bluuebunny/crossref_metadata_2025 huggingface dataset:
Long‐term survival in a patient after heterotopic segmental auxiliary liver transplantation
Authors: Haberal Mehmet , Sevmis Sinasi , Karakayali Hamdi , Ozcay Figen , Moray Gokhan , Arslan Gulnaz
Published: November 2007

Abstract:  Auxiliary liver transplantation has been used mostly for patients with acute liver failure, but between 1980 and 2000, it has gained wider application for patients with both acute and chronic liver diseases. It is particularly applicable in patients in whom there is specific indication for removing the native liver. However, to date, very few patients have survived auxiliary liver transplantation in the long term. In this report, we describe a patient with normal liver function following heterotopic segmental auxiliary liver transplantation whom we followed for nine yr.
Teaching (and learning from) metabolomics: The 2006 PlantMetaNet ETNA Metabolomics Research School
Authors: Böttcher Christoph , Centeno Danilo , Freitag Jens , Höfgen Rainer , Köhl Karin , Kopka Joachim , Kroymann Juergen , Matros Andrea , Mock Hans‐Peter , Neumann Stefan , Pfalz Marina , Von Roepenack‐Lahaye Edda , Schauer Nicolas , Trenkamp Sandra , Zubriggen Matias , Fernie Alisdair R.
Published: November 2007

Under the auspices of the European Training and Networking Activity programme of the European Union, a ‘Metabolic Profiling and Data Analysis’ Plant Genomics and Bioinformatics Summer School was hosted in Potsdam, Germany between 20 and 29 September 2006. Sixteen early career researchers were invited from the European Union partner nations and the so‐called developing nations (Appendix). Lectures from invited leading European researchers provided an overview of the state of the art of these fields and seeded discussion regarding major challenges for their future advancement. Hands‐on experience was provided by an example experiment – that of defining the metabolic response of Arabidopsis to treatment of a commercial herbicide of defined mode of action. This experiment was performed throughout the duration of the course in order to teach the concepts underlying extraction and machine handling as well as to provide a rich data set with which the required computation and statistical skills could be illustrated. Here we review the state of the field by describing both key lectures given at and practical aspects taught at the summer school. In addition, we disclose results that were obtained using the four distinct technical platforms at the different participating institutes. While the effects of the chosen herbicide are well documented, this study looks at a broader number of metabolites than in previous investigations. This allowed, on the one hand, not only to characterise further effects of the herbicide than previously observed but also to detect molecules other than the herbicide that were obviously present in the commercial formulation. These data and the workshop in general are all discussed in the context of the teaching of metabolomics.
New therapeutic options for adult chronic immune thrombocytopenic purpura: a brief review
Authors: Panzer S.
Published: November 2007

Background  Patients with chronic immune thrombocytopenic purpura (ITP) only require treatment if they are bleeding, or prior to scheduled operations. Patients are also treated if platelet counts are very low. Some patients become refractory, relapse or do not respond to treatment with steroids. Splenectomy is effective in raising the platelet count in most patients, but as spontaneous remission may occur even after 1 year or more, it is justified to defer splenectomy. Furthermore, splenectomy and/or first‐line treatment modalities may not suit all patients. Therefore, alternatives are desirable.

Materials  This review will focus on anti‐B cell therapy with rituximab, and two thrombopoietin mimetic agents that have entered clinical trials, AMG 531 and eltrombopag. These therapeutics have been studied in patients who were refractory to first‐line treatment and/or splenectomy, and to defer splenectomy.

Results  There are no controlled trials with rituximab, but clinical experience has shown a success rate of 40% to 60%. Encouraging phase 1 and 2 data have been published for both thrombopoietin mimetics; preliminary data from an open‐label extension trial with AMG 531 and from phase 3 studies with eltrombopag further confirm their efficacy.

Conclusion  Clinical experience will ultimately determine the appropriate indications of these new treatments for ITP.
PHARMACOKINETICS AND PHARMACODYNAMICS OF INDOMETHACIN: EFFECTS ON CEREBRAL BLOOD FLOW IN ANAESTHETIZED SHEEP
Authors: Upton Richard N , Rasmussen Mads , Grant Cliff , Martinez Allison M , Cold Georg E , Ludbrook Guy L
Published: November 2007

Indomethacin has been used to manage raised intracranial pressure (ICP) in humans during neuroanaesthesia and neurosurgery. Indomethacin causes cerebral vasoconstriction and reduces cerebral blood flow (CBF) and, therefore, ICP.

The systemic kinetics, cerebral kinetics and cerebral dynamics of indomethacin (0.2 mg/kg) were measured and modelled using a population approach. Data were collected using an instrumented sheep preparation with raised ICP and under either isoflurane or propofol anaesthesia to parallel the clinical use of indomethacin in neurosurgery.

The systemic kinetics of indomethacin could be described by a two‐compartment model, with small distribution volumes and a clearance of 0.68 L/min. The cerebral kinetics of indomethacin could be described using a model with a cerebral distribution volume between 5 and 8 mL and a loss term of 3.3 mL/min, the latter probably representing slow diffusion across the blood–brain barrier.

The changes in CBF lagged behind the blood concentrations of indomethacin. Indirect response models with turnover times of 1.70–4.08 min were generally better able to describe the effect of indomethacin on CBF than effect compartment models.

There was a non‐linear concentration–effect relationship, with the maximum possible reduction in CBF being to 73–74% of baseline.

