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Clinical Differences (clinical + difference)
Selected AbstractsGenetic and epigenetic classifications define clinical phenotypes and determine patient outcomes in colorectal cancer,BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 10 2009J. A. Sanchez Background: A molecular classification of colorectal cancer has been proposed based on microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and mutations in the KRAS and BRAF oncogenes. This study examined the prevalence of these molecular classes, and differences in clinical presentation and outcome. Methods: Demographics, tumour characteristics and survival were recorded for 391 subjects with colorectal cancer. Tumour DNA was analysed for MSI (high (MSI-H) or microsatellite stable (MSS)), CIMP (high (CIMP-H) or no (CIMP-neg)) and BRAF and KRAS mutations. Clinical differences between four phenotypes were examined. Results: Most tumours were MSS/CIMP-neg (69·8 per cent), with a nearly equal distribution of MSI-H/CIMP-H, MSI-H/CIMP-neg and MSS/CIMP-H types. MSS/CIMP-neg tumours were less likely to be poorly differentiated (P = 0·009). CIMP-H tumours were more common in older patients (P < 0·001). MSI-H/CIMP-H tumours had a high frequency of BRAF mutation and a low rate of KRAS mutation; the opposite was true for MSS/CIMP-neg tumours (P < 0·001). The four molecular phenotypes tended towards divergent survival (P = 0·067 for stages 1,III). MSI-H cancers were associated with better disease-free survival (hazard ratio 2·00 (95 per cent confidence interval 1·03 to 3·91); P = 0·040). Conclusion: Colorectal cancers are molecularly and clinically heterogeneous. These different molecular phenotypes may reflect variable prognosis. Copyright © 2009 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] Reproducibility, validity, and responsiveness of a disease-specific symptom questionnaire for gastroesophageal reflux diseaseDISEASES OF THE ESOPHAGUS, Issue 4 2000C. J. Allen The purpose of this study was to establish the reproducibility, validity, and responsiveness of a symptom questionnaire to assess patients with gastroesophageal reflux disease (GERD). A total of 300 patients with GERD completed questionnaires before and 6 months after laparoscopic Nissen fundoplication. Forty-six GERD patients who continued on omeprazole served as controls. Lower esophageal sphincter pressure, 24-h pH, and quality of life (SF36) were measured at baseline and follow-up. Reproducibility was calculated as an intraclass correlation coefficient (ICC) from a repeated-measures analysis of variance on symptom scores (SS) on two consecutive days. Validity was established by correlating SS with 24-h pH and SF36 scores. Responsiveness was calculated as the the ratio of the mean paired difference in score in the surgical group to the within-subject variability in control subjects. Reproducibility was very high, as revealed by an ICC of 0.92. Strong correlations between SS and SF36 scores at baseline and after surgery demonstrated high cross-sectional validity. Correlation between change in SS and change in pH, SF36 pain, general health, and physical health scores demonstrated longitudinal validity. The mean (95% confidence interval) paired differences in SS were 25.6 (23.7, 27.5) in the study and 2.0 (,3.2, 7.3) in the control groups, and the responsive index was 1.0. The estimated minimally important clinical difference was 7. We conclude that the symptom score is a reproducible, valid, and responsive instrument for assessing symptoms caused by GERD. [source] Performance of a new separator system for routine autologous hematopoietic progenitor cell collection in small childrenJOURNAL OF CLINICAL APHERESIS, Issue 6 2007Volker Witt Abstract The AMICUSÔ system was recently introduced for peripheral blood stem cell (PBSC) aphereses in adults. We conducted a single center field evaluation to obtain data about the performance of this system in children with a body weight (bw) < 25 kg. Results of blood priming procedures were compared to historical data obtained with the Fenwal CS3000+ (CS 3000). From August, 2001 to February, 2007, 47/178 (26%) PBSC aphereses procedures were performed in our institution with the AMICUSÔ system in 35 small patients (median bw 13.9 kg; range 6.7,24; age 2.78 years; range 0.97,7.06). The patients suffered from various malignant primary diseases or recurrences. We primed the system with packed RBC in case of >30% dilution of the RBC volume (n = 31) or with saline (n = 16). Compared to the CS3000, the AMICUSÔ revealed comparable collection efficiencies (CE) for CD34+ cells (median 67%, range 26,120), lymphocytes (75%, 25,138), monocytes (54%, 23,173), and granulocytes (10%, 1.5,36), MNC (57% 24,125), but a significantly higher erythrocyte and granulocyte, and a lower platelet CE. There was a significant negative correlation between total leukocyte count and CE for MNC (r = ,0.566; P < 0.001) and CD34+ cells (r = ,0.517; P < 0.001). There was no significant statistical or clinical difference between the CE in blood-primed procedures and saline-primed procedures. With the AMICUSÔ we saw statistically less citrate reactions compared to the CS 3000. We conclude that the AMICUSÔ system is safe and efficient to harvest PBSC on a routine basis in pediatric patients, even in children ,10 kg bw. J. Clin. Apheresis, 2007. © 2007 Wiley-Liss, Inc. [source] Gender-medicine aspects in allergologyALLERGY, Issue 5 2008E. Jensen-Jarolim Despite the identical immunological mechanisms activating the release of mediators and consecutive symptoms in immediate-type allergy, there is still a clear clinical difference between female and male allergic patients. Even though the risk of being allergic is greater for boys in childhood, almost from adolescence onwards it seems to be a clear disadvantage to be a woman as far as atopic disorders are concerned. Asthma, food allergies and anaphylaxis are more frequently diagnosed in females. In turn, asthma and hay fever are associated with irregular menstruation. Pointing towards a role of sex hormones, an association of asthma and intake of contraceptives, and a risk for asthma exacerbations during pregnancy have been observed. Moreover, peri- and postmenopausal women were reported to increasingly suffer from asthma, wheeze and hay fever, being even enhanced by hormone replacement therapy. This may be on account of the recently identified