bluuebunny/crossref_metadata_2025 huggingface dataset:
Recognition profiles of microsporidian Encephalitozoon cuniculi polar tube protein 1 with human immunoglobulin M antibodies
Authors: FURUYA K. , OMURA M. , KUDO S. , SUGIURA W. , AZUMA H.
Published: November 2007

Microsporidian Encephalitozoon cuniculi has a unique organelle called a polar tube (PT), the extrusion of which is absolutely required to invade a host cell. We recently detected anti‐E. cuniculi PT immunoglobulin (Ig) M antibodies in sera from many healthy individuals. The present one‐dimensional (1‐D) immunoblot analysis predominantly detected a band at 52 kDa in all of the examined human sera with anti‐PT IgM. The use of mouse monoclonal antibody confirmed that the 52‐kDa band detected in 1‐D immunoblots was an antigen derived from the PT, which represents a glycoprotein nature. In addition, from changes in the immunoreactivity of the 52‐kDa band before and after treatment with NaOH, we determined that the 24 human serum samples with anti‐PT IgM activities could be roughly grouped into three types: (i) sera containing antibodies against only a saccharic determinant (n = 3); (ii) sera containing antibodies against only a proteinic determinant (n = 11); and (iii) sera showing dual recognition of saccharic and proteinic determinants (n = 10). Further two‐dimensional (2‐D) immunoblot analysis followed by proteomic analysis confirmed that human sera with anti‐PT IgM reacted with E. cuniculi polar tube protein 1 (PTP1). Such circulating IgM antibodies may be important in the first line of defence against E. cuniculi infection.
SEX DIFFERENCES IN THE PHARMACOKINETICS, OXIDATIVE METABOLISM AND ORAL BIOAVAILABILITY OF OXYCODONE IN THE SPRAGUE‐DAWLEY RAT
Authors: Chan Samuel , Edwards Stephen R , Wyse Bruce D , Smith Maree T
Published: November 2007

The pharmacokinetics and oxidative metabolism of oxycodone were investigated following intravenous and oral administration in male and female Sprague‐Dawley (SD) rats.

High‐performance liquid chromatography (HPLC)–electrospray ionization (ESI)–tandem mass spectrometry (MS‐MS) was used to quantify plasma concentrations of oxycodone and its oxidative metabolites noroxycodone and oxymorphone following administration of single bolus intravenous (5 mg/kg) and oral (10 mg/kg) doses of oxycodone.

The mean (±SEM) clearance of intravenous oxycodone was significantly higher in male than female SD rats (4.9 ± 0.3vs3.1 ± 0.3 L/h per kg, respectively;P < 0.01). Mean areas under the plasma concentration versus time curves (AUC) for oxycodone were significantly higher in female than male SD rats following intravenous (~1.6‐fold;P < 0.01) and oral (~sevenfold;P < 0.005) administration.

The oral bioavailability of oxycodone was low (at 1.2 and 5.0%, respectively) in male and female SD rats, a finding consistent with high first‐pass metabolism. Noroxycodone : oxycodone AUC ratios were significantly higher in male than female SD rats after intravenous (~2.4‐fold;P < 0.005) and oral (~12‐fold;P < 0.005) administration.

Circulating oxymorphone concentrations remained very low following both routes of administration. Noroxycodone : oxymorphone AUC ratios were greater in male than female SD rats after intravenous (~13‐ and fivefold, respectively) and oral (~90‐ and sixfold, respectively) administration.

Sex differences were apparent in the pharmacokinetics, oxidative metabolism and oral bioavailability of oxycodone. Systemic exposure to oxycodone was greater in female compared with male SD rats, whereas systemic exposure to metabolically derived noroxycodone was higher in male than female SD rats.

