bluuebunny/crossref_metadata_2025 huggingface dataset:
Unwarranted Administration of Acetylcholinesterase Inhibitors Can Impair Genioglossus and Diaphragm Muscle Function
Authors: Eikermann Matthias , Fassbender Philipp , Malhotra Atul , Takahashi Masaya , Kubo Shigeto , Jordan Amy S. , Gautam Shiva , White David P. , Chamberlin Nancy L.
Published: March 2009

Background

It is standard practice to administer a cholinesterase inhibitor (e.g., neostigmine) at the end of a surgical case to reverse suspected effects of neuromuscular blocking agents regardless of whether such residual effects are present. The authors hypothesized that cholinesterase inhibition when given the in absence of neuromuscular blockade (NB) would decrease upper airway dilatory muscle activity and consequently upper airway volume.

Methods

The authors measured genioglossus and diaphragm electromyograms during spontaneous ventilation in anesthetized, tracheostomized rats before and after administration of neostigmine (0.03, 0.06, or 0.12 mg/kg), after recovery of the train-of-four ratio (quadriceps femoris muscle) to unity after NB (n = 18). For comparison, the authors made the same measurements in rats that had no previous NB (n = 27). In intact anesthetized rats, the authors measured upper airway volume and end-expiratory lung volume by magnetic resonance imaging before and after 0.12 mg/kg neostigmine (n = 9).

Results

Neostigmine treatment in rats that had fully recovered from NB based on the train-of-four ratio caused dose-dependent decreases in genioglossus electromyogram (to 70.3 +/- 7.6, 49.2 +/- 3.2, and 39.7 +/- 2.3% of control, respectively), decreases in diaphragm electromyogram (to 103.1 +/- 6.5, 83.1 +/- 4.7, and 68.7 +/- 7.3% of control), and decreases in minute ventilation to a nadir value of 79.6 +/- 6% of preneostigmine baseline. Genioglossus electromyogram effects were the same when neostigmine was given with no previous NB. Neostigmine caused a decrease in upper airway volume to 83 +/- 3% of control, whereas end-expiratory lung volume remained constant.

Conclusions

The cholinesterase inhibitor neostigmine markedly impairs upper airway dilator volume, genioglossus muscle function, diaphragmatic function, and breathing when given after recovery from vecuronium-induced neuromuscular block.
A New and Safe Device for Minimally Invasive Saphenous Vein Harvesting: Results after 100 Cases
Authors: D'Arrigo Giuseppe , Mauceri Gaetano , Mudanò Marco , Scolaro Antonio , Fraggetta Filippo , Grasso Giuseppe , Lomeo Alberto
Published: March 2009

Purpose

The saphenous vein is the most commonly used bypass conduit for coronary surgery. Endoscopic harvesting techniques are associated with significant reduction of wound complications but are time-consuming and expensive. The authors developed a device to perform minimally invasive harvesting of the saphenous vein—rapidly, inexpensively, and safely.

Description

Patients hospitalized for isolated CABG (n = 134) participated in the study. Each vein had been harvested through the use of our minimally invasive system.

Evaluation

The veins were harvested in 130 cases; 378 vein samples were collected for pathology study, with complete integrity of the vein as the result of the “no touch” technique with the device. This integrity could be very important for the long-term patency of the vein graft. After surgery, there were no wound dehiscences, infections, or major hematomas. There was 1 case (0.76%) of superficial hematoma and 3 cases (2.30%) of lymphoceles.

Conclusions

Although commercial disposable systems are now available to allow minimally invasive harvesting of the saphenous vein, the authors think that harvesting the greater saphenous vein with the cylinder steel device is easy to learn can be used safely and at much-reduced costs.
Significance of Bowel Wall Abnormalities at Ultrasound in Henoch‐Schönlein Purpura
Authors: Nchimi Alain , Khamis Jamil , Paquot Isabelle , Bury Françoise , Magotteaux Paul
Published: March 2009

Objectives:

To describe the polymorphism of intestinal ultrasound findings in children with gastrointestinal symptoms of Henoch Schönlein purpura (HSP) and to investigate the clinical relevance of these findings in terms of symptoms and length of hospitalization.

Patients and Methods:

Clinical and ultrasound data from 43 consecutive children with HSP (36 with and 7 without abdominal symptoms) were reviewed. Patients with abdominal symptoms of HSP were divided into 4 groups (0–III) representing at ultrasound normal appearance and differentiated, pseudodifferentiated, and dedifferentiated bowel wall thickening, respectively. The diagnostic value of ultrasound in diagnosing gastrointestinal involvement of HSP (grades I–III) was calculated using as the standard of reference the absence or presence of clinical symptoms. Average duration of symptoms and hospitalization in the 4 groups was compared.

Results:

The respective sensitivity, specificity, positive predictive value, and negative predictive value of ultrasound for the diagnosis of gastrointestinal involvement of HSP was 83.3%, 100%, 100%, and 53.8%. Groups 0 to III contained, respectively, 5/36 (13.9%), 6/36 (16.7%), 22/36 (61.1%), and 3/36 (8.3%) patients. The groups' average duration of symptoms, respectively, was 2.20 ± 2.06, 5.67 ± 1.88, 6.29 ± .94, and 17.67 ± 2.66 days, whereas the length of hospitalization, respectively, was 4.80 ± 2.96, 9.17 ± 2.70, 11.46 ± 1.35, and 24.67 ± 3.82 days. The duration of both symptoms and hospitalization was significantly higher in group III than in the other groups (P < 0.05).