oestradiol-receptor-dependent mast-cell activation. As a paradox of nature, women may even become hypersensitive against their own sex hormones, resulting in positive reactivity upon intradermal injection of oestrogen or progesterone. More importantly, this specific hypersensitivity is associated with recurrent miscarriages. Even though there is a striking gender-specific bias in IgE-mediated allergic diseases, public awareness of this fact still remains minimal today. [source] How I do it: sample size calculationsCLINICAL OTOLARYNGOLOGY, Issue 2 2008J. O'Hara Keypoints ,,Sample size calculations are integral to project design. ,,A description of the underlying theory behind them is set out. ,,Required are the significance level, the power, the clinical difference and the standard deviation. ,,Douglas Altman's nomogram is particularly useful for sample size calculations for comparing independent samples. [source] Relative vs. absolute measures of benefit and risk: what's the difference?ACTA PSYCHIATRICA SCANDINAVICA, Issue 2 2010L. Citrome Citrome L. Relative vs. absolute measures of benefit and risk: what's the difference? Objective:, When appraising evidence clinicians are confronted with two types of comparisons: ratios, such as relative risk, and absolute differences, such as number needed to treat (NNT) or number needed to harm (NNH). Method:, A review of the definition, calculation and interpretation of relative measures such as relative risk, odds ratio and the hazard ratio, and how they are different from absolute measures such as NNT and NNH. Results:, Relative and absolute measures provide different perspectives. Ratios can be misleading and exaggerate clinical differences, but NNT can appear to trivialize the risk of potentially important adverse events. Conclusion:, There is a need to understand both relative and absolute differences in order to make informed decisions. [source] Testing the stress-vulnerability hypothesis in ICD-10-diagnosed acute and transient psychotic disordersACTA PSYCHIATRICA SCANDINAVICA, Issue 1 2001S. K. Das Objective: ,To examine if family-history-positive (FHP) vis-à-vis family-history-negative (FHN) probands with ICD-10-diagnosed acute and transient psychotic disorders (ATPD) differ significantly with respect to number of life events and cumulative stress score prior to the onset of ATPD. Method: ,Forty probands with ICD-10-based clinical diagnosis of acute and transient psychotic disorders were studied with respect to: (a) history of psychiatric disorders in first-degree relatives, and (b) antecedent life events and cumulative stress. The FHP and FHN probands were compared on the latter variables using Mann,Whitney U -test. Results: ,FHP probands reported significantly less number of total life events compared to FHN probands (P=0.006). Similarly, FHP probands had significantly less stress score than FHN probands (P=0.002). There were no significant demographic or clinical differences between the two groups. Conclusion: ,The findings support the stress-vulnerability hypothesis in the aetiology of ATPD. [source] Childhood Epilepsy Due to Neurocysticercosis: A Comparative StudyEPILEPSIA, Issue 11 2001Lisiane S. Ferreira Summary: ,Purpose: To assess the clinical profile of pediatric patients with epilepsy and neurocysticercosis (NC), and compare them with a group of pediatric patients with benign partial epilepsy to determine clinical differences, response to treatment, and prognosis. Methods: We studied 28 patients (16 girls) with probable or definitive diagnosis of NC and epilepsy and 32 patients (16 girls) with partial benign epilepsy (BE). All patients had normal neurologic examination. We compared NC and BE patients looking for differences in demographics (age at first seizure, gender, family history); clinical presentation (type, frequency, duration, and total number of seizures, duration of epilepsy, status epilepticus, cluster, and postictal deficit); treatment [duration, number of antiepileptic drugs (AEDs), maximal dose, drug association, number of seizure-free patients, time to obtain control and recurrence after medication discontinuation]; complementary examinations (the first and the last EEG). Results: The mean follow-up was 5.4 years for the 28 NC patients and 4.6 years for the 32 BE patients (p = 0.98). We did not find statistical differences between NC and BE in gender, family history, types of seizures, frequency and length of seizures, previous status epilepticus, seizure clustering, and presence of postictal deficits. However, we found that NC compared with BE patients had significant longer AED treatment, more seizures after AED introduction, tried more AEDs and at maximal dose, and in 20%, required polytherapy. The recurrence rate in NC was 54.4% and this was not significantly associated with number of lesions and disease activity seen on CT scans or the presence of EEG abnormalities. Conclusions: NC presents with a mild form of epilepsy in terms of seizure severity; however, it is more challenging in regard to drug management and has a less favorable long-term prognosis in terms of seizure remission. The number of lesions or disease activity seen on computed tomography (CT) as well as EEG abnormalities have no prognostic value in childhood epilepsy due to NC. [source] Using translational medicine to understand clinical differences between botulinum toxin formulationsEUROPEAN JOURNAL OF NEUROLOGY, Issue 2006K. R. Aoki When using botulinum toxin-based products, the physician must decide the optimal location and dose required to alleviate symptoms and improve the patient's quality of life. To deliver effective treatment, the physician needs to understand the importance of accurate target muscle selection and localization and the implications of each product's migration properties when diluted in different volumes. Pre-clinical mouse models of efficacy and safety have been utilized to compare local and distal muscle relaxation effects following defined intramuscular administration. Data from the model allow the products to be ranked based on their propensity for local efficacy versus their distal migration properties. Using standardized dilutions, the non-parallel dose,response curves for the various formulations demonstrate that they have different efficacy profiles. Distal effects were also noted at different treatment doses, which are reflected in the different safety and/or therapeutic margins. Based on these pre-clinical