Oral administration of oxycodone to the SD rat is a poor model of the human for the study of the pharmacodynamic effects of oxycodone.
2,3,4′,5‐TETRAHYDROXYSTILBENE‐2‐O‐β‐d‐GLUCOSIDE SUPPRESSES MATRIX METALLOPROTEINASE EXPRESSION AND INFLAMMATION IN ATHEROSCLEROTIC RATS
Authors: Zhang Wei , Wang Chun‐Hua , Li Feng , Zhu Wei‐Zhong
Published: November 2007

In coronary artery disease, the typical atheromatous plaque consists of a lipid core containing various inflammatory cells and a fibrous cap composed mostly of extracellular matrix. Both matrix metalloproteinases (MMPs) and inflammation are involved in the initiation of atherosclerotic plaques and plaque instability.

2,3,4¢,5‐Tetrahydroxystilbene‐2‐O‐b‐d‐glucoside (TSG) reduces the blood lipid content and prevents the atherosclerotic process, but the mechanism of action of TSG is unclear. The purpose of the present study was to test whether TSG can suppress MMP activation and inflammation in atherosclerotic rats.

Sixty male Sprague‐Dawley rats were randomly divided into six groups. Atherosclerosis was induced by feeding rats a hyperlipidaemic diet; TSG (120, 60 or 30 mg/kg per day) was administered by oral gavage. After 12 weeks of treatment, rats were killed (ethyl carbamate 1200 mg/kg) and serum lipids, C‐reactive protein (CRP), interleukin (IL)‐6 and tumour necrosis factor (TNF)‐a were measured. Haematoxylin–eosin (H&E) staining was used to examine histopathological changes in the aorta. The mRNA and protein expression of MMPs were assayed by reverse transcription–polymerase chain reaction, immunohistochemistry and western blotting. Simvastatin (2 mg/kg per day) was administered as a positive control, whereas the vehicle (0.9% NaCl) group served as the untreated control.

In the present study, TSG significantly and dose‐dependently attenuated the hyperlipidaemic diet‐induced alterations in serum lipid profile and increases in CRP, IL‐6 and TNF‐a levels. In addition, TSG normalized the structure of the aortic wall and suppressed the expression of MMP‐2 and MMP‐9 at both the mRNA and protein level in the rat aortic wall.

In summary, TSG suppresses the expression of MMP‐2 and MMP‐9 and inhibits inflammation in the diet‐induced atherosclerotic rats.
EFFECTS OF SULPHITE SUPPLEMENTATION ON VASCULAR RESPONSIVENESS IN SULPHITE OXIDASE‐DEFICIENT RATS
Authors: Nacitarhan Cahit , Kucukatay Vural , Sadan Gulay , Ozturk Oktay Hasan , Agar Aysel
Published: November 2007

The aim of the present study was to explore the effect of dietary sulphite supplementation on vascular responsiveness in sulphite oxidase (SO)‐deficient rats.

Male albino rats were divided into four groups, namely control (n = 8), sulphite‐treated (n = 8), SO‐deficient (n = 8) and sulphite‐treated SO‐deficient (n = 8) groups. Sulphite oxidase deficiency was induced by administration of a low‐molybdenum diet with concurrent addition of 200 p.p.m. tungsten in the form of sodium tungstate in the drinking water for 9 weeks. Sulphite, in the form of sodium metabisulphite (Na2O5S2; 25 mg/kg) was given in the drinking water to sulphite‐treated and sulphite‐treated SO‐deficient groups for the last 6 weeks. The vascular responsiveness of isolated aortic rings to acetylcholine (ACh), sodium nitroprusside (SNP) and histamine was investigated in organ baths.

The responsiveness of aortic rings to SNP and histamine did not differ significantly between groups. Conversely, there was a significant decrease in ACh‐induced relaxation in aortic rings from the sulphite‐treated SO‐deficient group compared with the control group (pD2 6.2 ± 0.3 and 7.5 ± 0.1, respectively; P < 0.05). Incubation of aortic rings in the presence of either l‐arginine or superoxide dismutase significantly improved the ACh‐induced vasorelaxation in sulphite‐treated SO‐deficient group (pD2 7.2 ± 0.3 and 7.4 ± 0.3, respectively).