Conclusions:

In children with gastrointestinal involvement of HSP, dedifferentiated wall thickening as shown by ultrasound is associated with a poor clinical prognosis.
Brachial Plexopathies: Etiology, Frequency, and Electrodiagnostic Localization
Authors: Moghekar Ajit R , Moghekar Abhay R , Karli Necdet , Chaudhry Vinay
Published: March 2009

Objectives:

Brachial plexopathy is clinically, and electrodiagnostically, a well-recognized entity. However, the involvement pattern of different parts of the plexus with different etiologies has not been well-characterized.

Methods:

A retrospective analysis of clinical and electrophysiologic findings in 203 patients with brachial plexopathies was performed.

Results:

Of 203 patients with brachial plexopathy, 182 (90%) were supraclavicular and 21 (10%) were infraclavicular. The following localizations were noted: upper trunk (UT) 27%; lower trunk (LT) 11%; UT + MT (middle trunk) 11%; LT + MT 7%; UT + MT + LT 25%; and UT + LT 1. Among the patients with brachial neuritis, 47% patients did not have pain before the onset and only 28% had a definable antecedent illness.

Conclusion:

We report the largest to date reported case series of well-characterized brachial plexopathy patients. Upper trunk was the most frequently affected site of injury. In brachial neuritis, absence of pain and antecedent viral illness is more common than described in the literature.
Myotonic Dystrophy Type 1 Presenting With Ventilatory Failure
Authors: Souayah Nizar , Tick Chong Peter Siao , Dreyer Michael , Cros Didier , Schmahmann Jeremy D
Published: March 2009

Objective:

To report a series of patients with adult onset myotonic dystrophy type 1 (DM1) in whom the presenting symptom was ventilatory failure.

Background:

Ventilatory failure is a common complication of DM1 and may be a presenting symptom in the setting of anesthesia or surgery, but it is not known to be a heralding manifestation.

Method:

Case series.

Results and Discussion:

Three adults developed dyspnea leading to ventilatory failure, with no cardiac or pulmonary causes identified. Case 1 required intubation for ventilator support and was sedated with propofol. There was no clinical myotonia, and electromyography (EMG) demonstrated brief runs of myotonic discharges. Examination 3 weeks later off propofol revealed percussion myotonia, and EMG evidence of long runs of myotonic discharges. Genetic testing confirmed the diagnosis of DM1. Case 2 had cataracts and ptosis but no known diagnosis of DM and no previous neurological impairments. Case 3 was previously neurologically asymptomatic but her son had congenital DM1. The diagnosis was confirmed by EMG in cases 2 and 3, and both patients were managed with bilevel ventilation (BIPAP).

Conclusion:

Myotonic dystrophy type 1 should be considered in the differential diagnosis of acute ventilatory failure in adults.
Acute Axonal Poly-Radiculoneuropathy Associated With Partially Treated Brucellosis: A Case Report
Authors: Haghighi Afshin Borhani , Sabayan Behnam
Published: March 2009

We report a case of partially treated brucellosis that developed quadriparesis, sixth and seventh cranial nerve palsy, and apnea. Electrodiagnostic studies were in favor of acute axonal poly-radiculoneuropathy. Crossreactive immunological responses due to molecular mimicry between Brucella lipooligosaccharide and GM1 ganglioside may justify the development of acute axonal polyradiculoneuropathy after brucellosis.
Renal Outcome in Off-Pump Coronary Artery Bypass Grafting: Predictors for Renal Impairment with Multivariate Analysis
Authors: Ogawa Mitsugu , Doi Kiyoshi , Yamada Yoshiaki , Okawa Kazunari , Kan'bara Tamotsu , Koushi Keitarou , Yaku Hitoshi
Published: March 2009

Objective

Recent studies on the efficacy of off-pump coronary artery bypass grafting (OPCABG) have reported encouraging results on postoperative renal function, but improvements can still be made.

Methods

A total of 368 patients, none needing chronic dialysis, underwent isolated OPCABG at our institution between January 1999 and March 2005. They were divided into 3 groups according to renal function as indicated by the serum creatinine levels: group N (n = 332) with normal function, group M (n = 30) with mild to moderate renal dysfunction, and group S (n = 6), with severe renal dysfunction. Creatinine ratio and early outcomes were compared among the groups. Predictors for renal impairment were determined by multiple regression analysis.

Results

In-hospital mortality rate was similar (group N, 0.6%; group M, 0%; group S, 0%). The percentage of patients with a creatinine ratio greater than 1.6 was significantly larger in group S (group N, 13%; group M, 13%; group S, 50%; P < 0.05). Postoperative hemodialysis, which was temporary, was required more frequently in group S (group N, 0.3%; group M, 3%; group S, 67%; P < 0.05). In group N, 38 patients (11%) had new renal impairment after OPCABG. Preoperative serum creatinine levels ≥2.5 mg/dL, ejection fraction <0.4, amount of blood transfusion, and more than 4 bypasses were potent predictors for postoperative renal impairment.

Conclusions

Clinical results of OPCABG on renal function were satisfactory regardless of preoperative renal function. However, perioperative renal function should be closely monitored in patients with known risk factors, even when OPCABG is performed.
Thoracic Aortic Stent Grafting in Patients with Connective Tissue Disorders: A Word of Caution
Authors: Mohammadi Siamak , Normand Jean-Pierre , Voisine Pierre , Dagenais François
Published: March 2009

Objective

Use of thoracic Stent-graft in patients with connective tissue disorders (CTD) remains limited. We herein report 3 patients with CTD who underwent stent grafting.

