bluuebunny/crossref_metadata_2025 huggingface dataset:
Living‐related intestinal transplantation for a patient with hypoganglionosis
Authors: Ishii Tomohiro , Wada Motoshi , Nishi Kotaro , Kazama Takuro , Kawahara Yoshinori , Sasaki Hideyuki , Amae Shintaro , Yoshida Shigehiko , Nakamura Megumi , Nio Masaki , Kato Tomoaki , Hayashi Yutaka
Published: October 2005

Abstract:  A 14‐yr‐old boy with total parenteral nutrition‐dependent short‐bowel syndrome associated with hypoganglionosis underwent the LR‐IT by using a 150 cm segment of distal ileum taken from a healthy donor. The graft vessels were connected to infrarenal aorta and inferior vena cava. The immunosuppressive regimen consisted of daclizumab, tacrolimus, and steroid. The graft surveillance for ACR was accomplished using zoom endoscopy and mucosal biopsy. The blood trough level of tacrolimus was maintained between 20 and 25 ng/mL for the first 2 months, followed by 15–20 ng/mL thereafter. The 50 mg of daclizumab was administered on the day of operation, and same dosage was repeated at 2‐wk intervals. The first ACR occurred on POD‐9 and was progressive, and required a 14‐day course of OKT‐3 injection. After the treatment with OKT‐3, the graft recovered from the ACR, and began to function well enough to discontinue the intravenous nutrition on POD‐55. No infectious complication has occurred. The patient was discharged in POD‐112, and currently tolerates full oral intake without requiring intravenous nutritional or fluid supplementation. The donor was discharged without any complications. The LR‐IT could successfully be performed with minimal risk to the donor, and it can be a treatment of choice for patients with short‐gut syndrome associated with hypoganglionosis.
Adiponectin levels and arteriosclerotic risk factors in pediatric renal transplant recipients
Authors: Bakkaloglu Sevcan A. , Soylemezoglu Oguz , Buyan Necla , Oktar Suna Ozhan , Funahashi Tohru , Pasaoglu Hatice , Elhan Atilla H. , Peru Harun , Hasanoglu Enver
Published: October 2005

Abstract:  ADPN, a recently discovered adipocytokine, has attracted great attention because of its anti‐atherogenic properties. It was suggested as a protective factor for the cardiovascular system because of its close correlation with several risk factors. Our aim was to investigate serum ADPN levels in pediatric RTR and to document possible relationships between ADPN and arteriosclerotic risk factors. Twenty‐one RTR, aged 16.3 ± 4.0 yr, and 23 healthy age and sex‐matched control subjects were enrolled in this study. Serum lipid/lipoprotein fractions, homocysteine and ADPN levels as well as intima‐media thickness of the cIMT were determined in both groups. Significantly higher serum ADPN (p < 0.001) and homocysteine (p < 0.05) levels as well as higher cIMT (p < 0.001) were found in RTR compared with the control subjects, whereas apolipoprotein B and lipoprotein (a) levels were not significantly different. HDL cholesterol was positively correlated with log ADPN (r = 0.585, p < 0.01). There were inverse correlations between log time post‐transplantation and log ADPN as well as HDL cholesterol (r = −0.438, p < 0.05 and r = −0.578, p < 0.05, respectively). There were no correlation between log ADPN, log homocysteine, log apolipoprotein B, lipoprotein (a), creatinine clearance and cumulative steroid dose. Despite reasonable lipid profiles and remarkably elevated ADPN levels, our pediatric RTR with stable graft function displayed a risk for arteriosclerosis because of increased cIMT and mild hyperhomocysteinemia. Regarding the close positive correlation between ADPN and HDL cholesterol, it could be speculated that ADPN is a novel negative surrogate marker of arteriosclerosis. To our knowledge, this is the only report investigating levels and diverse correlates of ADPN in a pediatric RTR group. Further studies in larger groups of recipients are needed to clarify the interaction between arteriosclerotic risk factors and ADPN.
Pediatric renal transplantation: A single center experience over 14 years
Authors: Delucchi A. , Ferrario M. , Varela M. , Cano F. , Rodriguez E. , Guerrero J. L. , Lillo A. M. , Wolff E. , Godoy J. , Buckel E. , Gonzalez G. , Rodriguez J. , Cavada G.
Published: October 2005

Abstract:  Between 1989 and 2003, 100 transplants were performed in 96 patients at the pediatric nephrology unit of the Calvo Mackenna Children's Hospital. Mean age 10.9 ± 3.9 yr (1–17.6), 30% from LD. Donors were younger than 5 yr in five patients and all recipients received an ‘en bloc’ graft. Original disease was hypo/dysplasia 27%, reflux nephropathy 22 and 17% chronic glomerulonephritis. The immunosuppressive protocol during the first period (n = 56, 1989–2000): Cyclosporine, steroids and azathioprine, and during the second period (n = 44, 2001–2003): FK, steroids, MMF and anti‐CD25 antibody (mAbs). AR was reported in 22 patients, 11% in LD, 31% in DD (p < 0.01). The AR rate decreased from 40 to 8% after anti‐CD25 monoclonal induction. Patient actuarial survival rate at 1, 3 and 5 yr was 100% for LD and 96% for DD. The overall actuarial graft survival at 1,3, and 5 yr was 96.7, 96.7 and 71% for LD and 89, 76 and 73% for DD donors. Graft survival rate improved from the first period (1989–2000) to the second period (2001–2003; p = 0.05). No difference in graft survival rate with HLA‐A,B,DR matching was found. Graft survival rate was better when cold ischemia time was <24 h (p < 0.01). CMV infections increased from 19 to 40% when MMF and anti‐CD25 Ab were introduced (p < 0.01). The height/age Z score at 1, 3 and 5 yr post‐transplant was −2.2, −2.1, −2.2, respectively, for children older than 7 yr and −1.8, −1.9, −2.1 for those transplanted younger than 7 yr of age who were switched to alternate day steroids (p < 0.01). The cause of graft lost was: chronic rejection eight, non‐adherence four, AR four and vascular thrombosis two. The cause of death in two patients was fungus septicemia and accelerated rejection. Pediatric renal transplantation can be performed in our group with acceptable morbidity, low mortality and graft survival rates similar to other reports in North America and Western Europe. Graft survival rate improved with newer immunosuppression and greater experience at the center. Management of non‐adherence and chronic rejection remain the major challenges.
Impact of surveillance stool culture guided selection of antibiotics in the management of pediatric small bowel transplant recipients
Authors: John Minnie , Gondolesi Gabriel , Herold Betsy C. , Kaufman Stuart , Fishbein Thomas , Posada Roberto
Published: October 2005