The findings of the present study suggest that the increased production of reactive oxygen species and the resultant increment in l‐arginine/nitric oxideconsumption may play a role in the reduced endothelium‐dependent vasorelaxation in sulphite‐treated SO‐deficient rats.
EFFECTS OF LIVER FIBROSIS ON VERAPAMIL PHARMACOKINETICS IN RATS
Authors: Chen Man , Xu Dan , Hu Xiao‐Ling , Wang Hui
Published: November 2007

Liver fibrosis is the compensatory state of cirrhosis. In the long asymptomatic period, it is imperative to select a proper dosing regimen for drugs that are applicable to hepatic fibrosis owing to altered pharmacokinetics and bioavailability. The present study was designed to observe the changes in verapamil pharmacokinetics in rats with early liver fibrosis with respect to alterations in cytochrome P450 3A (CYP3A) and P‐glycoprotein (P‐gp).

A rat liver fibrosis model was successfully established using several inducers, including a high‐fat diet, alcohol and carbon tetrachloride. After rats received a single intravenous or oral dose of verapamil (5 mg/kg), the plasma concentrations of verapamil were determined at scheduled time‐points using HPLC. The activity of hepatic and small intestinal microsomal erythromycin N‐demethylase (a marker for CYP3A) and the expression of small intestinal cyp3a and multidrug resistance (mdr) mRNA were compared between normal rats and rats with liver fibrosis.

The results showed that when verapamil was administered intravenously, the area under the curve (AUC), elimination half‐life () and mean residence time (MRT) increased significantly, whereas clearance (Cl) decreased, in rats with liver fibrosis compared with normal rats. After oral administration of verapamil, the AUC, and maximum concentration (Cmax) increased, Cl decreased and the absorption half‐life () and time to peak concentration (Tmax) were unchanged compared with normal rats. The oral bioavailability of verapamil was 32.9% in normal rats and 34.4% in rats with liver fibrosis. Furthermore, decreased CYP3A activity in the liver was accompanied by upregulated cyp3a9/18 and unchanged mdr mRNA in the small intestine compared with normal rats. Expression of cyp3a9/18 and mdr mRNA in the intestine was significantly inhibited by verapamil.

The results suggest that the lowered Cl and increased AUC of verapamil after intravenous and oral administration in rats with liver fibrosis were due to downregulation of CYP3A in the liver. The absorption rate of verapamil in rats with liver fibrosis was unchanged because mdr was unchanged and cyp3a was inhibited in the intestine by verapamil itself. There was no notable difference in oral bioavailability between normal rats and rats with liver fibrosis.
EFFECT OF PERIPHERAL SYMPATHETIC NERVE DYSFUNCTION ON SALT SENSITIVITY OF ARTERIAL PRESSURE
Authors: Osborn John W , Collister John P , Guzman Pilar
Published: November 2007

Dysregulation of peripheral sympathetic pathways contributes to some forms of salt‐dependent hypertension. However, at the present time it is not known whether salt‐induced activation of sympathetic nerves or loss of normal sympathoinhibitory responses to salt‐induced volume expansion contributes to neurogenic salt‐dependent hypertension. The present study was performed to the test the hypothesis that loss of peripheral sympathetic nerve function results in salt‐dependent hypertension.

The effect of three pharmacological interventions of sympathetic nerve function on the long‐term salt‐sensitivity of mean arterial pressure (MAP) were measured: (i) blockade of ganglionic transmission with hexamethonium (HEX; n = 5); (ii) destruction of sympathetic nerve terminals with guanethidine (GUAN; n = 7); and (iii) a‐adrenoceptor blockade with two specific antagonists, namely prazosin (PRAZ; n = 7) and terazosin (TERAZ; n = 8).

Mean arterial pressure and heart rate were measured 24 h/day by radiotelemetry in conscious rats during 5 days of normal and 7 days of high (HNa) dietary sodium intake. Despite marked increases in both sodium and water intake during 7 days of the HNa diet, no statistically significant changes in MAP were observed in HEX, GUAN, PRAZ or TERAZ groups.