Methods and Results

Case 1; A male Marfan patient was operated for thoraco-abdominal aneurysm. On computed tomography (CT), large false aneurysm at the proximal anastomosis was documented which was excluded with a 30 mm Talent stent-graft with 10–15% oversize. Case 2; A female with Ehlers-Danlos syndrome had undergone resection of descending aortic thoracic aneurysm presented with an enlarging aneurysm distal to the graft. Three Talent stent-grafts (15% oversize) were deployed with balloon dilatation to exclude the aneurysm. The immediate postoperative period was complicated by an extensive intramural hematoma of the descending aorta with hemothorax, managed conservatively. Case 3; A female Marfan patient had undergone Bentall procedure and mitral repair followed with resection of the proximal descending aorta. Three months later a false aneurysm at the distal anastomosis was treated with a 24 mm Valiant stent-graft (30% oversize). Aortic dissection distal to stent was documented on the early postoperative CT. The dissected aneurysm enlarged significantly with a type I distal endoleak during follow-up. Concomitantly, the patient presented a class III dyspnea owing to a severe mitral regurgitation. The patient underwent a successful MVR and stent-graft explantation with replacement of the descending aorta.

Conclusion

Significant complications supervened when stent-grafts were deployed in native aorta. We thus recommend that deploying a stent-graft in a CTD diseased aorta should be considered a relative contraindication. In cases with prohibitive or high risk surgery, use of a stent-graft with minimal radial force and minimal oversizing without balloon dilatation should be considered.
Value of Sestamibi Scans in Tertiary Hyperparathyroidism
Authors: Loftus Kelly A. , Anderson Susan , Mulloy Anthony L. , Terris David J.
Published: March 2009

Objectives: To determine the value of preoperative 99mTc‐sestamibi scans and the incidence of ectopic glands in tertiary hyperparathyroidism.

Design: Prospective, non‐randomized analysis of a consecutive cohort of surgical patients from the Medical College of Georgia Thyroid/Parathyroid Center.

Materials and Methods: A consecutive series of patients with tertiary hyperparathyroidism undergoing parathyroidectomy was analyzed. Demographic data, preoperative 99mTc‐sestamibi scintigraphy results, location of diseased glands, pre‐ and postoperative calcium, and parathyroid hormone levels were collected.

Results: Twenty‐one patients underwent parathyroidectomy for tertiary hyperparathyroidism between March 2004 and September 2006. Of these 21 patients, 3 were re‐operative cases for persistent hypercalcemia and each was found to have a single diseased gland. Of the 18 patients undergoing first time surgery, 15 had four‐gland hyperplasia, 2 patients had single adenomas, and 1 patient had a double adenoma. Nine of the 21 patients (43%) had ectopic glands (2 of these patients had 2 ectopic glands each). The overall sensitivity of the preoperative 99mTc‐sestamibi scintigraphy was 76% and was not significantly different when comparing patients with ectopic glands (78%) and those without (75%).

Conclusions: 99mTc sestamibi scintigraphy has high positive predictive value and sensitivity in patients with tertiary hyperparathyroidism. Sestamibi scanning is particularly valuable in this patient population since the incidence of ectopic glands may be higher than previously recognized.
Resting Energy Expenditure in Children With Inflammatory Bowel Disease
Authors: Hill RJ , Cleghorn GJ , Withers GD , Lewindon PJ , Ee LC , Connor F , Davies PSW
Published: March 2009

Objectives:

There is controversy in the literature regarding the effect of inflammatory bowel disease (IBD) on resting energy expenditure (REE). In many cases this may have resulted from inappropriate adjustment of REE measurements to account for differences in body composition. This article considers how to appropriately adjust measurements of REE for differences in body composition between individuals with IBD.

Patients and Methods:

Body composition, assessed via total body potassium to yield a measure of body cell mass (BCM), and REE measurements were performed in 41 children with Crohn disease and ulcerative colitis in the Royal Children's Hospital, Brisbane, Australia. Log‐log regression was used to determine the power function to which BCM should be raised to appropriately adjust REE to account for differences in body composition between children.

Results:

The appropriate value to “adjust” BCM was found to be 0.49, with a standard error of 0.10.

Conclusions:

Clearly, there is a need to adjust for differences in body composition, or at the very least body weight, in metabolic studies in children with IBD. We suggest that raising BCM to the power of 0.5 is both a numerically convenient and a statistically valid way of achieving this aim. Under circumstances in which the measurement of BCM is not available, raising body weight to the power of 0.5 remains appropriate. The important issue of whether REE is changed in cases of IBD can then be appropriately addressed.
Eosinophilic Oesophagitis: Epidemiology, Clinical Aspects, and Association to Allergy
Authors: Nielsen Rasmus G , Husby Steffen
Published: March 2009

Eosinophilic oesophagitis is characterised by age‐dependent symptoms mimicking gastrooesophageal reflux disease, a distinct endoscopic appearance and a histological picture with extensive infiltration of eosinophils in the oesophageal mucosa. Eosinophilic oesophagitis is more frequently seen in males, and patients often belong to the paediatric or adolescence age groups. The exact prevalence of eosinophilic oesophagitis is unknown, but it has been suggested that the United States has a higher prevalence than Europe. Several treatment algorithms have been suggested, including elemental diets, oral steroids, inhaled (swallowed) steroids, and leucotriene receptor antagonists. Detailed information on the eosinophilic inflammatory processes in the oesophageal mucosa was initially obtained from animal models, in particular with regard to the role of interleukin‐5 and the chemokine eotaxin‐1 in eosinophilic recruitment. Studies have suggested a cytotoxic effect of eosinophilic degranulation products on nerve fibers in the gastric/intestinal mucosa, implicating a direct effect of allergic inflammation on gastrointestinal motility. Human studies recently have emphasized the role of eotaxin‐3 and identified a single nucleotide polymorphism probably related to disease susceptibility.
Subclinical Neurological Abnormalities in Children With Celiac Disease Receiving a Gluten‐free Diet
Authors: Cakir D , Tosun A , Polat M , Celebisoy N , Gokben S , Aydogdu S , Yagci RV , Tekgul H
Published: March 2009

Objectives:

Because clinically evident manifestations are frequent in adults with celiac disease (CD), we aimed to investigate whether early neurological abnormalities may be detected in children with CD.

