bluuebunny/crossref_metadata_2025 huggingface dataset:
Biliary Cast Syndrome Following Liver Transplantation: Predictive Factors and Clinical Outcomes
Authors: Gor Niraj V. , Levy Ronald M. , Ahn Joseph , Kogan Dmitriy , Dodson Forrest S. , Cohen Stanley Martin
Published: September 2008

Biliary cast syndrome (BCS), the presence of biliary casts and debris causing biliary obstruction, occurs in 4%-18% of orthotopic liver transplant (OLT) recipients. Potential consequences include cholangitis and graft damage or loss. Limited data exist regarding the etiology and outcomes of BCS. The purpose of this study was to evaluate donor and recipient risk factors and determine the impact of BCS. A retrospective review of 355 OLT cases identified 9 BCS patients (2.5%) diagnosed by cholangiography. Twenty-six matched controls were also identified. The warm ischemic time was significantly longer in BCS patients. Other recipient and donor preoperative and intraoperative characteristics, including the donor risk index, revealed no significant differences. Overall patient survival showed a trend toward worse outcomes at 6, 12, and 18 months and end of follow-up in the BCS group. Overall graft survival was also worse in the BCS group at all time periods, with statistical significance demonstrated at 18 months and end of follow-up. The number of therapeutic biliary procedures and hospital readmissions was significantly higher in the BCS group. Twenty-two percent of the BCS patients required repeat OLT versus none of the control patients. In conclusion, BCS is an uncommon complication of OLT. Except for a longer warm ischemic time, recipient and donor factors did not predict the occurrence of BCS. BCS patients showed a significantly worse graft survival, as well as a trend toward worse patient survival. Given the negative impact of BCS on liver transplant outcomes, further studies appear justified. Liver Transpl 14:1466–1472, 2008. © 2008 AASLD.
Risk Factors and Outcomes in Post–Liver Transplantation Bile Duct Stones and Casts: A Case-Control Study
Authors: Spier Bret J. , Pfau Patrick R. , Lorenze Katelin R. , Knechtle Stuart J. , Said Adnan
Published: September 2008

Bile duct stones and casts (BDS) after liver transplantation are associated with significant morbidity. Risk factors for BDS formation and the efficacy of treatment in liver transplant recipients have not been systematically studied. The aim of this study was to evaluate potential risk factors for the formation of BDS in patients post–liver transplant. A case-control study of consecutive liver transplant recipients at a university hospital from 1989 to 2007 was performed to identify risk factors for BDS formation. Cases included all liver transplant recipients with BDS, excluding those with concurrent t-tubes or biliary stents. Controls were chosen randomly from the total liver transplant population matched for year of transplantation. Pre- and post-OLT risk factors were analyzed with univariate and multivariate analyses. There were 49 cases and 101 controls over an 18-year-period (1289 liver transplants performed) with an incidence of 3.8% for BDS. In the cases, the median time to BDS diagnosis was 613 days from time of transplant. The controls had a median follow-up of 1530 days. Use of ursodeoxycholic acid was protective (P = 0.005), whereas bile duct pathology (P = 0.003), total cholesterol ≥ 200 mg/dL (P = 0.008), and triglyceride ≥ 150 mg/dL (P = 0.008) were significant risk factors for BDS formation. Endoscopic retrograde cholangiopancreatography (ERCP) was technically successful in all cases with resolution or improvement of liver chemistries in 59% (29) of patients. In conclusion, significant risk factors for forming BDS included bile duct pathology and elevated total cholesterol and triglyceride levels. Ursodeoxycholic acid had a significant effect in preventing the development of posttransplant BDS and should be used in those that are at increased risk. ERCP is a safe and effective diagnostic and therapeutic modality for these patients. Liver Transpl 14:1461–1465, 2008. © 2008 AASLD.
Use of the Molecular Adsorbents Recirculating System as a Treatment for Acute Decompensated Wilson Disease
Authors: Chiu Alexander , Tsoi Nai Shun , Fan Sheung Tat
Published: September 2008

Acute decompensated Wilson disease presenting as fulminant liver failure is a life-threatening condition for which liver transplantation is the ultimate treatment. It is listed as a status 1 indication according to the United Network for Organ Sharing classification. A massive amount of copper released during the attack induces hemolytic anemia and acute renal failure. Conventional chelating therapy attempting to remove copper from the patient is not satisfactory because there is inadequate time for these drugs to take action and patients are usually oliguric. The Molecular Adsorbents Recirculating System (MARS) is a form of modified dialysis that removes putative albumin-bound toxins associated with liver failure. It is believed that extracorporeal albumin dialysate absorbs the circulating copper molecules that are trapped in the patient's circulation. We report 2 patients with acute decompensated Wilson disease treated with MARS. In the first case, the patient was started on MARS once conventional treatment failed. A significant amount of copper was removed from her circulatory system, and her condition stabilized afterwards. The treatment gained her extra time, and she was eventually bridged to liver transplantation. In the second case, the patient was started on MARS treatment early in the course of his illness, and his condition soon stabilized after the treatment. He was able to return to his home country for liver transplantation. In both cases, MARS was used as a means of preventing deterioration rather than salvaging devastation. In conclusion, MARS may confer benefits to patients with acute decompensated Wilson disease if it is started early in the course of illness. Liver Transpl 14:1512–1516, 2008. © 2008 AASLD.
Abnormal Neurological Features Predict Poor Survival and Should Preclude Liver Transplantation in Patients with Deoxyguanosine Kinase Deficiency
Authors: Dimmock David P. , Dunn Kay J. , Feigenbaum Annette , Rupar Anthony , Horvath Rita , Freisinger Peter , de Camaret Bénédicte Mousson , Wong Lee-Jun , Scaglia Fernando
Published: September 2008