Abstract:  Surveillance stool cultures (SSC) have been used in immunocompromised populations to predict the organisms associated with invasive infections and aid in the selection of empiric antibiotic regimens. To evaluate the utility of this approach in pediatric small bowel transplant (SBT) recipients, we conducted a retrospective review of 33 patients who underwent SBT, 16 of whom had SSC done. In no case was the same organism isolated from SSC and subsequent blood, peritoneal fluid or wound cultures. In the first month post‐transplantation, blood cultures were positive in 44% and 35% of patients that had and did not have SSC done, respectively (p = 0.73); peritoneal fluid cultures in 44% and 65% (p = 0.30); and wound cultures in 44% and 24% (p = 0.28). There were no significant differences among both groups in time to first infection, duration of ICU stay following SBT, graft survival or long‐term patient survival. We conclude that SSC‐guided antibiotic selection does not have a significant impact on the incidence of invasive infections in the first month following SBT or on specific indicators of patient outcome. This suggests that empiric antibiotic regimens should be selected based on clinical presentation and hospital flora and susceptibility patterns.
Feasibility of duct‐to‐duct biliary reconstruction in pediatric living related liver transplantation: Report of three cases
Authors: Kimura Takuya , Hasegawa Toshimichi , Ihara Yoshiyuki , Nara Keigo , Sasaki Takashi , Dono Keizo , Mushiake Sotarou , Fukuzawa Masahiro
Published: October 2005

Abstract:  Feasibility of duct‐to‐duct biliary reconstruction in adult living related liver transplantation (LRLTx) has been recently reported; however, little has been known of its surgical outcome in children. To assess the feasibility and safety of duct‐to‐duct biliary reconstruction in children, the surgical outcomes of duct‐to‐duct biliary reconstruction were retrospectively analyzed. The subjects were three children who underwent LRLTx in our hospital each utilizing allografts with a right lobe, a left robe and a lateral segment, respectively. The cause of end‐stage liver disease in each of them was fulminant Wilson's disease, fulminant hepatic failure and unresectable hepatoblastoma. Duct‐to‐duct anastomosis was performed in younger patients and adolescents with interrupted and continuous sutures, respectively. The diameter of bile duct in allografts was from 4 to 6 mm and 12 or 13 stitches were required for anastomosis. Post‐operative choledochography from the external tube showed neither stenosis nor leakage and the tube was evacuated within 3 months after LRLTx. No biliary complications were observed with the median follow‐up of 28 months. In conclusion, our results show that duct‐to‐duct biliary reconstructions in pediatric LRLTx seemed to be feasible and safe. Further studies are required to elucidate its real impact on pediatric LRLTx.
An overview of methods for the detection and observation of arbuscular mycorrhizal fungi in roots†
Authors: Vierheilig Horst , Schweiger Peter , Brundrett Mark
Published: October 2005

One of the most cited papers in arbuscular mycorrhizal (AM) research was published by Phillips and Hayman in 1970 describing an easy standard method to stain AM fungi (AMF) in roots. Since then, a number of other methods (destructive–non‐destructive; vital–non‐vital) on how to visualize AMF in roots have been published. Our review provides an overview on present techniques used to visualize AMF in roots and gives recommendations on their use. We hope that the present review will help the readers to choose an appropriate method to visualize AMF in roots for their specific experimental set‐up.
The effects of erythromycin on the viability and the secretion of TNF‐α and TGF‐β1 and expression of connexin43 by human pleural mesothelial cells
Authors: XIE Canmao , HUANG Jian Qiang , LIGHT Richard W.
Published: October 2005

Objective:  The mechanism by which erythromycin produces pleurodesis remains unknown. The purpose of this study was to investigate the effects of erythromycin on human pleural mesothelial cell (HPMC) viability, the secretion of tumour necrosis factor‐α (TNF‐α) and transforming growth factor‐β1 (TGF‐β1) and the level of expression of connexin43.

Methodology:  HPMC were incubated with different concentrations of erythromycin. The inhibitory effects of erythromycin on HPMC growth were measured using a tetrazolium‐based colorimetric assay. The levels of TNF‐α and TGF‐β1 in supernatants were measured by ELISA and levels of connexin43 were assessed by Western blot.

Results:  Erythromycin injured HPMC in a dose and time‐dependent manner. The secretion of both TNF‐α and TGF‐β1 by HMPC increased significantly when they were incubated with 100 mg/L erythromycin for 3 or 5 days. The levels of connexin43 in HPMC decreased after incubation with 100 mg/L erythromycin and no relationship was observed between the levels and incubation time.

