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Selected AbstractsReduction of RV Pacing by Continuous Optimization of the AV IntervalPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 4 2006GORAN MILASINOVIC Background: In patients requiring permanent pacing, preservation of intrinsic ventricular activation is preferred whenever possible. The Search AV+ (SAV+) algorithm in Medtronic EnPulseÔ dual-chamber pacemakers can increase atrioventricular (AV) intervals to 320 ms in patients with intact or intermittent AV conduction. This prospective, multicenter study compared the percentage of ventricular pacing with and without AV interval extension. Methods: Among 197 patients enrolled in the study, the percentage of ventricular-paced beats was evaluated via device diagnostics at the 1-month follow-up. Patient cohorts were defined by clinician assessment of conduction via a 1:1 AV conduction test at the 2-week follow-up. The observed percentage of ventricular pacing with SAV + ON and the predicted percentage of ventricular pacing with SAV + OFF were determined from the SAV + histogram data for the period between the 2-week and 1-month follow-up visits. Results: Of 197 patients, 110 (55.8%) had intact 1:1 AV conduction, of which 109 had 1-month data. SAV + remained ON in 99/109 patients; 10 patients had intrinsic A-V conduction intervals beyond SAV + nominal and therefore SAV + disabled. The mean percentage of ventricular pacing in the 109 patients was SAV+ ON = 23.1% (median 3.7%) versus SAV + OFF = 97.2% (median 99.7%). In 87 patients without 1:1 AV conduction, SAV + was programmed OFF in 6, automatically disabled in 52, and remained ON in 29. In 8 of these patients, 80,100% reduction in ventricular pacing was observed with SAV + ON. Conclusion: The Search AV+ algorithm in the EnPulse pacemaker effectively promotes intrinsic ventricular activation and substantially reduces unnecessary ventricular pacing. [source] Pitfalls in the Diagnosis of Cerebellar InfarctionACADEMIC EMERGENCY MEDICINE, Issue 1 2007Sean I. Savitz MD Abstract Background Cerebellar infarctions are an important cause of neurologic disease. Failure to recognize and rapidly diagnose cerebellar infarction may lead to serious morbidity and mortality due to hydrocephalus and brain stem infarction. Objectives To identify sources of preventable medical errors, the authors obtained pilot data on cerebellar ischemic strokes that were initially misdiagnosed in the emergency department. Methods Fifteen cases of misdiagnosed cerebellar infarctions were collected, all seen, or reviewed by the authors during a five-year period. For each patient, they report the presenting symptoms, the findings on neurologic examination performed in the emergency department, specific areas of the examination not performed or documented, diagnostic testing, the follow-up course after misdiagnosis, and outcome. The different types of errors leading to misdiagnosis are categorized. Results Half of the patients were younger than 50 years and presented with headache and dizziness. All patients had either incomplete or poorly documented neurologic examinations. Almost all patients had a computed tomographic scan of the head interpreted as normal, and most of these patients underwent subsequent magnetic resonance imaging showing cerebellar infarction. The initial incorrect diagnoses included migraine, toxic encephalopathy, gastritis, meningitis, myocardial infarction, and polyneuropathy. The overall mortality in this patient cohort was 40%. Among the survivors, about 50% had disabling deficits. Pitfalls leading to misdiagnosis involved the clinical evaluation, diagnostic testing, and establishing a diagnosis and disposition. Conclusions This study demonstrates how the diagnosis of cerebellar infarction can be missed or delayed in patients presenting to the emergency department. [source] Risperidone long-acting injection: a 6-year mirror-image study of healthcare resource useACTA PSYCHIATRICA SCANDINAVICA, Issue 2 2009D. Taylor Objective:, To evaluate naturalistic use of risperidone long-acting injection (RLAI) and its effect on healthcare resource use. Method:, Mirror-image comparison of healthcare resource use for 3 years before RLAI initiation and 3 years after. Results:, In total, 211 of 277 patients consecutively prescribed RLAI were evaluable over the full 6-year study period. Median days in hospital/patient increased significantly in the 3 years after RLAI initiation [87 days (inter-quartile range 25,236) before vs. 192 days (47,426) after; P < 0.001]. Those 34 patients who continued RLAI for 3 years showed no change in median bed days [64 days (6.5,182) before vs. 64 days (12,180) after] and median number of admissions was decreased [1.5 (1,2.25) before vs. 1.00 (0,1.25) after; P = 0.001]. Healthcare costs more than doubled for the whole cohort (P < 0.001) and discontinuers (P < 0.001) and increased significantly for continuers (P = 0.010). Conclusion:, RLAI did not decrease either time spent in hospital or overall healthcare costs in this patient cohort. [source] High-density lipoprotein cholesterol, C-reactive protein, and prevalence and severity of coronary artery disease in 5641 consecutive patients undergoing coronary angiographyEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 6 2008H. F. Alber ABSTRACT Background, Although high-density lipoprotein cholesterol (HDL-C) and C-reactive protein (CRP) are well-established predictors for future cardiovascular events, little information is available regarding their correlation with the prevalence and severity of angiographically evaluated coronary artery disease (CAD). Material and methods,, Five thousand six hundred forty-one consecutive patients undergoing coronary angiography for the evaluation of CAD were analysed. Cardiovascular risk factors were assessed by routine blood chemistry and questionnaire. CAD severity was graded by visual estimation of lumen diameter stenosis with significant stenoses defined as lumen diameter reduction of , 70%. Coronary angiograms were graded as one-, two- or three-vessel disease, as nonsignificant CAD (lumen irregularities < 70%) or non-CAD. Results,, HDL-C (60·3 ± 18·5 vs. 51·9 ± 15·3 mg dL,1; P < 0·001) was higher and CRP was lower (0·65 ± 1·68 vs. 1·02 ± 2·38 mg dL,1; P < 0·001) in non-CAD (n = 1517) compared to overall CAD patients (n = 4124). CAD patients were older (65·2 ± 10·5 years vs. 59·9 ± 11·4 years), more often diabetics (19·2% vs. 10·6%) and hypertensives (79·2% vs. 66·0%) and included more smokers (18·8% vs. 16·5%) (all P < 0·005). Low-density lipoprotein cholesterol (124·5 ± 38·3 vs. 126·0 ± 36·3 mg dL,1; P = NS) was similar in overall CAD and non-CAD patients with more statin users (43·4% vs. 27·9%; P < 0·001) among CAD patients. Comparing non-CAD with different CAD severities using analysis of variance, results did not change substantially. In