bluuebunny/crossref_metadata_2025 huggingface dataset:
End‐to‐end portocaval shunt for venous drainage of the native foregut in combined liver–intestinal transplantation
Authors: Gondolesi Gabriel E. , Rodriguez‐Davalos Manuel , Soltys Kyle , Florman Sander , Kaufman Stuart , Fishbein Thomas
Published: October 2005

Abstract:  An end‐to‐side portocaval shunt has been classically described as the standard procedure that needs to be performed to obtain adequate venous drainage of the foregut in combined liver–intestinal transplant. The transplanted organs are placed en bloc in a piggyback fashion on the recipient's vena cava, and graft's porto‐mesenteric venous circulation is left intact. Recurrent portal hypertension with hemorrhage has been reported as a complication after such a procedure. In an effort to improve the technical aspects of this complex operation, we began to perform an end‐to‐end shunt from the recipient portal vein to the infrahepatic donor cava. Here, we describe this new surgical technique and discuss its potential advantages. The new technique is described in detail. Of the 70 intestinal transplants performed in 67 patients at The Mount Sinai Hospital from 1998 to December 2004, three were multivisceral transplants (MVTx) and 28 were combined liver intestine transplants (LITx), post‐surgical outcome including recurrent portal hypertension and the presence of splenomegaly and significant thrombocytopenia was retrospectively review between the group that received the classic end–side vs. the new end–end portocaval shunt. Of the 28 LITx, 23 were done with the classic end–side portocaval shunt and in five (one adult, four pediatric) the end‐to‐end portocaval shunt described in the present study. One patient in this group died on post‐operative day 31 (adult); after a mean follow up of 19.5 months there is a 100% patient and graft survival for the pediatric population. Post‐operatively there have been no complications related to this technique. Few modifications have been made to the original description of MVTx. This is the first description of this technique that is relatively simple to perform, creating a large vascular conduit with high flow rates and theoretically less turbulence compared with the end‐to‐side shunt.
Skin transplantation to monitor clinical donor‐related tolerance in mixed hematopoietic chimerism
Authors: Mache Christoph J. , Schwinger Wolfgang , Spendel Stephan , Zach Otto , Regauer Sigrid , Ring Ekkehard
Published: October 2005

Abstract:  Mixed hematopoietic chimerism usually carries with it the tolerance to any other tissue from the same donor. Consequently, the establishment of a sustained chimerism may allow long‐term acceptance of transplanted organs without immunosuppression. We report a girl with refractory severe aplastic anemia who developed low recipient level hematopoietic chimerism following transplantation of maternal highly purified CD34+ cells without prophylactic immunosuppression. Renal thrombotic microangiopathy led to chronic renal failure and she received skin allografts from her mother in view of a future kidney donation. The maternal skin grafts were accepted without immunosuppression and the hematopoietic chimerism remained stable. Skin transplantation may be a helpful and easily applicable tool to monitor donor‐related tolerance in hematopoietic chimerism clinically. It should contribute to minimize the risks of subsequent solid organ transplantation from the same donor without immunosuppression.
Tacrolimus‐induced cholestatic syndrome following pediatric liver transplantation and steroid‐resistant graft rejection
Authors: Ganschow Rainer , Albani Johannes , Grabhorn Enke , Richter Andrea , Burdelski Martin
Published: October 2005

Abstract:  Several factors may contribute to post‐transplant cholestatic complications after liver transplantation. These include ischemic reperfusion injury, hypoperfusion, bile duct strictures, and hepatotoxic drugs. Up to now, there have been no publications on tacrolimus cholestatic toxicity in clinical transplantation when the drug was used in therapeutic doses. We describe six pediatric liver graft recipients in whom cholestatic complications developed under a tacrolimus‐based immunosuppression following liver transplantation and all of them suffered from previous steroid‐resistant graft rejection. The overall incidence of cholestatic syndrome was 5.4% in children receiving tacrolimus. The immunosuppression was switched back to cyclosporine and prednisolone in all six patients resulting in completely resolved clinical signs and laboratory findings. We conclude from our observations that a cholestatic syndrome following pediatric liver transplantation may be caused by tacrolimus therapy following steroid‐resistant graft rejection, even if given in therapeutic doses.
Hyperbaric oxygen therapy for hepatic artery thrombosis following liver transplantation: Current concepts
Authors: Grover Ian , Conley Laura , Alzate Greg , Lavine Joel , Van Hoesen Karen , Khanna Ajai
Published: October 2005

Abstract:  This article presents the case of an infant who underwent an orthotopic liver transplant and then developed hepatic artery thrombosis that was detected on routine post‐operative right upper quadrant ultrasound. Alteplase (TPA) failed to open the artery, so the child received systemic heparin and hyperbaric oxygen (HBO) therapy. After six HBO treatments, the hepatic artery had recanalized and his liver function tests had returned to normal or near normal. There were no complications to the HBO therapy, and 1 yr after the transplant, the child's liver is functioning well. The present study discusses the beneficial effects of HBO therapy and the proposed mechanisms for its favorable results. In our patient, systemic heparin and HBO therapy prevented liver failure and need for retransplantation.
Emotional and behavioral problems after pediatric liver transplantation: A quantitative assessment
Authors: Gritti Antonella , Sicca Federico , Di Sarno Angela Maria , Di Cosmo Nicolina , Vajro Serena , Vajro Pietro
Published: October 2005