Conclusions:  Erythromycin injures HPMC in a dose‐ and time‐dependent manner and results in the secretion of TNF‐α and TGF‐β1. This is one possible mechanism of pleurodesis with erythromycin. Furthermore, erythromycin decreased the levels of connexin43 in HPMC, which could possibly affect the response of HPMC to pleurodesis with erythromycin.
Asthma control in adults in Asia‐Pacific
Authors: ZAINUDIN Bin M. Zin , KAI WEI LAI Christopher , SORIANO Joan B. , JIA‐HORNG Wang , DE GUIA Teresita S ,   Asthma Insights and Reality in Asia‐Pacific (AIRIAP) Steering Committee
Published: October 2005

Objective  The Asthma Insights and Reality in Asia‐Pacific (AIRIAP) survey collected detailed information on asthma severity and management in the urban centres of eight areas of the Asia‐Pacific region. This study compared asthma morbidity and management practices in these areas.

Methodology  Following recruitment, face‐to‐face interviews were completed with 2323 adults with diagnosed asthma, who had current symptoms or were using asthma medication. Comparisons between areas were made for asthma severity, asthma burden and management practices.

Results  Asthma severity varied significantly between areas (P < 0.01), with Vietnam and mainland China reporting the most cases with severe, persistent symptoms. Severity of asthma was significantly associated with advancing age and a lower level of education in a multivariate analysis (P < 0.001). The total use of acute healthcare for asthma was significantly associated with increased asthma severity. Work absence due to asthma was highest in the Philippines (46.6%) and lowest in South Korea (7.5%). The use of inhaled corticosteroids was associated with age in a non‐linear manner. There was significant variation among countries in usage of inhaled corticosteroids, from 1.3% in South Korea to 29.0% in Taiwan (P < 0.00001). A peak flow meter was owned by a total of 7.7% of respondents, and overall, 17.9% of adults had a written action plan for asthma management.

Conclusions  Within the Asia‐Pacific region, asthma in adults differs significantly in disease severity, management and treatment according to area of residence. International recommendations on the management of asthma are generally not being followed.
Assessment of an asthma quality of life scale using item‐response theory
Authors: ADAMS Robert , ROSIER Malcolm , CAMPBELL Donald , RUFFIN Richard
Published: October 2005

Objective  Health‐related quality of life (HRQOL) scores produced by simply summing individual item values have been criticized for lacking linearity and for not being equally discriminating across the range of scores. Differences in summed scores may depend more on their starting point on the scale rather than actual differences in the underlying dimension of HRQOL, making it difficult to judge what a particular score means. We sought to examine the usefulness of an alternative method of scoring questionnaires, item–response theory (IRT), for the clinical interpretation of a modified version of the Marks Asthma Quality of Life Questionnaire (MAQLQ‐M).

Methodology:  Using the MAQLQ‐M, we surveyed 293 adults with moderate to severe asthma, managed at two university teaching hospitals in Adelaide, South Australia. Scores obtained by usual summative Likert‐type scores were compared to estimates using the partial credit method of IRT.

Results  We found a non‐linear relationship between raw, summative scores and the IRT estimates. The departure from linearity was marked for summative scores below 3.0 and above 5.0 (range 1.0–7.0), values that included half of the study patients. Summative scoring did not produce scores at the interval level of measurement.

Conclusion  For an equivalent difference measured in the underlying dimension of actual HRQOL using IRT, traditional summated scores showed a much smaller difference in scores at both the lower and upper end of HRQOL, than at the mid‐range of HRQOL. Caution should be used when interpreting HRQOL surveys scored in the usual summative manner. Advantages may be gained by using IRT as an alternative method of scoring HRQOL questionnaires.
Pulmonary artery pressure and blood flow as predictors of outcome from lung cancer resection
Authors: PIERCE Robert J. , SHARPE Ken , JOHNS Jennifer , THOMPSON Bruce
Published: October 2005

Objective:  Pulmonary hypertension is a putative risk factor for lung resection but catheter measurements are invasive. The aim of the present study was to assess prediction of mortality and complications from lung resection by Doppler echocardiographic estimates of pulmonary artery pressure (PAp) and soluble gas uptake estimates of effective pulmonary blood flow (Q̇RB).

Methodology:  In 33 lung cancer patients, resting PAp (sys) and Q̇RB were measured preoperatively. In 13 patients, supine exercise estimates of PAp (sys) were also made and in five patients catheter PAp estimates were made.

Results:  Baseline PAp (sys) was 35 ± 5 mmHg in four patients who died and 35 ± 5 mmHg in 27 survivors. Post‐exercise PAp (sys) was 58 ± 11 mmHg in non‐survivors and 60 ± 11 mmHg in survivors (both not significant). Resting Q̇RB was 3.9 ± 0.35 L/min in two non‐survivors compared with 4.7 ± 0.90 L/min in 22 survivors (P = 0.12) and was significantly lower in those experiencing complications. Regression analysis showed no significant relationship between resting or post‐exercise PAp and mortality, although low Q̇RB tended towards predicting mortality (P = 0.07). There were also trends for higher PAp (sys) to predict respiratory and cardiac complications (P = 0.08) and for lower Q̇RB to predict unspecified or surgical complications.

Conclusion:  PAp and Q̇RB did not predict outcome from lung resection better than baseline respiratory function indices.
Gemcitabine and carboplatin in the treatment of locally advanced and metastatic non‐small cell lung cancer
Authors: LEOW Chai‐Hooi , LIAM Chong‐Kin
Published: October 2005

Objective:  The aim of the study was to evaluate the response, survival advantage and toxicity profile of gemcitabine–carboplatin combination cytotoxic chemotherapy in patients with locally advanced and metastatic non‐small cell lung cancer (NSCLC).