The data and model support the concept of indomethacin having limited uptake into the brain, with its effect on CBF being the result of its action on the endothelium, where it indirectly modifies the turnover of a compound regulating vascular tone.
PROTECTION BY AND ANTI‐OXIDANT MECHANISM OF BERBERINE AGAINST RAT LIVER FIBROSIS INDUCED BY MULTIPLE HEPATOTOXIC FACTORS
Authors: Zhang Ben‐Jian , Xu Dan , Guo Yu , Ping Jie , Chen Liao‐bin , Wang Hui
Published: November 2007

The aim of the present study was to investigate the effect and mechanism of berberine, an alkaloid extracted from the traditional Chinese medicine coptis, on rat liver fibrosis induced by multiple hepatotoxic factors.

Male Wistar rats were separated into five groups, a normal control group, a fibrotic control group and fibrotic groups treated with three different doses of berberine. The fibrotic models were established by introduction of multiple hepatotoxic factors, including CCl4, ethanol and high cholesterol. Rats in the treatment groups were administered 50, 100 or 200 mg/kg berberine, intragastrically, daily for 4 weeks. Serum levels of alanine aminotransferase (ALT) and serum aspartate aminotransferase (AST), hepatic activity of superoxide dismutase (SOD) and hepatic malondialdehyde (MDA) and hepatic hydroxyproline (Hyp) content were determined. Liver biopsies were obtained for histological and immunohistochemical studies to detect the expressions of a‐smooth muscle actin (SMA) and transforming growth factor (TGF)‐b1.

The results showed that, compared with the fibrotic control group, serum levels of ALT and AST and hepatic content of MDA and Hyp were markedly decreased, but the activity of hepatic SOD was significantly increased in berberine‐treated groups in a dose‐dependent manner. In addition, histopathological changes, such as steatosis, necrosis and myofibroblast proliferation, were reduced and the expression of a‐SMA and TGF‐b1 was significantly downregulated in the berberine‐treated groups (P < 0.01).

These results suggest that berberine could be used to prevent experimental liver fibrosis through regulation of the anti‐oxidant system and lipid peroxidation.
SYSTEMIC DELIVERY OF ADULT STEM CELLS IMPROVES CARDIAC FUNCTION IN SPONTANEOUSLY HYPERTENSIVE RATS
Authors: De Macedo Braga Luisa MG , Rosa Kaleizu , Rodrigues Bruno , Malfitano Christiane , Camassola Melissa , Chagastelles Pedro , Lacchini Silvia , Fiorino Patricia , De Angelis Kátia , D’Agord Schaan Beatriz , Irigoyen Maria C , Beyer Nardi Nance
Published: November 2007

Heart regeneration after myocardial infarction (MI) can occur after cell therapy, but the mechanisms, cell types and delivery methods responsible for this improvement are still under investigation. In the present study, we evaluated the impact of systemic delivery of bone marrow cells (BMC) and cultivated mesenchymal stem cells (MSC) on cardiac morphology, function and mortality in spontaneously hypertensive rats (SHR) submitted to coronary occlusion.

Female syngeneic adult SHR, submitted or not (control group; C) to MI, were treated with intravenous injection of MSC (MI + MSC) or BMC (MI + BM) from male rats and evaluated after 1, 15 and 30 days by echocardiography. Systolic blood pressure (SBP), functional capacity, histology, mortality rate and polymerase chain reaction for the Y chromosome were also analysed.

Myocardial infarction induced a decrease in SBP and BMC, but not MSC, prevented this decrease. An improvement in functional capacity and ejection fraction (38 ± 4, 39 ± 3 and 58 ± 2% for MI, MI + MSC and MI + BM, respectively; P < 0.05), as well as a reduction of the left ventricle infarcted area, were observed in rats from the MI + BM group compared with the other three groups. Treated animals had a significantly reduced lesion tissue score. The mortality rate in the C, MI + BM, MI + MSC and MI groups was 0, 0, 16.7 and 44.4%, respectively (P < 0.05 for the MI + MSC and MI groups compared with the C and MI + BM groups).

The results of the present study suggest that systemic administration of BMC can improve left ventricular function, functional capacity and, consequently, reduce mortality in an animal model of MI associated with hypertension. We speculate that the cells transiently home to the myocardium, releasing paracrine factors that recruit host cells to repair the lesion.
Neuropathology of schizophrenia: A mini review
Authors: Iritani Shuji
Published: November 2007

The neuropathology of schizophrenia remains obscure despite the fact that many neuropathologists have investigated this area for over 100 years. While remarkable progress has been made in the neuropathological study of neurodegenerative diseases including Alzheimer's disease, progress in studying the neuropathological entity of schizophrenia has not kept pace; the phrase “schizophrenia is the graveyard of neuropathologists” has been stated in the field. Since the 1980s, the morphological or functional abnormalities in the brains of schizophrenia patients have been reported by means of CT or MRI and with advanced functional brain image technology such as positron emission tomography or single photon emission computed tomography. Results from such imaging studies have led to neuropathological examination of the post mortem brains of schizophrenia patients being undertaken again. These neuroimaging studies have influenced the neuropathological investigation of the schizophrenic brain. Not only the classical microscopic observation of neuropathology, but also measurement and statistical analysis using computer imaging software or using immunohistological techniques has been performed. Based on the neuropathological studies of schizophrenia over the last 20 years, it is clear that schizophrenia is not a pure functional disease without organic factors. Reports of neuropathological abnormalities in the post mortem schizophrenic brain indicated they were found in almost all areas of the brain, but there are more reports describing the temporal lobe and frontal lobe compared to those describing other areas of the brain. These observed neuropathological abnormalities are explained rationally by the hypothesis of a neurodevelopmental disorder in this disease. In recent molecular biology studies, several putative candidate genes were reported, and some of these genes might have the function of neurodevelopment or making neuronal networks. It is important to consider together these findings with morphometric studies in neuropathological observation, neuroimaging studies and genome studies to pursue the etiology of schizophrenia from various perspectives.
A case of congenital supratentorial tumor: Atypical teratoid/rhabdoid tumor or primitive neuroectodermal tumor?
Authors: Nishihira Yasushi , Tan Chun‐Feng , Hirato Junko , Yoshimura Junichi , Nishiyama Kenichi , Takahashi Hideaki , Fujii Yukihiko , Takahashi Hitoshi
Published: November 2007