Abstract:  Several uncertainties regarding psychological problems in children who underwent liver transplantation and the need to differentiate these disturbances from those related to the underlying previous chronic liver disease itself exist. This background triggered the present pilot study to investigate, using quantitative assessment methods, the incidence and the type of emotional and behavioral disturbances after liver transplantation. Sixteen liver transplant recipients (aged 5.7–14.4 yr) and 12 age‐matched controls with stable chronic liver disease were assessed through the parent report form of Child Behavior Checklist/ 4–18. The mean time elapsed since transplantation was 8.1 yr. No patient or family had received psychological support during chronic liver disease or at any phase of the transplantation process. Transplanted children scored within borderline range for Internalizing and Total Behavioral Problems and within pathological range for Competences, except for the Activity Scale. Transplanted children showed more Total Behavioral (p = 0.005) and Externalizing Problems (p = 0.0005) than controls. Both groups scored within the pathological range for Total Competences with no significant differences between the two groups. Our findings suggest that in the absence of support programs a psychological risk does exist for a long period of time, after transplantation. Regarding Total Behavioral Problems and Externalizing Problems, this risk is higher than in children with chronic liver disease.
Skin changes in pediatric transplant patients
Authors: Manzoni Ana Paula Dornelles da Silva , Kruse Ricardo Lapa , Troian Carina , Cunha Vanessa Santos , Cestari Tania Ferreira
Published: October 2005

Abstract:  The advent of organ transplantation identified a new group of diseases. Dermatologists are studying transplant‐associated diseases along with the atypical behavior of already known dermatoses. Pediatric patients have been treated as an extension of adult population, but unique aspects of age required clarification. A prospective cohort was studied including patients from both genders up to 17 yr of age who were recipients of kidney, liver or BMT during 2003 in Porto Alegre, Brazil. Regular skin examinations were performed up to the sixth month after the procedure, and an analysis was determined by ID (i.e. = number of skin changes/number of patients‐month × 100). Thirty‐nine patients were examined: 20 were kidney transplant recipients; 11 were BMT recipients (10 autologous transplants and 1 allogeneic transplant); and 8 were liver transplant recipients. Skin changes result primarily from the use of medication (87.2). Individually, kidney transplant patients presented the highest ID of skin changes because of medications (104.1). BMT recipients presented the highest ID of alterations occurring on skin appendages (85.4) and liver transplant recipients had the highest ID of vascular changes (94.9). In conclusion, this study shows that cutaneous alterations in pediatric transplant recipients present some particularities not described in adult recipients, such as ichthyosiform xerosis in renal recipients and skin scaling with pellagroid appearance in bone marrow recipients. Also, dermatoses secondary to medication use were the main finding in pediatric population.
Update in screening of lung cancer
Authors: ARTINIAN Vasken , KVALE Paul A.
Published: October 2005

Abstract:  In the USA, lung cancer is the leading cause of cancer death. Earlier studies of CXR and sputum cytology screening conducted in the 1970s showed no mortality benefit. Accordingly, mass screening for lung cancer was abandoned and is not currently recommended. Recently, interest in lung cancer screening has been revived due to various reports showing an advantage of low‐dose CT over CXR in detecting smaller size tumours and at an earlier stage. Although these reports generated much enthusiasm for screening among clinicians and the general public, the effectiveness of low‐dose CT in reducing lung cancer‐specific mortality rates has not been demonstrated. Large‐scale randomized controlled trials are currently in progress to determine the efficacy of CXR and low‐dose CT screening. This review highlights the advantages and limitations of current modalities for lung cancer screening. The cases for and against screening with currently available modalities are examined. Additional new screening modalities are also discussed.
COPD: A prevalence estimation model
Authors: PEABODY John W. , SCHAU Brigitte , LOPEZ‐VIDRIERO Maite , VESTBO Jørgen , WADE Sally , IQBAL Ahmar
Published: October 2005

Objectives: COPD is increasingly recognized as a leading cause of global morbidity and mortality. Prevalence estimates for COPD are generally unavailable or unreliable. Thus, a simple and valid model for estimating COPD prevalence would provide essential information for policymakers in addressing a major burden of worldwide illness.

Methodology: We modelled the relationships among readily available demographic data (e.g. age, gender), smoking prevalence, and COPD prevalence based on a literature review. We also included risks of COPD from environmental pollution and associations with socioeconomic status.

Results: The model specifies a minimum of eight input variables to predict COPD prevalence in a given population: population by age, gender, smoking prevalence, prevalence of COPD among smokers, proportion living in rural areas, country by level of development, and exposures to environmental pollution. Actual COPD prevalence data from large population‐based studies in Spain, Norway, Poland and Nepal compared favourably with the model projections (P ≥ 0.10).

Conclusion: The model is a simple tool for estimating the prevalence of COPD populations in a given region or country. Further studies are needed to prospectively validate the model and test the assumptions upon which it is based.
Response to bronchodilator in infants with bronchiolitis can be predicted from wheeze characteristics
Authors: SÁNCHEZ Ignacio , VIZCAYA Cecilia , GARCÍA Daniela , CAMPOS Eugenia
Published: October 2005

Objective:  Lung sounds analysis has been used for clinical care. Our objectives were to characterize the spectral pattern of lung sounds and their relation to bronchodilator effects in acute bronchiolitis (AB). We hypothesized that patients with sinusoidal wheezes (SW) would show a more significant bronchodilator response.