a multivariate analysis, HDL-C and CRP remained independently associated with the prevalence of CAD. In addition, HDL-C is also a potent predictor for the severity of CAD. Conclusions,, In this large consecutive patient cohort, HDL-C and CRP are independently associated with the prevalence of CAD. In this analysis, HDL-C is an even stronger predictor for CAD than some other major classical risk factors. [source] Allogeneic haematopoietic cell transplantation for chronic myelogenous leukaemia in the era of imatinib: a retrospective multicentre studyEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 1 2006Martin Bornhäuser Abstract:,Objective:,To analyse the results of allogeneic haematopoietic cell transplantation (HCT) in patients with advanced stages of Philadelphia chromosome-positive chronic myelogenous leukaemia (CML) who had previously been treated with imatinib mesylate (IM). Methods:,We analysed the outcome of 61 patients with CML who had received allogeneic HCT from sibling (n = 18) or unrelated (n = 43) donors after having been treated with IM. Forty-one patients had received IM because of accelerated or blast phase CML. Conditioning therapy contained standard doses of busulfan (n = 25) or total-body irradiation (n = 20) in conjunction with cyclophosphamide in the majority of cases. Sixteen patients received dose-reduced conditioning with fludarabine-based regimens. Results:,The incidence of grades II,IV and III,IV graft-versus-host disease was 66% and 38% respectively. The probability of overall survival (OS), disease-free survival (DFS) and relapse at 18 months for the whole patient cohort were 37%, 33% and 24% respectively. The probability of non-relapse mortality (NRM) at 100 d and 12 months was 30% and 46% respectively. Univariate analysis showed that fludarabine-based conditioning therapy, age ,40 yr and >12 months interval between diagnosis and transplantation were associated with a significantly lower OS and DFS and a higher NRM. Conclusion:,These data suggest that although pretreatment with IM is not an independent negative prognostic factor, it cannot improve the dismal prognosis of CML patients at high risk for transplant-related mortality. [source] Functional C3435T polymorphism of MDR1 gene: an impact on genetic susceptibility and clinical outcome of childhood acute lymphoblastic leukemiaEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5 2004Krzysztof Jamroziak Abstract: The significance of genetic background in childhood acute lymphoblastic leukemia (ALL) is not well understood. Polymorphisms of genes encoding for xenobiotics and drug transporters are potential factors, which can influence the risk of developing ALL and its clinical outcome. P-glycoprotein (P-gp) is an adenosine triphosphate-binding cassette (ABC)-family transporter involved in protection against xenobiotics and multi-drug resistance. Recently, the single-nucleotide polymorphism C3435T of MDR1 gene has been found to be associated with altered tissue expression and function of P-gp. To evaluate whether C3435T MDR1 polymorphism is associated with the occurrence and outcome of ALL, 113 children with ALL (median age 5.1 yr) and 175 healthy individuals of Polish Caucasian origin were studied by polymerase chain reaction-restriction fragment-length polymorhism (PCR-RFLP) assay. The mutant homozygous TT genotype was found to be associated with occurrence of ALL (OR, 95% CI; 1.8, 1.1,3.1; P = 0.037). Besides, the analysis of factors influencing clinical outcome of our ALL patient cohort showed that CC genotype carriers had significantly lower event-free survival probability (pEFS) (0.62 vs. 0.87; P = 0.007) and overall survival probability (pOS) (0.72 vs. 0.91; P = 0.006). The Cox proportional hazards model-based analysis revealed that the hazard ratios for lower pEFS and lower pOS among CC homozygous subjects were 3.9 (P = 0.008) and 3.3 (P = 0.02), respectively. In conclusion, the results of the present study provide evidence that C3435T MDR1 polymorphism may involve both the susceptibility to and the clinical outcome of childhood ALL. Carriers of the TT genotype are more at risk of developing ALL than other individuals, whereas CC genotype carriers are supposed to have worse prognosis. [source] Hypertrophic cardiomyopathy in the elderlyGERIATRICS & GERONTOLOGY INTERNATIONAL, Issue 1 2010Toru Kubo Hypertrophic cardiomyopathy (HCM) is a relatively common genetic cardiac disorder with heterogeneous morphological, functional and clinical features. Although the risk of sudden death and incapacitating symptoms in young patients has been focused upon, the disease has been found with increasing frequency in elderly patients. However, there have been few studies on clinical features of HCM in the elderly. We established a cardiomyopathy registration study in Kochi Prefecture, which is one of the most aged communities in Japan, to provide detailed descriptions of the clinical features of HCM in a community-based patient cohort. The unselected regional HCM population consisted largely of elderly patients (70% of the study cohort being ,60 years of age at registration), although HCM has been regarded largely as a disease of the young. Cardiac hypertrophy that becomes clinically apparent late in life can be a genetic disorder, and mutations in the cardiac myosin-binding protein C gene are the most common cause of late-onset or elderly HCM. In the morphological features, sarcomere gene defects seem to have a predilection for a crescent-shaped left ventricular cavity with reversed septal curvature even in elderly patients, although an ovoid left ventricular shape was frequently seen in elderly patients in previous clinical studies on morphological characteristics of HCM. In middle-aged or elderly patients with HCM, heart failure and embolic events, which were strongly associated with atrial fibrillation, were very important. It is important to manage HCM patients from the standpoint of longitudinal evolution in order to prevent those clinical complications. [source] Impact of young age on prognosis for head and neck cancer: A matched-pair analysisHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 4 2005Jeffrey S. Gilroy MD Abstract Background. The purpose of this study was to review outcomes of young patients (age <40 years) treated with definitive radiotherapy alone for squamous cell carcinoma of the oropharynx, and larynx, and to compare these results with an older matched patient cohort. Methods. Since 1983, 30 previously untreated young patients underwent definitive radiotherapy at the University of Florida and were matched with an older group of patients (age >45 years) with respect to primary site, stage of disease, and sex. Results. There was no difference in cause-specific survival, locoregional control, or long-term complications between the two groups; however, there was a significant