Methodology:  Patients who received gemcitabine‐carboplatin combination chemotherapy over a 2.5‐years period were analyzed. Carboplatin at a dose of 5 mg/mL/min (area under the concentration‐time curve) was given on day 1 and gemcitabine (1000 mg/m2) on days 1 and 8, every 3 weeks.

Results:  Of 49 chemotherapy‐naive patients (median age, 62 years) who received this treatment, 57% were males, 12% had stage IIIa, 39% stage IIIb and 49% metastatic disease. The Eastern Cooperative Oncology Group (ECOG) performance status of 70% of the patients was 1 at the time of commencement of chemotherapy and 2 for the remaining 30% of patients. The overall response rate, based on 33 evaluable patients, was 27.3%. The response rate was not affected by age, stage of disease or performance status. The median survival was 9 months. Median survival among patients with an ECOG performance status of 1 was 11 months, as compared with 4 months for patients with an ECOG performance status of 2 (P < 0.001). Toxicity was generally well tolerated and there were no treatment‐related deaths.

Conclusions:  Gemcitabine‐carboplatin combination chemotherapy is an effective and well‐tolerated cytotoxic regimen among Malaysian patients with advanced NSCLC. A performance status of 1 or less was associated with a better survival.
The prevalence of acute response to bronchodilator in pulmonary lymphangioleiomyomatosis
Authors: YEN Kenneth T. , PUTZKE John D. , STAATS Bruce A. , BURGER Charles D.
Published: October 2005

Objective:  The objective of this study was to evaluate the prevalence of acute bronchodilator responses in patients who were evaluated for pulmonary lymphangioleiomyomatosis.

Methodology:  This study was a retrospective review of the medical records of 50 patients, who were assessed for lymphangioleiomyomatosis from 1978 to 2002 at Mayo Clinic in Rochester, Minnesota, and Jacksonville, Florida, USA. Each medical record was reviewed for pertinent clinical and pulmonary function test data, including results for lung volume and flow, diffusing capacity and response to bronchodilator.

Results:  At initial testing, the mean FEV1/FVC ratio for the whole group was 60%; 35 patients (70%) had airflow obstruction; five patients (10%) had only restriction; and 10 (20%) had neither restriction nor obstruction. Three patients (6%) showed a positive response to bronchodilator at initial testing and only one patient showed a positive response at 1 year. Pulmonary function testing at 1‐year follow up was available in a subgroup of this cohort (23 patients; 46%), and only one patient (2%) had a positive response to bronchodilator. Although there was a statistically significant decrease in the FEV1/FVC ratio (from 64% to 62%; P = 0.02), no other differences were found at 1‐year follow up.

Conclusions:  In its advanced state, lymphangioleiomyomatosis produces irreversible airflow obstruction. A positive response to bronchodilator was unusual. Other measures of pulmonary function showed little or no change over a 12‐month period.
Prolonged survival after talc poudrage for malignant pleural mesothelioma: Case series
Authors: AELONY Yossef , YAO Janis F.
Published: October 2005

Objective:  Malignant pleural mesothelioma is a fatal disease with a mean life expectancy of 6–12 months. Since 1982, we have performed thoracoscopic talc poudrage (TTP) as a primary therapy in mesothelioma patients presenting with pleural effusion. As the survival data for our patients surpassed that of many published series, the patient data was analyzed to determine whether talc poudrage can be considered as a contemporary palliative option.

Methodology:  We reviewed all 26 patients with a final diagnosis of malignant pleural mesothelioma from our prospective database of 228 consecutive patients who received thoracoscopy from the same physician for recurrent symptomatic pleural effusion. Patients were followed up until their death.

Results:  Mean survival after TTP was 23.8 ± 16.3 months (median 19.4, range 2.9–68). Pleurodesis palliated dyspnoea in all patients. No perioperative deaths and one postoperative complication (pneumonia) occurred. Mean hospital stay was 3.9 ± 2.7 days.

Conclusion:  TTP remains a safe, low‐morbidity, inexpensive primary palliative treatment option for malignant pleural mesothelioma and a valid control arm option for therapeutic trials. TTP is ideal for patients who wish to avoid thoracotomy, long hospital stays and morbidity from multimodality therapy. Prospective randomized studies are needed to compare quality of life and survival after talc poudrage and other therapies.
Clinicopathological analysis of lung cancer resembling malignant pleural mesothelioma
Authors: KOBASHI Yoshihiro , MATSUSHIMA Toshiharu , IREI Tsutomu
Published: October 2005

Objective:  The aim of this study was to evaluate the clinicopathological features of lung cancer resembling malignant pleural mesothelioma.

Methodology:  The seven patients studied had tumours showing an extensive pleural growth pattern, and were chosen from 1516 lung cancer patients diagnosed at two affiliated hospitals over a 17‐year period.

Results:  Histologically, five of these lung cancers were adenocarcinomas, one was a small cell carcinoma, and one a large cell carcinoma. Tumour markers such as carcinoembryonic antigen (CEA) were elevated in six patients at admission. However, a clinical diagnosis was difficult and these cancers could only be distinguished from malignant pleural mesothelioma by thoracentesis in two cases, pleural biopsy in two, thoracotomy in two, and in case 7 at autopsy. Treatment consisted of chemotherapy or radiation therapy in four patients, but with little clinical effect. The mean survival time was 6.7 months, which is much less than for true malignant pleural mesothelioma.