We conclude that loss of peripheral sympathetic neural pathways alone does not cause salt‐dependent hypertension in the rat.
Neuroimaging of epilepsy
Authors: Maehara Taketoshi
Published: November 2007

It can sometimes be difficult, when examining surgical specimens, to detect underlying pathological abnormalities that may account for disordered electrical activity. For accurate diagnosis, neuropathologists and clinicians need to share common preoperative information about resected brain tissue. Our group has been able to use structural, functional, and electrophysiological neuroimaging techniques to visualize epileptogenic areas preoperatively. MRI is the most sensitive and useful examination to demonstrate structural abnormalities in patients with partial or localization‐related epilepsy. Temporal lobe epilepsy, neoplastic lesions, vascular lesions, and developmental anomaly can all be surgically corrected under favorable circumstances. Functional neuroimaging by positron emission tomography (PET) and single‐photon emission computed tomography (SPECT) are useful tools for detecting epileptic foci. PET and SPECT demonstrate subtle functional changes related to epilepsy that ultimately may enable the detection of epileptogenic areas invisible to MRI. PET/SPECT images coregistered to MRI and statistical parametric mappings are of more value for detecting than PET/SPECT images alone. Electrophysiological neuroimaging with analytical software is very useful for visually understanding epileptogenic phenomena. Computerized voltage topographic mappings overlapped on three‐dimensional MRI with multichannel electrodes visually demonstrate ictal onset areas and seizure propagation. A new method of multimodal image‐guided intervention enables the detection of epileptogenic areas by electrocorticography, PET images, and MRI during epilepsy surgery. Neuropathologists using this method can collect precise structural, functional, and electrophysiological findings on surgical specimens. Neuroimaging of epilepsy is useful for visually clarifying structural, functional, and electrophysiological information on epilepsy patients. This approach is key for diagnosing the background pathological abnormalities of resected tissue.
The role of neuroimaging in mild cognitive impairment
Authors: Matsuda Hiroshi
Published: November 2007

The main purposes of neuroimaging in Alzheimer's disease (AD) have been moved from diagnosis of advanced AD to diagnosis of very early AD at a prodromal stage of mild cognitive impairment, prediction of conversion from mild cognitive impairment (MCI) to AD, and differential diagnosis from other diseases causing dementia. Structural MRI studies and functional studies using F‐18 fluorodeoxyglucose‐positron emission tomography (FDG‐PET) and brain perfusion single‐photon emission computed tomography (SPECT) are widely used in diagnosis of AD. Outstanding progress in diagnostic accuracy of these neuroimaging modalities has been obtained using statistical analysis on a voxel‐by‐voxel basis after spatial normalization of individual scans to a standardized brain‐volume template instead of visual inspection or a conventional region of interest technique. In a very early stage of AD, this statistical approach revealed gray matter loss in the entorhinal and hippocampal areas and hypometabolism or hypoperfusion in the posterior cingulate cortex and precuneus. These two findings might be related in view of anatomical knowledge that the regions are linked through the circuit of Papez. This statistical approach also offers prediction of conversion from MCI to AD. Presence of hypometabolism or hypoperfusion in parietal association areas and entorhinal atrophy at the MCI stage has been reported to predict rapid conversion to AD.
Coexistence of amyotrophic lateral sclerosis and argyrophilic grain disease: A non‐demented autopsy case showing circumscribed temporal atrophy and involvement of the amygdala
Authors: Yokota Osamu , Tsuchiya Kuniaki , Noguchi Yoshimasa , Akabane Hisamasa , Ishizu Hideki , Saito Yukinobu , Akiyama Haruhiko
Published: November 2007