Methodology:  We studied 22 asleep hospitalized infants (14 boys, eight girls), aged 5.2 ± 1 months, 16 with a positive respiratory syncytial virus test, during their first 3 days after admission. Patients breathed spontaneously through a face mask connected to a pneumotachograph during normal breathing, and only target flows of 0.1 ± 0.02 L/s were analyzed. Sounds were obtained using two contact sensors attached over both posterior lower lobes. For inspiratory and expiratory sounds, we determined the frequencies below which 25% (F25), 50% (F50), 75% (F75) and 99% (SEF99) of the spectral power between 100 and 1000 Hz was contained. We repeated the measurements 20 min after bronchodilator therapy in all patients.

Results:  We found classic SW in 11 patients, while the other 11 had complex wheezes (CW). There were positive bronchodilator responses in 9/11 with SW and 3/11 with CW (P < 0.01). Patients who responded to salbutamol showed an increase in power at low frequencies after medication (P < 0.01), and a positive correlation between wheezing and the increase in the power spectra measured by F50 and SEF99 (P < 0.001).

Conclusions:  We conclude that sinusoidal and complex wheezes occur in patients with AB, that a positive response to bronchodilator is significantly more common in those with classic SW and that lung sounds analysis is a reproducible, safe and non‐invasive method for assessing wheeze in infants.
Inflammatory activity is still present in the advanced stages of idiopathic pulmonary fibrosis
Authors: MURA Marco , BELMONTE Gelorma , Fanti Stefano , CONTINI Paola , PACILLI Angela Maria Grazia , FASANO Luca , ZOMPATORI Maurizio , SCHIAVINA Mario , FABBRI Mario
Published: October 2005

Objective:  The role of active inflammation in idiopathic pulmonary fibrosis (IPF) is controversial. A gallium‐67 citrate (Ga67 scan) is a sensitive indicator of inflammatory activity. The aim of this study was to assess the Ga67 uptake and other markers of inflammation at different stages of IPF and to investigate its prognostic role.

Methodology:  Twenty‐two patients (aged 66 ± 11 years, 18 males) with IPF were monitored for a period of 6–20 months (mean 13 months). At presentation (T0), high resolution CT (HRCT) scans showed reticular opacities and traction bronchiectasis with bi‐basilar and peripheral distribution in all cases. At both T0 and follow‐up (T1), we measured pulmonary function (PaO2, FVC, DLco), overall radiographic extent of fibrosis (HRCT visual score), Ga67 uptake, serum concentrations of lactate dehydrogenase (LDH) and C‐reactive protein (CRP), and erythrocyte sedimentation rate (ESR).

Results:  All parameters showed a significant deterioration during the T0–T1 interval, though the increase in Ga67 uptake and serum markers was not significant. Patients with Ga67 uptake indices graded as normal or mildly increased (group I), and graded as considerably or severely increased (group II) at presentation, were compared. There was no significant difference with respect to lung function or HRCT score between the two groups at T1. Ga67 uptake, LDH, CRP and ESR at presentation did not correlate significantly with the interval change in pulmonary function and disease extent.

Conclusions:  Our findings indicate that inflammatory activity in the advanced stage of IPF is still relevant, although a Ga67 scan is not predictive of the clinical course.
Frozen section of pleural biopsies at medical thoracoscopy assists in correctly identifying benign disease
Authors: FIELDING David , HOPKINS Peter , SERISIER David
Published: October 2005

Objectives:  Medical thoracoscopy and thoracoscopic talc poudrage (TTP) are accepted procedures in the management of pleural effusions. The relative merits of TTP compared with pleurodesis via intercostal catheter (ICC) continue to be debated. However, of the two procedures, only medical thoracoscopy allows both tissue diagnosis and pleurodesis to be achieved reliably in one procedure. The aim of this study was to assess the feasibility and accuracy of using frozen section analysis of samples taken during medical thoracoscopy to assist the thoracoscopist's decision to complete the procedure with a TTP.

Methodology:  Twenty patients with undiagnosed pleural effusions after at least one diagnostic pleurocentesis underwent medical thoracoscopy and biopsy.

Results:  Frozen sections were easily performed within the timeframe of medical thoracoscopy. The final diagnosis based on paraffin sections was malignant in 10 cases and benign in 10 cases. Frozen section at the time of thoracoscopy (before TTP) correctly identified nine of 10 cases as being benign and six of 10 cases as malignant. In the malignant group, reasons for incorrect identification as benign were sampling from superficial benign adipose tissue overlying the malignant deposits, difficult access to the most involved parts of the pleura and intense cellular infiltrate initially thought to be benign.

Conclusion:  Frozen sections taken during medical thoracoscopy have the potential to facilitate decision‐making prior to pleurodesis, particularly for accurate identification of benign histology on thoracoscopic pleural biopsies, in order that pleurodesis is not performed unnecessarily.
Leptospirosis and its pulmonary complications
Authors: THAMMAKUMPEE Kreetha , SILPAPOJAKUL Khachornsakdi , BORRIRAK Baralee
Published: October 2005

Objective:  The aim of this study was to assess the incidence and factors associated with pulmonary complications of leptospirosis.

Methodology:  In a retrospective study, patients with a definite diagnosis of leptospirosis following a 6‐week period of severe flooding in Hadyai city, Thailand, were reviewed. Pulmonary complications of leptospirosis were defined as the occurrence of respiratory symptoms and an abnormal CXR. The clinical and laboratory test results for patients with and without pulmonary complications were compared.

