Zhou Abstract Semi-crystalline polymer nanocomposites were prepared using successive meltings and recrystallizations techniques by intercalation of small guest molecules such as 4-chlorotoluene (PCT), 4-bromotoluene (PBT) and 1,4-dibromobenzene (PDBB) into poly(ethylene oxide) (PEO) crystals. Differential scanning calorimetry, Fourier transform infrared spectroscopy and wide-angle X-ray diffraction experimental results show that supramolecular selectivity exists for the PEO,PDBB/PBT ternary system, while there is no supramolecular selectivity for PEO,PCT/PBT ternary nanocomposites. The interactions between PEO chains and small guest molecules have an important influence on the polymer conformation, which results in the dramatic difference in intercalation behavior. Copyright © 2007 Society of Chemical Industry [source] Specials: a financial warning!PRESCRIBER, Issue 19 2008Leslie Klein MSc, MB ChB An analysis of specials prescribing in one PCT found the average cost to be £102, with prices reaching over £2000. The authors suggest how the expense of prescribing specials can be kept to a minimum. Copyright © 2008 Wiley Interface Ltd [source] Latest news and product developmentsPRESCRIBER, Issue 6 2008Article first published online: 24 APR 200 Government responds to NICE report The Government has published its response to the Health Select Committee's report into NICE, broadly arguing that the Committee's recommendations are either already being dealt with or are not appropriate. The Committee recommended appraisals for all new drugs, shorter, rapid appraisals to coincide with their launch, and improved mechanisms for setting drug prices. The Government says its negotiations on the PPRS preclude a detailed response but suggests a rapid system may not be transparent or legally robust. It is exploring how high-cost drugs can be brought within the payment-by-results tariff. While defending NICE's reliance on QALYs, the Government accepts the need to explore how wider economic factors can be considered. As for the threshold cost per QALY by which NICE defines cost effectiveness, it says this is being validated scientifically and NICE will continue to determine the threshold. More topically, the Committee criticised the quality of clinical trial data available to NICE. The Government sees no need to compel pharmaceutical companies to disclose information and says NICE is already becoming more involved with research programmes. All clinical trials must be registered (confidentially) with the EU and the Government believes mandatory registration in the UK would be ineffective and illegal. Prescription charge up again from April The Government has raised the prescription charge by 25p to £7.10 per item with effect from 1 April. Prescription prepayment certificates will cost £27.85 for three months and £102.50 for 12 months. The increase, below the annual rate of inflation for the 10th successive year, will be levied on the 12 per cent of prescriptions that are liable for the charge: 5 per cent via prepayment certificates and 7 per cent from other prescriptions. The charge will generate £435 million in England in 2008/09; this excludes money from prescriptions written by dispensing doctors, which is retained by the PCT. Following criticism of the charge by the Health Select Committee, the Government says it has reviewed the charge and is now consulting on ,cost-neutral' options. MHRA safety update The MHRA warns of possible dose errors associated with Boots Medisure Domiciliary Dosage System in its latest issue of Drug Safety Update (2008;1:issue 8). One case has been reported in which incomplete sealing allowed tablets to mix between compartments. No other cases are known and the MHRA says no harm was reported but the risk is serious. The system should be carefully sealed and inspected visually and physically. The MHRA reaffirms its plans to reclassify all pseudoephedrine and ephedrine products to prescription-only status in 2009 if the new restrictions on sales do not reduce misuse. Other topics in this month's Update include revised indications for oral ketoconazole (Nizoral), restricting its use to selected conditions unresponsive to topical therapy; reformulation of the injectable antibiotic Tazocin (piperacillin plus tazobactum); the risk of peripheral neuropathy associated with pegylated interferon and telbivudine (Sebivo) in the treatment of hepatitis B; and serious adverse events associated with modafinil (Provigil). First oral anticoagulant since warfarin In January this year the EMEA issued a positive opinion to recommend marketing authorisation of the oral, fixed-dose, direct thrombin inhibitor dabigatran etexilate (Pradaxa) for the primary prevention of venous thromboembolism (VTE) in adult patients that have undergone elective knee or hip replacement surgery. Marketing authorisation for the EU (including the UK) is expected from the European Commission in the next few weeks, making dabigatran the first oral anticoagulant since warfarin was introduced in 1954. Dabigatran etexilate has been shown to be as safe and effective as enoxaparin (Clexane) with a similar adverse event profile in the noninferiority phase III RENOVATE (Lancet 2007;370: 949-56) and RE-MODEL (J Throm Haemost 2007;5:217885) trials, which investigated the efficacy and safety of dabigatran compared to enoxaparin in reducing the risk of VTE after total hip and knee surgery respectively. Dabigatran has the practical advantage over low-molecular-weight