We report a case of a 68‐year‐old right‐handed man with sporadic amyotrophic lateral sclerosis (ALS) and argyrophilic grain disease (AGD) having a 22‐month duration. His initial symptoms were dysarthria and swallowing difficulty at the age of 67. Subsequently bulbar palsy and pyramidal signs developed. His cognitive functions including face recognition, personality, and behavior were not changed compared with that of before the disease onset. However, magnetic resonance imaging disclosed severe right side‐predominant temporal atrophy. The neurological diagnosis was bulbar type ALS. Pathological examination disclosed histological evidence of ALS, including loss of Betz cells and lower motor neurons, corticospinal tract degeneration, and Bunina bodies. In addition, severe neuronal loss in the bilateral temporal cortex with an anterior gradient was found. Ubiquitin‐positive inclusions were encountered in the spinal anterior horn cells and hippocampal dentate gyrus, while few ubiquitin‐positive inclusions were noted in the affected temporal cortex. The amygdala, especially the basolateral nuclear group, was severely affected by neuronal loss with tissue rarefaction. Moderate neuronal loss was encountered in the parahippocampal gyrus, and to a lesser degree, in the ambient gyrus. Unexpectedly, many argyrophilic grains, coiled bodies, tau‐positive bush‐like astrocytes, pretangles, and ballooned neurons were found in the limbic system and temporal cortex. In the hippocampus, selective tau accumulation with minor neurofibrillary changes was observed in CA2 neurons. The present case suggests that (i) ALS and AGD do rarely coexist, and (ii) when ALS patients have severe temporal atrophy, not only ALS with dementia but also concurrent AGD should be considered in the differential diagnosis.
Neuropathology of mild cognitive impairment
Authors: Saito Yuko , Murayama Shigeo
Published: November 2007

We aim to investigate the pathological background of mild cognitive impairment (MCI). The most recent 545 cases from the Brain Bank for Aging Research (BBAR) were studied, with a mean age of 80.7 years and male : female ratio of 324 : 221. Cases with clinical dementia rating scale (CDR) 0.5 were retrieved as the best substitute of MCI. CDR was retrospectively determined from clinical charts. Pathological examinations followed the BBAR protocol (JNEN 2004). Post mortem assessment of CDR was possible for 486 cases, and was 0 in 201 cases, 0.5 in 57 cases and 1–3 in 228 cases. CDR 0.5 group was clinicopathologically classified into 33 cases with degenerative changes, nine cases with vascular changes, four cases with combined degenerative and vascular changes, two with hippocampal sclerosis, two with trauma, one with metabolic disease and six with unremarkable changes. The degenerative group was further subclassified into groups with pure and combined pathology. The former consisted of six cases each with Alzheimer change (AC), argyrophilic grain change (AGC) and neurofibrillary tangle predominant change (NFTC), three each with Lewy body disease change without parkinsonism (DLBC) or Parkinson's disease (PDMCI) and one case with progressive supranuclear palsy. The latter consisted of three cases with AC plus AGC, two with AGC plus NFTC and one each with AC plus DLBC, DLBC plus amyotrophic lateral sclerosis and AGC plus DLBC. The pathological backgrounds of patients of class CDR 0.5 were varied and not restricted to AC.
Diagnostic surgical neuropathology of intractable epilepsy
Authors: Arai Nobutaka , Takahashi Tatsuya , Komori Takashi , Yagishita Akira , Shimizu Hiroyuki
Published: November 2007

As neurosurgical treatments have been increasingly applied to patients who have intractable epilepsy, much knowledge on pathological changes in surgically removed brain tissues have become clearer in recent years, as well as on the neuroimaging findings which are analyzed with a variety of techniques, including computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), single photon emission computed tomography (SPECT) in combination with digital imaging and communication in medicine (DICOM), statistical parametric mapping (SPM), subtraction ictal SPECT coregistered to MRI (SISCOM) and/or PET‐guided intraoperative navigation system, as mentioned in detain in another article in this issue by Maehara et al. Representative and relatively common diseases, treated by epilepsy‐surgery, are as follows; hippocampal sclerosis, amygdaloid sclerosis, coarse and macroscopic brain malformation (focal cortical dysplasia, hemimegalencephaly, tuberous sclerosis), tumors (dysembryoplastic neuroepithelial tumor, ganglioglioma, etc.), destructive lesions and the others. It is a fact, however, that there remains many problems in the diagnostic criteria or histological grading systems, especially in various cortical dysplasias described above. On the other hand, histologically minor but clinically serious lesions have become to be known through careful observations on surgically removed tissues which showed no neuroradiological findings. A good well‐known example is microdysgenesis of the cerebrum which is characterized by the presence of both the white mater ectopic neurons and the vascular meandering abnormalities with glial satellitosis. There must be another important histological phenotypes of microdysgenesis, except the above‐mentioned ones, that are not yet established at present. Therefore, it is believed that there remains various problems on the diagnostic neuropathology of epileptic lesions with or without neuroimaging findings in which we have to give answers in a few days to come.
Active necrotizing cerebral vasculitis in systemic lupus erythematosus
Authors: Goel Deepa , Reddy S Rajashekhar , Sundaram Challa , Prayaga Aruna K , Rajasekhar Liza , Narsimulu Gumdal
Published: November 2007