Deoxyguanosine kinase (DGUOK) deficiency is the commonest type of mitochondrial DNA depletion associated with a hepatocerebral phenotype. In this article, we evaluate predictors of survival and therapeutic options in patients with DGUOK deficiency. A systematic search of MEDLINE, LILAC, and SCIELO was carried out to identify peer-reviewed clinical trials, randomized controlled trials, meta-analyses, and other studies with clinical pertinence. DGUOK deficiency was searched with the terms dGK, DGUOK, mitochondrial DNA depletion, mtDNA, and hepatocerebral. Bibliographies of identified articles were reviewed for additional references. Thirteen identified studies met the inclusion criteria and were used in this study. The analysis revealed that DGUOK deficiency is associated with a variable clinical phenotype. Long-term survival is best predicted by the absence of profound hypotonia, significant psychomotor retardation, or nystagmus. In the presence of these features, there is increased mortality, and liver transplantation does not confer increased survival. In summary, liver transplantation appears to be futile in the presence of specific neurological signs or symptoms in patients affected with DGUOK deficiency. Conversely, in the absence of these neurological features, liver transplantation may be considered a potential treatment. Liver Transpl 14:1480–1485, 2008. © 2008 AASLD.
Incidence and Diagnosis of Active Toxoplasma Infection Among Liver Transplant Recipients in Western Turkey
Authors: Caner Ayşe , Döşkaya Mert , Karasu Zeki , Değirmenci Aysu , Guy Edward , Kılıç Murat , Zeytunlu Murat , Francis Janet , Bozoklar Ata , Gürüz Yüksel
Published: September 2008

Toxoplasmosis is a serious and potentially life-threatening disease in liver transplant recipients while they are immunosuppressed. We report the clinical and laboratory findings related to active toxoplasma infection associated with 40 immunosuppressed liver transplant procedures that took place over a 12-month period at a major transplant unit in Izmir, Turkey. Twenty-seven (67.5%) of the 40 transplant recipients were found to be seropositive for toxoplasma infection and therefore at risk of reactivated infection. From the serological status of the donors, which was ascertained in 38 of 40 cases, we identified 3 (7.9%) of 38 transplants to be from a seropositive donor to a seronegative recipient. In 10 (26.3%) of 38 transplants, both the donor and recipient were seronegative, and this excluded toxoplasma as a risk. A comparison of real-time polymerase chain reaction (PCR) and nested PCR was undertaken in combination with a range of serological assays (the Sabin-Feldman dye test, enzyme immunoassay immunoglobulin M, and immunosorbent agglutination assay immunoglobulin M). Ethylene diamine tetraacetic acid blood samples from 3 of the 30 recipients at risk from toxoplasma were found positive by PCR, but only 1 of these was found positive in both assays. Among the 3 PCR-positive patients, immunoglobulin M and immunoglobulin G antibody levels increased in only 1 patient. Correlations between symptoms, laboratory findings, and clinical management (use of anti-toxoplasma therapy) are presented. Our findings suggest that toxoplasma presents a significant risk to our liver transplant population and that PCR is a helpful addition in identifying active infections and hence in informing clinical management decisions. Liver Transpl 14:1526–1532, 2008. © 2008 AASLD.
Early Posttransplant Hepatic Venous Outflow Obstruction: Long-Term Efficacy of Primary Stent Placement
Authors: Ko Gi-Young , Sung Kyu-Bo , Yoon Hyun-Ki , Kim Kyung Rae , Kim Jin Hyoung , Gwon Dong Il , Lee Sung Gyu
Published: September 2008

Although balloon angioplasty has been accepted as the safe and effective initial treatment to manage hepatic venous outflow abnormalities, it may induce rupture of the fresh anastomosis but also may be ineffective to eliminate various etiologies of venous outflow abnormalities in the early post-transplant period. Therefore, we performed primary stent placement in 108 patients to treat early-onset (≤4 weeks) post-transplant hepatic venous outflow abnormality. The following parameters were documented retrospectively: technical success and complications: clinical success; recurrence; and patency of stent-inserted hepatic veins.

Technical success was achieved in 166 (97.6%) of 170 anastomoses (107 patients). Major complications occurred in 5 (4.6%) patients: partial stent migration (n = 2) and stent malposition (n = 3). Clinical success was achieved in 83 (82.2%) of 101 patients who had abnormal liver enzymes or clinical symptoms. Seven patients without initial clinical symptoms have remained healthy. Restenosis or occlusion of the stent-inserted hepatic veins was documented in 22 patients at a mean of 9.6 ± 8.6 months after stent placement. Four of them underwent stent replacement or retransplantation due to liver function deterioration. Overall 1-, 3-, and 5-year primary patency rates were 82.3 ± 0.3%, 75.0 ± 0.4%, and 72.4 ± 0.5%, respectively. Multivariate Cox regression analysis showed that diameter of stents was an independent factor associated with patency of stents (p = 0.001).