Results:  Among the 157 patients with leptospirosis, eight patients had pulmonary complications. Three patients had acute renal failure (ARF) and pulmonary oedema. One patient had ARF and adult respiratory distress syndrome (ARDS). Two patients had ARF, congestive heart failure and pulmonary oedema. One patient had congestive heart failure and pulmonary oedema. One patient had only ARF. Factors associated with pulmonary complications were delayed antibiotic treatment and thrombocytopenia (platelet count < 100 × 109/L). Three patients developed adult respiratory distress syndrome and one died from respiratory failure.

Conclusions:  Pulmonary complications and death occur in a low percentage of patients with leptospirosis. Delayed antibiotic treatment and thrombocytopenia are risk factors for the development of pulmonary involvement in leptospirosis.
Microscopic polyangiitis with unusual lung involvement
Authors: GÜLBAY Banu Eriş , CELIK Gökhan , KUMBASAR ÖZlemÖzdemir , GÜLBAY Mutlu , ALPER Doǧanay , TULUNAY ÖZden
Published: October 2005

Abstract:  Microscopic polyangiitis (MPA) is a non‐granulomatous, systemic and small vessel vasculitis accompanied by segmental necrotizing glomerulonephritis with no evidence of other small vessel disease. We report a patient with weakness, fever, and arthralgia whose CXR and thoracic CT showed widespread nodular infiltration. His proteinase‐3 anti‐neutrophilic cytoplasmic antibody (c‐ANCA) was positive. The serum creatinine was increased and haematuria subsequently developed. Renal biopsy revealed a focal segmental necrotizing glomerulonephritis which was compatible with MPA. He was treated with high‐dose corticosteroid and cyclophosphamide. Because of a worsening CXR and hypoxaemia, mechanical ventilation was applied. Despite this he died of respiratory failure following 20 days of treatment. Nodular infiltration is an unusual radiological pattern in patients with MPA and is the reason for this report.
Climatic, high tide and vector variables and the transmission of Ross River virus
Authors: Tong S. , Hu W. , Nicholls N. , Dale P. , MacKenzie J. S. , Patz J. , McMichael A. J.
Published: October 2005

Abstract

This report assesses the impact of the variability in environmental and vector factors on the transmission of Ross River virus (RRV) in Brisbane, Australia. Poisson time series regression analyses were conducted using monthly data on the counts of RRV cases, climate variables (Southern Oscillation Index and rainfall), high tides and mosquito density for the period of 1998–2001. The results indicate that increases in the high tide (relative risk (RR): 1.65; 95% confidence interval (CI): 1.20–2.26), rainfall (RR: 1.45; 95% CI: 1.21–1.73), mosquito density (RR: 1.17; 95% CI: 1.09–1.27), the density of Culex annulirostris (RR: 1.25; 95% CI: 1.13–1.37) and the density of Ochlerotatus vigilax (RR: 2.39; 95% CI: 2.30–2.48), each at a lag of 1 month, were statistically significantly associated with the rise of monthly RRV incidence. The results of the present study might facilitate the development of early warning systems for reducing the incidence of this wide‐spread disease in Australia and other Pacific island nations. (Intern Med J 2005; 35: 677–680)
Survey of the Royal Australasian College of Physicians examination candidates: preparation and impact on lifestyle
Authors: Perrin K. , Prasad S. , Robinson G.
Published: October 2005

Abstract

Candidates currently view the Royal Australasian College of Physicians’ written examination as a major undertaking, knowing that approximately one‐third fail on their first attempt. We anonymously surveyed New Zealand registrars who sat the written examination in 2004. We found that the majority of candidates spend long hours preparing over a several months, and that the examination had a detrimental impact on their personal lives. The results of this survey have important implications in the context of efforts to reduce the stress of doctors, and should lead to a change in either the examination itself or an increase in support provided to registrars preparing for it. (Intern Med J 2005; 35: 680–682)
Paracetamol overdose and hepatotoxicity at a regional Australian hospital: a 4‐year experience
Authors: Ayonrinde O. T. , Phelps G. J. , Hurley J. C. , Ayonrinde O. A.
Published: October 2005

Abstract

Background: Paracetamol is a component of a number of drugs taken in overdose (OD). The influence of alcohol use (acute or chronic) on the presentation and clinical course of paracetamol OD is contentious. This study explores the relationship between paracetamol OD, alcohol consumption and clinical outcomes at a regional Australian hospital.

Aims: To determine the frequency, circumstances and outcomes of paracetamol OD presentations to a regional Australian general hospital over a 4‐year period.

Methods: Medical records of patients admitted to the Ballarat Health Services (BHS) as a result of paracetamol OD between January 2000 and December 2003 were reviewed. Patient demographics, amount of paracetamol ingested, other drug coingestions, alcohol history, previous medication OD, clinical course and outcomes were recorded.