difference in overall survival favoring young patients (p = .0174). Older patients had twice as many second malignancies. Conclusion. Young age does not confer a worse prognosis in patients treated with definitive radiotherapy for squamous cell carcinoma of the oropharynx and larynx. © 2005 Wiley Periodicals, Inc. Head Neck27: XXX,XXX, 2005 [source] Postradiotherapy surveillance practice for head and neck squamous cell carcinoma,too much for too little?,HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 12 2003David L. Schwartz MD Abstract Introduction. Limited information is available regarding surveillance patterns after head and neck cancer radiotherapy. We cataloged follow-up for a specified patient cohort treated at three neighboring university, community, and Veterans Administration institutions. Methods. One hundred fifteen patients were treated with curative intent between 1994,1998 with definitive or postoperative radiotherapy for newly diagnosed squamous cell carcinoma of the oral cavity, oropharynx, larynx, or hypopharynx. One hundred patients had continuous follow-up at their treating institution and were included for analysis. Median follow-up until disease recurrence or censorship was 28.5 months. Results. Median follow-up frequency was 5.7 visits/year and was highly variable. Although visit frequency correlated with disease stage and the presence of high-risk disease features, this association was lost when patients with early recurrences were removed from analysis. Procedure and test utilization closely mirrored visit frequency, resulting in a wide range of estimated yearly charges ($0,15,668/year; median, $1,772/year). Actuarial 3-year overall survival for the study group was 71%. Eighty-six percent (19 of 22) of potentially salvageable locoregional failures were discovered secondary to symptomatic complaint rather than by test results. Disease failure, whether detected by symptom or testing, predicted for poor survival (22% at 24 months after recurrence). Conclusions. Postradiotherapy surveillance for head and neck cancer is inconsistently pursued. A proven correlation between intensive follow-up and improved patient survival is lacking. Surveillance directed by patient symptoms should be investigated as an alternative approach. © 2003 Wiley Periodicals, Inc. Head Neck 25: 000,000, 2003 [source] Bioreactance: A new tool for cardiac output and thoracic fluid content monitoring during hemodialysisHEMODIALYSIS INTERNATIONAL, Issue 4 2009Niloufar KOSSARI Abstract Outpatient hemodialysis therapy (HD) can be associated with hemodynamic compromise. Bioreactance® has recently been shown to provide accurate, noninvasive, continuous, measurements of cardiac output (CO) and thoracic impedance (Zo) from which thoracic fluid content (TFC) can be derived assuming TFC=1000/Zo. This study was designed to evaluate the changes in TFC in comparison with the traditional indices of fluid removal (FR) and to understand the trends in CO changes in HD patients. Minute-by-minute changes in TFC and CO were prospectively collected using the bioreactance system (NICOM®) in HD patients of a single unit. Changes in body weight (,W), hematocrit (,Hct), and amount of FR were also measured. Twenty-five patients (age 77 ± 11 years) were included. The TFC decreased in all patients by an average of 5.4 ± 7.9 k,,1, weight decreased by 1.48 ± 0.98 kg, and FR averaged 2.07 ± 1.93 L over a 3- to 4-hour HD session. There were good correlations between ,TFC and ,W (R=0.80, P<0.0001) and FR (R=0.85, P<0.0001). ,Hct (4.13 ± 3.42%) was poorly correlated with ,TFC (R=0.35, P=0.12) and FR (R=0.40, P=0.07). The regression line between FR and TFC yielded FR=1.0024,0.1985TFC; thus, a 1 k,,1 change of Zo correlates with an ,200 mL change in total body water. The change in CO (,0.52 ± 0.49 L/min m2) during HD did not correlate with FR (R=0.15, P=NS). Changes in TFC represented the monitored variable most closely related to FR. CO remained fairly constant in this stable patient cohort. Further studies in high-risk patients are warranted to understand whether TFC and CO monitoring can improve HD session management. [source] Outcomes of a patient-to-patient outbreak of genotype 3a hepatitis C,HEPATOLOGY, Issue 2 2009Mark E. Mailliard Between March 2000 and July 2001, at least 99 persons acquired a hepatitis C virus genotype 3a (HCV-3a) infection in an oncology clinic. This nosocomial HCV outbreak provided an opportunity to examine the subsequent clinical course in a well-defined cohort. This was a retrospective/prospective observational study of the short-term significant health outcomes of a large, single-source, patient-to-patient HCV-3a outbreak. Outbreak patients or their legal representatives consenting to study were enrolled between September 2002 and December 2007. We measured history and physical examinations, medical records, HCV serology, HCV RNA and genotype, liver enzymes, histology, response to antiviral therapy, and liver-related morbidity and mortality. Sixty-four of the 99 known HCV-3a outbreak patients participated. During a 6-year period, six patients developed life-threatening complications from liver disease, three died, one received a liver transplant, and two were stable after esophageal variceal banding or diuretic therapy of ascites. Thirty-three patients underwent antiviral therapy, with 28 achieving a sustained viral remission. One patient acquired HCV-3a infection sexually from an outbreak patient and was successfully treated. Eleven study patients died of malignancy, including two that had achieved a sustained viral remission after antiviral therapy. Conclusion: Our patient cohort had a nosocomial source and an oncologic or hematologic comorbidity. Compared with previous HCV outcome studies, a patient-to-patient HCV outbreak in an oncology clinic exhibited significant morbidity and mortality. Attention is needed to the public health risk of nosocomial HCV transmission, emphasizing infection control, early diagnosis, and therapy. (HEPATOLOGY 2009.) [source] Immunohistochemical detection of EGFR, fibrillin-2, P-cadherin and AP2, as biomarkers for rhabdomyosarcoma diagnosticsHISTOPATHOLOGY, Issue 7 2009Beate Grass Aims:, Subclassification of rhabdomyosarcoma (RMS) has clinical relevance, as the two major subclasses embryonal (ERMS) and alveolar (ARMS) rhabdomyosarcoma differ greatly in terms of aggressiveness and prognosis. However, histological analysis is not always sufficient for an unequivocal subclassification of RMS. Furthermore, clinical presentation of ARMS has been reported to mimic other tumour types, specifically lymphoma. The aim was to determine the role of four biomarkers in the diagnosis of rhabdomyosarcoma. Methods and results:, Recently, we identified four potential biomarkers to subclassify RMS with high sensitivity and specificity. These included epidermal growth factor receptor (EGFR) and fibrillin-2 as markers for ERMS, and AP2, and P-cadherin as markers for translocation-positive ARMS. Here, we further validate the potential of these four markers in a second, independent patient cohort by immunohistochemistry on 80 sections of RMS biopsy specimens as well as a tissue microarray representing 18 different additional tumour types, including seven lymphomas. The combination of EGFR and fibrillin-2 was able to detect ERMS with a specificity of 76% and sensitivity of 90%. The combination of AP2, and P-cadherin detected ARMS with a specificity of 97% and sensitivity of 90%, data very similar to our previous study. Furthermore, all lymphomas were clearly negative for AP2, and P-cadherin. Conclusions:, These four biomarkers are suitable for clinical implementation in the future diagnosis of RMS. [source] Mutation frequencies of X-linked mental retardation genes in families from the EuroMRX consortium,,HUMAN MUTATION, Issue 2 2007Arjan P.M. de Brouwer Abstract The EuroMRX family cohort consists of about 400 families with non-syndromic and 200 families with syndromic X-linked mental retardation (XLMR). After exclusion of Fragile X (Fra X) syndrome, probands from these families were tested for mutations in the coding sequence of 90 known and candidate XLMR genes. In total, 73 causative mutations were identified in 21 genes. For 42% of the families with obligate female carriers, the mental retardation phenotype could be explained by a mutation. There was no difference between families with (lod score >2) or without (lod score <2) significant linkage to the X chromosome. For families with two to five affected brothers (brother pair=BP families) only 17% of the MR could be explained. This is significantly lower (P=0.0067) than in families with obligate carrier females and indicates that the MR in about 40% (17/42) of the BP families is due to a single genetic defect on the X chromosome. The mutation frequency of XLMR genes in BP families is lower than can be expected on basis of the male to female ratio of patients with MR or observed recurrence risks. This might be explained by genetic risk factors on the X chromosome, resulting in a more complex etiology in a substantial portion of XLMR patients. The EuroMRX effort is the first attempt to unravel the molecular basis of cognitive dysfunction by large-scale approaches in a large patient cohort. Our results show that it is now possible to identify 42% of the genetic defects in non-syndromic and syndromic XLMR families with obligate female carriers. © 2007 Wiley-Liss, Inc. [source] An adaptive clinical Type 1 diabetes control protocol to optimize conventional self-monitoring blood glucose and multiple daily-injection therapyINTERNATIONAL JOURNAL OF ADAPTIVE CONTROL AND SIGNAL PROCESSING, Issue 5 2009Xing-Wei Wong Abstract The objective of this study was to develop a safe, robust and effective protocol for the clinical control of Type 1 diabetes using conventional self-monitoring blood glucose (SMBG) measurements, and multiple daily injection (MDI) with insulin analogues. A virtual patient method is used to develop an in silico simulation tool for Type 1 diabetes using data from a Type 1 diabetes patient cohort (n=40) . The tool is used to test two prandial insulin protocols, an adaptive protocol (AC) and a conventional intensive insulin therapy (IIT) protocol (CC) against results from a representative control cohort as a function of SMBG frequency. With the prandial protocols, optimal and suboptimal basal insulin replacement using a clinically validated, forced-titration regimen is also evaluated. A Monte Carlo (MC) analysis using variability and error distributions derived from the clinical and physiological literature is used to test efficacy and robustness. MC analysis is performed for over 1 400 000 simulated patient hours. All results are compared with control data from which the virtual patients were derived. In conditions of suboptimal basal insulin replacement, the AC protocol significantly decreases HbA1c for SMBG frequencies ,6/day compared with controls and the CC protocol. With optimal basal insulin, mild and severe hypoglycaemia is reduced by 86,100% over controls for all SMBG frequencies. Control with the CC protocol and suboptimal basal insulin replacement saturates at an SMBG frequency of 6/day. The forced-titration regimen requires a minimum SMBG frequency of 6/day to prevent increased hypoglycaemia. Overaggressive basal dose titration with the CC protocol at lower SMBG frequencies is likely caused by uncorrected postprandial hyperglycaemia from the previous night. From the MC analysis, a defined peak in control is achieved at an SMBG frequency of 8/day. However, 90% of the cohort meets American Diabetes Association recommended HbA1c with just 2 measurements a day. A further 7.5% requires 4 measurements a day and only 2.5% (1 patient) required 6 measurements a day. In safety, the AC protocol is the most robust to applied MC error. Over all SMBG frequencies, the median for severe hypoglycaemia increases from 0 to 0.12% and for mild hypoglycaemia by 0,5.19% compared with the unrealistic no error simulation. While statistically significant, these figures are still very low and the distributions are well below those of the controls group. An adaptive control protocol for Type 1 diabetes is tested in silico under conditions of realistic variability and error. The adaptive (AC) protocol is effective and safe compared with conventional IIT (CC) and controls. As the fear of hypoglycaemia is a large psychological barrier to appropriate glycaemic control, adaptive model-based protocols may represent the next evolution of IIT to deliver increased glycaemic control with increased safety over conventional methods, while still utilizing the most commonly used forms of intervention (SMBG and MDI). The use of MC methods to evaluate them provides a relevant robustness test that is not considered in the no error analyses of most other studies. Copyright © 2008 John Wiley & Sons, Ltd. [source] REG1A expression is a prognostic marker in colorectal cancer and associated with peritoneal carcinomatosisINTERNATIONAL JOURNAL OF CANCER, Issue 2 2008Christian Astrosini Abstract By expression profiling of early staged colon carcinomas, we found regenerating islet-derived 1 alpha (REG1A) to be upregulated in patients with an unfavorable clinical outcome. For validation, REG1A expression was quantified in another colorectal cancer (CRC) patient cohort by Taqman PCR. Aside from tumor and normal tissue from 63 nonpretreated CRC patients, 31 mucosa biopsies from healthy individuals as well as 22 adenomas were included in the investigation. REG1A was significantly upregulated in tumor specimens (p < 0.001) and adenoma (p < 0.01) as compared to normal colorectal tissue. REG1A expression in normal peritumoral tissue in turn proved to be