data, the safety and therapeutic margin rankings are ordered, largest to smallest, as BOTOX®, Dysport® and Myobloc®. The results of subsequent clinical trials are variable and dose comparisons are inconclusive, thus supporting the regulatory position that the dose units of the individual preparations are unique and cannot be simply converted between products. [source] Myotonic dystrophy type 2EUROPEAN JOURNAL OF NEUROLOGY, Issue 5 2002J. Finsterer Myotonic dystrophy type 2 (DM2) is a clinically but not genetically heterogeneous, multisystem disorder, that is clinically similar to, but distinct from myotonic dystrophy type 1 (DM1). Initially, different phenotypes of DM2 were described by Ricker (proximal myotonic myopathy, PROMM), Ranum (myotonic dystrophy 2, DM2) and Udd (proximal myotonic dystrophy, PDM). Clinical features these three phenotypes had in common were diffuse, proximal or distal weakness, wasting, myotonia, cataract, cerebral, endocrine and cardiac abnormalities. Initially, the clinical differences between DM1 and PROMM seemed unmistakable, but meanwhile it has become apparent that the clinical differences between these entities are blurring. In 1999, Day et al., Meola et al. and Ricker et al. mapped the mutated gene of all three phenotypes to chromosome 3q. In 2001, the three different phenotypes were found to rely on the same mutation in the ZNF9 gene on chromosome 3q21.3. Although DM2 may be clinically heterogeneous, it is by result of a mutation in a single gene. The mutation responsible for DM2 is a CCTG-repeat expansion of 75,11 000 repeats in intron 1 of the ZNF9 gene on chromosome 3q21.3. Because of the clinical heterogeneity, the diagnosis of DM2 should rely on DNA analysis alone. [source] Upper and Lower Cluster Headache: Clinical and Pathogenetic Observations in 608 PatientsHEADACHE, Issue 7 2002Carola Cademartiri MD Objective, Background, and Methods.,Ever since it was proposed by Ekbom and Kugelberg back in 1968 on the basis of the different location of head pain during attacks, the differentiation of cluster headache into an upper syndrome (US) and a lower syndrome (LS) has been regarded as a purely academic distinction. To evaluate whether this differentiation is indeed well founded and to understand its possible significance in the light of current pathogenetic knowledge, we rigorously applied Ekbom and Kugelberg's classification criteria to a sample of 608 patients with cluster headache (CH; 440 men and 168 women), including 483 with episodic CH, 69 with chronic CH, and 56 with CH periodicity undetermined. Results.,Of these patients, 278 could be classified as US sufferers and 330 as LS sufferers. Our data analysis showed statistically significant clinical differences between the two syndromes: pain location was more common in the ocular, temporal, and nuchal regions among LS sufferers; in addition, patients with LS reported not only a higher rate of autonomic symptoms, but also a higher predominance of nasal congestion, ptosis, and forehead and facial sweating among these symptoms. Conclusions.,Based on current anatomofunctional knowledge and on the most recent pathogenetic findings, we believe that changes in hypothalamic activity posteroinferiorly may lead to activation of the caudal part of the spinal trigeminal nucleus by way of the hypothalamus, midbrain, and trigeminal nerve fibers and consequently to activation of the trigeminovascular system with a different location in the two syndromes. More specifically, there seems to be a larger and more extensive involvement of the subnucleus caudalis in LS compared with US, where only its ventrocaudal portions are likely to be affected. [source] Elevated prevalence of hepatitis C infection in users of United States veterans medical centers,HEPATOLOGY, Issue 1 2005Jason A. Dominitz Several studies suggest veterans have a higher prevalence of hepatitis C virus infection than nonveterans, possibly because of military exposures. The purpose of this study was to estimate the prevalence of anti,hepatitis C antibody and evaluate factors associated with infection among users of Department of Veterans Affairs medical centers. Using a two-staged cluster sample, 1,288 of 3,863 randomly selected veterans completed a survey and underwent home-based phlebotomy for serological testing. Administrative and clinical data were used to correct the prevalence estimate for nonparticipation. The prevalence of anti,hepatitis C antibody among serology participants was 4.0% (95% CI, 2.6%-5.5%). The estimated prevalence in the population of Veterans Affairs medical center users was 5.4% (95% CI, 3.3%-7.5%) after correction for sociodemographic and clinical differences between participants and nonparticipants. Significant predictors of seropositivity included demographic factors, period of military service (e.g., Vietnam era), prior diagnoses, health care use, and lifestyle factors. At least one traditional risk factor (transfusion or intravenous drug use) was reported by 30.2% of all subjects. Among those testing positive for hepatitis C antibody, 78% either had a transfusion or had used injection drugs. Adjusting for injection drug use and nonparticipation, seropositivity was associated with tattoos and incarceration. Military-related exposures were not found to be associated with infection in the adjusted analysis. In conclusion, the prevalence of hepatitis C in these subjects exceeds the estimate from the general US population by more than 2-fold, likely reflecting more exposure to traditional risk factors among these veterans. (HEPATOLOGY 2005;41:88,96.) [source] Intracardiac Ultrasound Detection of Thrombus on Transseptal Sheath: Incidence, Treatment, and PreventionJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 6 2005KATANEH MALEKI M.D. Background: Transseptal (TS) catheterization is used for left atrial (LA) ablation procedures and a major risk is thromboembolism. The purpose of this study was to assess (1) the value of intracardiac ultrasound (ICUS) monitoring during LA ablation procedures, and (2) a new technique to reduce the risk of thrombus formation. Methods and Results: One hundred and eighty consecutive patients underwent TS catheterization under ICUS guidance with two sheaths for atrial fibrillation ablation and one for other LA procedures. Group I included the initial 90 patients in whom TS sheaths were flushed with a standard 2 U/cc concentration of heparin; group II consisted of the next 90 