Results: Annual admissions resulting from paracetamol OD almost doubled during the 4 years studied. The risk of a repeat paracetamol OD was highest within 4 weeks of the initial OD. Alcohol, benzodiazepines and antidepressants were commonly coingested. The strongest predictor of severe hepatotoxicity was delayed or no N‐acetyl cysteine treatment in patients consuming greater than 10 g of paracetamol or with toxic serum paracetamol levels. A history of alcohol consumption did not appear to worsen outcomes. (Intern Med J 2005; 35: 655–660)
Are humans infected by Hantaviruses in Australia?
Authors: Bi P. , Cameron S. , Higgins G. , Burrell C.
Published: October 2005

Abstract

Hantavirus antibody‐positive rodents have been found across Australia although, to date, there are no reports of infections in humans. This could be due to misdiagnosis clinically and/or inadequate laboratory technique/skills. There are close trading ties between Australia and Asian countries as well as our geographical neighbours where both human and rodent infections are found, so importation is a continuing threat. We consider that further sero‐epidemiological surveys are warranted among rodents (especially those captured from ports in Australia), in patients from renal and respiratory wards of hospitals, and in residents and employees close to harbours using more specific and sensitive laboratory techniques than have been available in the past. (Intern Med J 2005; 35: 672–674)
Sputum bacteriology in patients hospitalized with acute exacerbations of chronic obstructive pulmonary disease and concomitant pneumonia in Hong Kong
Authors: Ko F. W. S. , Lam R. K. Y. , Li T. S. T. , Fok J. P. C. , Chan M. C. H. , Ng T. K. C. , Chan D. P. S. , Hui D. S. C.
Published: October 2005

Abstract

Aim:  To study the sputum microbiology of patients admitted to a teaching hospital with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) with concomitant pneumonia.

Methods:  This was a retrospective study in a tertiary university hospital in Hong Kong. All episodes of AECOPD with pneumonia, patient demographics, length of stay, sputum culture and radiological results admitted in the first half of the year 2000 were retrieved from hospital records.

Results:  There were 118 patients (91 male) with 150 episodes of AECOPD with concomitant pneumonia. The age of the patients was 74.8 ± 10.0 years. Positive routine sputum culture was detected in 45.6% of the patients. Among these hospital admissions, 8.7, 4.0 and 12.0%, respectively, required intensive care unit admissions, mechanical ventilation and non‐invasive positive pressure ventilation. Haemophilus influenzae was the commonest organism found in sputum (26.0%), followed by Pseudomonas aeruginosa (5.5%), Streptococcus pneumoniae (3.4%), and Moraxella catarrhalis (3.4%). Mycobacterium tuberculosis was found in 1.5% of the admissions. The presence of P. aeruginosa in sputum was associated with a longer hospital length of stay (9.1 ± 3.1 vs. 7.1 ± 4.2 days, P = 0.03).

Conclusion:  In contrast to most other studies reporting S. pneumoniae as the most likely bacterial pathogen, H. influenzae was the commonest bacterium isolated in sputum in our patients with AECOPD and concomitant pneumonia. (Intern Med J 2005; 35: 661–667)
Why do acute myocardial infarction patients not call an ambulance? An interview with patients presenting to hospital with acute myocardial infarction symptoms
Authors: Lozzi L. , Carstensen S. , Rasmussen H. , Nelson G.
Published: October 2005

Abstract

Background: Studies from overseas indicate that patients with acute myocardial infarction (AMI) symptoms often fail to use the emergency services as recommended, thereby depriving themselves from life‐saving treatment in case of cardiac arrest and delaying the time to myocardial reperfusion in the presence of a coronary occlusion.

Aims: To compare patients brought in by ambulance to those not brought in by ambulance and to question why some patients do not use the emergency services when presenting to hospital with AMI symptoms.

Methods: Prospective interview and follow up of consecutive patients presenting with AMI symptoms to the emergency department of a tertiary hospital in a metropolitan area within a 1‐month period.

Results: Of the 215 patients presenting to the emergency department, 113 (53%) arrived by private transportation. Sixty (53%) of these felt their symptoms did not warrant calling the ambulance, 17 (15%) had first consulted their general practitioner. The private transport group accounted for 28% of documented AMI.

Conclusions: A large proportion of patients with AMI symptoms refrain from calling the emergency services because they do not consider themselves critically ill. Education programmes appear to be warranted because more appropriate use of emergency services will save lives. (Intern Med J 2005; 35: 668–671)
Inputs to nucleus pontis caudalis from adjacent trigeminal areas
Authors: Dal Bo G. , Lund J. P. , Verdier D. , Kolta A.
Published: October 2005

Recent studies suggest that the nucleus pontis caudalis (nPontc) plays a role in patterning mastication through interactions with the adjacent lateral tegmentum. In this study, we used in vitro intracellular recording and staining to describe the basic membrane properties and morphology of nPontc neurones and to further explore interactions with adjacent structures, using coronal sections of the brainstem of 78 rats, aged 9–28 days. Neurones were large, with dendrites that spread in all directions, and about 64% fired tonically even in the absence of synaptic inputs. Tonic neurones were predominant in the centre of the nucleus. Electrical stimulation of all regions of the nPontc produced mixed excitatory and inhibitory effects on interneurones of lateral tegmental nuclei. Focal inactivation of the dorsal nPontc with injections of tetrodotoxin also had mixed effects on the spontaneous firing of both interneurones and motoneurones but similar injections in the ventral nPontc produced mostly increases of firing. Sixty‐five percent of nPontc neurones received synaptic inputs from the lateral tegmental areas and most of these (68%) were excitatory and mediated by glutamatergic receptors. Inhibitory postsynaptic potentials were mediated by GABAA or glycinergic receptors. Although most responses occurred at relatively long latencies (> 2 ms), they could follow relatively high‐frequency stimulation (> 50 Hz). Excitatory and inhibitory connections between ipsi‐ and contralateral nPontc neurones were also documented, which could contribute to bilateral coordination of jaw movements. This study provides evidence that the nPontc exerts both tonic and phasic influences on the premotor components of the masticatory central pattern generator.
Increased generation of granule cells in adult Bcl‐2‐overexpressing mice: a role for cell death during continued hippocampal neurogenesis
Authors: Kuhn H. Georg , Biebl Manfred , Wilhelm Daniel , Li Mingwei , Friedlander Robert M. , Winkler Jürgen
Published: October 2005