significantly elevated compared to mucosa from healthy individuals (p < 0.01). Determination of REG1A expression might be useful for early tumor diagnosis with a sensitivity of 90.6%, and a specificity of 77.9%. REG1A expression was significantly increased in tumors with peritoneal carcinomatosis (p < 0.01). Moreover, REG1A turned out to be a significant predictor of disease-free survival (p < 0.05). In conclusion, we present evidence that REG1A is a molecular marker of prognostic value and is associated with peritoneal carcinomatosis in CRC. REG1A turned out to be already significantly raised in peritumoral normal tissue compared to mucosa from healthy individuals, suggesting a molecular field effect of secreted REG1A. © 2008 Wiley-Liss, Inc. [source] Identification of a novel single nucleotide polymorphism in the first tandem repeat sequence of the thymidylate synthase 2R alleleINTERNATIONAL JOURNAL OF CANCER, Issue 9 2007Lisa F. Lincz Abstract Thymidylate synthase (TS) activity is an important determinant of response to chemotherapy with fluoropyrimidine prodrugs and its expression is largely determined by the number of functional upstream stimulatory factor (USF) E-box consensus elements present in the 5,regulatory region of the TYMS gene. Two known polymorphisms in this area, a variable number of tandem repeat (VNTR) consisting of 2 or 3 repeats (2R/3R) of a 28-bp sequence and a further G > C single nucleotide substitution within the second repeat of the 3R, result in genotypes with between 2 and 4 functional repeats in most humans. Here, we identify a further G > C SNP in the first repeat of the TYMS 2R allele, which effectively abolishes the only functional USF protein binding site in this promoter. The frequency of the new allele was found to be 4.2% (95% CI = 1.4,9.6%), accounting for 8.8% (95% CI = 2.9,19.3%) of all 2R alleles in our patient cohort. Thus, we observed that the lowest number of inherited functional binding sites is 1 instead of 2 as previously thought, and could potentially be 0 in a homozygous individual. This would severely decrease TS expression and may have implications for predicting efficacy and toxicity of therapy with commonly used fluorouracil-based therapy regimes. © 2007 Wiley-Liss, Inc. [source] Investigation of dopamine receptors in susceptibility to behavioural and psychological symptoms in Alzheimer's diseaseINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 9 2009Antonia L. Pritchard Abstract Objective Alzheimer's disease (AD) patients commonly suffer from behavioural and psychological symptoms of dementia (BPSD). A genetic component to the development of BPSD in AD has been supported. Polymorphisms within dopamine receptors DRD1, DRD2, DRD3 and DRD4 have previously been investigated in a few interesting studies that are reviewed here and extended using our patient cohort. Methods Our large cohort of 395 probable AD patients had longitudinal information on the BPSD (Neuropsychiatric Inventory), which was used to dichotomise patients into whether they had ever suffered from a given symptom within the study period, or not. These measures were related to the DRD1 (A-48G), DRD2 (ser311cys; C-ins/del), DRD3 (ser9gly) and DRD4 (VNTR) genotype and allele frequencies. Results Associations were revealed between DRD3 and elation, and between DRD4 with agitation/aggression and with depression; however, these findings do not remain significant after correction for multiple testing. No associations were found with the other genetic variants and these symptoms and no associations were observed between any of the polymorphic variants examined and delusions, hallucinations, psychosis and aberrant motor behaviour. Conclusion Our data, in combination with a review of the literature, reveal a potential role for the VNTR variant of DRD4 in the development of depression in AD patients. The findings presented here need to be replicated in large, well characterised longitudinal cohorts. Copyright © 2009 John Wiley & Sons, Ltd. [source] The Permanency of Pulmonary Vein Isolation Using a Balloon Cryoablation CatheterJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 7 2010HUMERA AHMED B.A. Chronic PV Isolation With the Cryoballoon.,Background: Because of its technical feasibility and presumed safety benefits, balloon cryoablation is being increasingly employed for pulmonary vein (PV) isolation. While acute isolation has been demonstrated in most patients, little data are available on the chronic durability of cryoballoon lesions. Methods and Results: Twelve atrial fibrillation patients underwent PV isolation using either a 23-mm or 28-mm cryoballoon. For each vein, after electrical isolation was verified with the use of a circular mapping cathether, 2 bonus balloon ablation lesions were placed. Gaps in balloon occlusion were overcome using either a spot cryocatheter or a "pull-down" technique. A prespecified second procedure was performed at 8,12 weeks to assess for long-term PV isolation. Acute PV isolation was achieved in all PVs in the patient cohort (n = 48 PVs), using the cryoballoon alone in 47/48 PVs (98%); a "pull-down" technique was employed for 5 PVs (1 right superior pulmonary vein, 2 right inferior pulmonary veins, and 2 left inferior pulmonary veins). The gap in the remaining vein was ablated with a spot cryocatheter. During the second mapping procedure, 42 of 48 PVs (88%) remained isolated. One vein had reconnected in 2 patients, while 2 veins had reconnected in another 2 patients. All PVs initially isolated with the "pull-down" technique remained isolated at the second procedure. Conclusions: Cryoballoon ablation allows for durable PV isolation with the use of a single balloon. With maintained chronic isolation in most PVs, it may represent a significant step toward consistent and lasting ablation procedures. (J Cardiovasc Electrophysiol, Vol. pp. 731-737, July 2010) [source] Gingivitis as a risk factor in periodontal diseaseJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 2009Niklaus P. Lang Abstract Background: Dental plaque has been proven to initiate and promote gingival inflammation. Histologically, various stages of gingivitis may be characterized prior to progression of a lesion to periodontitis. Clinically, gingivitis is well recognized. Material & Methods: Longitudinal studies on a patient cohort of 565 middle class Norwegian males have been performed over a 26-year period to reveal the natural history of initial periodontitis in dental-minded subjects between 16 and 34 years of age at the beginning of the study. Results: Sites with consistent bleeding (GI=2) had 70% more attachment loss than sites that were consistenly non-inflamed (GI=0). Teeth with sites that were consistently non-inflamed had a 50-year survival rate of 99.5%, while teeth with consistently inflamed gingivae yielded a 50-year survival rate of 63.4%. Conclusion: Based on