heparin of oral postoperative administration and no risk of heparin-induced thrombocytopenia and, unlike warfarin, does not require monitoring or dose titration. Risk scale predicts anticholinergic effects US investigators have developed a scale for predicting the risk of anticholinergic side-effects from older patients' medicines (Arch Intern Med 2008;168: 508-13). The scale assigns a score from 1 (low) to 3 (high) for the risk of anticholinergic effects such as dry mouth, constipation and dizziness associated with commonly prescribed medicines. Checking the scale retrospectively in older patients in residential care, a higher score was associated with a 30 per cent increased risk of side-effects after adjustment for age and number of medicines. When this was repeated prospectively in a primary-care cohort, the increased risk was 90 per cent. HRT cancer risk persists The latest analysis of the Women's Health Initiative (WHI) trial of HRT shows that the small increase in the risk of cancer persists for up to three years after stopping treatment (J Am Med Assoc 2008;299:1036-45). WHI was stopped after 5.6 years' follow-up when it became clear the risks of HRT outweighed its benefits. This follow-up after a further three years (mean 2.4) involved 15 730 women. The annual risk of cardiovascular events was similar for HRT (1.97 per cent) and placebo (1.91 per cent). Cancers were more common among women who had taken HRT (1.56 vs 1.26 per cent), in particular breast cancer (0.42 vs 0.33 per cent). All-cause mortality was higher, but not statistically significantly so, with HRT (1.20 vs 1.06 per cent). Tight glycaemic control may increase falls Maintaining HbA1C at or below 6 per cent with insulin is associated with an increased risk of falls, a US study suggests (Diabetes Care 2008;31:391-6). The Health, Aging and Composition study involved 446 older people with type 2 diabetes (mean age 74) followed up for approximately five years. The incidence of falls ranged from 22 to 30 per cent annually. Comparing subgroups with HbA1C of ,6 per cent and >8 per cent, an increased risk of falls was associated with insulin use (odds ratio 4.4) but not oral hypoglycaemic drugs. Copyright © 2008 Wiley Interface Ltd [source] Latest news and product developmentsPRESCRIBER, Issue 2 2008Article first published online: 11 FEB 200 NICE should evaluate all new medicines NICE should determine the cost effectiveness of all new medicines, the Health Select Committee has concluded in its second review of the Institute. The review, prompted by criticisms from patients, health professionals and the pharmaceutical industry, found that NICE is doing ,a vital job in difficult circumstances'. The Committee called for the costs to carers and society to be included in cost effectiveness estimates (this is currently prohibited) and for cost per QALY thresholds to be aligned with NHS affordability. NICE should publish brief appraisals at the time of a product launch , these could be used to negotiate prices. GPs responsible for unlicensed co-proxamol GPs who prescribe co-proxamol are now responsible for the consequences, the MHRA warns. The Agency agrees that the drug may be needed by ,a small group of patients who are likely to find it very difficult to change from co-proxamol or where alternatives appear not to be effective or suitable'. Following the withdrawal of product licences, stock that is currently in the supply chain may be dispensed but no new stock should be released by suppliers. The Drug Tariff price of co-proxamol has now increased from £2.79 to £20.36 per 100 tablets. Vitamin D deficiency on the increase Pregnant and breastfeeding women may need vitamin D supplements, the Department of Health has warned, and GPs are seeing increasing numbers of patients with vitamin D deficiency. Endogenous synthesis may be low in some ethnic groups and dark-skinned people, and north of Birmingham there is no light of the appropriate wavelength for the synthesis of vitamin D during the winter. The Department says free vitamin supplements are available for eligible patients through its Healthy Start Scheme (www.healthystart.nhs.uk) and may also be supplied at low cost by some PCTs. Innovation and good practice recognised Innovative practice and better outcomes for patients have been recognised through awards from the NHS Alliance and Improvement Foundation presented by the Secretary of State for Health, Rt Hon Alan Johnson, at the annual NHS Alliance conference held in Manchester. The Mountwood Surgery in Northwood, Middlesex, won the CHD QOF GP Practice Award sponsored by Schering Plough for their outstanding multidisciplinary approach to tackling CHD. In addition to having a highly organised in-house cardiology team, they have produced an interactive, patient-empowering booklet for CHD. Mountwood Surgery achieved blood pressure targets of 96.79 per cent in their CHD patients. North Tees PCT wins the CHD QOF PCO Award, also sponsored by Schering Plough, for their support and encouragement to GP practices to ,own' CHD care. They provide timely feedback of performance data using funnel plots and regular communication by the CHD LIT and Cardiac Network. Even though North Tees PCT has a high CHD prevalence, 4.2 per cent vs 3.6 per cent nationally, across the 27 practices 85 per cent of patients achieved cholesterol targets and 91 per cent reached the QOF blood pressure target. The St Benedict's Hospice Day Centre Project (for the Sunderland Teaching Primary Care