Two embryonal CNS tumors, atypical teratoid/rabdoid tumor (AT/RT) and primitive neuroectodermal tumor (PNET), may be confused with each other and misdiagnosed. Here we report an infant with a congenital supratentorial tumor, which was detected by fetal MRI at 37 weeks gestation. On routine histological examination, the tumor was composed mainly of small undifferentiated cells, among which many rhabdoid cells and occasional sickle‐shaped embracing cells were observed. No mesenchymal or epithelial areas were evident. Our impression was that the tumor was an atypical example of AT/RT. Immunohistochemically, almost all the tumor cells were strongly positive for vimentin. However, epithelial membrane antigen was notably negative, and most of the tumor cell nuclei were clearly positive for INI1. In addition, many tumor cells were positive for neurofilament protein. There were also occasional small areas containing many tumor cells positive for glial fibrillary acidic protein. Finally, a diagnosis of PNET, with a rhabdoid phenotype and expression of neuronal and glial markers, was made. In the present case, application of INI1 immunostaining was very helpful for distinguishing PNET from AT/RT.
Concurrent gain of 17q and the MYC oncogene in a medullomyoblastoma
Authors: Lindberg Eva , Persson Annette , Øra Ingrid , Mertens Fredrik , Englund Elisabet , Gisselsson David
Published: November 2007

Medullomyoblastoma (MMB) is a rare cerebellar childhood tumor containing both myoblastic and primitive neuroectodermal components. Similar to the scenario in classical medulloblastoma, which contains the primitive neuroectodermal component only, gain of sequences from the long arm of chromosome 17 (17q) and gain of the MYC gene in 8q have been implicated in the pathogenesis of MMB. Because karyotypic analysis has not previously been performed for MMB, the mechanisms behind genomic imbalances in this tumor have remained unknown. Several other central aspects of this tumor, such as histocytogenetic origin, clinical characteristics, tumor behavior and prognosis, also remain unknown. We here report neuropathological and cytogenetic features of an MMB in a 3‐year‐old boy. Chromosome banding analysis and multicolor karyotyping revealed a hyperdiploid karyotype including an unbalanced 1; 17 translocation and isochromosome 17q formation, both leading to gain of 17q. There were also two extra copies of chromosome 8, leading to gain of the MYC oncogene, trisomies 5 and 13, and monosomy 9. Clonal chromosome changes were present in both the myoblastic and neuroectodermal components. Our findings support the notion that MMB and classical medulloblastoma arise through similar genetic mechanisms and that the two main tissue components in MMB are clonally related.
The value and correlation between PRL‐3 expression and matrix metalloproteinase activity and expression in human gliomas
Authors: Kong Lingfei , Li Qing , Wang Lifu , Liu Zhengguo , Sun Tingyi
Published: November 2007

Local invasion of tumor cells is characteristic of most human glioma invasions. It is associated with increased motility and a potential to degrade the extracellular matrix. Matrix metalloproteinases (MMPs) have been proved to be a main process in local invasion of brain tumor. PRL‐3 is a new protein tyrosine phosphatase which would also degrade the extracellular matrix and has been proved to be expressed in liver metastases derived from colorectal cancer. In this study, we sought to investigate the expression of PRL‐3 in glioma tissues and investigate the relationship between MMPs (MMP2, MMP9, membrane‐type matrix metalloproteinase 1 [MT1‐MMP]) activity and expression in gliomas. The modifications of in situ hybridization of mRNA phosphatase of regenerating liver‐3 (PRL‐3) methods are preformed in the study of paraffin‐embedded slides. The immunohistochemistry and gelatin zymography are used to detect the expression of PRL‐3 and activity of MMPs. The results show that PRL‐3 mRNA and antibody of PRL‐3 are detected in glioma tissues mainly in grades IV and III, only a little in grade II, but not in normal brain tissue and glioma grade I. MMP2 and MMP9 are observed mainly in glioma tissues of grades IV and III in activity and expression. MT1‐MMP protein is located in glioma tissues and vessel endothelial cells. This is the first report of detecting PRL‐3 expression in gliomas, especially in grades III and IV, which may play an important role in progression of gliomas. PRL‐3, MMP2 and MT1‐MMP cooperatively contribute to gliomas invasion. Intermediate MMP2 (MT1‐MMP, TIMP‐2, MMP2 trimeric complex) is detected in high grades of glioma tissues by gelatin zymography and may be a marker indicating latent malignance of gliomas.
Brain imaging in schizophrenia
Authors: Hirayasu Yoshio
Published: November 2007

Pathophysiology has remained unknown in schizophrenia. Recent neuroimaging advances have enabled us to find structural volume reduction in cortical structures, including the superior temporal gyrus which is associated with auditory information processing and language. These structures also change over time in the clinical course of patients with schizophrenia.
Hypoglycemia in a patient with a huge malignant solitary fibrous tumor of the pleura
Authors: Chang Jui‐Chih , Su Kuei‐Ying , Chao Shen‐Feng , Hsu Yung‐Hsiang , Yang Gee‐Gwo , Chang Bee‐Song
Published: November 2007