Methods:

Electroencephalography, electromyography, and somatosensory evoked potentials were performed in children with CD receiving a gluten‐free diet.

Results:

The neurophysiological tests revealed subclinical neurological abnormalities associated with CD in 3 (11%) of 27 children: 2 had peripheral polyneuropathy documented with electromyography, and 1 had prolonged latencies in somatosensory evoked potential. Magnetic resonance imaging showed abnormalities in 2 (7.4%) of children: pontine demyelinization in 1 and cortical atrophy in the other.

Conclusions:

Because the rate of neurological problems is increased in children with CD, neurological abnormalities should be carefully investigated early after the diagnosis of CD is made.
Natural History of Antibodies to Deamidated Gliadin Peptides and Transglutaminase in Early Childhood Celiac Disease
Authors: Liu Edwin , Li Marcella , Emery Lisa , Taki Iman , Barriga Kathy , Tiberti Claudio , Eisenbarth George S , Rewers Marian J , Hoffenberg Edward J
Published: March 2009

Introduction:

Gliadin proteins play a key role in the pathogenesis of celiac disease; however, as a screen for celiac disease, anti‐gliadin antibody testing has been replaced by the more sensitive and specific serological assays for transglutaminase autoantibodies (TGAA). A new generation of anti‐gliadin antibody assays has been developed to detect synthetic, deamidated homologous gliadin peptides (DGP) with high sensitivity and specificity.

Methods:

Sera were collected prospectively from children with an increased risk for celiac disease as part of an ongoing study at Denver, and studied for the development of celiac autoimmunity. We investigated the high‐performance DGP antibody assay in 50 TGAA‐positive children both before the development of celiac autoimmunity and following the institution of a gluten‐free diet to determine the relationship of DGP antibodies to TGAA. TGAA were measured by an in‐house radioassay.

Results:

DGP antibodies and TGAA parallel each other over the period of years children were studied. DGP antibodies resolved sooner than TGAA in subjects on a gluten‐free diet. DGP antibodies appeared earlier than TGAA in 9 children.

Conclusions:

Measuring DGP antibodies may be more useful than TGAA in monitoring children on a gluten‐free diet. DGP antibodies can precede the appearance of TGAA in some at‐risk children.
Early Stage of Biliary Atresia Is Associated With Significant Changes in 8‐Hydroxydeoxyguanosine and Mitochondrial Copy Number
Authors: Tiao Mao‐Meng , Lin Tsu‐Kung , Kuo Fang‐Ying , Huang Chao‐Cheng , Du Yung‐Ying , Chen Chao‐Long , Chuang Jiin‐Haur
Published: March 2009

Objectives:

Oxidative stress is known to be involved in the pathogenesis of biliary atresia (BA), but the mechanism has yet to be elucidated. We studied 8‐hydroxydeoxyguanosine (8‐OHdG) and mitochondrial copy number as potential markers for oxidative stress in BA.

Methods:

Hepatic immunoreactive 8‐OHdG expression was investigated during the early stage of BA when the patients received Kasai portoenterostomy (KP), during the late stage when the patients received liver transplantation (LT), in patients with choledochal cyst as disease control, and in patients with histologically normal liver as normal control. Apoptosis of liver cells was examined by terminal deoxynucleotidyl transferase–mediated 2′‐deoxyuridine 5′‐triphosphate‐biotin nick end‐labeling stain. The mitochondrial DNA copy number was measured by real‐time polymerase chain reaction.

Results:

The number of hepatocytes positive for immunoreactive 8‐OHdG was significantly increased in KP (65% ± 18%) compared with LT (30% ± 32%; P = 0.029) and choledochal cyst (25% ± 20%; P = 0.037). The 8‐OHdG labeling index was significantly correlated with the grade of chronic hepatitis activity (Spearman r = 0.495; P = 0.037). The hepatocyte terminal deoxynucleotidyl transferase–mediated 2′‐deoxyuridine 5′‐triphosphate‐biotin nick end‐labeling index in KP (15% ± 4%) was significantly higher than that in LT (5% ± 2%; P = 0.018) and in choledochal cyst (3% ± 2%; P = 0.010). Mitochondrial copy number was significantly less in KP than in LT (7.33 ± 0.75 vs 8.91 ± 1.32; P = 0.045) and in normal control (7.33 ± 0.75 vs 9.20 ± 1.20; P = 0.021).

Conclusions:

The early stage of BA is associated with stronger inflammatory reaction, augmented oxidative DNA, and mitochondrial DNA damage as manifested by higher immunoreactive 8‐OHdG and apoptotic activities and by a decrease in mitochondrial copy number.
Prevalence of antimicrobial resistance among serotypes ofCampylobacter jejuniisolates from cattle and poultry in Japan
Authors: Harada Kazuki , Ozawa Manao , Ishihara Kanako , Koike Ryoji , Asai Tetsuo , Ishikawa Hitoshi
Published: March 2009

Penner serotypes ofC. jejuniin a total of 601 isolates from apparently healthy cattle, layer and broiler chickens in Japan were examined between 2001 and 2006. Predominant serotypes were B (O: 2, 19.1%), D (O: 4, 13.5%), Y (O: 37, 7.3%) and G (O: 8, 5.8%), whereas the remaining serotypes made up less than 5% of the total isolates. The frequency of ampicillin resistance in serotype G (65.6%) was significantly higher than in serotypes D (12.5%), B (11.2%), and Y (0%). Our results suggest that serotype is one factor contributing to the prevalence of ampicillin resistance inC. jejuniisolates.
Presence of a novel Ehrlichia sp. in Ixodes granulatus found in Okinawa, Japan
Authors: Takano Ai , Ando Shuji , Kishimoto Toshio , Fujita Hiromi , Kadosaka Teruki , Nitta Yoshiki , Kawabata Hiroki , Watanabe Haruo
Published: March 2009