Trust) won the Guy Rotherham Award for its excellent multidisciplinary team improvement of the palliative care provided. This team demonstrated a thorough understanding of the use of quality improvement methods to improve patient care, and carefully measured the individual improvements they made. Through the use of a referral ,decision tree', nonattenders were reduced by 300 per cent and average waiting times halved. The Extended Primary Care (EPC) Gynaecology Service (for the Practice Based Commissioning Consortium South Manchester Hub) was highly commended for its development of an effective and innovative service offering gynaecological treatment managed within a primary care setting, allowing patients improved access closer to home. The Salford Perinatal Mental Health Project was also highly commended for effectively challenging the high levels of maternal suicides. The awards were also supported by Prescriber, the British Cardiac Patients Association and the British Cardiac Society. Anastrozole superior to tamoxifen in long term A new analysis of the ATAC trial (Lancet Oncology 2008;9:45-53) shows that the advantages of the aromatase inhibitor anastrozole (Arimidex) over tamoxifen as adjuvant therapy for breast cancer persist for at least four years after the end of treatment. After primary treatment with surgery, chemotherapy or radiotherapy, postmenopausal women with localised invasive breast cancer were randomised to five years' treatment with anastrozole or tamoxifen. Among 5216 women who were hormone-receptor positive, anastrozole increased disease-free survival by 15 per cent after 100 months. Time to recurrence and distant recurrence were also increased, though overall survival was similar; the absolute difference in time to recurrence was greater at nine years (4.8 per cent) than at five years (2.8 per cent). Joint symptoms and fractures were more frequent with anastrozole during treatment but not thereafter. Use a steroid with a LABA , MHRA reminder The MHRA has reminded clinicians that patients treated with an inhaled long-acting beta-agonist (LABA) should also use an inhaled steroid. In the latest edition of Drug Safety Update (2008;1:No.6), the Agency reviews the implications of the SMART study (Chest 2006;129:15-26), which reported an increased risk of respiratory- and asthma-related deaths among patients using salmeterol (Serevent). This is contradicted by epidemiological data suggesting that asthma-related admissions have declined since LABAs were introduced. Randomised trials also do not support such a risk, probably because inhaled steroids are used more consistently in trial settings. The latest Update notes that product licences for carisoprodol (Carisoma) have been suspended due to concerns about the risk of abuse and psychomotor effects. It also includes a comprehensive summary of drug interactions with statins, a warning that methylene blue should not be prescribed for a patient taking a drug with serotonergic activity, and a reminder that only oral formulations of desmopressin are now licensed for primary nocturnal enuresis. This issue of Update is available at www.mhra.gov.uk. Copyright © 2008 Wiley Interface Ltd [source] Nonmedical prescribing: managing patients with respiratory diseasePRESCRIBER, Issue 13 2007DipPresSci, Keith Pearson MA, MRPharmS Our series Nonmedical prescribing gives an overview of the work that can be done by nonmedical prescribers and what can be achieved. Here Keith Pearson, a supplementary prescriber for Salford PCT, describes his roles within local GP practices. Copyright © 2007 Wiley Interface Ltd [source] Latest news and product developmentsPRESCRIBER, Issue 12 2007Article first published online: 4 OCT 200 NAO: GPs still not prescribing efficiently The National Audit Office (NAO) says NHS funds are being wasted through inefficient GP prescribing and patients not taking their medicines. The NAO's long-awaited report, Prescribing Costs in Primary Care (www.nao.org.uk), found large variations between PCTs in generic prescribing of statins, ACE inhibitors and angiotensin-II antagonists, and protonpump inhibitors; PCTs were also paying widely differing prices for these products. There was a five-fold variation in prescribing volume for clopidogrel between PCTs. These four drugs accounted for only 19 per cent of total spending but, if all practices matched the performance of the best 25 per cent, the NHS would save £200 million annually. PCTs should do more to rationalise prescribing and support their GPs, the NAO concludes. The NAO says that the cost of medicines dispensed for but not taken by patients lies somewhere in the range £100-£800 million annually. Strategies to reduce waste include public awareness campaigns and restricting supplies to four weeks (or two weeks for new medicines). Rosiglitazone may increase CV death risk A meta-analysis of 42 clinical trials has suggested that rosiglitazone is associated with increased risks of myocardial infarction (MI) and cardiovascular death (N Engl J Med 2007; published online 21 May: doi 10.1056/ NEJMoa072761). Like the COX-2 inhibitors, rosiglitazone was licensed without determining its possible effects on long-term cardiovascular outcomes, and interpretation of the latest findings is complicated by the multiple comparisons involved. For risk of MI, there was no significant difference between rosiglitazone and placebo (though this was of borderline statistical signifi-cance , p=0.07), metformin, sulphonylureas or