Conclusions:  Lung cancer resembling malignant pleural mesothelioma is most frequently observed in patients with adenocarcinoma, which is suspected to occur peripherally. To distinguish pseudomesotheliomatous carcinoma from malignant pleural mesothelioma in patients with diffuse pleural thickening and effusion, requires adequate tissue sampling by thoracotomy or video‐assisted thoracoscopic surgery and a panel of immunohistochemical stains.
Cranial optic nerve involvements in patients with severe COPD
Authors: ÖZGE Cengiz , ÖZGE Aynur , YILMAZ Ayça , YALÇINKAYA Deniz E. , ÇALIKOĞLU Mukadder
Published: October 2005

Objective:  The relationship between neuropathy and increased morbidity in patients with COPD is clear, but few studies have assessed cranial neuropathies, especially optic nerve involvement, in COPD patients. We evaluated peripheral involvement of the optic nerve and determined factors influencing this condition in patients with severe COPD.

Methodology:  Twenty‐eight patients, mean age 59.4 ± 9.4 years, diagnosed with severe stable COPD according to the GOLD criteria, and 20 age‐ and gender‐matched healthy individuals, mean age 55.6 ± 8.5 years, were included in the study. All subjects underwent visual evoked potential (VEP) assessment together with detailed clinical and laboratory examination to exclude concurrent risk factors for neuropathy.

Results:  VEP assessment showed significant abnormalities in COPD patients (82.1%) (commonly amplitude abnormalities) when compared with healthy controls.

Conclusions:  The optic nerve is often involved in patients with severe COPD, possibly as part of a polyneuropathy, and this is related to acidosis, hypercarbia and airway obstruction, independent of disease duration, smoking and age. These results should be taken into consideration when determining management strategies for these patients.
The feasibility of nitric oxide delivery with high frequency jet ventilation
Authors: ARABI Yaseen , KUMAR Anand , WOOD Kenneth , FLATEN Anne
Published: October 2005

Abstract:  A 27‐year‐old female with acute monocytic leukaemia (M5) developed acute respiratory distress syndrome (ARDS). Because of refractory hypoxaemia and severe barotrauma during conventional mechanical ventilation, the patient was switched to high frequency jet ventilation (HFJV) as a salvage therapy. Her refractory hypoxaemia improved temporarily but worsened again. Approval of the Institutional Review Board and the Food and Drug Administration was obtained to use nitric oxide (NO) with HFJV on a compassionate basis considering the grave situation. The NO delivery system was connected to the secondary flow circuit of the HFJV immediately after the humidifier. We measured the concentration of NO at least every hour by inserting a 7‐Fr catheter connected to a McNeill analyzer into the endotracheal tube. Despite improvement of oxygenation, the patient's respiratory status deteriorated further and she died. In this case we were able to achieve reliable and constant levels of NO. The purpose of this report is to discuss the technical aspects and pitfalls of this method.
Chronic pulmonary scedosporiosis simulating aspergillosis
Authors: KOGA Takeharu , KITAJIMA Takao , TANAKA Reiko , HIROKAWA Masashi , ICHIKI Masao , RIKIMARU Toru , AIZAWA Hisamichi
Published: October 2005

Abstract:  Scedosporium apiospermum, a ubiquitously distributed saprophyte, is emerging as an important pathogen in immunocompromised patients. We describe a 72‐year‐old patient with chronic S. apiospermum infection of the lung simulating aspergilloma. His medical history was unremarkable except that he had undergone partial lung resection as a treatment for pulmonary tuberculosis several decades previously. He had no underlying immunosuppressive conditions. This patient illustrates that pulmonary scedosporiosis is not confined to immunocompromised patients and that the clinical presentation may be indistinguishable from that of aspergilloma.
Intralobar sequestration with tuberculous infection confined to the sequestrated lung
Authors: YATERA Kazuhiro , IZUMI Miiru , IMAI Makoto , IKEGAMI Tomomi , MIYAZAKI Naoki , KIDO Masamitsu
Published: October 2005

Abstract:  A 22‐year‐old female was referred to the hospital suffering from a persistent, non‐productive cough and repeated exacerbations of a right lower zone infiltrate suggestive of pulmonary sequestration. Angiography revealed an aberrant artery that originated from the left side of the descending aorta, crossed the aorta anteriorly, flowed through the right lower lobe and drained into the right inferior pulmonary vein. Right lower lobectomy was conducted by open thoracotomy. Gross examination revealed mucoid impaction of bronchi in the sequestration. Microscopy demonstrated a clear boundary between sequestrated and normal lung, as well as caseating epitheloid granulomas confined to the sequestration. As the aberrant artery fed both sequestrated and adjacent normal lung and the boundary did not involve the pleura, the lesion was classified as a Pryce's type II intralobar sequestration. No acid‐fast bacilli were observed, but homogenates of the sequestration were positive for Mycobacterium tuberculosis by polymerase chain reaction. The patient was treated with isoniazid and rifampicin daily for 9 months, and 6 years later her clinical status remained excellent. Tuberculosis confined to a sequestration is extremely rare and characteristics of the aberrant artery suggested this intralobar sequestration was likely to be congenital in origin.
Ethics committee reviews and mutual acceptance: a pilot study
Authors: Rosenthal M. A. , Sarson‐Lawrence M. , Alt C. , Arkell K. , Dodds M.
Published: October 2005

Abstract

Aims:  To develop a human research ethics committee (HREC) mutual acceptance (MA) model, based on the National Health and Medical Research Council's guidelines. The MA model aims to facilitate aspects of multicentre research and decrease the time taken to finalise the HREC review process.

Methods:  Four HREC (The Alfred Hospital, Austin Health, Peter MacCallum Cancer Centre and Melbourne Health) agreed to participate in a 13‐month pilot project to evaluate the MA model. Evaluation included times from submission to approval and stakeholder surveys.