Primary stent placement seems to be an effective treatment modality with an acceptable long-term patency to treat early post-transplant hepatic venous outflow obstruction. Liver Transpl 14:1505–1511, 2008. © 2008 AASLD.
Quality of Life up to 30 years Following Liver Transplantation
Authors: Desai Rajendra , Jamieson Neville V. , Gimson Alexander E. , Watson Christopher J. , Gibbs Paul , Bradley Andrew J. , Praseedom Raaj K.
Published: September 2008

Liver transplantation provides a return to a satisfactory quality of life (QOL) for the majority of patients in the short to medium term (first 5 years), but there is very little information on the QOL in the longer term and the factors influencing it. We therefore undertook a single-center cross-sectional analysis to determine QOL in patients 10 or more years after liver transplantation. All liver transplant recipients who were followed up at the Cambridge Transplant Unit for 10 or more years (transplanted between 1968 and 1994) and resident in the United Kingdom were asked to complete by post the Short Form 36 version 2 and the Ferrans and Powers questionnaires to evaluate their QOL. Univariate and multivariate analysis were performed to assess the relationship between a range of clinical parameters and QOL. One hundred two patients were invited to participate, and 61 (59.8%) responded. Overall, the patients reported a satisfactory QOL. On the Ferrans and Powers questionnaire, the patients had a mean Quality of Life Index score of 24.5. Factors associated with reduced physical functioning were age > 50 years at transplantation, female gender, and recurrence of the primary liver disease. On the Short Form 36 version 2 questionnaire, recipients had reduced physical functioning but normal mental health parameters in comparison with the normal population. Age > 60 years at the time of survey, female gender, and posttransplant complications were associated with reduced physical functioning. In conclusion, patients 10 or more years after liver transplantation generally have a good QOL, although physical functioning is reduced. Addressing issues such as recurrent disease and posttransplant problems such as osteoporosis may help to improve long-term QOL. Liver Transpl 14:1473–1479, 2008. © 2008 AASLD.
Impact of the Hepatitis B Virus Genotype on Pre– and Post–Liver Transplantation Outcomes
Authors: Gaglio Paul , Singh Sundeep , Degertekin Bulent , Ishitani Michael , Hussain Munira , Perrillo Robert , Lok Anna S.
Published: September 2008

Emerging data suggest that the hepatitis B virus (HBV) genotype and the precore and core promoter variants impact the outcome of orthotopic liver transplantation (OLT) for hepatitis B. The aim of this study was to determine if there is a correlation between HBV genotype, precore and core promoter variants, and pre- and post-OLT outcomes. Serum samples from patients participating in the National Institutes of Health HBV-OLT study were tested for HBV genotype and precore and core promoter variants. A total of 123 patients were studied: 43% were Asians, 46% were Caucasians, and 8% were African Americans. HBV genotypes A (35%) and C (35%) were the most prevalent, followed by genotypes D and B. Precore and core promoter variants were detectable in 44% and 90% of patients. Patients with genotype C were more likely to have hepatocellular carcinoma (HCC) at listing (P < 0.001). Waitlist mortality was highest among patients with genotype D, while posttransplant mortality was highest among patients with genotype C. Precore or core promoter variants did not correlate with pre- or post-OLT survival. In conclusion, in this US patient population, patients with genotype C were more likely to have HCC at the time of transplant listing and to die after transplant than patients with non-C genotypes. Patients with genotype D had the highest posttransplant survival, but this was offset by higher waitlist mortality. Our study suggests that HBV genotypes but not precore or core promoter variants may have an impact on pre- and post-OLT outcomes of hepatitis B patients. Liver Transpl 14:1420–1427, 2008. © 2008 AASLD.
Detection and Diagnosis of Herpes Simplex Virus Infection in Adults with Acute Liver Failure
Authors: Levitsky Josh , Duddempudi Anupama T. , Lakeman Fred D. , Whitley Richard J. , Luby James P. , Lee William M. , Fontana Robert J. , Blei Andres T. , Ison Michael G.
Published: September 2008

Disseminated herpes simplex virus (HSV) infection may lead to acute liver failure (ALF) and the need for emergency liver transplantation (LT). The primary aim of this study was to determine the utility of HSV serological testing and HSV DNA testing by polymerase chain reaction (PCR) in the diagnosis and management of indeterminate, pregnancy-related, and known HSV-related ALF. Stored sera obtained on study day 1 or 2 from patients enrolled in the United States ALF Study Group with indeterminate (n = 51), pregnancy-related (n = 12), and HSV-related (n = 4) ALF were screened for HSV DNA by PCR and serology. While 7 of the indeterminate and pregnant patients had positive anti-HSV immunoglobulin M, none had detectable HSV DNA. The 4 known HSV cases all had high-titer HSV DNA on presentation (range: 3.5 to 36 × 108 copies/mL). Two HSV patients underwent LT but developed posttransplant extrahepatic HSV infection despite suppression of HSV DNA with acyclovir treatment, and one of them eventually died. The 2 other fulminant HSV patients died within 48 hours of presentation. In conclusion, serum HSV DNA indicative of occult HSV infection was not detected in 51 indeterminate and 12 pregnancy-related ALF patients. The 4 patients with known HSV-related ALF all had high HSV DNA levels at presentation, and despite the rapid use of antiviral therapy and emergency LT, substantial morbidity and mortality were encountered, highlighting the poor prognosis with severe disseminated HSV infection. Liver Transpl 14:1498–1504, 2008. © 2008 AASLD.
Auxiliary Transplantation for Acute Liver Failure: Histopathological Study of Native Liver Regeneration
Authors: Quaglia Alberto , Portmann Bernard C. , Knisely Alex S. , Srinivasan Parthi , Muiesan Paolo , Wendon Julia , Heneghan Michael A. , O'Grady John G. , Samyn Marianne , Hadzic Dino , Dhawan Anil , Mieli-Vergani Giorgina , Heaton Nigel , Rela Mohamed
Published: September 2008