patients in whom sheaths were flushed with 1,000 U/cc concentration. All patients received bolus and infusion of heparin to maintain ACT between 250,300 seconds. ICUS was monitored throughout. In group I, echodense material at the tip of the sheath consistent with thrombus was observed on ICUS in 8 of 90 patients (9%) within 5,15 minutes of entering the LA. In group II, only 1 of 90 patient (1%) demonstrated thrombus (P < 0.001). There were no significant clinical differences in group I patients with and without thrombus. In all nine patients, the clot was removed with vigorous aspiration. No patients suffered a neurological event. Conclusion: Thrombus formation on TS sheath, detected by ICUS, may be more common than expected despite adequate anticoagulation. Using a higher concentration of heparin for the TS system before deployment reduced the risk. The thrombus was retrieved with aspiration without the need to abort the procedure. [source] Clinical Experience with a Novel Intracoronary Perfusion Catheter to Treat No-Reflow Phenomenon in Acute Coronary SyndromesJOURNAL OF INTERVENTIONAL CARDIOLOGY, Issue 2 2010GABRIEL MALUENDA M.D. Background:,The no-reflow phenomenon is an often seen complication in patients presenting with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). This event is associated with poor prognosis and poses a therapeutic challenge. Methods:,This retrospective study cohort was composed of 30 patients who presented with ACS between September 2007 and April 2009, and developed no-reflow during subsequent PCI. The primary end-point was defined as normal Thrombolysis In Myocardial Infarction (TIMI) 3 flow with myocardial blush grade (MBG) ,2 or an increase in TIMI flow by ,2 grades with a MBG ,2 after intracoronary drug infusion via the ClearWay (CW) RX perfusion catheter. Results:,The population presented with a relatively high prevalence of cardiovascular risk factors. ST-elevation myocardial infarction was the most common presentation (60.0%), while 20% of the patients presented with cardiogenic shock. After intracoronary infusion of nicardipine or nitroprusside using the CW catheter, TIMI flow improved from the baseline in 19 cases (63.3%, P < 0.001), and 16 patients (53.3%, P < 0.001) achieved normal coronary flow at the end of the procedure. The rate of in-hospital death was 6.7% (2 cases). No clinical differences were noted between those patients who successfully achieved normal coronary flow and those with persistent no-reflow. Conclusion:,The infusion of intracoronary drugs using the novel perfusion CW RX catheter seems to be safe and could help to improve myocardial perfusion in a selected group of patients presenting with ACS who developed no-reflow during PCI. (J Interven Cardiol 2010;23:109-113) [source] Hepatitis B virus genotypes and spontaneous hepatitis B e antigen seroconversion in Taiwanese hepatitis B carriersJOURNAL OF MEDICAL VIROLOGY, Issue 3 2004Jia-Horng Kao MD Abstract Hepatitis B virus (HBV) is classified into eight genotypes (A,H), and genotype C is associated with more aggressive liver disease compared to genotype B. However, the mechanisms responsible for the clinical differences remain unclear. To test whether genotype C patients had with lower rates of spontaneous hepatitis B ge antigen (HBeAg) seroconversion than genotype B patients, stored serum samples from 146 Taiwanese adult HBeAg-positive hepatitis B carriers followed-up for a mean of 52 months (range, 12,120 months) were tested for HBV genotype by a molecular method. Genotype C patients were significantly older than genotype B patients (mean age, 37,±,12 vs. 29,±,10 years, P,<,0.001). During the follow-up period, genotype C patients had a significantly lower rate of spontaneous HBeAg seroconversion than genotype B patients (27 vs. 47%, P,<,0.025). Spontaneous HBeAg seroconversion occurred one decade later in genotype C patients compared with genotype B patients. Multivariate analyses identified age ,35 years (odds ratio: 2.08; 95% confidence interval [CI], 1.07,4.0; P,<,0.05), high baseline serum alanine aminotransferase level (odds ratio: 2.34; 95%CI, 1.39,4.09; P,<,0.005), and HBV genotype B (odds ratio: 1.94; 95%CI, 1.03,3.63; P,<,0.05) as independent factors associated with spontaneous HBeAg seroconversion. In conclusion, genotype C patients, compared to genotype B patients, have a delayed HBeAg seroconversion in the immune clearance phase of chronic HBV infection, which may contribute to a more progressive liver disease and more refractory to antiviral therapy. J. Med. Virol. 72:363,369, 2004. © 2004 Wiley-Liss, Inc. [source] CMT1A Associated With The 17p11.2 Duplication: Differential Features And CorrelationJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2001D Pareyson A duplication on chromosome 17p11.2 encompassing the gene coding for the peripheral myelin protein-22 (PMP22) is the most common genetic abnormality underlying Charcot-Marie-Tooth disease (CMT). We report clinical and electrophysiologic features of our series of CMT1A patients harboring the duplication. There were 92 patients from 53 families representing 42% of all CMT index cases (n = 125) and 64% of CMT1 probands (n = 83). In CMT1A patients, mean age at onset was 9.7 ± 11.4 and was significantly lower than in non-duplicated CMT1 cases (12.6 ± 9.7, p < 0.01) and CMT2 cases (21.5 ± 17, p < 0.001). Clinical severity was similar to that of CMT2 patients, but significantly milder than in non-duplicated CMT1 cases. Pes cavus, upper limb involvement, deep tendon reflexes abnormalities, and sensory loss were more frequent compared to CMT2. Electrophysiologic examination revealed motor and sensory conduction velocity (MCV, SCV) slowing below 32 m/s in upper limbs. MCV and SCV were significantly lower than in non-duplicated CMT1 patients. Amplitudes of upper limb compound muscle action potentials (CMAPs) and of upper and lower limb sensory action potentials (SAPs) were significantly lower than in CMT2, paralleling clinical differences. Clinical severity correlated with CMAP amplitudes and with disease duration. On the other hand, MCV slowing was not correlated with either severity or duration of the disease. We found a direct correlation between age at onset and upper limb MCV slowing. Conclusions: CMT1A is an early-onset but slowly progressive disorder, on average milder than other CMT1. Axonal loss rather than demyelination per se underlies disease progression. [source] Major differences