Results:  Seventeen consecutive studies were submitted to the MA pilot project. Stakeholders agreed that the MA model was efficient and effective and that submission and review processes had improved, with a demonstrable reduction in the levels of duplication. There was a 27% improvement in approval times for multicentre studies.

Conclusions:  Our (MA) model resulted in clear improvements in HREC processes and timelines. Stakeholder acceptance was high. This model provides a framework for a broader program of MA. (Intern Med J 2005; 35: 650–654)
‘On being both professional and human’: one woman's journey
Authors: With An Introductory Note By P.Komesaroff Anonymous
Published: October 2005

Introductory note by Paul Komesaroff

The following reflection was written by the wife of a patient who died in the intensive care unit of a large public hospital after a stay of nearly 5 months. The author has chosen to remain anonymous to protect her privacy.

The article is presented because we believe it offers deep insights into the experiences of relatives and other carers of patients with serious illnesses. Caring for carers or relatives is usually considered to lie outside the boundaries of the doctor–patient relationship. Although meticulous attention is often given to providing information and consulting about medical decisions, clinicians rarely consider that they have a responsibility to those closest to the patient, even though it is these people who will carry the burden of the experiences of the illnesses of their loved ones, perhaps for many decades.

Clinical communication is concerned not only with the transmission of information. It is not a purely formal process of conveying facts or data. It is also about engaging another person in a dialogue about fears, uncertainties and hopes and, where appropriate, negotiating with him or her about priorities, goals and values. In many cases the perceptions of the health‐care team are very different from those of patients and their relatives; accordingly, there may be no way of avoiding the need for such dialogue and negotiation.

This article draws attention to the importance of ‘recognition’ as an ethical act: recognition of the roles carers and relatives play in the lives of their loved ones, and of the pain and loss they themselves are suffering. When a physician cares for a patient it is not just an isolated individual who is being treated but the full, complex network of social relations in which he or she is embedded.

Recognition also entails acknowledgment of error or of bad outcomes. In the world of someone undergoing bereavement, such acknowledgment might acquire great intensity. Small gestures can make a big impact. Where appropriate – for example, in the case of an adverse outcome – a formal apology, independent of any admissions of legal liability, may play a powerful therapeutic role. This article emphasises the fundamental healing potential of the apology.

The voices of patients and relatives must be acknowledged and interpreted in their proper contexts. It is not suggested here that these expressions are of greater validity or authenticity than the perspective of the medical team. Nor should they be regarded as demonstrating the existence of a pathology within the psyches of patients and relatives that can only be understood through the instrumental discourses of medicine1. Rather, as this case demonstrates, patient narratives constitute a supplement to the medical ones, but also offer a commentary on them and provide insights from which clinical practice can be enriched and refined.
Relaxin receptor activation in the basolateral amygdala impairs memory consolidation
Authors: Ma Sherie , Roozendaal Benno , Burazin Tanya C. D. , Tregear Geoffrey W. , McGaugh James L. , Gundlach Andrew L.
Published: October 2005

The peptide‐hormone relaxin has well‐established actions in male and female reproductive tracts, and has functional effects in circumventricular regions of brain involved in neurohormonal secretion. In the current study, we initially mapped the distribution of mRNA encoding the relaxin receptor − leucine‐rich repeat‐containing G‐protein‐coupled receptor 7 (LGR7)‐ and [33P]‐human relaxin‐binding sites in extra‐hypothalamic sites of male Sprague–Dawley rats. The basolateral amygdala (BLA) expressed high levels of LGR7 mRNA and relaxin‐binding sites and, although relaxin peptide was not detected in the BLA, several brain regions that send projections to the BLA were found to contain relaxin‐expressing neurons. As it is well established that the BLA is involved in regulating the consolidation of memory for emotionally arousing experiences, we investigated whether activation of LGR7 in the BLA modulated memory consolidation for aversively motivated inhibitory avoidance training. Bilateral infusions of human relaxin (10–200 ng in 0.2 µL) into the BLA immediately after inhibitory avoidance training impaired 48‐h retention performance in a dose‐dependent manner. Delayed infusions of relaxin into the BLA 3 h after training were ineffective, indicating that the retention impairment was due to influences on memory consolidation. Post‐training infusions of relaxin into the adjacent central amygdala, which is devoid of LGR7, did not impair retention. These findings suggest a novel function for endogenous relaxin–LGR7 signalling in rat brain involving regulation of memory consolidation.
Reduced extracellular space in the brain of tenascin‐R‐ and HNK‐1‐sulphotransferase deficient mice
Authors: Syková Eva , Voříšek Ivan , Mazel Tomáš , Antonova Tatiana , Schachner Melitta
Published: October 2005