Ehrlichia‐specific DNA fragments of Ehrlichia omp‐1 and groEL genes were found in two I. granulatus ticks which had been collected from wild small mammals in a subtropical zone in Japan. The DNA sequences of groEL and 16SrDNA of the suspected Ehrlichia were clustered into a group of E. chaffeensis, E. muris, and Ehrlichia sp. HF565 found in I. ovatus, but were distinctly different. Therefore the Ehrlichia strain was designated as a novel Ehrlichia sp. 360. The Ehrlichia sp. 360 was detected in I. granulatus but not in any other ticks. This suggests that I. granulatus is a probable vector of Ehrlichia sp. 360 in Japan.
Phospholipase C‐mediated calcium signalling is required for fungal development and pathogenicity inMagnaporthe oryzae
Authors: RHO HEE‐SOOL , JEON JUNHYUN , LEE YONG‐HWAN
Published: March 2009

Calcium signalling has profound implications in the fungal infection of plants and animals, during which a series of physiological and morphological transitions are required. In this article, using a model fungal pathogen,Magnaporthe oryzae, we demonstrate that the regulation of the intracellular calcium concentration ([Ca2+]int) is essential for fungal development and pathogenesis. Imaging of [Ca2+]intshowed that infection‐specific morphogenesis is highly correlated with the spatiotemporal regulation of calcium flux. Deletion of the fungal phospholipase C gene (M. oryzaephospholipase C 1,MoPLC1) suppressed calcium flux, resulting in a fungus defective in developmental steps, including appressorium formation and pathogenicity. Surprisingly, thePLC‐δ1gene of mouse was able to functionally substitute forMoPLC1by restoring the calcium flux, suggesting the evolutionary conservation of the phospholipase C‐mediated regulation of calcium flux. Our results reveal that MoPLC1 is a conserved modulator of calcium flux that is essential for the regulation of key steps in fungal development and pathogenesis.
The benefits of prophylactic treatment with APCC in patients with haemophilia and high‐titre inhibitors: a retrospective case series
Authors: VALENTINO L. A.
Published: March 2009

Summary.  Prophylactic infusion of factor concentrates is a safe, effective intervention for preventing arthropathy in patients with haemophilia; on‐demand treatment is insufficient to prevent the orthopaedic complications and subsequent haemophilic arthropathy that stem from recurrent joint haemorrhages. The usefulness of prophylaxis in haemophilia patients without inhibitors suggests that patients with haemophilia and inhibitors could derive similar benefits. In patients with haemophilia and high‐titre (>5 BU mL−1) inhibitors, bleeding episodes are treated with bypassing agents such as activated prothrombin complex concentrates (APCCs) and recombinant activated factor VII (rFVIIa, NovoSeven®; Novo Nordisk A/S, Bagsvaerd, Denmark). It is possible to administer bypassing therapy regularly to prevent haemorrhages, with the goal of limiting arthropathy and serious life‐ and limb‐threatening bleeding. The data evaluating the efficacy and safety of this approach in patients with inhibitors are limited, consisting of results from one prospective trial and retrospective case reports. This report describes our experience with the prophylactic use of the APCC Factor Eight Inhibitor Bypassing Activity, Anti‐Inhibitor Coagulant Complex, Vapor Heated (FEIBA™; Baxter AG, Vienna, Austria). Data from patients at one treatment centre were retrospectively evaluated. Case records of six patients with haemophilia A or B and high‐titre inhibitors were identified. When APCC was administered regularly, most patients exhibited a reduction in the numbers of haemorrhages, an improvement in orthopaedic status, and an improvement in quality of life. Prophylaxis with APCC can reduce haemorrhages and halt further joint deterioration in patients with haemophilia and inhibitors.
Performance of recalibrated ReFacto® laboratory standard in the measurement of FVIII plasma concentration via the chromogenic and one‐stage assays after infusion of recalibrated ReFacto® (B‐domain deleted recombinant factor VIII)
Authors: SANTORO C. , IORIO A. , FERRANTE F. , PALLOTTA A. , PIGNOLONI P. , BIONDO F. , AGNELLI G. , MAZZUCCONI M. G.
Published: March 2009

Summary.  The use of ReFacto Laboratory Standard (RLS) in the one‐stage clotting assay was proposed to reduce the underestimation of factor VIII (FVIII) plasma concentration after the infusion of ‘ReFacto®’ (B‐domain deleted recombinant FVIII) in haemophilia A patients. Both ReFacto® and RLS were recently recalibrated, with the resulting materials containing approximately 20% more protein than the previous products. The aim of this study was to evaluate the performance of recalibrated RLS in the measurement of FVIII plasma concentration after the infusion of recalibrated ReFacto®. In 13 severe haemophilia A patients, 25 IU kg−1 of ReFacto® were injected intravenously. Venous blood samples were collected at 0.25, 0.5, 1, 3, 6, 9, 24, 28 and 32 h after the end of the infusion. Pharmacokinetic parameters were measured for the chromogenic and one‐stage assays using International Plasma Standard (IPS) and RLS for both assays and assuming a non‐compartmental drug disposition. Comparisons among assays and standards were performed using anova. Pharmacokinetic estimates obtained with the chromogenic method were in agreement with those published in the literature. The one‐stage method was confirmed to be more sensitive to lower plasma concentrations of FVIII. The measured maximum plasma concentration (Cmax) was slightly higher than theoretical values and independent of the assay used. Cmax, area under the curve (AUC) and volume of distribution at steady state (Vss) presented non‐significant differences among the methods and standards used. The clinical utility of RLS in the evaluation of FVIII concentration after the infusion of ReFacto® seems to be reduced since recalibration of the product.
Measurement of von Willebrand factor‐FVIII binding activity in patients with suspected von Willebrand disease type 2N: application of an ELISA‐based assay in a reference laboratory
Authors: ZHUKOV O. , POPOV J. , RAMOS R. , VAUSE C. , RUDEN S. , SFERRUZZA A. , DLOTT J. , SAHUD M.
Published: March 2009