Programmed cell death is an important mechanism during brain development in order to control neuronal cell numbers and to correctly form neuronal circuitries. Programmed cell death is also present in neurogenic regions of the adult brain, and a significant portion of the adult‐born cells is eliminated during the first months of maturation. We here address the question whether overexpression of the anti‐apoptotic protein Bcl‐2 would improve the survival of neural progenitor cells and, as a consequence, increase neurogenesis in the adult hippocampus. Transgenic animals, which express human Bcl‐2 under the neuron‐specific enolase promoter (NSE‐huBcl‐2), show a significant reduction of apoptotic cells in the hippocampal granule cell layer to about half of the wild‐type level. These apoptotic cells are almost exclusively found in the zone of hippocampal progenitor activity and frequently co‐label with the neuronal progenitor marker doublecortin (DCX). The rate of adult neurogenesis is doubled in the dentate gyrus of Bcl‐2‐overexpressing mice as demonstrated by quantification of progenitor cells using DCX and new neurons using bromodeoxyuridine (BrdU)/neuronal nuclei antigen (NeuN) double‐labelling. The effect of Bcl‐2 is limited to the late phase of progenitor maturation, as proliferation and early‐phase progenitor cells were not affected. The increased level of neurogenesis leads to a significantly higher total number of granule cells in the dentate gyrus. These results underline the importance of developmental cell death during neurogenesis in the adult brain.
The SDF‐1/CXCR4 pathway and the development of the cerebellar system
Authors: Vilz Tim O. , Moepps Barbara , Engele Jürgen , Molly Sabine , Littman Dan R. , Schilling Karl
Published: October 2005

Mice deficient for the chemokine receptor CXCR4 show premature translocation of granule cell neuroblasts from their germinal zone into the nascent cerebellum [Y.‐R. Zuo et al. (1998)Nature, 393, 595–599]. Here, we used CXCR4‐null mice to analyse the early development of cerebellar cortical inhibitory interneurons and pontine neurons which, in the adult, are synaptically integrated with granule cells. Cortical inhibitory interneuronal precursors normally invade the cerebellar anlage of CXCR4‐deficient mice, but their dispersal is impeded by dislocated foci of proliferating granule cells, from which they are excluded. This is reminiscent of the strict exclusion of inhibitory interneuronal precursors from the superficial external granule cell layer. As inhibitory interneuronal precursors readily mingle with post‐mitotic granule cells both in wild‐type and CXCR4‐null mice, these findings indicate that the developmentally regulated interactions between granule and inhibitory interneuronal precursors are independent of SDF‐1/CXCR4 signalling. In contrast, the transit of pontine neurons from the rhombic lip through the anterior extramural stream to the basilar pons is disrupted in CXCR4‐deficient animals. Migrating pontine neurons express CXCR4, and in CXCR4‐null animals these cells are found displaced deep into the brainstem. Consequently, nascent pontine nuclei in CXCR4‐deficient animals are hypoplastic. Moreover, they fail to express plexin D1, suggesting that SDF‐1/CXCR4 signalling may also impinge on axon guidance critical to the orderly formation of granule cell mossy fibre afferents.
Neurite guidance by the FnC repeat of human tenascin‐C: neurite attraction vs. neurite retention
Authors: Liu Hsing‐Yin , Nur‐E‐Kamal Alam , Schachner Melitta , Meiners Sally
Published: October 2005

The alternatively spliced fibronectin type‐III repeat C of human tenascin‐C (fnC) provides directional cues to elongating neurites in vitro. When given a choice at an interface with poly l‐lysine (PLL), rat cerebellar granule neurites preferentially crossed onto fnC (defined herein as neurite attraction) whereas neurites originating on fnC preferentially remained on fnC (defined as neurite retention). Guidance motifs were further refined using synthetic peptides spanning the sequence of fnC. We found that a peptide with amino acid sequence DINPYGFTVSWMASE was sufficient to attract and retain neurites. Peptides with alterations in NPYG facilitated neurite retention but not attraction and, conversely, molecules with alterations in ASE facilitated neurite attraction but not retention. Hence neurite attraction and neurite retention mediated by fnC are separable events that can be independently regulated. This property may prove valuable for the strategic design of peptide reagents for use in strategies to facilitate directed axonal regrowth following CNS injury.
Histamine‐immunoreactive neurons in the mouse and rat suprachiasmatic nucleus
Authors: Michelsen Kimmo A. , Lozada Adrian , Kaslin Jan , Karlstedt Kaj , Kukko‐Lukjanov Tiina‐Kaisa , Holopainen Irma , Ohtsu Hiroshi , Panula Pertti
Published: October 2005