this longitudinal study on the natural history of periodontitis in a dentally well-maintained male population it can be concluded that persistent gingivitis represents a risk factor for periodontal attachment loss and for tooth loss. [source] Seizures, ataxia, developmental delay and the general paediatrician: Glucose transporter 1 deficiency syndromeJOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 5 2006David J Coman Aim Glucose transporter 1 deficiency syndrome (GLUT1-DS) is an important condition for the general paediatrician's differential armamentarium. We describe a case series of eight patients in order to raise awareness of this treatable neurometabolic condition. The diagnosis of GLUT1-DS is suggested by a decreased absolute cerebrospinal fluid (CSF) glucose value (<2.2 mmol/L) or lowered CSF: plasma glucose ratio (<0.4). Methods This is a review of eight Queensland patients with GLUT1-DS. The clinical presentation, clinical course, laboratory investigations and treatment outcomes are discussed. Results The clinical features noted in our patient cohort include combinations of ataxia, developmental delay and a severe seizure disorder that is refractory to anticonvulsant medications. Seizures are the most common clinical manifestation and may be exacerbated by phenobarbitone. The paired CSF: plasma glucose results ranged from 0.2 to 0.39 (normal <0.6) with an average of 0.33. 3-O-Methyl-D-Glucose uptake and GLUT1 Genotyping analysis have been performed on five patients thus far. Rapid and impressive seizure control was observed in 100% of our patients once the ketogenic diet was instituted, with half of the cohort being able to wean completely from anticonvulsants. Conclusion Children presenting with a clinical phenotype consisting of a refractory seizure disorder, ataxia and developmental delay should prompt the consideration of Glucose transporter 1 deficiency syndrome. While the diagnostic test of lumbar puncture is an invasive manoeuvre, the diagnosis provides a viable treatment option, the ketogenic diet. GLUT1-DS displays clinical heterogeneity, but the value of early diagnosis and treatment is demonstrated by our patient cohort. [source] Prevalence of cardiovascular disease and risk factors in a type 2 diabetic population of the North Catalonia diabetes studyJOURNAL OF THE AMERICAN ACADEMY OF NURSE PRACTITIONERS, Issue 3 2009DNS (Diabetes Nurse Specialist & Clinical Researcher), Jeronimo Jurado RN Abstract Purpose: The purpose of the study was to evaluate the prevalence of cardiovascular disease (CVD), cardiovascular risk factors (CVRFs), and their control in patients with type 2 diabetes mellitus (T2DM) at primary care settings from the North Catalonia Diabetes Study (NCDS). Data sources: In this multicentre cross-sectional descriptive study, data were collected from a random sample of 307 patients with T2DM. The prevalence of CVD, CVRF, metabolic syndrome (MS), coronary heart disease (CHD) risk at 10 years (Framingham Point Scores), and CVRF control was evaluated. MS and lipid profiles were established according to Adult Treatment Panel III criteria. Conclusions: CVD prevalence was 22.0% (CHD: 18.9% and peripheral ischemia: 4.5%) and more frequent in men. The prevalence of selected CVRF was: hypertension: 74.5%; dyslipidemia: 77.7%; smoking: 14.9%; obesity 44.9%, and familial CVD: 38.4%. Three or more CVRFs, including T2DM, were observed in 91.3%. MS prevalence was 68.7%. Framingham score was 10.0%, higher in men than in women. CVD prevalence was related to: age, number of CVRFs, duration of diabetes, familial history of CVD, waist circumference, hypertension, lipid profile, kidney disease, and Framingham score, but not to MS by itself. Correct lipid profiles and blood pressure were only observed in 18.9% and 24.0%, respectively, whereas platelet aggregation inhibitors were only recorded in 16.1% of the patient cohort. MS presence was not an independent risk factor of CVD in our study. Implications for practice: The high prevalence of CVD and an inadequate control of CVRF, which were apparent in the NCDS population, would suggest that advanced practice nurses should consider incorporating specific cardiovascular assessment in their routine care of persons with T2DM. [source] Changes in quality of life and sexual health are associated with low-dose peginterferon therapy and disease progression in patients with chronic hepatitis CALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 7 2010K. K. SNOW Aliment Pharmacol Ther,31, 719,734 Summary Background, Primary analysis of the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) Trial showed long-term peginterferon therapy did not reduce complications in patients with chronic hepatitis C and advanced fibrosis or cirrhosis. Aim, To assess the effects of long-term peginterferon therapy and disease progression on health-related quality of life (HRQOL), symptoms and sexual health in HALT-C patients. Methods, A total of 517 HALT-C patients received peginterferon alfa-2a (90 ,g/week); 532 received no additional treatment for 3.5 years. Patients were followed up for outcomes of death, hepatocellular carcinoma and hepatic decompensation. Sexual health, SF-36 scores and symptoms were serially assessed by repeated-measures analyses of covariance. Results, Patients with cirrhosis (n = 427) reported lower general well-being and more fatigue (P < 0.001) than patients with fibrosis (n = 622). Physical scores declined significantly over time, independent of treatment, and patients with cirrhosis reported lower scores. Vitality scores were lower in those with cirrhosis, and treated patients experienced a greater decline over time than untreated patients; HRQOL rebounded after treatment ended. Patients with a clinical outcome had significantly greater declines in all SF-36 and symptom scores. Among men, Sexual Health scores were significantly worse in treated patients and in those with a clinical outcome. Conclusion, Clinical progression of chronic hepatitis C and maintenance peginterferon therapy led to worsening of symptoms, HRQOL and, in men, sexual health in a large patient cohort followed up over 4 years (NCT00006164). [source] Clinical course of hepatitis B virus infection during pregnancyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 7 2009G. NGUYEN Summary Background, For women with hepatitis B virus (HBV) infection, little is known about the natural progression of the disease during pregnancy or its impact on pregnancy outcomes. Objectives, To investigate the natural progression of HBV infection during pregnancy or its impact on pregnancy outcomes. Methods, In this retrospective cohort study, we reviewed medical records of all patients who were pregnant and presented with HBsAg-positivity between 2000 and 2008 at a community gastroenterology practice and a university hepatology clinic. Maternal characteristics were