Systemic lupus erythematosus (SLE) is a multisystemic disease with varied clinical manifestations. Focal cortical brain infarcts and CNS infections are the most common neuropathological features reported in most studies. This report describes a 32‐year‐old woman who had repeated episodes of strokes over 5 years. In view of polyarthritis, oral ulcers, presence of high titres of serum antinuclear antibodies, high titres of double‐stranded DNA and strokes, she was treated as SLE. Despite prolonged immunosuppressive therapy with azathioprine and pulse cyclophosphamide, she succumbed to a brainstem stroke. Complete body autopsy showed multiple cerebral cortical and brainstem infarcts with fibrinoid necrosis of the vessel wall. Renal infarction with healed vasculitis and systemic vasculitis involving small vessels was seen. Extensive thrombosis was remarkable by its absence. Active necrotizing vasculitis of cerebral and renal vessels is a rare complication of SLE, which contributed to a fatal outcome in this patient.
Cyclooxygenase‐2 (Cox‐2) expression and angiogenesis in glioblastoma
Authors: Onguru Onder , Gamsizkan Mehmet , Ulutin Cuneyt , Gunhan Omer
Published: November 2007

Cyclooxygenase‐2 (Cox‐2), the key enzyme that catalyzes the first steps in the biosynthesis of the prostaglandins from arachidonic acid, appears to play a role in the regulation of progression, invasiveness and angiogenesis of various neoplasms. We analyzed the immunohistochemical expression of Cox‐2 and angiogenic parameters (microvessel density (MVD) and vascular patterns) in 54 glioblastomas. We also examined their relation with prognosis. Cox‐2 immunohistochemical expression was observed in 48 tumors (89%). There was no staining in six tumors (11%). On univariate analysis, MVD was correlated with a poor outcome (MVD > 70; hazard ratio, 0.441; 95% confidence interval, 0.200–0.975, P = 0.041). But MVD showed no prognostic impact on multivariate analysis. Neither Cox‐2 expression nor vascular pattern showed prognostic value. The difference in Cox‐2 expression between the classical and bizarre vascular pattern in glioblastomas was statistically significant (P = 0.047). However, no correlation was found between Cox‐2 expression and MVD. These findings suggest that Cox‐2 is heterogeneously expressed in glioblastomas without a significant association with MVD. However, Cox‐2 expression may be related to vascular pattern in glioblastomas.
Expression of cell cycle inhibitors p21, p27, p14 and p16 in gliomas. Correlation with classic prognostic factors and patients' outcome
Authors: Zolota Vassiliki , Tsamandas Athanassios C. , Aroukatos Panagiotis , Panagiotopoulos Vassilios , Maraziotis Theodore , Poulos Constantinos , Scopa Chrisoula D.
Published: November 2007

Gliomas are among the most aggressive and treatment‐refractory of all human tumors. The aim of the present study is to evaluate the role of the expression of cell cycle molecules as prognostic indicators in gliomas. We immunohistochemically analyzed the expression of p21, p27, p14, p16, p53 and proliferation marker Ki67, in 67 low and high grade astrocytic tumors. High grade tumors exhibited higher labeling indices for Ki67 (P = 0.004), p53 (P = 0.039) and slightly higher index for p21 (P = 0.07) compared to low grade tumors. p14 and p16 were more frequently present in low grade tumors (P = 0.001 and P = 0.052, respectively). Worse survival was correlated with high grade tumors (P < 0.0001) and higher Ki67 index (P < 0.0001). Cox regression analysis revealed that only age, grade and marginally Ki67 index were independent prognostic factors. Cell cycle alterations are involved in the malignant progression of astrocytomas, but only age, tumor grade and proliferating index can predict the outcome of the patients with glioma.
Clinicopathologic characteristics of five autopsied cases of dura mater‐associated Creutzfeldt‐Jakob disease
Authors: Iwasaki Yasushi , Mimuro Maya , Yoshida Mari , Hashizume Yoshio , Kitamoto Tetsuyuki , Sobue Gen
Published: November 2007