Among the well‐established roles of the neurotransmitter histamine (HA) is that as a regulator of the sleep–wake cycle, which early gained HA a reputation as a ‘waking substance’. The tuberomammillary nucleus (TMN) of the posterior hypothalamus, which contains the sole source of neuronal HA in the brain, is reciprocally connected to the suprachiasmatic nucleus (SCN) which, in turn, is best known as the pacemaker of circadian rhythms in mammals. We report HA‐immunoreactive (‐ir) neurons in the mouse and rat SCN that neither display immunoreactivity (‐iry) for the HA‐synthesizing enzyme histidine decarboxylase (HDC) nor contain HDC mRNA. Further, HA‐iry was absent in the SCN of HDC knockout mice, but present in appropriate control animals, indicating that the observed HA‐iry is HDC dependent. Experiments with hypothalamic slice cultures and i.c.v. injection of HA suggest that HA in the SCN neurons originates in the TMN and is transported from the TMN along histaminergic fibres known to innervate the SCN. These results could indicate the existence of a hitherto unknown uptake mechanism for HA into neurons. Through HA uptake and, putatively, re‐release of the captured HA, these neurons could participate in the HA‐mediated effects on the circadian system in concert with direct histaminergic inputs from the TMN to the SCN. The innervation of the SCN by several neurotransmitter systems could provide a way for other systems to affect the HA‐containing neuronal cell bodies in the SCN.
Contributions of protein phosphatases PP1, PP2A, PP2B and PP5 to the regulation of tau phosphorylation
Authors: Liu Fei , Grundke‐Iqbal Inge , Iqbal Khalid , Gong Cheng‐Xin
Published: October 2005

Abnormal hyperphosphorylation of tau is believed to lead to neurofibrillary degeneration in Alzheimer's disease (AD) and other tauopathies. Recent studies have shown that protein phosphatases (PPs) PP1, PP2A, PP2B and PP5 dephosphorylate tau in vitro, but the exact role of each of these phosphatases in the regulation of site‐specific phosphorylation of tau in the human brain was unknown. Hence, we investigated the contributions of these PPs to the regulation of tau phosphorylation quantitatively. We found that these four phosphatases all dephosphorylated tau at Ser199, Ser202, Thr205, Thr212, Ser214, Ser235, Ser262, Ser396, Ser404 and Ser409, but with different efficiencies toward different sites. The Km values of tau dephosphorylation catalysed by PP1, PP2A and PP5 were 8–12 µm, similar to the intraneuronal tau concentration of human brain, whereas the Km of PP2B was fivefold higher. PP2A, PP1, PP5 and PP2B accounted for ∼ 71%, ∼ 11%, ∼ 10% and ∼ 7%, respectively, of the total tau phosphatase activity of human brain. The total phosphatase activity and the activities of PP2A and PP5 toward tau were significantly decreased, whereas that of PP2B was increased in AD brain. PP2A activity negatively correlated to the level of tau phosphorylation at the most phosphorylation sites in human brains. Our findings indicate that PP2A is the major tau phosphatase that regulates its phosphorylation at multiple sites in human brain. The abnormal hyperphosphorylation of tau is partially due to a downregulation of PP2A activity in AD brain.
Ultrastructural evidence for a pre‐ and postsynaptic localization of full‐length trkB receptors in substantia gelatinosa (lamina II) of rat and mouse spinal cord
Authors: Salio Chiara , Lossi Laura , Ferrini Francesco , Merighi Adalberto
Published: October 2005

Brain‐derived neurotrophic factor (BDNF) exerts its trophic effects by acting on the high‐affinity specific receptor trkB. BDNF also modulates synaptic transmission in several areas of the CNS, including the spinal cord dorsal horn, where it acts as a pain modulator by yet incompletely understood mechanisms. Spinal neurons are the main source of trkB in lamina II (substantia gelatinosa). Expression of this receptor in dorsal root ganglion (DRG) cells has been a matter of debate, whereas a subpopulation of DRG neurons bears trkA receptors and contains BDNF. By the use of two different trkB antibodies we observed that 7.7% and 10.8% of DRG neurons co‐expressed BDNF + trkB but not trkA, respectively, in rat and mouse. Ultrastructurally, full‐length trkB (fl‐trkB) receptors were present at somato‐dendritic membranes of lamina II neurons (rat: 66.8%; mouse: 73.8%) and at axon terminals (rat: 33.2%; mouse: 26.2%). In both species, about 90% of these terminals were identified as primary afferent fibres (PAFs) considering their morphology and/or neuropeptide content. All fl‐trkB‐immunopositive C boutons in type Ib glomeruli were immunoreactive for BDNF and, at individual glomeruli and axo‐dendritic synapses, fl‐trkB receptors were located in a mutually exclusive fashion at pre‐ or postsynaptic membranes. Thus, only a small fraction of fl‐trkB‐immunoreactive dendrites were postsynaptic to BDNF‐immunopositive PAFs. This is the first ultrastructural description of fl‐trkB localization at synapses between first‐ and second‐order sensory neurons in lamina II, and suggests that BDNF may be released by fl‐trkB‐immunopositive PAFs to modulate nociceptive input in this lamina of dorsal horn.
Long‐range oscillatory Ca2+ waves in rat spinal dorsal horn
Authors: Ruscheweyh Ruth , Sandkühler Jürgen
Published: October 2005