in bleeding symptoms between factor VII deficiency and hemophilia BJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 5 2009F. BERNARDI Summary.,Background:,The autosomally-inherited factor VII (FVII) deficiency and X-linked hemophilia B offer an attractive model to investigate whether reduced levels of FVII and FIX, acting in the initiation and amplification of coagulation respectively, influence hemostasis to a different extent in relation to age and bleeding site. Methods:,Hemophilia B patients (n = 296) and FVII-deficient males (n = 109) were compared for FVII/FIX clotting activity, F7/F9 genotypes and clinical phenotypes in a retrospective, multi-centre, cohort study. Results:,Major clinical differences between diseases were observed. Bleeding occurred earlier in hemophilia B (median age 2.0 years, IR 0.9,5.0) than in FVII deficiency (5.2 years, IR 1.9,15.5) and the bleeding-free survival in FVII deficiency was similar to that observed in ,mild' hemophilia B (P = 0.96). The most frequent disease-presenting symptoms in hemophilia B (hematomas and oral bleeding) differed from those in FVII deficiency (epistaxis and central nervous system bleeding). Differences were confirmed by analysis of FVII-deficient women. Conclusions:,Our data support the notion that low FVII levels sustain hemostasis better than similarly reduced FIX levels. On the other hand, minute amounts of FVII, differently to FIX, are needed to prevent fatal bleeding, as indicated by the rarity of null mutations and the associated life-threatening symptoms in FVII deficiency, which contributes towards shaping clinical differences between diseases in the lowest factor level range. Differences between diseases are only partially explained by mutational patterns and could pertain to the specific roles of FVII and FIX in coagulation phases and to vascular bed-specific components. [source] Pegylated interferons: chemical and clinical differencesALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2004G. R. Foster Summary Pegylated interferon therapy for the treatment of chronic hepatitis C virus provides significant increases in sustained virological response rates compared with standard interferons. Two pegylated interferons are now available and are used in conjunction with ribavirin to maximize response rates in infected patients. The two pegylated interferons, peginterferon, -2a and peginterferon, -2b, differ substantially in terms of their chemical and structural characteristics, pharmacokinetic and pharmacodynamic properties, and dosing and administration. A full understanding of the differences between the two drugs is important to maximize the clinical benefits. Controlled studies designed to characterize the effects of the two drugs on viral kinetics and sustained virological response rates are emerging and may help to shed additional light on the use of these compounds in patients with chronic hepatitis C. [source] Morphine-6-glucuronide: Actions and mechanismsMEDICINAL RESEARCH REVIEWS, Issue 5 2005Gavin J. Kilpatrick Abstract Morphine-6-glucuronide (M6G) appears to show equivalent analgesia to morphine but to have a superior side-effect profile in terms of reduced liability to induce nausea and vomiting and respiratory depression. The purpose of this review is to examine the evidence behind this statement and to identify the possible reasons that may contribute to the profile of M6G. The vast majority of available data supports the notion that both M6G and morphine mediate their effects by activating the µ-opioid receptor. The differences for which there is a reasonable consensus in the literature can be summarized as: (1) Morphine has a slightly higher affinity for the µ-opioid receptor than M6G, (2) M6G shows a slightly higher efficacy at the µ-opioid receptor, (3) M6G has a lower affinity for the ,-opioid receptor than morphine, and (4) M6G has a very different absorption, distribution, metabolism, and excretion (ADME) profile from morphine. However, none of these are adequate alone to explain the clinical differences between M6G and morphine. The ADME differences are perhaps most likely to explain some of the differences but seem unlikely to be the whole story. Further work is required to examine further the profile of M6G, notably whether M6G penetrates differentially to areas of the brain involved in pain and those involved in nausea, vomiting, and respiratory control or whether µ-opioid receptors in these brain areas differ in either their regulation or pharmacology. © 2005 Wiley Periodicals, Inc. Med Res Rev [source] Restless legs syndrome in Parkinson's diseaseMOVEMENT DISORDERS, Issue 13 2007Juan C. Gómez-Esteban MD Abstract The present study explores the frequency of RLS in PD and focuses on the clinical differences between patients with and without restless legs syndrome (RLS). A cross-sectional study was designed, comprising 114 patients diagnosed with PD. Those patients positive for RLS were assessed for intensity of the syndrome (IRLS). We compared the clinical characteristics of the patients with and without RLS, using specific scales: Unified Parkinson's Disease Rating Scale (UPDRS I-IV), quality of life (Parkinson's Disease Questionnaire, PDQ 39), sleep symptoms (Parkinson's Disease Sleep Scale, PDSS), and diurnal hypersomnia (Epworth Sleepiness Scale). Twenty-five patients (21.9%) out of a total of 114 subjects diagnosed with PD met the RLS diagnostic criteria. RLS was more frequent in women (68%). The patients with RLS showed poorer scores on the PDSS (PD-RLS+: 102.4 ± 15.1 vs PD-RLS-: 113.2 ± 16.4) (P = 0.005) and in the bodily discomfort dimension of the PDQ-39 (PD-RLS+ 6.1 ± 3.4 vs PD-RLS- 3.8 ± 2.6) (P = 0.002). Analysis of the subscales of the PDSS showed significant differences (P < 0.001) between both groups of patients in items 4 and 10, and to a lesser degree in items 5 (P = 0.01) and 11 (P = 0.02) There was no increased incidence of diurnal hypersomnia in the group of patients with RLS. There were no differences in the rest of the variables. RLS is frequent in patients with PD, though this condition doesn't apparently affect quality of life or lead to an increased presence of diurnal hypersomnia. It would be advisable to validate the diagnostic criteria of RLS in this specific group of patients. © 2007 Movement Disorder Society [source] Effect of Ventricular Fibrillation Duration on the Defibrillation Threshold in HumansPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 