Tenascin‐R (TN‐R), a large extracellular glycoprotein, is an important component of the adult brain's extracellular matrix (ECM); tenascin‐C (TN‐C) is expressed mainly during early development, while human natural killer 1 (HNK‐1) is a sulphated carbohydrate epitope that attaches to these molecules, modifying their adhesive properties. To assess their influence on extracellular space (ECS) volume and geometry, we used the real‐time iontophoretic method to measure ECS volume fraction α and tortuosity λ, and diffusion‐weighted magnetic resonance imaging (MRI) to measure the apparent diffusion coefficient of water (ADCW). Measurements were performed in vivo in the cortex and CA1 hippocampal region of TN‐R‐, TN‐C‐ and HNK‐1 sulphotransferase (ST)‐deficient adult mice and their wild‐type littermate controls. In both cortex and hippocampus, the lack of TN‐R or HNK‐1 sulphotransferase resulted in a significant decrease in α and λ. Compared with controls, α in TN‐R–/– and ST–/– mice decreased by 22–26% and 9–15%, respectively. MRI measurements revealed a decreased ADCW in the cortex, hippocampus and thalamus. ADCW reflected the changes in α; the decrease in λ indicated fewer diffusion obstacles in the ECS, presumably due to a decreased macromolecular content. No significant changes were found in TN‐C–/– animals. We conclude that in TN‐R–/– and ST–/– mice, which show morphological, electrophysiological and behavioural abnormalities, the ECS is reduced and its geometry altered. TN‐R, as an important component of the ECM, appears to maintain an optimal distance between cells. The altered diffusion of neuroactive substances in the brain will inevitably affect extrasynaptic transmission, neuron–glia interactions and synaptic efficacy.
Sleep deprivation suppresses neurogenesis in the adult hippocampus of rats
Authors: Guzman‐Marin Ruben , Suntsova Natalia , Methippara Melvi , Greiffenstein Richard , Szymusiak Ronald , McGinty Dennis
Published: October 2005

We reported previously that 96 h of sleep deprivation (SD) reduced cell proliferation in the dentate gyrus (DG) of the hippocampus in adult rats. We now report that SD reduces the number of new cells expressing a mature neuronal marker, neuronal nuclear antigen (NeuN). Rats were sleep‐deprived for 96 h, using an intermittent treadmill system. Total sleep time was reduced to 6.9% by this method in SD animals, but total treadmill movement was equated in SD and treadmill control (CT) groups. Rats were allowed to survive for 3 weeks after 5‐bromo‐2‐deoxyuridine (BrdU) injection. The phenotype of BrdU‐positive cells in the DG was assessed by immunofluorescence and confocal microscopy. After 3 weeks the number of BrdU‐positive cells was reduced by 39.6% in the SD group compared with the CT. The percentage of cells that co‐localized BrdU and NeuN was also lower in the SD group (SD: 46.6 ± 1.8% vs. CT: 71.9 ± 2.1, P < 0.001). The percentages of BrdU‐labeled cells co‐expressing markers of immature neuronal (DCX) or glial (S100‐β) cells were not different in SD and CT groups. Thus, SD reduces neurogenesis in the DG by affecting both total proliferation and the percentage of cells expressing a mature neuronal phenotype. We hypothesize that sleep provides anabolic or signaling support for proliferation and cell fate determination.
Involvement of spinal cord nuclear factor κB activation in rat models of proinflammatory cytokine‐mediated pain facilitation
Authors: Ledeboer Annemarie , Gamanos Michael , Lai Wenmin , Martin David , Maier Steven F. , Watkins Linda R. , Quan Ning
Published: October 2005

Proinflammatory cytokines, such as interleukin‐1β and tumour necrosis factor‐α, are released by activated glial cells in the spinal cord and play a major role in pain facilitation. These cytokines exert their actions, at least partially, through the activation of the transcription factor, nuclear factor κB (NF‐κB). In turn, NF‐κB regulates the transcription of many inflammatory mediators, including cytokines. We have previously shown that intrathecal injection of the human immunodeficiency virus‐1 (HIV‐1) envelope glycoprotein, gp120, induces mechanical allodynia via the release of proinflammatory cytokines. Here, we investigated whether NF‐κB is involved in gp120‐induced pain behaviour in Sprague–Dawley rats. Intrathecal administration of NF‐κB inhibitors, pyrrolidinedithiocarbamate (PDTC) and SN50, prior to gp120 partially attenuated gp120‐induced allodynia. In addition, PDTC delayed and reversed allodynia in a model of neuropathic pain induced by sciatic nerve inflammation. These observations suggest that intrathecal gp120 may lead to activation of NF‐κB within the spinal cord. To reveal NF‐κB activation, we assessed inhibitory factor κBα (IκBα) mRNA expression by in situ hybridization, as NF‐κB activation up‐regulates IκBα gene expression as part of an autoregulatory feedback loop. No or low levels of IκBα mRNA were detected in the lumbar spinal cord of vehicle‐injected rats, whereas IκBα mRNA expression was markedly induced in the spinal cord following intrathecal gp120 in predominantly astrocytes and endothelial cells. Moreover, IκBα mRNA expression positively correlated with proinflammatory cytokine protein levels in lumbosacral cerebrospinal fluid. Together, these results demonstrate that spinal cord NF‐κB activation is involved, at least in part, in exaggerated pain states.
Distinct and overlapping fMRI activation networks for processing of novel identities and locations of objects
Authors: Pihlajamäki Maija , Tanila Heikki , Könönen Mervi , Hänninen Tuomo , Aronen Hannu J. , Soininen Hilkka
Published: October 2005