Summary.  Laboratory diagnosis of von Willebrand disease type 2N (VWD2N) is based on costly mutation analysis or in vitro measurement of the ability of plasma von Willebrand factor (VWF) to bind exogenous factor VIII (FVIII); however, the VWF‐FVIII binding activity assay is complex and not widely used. Our aim was to assess the utility of the in‐house VWF‐FVIII binding assay in the investigation of patients with suspected VWD2N. A previously described ELISA‐based FVIII binding method was simplified and adapted for the clinical laboratory use by optimizing incubation time, reagent concentrations and assay standardization. The assay was validated using samples from eight individuals with known homozygous or heterozygous VWD2N mutations, and 100 healthy adults. An additional 392 patient samples were tested, including 314 with FVIII activity <50% of normal and 78 received for routine VWF‐FVIII binding activity testing. Intra‐ and inter‐assay variations were less than 10% and 17%, respectively, and the limit of quantification was estimated as 0.12. The reference range for healthy adults was 0.73–1.42. VWF:FVIII binding activity was consistent with the genotype in subjects with available genetic data, being low in three individuals with homozygous mutation (<0.12) and intermediate in five heterozygous individuals (0.44–0.61). Screening of the 392 clinical samples identified reduced VWF:FVIII binding in 19 subjects. This assay provides accurate measurement of VWF:FVIII binding activity and successfully identifies homozygous VWD2N patients and heterozygous carriers. Use of this ELISA‐based assay may help avoid the need for mutation analysis in patients with unexplained low FVIII activity.
Risk factors for deterioration of erectile function: the Krimpen study
Authors: Schouten Boris W. V. , Bohnen Arthur M. , Dohle Gert R. , Groeneveld Frans P. M. J. , Willemsen Sten , Thomas Siep , Bosch J. L. H. Ruud
Published: March 2009

This report from the Krimpen study explored the relationship between the determinants for worsening of erectile function in the open population. In Krimpen aan den IJssel (a municipality near Rotterdam), all men aged 50–75 years, without cancer of the prostate or the bladder and without a history of radical prostatectomy or neurogenic bladder disease, were invited to participate in June 1995. The response rate was 50%. The follow‐up was until June 2004. At baseline a visit to a health centre for the measurement of urinalysis, height, weight and blood pressure was part of the ongoing study. During baseline and at the first follow‐up, second follow‐up and third follow‐up, a self‐administered booklet consisting of a compilation of validated questionnaires including the International Continence Society male sex questionnaire was completed. At the urology outpatient clinic, a urological workup was measured. All participants were asked to keep a frequency–volume chart for 3 days. A multivariate Cox‐proportional hazard model was constructed to find the determinants of worsening of erectile function, correcting for age. Total follow‐up time was 4948 person years consisting of 975 men. During follow‐up, 441 events of worsening of erectile function occurred. Multivariate Cox‐proportional hazard ratio analyses showed that body mass index (BMI), irritative lower urinary tract symptoms, diabetes mellitus, chronic obstructive pulmonary disease (COPD) and sexual inactivity were determinants with significant hazard ratios. In addition to age, determinants for a deterioration of erectile function based on multivariate longitudinal analyses are BMI, diabetes mellitus, COPD, sexual inactivity and irritative IPSS. The mechanism of various determinants is discussed.
Zinc status and vacuolar zinc transporters control alkaline phosphatase accumulation and activity in Saccharomyces cerevisiae
Authors: Qiao Wei , Ellis Charissa , Steffen Janet , Wu Chang‐Yi , Eide David J.
Published: March 2009

Little is known about how metalloproteins in the secretory pathway obtain their metal ion cofactors. We used the Pho8 alkaline phosphatase of the yeast Saccharomyces cerevisiae to probe this process in vivo. We found that both Pho8 activity and protein accumulation are zinc‐dependent and decrease in zinc‐limited cells. Low Pho8 accumulation was the result of degradation by vacuolar proteases. Surprisingly, the protective effect of zinc on Pho8 stability was not solely due to Zn2+ binding to the active‐site ligands suggesting that the Pho8 protein is targeted for degradation in zinc‐limited cells by another mechanism. Pho8 appears to be a rare example of a metalloprotein whose stability is regulated by its metal cofactor independently of active‐site binding. We also assessed which zinc transporters are responsible for supplying zinc to Pho8. We found that the Zrc1 and Cot1 vacuolar zinc transporters play the major role while the Msc2/Zrg17 zinc transporter complex active in the endoplasmic reticulum is not involved. These results demonstrate that the vacuolar zinc transporters, previously implicated in metal detoxification, also deliver zinc to certain metalloproteins within intracellular compartments. These data suggest that Pho8 receives its metal cofactor in the vacuole rather than in earlier compartments of the secretory pathway.
Stringent response in Vibrio cholerae: genetic analysis of spoT gene function and identification of a novel (p)ppGpp synthetase gene
Authors: Das Bhabatosh , Pal Ritesh Ranjan , Bag Satyabrata , Bhadra Rupak K.
Published: March 2009