1 2002RAINER GRADAUS GRADAUS, R., et al.: Effect of Ventricular Fibrillation Duration on the Defibrillation Threshold in Humans. Early during ventricular fibrillation, the defibrillation threshold may be low, as ventricular fibrillation most probably arises from a localized area with only a few wavefronts and the effects of global ischemia, ventricular dilatation, and sympathetic discharge have not yet fully developed. The purpose of this study was to explore the effect of the timing of shock delivery in humans. During implantation of an ICD in 26 patients (24 men, 60 ± 11 years, 19 coronary artery disease, NYHA 2.2 ± 0.4, left ventricular ejection fraction 0.42 ± 0.16), the defibrillation threshold was determined after approximately 10 and 2 seconds of ventricular fibrillation. Ventricular fibrillation was induced by T wave shocks. Mean defibrillation threshold was 9.9 ± 3.6 J after 10.3 ± 1.0 seconds. Within 2 seconds, 20 of 26 patients could be successfully defibrillated with , 8 J. In these patients, the mean defibrillation threshold was 4.0 ± 2.1 J after 1.4 ± 0.3 seconds compared to 9.5 ± 3.1 J after 10.2 ± 1.1 seconds (P < 0.001). There were no clinical differences between patients who could be successfully defibrillated within 2 seconds and those patients without successful defibrillation within 2 seconds. In the majority of patients, the defibrillation threshold was significantly lower within the first few cycles of ventricular fibrillation than after 10 seconds of ventricular fibrillation. These results should lead to exploration of earlier shock delivery in implantable devices. This could possibly reduce the incidence of syncope in patients with rapid ventricular tachyarrhythmias and ICDs. [source] Effects of socioeconomic status on presentation with acute lower respiratory tract disease in children in Salvador, Northeast BrazilPEDIATRIC PULMONOLOGY, Issue 4 2002Cristiana M. Nascimento-Carvalho MD Abstract Two different socioeconomic groups of children with pneumonia were studied, and their clinical and demographic aspects were evaluated. The diagnosis of pneumonia was based on findings of cough and tachypnea, or on crackles on auscultation or on radiologically confirmed infiltrate. This was a prospective cross-sectional study conducted at the Professor Hosannah de Oliveira Pediatric Center, which cares for children of lower socioeconomic status (PHOPC), and at one private hospital which cares for children from middle to high socioeconomic status (Aliança Hospital, AH). Demographics and clinical differences were assessed by the Pearson chi-square test or Fisher's exact test as appropriate; means of continuous variables were compared by Mann-Whitney U-test. In a 26-month period, 3,431 cases were recruited. The 2,476 cases identified at the PHOPC were younger than the 955 identified at AH (2.2,±,2.3 vs. 4.5,±,3.1 years, P,<,0.0001) and had higher scores for severity (3.5,±,1.5 vs. 2.7,±,1.7, P,<,0.0001), duration of hospitalization (days) (10.9,±,12.1 vs. 6.2,±,7, P,<,0.0001), frequency of tobacco smoker in the household (48% vs. 31%, P,<,0.0001), cardiopathy (15.3% vs. 5.9%, P,=,0.003), fever (44.4% vs. 36.3%, P,=,0.0001), tachypnea (67.6% vs. 32.3%, P,<,0.0001), crackles (69.5% vs. 64.9%, P,=,0.02), somnolence (19.9% vs. 10.4%, P,<,0.0001), malnutrition (13.7% vs. 5%, P,<,0.0001), hospitalization rate (27.4% vs. 22.5%, P,=,0.003), and death (0.9% vs. 0.1%, P,=,0.009). However, other features were more frequent among AH cases: parent's university level of education (38.2% vs. 1.0%, P,<,0.0001), underlying chronic illness (40.6% vs. 28.5%, P,<,0.0001), asthma (62.7% vs. 50.8%, P,=,0.01), rhinitis (9.2% vs. 0.4%, P,<,0.0001), previous use of antibiotics (34.3% vs. 27.1%, P,=,0.001), and wheezing (53.1% vs. 42.2%, P,<,0.0001). Children of lower socioeconomic status have more serious lower respiratory tract disease, whereas children with pneumonia of middle to high socioeconomic status have more allergic diseases (rhinitis, asthma) and wheezing. Pediatr Pulmonol. 2002; 33:244,248. © 2002 Wiley-Liss, Inc. [source] Polychromatic phototest as a prognostic tool for polymorphic light eruptionPHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE, Issue 4 2000D. Leroy Background: Diagnosis of polymorphic light eruption (PLE) is based on the patient's history, the morphology of the lesions and the results of phototesting. Skin lesions of PLE can be provoked by repetitive UVB or UVA irradiation. However, about 20% of the patients with PLE have negative phototests. As 24% of the patients with PLE go into remission, it was of interest to search for a link between the results of the phototests and the evolution of the photodermatosis. Methods: Forty patients with PLE were recruited and repetitive phototests were performed. To ensure a good reproducibility of the phototests, one to three phototests were performed on each patient at different stages of the disease including the period when the PLE had gone into remission. Results: Except for one patient, there was a good reproducibility of the repetitive polychromatic phototests: in each patient, the tests remained positive or negative throughout the disease. After long-term follow-up, two different subgroups were identified: 30 patients with active PLE and 10 patients in remission. There were no clinical differences between these two groups apart from the age of onset and the clinical lesions of the PLE. PLE began at an earlier age in the patients in remission and presented mainly with a plaque-type eruption. In total, 52.5% of the patients had at least one positive polychromatic phototest. Phototests were positive only in patients with active disease. All the patients in remission had negative phototests. Conclusions: Repetitive phototests could be a prognostic marker for PLE. Two subtypes of PLE were identified on the basis of phototest results: the benign form of PLE with negative phototests, which tends to go into remission, and the more severe and more chronic PLE, with positive phototests. [source] Tramadol versus Buprenorphine for the Management of Acute Heroin Withdrawal: A Retrospective Matched Cohort Controlled StudyTHE AMERICAN JOURNAL ON ADDICTIONS, Issue 2 2006Threlkeld Threlkeld MD Many medications have been used over the past thirty years for the treatment of opioid withdrawal, including propoxyphene, methadone, clonidine, parenteral buprenorphine, and, more recently, sublingual buprenorphine. Each