Solitary fibrous tumor of the pleura (SFTP) is rare. A 73‐year‐old man, without past history of diabetes mellitus, was admitted to hospital with profound hypoglycemia, loss of consciousness and respiratory failure. CT indicated a huge heterogenous mass lesion (12 × 12 × 17 cm) at the right thoracic cavity with total atelectasis of the right lower lung. He underwent a standard thoracotomy with complete excision of the tumor. Pathology indicated malignant SFTP with insulin‐like growth factor‐binding protein‐2 production. There were no further incidences of hypoglycemia or respiratory failure after excision of the tumor. Hypoglycemia resulting from a solitary fibrous tumor is uncommon. Standard thoracotomy and complete resection of this giant tumor provided a good result for the present patient.
Invasive biliary cystic tumor without ovarian‐like stroma
Authors: Ishibashi Yuji , Ojima Hidenori , Hiraoka Nobuyoshi , Sano Tsuyoshi , Kosuge Tomoo , Kanai Yae
Published: November 2007

Presented herein is a rare case of invasive biliary cystic tumor without an ovarian‐like stroma, and the apparent sequence underlying its malignant transformation, which was identified on detailed histological examination. A 54‐year‐old woman was incidentally diagnosed as having a cystic tumor in segment VIII of the liver, and central bisegmentectomy was performed. Macroscopically the tumor measured 4.6 × 3.5 cm; and unilocular cystic and solid areas were seen on cut surface. Microscopically the tumor showed three types of neoplasia: adenoma and tubulopapillary adenocarcinoma in the cystic area, and invasive adenocarcinoma in the solid area. The relative area of the tumor occupied by each of these histological types was approximately 3%, 50% and 47%, respectively. Moreover, transitional zones between adenoma and tubulopapillary adenocarcinoma, and between tubulopapillary adenocarcinoma and invasive adenocarcinoma were noted. The immunohistochemical expression of Ki‐67 and p53 increased gradually from adenoma through to tubulopapillary adenocarcinoma, and was highest in invasive adenocarcinoma. MUC1 was positive, and MUC2 and MUC5AC were both negative. No ovarian‐like stroma or communication with the bile ducts around the tumor was found in any area of the specimen. On the basis of the World Health Organization histological classification and these pathological findings, the present case was diagnosed as invasive‐type biliary cystadenocarcinoma.
Preventive effect of hochu‐ekki‐to, a Japanese herbal medicine, on bleomycin‐induced lung injury in mice
Authors: TAJIMA Shunji , BANDO Masashi , YAMASAWA Hideaki , OHNO Shoji , MORIYAMA Hiroshi , TERADA Masaki , TAKADA Toshinori , SUZUKI Eiichi , GEJYO Fumitake , SUGIYAMA Yukihiko
Published: November 2007

Objective:  Pulmonary fibrosis is thought to be closely associated with the T‐helper type‐2 (Th2) immune response. Recent studies have shown that hochu‐ekki‐to (TJ‐41), a Japanese herbal medicine, may correct the Th1/Th2 imbalance skewed to Th2. The present study was designed to investigate the preventive effect of TJ‐41 on the development of bleomycin (BLM)‐induced lung injury in mice.

Methods:  Female C57BL/6 mice were divided into a group given ordinary feed and another group given the same feed plus TJ‐41 mixed in at a dose of 1 g/kg/day. Both groups were maintained on this diet for 8 weeks before and 5 weeks after administration of 2 mg/kg BLM intratracheally.

Results:  Mortality after BLM‐induced lung injury was significantly lower in the TJ‐41‐treated mice. The hydroxyproline content and fluid content in the lung on day 35 was significantly lower in the TJ‐41‐treated mice. Histologically, TJ‐41 reduced the number of infiltrating cells, thus ameliorating the destruction of the lung architecture, and attenuated the lung fibrosis score. Furthermore, TJ‐41 inhibited the expression of the interleukin‐5/interferon‐γ mRNA ratio in the lung on day 7.

Conclusions:  Treatment with TJ‐41 partially prevented experimental lung fibrosis through the correction of the Th1/Th2 imbalance skewed to Th2.
Nosocomial Acinetobacter pneumonia
Authors: LUNA Carlos M. , ARUJ Patricia K.
Published: November 2007

Abstract:  Acinetobacter spp. (A. baumannii is the prevalent genomic species, but others may cause infection) has become an increasingly important cause of nosocomial pneumonia, particularly in mechanically ventilated patients (VAP). This organism has intrinsic resistance to some antimicrobials but easily acquires resistance to many others; Acinetobacter spp. can survive for long periods of time in the environment. All of these characteristics have contributed to protracted outbreaks associated with significant morbidity and mortality. High rates of colonization are found in debilitated hospitalized patients. Infecting or colonizing organisms in nosocomial infections are more likely to be from cross‐transmission or from the hospital environment than from endogenous sources. VAP caused by Acinetobacter spp. is emerging as a prominent hospital complication. The incidence of this microorganism varies from site to site, but it is the second commonest aetiological agent among the gram‐negative bacteria. Longer periods of hospitalization, longer time on mechanical ventilation and prior use of antibiotics are the recognized factors increasing the risk of VAP due to Acinetobacter spp. Treatment needs to clearly differentiate infection from colonization, and the agents with the most antimicrobial activity are imipenem/cilastatin, amikacin, colistin, ampicillin/sulbactam and tigecycline. Monotherapy can be adequate if the patient does not have significant comorbidities. Infection control procedures have a major role to play in preventing transmission of this microorganism. Emphasis on initial control measures should, however, be on strict isolation of infected or colonized patients to limit dissemination of outbreak strains in the environment. The variety of potential sources of contamination with Acinetobacter spp. in the hospital environment makes control of these outbreaks one of the more difficult challenges. Persistence of Acinetobacter spp. in the environment provides ample opportunities for contamination of patients and staff and may explain continuing long‐term outbreaks.
Primary Sjogren's syndrome complicated by bilateral pleural effusion
Authors: TESHIGAWARA Katsunobu , KAKIZAKI Satoru , HORIYA Madoka , KIKUCHI Yuki , HASHIDA Tetsu , TOMIZAWA Yoshio , SOHARA Naondo , SATO Ken , TAKAGI Hitoshi , MATSUZAKI Shinichi , MORI Masatomo
Published: November 2007