insulin. Rosiglitazone was associated with a statistically significant 43 per cent increased risk compared with all comparators combined but the absolute increase in risk was very small (0.02 per cent). The trends were similar for risk of cardiovascular death, though rosiglitazone was associated with a 64 per cent increased risk compared with all comparators combined that was of borderline statistical significance (p=0.06). The authors acknowledge that their analysis pooled short-term studies that excluded patients at risk of heart disease and was not designed to determine cardiovascular outcomes, and they had no access to patientlevel data; as a result, there is uncertainty about their findings. Nevertheless, they say there is now an urgent need to clarify the risk associated with rosiglitazone. GlaxoSmithKline has rebutted the findings, stating that the cardiovascular risk profile of rosiglitazone is comparable with that of other oral antidiabetic drugs. The MHRA says warnings in the current SPCs for Avandia and Avandamet already reflect most of the data in the latest US review. The possible effects of rosiglitazone on cardiovascular events is currently being evaluated in the Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of glycaemia in Diabetes (RECORD) study. Good management tool The Department of Health has published a disease management tool to enable PCTs to model local interventions that could reduce emergency admissions. The web-based ,voluntary good practice tool' will demonstrate how interventions in primary care and social care settings can improve the management of long-term conditions including cardiovascular disease, asthma and COPD, and dementia and depression. Counterfeit medicines The MHRA has issued an unprecedented three alerts about fake medicines in the legitimate supply chain, recalling all affected lot numbers. Three batches of Zyprexa 10mg tablets (olanzapine) were withdrawn after a company printing labels became suspicious and alerted Eli Lilly. Two of the batches, which contained 60 per cent of the stated active ingredient, had reached patients but no adverse events were reported. Two lots of parallel-imported Plavix 75mg tablets (clopidogrel) have been withdrawn after counterfeit packs were identified. The lots were in French original packaging but will have been overlabelled for the UK market. The counterfeits were mixed with genuine packs from Sanofi-Aventis. Fake Casodex 50mg tablets (bicalutamide) have been identified in a parallel import from France. The Royal Pharmaceutical Society reports that the fake contains 75 per cent of the stated dose of bicalutamide. Alcohol-free mometasone Schering-plough has introduced an alcohol-free formulation of mometasone furoate nasal spray (Nasonex) for hay fever. The company says that an alcohol vehicle causes nasal irritation and leaves an unpleasant aftertaste, adding that over 40 per cent of patients cite this as the main reason for stopping treatment, and over 50 per cent state a preference for an alcohol-free product. Aid to improve statin adherence Adherence to statin therapy can be improved if patients use a decision aid when they are offered treatment,US investigators say (Arch Intern Med 2007;167:1076-82). The decision aid estimated the individual's 10-year cardiovascular risk and the risk reduction from treatment, and summarised the disadvantages of statins.Patients with diabetes who used the aid knew more about their risk and were less indecisive about treatment than those who did not. The odds of having missed a dose over three months were three times higher for patients who had not used the aid. Online tool calculates switch savings A new online tool can help GPs estimate the savings achievable from switching patients to cheaper medicines. The Switch Saving Calculator, developed by the Prescribing Analysis & Support Team at the NHS Regional Drug and Therapeutics Centre in Newcastle, calculates potential savings based on past, current or projected use of the target drug. It can be applied to individual prescribers or scaled up to practice, commissioning group, PCT, health authority or even national level. Separate calculators are available for primary and secondary care. The current version calculates potential savings by switching from atorvastatin to simvastatin. The Newcastle team says other drugs will be added and they will update prices regularly. The calculator is at www.nyrdtc.nhs.uk:80/Services/presc_supp/ switch_saving_calculator/switch_saving_calculator.html. No improvement in drug information for patients leaving hospital The information given to patients discharged from hospital is not improving, according to the Healthcare Commission's annual patient survey (www.healthcare commission.org.uk). The 2006 survey found that the commonest reason patients were kept waiting for at least four hours to leave hospital was the delay in providing discharge medicines. Provision of written information increased from 62 per cent of patients in 2005 to 65 per cent in 2006. However, only 76 per cent said they had been told about their medicines in a way they could ,completely' understand (79 per cent in 2002). The proportion of patients reporting complete information about sideeffects also fell (from 40 per cent in 2005 to 37 per cent). Aspirin in preeclampsia A new meta-analysis has found that primary prevention with low-dose aspirin modestly but consistently reduces the risk of preeclampsia (Lancet 2007; published online 18 May). The study of 31 