RelA and SpoT of Gram‐negative organisms critically regulate cellular levels of (p)ppGpp. Here, we have dissected the spoT gene function of the cholera pathogen Vibrio cholerae by extensive genetic analysis. Unlike Escherichia coli, V. choleraeΔrelAΔspoT cells accumulated (p)ppGpp upon fatty acid or glucose starvation. The result strongly suggests RelA‐SpoT‐independent (p)ppGpp synthesis in V. cholerae. By repeated subculturing of a V. choleraeΔrelAΔspoT mutant, a suppressor strain with (p)ppGpp0 phenotype was isolated. Bioinformatics analysis of V. cholerae whole genome sequence allowed identification of a hypothetical gene (VC1224), which codes for a small protein (∼29 kDa) with a (p)ppGpp synthetase domain and the gene is highly conserved in vibrios; hence it has been named relV. Using E. coliΔrelA or ΔrelAΔspoT mutant we showed that relV indeed codes for a novel (p)ppGpp synthetase. Further analysis indicated that relV gene of the suppressor strain carries a point mutation at nucleotide position 676 of its coding region (ΔrelAΔspoT relV676), which seems to be responsible for the (p)ppGpp0 phenotype. Analysis of a V. choleraeΔrelAΔspoTΔrelV triple mutant confirmed that apart from canonical relA and spoT genes, relV is a novel gene in V. cholerae responsible for (p)ppGpp synthesis.
Mechanisms of polar arrest of a replication fork
Authors: Kaplan Daniel L. , Bastia Deepak
Published: March 2009

A DNA replication terminator sequence blocks an approaching replication fork when the moving replisome approaches from just one direction. The mechanism underlying polar arrest has been debated for years, but recent work has helped to reveal how a replication fork is blocked in Escherichia coli. Early work suggested that asymmetric interaction between terminator protein and terminator DNA contributes to polar fork arrest. A later study demonstrated that if the terminator DNA is partially unwound, the resulting melted DNA could bind tightly to the terminator protein, suggesting a mechanism for polar arrest that involves a locked complex. However, recent evidence suggests that the terminator protein–DNA contacts are not sufficient for polar arrest in vivo. Furthermore, polar arrest of a replication fork still occurs in the absence of a locked complex between the terminator protein and DNA. In E. coli and Bacillus subtilis, the bound terminator protein makes protein–protein contacts with the replication fork helicase, and these contacts are critical in blocking progression of the advancing fork. Thus, we propose that interactions between the replication fork helicase and terminator protein are the primary mechanism for polar fork arrest in bacteria, and that this primary mechanism is modulated by asymmetric contacts between the terminator protein and its cognate DNA sequence. In yeast, terminator sequences are present in rDNA non‐transcribed spacers and a region immediately preceding the mating type switch locus Mat1, and the mechanism of polar arrest at these regions is beginning to be elucidated.
Erythropoietin receptor is expressed in meningiomas and lower levels are associated with tumour recurrence
Authors: Küster O. , Simon P. , Mittelbronn M. , Tabatabai G. , Hermann C. , Strik H. , Dietz K. , Roser F. , Meyermann R. , Schittenhelm J.
Published: March 2009

Aims: The Epo‐EpoR pathway plays a role in tumour growth, metastasis and treatment resistance and is a potential target in oncological treatment. As the EpoR status in human meningiomas is unknown, our aim was to characterize EpoR expression in these tumours. Methods: We examined 131 meningioma samples of all WHO grades from 116 patients by immunohistochemistry for EpoR. Among these, 25 meningiomas showed brain invasion and 29 patients had a further tumour recurrence. A group of 20 patients without tumour recurrence served as controls. In 12 cases we were able to compare both the primary and the following recurrent tumours. The presence of EpoR in meningiomas was confirmed by RT‐PCR and Western blot. Results: EpoR was expressed in all meningiomas. Statistical analysis revealed that the mean expression levels of EpoR were significantly lower in primary tumours with known recurrence compared with a recurrence‐free control group. Additional matched pair analysis in individual cases showed no significant differences between primary and recurrent tumours. No significant correlation between EpoR expression and WHO grade, age, sex or brain invasion was detected. Using specific primer pairs for RT‐PCR, we were able to detect all three known isoforms of EpoR: the full‐length isoform EpoR‐F, the truncated isoform EpoR‐T and the soluble isoform EpoR‐S. Conclusions: Our results demonstrate the expression of EpoR in meningiomas. Lower EpoR mean levels might be a useful marker for a higher recurrence risk, but further studies are needed to clarify the influence of EpoR on recurrences and the role of the different isoforms.
A direct association of polyomavirus BK viruria with deterioration of renal allograft function in renal transplant patients
Authors: Li Yi‐Jung , Chen Yung‐Chang , Lai Ping‐Chin , Fang Ji‐Tseng , Yang Chih‐Wei , Chiang Yang‐Jen , Chu Sheng‐Hsien , Wu Ming‐Ju , Tian Ya‐Chung
Published: March 2009

Abstract: Background:  Polyomavirus BK virus (BKV) causes a BKV‐associated nephropathy (BKVAN), frequently causing allograft dysfunction in renal transplant recipients. As BK viruria is a surrogate marker for early detection of BKVAN, the aim of this study was to clarify an association between BK viruria and allograft dysfunction in renal transplant recipients.

Methods:  One hundred and six renal transplant recipients with average 5.9‐yr transplant duration received screening for quantification of BK viruria detected by real time polymerase chain reaction and were followed up for 12 months.

Results:  Twenty‐six patients (25%) had detectable BK viruria. In comparison of the patients without BK viruria, more patients in the BK viruria group were treated with steroids and had a past history of acute rejection. There was no difference in sex, age, transplant duration, allograft type and previous cytomegalovirus infection. During follow‐up, the patients with BK viruria had higher serum creatinine levels at the sixth, ninth and 12th month. Multiple logistic regression analysis revealed that BK viruria was the only risk factor for more than 25% or 50% rise of serum creatinine level above baseline at the end of one yr follow‐up.