Abstract:  Sjogren's syndrome can cause many organic changes, but is rarely accompanied by pleuritis. We report a 65‐year‐old patient with primary Sjogren's syndrome who developed bilateral pleuritis with moderately large effusions. He was diagnosed as having Sjogren's syndrome, based on xerophthalmia, xerostomia, positive results for anti‐Sjogren's syndrome (anti‐SS‐A/SS‐B) antibodies, the Schirmer test and biopsy findings in the minor salivary glands. The pleural fluid was lymphocyte rich and contained high levels of anti‐SS‐A/SS‐B antibodies. There was no evidence of infection, malignancy or other collagen diseases which cause pleuritis. We conclude that this case adds to the eight previously published reports of primary Sjogren's syndrome complicated by pleural effusion.
A case of dermoid cyst ruptured into the lung
Authors: YANG Chih‐Jen , CHENG Yu‐Jen , KANG Wang‐Yi , HUANG Ming‐Shyan , HWANG Jhi‐Jhu
Published: November 2007

Abstract:  Ruptured cystic teratomas (dermoid cysts) are rare and always symptomatic, presenting as haemothorax, pleural effusion or pericardial effusion. We present an extremely rare case of a 45‐year‐old woman who, during a routine health assessment was noted to have a well‐defined anterior mediastinal tumour with peripheral ground glass opacity on chest CT. The patient was asymptomatic. She underwent video‐assisted thoracoscopic surgery and a ruptured dermoid cyst was observed and the contents had infiltrated into the right pulmonary parenchyma. There were no complications and no evidence of recurrence 10 months later. Despite most cystic teratomas being asymptomatic and benign, rupture into the pulmonary parenchyma may induce further damage, for which emergency surgical intervention is always necessary.
Pulmonary complications of HIV infection
Authors: ROSEN Mark J.
Published: November 2007

Abstract:  The AIDS epidemic has had a devastating global impact in the last two decades; although prevalence rates are low in Asia and the Pacific, their enormous population is associated with an estimated 1 million people infected with HIV in 2006 alone. Survival from what had been a uniformly fatal illness has improved markedly with combination antiretroviral therapy and restoration of the immune system, but these treatments are expensive and difficult to distribute to the millions who need them around the world. In addition, millions more do not know they are infected with HIV until they develop an opportunistic infection. The lungs are the most frequent sites of these infections, and in different geographic regions, tuberculosis, bacterial pneumonia and Pneumocystis jiroveci are the dominant pathogens. The incidences of lung cancer and HIV‐associated pulmonary arterial hypertension are also increasing in patients with HIV infection, and with the use of antiretrovirals, inflammatory disorders associated with immune restoration are being recognized.
BODE score is a useful predictor of hospital admission in rural patients with chronic obstructive pulmonary disease
Authors: MCKELLAR Alice , COTTRELL W. Neil , WHELAN Anthony
Published: November 2007

Background and objective:  COPD is a chronic illness with frequent episodic exacerbations that require admission to hospital. The aim of this study was to identify risk factors (or predictors) for hospital admission in a sample of rural COPD patients.

Methods:  COPD patients from the Goulburn and Crookwell areas of New South Wales, Australia, were included in the study. Patients were divided into two groups: those with two or fewer admissions, and those with three or more admissions in the last year. Patient interviews were conducted, and data were collected on demographics, consumption of health resources, COPD severity measures (BODE score) and quality of life.

Results:  There were 32 patients recruited with a median age of 68 years, and 21 (65.6%) were male. There were no significant differences in risk factors (or predictors) identified between the two groups. A statistical difference was found between the two groups, with patients with three or more hospital admissions having a higher BODE score (P = 0.004), poorer quality‐of‐life score (P = 0.015) and reduced exercise tolerance (P = 0.001).

Conclusions:  In this small sample of COPD patients, there were no clear differences in terms of risk factors for COPD admission between the two groups. The BODE score was found to be a useful predictor of disease severity and likelihood of hospital admission.
Combination therapy with prostacyclin and tadalafil for severe pulmonary arterial hypertension: A pilot study
Authors: BENDAYAN Daniele , SHITRIT David , KRAMER Mordechai R.
Published: November 2007

Abstract:  Despite the introduction of new drugs that have changed the course of pulmonary arterial hypertension (PAH), some patients are still refractory to treatment and deteriorate rapidly. Long‐acting phosphodiesterase‐5 inhibitors are a new class of drugs that are effective in PAH. This prospective study assessed the potential of combination therapy with prostacyclin and tadalafil for treatment of severe PAH. We report four cases of severe PAH that deteriorated despite prostacyclin therapy. Two patients had Eisenmenger syndrome, one had pulmonary hypertension associated with scleroderma and one had histiocytosis X. All were treated with tadalafil, 10–20 mg once daily, in addition to prostacyclin. After 3 months of treatment, all patients improved clinically, with an increase in mean 6MWD from 214 to 272 m. In three patients, the New York Heart Association functional class decreased from IV to III. Echocardiograms showed no significant changes in pulmonary arterial pressure. Although this study was limited by the small sample size, it suggests that tadalafil in combination with prostacyclin is an effective treatment for severe PAH. Tadalafil may be beneficial for the treatment of patients with advanced disease.
Beneficial effects of hydrocortisone and papaverine on a model of pulmonary embolism induced by autologous blood clots in isolated and perfused rabbit lungs
Authors: TREJO Humberto E. , URICH Daniela , PEZZULO Alejandro A. , CARABALLO Juan C. , GUTIÉRREZ Jeydith , CASTRO Ignacio J. , CENTENO Greenmy R. , SÁNCHEZ DE LEÓN Roberto
Published: November 2007

Background and objective:  Mechanical obstruction has been considered the prime determinant of haemodynamic changes after pulmonary embolism (PE); however, the function of vasoconstrictive and inflammatory mediators in the physiopathology of this disease is unclear. The aim of this investigation was to study the effect of an anti‐inflammatory and a vasodilator in a setting of induced PE.