Auxiliary liver transplantation (ALT) permits the serial assessment of regeneration in livers of patients with acute liver failure (ALF). Forty-nine ALF patients [32 adults (median age, 23 years; range, 16-40 years) and 17 children (median age, 12 years; range, 1-15 years)] underwent ALT between 1994 and 2004 at King's College Hospital. Twenty-four patients had seronegative liver failure, 15 had acetaminophen toxicity, 4 had hepatitis B virus (HBV) infection, 3 had drug-induced liver failure, 2 had autoimmune hepatitis, and 1 had mushroom poisoning. Nine patients without post-ALT native liver histology were excluded from review. All acetaminophen-induced, HBV, and drug-related patients had diffuse injury. Twelve seronegative patients and the autoimmune hepatitis patient had a map-like injury. On follow-up, 9 acetaminophen-induced patients, 9 seronegative patients, 2 drug-induced ALF patients, 3 HBV patients, and the autoimmune patient recovered to a near-normal native liver with inconsequential scarring. The hepatocyte proliferative rate in diffuse necrosis was 27.4% (range, 3.1%-69.4%) at hepatectomy and sharply decreased after 8 days post-ALT, being minimal months and years after ALT. In conclusion, in patients undergoing ALT for ALF with a diffuse pattern of liver injury—mainly acetaminophen toxicity—hepatocyte proliferation occurs in the native liver within a few days of transplantation. If the injury is map-like (most cases of seronegative ALF), regeneration seems to involve variable hepatocellular proliferation and potential ductular hepatopoiesis, but sequential assessment is difficult because of sampling variation. The likelihood of histological recovery appears to be minimal in livers with total hepatocyte loss at the time of ALT. Liver Transpl 14:1437–1448, 2008. © 2008 AASLD.
High Mobility Group Box 1 Protein as a Marker of Hepatocellular Injury in Human Liver Transplantation
Authors: Ilmakunnas Minna , Tukiainen Eija M. , Rouhiainen Ari , Rauvala Heikki , Arola Johanna , Nordin Arno , Mäkisalo Heikki , Höckerstedt Krister , Isoniemi Helena
Published: September 2008

High mobility group box 1 protein (HMGB1), a cytokine actively secreted by phagocytes and passively released from necrotic cells, is an inflammatory mediator in experimental hepatic ischemia/reperfusion injury. We characterized its expression in human liver transplantation. In 20 patients, in addition to systemic samples, blood was drawn from portal and hepatic veins during and after reperfusion to assess changes within the graft. Plasma HMGB1, tumor necrosis factor α (TNF-α), and interleukin-6 (IL-6) levels were measured, and HMGB1 immunohistochemistry was performed on biopsies taken before and after reperfusion. Plasma HMGB1 was undetectable before reperfusion, and levels in systemic circulation peaked after graft reperfusion. At portal declamping, HMGB1 levels were substantially higher in the caval effluent [188 (80-371) ng/mL] than in portal venous blood [0 (0-3) ng/mL, P < 0.001]. HMGB1 release from the graft continued thereafter. HMGB1 levels were not related to TNF-α or IL-6 levels. HMGB1 expression was up-regulated in biopsies taken after reperfusion (P = 0.020), with intense hepatocyte and weak neutrophil staining. HMGB1 levels in hepatic venous blood correlated with graft steatosis (r = 0.497, P = 0.03) and peak postoperative alanine aminotransferase levels (r = 0.588, P = 0.008). Our results indicate that HMGB1 originates from the graft and is a marker of hepatocellular injury in human liver transplantation. Liver Transpl 14:1517–1525, 2008. © 2008 AASLD.
Expanded Criteria for Liver Transplantation in Patients with Cirrhosis and Hepatocellular Carcinoma
Authors: Silva Mauricio , Moya Angel , Berenguer Marina , Sanjuan Fernando , López-Andujar Rafael , Pareja Eugenia , Torres-Quevedo Rodrigo , Aguilera Victoria , Montalva Eva , De Juan Manuel , Mattos Angelo , Prieto Martín , Mir José
Published: September 2008

Orthotopic liver transplantation (OLT) selection for patients with hepatocellular carcinoma (HCC) is a matter of debate. The Milan criteria (MC) have been largely adopted by the international community. The main aim of this study was to evaluate the survival rates and recurrence probabilities of a new proposal for criteria (up to 3 tumors, each no larger than 5 cm, and a cumulative tumor burden ≤ 10 cm). Patients with cirrhosis and HCC included on the waiting list (WL) from 1991 to 2006 were retrospectively analyzed. Outcomes in patients who had tumors within and beyond the MC were compared. The survival analysis was done (1) with the intention-to-treat principle and (2) among transplanted patients. A total of 281 patients were included in WL. Twenty-four cases did not undergo OLT (a dropout rate of 8.5%); all but 1 case had tumors within the MC. Of the 257 transplanted patients, 26 had tumors beyond the MC in the pre-OLT evaluation. Based on the intention-to-treat analysis, the 5-year survival was 56% versus 66% in patients who had tumors within and beyond the MC, respectively (P = 0.487). Among transplanted patients, the 5-year survival was 62% versus 69%, respectively (P = 0.734). Through multivariate analysis, microvascular invasion was an independent prognostic factor of poor survival (P = 0.004). The recurrence probabilities at 1 and 5 years were 7% versus 12% and 14% versus 28% in patients with tumors within and beyond the MC, respectively (P = 0.063). The multivariate analysis demonstrated that both poorly differentiated tumors (P < 0.001) and microvascular invasion (P < 0.001) increased the risk of recurrence. The expansion to up to 3 nodules, each up to 5 cm, and a cumulative tumor burden ≤ 10 cm did not result in a reduction of survival in comparison with patients who had tumors within the MC. Liver Transpl 14:1449–1460, 2008. © 2008 AASLD.
Electron Spin Resonance Spin Trapping Technique: Application to the Cleavage Process of Photoinitiators
Authors: Criqui Adrien , Lalevée Jacques , Allonas Xavier , Fouassier Jean‐Pierre
Published: September 2008