Synchronous activity of large populations of neurons shapes neuronal networks during development. However, re‐emergence of such activity at later stages of development could severely disrupt the orderly processing of sensory information, e.g. in the spinal dorsal horn. We used Ca2+ imaging in spinal cord slices of neonatal and young rats to assess under which conditions synchronous activity occurs in dorsal horn. No spontaneous synchronous Ca2+ transients were detected. However, increasing neuronal excitability by application of 4‐aminopyridine after pretreatment of the slice with blockers of (RS)‐alpha‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA)/kainate, γ‐aminobutyric acid (GABA)A and glycine receptors evoked repetitive Ca2+ waves in dorsal horn. These waves spread mediolaterally with a speed of 1.0 ± 0.1 mm/s and affected virtually every dorsal horn neuron. The Ca2+ waves were associated with large depolarizing shifts of the membrane potential of participating neurons and were most likely synaptically mediated because they were abolished by blockade of action potentials or N‐methyl‐d‐aspartate (NMDA) receptors. They were most pronounced in the superficial dorsal horn and absent from the ventral horn. A significant proportion of the Ca2+ waves spread to the contralateral dorsal horn. This seemed to be enabled by disinhibition as primary afferent‐induced dorsal horn excitation crossed the midline only when GABAA and glycine receptors were blocked. Interestingly, the Ca2+ waves occurred under conditions where AMPA/kainate receptors were blocked. Thus, superficial dorsal horn NMDA receptors are able to sustain synchronous neuronal excitation in the absence of functional AMPA/kainate receptors.
Putaminal gray matter volume decrease in panic disorder: an optimized voxel‐based morphometry study
Authors: Yoo Hanik K. , Kim Minue J. , Kim Seog Ju , Sung Young Hoon , Sim Minyoung E. , Lee Yujin S. , Song Seong Yong , Kee Baik Seok , Lyoo In Kyoon
Published: October 2005

Our study aimed to identify gray matter volume differences between panic disorder patients and healthy volunteers using optimized voxel‐based morphometry. Gray matter volume was compared between 18 panic subjects and 18 healthy volunteers. Panic disorder severity scale (PDSS) and Zung self‐rating anxiety scale (Z‐SAS) were administered. Gray matter volumes of bilateral putamen were decreased in panic subjects relative to healthy comparison subjects (corrected P < 0.05). Decreased gray matter volume was also observed in the right precuneus, right inferior temporal gyrus, right inferior frontal gyrus, left superior temporal gyrus, and left superior frontal gyrus at a less conservative level of significance. PDSS score negatively correlated with gray matter volume in the left putamen, right putamen, right inferior frontal gyrus, and left superior frontal gyrus in panic subjects. The duration of illness negatively correlated with left putaminal gray matter volume. There was also a negative correlation between gray matter volume in right putamen and Z‐SAS score in panic subjects. The current study reports a putaminal gray matter volume decrease in panic subjects, which may be related to the clinical severity of panic disorder.
The fate of neural progenitor cells expressing astrocytic and radial glial markers in the postnatal rat dentate gyrus
Authors: Namba Takashi , Mochizuki Hideki , Onodera Masafumi , Mizuno Yoshikuni , Namiki Hideo , Seki Tatsunori
Published: October 2005

In the dentate gyrus neurons continue to be generated from late embryonic to adult stage. Recent extensive studies have unveiled several key aspects of the adult neurogenesis, but only few attempts have so far been made on the analysis of the early postnatal neurogenenesis, a transition state between the embryonic and adult neurogenesis. Here, we focus on the early postnatal neurogenesis and examine the nature and development of neural progenitor cells in Wistar rats. Immunohistochemistry for Ki67, a cell cycle marker, and 5‐bromo‐2‐deoxyuridine (BrdU) labelling show that cell proliferation occurs mainly in the hilus and partly in the subgranular zone. A majority of the proliferating cells express S100β and astrocyte‐specific glutamate transporter (GLAST) and the subpopulation are also positive for glial fibrillary acidic protein (GFAP) and nestin. Tracing with BrdU and our modified retrovirus vector carrying enhanced green fluorescent protein (GFP) indicate that a substantial population of the proliferating cells differentiate into proliferative neuroblasts and immature neurons in the hilus, which then migrate to the granule cell layer (66.8%), leaving a long axon‐like process behind in the hilus, and the others mainly become star‐shaped astrocytes (12.0%) and radial glia‐like cells (4.7%) in the subgranular zone. These results suggest that the progenitors of the granule cells expressing astrocytic and radial glial markers, proliferate and differentiate into neurons mainly in the hilus during the early postnatal period.
Formative research on an early stage of the systemic change process in a small school district
Authors: Joseph Roberto , Reigeluth Charles M.
Published: October 2005

This study utilised a qualitative research methodology known as formative research to improve the process guidelines that are described in the Guidance System for Transforming Education (GSTE). This study took place in a small (5447 students), partly urban and partly rural school district in Indiana. The researchers, also serving as change facilitators, investigated an early stage of the systemic change process as outlined in the GSTE. Specifically, the research focused on field‐testing and improving the process for assessing the district's readiness for change. It was found that this process could have been improved if the facilitators had had more guidance to help them develop the interview protocols.
Supporting change and scholarship through review of online resources in professional development settings
Authors: Ravitz Jason , Hoadley Christopher
Published: October 2005

How can we accelerate innovation and ensure effective dissemination of knowledge about online learning resources? This paper advocates strategies that systematically link online professional development with the research, development and diffusion cycle. The systemic approach we describe can accelerate knowledge advancement and help manage change by improving communication among teachers, trainers, developers and researchers. The examples that are provided are set within two funded projects in the United States that led to the development of two distinct but related strategies—the Online Site Evaluation Form for educators (a web‐based review form used in workshops) and a six‐week online course on technology‐supported assessments. Both strategies make it easier to give feedback to developers and offer incentives to do so in ways that help teachers to learn about online resources individually and with colleagues. The examples are discussed with analysis of their strengths and weaknesses in supporting different modes of interaction. We highlight implications for instructional development, professional development, research and knowledge management in online communities.