Conclusions:  BK viruria alone is associated with allograft dysfunction and early intervention is indicated.
Mating compatibility among populations of codling moth Cydia pomonella Linnaeus (Lepidoptera: Tortricidae) from different geographic origins
Authors: Taret G. , Sevilla M. , Wornoayporn V. , Islam A. , Ahmad S. , Caceres C. , Robinson A. S. , Vreysen M. J. B.
Published: March 2009

The codling moth Cydia pomonella (Linnaeus) (Lepidoptera: Tortricidae) is a serious pest of pome fruit worldwide and the sterile insect technique (SIT) provides an environmentally acceptable approach for its control. As the pest is present in both the southern and northern hemispheres it would be possible for a rearing facility in the northern hemisphere to supply sterile moths to an SIT programme in the southern hemisphere during the northern winter and vice versa. This could greatly improve the economics of moth production and the running costs of rearing facilities. However in order to develop this concept, it is important to assess if populations of codling moth from different geographical regions share mating compatibility. Twelve different laboratory and field populations from both hemispheres were sampled and field cage bisexual mating compatibility tests were carried out between selected combinations. The index of sexual isolation (ISI) and the female and male relative performance index (FRPI and MRPI, respectively) were calculated for each mating combination. In only two of the combinations was there a slight but significant deviation from random mating. There were also some significant differences in mating duration between the homotypic matings and the duration of a particular homotypic mating seemed to depend on the origin of the other population in the cage. It was concluded that there exist no barriers to mating between populations of codling moth from many parts of the world and that it would be feasible for sterile moths to be shipped from one rearing facility to SIT programmes in other parts of the world.
Recent advances in molecular targeted therapy for metastatic renal cell carcinoma
Authors: Mizutani Yoichi
Published: March 2009

Advanced renal cell carcinoma (RCC) is resistant to chemotherapy and radiotherapy. Immunotherapy is relatively effective against RCC. However, the response rate is approximately 15–20%. Therefore, new therapeutic approaches are necessary. Recently, molecular mechanisms responsible for the proliferation of RCC are identified, and molecular targeted therapy is developed. Bevacizumab, sorafenib, sunitinib, axitinib, temsirolimus, everolimus are promising molecular targeted therapeutic agents for metastatic RCC, and will be used widely in clinics in the near future. In addition, combination therapy with molecular targeted therapy and other therapies including immunotherapy may also be developed soon.
Reduced event‐related low frequency EEG activity in schizophrenia during an auditory oddball task
Authors: Doege K. , Bates A. T. , White T. P. , Das D. , Boks M. P. , Liddle P. F.
Published: March 2009

This study examines EEG low frequency characteristics which have been linked to specific cognitive functions such as stimulus encoding and attention during an auditory oddball task in schizophrenia patients and healthy controls. EEG data was recorded from 17 young schizophrenia patients in a stable phase of their illness and 17 healthy controls performing an auditory oddball task. Evoked and induced delta and theta activity, N100, P300 amplitude were computed. Between 200–500 ms after a stimulus was presented, patients displayed significantly reduced P300, less evoked and induced delta and theta activity than controls. We conclude that the well known finding of P300 reduction in schizophrenia can be linked to reductions in delta and theta activity, which are a manifestation of impaired stimulus evaluation, memory retrieval, and a lack of sustained attention.
Serum concentration/dose ratio of topiramate during pregnancy
Authors: Westin Andreas Austgulen , Nakken Karl Otto , Johannessen Svein I. , Reimers Arne , Lillestølen Kari Mette , Brodtkorb Eylert
Published: March 2009

Purpose:  To study the impact of pregnancy on the serum concentration/dose ratio (C/D‐ratio) of topiramate (TPM).

Methods:  Twelve women with epilepsy using TPM during pregnancy, and 15 pregnancies were studied. The main target variable was the C/D‐ratio at baseline and during pregnancy. Additional variables were changes in TPM dose, concomitant use of other antiepileptic drugs, seizure frequency, and pregnancy outcome. Clinical and pharmacological data were obtained from the women's medical records.

Results:  The average C/D‐ratios in the second and third trimester were 30% (p = 0.002, n = 11) and 34% (p = 0.001, n = 8) lower than the baseline values, respectively. The interindividual variability was pronounced. Increased seizure frequency was common in pregnant women using TPM, but a correlation to the decline in TPM C/D‐ratio could not be established from our data.

Discussion:  Dose‐corrected serum concentrations of TPM appear to decline gradually throughout pregnancy. The underlying mechanisms are not known. Increased glomerular filtration may play a major role. During pregnancy, therapeutic drug monitoring of TPM may be useful.
Percutaneous Lumbar Discectomy Using the Dekompressor® System under CT‐Control
Authors: Lierz Peter , Alo Kenneth M. , Felleiter Peter
Published: March 2009

In recent years, new minimally invasive therapies for the treatment of radicular pain associated with contained disc herniation have been introduced. These techniques have changed the field of interventional pain management. In a prospective, nonrandomized case study, we treated patients using the Dekompressor® system guided by computed tomography instead of fluoroscopy. Pain scores, analgesic usage, and activities of daily living were assessed via structured telephone interviews 6 and 12 months after the procedure.

Sixty‐four patients were treated at 76 lumbar levels. Follow‐up data after 12 months were obtained for all patients. The average reported pain level as measured by visual analog scale was 7.3 before the procedure and 2.1 after 12 months. Before the procedure, 61 patients (95%) used opioid or nonopioid analgesics regularly; after 1 year, a reduction in analgesic use was seen in 51 patients (80%). None of the patients reported procedure‐related complications. When standardized patient selection criteria are used, treatment of patients with radicular pain associated with contained disc herniation using the Dekompressor® can be a safe and efficient procedure.