trials involving 32 217 women at low to moderate risk found that antiplatelet agents (mostly aspirin) reduced the risk of pre-eclampsia and preterm birth by 10 per cent without an increased risk of bleeding. The benefit was similar across subgroups. There were also nonsignificant reductions in the risk of small for age, stillborn and death before discharge. New from NICE NICE approves varenicline for NHS NICE has endorsed the use of varenicline (Champix) as an aid to smoking cessation within the NHS for England and Wales; it has already been approved for use in Scotland by the Scottish Medicines Consortium. Varenicline is a partial agonist at the ,4,2 nicotinic receptor. It alleviates craving and withdrawal symptoms, and reduces the rewarding and reinforcing effects of smoking. The commonest adverse effect is mild to moderate nausea, which improves with time.1 Varenicline is licensed for smoking cessation in adults; NICE says it should be offered as an option for smokers who say they want to quit as part of a programme of behavioural support. However, treatment should not be withheld if counselling and support are not available. NICE was critical of manufacturer Pfizer's economic arguments in favour of varenicline, which inappropriately included US data, assumed a single quit attempt and may have overestimated its efficacy. It nonetheless concluded that varenicline is more effective than nicotine replacement therapy (NRT) or bupropion (Zyban) in achieving continuous abstinence. NICE estimated that, compared with NRT, the odds of abstinence at one year with varenicline were 54 per cent greater. A Cochrane review1 concluded that abstinence was 66 per cent more likely with varenicline than with bupropion, and three times more likely than with placebo. There was also a benefit from offering smokers a wider choice of treatments. A 12-week course of varenicline costs £163.80; it is also licensed for an additional 12-week course and dose tapering may be considered for those at high risk of relapse. The final appraisal determination does not state which is the treatment of first choice for smoking cessation. NICE is currently preparing guidance on smoking cessation in pri-mary care, pharmacies and workplaces. Copyright © 2007 Wiley Interface Ltd [source] Latest news and product developmentsPRESCRIBER, Issue 3 2007Article first published online: 14 MAR 200 PPIs and hip fracture Treatment with a PPI may increase the risk of hip fracture, with longer use associated with higher risk according to a study in UK patients (J Am Med Assoc 2006;297:2947-53). The case control study compared use of PPIs by 13 556 patients with hip fracture and 135 386 controls in the UK General Practice Research Database. Use of a PPI for more than one year was associated with an increase of 44 per cent in the odds of hip fracture. The risk was higher for longer- term use (59 per cent after four years) and at higher doses (more than doubled with long-term high doses). The mechanism for this possible effect may be impaired calcium absorption associated with hypochlorhydria and reduced bone resorption. CHD NSF Statin prescribing has increased by 30 per cent every year since the publication of the Coronary Heart Disease NSF, the Department of Health says. The estimated number of lives saved attributable to statins had risen to 9700 in 2005. The proportion of patients with acute MI who were given thrombolysis within 30 minutes of admission has increased to 83 per cent. Flu jabs cut pneumonia deaths A US study suggests that flu vaccine protects against death during the flu season in patients admitted with community-acquired pneumonia (Arch Intern Med 2007;167:53-9). Nineteen per cent of patients admitted with pneumonia during the winters of 1999-2003 were known to have been vaccinated against flu. Their risk of death during their hospital stay was 70 per cent lower than that of nonvaccinated individuals. After adjustment for antipneumococcal vaccination and comorbidity, the odds of death were still 39 per cent lower. Model to predict admissions The King's Fund, together with New York University and Health Dialog, has published a model that predicts the risk of emergency hospital admission (see www.kingsfund.org.uk). The model is intended for use by PCTs and draws on data from secondary and primary care to define clinical profiles, allowing patients whose condition is deteriorating to be identified before they need admission. Problem drinking The National Treatment Agency for Substance Misuse (NTA), a special authority within the NHS, has published a critical appraisal of the evidence for various treatments for alcohol problems (www.nta.nhs.uk). The 212-page document estimates that over seven million hazardous or harmful drinkers may benefit from brief interventions by any health workers, and over one million dependent drinkers may benefit from specialist intervention. It concludes that cognitive behavioural approaches to specialist treatment are most effective and that treatment probably accounts for about one-third of improvements made in problem drinking. of patients remained on the same treatment after one year, falling to half at two years and about 40 per cent at three years. Treatment was more frequently stopped for lack of efficacy than for adverse effects. Stopping anti-TNFs Discontinuation of treatment with anti-TNF agents is more common in clinical practice than in clinical trial populations, a French study has found (J Rheumatol 2006;33:2372-5). The