has been found to have clinical strengths and limitations. Tramadol is a centrally acting synthetic analgesic with opiate activity primarily due to the binding ofa metabolite to the , receptor. Despite this , receptor activity, tramadol appears to have low abuse potential and is a non-scheduled analgesic. The pharmacologic profile of tramadol makes it a candidate for opiate withdrawal treatment. A chart review was undertaken to retrospectively compare treatment outcomes of heroin-dependent patients when detoxified with parenteral buprenorphine (1996,1997) versus tramadol (1999,2000). Inclusion criteria for this study were heroin as drug of choice, current opioid physical dependence (ie, withdrawal symptoms), no current abuse of oral opioid analgesics, and no alcohol or benzodiazepine withdrawal symptoms. Patient cases that met inclusion criteria were group-matched between buprenorphine and tramadol on the basis of age, sex, and amount of heroin used (bags/ day). Charts were audited for patient demographics, daily heroin use at admission, withdrawal symptoms, and discharge status. In total, 129 patient charts were reviewed, and 115 met all inclusion criteria and were group-matched (45 patients in the buprenorphine group, seventy in the tramadol group). There were no differences in demographics between the two groups of patients. Fifty-six percent of the buprenorphine group and 71% of the tramadol group completed detoxification; tramadol-treated patients had significantly higher average withdrawal symptoms when compared to the buprenorphine group and a greater reduction in withdrawal symptoms over time. Finally, the number of side effects was small and did not differ between the groups. The results of this study are consistent with previous pilot reports that indicated few clinical differences between parenteral buprenorphine and oral tramadol protocols when used in the management of acute heroin withdrawal. As a consequence, tramadol shows some promise as an opioid withdrawal management medication. [source] Baseline Clinical Characteristics and Midterm Prognosis of STE-ACS and NSTE-ACS Patients with Normal Coronary ArteriesANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 1 2009Lukasz Mazurkiewicz M.D. Objective: We sought to compare clinical profiles and midterm prognosis of patients with normal coronary arteries presenting with ST-elevation ACS (STE-ACS) versus non-ST-elevation ACS (nSTE-ACS). Background: There are limited data regarding ACS in patients with normal coronary arteries, and especially clinical differences between ST-ACS and nSTE-ACS patients have not been evaluated sufficiently. Methods: The study group comprised 190 patients (mean age: 53.2 years, 63.1% males, 63.6% STE-ACS) presenting with ACS and normal coronary angiograms. The participants were evaluated in terms of 42 clinical variables. MACE [cardiac death (CD) and hospitalization for angina (HA)] were the study end points. Results: STE-ACS in comparison to nSTE-ACS patients were younger (P < 0.01), were more frequently males (P < 0.01), had more often infection prior to ACS (P < 0.01), higher hsCRP on admission (P < 0.01), and greater infarct size, measured by maximal troponin I (P < 0.01). By multivariate analysis in this subgroup, predictors of outcome were hsCRP (P = 0.03) and raised troponin I (P = 0.02). nSTE-ACS in comparison to STE-ACS patients were more obese (BMI, P < 0.01), had higher LDL cholesterol (P < 0.01), fasting glucose (P = 0.03). LDL cholesterol (P = 0.02) and fasting glucose (P = 0.03) emerged as independent predictors of outcome in these patients. Mean follow-up period was 25.4 months. STE-ACS patients had twice fewer MACE rate than nSTE-ACS patients [(1-CD, 12-HA; 11%) vs (1-CD, 16-HA; 25%), respectively, log rank P < 0.01]. Conclusions: STE-ACS and nSTE-ACS patients with normal coronary arteriography have different clinical profiles. In nSTE-ACS patients more pronounced metabolic abnormalities were identified, while in STE-ACS patients inflammatory background was more significant. [source] Systemic lupus erythematosus in a multiethnic US cohort: Clinical features, course, and outcome in patients with late-onset diseaseARTHRITIS & RHEUMATISM, Issue 5 2006Ana M. Bertoli Objective To examine the clinical differences and the type and extent of organ damage in late- versus early-onset systemic lupus erythematosus (SLE). Methods A nested case,control study was performed in the context of LUMINA (LUpus in MInorities, NAture versus nurture), a large, longitudinal, multiethnic cohort. Patients who developed SLE at or after the age of 50 years were considered cases. Two controls (patients who developed SLE at age ,49 years) per case, matched for sex and disease duration, were randomly chosen. Selected baseline socioeconomic/demographic, behavioral, and psychological features, self-reported quality of life, and cumulative clinical data (clinical manifestations, laboratory data, disease activity, damage, and mortality) were compared between cases and controls. Multivariable analyses with late-onset lupus, damage accrual, and mortality as dependent variables were then performed. Results Two hundred seventeen patients were studied. Of them, 73 were cases. Cases were more likely to have neurologic involvement, arterial thrombotic events, osteoporosis, and hypertriglyceridemia, while renal involvement and anti-Sm antibodies were less frequent. Disease activity at baseline was lower among cases. Cases also exhibited more cardiovascular and ocular damage. Late-onset lupus was an independent predictor of damage accrual (t -test = 2.23, P = 0.028), any damage at last visit (odds ratio [OR] 23.32, 95% confidence interval [95% CI] 3.98,141.56) (P < 0.001), and mortality (OR 10.74, 95% CI 3.07,37.56) (P < 0.001). Conclusion Patients with late-onset lupus exhibit distinct clinical features. Although disease activity tends to be lower in these patients, they tend to accrue more damage and experience higher mortality than patients with early-onset lupus. These findings probably reflect the contribution exerted by other comorbid conditions in the overall impact of lupus in these patients. [source] Toward an Understanding of Polyglutamine NeurodegenerationBRAIN PATHOLOGY, Issue 2 2000Henry L. Paulson Polyglutamine expansion is now recognized to be a major cause of inherited human neurodegenerative disease. The polyglutamine expansion diseases identified so far are slowly progressive disorders