Methods:  A prospective, laboratory study was undertaken using 30 New Zealand white rabbits. A model of isolated and perfused rabbit lungs was used; PE was induced using autologous blood clots. Six study groups were established (each n = 5): PE without any drug (PG); PE + papaverine (PpG); PE + hydrocortisone (HG); PE in West's Zone III (ZIIIG); PE using acellular perfusate (AG) and PE using acellular perfusate + papaverine (APpG). The pulmonary artery pressure (PAP) and fluid filtration rate (FFR) were continuously measured during the experiments.

Results:  Increases in PAP and oedema formation were observed in the PG after embolization. The PpG and the APpG showed neither oedema nor significant PAP increases. The HG group developed less oedema and less increase in PAP compared with the PG. The ZIIIG developed oedema the fastest. The AG developed less oedema and increases in PAP compared with the PG.

Conclusion:  These findings suggest that vasoconstriction and inflammatory mediators play an important role in the physiopathology of PE, as neither PAP increases nor oedema were observed in the PpG and a reduction of oedema and PAP was seen in the HG group. The decrease in oedema and PAP in the acellular group strongly suggests a key role of circulating blood cells.
Surfactant degradation activity in bronchoalveolar lavage fluid from guinea pigs challenged with antigen
Authors: ABO Miki , KURASHIMA Kazuyoshi , FUJIMURA Masaki , MYOU Shigeharu , NAKAO Shinji , TASHIRO Katsumi , KOBAYASHI Tsutomu
Published: November 2007

Background and objective:  Surfactant dysfunction is a characteristic of bronchial asthma, but mechanisms of dysfunction following antigen exposure are not understood. The aim of this study was to examine whether bronchoalveolar lavage fluid (BALF) has surfactant degradation activity after antigen challenge, using an animal model of asthma.

Methods:  BALF was collected 24 h after a challenge with aerosolized antigen solution in actively sensitized guinea pigs and from non‐sensitized control guinea pigs. The surface tension of BALF was measured by pulsating bubble surfactometer. Surfactant activity was expressed as the minimum surface tension of BALF after 5 min of pulsation. BALF was separated into a cellular phospholipid fraction and supernatant, and reconstituted into ‘pellet + supernatant’ and ‘pellet + saline’ fractions.

Results:  Surfactant activity of BALF from sensitized antigen‐challenged animals was reduced after 4 h of incubation at 37°C but a decrease was not observed in BALF from non‐sensitized control animals. The decrease of surfactant activity in BALF from challenged animals was prevented by incubation at 4°C. Disappearance of surfactant activity after incubation at 37°C was observed in the ‘pellet + supernatant’, but not in the ‘pellet + saline’ fraction. The decrease of surfactant activity in BALF was also partially suppressed by the secretory phospholipase A2 inhibitor, indoxam, and by a cocktail of protease inhibitors.

Conclusion:  Surfactant‐degrading activity was present in the supernatant of BALF from antigen‐challenged guinea pigs. This activity may be attributed to secretory phospholipase A2 and to proteases present in the antigen‐challenged airway.
Design and validation of an interpretative strategy for cardiopulmonary exercise tests
Authors: SCHMID Andreas , SCHILTER Daniel , FENGELS Ingo , CHHAJED Prashant N. , STROBEL Werner , TAMM Michael , BRUTSCHE Martin H.
Published: November 2007

Background and objective:  Cardiopulmonary exercise testing (CPET) is a common investigation for the evaluation of exertional dyspnoea. At present, there is no consensus on the best interpretative strategy and none of the available algorithms have been validated. The aim of this study was to develop and validate a standardized strategy for the interpretation of CPET.

Methods:  This study analysed 199 CPETs from patients with exertional dyspnoea. Using a set of 100 CPETs a standardized interpretation using a four‐step approach was developed that scored: examination quality, performance, exercise limitation and cofactors. A second set of 99 CPETs was interpreted by two experts in the field, initially independently and then in a consensus conference. The standardized interpretation was compared with each expert, the expert's consensus and the original clinical reports.

Results:  Matching between the standardized interpretation strategy and the expert consensus was 82%, 82% with one expert and 86% with a second expert and 64% with the original clinical reports. From one to four exercise‐relevant cofactors were found in 77% of the patients.

Conclusion:  The standardized interpretation showed a precision comparable to the opinion of a single expert and significantly improved the consistency in CPET reports in a pulmonary centre with different physicians and varying degrees of expertise.
Latent tuberculosis infection in a military setting diagnosed by whole‐blood interferon‐γ assay
Authors: CHOI Chang‐Min , HWANG Seung Sik , LEE Chang‐Hoon , LEE Hye Won , KANG Cheol‐In , KIM Chang‐Hoon , HAN Sung Koo , SHIM Young‐Soo , YIM Jae‐Joon
Published: November 2007

Background and objectives:  Rapid and accurate diagnosis of latent tuberculosis infection (LTBI) is crucial in military settings. This study aimed to detect the prevalence of LTBI using a whole‐blood interferon‐γ assay based on Mycobacterium tuberculosis‐specific antigens, and to identify risk factors for LTBI among military personnel in contact with patients with active pulmonary TB.