retrospective analysis of a single centre's experience of treating 770 patients with etanercept (Enbrel), infliximab (Remicade) or adalimumab (Humira) found that fewer than two-thirds of patients remained on the same treatment after one year, falling to half at two years and about 40 per cent at three years. Treatment was more frequently stopped for lack of efficacy than for adverse effects. There were no statistically significant differences between the three agents but there was a trend for infliximab to be least well tolerated. Generic statin savings The Department of Health has estimated that prescribing simvastatin and pravastatin generically would save £85 million per year. Its analysis of the ,Better care, better value' indicators (see www.productivity.nhs.uk) shows that statin prescribing has increased by 150 per cent in the past five years, with costs totalling £600 million in 2005. The Department says that if every PCT prescribed pravastatin and simvastatin by generic name in only 69 per cent of cases ,the level achieved by the top quarter of trusts ,the savings would be over £85 million a year. Herceptin reporting Press reports of a two-year trial of trastuzumab (Herceptin) were generally accurate in reporting its effectiveness but few reported an increased risk of adverse effects, according to the NHS National Library for Health (www.library.nhs.uk). The Herceptin Adjuvant (HERA) trial (Lancet 2007;369:29-36) found that, after an average follow-up of two years, 3 per cent of women treated with trastuzumab died compared with 5 per cent of controls; estimated three-year survival rates were 92.4 and 89.7 per cent respectively. All four press articles reported these findings accurately, but only two mentioned the increased risk of adverse effects. Updated guidance on CDs The Department of Health has published updated guidance on the strengthened governance requirements for managing controlled drugs, taking into account new regulations that came into force on 1 January (seewww.dh.gov.uk/asset Root/04/14/16/67/04141667.pdf). Statin adherence lowers MI mortality Patients with acute myocar- dial infarction (MI) who take their statins as prescribed are significantly more likely to survive for two to three years than those with low adherence (J Am Med Assoc 2007;297: 177-86). The four-year observational study of 31 455 patients with acute MI found that, compared with those who had taken at least 80 per cent of prescribed daily doses, the risk of death in those with less than 40 per cent adherence was 25 per cent greater over 2.4 years. For individuals with intermediate adherence (40-79 per cent), the risk was 12 per cent greater. Both differences were statistically significant after adjustment for potential confounding factors. The authors believe their finding is explained by differences in adherence rather than healthier behaviour because the excess risk of low adherence was less marked with beta-blockers and not significant for calcium-channel blockers. Improving community medicines management Mental health trusts need to improve medicines management by their community teams and improve information sharing with GPs, the Healthcare Commission has found (www.healthcare commission.org.uk). Its national report revealed limited evidence of pharmacist involvement in community mental health teams, even though 90 per cent of patients were cared for in the community. Only 11 per cent of assertive outreach patients had the tests necessary to ensure safe use of their medicines. Medication reviews found that 46 per cent of patients in mental health trusts and 12 per cent of those in acute trusts were not taking their medication appropriately. The Commission also reported that acute trusts received a complete drug history from GPs for fewer than half of audited patients when they were admitted to hospital, and only 30 per cent of PCTs reported that GPs received adequate information on patients' medicines on discharge. Copyright © 2007 Wiley Interface Ltd [source] Prediction of partial membrane protein topologies using a consensus approachPROTEIN SCIENCE, Issue 12 2002Johan Nilsson PCT, partial consensus topology; TMH, transmembrane helix Abstract We have developed a method to reliably identify partial membrane protein topologies using the consensus of five topology prediction methods. When evaluated on a test set of experimentally characterized proteins, we find that approximately 90% of the partial consensus topologies are correctly predicted in membrane proteins from prokaryotic as well as eukaryotic organisms. Whole-genome analysis reveals that a reliable partial consensus topology can be predicted for ,70% of all membrane proteins in a typical bacterial genome and for ,55% of all membrane proteins in a typical eukaryotic genome. The average fraction of sequence length covered by a partial consensus topology is 44% for the prokaryotic proteins and 17% for the eukaryotic proteins in our test set, and similar numbers are found when the algorithm is applied to whole genomes. Reliably predicted partial topologies may simplify experimental determinations of membrane protein topology. [source] Is procalcitonin a reliable marker for the diagnosis of infected pancreatic necrosis?ANZ JOURNAL OF SURGERY, Issue 7 2004Nadir Yonetci Background: Infected necrosis in acute pancreatitis is the main factor in determining the prognosis of the disease. Early and accurate diagnosis of infected pancreatic necrosis might decrease mortality. The aim