analysed according to maternal and perinatal outcomes. Results, A total of 29 cases with at least 2 measurements of either HBV DNA or alanine aminotransferase (ALT) levels were included. Older age was the only predictor of a trend towards higher risk of an adverse clinical outcome [OR = 1.21 (0.97,1.51), P = 0.089], defined as either a negative foetal outcome (premature delivery, spontaneous abortion), or a negative maternal outcomes (gestational diabetes mellitus, pre-eclampsia, hepatic flare, liver failure). This trend for age remained even after adjusting for baseline ALT. Baseline serum HBV DNA, ALT, hepatitis B e antigen status, gravida and parity were not significant predictors for adverse clinical outcomes. Four patients developed liver failure. Conclusions, Maternal and neonatal outcomes are highly variable in this clinic-based patient cohort. Severe complications due to HBV infection can occur during pregnancy in previously asymptomatic patients. It is unclear how generalizable the results observed in this cohort would be to the general population; therefore, further studies are needed to identify reliable predictors for significant adverse outcomes and until more data are available, pregnant patients with HBV infection should be monitored with periodic serum HBV DNA and ALT levels. [source] Muscle preservation using an implantable electrical system after nerve injury and repairMICROSURGERY, Issue 6 2001F.R.C.S.(C), Stephen C. Nicolaidis M.D. The value of continuous electrical stimulation of denervated muscles after nerve injury and repair has been clearly shown in a series of laboratory experiments in three animal models. This experimental background, which showed improved muscle preservation and better functional results, evolved into a clinical study that included 15 patients with peripheral nerve injuries in the upper extremities, 3 patients with brachial plexus injuries, and three patients with facial nerve paralysis. Improved functional results were obtained using this implantable system, which were similar to those achieved with the animal experiments. All patients had muscle stimulation for extended periods ranging from 127 to 346 days. Analysis of the results showed satisfactory nerve regeneration on clinical examination and with electromyographic studies. Functional muscle analysis varied somewhat from patient to patient, but every patient had a satisfactory to excellent recovery. The results from this study have clearly shown the benefits of continuous muscle stimulation using an implantable electrical system after nerve injury and repair expansion of the project to a larger patient cohort is indicated. © 2001 Wiley-Liss, Inc. MICROSURGERY 21:241,247 2001 [source] Are Implantable Loop Recorders Useful in Detecting Arrhythmias in Children with Unexplained Syncope?PACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 11 2009KHALID N. AL DHAHRI M.B.B.S. Introduction: Syncope and presyncope are symptoms that occur infrequently in children, are unpredictable, and represent a diagnostic challenge to the physician. Conventional diagnostic investigations are often unable to establish a diagnosis, making it difficult to determine patient risk and direct appropriate therapy. The implantable loop recorder (ILR) is a medical device that was created for prolonged monitoring of heart rate and rhythm and has been used in a limited number of pediatric studies in which the cause of the syncope is unknown. Methods: This is a retrospective review of the clinical, surgical, and follow-up data of patients who had ILR devices implanted after conventional testing failed to identify a cause for their symptoms. Results: The diagnostic yield of the ILR device in unmasking the cause for symptoms in our patient cohort was 64%. In our study, manually activated events accounted for 71% of all documented episodes and 68% of the cases involving hemodynamically important arrhythmias or transient rhythm changes. The ILR device can be safely implanted and explanted in children without significant morbidity, in most cases. None of our patients experienced any long-term adverse events associated with placement of the device and all were alive at last follow-up. Conclusions: The use of the ILR device is a useful tool to help unmask arrhythmias as a cause of unexplained syncope in children. Patient selection for who should and should not have an ILR device implanted will continue to influence its diagnostic utility and generate controversy among stakeholders. [source] Geminin predicts adverse clinical outcome in breast cancer by reflecting cell-cycle progressionTHE JOURNAL OF PATHOLOGY, Issue 2 2004Michael A Gonzalez Abstract Geminin inhibits DNA replication by preventing Cdt1 from loading minichromosome maintenance (MCM) proteins onto DNA. The present study has investigated whether the frequency of geminin expression predicts clinical outcome in breast cancer. Immunohistochemistry was used first to examine geminin expression in normal and malignant breast tissue (n = 67). Correlations with cell-cycle parameters, pathological features, and clinical outcome were then determined using an invasive breast carcinoma tissue microarray (n = 165). Breast carcinomas were scanned for mutations (n = 61) and copy number imbalances (n = 241) of the geminin gene. Finally, the cell cycle distribution of geminin in breast cancer cells was investigated in vivo and in vitro. Despite a putative tumour suppressor function, it was found that increased geminin expression is a powerful independent indicator of adverse prognosis in invasive breast cancer. Both poor overall survival (p = 0.0002) and the development of distant metastases (p = 0.005) are predicted by high geminin expression, which performs better in this patient cohort than traditional factors currently used to determine prognosis and appropriate therapy. No mutations or deletions of the geminin gene and no evidence that a high frequency of protein expression is related to gene amplification were found. It is shown that geminin is expressed from S to M phase in breast carcinoma tissue and cell lines, disappearing at the metaphase,anaphase transition. While MCM proteins identify all non-quiescent cells, geminin identifies the sub-fraction that have entered S phase, but not exited mitosis, thereby indicating the rate of cell-cycle progression. It is suggested that this explains its unexpected value as a prognostic marker in breast cancer. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] ORIGINAL RESEARCH,ERECTILE DYSFUNCTION: Baseline Prevalence of Erectile Dysfunction in a Prostate Cancer Screening PopulationTHE JOURNAL OF SEXUAL MEDICINE, Issue 2 2008Jochen Walz MD ABSTRACT Introduction., Erectile dysfunction (ED) is common in older men and can be worsened by prostate cancer (PCa) treatment. True ED rates before PCa treatment are mandatory, in order to assess the rate of ED attributable to PCa treatment. Data derived from population-based studies or from patients surveyed after PCa diagnosis, as well as just prior to treatment may not represent a valid benchmark, as health profiles of the general population might be different to those undergoing PCa screening or as anxiety may worsen existent ED. Aim., To circumvent these limitations, we assessed the baseline rate of ED in PCa diagnosis-free men participating in a PCa awareness event. Methods., ED was classified according to the International Index of Erectile Function (IIEF) score as absent (IIEF: 25,30), mild (22,24), mild to moderate (17,21), moderate (11,16), or severe (,10). Analyses were adjusted according to age and socioeconomic status. Main Outcome Measures., Of 1,273 asymptomatic men who participated in the event, 1,134 (89.1%) completed the IIEF score. Results., Mean age was 57.6 years (range 40,89 years). Of all participating men, 50.0% (N = 566) were potent, 8.8% (N = 100) reported mild, 10.4% (N = 118) mild to moderate, 9.4% (N = 107) moderate, and 21.4% (N = 243) severe ED. Men with ED were significantly older (P < 0.001), had no stable partner (P < 0.001), lower education (P < 0.001), and lower annual income (P < 0.001) than men without ED. Conclusions., One in two men who participated in this PCa awareness event is affected by ED, independent of PCa diagnosis or treatment. Such high prevalence of baseline ED in a PCa screening cohort suggests that in patients treated for PCa, ED may represent a common disorder already present prior to treatment. Moreover, socioeconomic variables were seen to have an important influence on erectile function in this patient cohort. Walz J, Perrotte P, Suardi N, Hutterer G, Jeldres C, Bénard F, Valiquette L, Graefen M, Montorsi F, and Karakiewicz PI. Baseline prevalence of erectile dysfunction in a prostate cancer screening population. J Sex Med 2008;5:428,435. [source] Predictive value of PCA3 in urinary sediments in determining clinico-pathological characteristics of prostate cancer,THE PROSTATE, Issue 1 2010Daphne Hessels Abstract PURPOSE PCA3 urine tests have shown to improve the specificity in prostate cancer (PCa) diagnosis, and have thus the potential to reduce the number of unnecessary prostate biopsies and to predict repeat biopsy outcomes. In this study, PCA3 was correlated with clinical stage, biopsy Gleason score (GS), radical prostatectomy GS, tumor volume, and pathological stage to assess its potential as predictor of PCa aggressiveness. METHODS In this study, 351 men admitted for prostate biopsies based on serum PSA levels >3,ng/ml, an abnormal DRE, and/or a family history of PCa were included. Post-DRE urinary sediments from 336 men were tested using a transcription-mediated amplification-based PCA3 test, and assay results were correlated with clinical stage and biopsy GS. In a sub-cohort of 70 men who underwent radical prostatectomy, the PCA3 values were correlated to their radical prostatectomy GS, tumor volume, and pathological stage. RESULTS In this patient cohort we could not find a correlation between clinical stage, biopsy GS, radical prostatectomy GS, tumor volume, and pathological stage. CONCLUSIONS The predictive value of PCA3 for PCa aggressiveness features as reported in earlier studies cannot be confirmed in our study. Experimental differences (urine sediments vs. whole urine) and cohort may explain this. The exact place of PCA3 as prognostic test for PCa remains the subject of investigation. Prostate 70: 10,16, 2010. © 2009 Wiley-Liss, Inc. [source] The Diagnostic Conundrum and Liver Transplantation Outcome for Combined Hepatocellular-CholangiocarcinomaAMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2010C. Panjala Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is a rare primary liver malignancy with mixed hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) histological features. It is almost impossible to obtain an accurate, preoperative noninvasive diagnosis of cHCC-CC with tumor markers or cross-sectional abdominal imaging due to the mixed histological features. Despite these difficulties, accurate cHCC-CC diagnosis remains an important goal with prognostic significance. In our study, we retrospectively reviewed the tumor markers: AFP and CA 19-9, and cross-sectional liver imaging, in light of liver explant findings, to identify and characterize cHCC-CC features followed by liver transplantation (LT) outcome analysis. The results from this 12 patient cohort failed to identify characteristic features for cHCC-CC. None of the imaging features helped to identify the cHCC-CC tumor and they mimicked either HCC or CC, depending on the degree of glandular differentiation expressed histologically. In our cHCC-CC LT recipients, the 1-, 3- and 5-year cumulative survival probabilities were 79%, 66% and 16%, respectively with a 5-year survival comparable to or better than LT for intrahepatic CC but poorer than LT for HCC following the Milan criteria. Conceivably explained by its cholangiocarcinoma component the LT outcome for this rare and hard to diagnose tumor appears poor. [source] CT15 RISK STRATIFICATION MODELS FOR HEART VALVE SURGERYANZ JOURNAL OF SURGERY, Issue 2007C. H. Yap Purpose Risk stratification models may be useful in aiding surgical decision-making, preoperative informed consent, quality assurance and healthcare management. While several overseas models exist, no model has been well-validated for use in Australia. We aimed to assess the performance of two valve surgery risk stratification models in an Australian patient cohort. Method The Society of Cardiothoracic Surgeons of Great Britain and Ireland (SCTS) and Northern New England (NNE) models were applied to all patients undergoing valvular heart surgery at St Vincent's Hospital Melbourne and The Geelong Hospital between June 2001 and November 2006. Observed and predicted early mortalities were compared using the chi-square test. Model discrimination was assessed by the area under the receiver operating characteristic (ROC) curve. Model calibration was tested by applying the chi-square test to risk tertiles. Results SCTS model (n = 1095) performed well. Observed mortality was 4.84%, expected mortality 6.64% (chi-square p = 0.20). Model discrimination (area under ROC curve 0.835) and calibration was good (chi-square p = 0.9). the NNE model (n = 1015) over-predicted mortality. Observed mortality 4.83% and expected 7.54% (chi-square p < 0.02). Model discrimination (area under ROC curve 0.835) and calibration was good (chi-square p = 0.9). Conclusion Both models showed good model discrimination and calibration. The NNE model over-predicted early mortality whilst the SCTS model performed well in our cohort of patients. The SCTS model may be useful for use in Australia for risk stratification. [source] | ||||||||||||||||||||||||||||||||||||||||