The cleavage of different photoinitiators (PIs) of polymerization is investigated by the ESR spin trapping using two different spin traps (STs): 5,5′‐dimethyl‐1‐pyrrolineN‐oxide (DMPO) and phenylN‐tert‐butyl nitrone (PBN). The hyperfine splitting constants for the different adducts are measured and provide a new set of data. These results show a difference of selectivity between the two (STs) and outline their complementarities.

magnified image
Copolymerization of Hepta‐1,6‐diene with Ethylene Catalyzed by Cobalt Complexes
Authors: Takeuchi Daisuke , Matsuura Ryuichi , Osakada Kohtaro
Published: September 2008

Copolymerization of hepta‐1,6‐diene with ethylene using a cobalt–bis(imino)pyridine complex affords a polymer that contains trans‐1,2‐five‐membered rings in the repeating unit from hepta‐1,6‐diene. The ratio of the repeating units of diene to those of ethylene is controlled from 3: 97 to 50:50, depending on the reaction conditions. Isotope‐labeling reactions reveal that the major chain transfer pathway involves β‐hydrogen elimination of the polymer end formed after ethylene insertion.

magnified image
Spectrum of movement disorders associated with glutaric aciduria type 1: A study of 16 patients
Authors: Gitiaux Cyril , Roze Emmanuel , Kinugawa Kiyoka , Flamand‐Rouvière Constance , Boddaert Nathalie , Apartis Emmanuelle , Valayannopoulos Vassili , Touati Guy , Motte Jacques , Devos David , Mention Karine , Dobbelaere Dries , Rodriguez Diana , Roubertie Agathe , Chabrol Brigitte , Feillet François , Vidailhet Marie , Bahi‐Buisson Nadia
Published: September 2008

Glutaric aciduria type 1 (GA1) is an autosomal recessive neurometabolic disorder due to glutaryl CoA dehydrogenase deficiency. Comprehensive descriptions of GA1‐associated movement disorders are rare. In order to refine the description of the motor phenotype, we prospectively studied 16 consecutive pediatric and adult GA1 patients, focusing on the movement disorders and their time course. In most patients, generalized dystonia, superimposed on baseline axial hypotonia, remained the predominant feature throughout the disease course. With aging, it tended to evolve from mobile to fixed dystonia and to be associated with akinetic‐rigid parkinsonism. Prominent orofacial involvement was a consistent feature in GA1 patients with movement disorders, resulting in speech disorders with features of combined hyperkinetic dysarthria and speech apraxia. The types and outcome of movement disorders in this setting should be taken into consideration during rehabilitation and for patient selection and evaluation in therapeutic trials. © 2008 Movement Disorder Society
Levodopa affects functional brain networks in parkinsonian resting tremor
Authors: Pollok Bettina , Makhloufi Houssain , Butz Markus , Gross Joachim , Timmermann Lars , Wojtecki Lars , Schnitzler Alfons
Published: September 2008

Resting tremor in idiopathic Parkinson's disease (PD) is associated with an oscillatory network comprising cortical as well as subcortical brain areas. To shed light on the effect of levodopa on these network interactions, we investigated 10 patients with tremor‐dominant PD and reanalyzed data in 11 healthy volunteers mimicking PD resting tremor. To this end, we recorded surface electromyograms of forearm muscles and neuromagnetic activity using a 122‐channel whole‐head magnetometer (MEG). Measurements were performed after overnight withdrawal of levodopa (OFF) and 30 min after oral application of fast‐acting levodopa (ON). During OFF, patients showed the typical antagonistic resting tremor. Using the analysis toolDynamic Imaging of Coherent Sources, we identified the oscillatory network associated with tremor comprising contralateral primary sensorimotor cortex (S1/M1), supplementary motor area (SMA), contralateral premotor cortex (PMC), thalamus, secondary somatosensory cortex (S2), posterior parietal cortex (PPC), and ipsilateral cerebellum oscillating at 8 to 10 Hz. After intake of levodopa, we found a significant decrease of cerebro‐cerebral coupling between thalamus and motor cortical areas. Similarly, in healthy controls mimicking resting tremor, we found a significant decrease of functional interaction within a thalamus–premotor–motor network during rest. However, in patients with PD, decrease of functional interaction between thalamus and PMC was significantly stronger when compared with healthy controls. These data support the hypothesis that (1) in patients with PD the basal ganglia and motor cortical structures become more closely entrained and (2) levodopa is associated with normalization of the functional interaction between thalamus and motor cortical areas. © 2008 Movement Disorder Society
Structural findings in the basal ganglia in genetically determined and idiopathic Parkinson's disease
Authors: Reetz Kathrin , Gaser Christian , Klein Christine , Hagenah Johannes , Büchel Christian , Gottschalk Stefan , Pramstaller Peter P. , Siebner Hartwig R. , Binkofski Ferdinand
Published: September 2008