of the present study is to identify a reliable marker for the onset infection in three different experimentally induced pancreatitis models. Methods: Ninety female Wistar albino rats were randomly divided into nine groups. In three different experimental models, including cerulein induced acute oedematous pancreatitis (AEP), sterile pancreatic necrosis due to taurocholate-induced acute pancreatitis (SPN) and infected pancreatic necrosis taurocholate-induced acute pancreatitis (IPN). Serum levels of procalcitonin (PCT), C-reactive protein (CRP), tumour necrosis factor a (TNF-,), interleukin 6 (IL-6) and interleukin 8 (IL-8), amylase were measured. The degree of pancreatic damage also evaluated pathologically. Results: Procalcitonin levels were increased significantly in AEP, SPN and IPN compared to control groups (P < 0.05). PCT and IL-6 level were the highest in the IPN group (P < 0.05). Serum amylase, CRP, TNF-,, IL-2, and IL-8 levels were similar between IPN and SPN groups (P > 0.05), but higher than in other groups. The results of histological evaluation also correlated with the advent of the disease. Conclusion: Procalcitonin and IL-6 acts as reliable acute phase reactant in an experimental model of AEP, SPN and IPN in the rat. PCT and IL-6 combination might be surrogate marker of infected pancreatic necrosis and should be preferred to other markers assay especially in severe pancreatitis. [source] High prevalence of HFE gene mutations in patients with porphyria cutanea tarda in the Czech RepublicBRITISH JOURNAL OF DERMATOLOGY, Issue 3 2008K. Kratka Summary Background, Iron overload and hepatitis C virus (HCV) infection are independent factors which are thought to play a role in the pathogenesis of porphyria cutanea tarda (PCT). Objectives, To determine the prevalence of the HFE gene mutations p.Cys282Tyr (C282Y), p.His63Asp (H63D) and p.Ser65Cys (S65C), the p.Tyr250X (Y250X) mutation of the TFR2 gene, and HCV infection in patients with PCT in the Czech population, and to make comparison of the iron status among the respective genotypes. Methods, Iron metabolism indices, results of mutational analysis and serological markers of HCV infection were examined in 63 patients with PCT. Results, The HFE gene mutations were detected in 70% of patients with PCT compared with 35% in the control group (P < 0·001). Mean serum ferritin levels were increased in all genotypes, the highest being in homozygotes for the p.Cys282Tyr mutation. HCV infection was detected in only 8% of patients with PCT. Conclusions, There was a very high prevalence of the p.Cys282Tyr and p.His63Asp mutations observed in patients with PCT accompanied by mild degrees of iron overload, which was genotype dependent. [source] Molecular heterogeneity of familial porphyria cutanea tarda in Spain: characterization of 10 novel mutations in the UROD geneBRITISH JOURNAL OF DERMATOLOGY, Issue 3 2007M. Méndez Summary Background, Porphyria cutanea tarda (PCT) results from decreased hepatic uroporphyrinogen decarboxylase (UROD) activity. In the majority of patients, the disease is sporadic (S-PCT or type I) and the enzyme deficiency is limited to the liver. Familial PCT (F-PCT or type II) is observed in 20,30% of patients in whom mutations on one allele of the UROD gene reduce UROD activity by approximately 50% in all tissues. Another variant of PCT (type III) is characterized by family history of the disease although it is biochemically indistinguishable from S-PCT. Objectives, To investigate the molecular basis of PCT in Spain and to compare enzymatic and molecular analysis for the identification of patients with F-PCT. Methods, Erythrocyte UROD activity measurement and mutation analysis of the UROD gene were carried out in a cohort of 61 unrelated Spanish patients with PCT and 50 control individuals. Furthermore, each novel missense mutation identified was characterized by prokaryotic expression studies. Results, Of these 61 patients, 40 (66%) were classified as having S-PCT, 16 (26%) as having F-PCT and five (8%) as having type III PCT. Discordant results between enzymatic and molecular analysis were observed in two patients with F-PCT. In total, 14 distinct mutations were found, including 10 novel mutations: five missense, one nonsense, three deletions and an insertion. Prokaryotic expression of the novel missense mutations demonstrated that each results in decreased enzyme activity or stability. Conclusions, These results confirm the high degree of molecular heterogeneity of F-PCT in Spain and emphasize the usefulness of molecular genetic analysis to distinguish between F-PCT and S-PCT. [source] A case of porphyria cutanea tarda in association with idiopathic myelofibrosis and CREST syndromeBRITISH JOURNAL OF DERMATOLOGY, Issue 1 2001S.C. Lee We report a 56-year-old Korean woman with porphyria cutanea tarda (PCT), showing multiple scarring bullae and hypertrichosis on sun-exposed areas of skin with postinflammatory hyperpigmentation. Sclerodermoid changes were also found on both hands, the face and neck. The patient had suffered from CREST syndrome, manifesting with Raynaud's phenomenon and sclerodactyly, for more than 15 years. Anticentromere antibody was positive. She had presented with splenomegaly 3 years before the development of PCT, and was diagnosed as having idiopathic myelofibrosis, based on bone marrow biopsy. In summary, she had had CREST syndrome for 15 years and later developed idiopathic myelofibrosis and PCT. This is the first reported case of PCT