Methods:  This prospective study investigated contacts in military camps in South Korea of soldiers with active pulmonary TB. The whole‐blood interferon‐γ assay was performed using QuantiFERON TB‐Gold.

Results:  Among the 175 contacts, 25 (14.3%) showed positive results to the assay. Long duration of exposure (OR 2.83; 95% CI: 1.63–4.91), laryngeal TB (OR 6.04; 95% CI: 1.54–23.67) and intensive exposure (OR 5.13; 95% CI: 1.63–16.12) were associated with a positive result.

Conclusions:  A relatively small number of TB contacts in a military setting had LTBI.
13C‐phenylalanine breath test correlates with liver fibrosis in postoperative biliary atresia
Authors: WADA MASAKI , WADA YUKO , UCHIYAMA MAKOTO , KAJIWARA MASAHIRO , TAKATORI KAZUHIKO
Published: November 2007

Background: Values derived from the 13C‐phenylalanine breath test (PBT) may serve as an index for liver fibrosis and clinically predictive readings for liver diseases in adults. In the present study the PBT was conducted in postoperative biliary atresia (BA) children to evaluate phenylalanine metabolism in the liver, and the results based on biochemical data, especially the index on liver fibrosis, were compared with PBT findings.

Methods: Hepatofunctional evaluations were conducted in 10 postoperative BA children with moderate (group B; n = 4) and severe (group A; n = 6) liver dysfunction, and the PBT results were compared with those of 13 normal healthy children (group C). Subjects were orally given single‐bolus 13C‐phenylalanine at 3.5 mg/kg (maximum dosing: 100 mg) in the morning. Time‐related exhaled gas was periodically collected until 120 min after dosing. The 13CO2 levels were monitored with gas chromatography–mass spectrometry before and after administration, and the 13C excretion rate, 13C cumulative excretion and time of maximum 13C excretion rate were monitored accordingly.

Results: Total bile acid, hyaluronic acid, type IV collagen 7S, total bilirubin or albumin and the PBT findings were significantly correlated. The PBT findings in group A were significantly lower those of group B, indicating that phenylalanine metabolism was markedly attenuated in the former.

Conclusion: The PBT values correlated well with liver fibrosis in postoperative BA children. Because PBT is a non‐invasive approach, results from this method may serve as a useful and reliable index for post‐surgical monitoring of children operated on for liver fibrosis.
Correlation between white blood cell count and metabolic syndrome in adolescence
Authors: HSIEH CHANG‐HSUN , PEI DEE , KUO SHI‐WEN , CHEN CHENG‐YU , TSAI SHIH‐LI , LAI CHUN‐LUNG , LEE CHIEN‐HSING , WU CHUNG‐ZE , HUNG YI‐JEN , HSIEH MING‐CHEN
Published: November 2007

Background: Metabolic syndrome (MetS) is associated with increased risk for diabetes and coronary heart disease. Data suggest that MetS starts even in children. Thus, it is important to understand the role of MetS and the risks related to it. Furthermore, white blood cell count (WBCC) is available in routine examination and it has been proved to be related to risks of MetS.

Methods: A total of 1657 subjects aged 14–19 years were enrolled, with normal WBCC (≤10 × 109 cells/L). The subjects were divided into four quartiles according to WBCC (WBCC1–4, from the lowest to highest WBCC) in both genders.

Results: The female subjects had significantly lower systolic blood pressure, fasting plasma glucose (FPG), triglyceride (TG), body mass index (BMI) and higher high‐density lipoprotein‐cholesterol (HDL‐C) than the male subjects. When comparing the risks of the quartiles of WBCC, WBCC4 had significant higher BMI than WBCC1 and WBCC2 in both genders; and lower HDL‐C than WBCC3 in male subjects. On multiple regression WBCC was positively related with BMI and TG and negatively related to HDL‐C in male subjects. In female subjects only BMI was positively correlated with WBCC. Subjects with MetS did not have significant higher WBCC than those without MetS.

Conclusions: In adolescents with normal WBCC, BMI is significantly related to the levels of WBCC and is the earliest component of MetS to be noted in adolescents. Elevated TG and decreased HDL‐C could also be important markers for future risk factors only in male subjects.
Immunoadsorbent apheresis eliminates pathogenic IgG in childhood lupus nephritis
Authors: TAKAHASHI SHORI , WADA NAOHIRO , HARADA KENSUKE
Published: November 2007

Background: It is suggested that the highly cation‐charged fraction of the IgG and IgG3 subclasses may play a pathogenic role in lupus nephritis. In contrast, immunoadsorbent therapy using a sodium dextransulfate fixed cellulose gel column–low invasive selective immunoadsorbent apheresis therapy (SDSC‐IAT) has been applied to lupus nephritis with favorable results. However, elimination using pathogenic IgG by SDSC‐IAT has never been investigated.

Method: Two patients with diffuse proliferative lupus nephritis were treated using SDSC‐IAT concomitant with immunosuppressive therapy. The eluates from the SDSC, and the patients’ serum obtained before and just after SDSC‐IAT were subjected to an IgG charge analysis using isoelectric focusing and immunoblotting, and also to laser nephelometry assay, which is used for measuring IgG subclass concentration. Indirect immunofluorescence staining was performed to detect IgG subclass deposition in the glomerulus.

Results: Both of the patients had an immediate decrease in anti‐double‐strand DNA antibody and in the circulating immune complex with a following clinical improvement. Repeated biopsies demonstrated improvement of glomerular lesions with a marked reduction of IgG and C3 deposition. The IgG of the SDSC eluates consisted of highly cation charged (isoelectric points: 9–10) fractions. In addition, IgG3 was specifically removed from the patients’ serum using an SDSC among the IgG subclasses. The subclass of deposited IgG in the glomeruli showed IgG3 predominance.