in which distinct yet overlapping brain regions are selectively vulnerable to degeneration. Despite their clinical differences these diseases likely share a common pathogenic mechanism, occurring at the protein level and centered on an abnormal conformation of expanded polyglutamine in the respective disease proteins. Recently there has been remarkable progress in our understanding of polyglutamine disease, but still there are many unanswered questions. In this review, I first outline some of the shared features of polyglutamine diseases and then discuss several issues relevant to an understanding of pathogenesis, paying particular attention to possible mechanisms of neurotoxicity. [source] Risk of pancreatic adenocarcinomaCANCER, Issue 2 2005Disparity between African Americans, other race/ethnic groups Abstract BACKGROUND African Americans have a higher incidence of pancreatic adenocarcinoma compared with non-Hispanic whites. Whether other clinical differences exist between these two groups is not well known. METHODS The authors conducted a population-based retrospective analysis of all patients with pancreatic adenocarcinoma in both a regional and a statewide database between 1988 and 1998. Their goal was to evaluate differences in incidence rates, clinical presentation, including age at diagnosis, gender, and tumor characteristics, and treatment among race/ethnic groups. RESULTS African Americans had a higher age-adjusted incidence rate of pancreatic adenocarcinoma (8.78) compared with non-Hispanic whites (5.89), Hispanics (5.09), Asians (4.75), and all race/ethnicities combined (5.82). African Americans also presented at a later stage of disease and received less surgery than all other race/ethnicities, despite equal availability of medical insurance. The analyses also revealed gender differences. In general, males maintained a higher incidence rate of pancreatic adenocarcinoma than females across all race/ethnicities. In all race/ethnic groups, females were diagnosed at an older age and an earlier stage of disease than males. The proportional hazard mortality ratio for females age < 60 was significantly less than that for males in the same age group (P < 0.02), even after accounting for stage and treatment. CONCLUSIONS African Americans in California had a higher incidence rate of pancreatic adenocarcinoma, had a slightly higher risk of presenting with advanced-stage diseas and with nonresectable tumors (i.e., tumors located in the body or tail of the pancreas), and underwent less surgical treatment than all other race/ethnicities. Younger females in all race/ethnic groups had a survival advantage over males of the same age. Cancer 2005. © 2004 American Cancer Society. [source] Randomized cross-over clinical trial of injectable vs. implantable depot testosterone for maintenance of testosterone replacement therapy in androgen deficient menCLINICAL ENDOCRINOLOGY, Issue 1 2010Carolyn Fennell Summary Background, Life-long testosterone replacement therapy (TRT) for younger men with organic androgen deficiency is best provided by depot testosterone (T) products. This study compared directly the two long-acting depot T products, subdermal T implants (TI) and injectable T undecanoate (TU) for maintenance of TRT. Design, setting and participants, Men with organic androgen deficiency (n = 38) undergoing regular TRT at an academic Andrology centre were recruited for a two period, randomized sequence, cross-over clinical trial without intervening wash-out period of TRT maintenance. Outcomes, For both depot T products, their pharmacokinetics and pharmacodynamics were evaluated using a range of androgen sensitive clinical, laboratory and quality of life measures as well as preference for ongoing treatment after experience of both products. Results, The two depot T products had distinct pharmacokinetics and were not bioequivalent. However, there were no consistent clinical differences in a comprehensive range of pharmacodynamic measures reflecting androgen effects on biochemistry and haematology, muscle mass and strength, and quality of life, mood and sexual function. The majority (91%) of participants chose TU over TI at study completion. Conclusion, Despite significant pharmacokinetic differences, the two depot T products are clinically interchangeable allowing for choice dependent on patient and physician delivery preference in practice but most patients preferred the injectable over the implantable form. [source] A Clinical, Radiographic, and Microbiologic Comparison of Astra Tech and Brånemark Single Tooth ImplantsCLINICAL IMPLANT DENTISTRY AND RELATED RESEARCH, Issue 2 2000Lorena Puchades-Roman BDS, M Clin Dent ABSTRACT Background: The soft tissues around single tooth implants differ fundamentally from the gingiva around natural teeth. There are very limited data comparing soft tissues around different implant systems. Aim: To assess whether the design characteristics of dental implants, particularly the implant-abutment junction, may affect the dimensions and health of the peri-implant soft tissues and radiographic bone levels. Subjects and Method: Fifteen Astra Tech and 15 Brånemark single tooth implants that had been in function for a minimum of 2 years in 30 partially dentate subjects were examined for plaque accumulation, probing depth, and bleeding on probing and compared to contralateral healthy teeth. Standardized radiographs were taken to measure the most coronal bone to implant contact on the mesial and distal surfaces. In addition, samples of subgingival plaque were taken on paper points and examined by darkfield microscopy. Results: Significantly higher mean probing depths (p < .001) and higher mean percentage of spirochetes (p= .003) were found at implants compared to teeth. In this sample, the Brånemark implants had significantly higher probing depths than the Astra Tech implants (median and interquartile range: Astra Tech 2.7 mm [2,3], Brånemark 3.3 mm [3,3.7] p= .026) and the most coronal bone to implant contact was closer to the implant,abutment junction in the Astra Tech implants (Astra Tech 0.6 mm [0.2,0.9], Brånemark 1.6 mm [1.4,2.0]. p < .001). Conclusion: Although there were statistically significant differences between the two implant systems, the clinical differences were small and probably reflect differences in the biologic width in relation to the location and design of the implant-abutment junction. [source] | |||||||||||||||||||||||||||||||