in association with idiopathic myelofibrosis and CREST syndrome. [source] Procalcitonin-reduced sensitivity and specificity in heavily leucopenic and immunosuppressed patientsBRITISH JOURNAL OF HAEMATOLOGY, Issue 1 2001M. Svaldi Procalcitonin (PCT) has proven to be a very sensitive marker of sepsis for non-leucopenic patients. Little is known about its relevance in immunosuppressed and leucopenic adults. Four hundred and seventy-five PCT determinations were carried out in 73 haematological patients: on 221 occasions the white blood cell (WBC) count was <,1·0 × 109/l and on 239 occasions it was >,1·0 × 109/l leucocytes. Patients were classified as: non-systemic infected controls (n = 280), patients with bacteraemia (n = 32), sepsis (n = 30), severe sepsis (n = 3), septic shock (n = 3) and systemic inflammatory response syndrome (SIRS) (n = 62). When the WBC count was >,1·0 × 109/l, gram-negative bacteria induced higher PCT levels (median 9·4 ng/ml) than gram-positives (median 1·4 ng/ml). In cases with a WBC <,1·0 × 109/l, PCT levels were similar for gram-negative and gram-positive bacteria (1·1 ng/ml versus 0·85 ng/ml). Regardless of the leucocyte count, the median PCT level in bacteraemia cases always remained <,0·5 ng/ml. In heavily leucopenic situations, PCT levels were never >,2 ng/ml even in the sepsis and severe sepsis/septic shock groups, whereas a WBC count >,1·0 × 109/l resulted in median PCT values of 4·1 ng/ml and 45 ng/ml respectively. The positive predictive value for sepsis (cut-off 2 ng/ml) was 93% in cases of WBC count >,1·0 × 109/l, but only 66% in leucopenic conditions. The negative predictive value (cut-off 0·5 ng/ml) was 90% when the WBC count was >,1·0 × 109/l and 63% in leucopenic conditions. Procalcitonin is an excellent sepsis marker with a high positive- and negative-predictive value in patients with WBC count >,1·0 × 109/l, but it does not work satisfactorily below this leucocyte count. [source] Early 18F-2-fluoro-2-deoxy-d-glucose positron emission tomography may identify a subset of patients with estrogen receptor-positive breast cancer who will not respond optimally to preoperative chemotherapyCANCER, Issue 4 2010Andrea A. Martoni MD Abstract BACKGROUND: A pathologic complete response (pCR) and minimal residual disease (pMRD) after preoperative chemotherapy (PCT) for early stage or locally advanced breast cancer (BC) correlates with a good prognosis. METHODS: Patients who received from 6 to 8 cycles of PCT for BC were monitored by 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG-PET), and the maximal standardized uptake value (SUVmax) was calculated at baseline, after 2 cycles, after 4 cycles, and at the end of PCT. SUVmax percentage changes (,-SUV) were compared with the pathologic response rate. Patients who had a pCR or pMRD in the tumor and an absence of cancer cells in ipsilateral axillary lymph nodes were defined as having obtained an optimal pathologic response (pR), whereas all the other conditions were classified as a pathologic nonresponse (pNR). RESULTS: Of 34 patients, 7 (21%) achieved a pR (3 patients had a pCR, and 4 patients had pMRD). After the second cycle, the ,-SUV threshold with optimal negative predictive value to predict a pR was 50%. Twenty-six patients (76%) had a ,-SUV >50%, including all 7 patients who had a pR and 19 patients who had a pNR. Conversely, all 8 patients who had a ,-SUV ,50% had a pNR. All 8 of those patients had estrogen recepetor-positive tumors. CONCLUSIONS: Early evaluation of metabolic response by 18F-FDG-PET during PCT was able to identify 30% of patients, all with estrogen receptor-positive tumors, who would not obtain pR after completion of chemotherapy program. Cancer 2010. © 2010 American Cancer Society. [source] A simple, and potentially low-cost method for measuring the prevalence of childhood obesityCHILD: CARE, HEALTH AND DEVELOPMENT, Issue 2 2006K. Routh Abstract Background, Recent official publications have highlighted obesity as one of the biggest threats to public health and the prevalence of obesity in children is widely believed to be rising rapidly. However, there are no data on the prevalence of childhood obesity at a local level. We have developed a simple low-cost method of gaining such data by working with local schools. Method, We designed our method on the observation that numeracy and data handling skills are often taught in schools by getting children to measure their height and weight. We recruited seven schools and offered them a numeracy lesson plan suitable for year 5 (aged 9,10) children together with healthcare staff to attend the lesson. As part of the lesson, each child's height and weight was measured and recorded anonymously. Parental consent was obtained on an ,opt out' basis. The method was evaluated by questionnaire. Results, We gained data on body mass index for 252 children. In total, 20% of the children were overweight, and 7% obese. The brief questionnaire survey indicated that both teachers and school nurses were happy with the method and would repeat it. Weighing was carried out sensitively. Conclusion, Our findings were in line with national studies of the prevalence of childhood obesity. The method was simple, low-cost and acceptable to schools and school nurses. There seems no reason why this project cannot be used more widely across the Primary Care Trust (PCT) and beyond. We now propose to roll out the method across all primary schools in Birmingham. [source] | ||||||||||||||||||||||||||||||||||