A bilateral compensatory increase of basal ganglia (BG) gray matter value (GMV) was recently demonstrated in asymptomatic Parkin mutation carriers, who likely have an increased risk to develop Parkinson's disease (PD). We hypothesized BG morphological changes in symptomatic Parkin mutation carriers (sPARKIN‐MC) and idiopathic PD patients (iPD) after the occurrence of PD symptoms, reflecting the breakdown of compensatory mechanisms. Nine sPARKIN‐MC, 14 iPD, and 24 controls were studied clinically and with voxel‐based morphometry. Analysis of variance revealed mainly BG decrease of GMV in sPARKIN‐MC and to a lesser extent in iPD. However, a slight increase in GMV was also found in the right globus pallidus externus in sPARKIN‐MC and in the right putamen in iPD. This may reflect a structural correlate of functional compensation that can only partially be maintained when nigrostriatal neurodegeneration becomes manifest. Simple regression analyses with the UPDRS‐III and disease duration score revealed a distinct more bilateral linear decrease of BG GMV in sPARKIN‐MC than in iPD that may correspond to previous findings showing a symmetric reduction in putaminal 18F‐DOPA‐uptake and bilateral manifestation of symptoms in sPARKIN‐MC. In symptomatic PD, BG are subject to a progressive atrophy, which gradually increases with disease severity and duration. © 2008 Movement Disorder Society
The effect of weather conditions on the Oxford–Cambridge University Boat Race
Authors: Morris Benjamin J. , Phillips Ian D.
Published: September 2008

The sensitivity of Oxford–Cambridge University Boat Race finishing times to changing weather conditions was assessed over the period 1949–2006. Predictors of race times included tide height and river discharge as well as standard weather variables (temperature, humidity, wind speed and wind direction). As the Race is rowed against the flow of the River Thames, quicker races are favoured when a low river discharge is combined with a high tide and a SE wind. Wind speed and direction exert a much greater influence on race times than temperature and humidity. The zonal (W–E) wind speed explained 28.5% of the year‐to‐year variations in finishing times between 1967 and 2005, with races taking place under a westerly wind being on average 1 min and 27 s slower than races rowed under easterly conditions. The combined effects of the wind, river discharge and tide height accounted for 42.9% of the inter‐annual variance in race times over a 39 year period. Races rowed under cooler conditions tended to be slightly slower. The results are discussed in the context of the biometeorological literature and the hydrodynamics of the Boat Race course. Copyright © 2008 Royal Meteorological Society
Evaluation of the WCRP‐CMIP3 model simulations in the La Plata basin
Authors: Silvestri Gabriel , Vera Carolina
Published: September 2008

In this article, an assessment of the climate simulations for the La Plata Basin (LPB) by the Phase 3 of the World Climate Research Programme—Coupled Model Intercomparison Project is made. The LPB covers a wide area over south‐eastern South America, and is the fifth largest basin in the world in terms of geographical extent.

It was found that the observed warm summer—cold winter pattern of temperature is well represented by the climate models but they have deficiencies in reproducing the monthly mean temperature values. The largest differences take place during spring and summer, seasons in which the models exhibit temperatures higher than observations.

Models are able to represent the annual cycle of precipitation in the north of the LPB but some deficiencies are observed in the centre and south. In addition, there is an overestimation of heavy (light) rain events at the northern (central and southern) portion of the basin.

Results also show that the projected precipitation future change is positive in autumn and winter in the northern LPB as well as in most of the year in the centre and south of the basin. The precipitation distributions show an increase (decrease) in the frequency of low rainfall (heavy rainfall) events in the north of LPB and opposite change in the centre and south. Nevertheless, considerable inter‐model variability is found in the representation of the precipitation features at both present and future climate that make quite uncertain the quantification of those projected changes. Copyright © 2008 Royal Meteorological Society
Eine neue Calopepla‐Art
Authors: Stål C.
Published: September 2008

Calopepla bohemaniana sp. nov.
Pedagogy for policy analysis and management
Authors: O'Hare Michael
Published: September 2008

This essay presents two pedagogical models found in public policy programs, and attends (less exhaustively) to the managerial environment in which they coexist. The models are, of course, lecturing in all its various versions, and the cluster of teaching practices called case‐method teaching, student‐centered learning, active learning, experiential learning, discussion‐based teaching, and the like. The central question addressed is: How can it be that we still don't know which is better, or which is better for what, if know means anything like what it means in the larger policy analytic paradigm? Research comparing practices can improve our choices and outcomes.1212

Thanks to myriad colleagues (especially) John Boehrer, J. Mark Schuster, Eugene Bardach, and David Kirp, plus my cohort of 2005–06 Presidential Chair Fellows and that program's very committed leader, Steve Tollefson, for discussions of pedagogy that have reminded me over the years that teaching could be an intellectually demanding, rigorous, and collaborative enterprise, and to Robert MacCoun for comments on drafts of this paper.
Ranking state fiscal structures using theory and evidence
Authors: Bania Neil , Stone Joe A.
Published: September 2008