Conclusion: SDSC‐IAT specifically removed the highly cation charged fractions of IgG and IgG3 from the patients’ serum and the elimination of these fractions may have resulted in clinical improvement.
Home mechanical ventilation in children: Retrospective survey of a pediatric population
Authors: OTTONELLO GIANCARLO , FERRARI ILARIA , PIRRODDI INES MARIA GRAZIA , DIANA MARIA CRISTINA , VILLA GIOVANNA , NAHUM LAURA , TUO PIETRO , MOSCATELLI ANDREA , SILVESTRI GILBERTO
Published: November 2007

Background: Home care support is beneficial for children needing mechanical ventilation, when clinically stable.

Methods: A retrospective analysis was carried out of the long‐term home ventilation management of a pediatric population with chronic respiratory failure composed of 20 ventilator‐dependent children categorized according to age, diagnosis and ventilation support. Age groups consisted of 10% under 1 year, 30% between 2 and 5 years, 30% between 6 and 12 years, and 30% older than 12 years. Diagnostic categories included myopathic disorder, n = 5; congenital central hypoventilation syndrome, n = 6; chest wall disorder, n = 5; cystic fibrosis, n = 1; pulmonary hypertension, n = 1; and diaphragmatic paralysis, n = 2.

Results: Sixty‐five percent were ventilated using non‐invasive mode (NIMV): eight with nasal mask, five with full‐face mask, and two children in NIMV also used negative pressure mode; 35% were ventilated using tracheostomy, one of them also used a diaphragmatic pacer. Seventy percent needed nocturnal ventilatory support, (20% 12–18 h, 10% full‐day). A total of 18 children were included in the home care and follow‐up program. Two children died: one because of worsening of his chronic disease and one because of septic shock.

Conclusion: Although home care ventilation is not yet widely diffused, it represents a valid alternative to long hospitalization for children with stable chronic respiratory failure.
Quantitative measurements of Hemophilus influenzae type b capsular polysaccharide antibodies in Japanese children
Authors: ISHIWADA NARUHIKO , FUKASAWA CHIE , INAMI YUKIKO , HISHIKI HARUKA , TAKEDA NOBUE , SUGITA KATSUO , KOHNO YOICHI
Published: November 2007

Background: Hemophilus influenzae type b (Hib) infection has a high morbidity and mortality rate in children. The frequency of natural immunity against Hib in Japanese children is not known, and Hib vaccine has not yet been introduced in Japan.

Methods: Anti‐capsular polysaccharide‐specific IgG (anti‐CP) antibody titers were examined in serum samples from 100 children and 107 young adults who were not vaccinated against Hib, in serum samples from eight patients with Hib systemic infection and in 10 commercially available human immune globulin preparations on enzyme‐linked immunosorbent assay.

Results: A total of 44% (44/100) of Japanese children and all patients with Hib systemic infection in the acute phase did not have the minimum protective level of anti‐CP antibodies (>0.15 μg/mL). The rate of natural Hib immunity was lowest in children under 1 year of age and gradually increased with age. Only 3.74% (4/107) of Japanese young adults did not have the minimum protective level of anti‐CP antibodies. Analysis of 10 commercially available human immune globulin preparations indicated an average level of 28.25 μg anti‐CP antibody/mL immune globulin (range 14.96–44.17 μg/mL).

Conclusions: Approximately half of Japanese children are not protected against Hib infection. Therefore, Hib vaccine should immediately be included as part of the routine immunization program in Japan. It was also found that all tested commercially available immune globulin preparations had high anti‐CP titers. Well‐controlled clinical trials of i.v. immune globulin administration for prevention and treatment of Hib systemic infection are needed in Japan.
Post‐mortem analysis for two prevalent β‐oxidation mutations in sudden infant death
Authors: YANG ZI , LANTZ PATRICK E , IBDAH JAMAL A
Published: November 2007

Background: Fatty acid oxidation disorders may cause sudden and unexpected infant death and are associated with the histological hallmark of hepatic steatosis. The goal of the present study was to assess the value of post‐mortem molecular analysis for medium‐chain acyl‐coenzyme A dehydrogenase (MCAD) and mitochondrial trifunctional protein (MTP) defects in unexplained sudden infant death (SID) associated with fatty infiltration of the liver. MCAD catalyzes the first step of medium‐chain fatty acid oxidation while MTP catalyzes the last three steps of long‐chain fatty acid oxidation.

Methods: In a retrospective study, 220 consecutive cases of sudden and unexplained infant death certified by medical examiners at Wake Forest University Medical Center were assessed for hepatic steatosis. Subjects with evidence of hepatic steatosis were screened for mutations in MCAD and MTPα‐subunit using DNA isolated from paraffin‐embedded liver tissue, single‐strand conformation variance, and nucleotide sequence analyses.

Results: Sixteen cases (7.3%) were associated with diffuse micro‐vesicular or mixed micro‐ and macro‐vesicular hepatic steatosis. Two of these 16 cases (12.5%) had disease‐causing mutations. One was homozygous for the prevalent MCAD A985G mutation. The second was a compound heterozygous for the prevalent MTP G1528C mutation and a novel 1 bp deletion in exon 18 of the MTPα‐subunit gene.

Conclusions: A significant proportion (7.3%) of SID is associated with hepatic steatosis. The present data support post‐mortem molecular analysis for the MCAD A985G and MTP G1528C prevalent mutations in cases of sudden and unexplained infant death associated with hepatic steatosis.