The ventral visual stream processes information about the identity of objects (‘what’), whereas the dorsal stream processes the spatial locations of objects (‘where’). There is a corresponding, although disputed, distinction for the ventrolateral and dorsolateral prefrontal areas. Furthermore, there seems to be a distinction between the anterior and posterior medial temporal lobe (MTL) structures in the processing of novel items and new spatial arrangements, respectively. Functional differentiation of the intermediary mid‐line cortical and temporal neocortical structures that communicate with the occipitotemporal, occipitoparietal, prefrontal, and MTL structures, however, is unclear. Therefore, in the present functional magnetic resonance imaging (fMRI) study, we examined whether the distinction among the MTL structures extends to these closely connected cortical areas. The most striking difference in the fMRI responses during visual presentation of changes in either items or their locations was the bilateral activation of the temporal lobe and ventrolateral prefrontal cortical areas for novel object identification in contrast to wide parietal and dorsolateral prefrontal activation for the novel locations of objects. An anterior‐posterior distinction of fMRI responses similar to the MTL was observed in the cingulate/retrosplenial, and superior and middle temporal cortices. In addition to the distinct areas of activation, certain frontal, parietal, and temporo‐occipital areas responded to both object and spatial novelty, suggesting a common attentional network for both types of changes in the visual environment. These findings offer new insights to the functional roles and intrinsic specialization of the cingulate/retrosplenial, and lateral temporal cortical areas in visuospatial cognition.
Eph/ephrin expression in the adult rat visual system following localized retinal lesions: localized and transneuronal up‐regulation in the retina and superior colliculus
Authors: Rodger J. , Symonds A. C. E. , Springbett J. , Shen W‐Y. , Bartlett C. A. , Rakoczy P. E. , Beazley L. D. , Dunlop S. A.
Published: October 2005

Following unilateral optic nerve section in adult PVG hooded rat, the axon guidance cue ephrin‐A2 is up‐regulated in caudal but not rostral superior colliculus (SC) and the EphA5 receptor is down‐regulated in axotomised retinal ganglion cells (RGCs). Changes occur bilaterally despite the retino‐collicular projection being mostly crossed. Here we investigate the dynamics of Eph/ephrin expression using in situ hybridization and semi‐quantitative immunohistochemistry after localized retinal lesions. Unilateral krypton laser lesions to dorso‐nasal retina ablated contralaterally projecting RGCs (DN group); ventro‐temporal lesions ablated contralaterally and ipsilaterally projecting RGCs (VT group). Lesions of the entire retina served as controls (Total group). Results are compared to normal animals in which tectal ephrin‐A2 and retinal EphA5 are expressed, respectively, as shallow ascending rostro‐caudal and naso‐temporal gradients. In both SCs of DN and Total groups, tectal ephrin‐A2 was up‐regulated caudally; in the VT group, expression remained normal bilaterally. Unilateral collicular ablation indicated that bilateral changes in ephrin‐A2 expression are mediated via intercollicular pathways. EphA5 expression in the VT group was elevated in the intact nasal region of experimental retinae. For each experimental group, EphA5 expression was also elevated in nasal retina of the opposite eye, resulting in uniform expression across the naso‐temporal axis. Up‐regulation of ephrin‐A2 in caudal, but not rostral, SC suggests the enhancement of developmental positional information as a result of injury. Bilateral increases in retinal EphA5 expression demonstrate that signals for up‐regulation operate interocularly. The study demonstrates that signals regulating guidance cue expression are both localized and relayed transneuronally.
The T1 domain of Kv1.3 mediates intracellular targeting to axons
Authors: Rivera Jacqueline F. , Chu Po‐Ju , Arnold Don B.
Published: October 2005

Shaker K+ channels play an important role in modulating electrical excitability of axons. Recent work has demonstrated that the T1 tetramerization domain of Kv1.2 is both necessary and sufficient for targeting of the channel to the axonal surface [Gu, C., Jan, Y.N. & Jan, L.Y. (2003)Science,301, 646–649]. Here we use a related channel, Kv1.3, as a model to investigate cellular mechanisms that mediate axonal targeting. We show that the T1 domain of Kv1.3 is necessary and sufficient to mediate targeting of the channel to the axonal surface in pyramidal neurons in slices of cortex from neonatal rat. The T1 domain is also sufficient to cause preferential axonal localization of intracellular protein, which indicates that the domain probably does not work through compartment‐specific endocytosis or compartment‐specific vesicle docking. To determine whether the T1 domain mediates axonal trafficking of transport vesicles, we compared the trafficking of vesicles containing green fluorescent protein‐labelled transferrin receptor with those containing the same protein fused with the T1 domain in living cortical neurons. Vesicles containing the wild‐type transferrin receptor did not traffic to the axon, in accord with previously published results; however, those containing the transferrin receptor fused to T1 did traffic to the axon. These results are consistent with the T1 domain of Kv1.3 mediating axonal targeting by causing transport vesicles to traffic to axons and they represent the first evidence that such a mechanism might underlie axonal targeting.
Disruption of the neurogenic potential of the dentate gyrus in a mouse model of temporal lobe epilepsy with focal seizures
Authors: Kralic Jason E. , Ledergerber Debora A. , Fritschy Jean‐Marc
Published: October 2005

Adult hippocampal neurogenesis is enhanced in response to multiple stimuli including seizures. However, the relationship between neurogenesis and the development of temporal lobe epilepsy (TLE) remains unclear. Unilateral intrahippocampal injection of kainate in adult mice models the morphological characteristics (e.g. neuronal loss, gliosis, granule cell dispersion and hypertrophy) and occurrence of chronic, spontaneous recurrent partial seizures observed in human TLE. We investigated the influence of a kainate‐induced epileptogenic focus on hippocampal neurogenesis, comparing neural stem cell proliferation following status epilepticus and spontaneous recurrent partial seizures. Cell proliferation in the subgranular zone was transiently increased bilaterally after kainate treatment. As a result, neurogenesis was stimulated in the contralateral dentate gyrus. In contrast, the epileptic hippocampus exhibited a strongly reduced neurogenic potential, even after onset of spontaneous recurrent partial seizures, possibly due to an alteration of the neurogenic niche in the subgranular zone. These results show that neurogenesis does not contribute to the formation of the epileptic focus and may be affected when dispersion of dentate gyrus granule cells occurs. Therefore, in patients with TLE, hippocampal sclerosis and granule cell dispersion may play a significant role in disrupting the potential for hippocampal neurogenesis.