This paper offers unique rankings of the extent to which fiscal structures of U.S. states contribute to economic growth. The rankings are novel in two key respects: They are well grounded in established growth theory, in which the effect of taxes depends both on the level of taxes and on the composition of expenditures; and they are derived from actual estimates of the link between fiscal structures and economic growth. Estimates for the latter yield a growth hill, in which the incremental effect of taxes spent on productive services and infrastructure initially rises, reaches a peak, and then declines. Rankings derived from these estimates differ sharply from typical rankings based on levels of taxation alone. Two hypothetical policy experiments highlight both the growth‐hill effects of tax investments in productive services and infrastructure and the short‐ and long‐term tradeoffs in attempting to fund strong social services. © 2008 by the Association for Public Policy Analysis and Management.
Do social policy reforms have different impacts on employment and welfare use as economic conditions change?
Authors: Herbst Chris M.
Published: September 2008

This paper uses March Current Population Survey data from 1985 to 2004 to explore whether social policy reforms implemented throughout the 1990s have different impacts on employment and welfare use depending on economic conditions, a topic with important policy implications but which has received little attention from researchers. I find evidence that many reforms operate differently as labor market conditions fluctuate. Although social policies increase employment during economic slowdowns, the largest effects are generated in favorable labor market conditions. The impact of time limits, mandatory job search, and cash diversion programs are particularly sensitive to the macroeconomy, while the earned income tax credit is associated with similar employment effects in most environments. The results vary substantially across policy “carrots” and “sticks,” levels of work intensity, and subsamples of single mothers, but a tentative conclusion is that a strong economy reinforces the positive incentives created by social policy reforms. © 2008 by the Association for Public Policy Analysis and Management.
Spatio‐temporal image correlation (STIC) used by general obstetricians is marginally clinically effective compared to 2D fetal echocardiography scanning by experts
Authors: Wanitpongpan Prapat , Kanagawa Takeshi , Kinugasa Yukiko , Kimura Tadashi
Published: September 2008

Objectives

To assess the effectiveness of spatio‐temporal image correlation (STIC) used by general obstetricians as compared with 2D scanning.

Methods

As many as 30 pregnant women at 17–21 weeks' gestation were enrolled. 2D ultrasound was performed by a fetal echocardiologist; STIC was performed by a general obstetrician. Time, accuracy of measurement of diameter of great vessels and quality of the pictures obtained by the two methods were compared.

Results

The mean time required by 2D ultrasound was significantly shorter than that by STIC (5.2 ± 1.9 min vs 9.8 ± 2.7 min; P < 0.001). The measurement of the diameter of the great vessels showed some difference but the mean score of the pictures obtained by both methods were not significantly different. By using 2D ultrasound, acceptable quality pictures were obtained in 51.9, 44.4 and 51.9% of cases for 4‐chamber, 5‐chamber and 3‐vessel views, respectively. Meanwhile by using STIC, the percentages were 77.8, 59.3 and 37%.

Conclusion

Our study suggested that STIC used by general obstetricians to check normality of fetal cardiac structures at 17–21 weeks' gestation has marginal clinical effectiveness when compared to 2D scanning by a fetal echocardiologist, and should need some improvement before it can be used as a tool to expand a fetal cardiac screening program Copyright © 2008 John Wiley & Sons, Ltd.
A microfluidics approach for the isolation of nucleated red blood cells (NRBCs) from the peripheral blood of pregnant women
Authors: Huang R. , Barber T. A. , Schmidt M. A. , Tompkins R. G. , Toner M. , Bianchi D. W. , Kapur R. , Flejter W. L.
Published: September 2008

Objective

Nucleated red blood cells (NRBCs) have been identified in maternal circulation and potentially provide a resource for the monitoring and diagnosis of maternal, fetal, and neonatal health and disease. Past strategies used to isolate and enrich for NRBCs are limited to complex approaches that result in low recovery and less than optimal cell purity. Here we report the development of a high‐throughput and highly efficient microfluidic device for isolating rare NRBCs from maternal blood.

Material and Methods

NRBCs were isolated from the peripheral blood of 58 pregnant women using a microfluidic process that consists of a microfluidic chip for size‐based cell separation and a magnetic device for hemoglobin‐based cell isolation.

Results

The microfluidic–magnetic combination removes nontarget red blood cells and white blood cells at a very high efficiency (∼99.99%). The device successfully identified NRBCs from the peripheral blood of 58/58 pretermination samples with a mean of 37.44 NRBC/mL (range 0.37–274.36 NRBC/mL). These results were compared with those from previous studies.

Conclusion

The microfluidic device results in an approximate 10‐ to 20‐fold enrichment of NRBCs over methods described previously. The reliability of isolation and the purity of the NRBC product have the potential to enable the subsequent application of molecular diagnostic assays. Copyright © 2008 John Wiley & Sons, Ltd.
Nimesulide associated fulminant hepatic failure
Authors: Walker Sarah L. , Kennedy Fionnuala , Niamh Nolan , McCormick P. Aiden
Published: September 2008

Purpose

It is controversial whether the non‐steroidal inflammatory drug nimesulide is associated with severe hepatotoxicity. Our objective was to determine whether nimesulide is associated with fulminant hepatic failure.

Methods

Retrospective cohort study in the Irish national liver transplant unit. All patients who received a liver transplant for fulminant hepatic failure of unknown cause, between January 1994 and March 2007, were evaluated. New medications started within 6 months prior to transplant were identified. Likelihood of association assessed using the Naranjo and Roussel UCLAF Causality Assessment Method (RUCAM) scoring systems.

Results

Thirty‐two patients with sero‐negative, non‐paracetamol fulminant hepatic failure, who received an emergency liver transplant, were identified. Nimesulide had been started within 6 months in 6 patients. Five of the six were middle aged females. Nimesulide was assessed as probably associated with liver injury in all six cases.

Conclusions

Nimesulide was associated with fulminant hepatic failure requiring liver transplant in 6/32 cases of unknown origin. This association requires further investigation. Copyright © 2008 John Wiley & Sons, Ltd.
Prescriber adoption of newly approved selective COX‐2 inhibitors
Authors: Layton Deborah , Souverein Patrick C. , Heerdink Eibert R , Shakir Saad AW , Egberts AGC
Published: September 2008

Introduction

There is no consistent definition of prescribers who adopt new drug treatments early. This study examines if COX‐2 inhibitors (coxibs) were prescribed by subsets of practitioners and describes GP adoption patterns of coxibs and existing NSAIDs over time.

Methods

A population‐based drug utilisation study using a Dutch medication claims database. Prescribers of patients (18 + yrs) prescribed an NSAID January 1999—December 2003 were identified. Four NSAID categories were chosen reflecting selectivity (coxibs, preferential COX‐2 inhibitors and non‐selective (ns) NSAIDs (sub‐categorised as first or second line treatment)). The characteristics of prescribers issuing >10 prescriptions examined were: Type (GP, Specialist, Other); GP NSAID prescribing preference ratio (nsNSAIDs/coxib first prescription); coxib (ratio < 3); prescriber proportion responsible for 100%, 80% and 50% of initiations. Odds Ratios (95%CI) were calculated (first‐line nsNSAIDs as reference). Plots of prescribing proportions by quarter year were examined.

Results

NSAID cohorts comprised: first‐line ns (N = 38783); second‐line ns (N = 1459); COX‐2 preferential (N = 3107); coxib (N = 4202) patients. For all four cohorts, GPs were the most common prescriber type (>67%); the most frequent prescribing preference was for first‐line nsNSAIDs; 50% percentile prescribing proportions were low (<9%). GPs were equally as likely to prescribe coxibs as first‐line nsNSAIDs [OR 1.0 (0.9, 1.1)]. Plots of 100% prescriber proportion for first‐line nsNSAIDs and coxibs showed convergence; 50th percentile prescriber proportions plots were constant.

Conclusions

Small subsets of prescribers accounted for the majority of initiations regardless of NSAID type. Further studies are needed on such prescribers to inform healthcare policies and encourage participation in post‐marketing safety studies. Copyright © 2008 John Wiley & Sons, Ltd.
The impact of co‐payment increases on dispensings of government‐subsidised medicines in Australia
Authors: Hynd Anna , Roughead Elizabeth E. , Preen David B. , Glover John , Bulsara Max , Semmens James
Published: September 2008

Purpose

Patient co‐payments for medicines subsidised under the Australian Pharmaceutical Benefits Scheme (PBS) increased by 24% in January 2005. We investigated whether this increase and two related co‐payment changes were associated with changes in dispensings of selected subsidised medicines in Australia.

Method

We analysed national aggregate monthly prescription dispensings for 17 medicine categories, selected to represent a range of treatments (e.g. for diabetes, cardiovascular diseases, gout). Trends in medication dispensings from January 2000 to December 2004 were compared with those from January 2005 to September 2007 using segmented regression analysis.

Results

Following the January 2005 increase in PBS co‐payments, significant decrease in dispensing volumes were observed in 12 of the 17 medicine categories (range: 3.2–10.9%), namely anti‐epileptics, anti‐Parkinson's treatments, combination asthma medicines, eye‐drops, glaucoma treatments, HmgCoA reductase inhibitors, insulin, muscle relaxants, non‐aspirin antiplatelets, osteoporosis treatments, proton‐pump inhibitors (PPIs) and thyroxine. The largest decrease was observed for medicines used in treating asymptomatic conditions or those with over‐the‐counter (OTC) substitutes. Decrease in dispensings to social security beneficiaries was consistently greater than for general beneficiaries following the co‐payment changes (range: 1.8–9.4% greater, p = 0.028).

Conclusions

The study findings suggest that recent increase in Australian PBS co‐payments have had a significant effect on dispensings of prescription medicines. The results suggest large increase in co‐payments impact on patients' ability to afford essential medicines. Of major concern is that, despite special subsidies for social security beneficiaries in the Australian system, the recent co‐payment increase has particularly impacted on utilisation for this group. Copyright © 2008 John Wiley & Sons, Ltd.
Electrical conductivity and rheological behavior of multiphase polymer composites containing conducting carbon black
Authors: Zhang Qinghua , Xiong Hui , Yan Weixia , Chen Dajun , Zhu Meifang
Published: September 2008

Multiphase polymer composites of carbon black (CB), polypropylene (PP) and low density polyethylene (LDPE) were prepared by melt‐mixing method to reduce the amount of CB in the conductive composites. SEM images showed that CB preferably located in LDPE phase and formed electrically conductive path. The measurement of conductive properties showed that the ternary materials possessed lower percolation than binary composites of CB/PP or CB/LDPE, the former was ∼6 wt% and the latter was 9–10 wt%. Positive temperature coefficient (PTC) effects of the binary and ternary composites were investigated, indicating that the latter exhibited a relatively high PTC intensity. A rheological percolation estimated by a power law function is 2.66 wt% of CB loading, suggesting an onset of solid‐like behavior at low frequencies. This difference between the electrical and rheological percolation thresholds may be understood in terms of the smaller CB–CB distance required for electrical conductivity as compared with that required to impede polymer mobility. POLYM. ENG. SCI., 2008. © 2008 Society of Plastics Engineers