We present five cases of dura mater‐associated Creutzfeldt‐Jakob disease (dura‐CJD) that were analyzed clinicopathologically and review previous reports. The average age at dura mater transplantation was 54.4 ± 7.3 years, and the average age at CJD onset was 66.0 ± 8.2 years, with an average latency period of 11.6 ± 1.1 years. The average age at death was 67.6 ± 8.7 years, with an average CJD disease duration of 16.8 ± 10.4 months. Symptoms of CJD onset in four patients who received dura mater transplantation below the cerebellar tent reflected cerebellar or brainstem dysfunction, whereas symptoms of one patient who received transplantation above the cerebellar tent reflected cerebral cortical involvement. All patients showed rapidly progressive cognitive impairment, and both periodic sharp‐wave complexes on electroencephalogram and myoclonus were observed in the early disease stage. Neuropathologic evaluation showed one case of subacute spongiform encephalopathy and four cases of panencephalopathic‐type CJD. Widespread cerebral neocortical, subcortical gray matter and cerebellar cortical involvement were observed to varying degrees, and severity tended to be associated with CJD disease duration. There were no instances of kuru plaques or florid plaques. Prion protein (PrP) immunostaining showed widespread synaptic‐type PrP deposition. No differences between our dura‐CJD cases and typical cases of sporadic CJD were found with respect to clinicopathologic findings, except history of dura mater transplantation. Although a specific association between the dura mater graft site and neuropathologic observations was not evaluated in the present study, the initial symptoms appear to be closely related to the graft site, indicating a direct transmission of CJD from the graft site to the adjacent brain.
Positron emission tomography in interstitial lung disease
Authors: NUSAIR Samir , RUBINSTEIN Rina , FREEDMAN Nanette M. , AMIR Gail , BOGOT Naama R. , IZHAR Uzi , BREUER Raphael
Published: November 2007

Background and objectives:  A high rate of glycolysis may reflect the inflammatory activity of interstitial lung disease (ILD). This prospective study investigated whether PET can distinguish IPF, a primarily fibrotic process, from other entities of ILD that have a marked inflammatory component.

Methods:  Twenty‐one patients referred for surgical lung biopsy because of diffuse ILD underwent PET at the time of the lung biopsy. PET transmission scans were obtained after injecting 18FDG intravenously. Regions of interest (ROI) were drawn on the lung images, and the standardized uptake value (SUV) was calculated for these ROI.

Results:  Of the 21 patients studied, 14 had IPF, four had non‐specific interstitial pneumonia, and the remaining three patients each had respiratory bronchiolitis‐ILD, sarcoidosis and Langerhan's cell histiocytosis. There was no statistically significant difference in the SUV between IPF patients and non‐IPF patients (P = 0.26), although patients with IPF tended to have higher SUV. Radiographic changes tended to be more prominent in the lung bases in patients with IPF compared with non‐IPF patients; however, the median ratio of SUV measured in the upper fields to the whole lungs in IPF patients was not significantly different compared with the median ratio in non‐IPF patients (P = 0.31).

Conclusion:  PET does not allow differentiation of IPF from a non‐IPF diffuse interstitial pulmonary process.
High CD95 expression of BAL lymphocytes predicts chronic course in patients with sarcoidosis
Authors: OZDEMIR Ozlem Kumbasar , CELIK Gokhan , DALVA Klara , ULGER Fusun , ELHAN Atilla , BEKSAC Meral
Published: November 2007

Background and objectives:  The prognosis of sarcoidosis is highly variable, with spontaneous remission in some patients. Apoptosis may be associated with spontaneous resolution of the granulomata. CD95 (Fas), an apoptotic molecule, and CD29 and CD45RO (T‐cell memory markers) are expressed at higher levels on T lymphocytes from sarcoid patients compared with normal subjects. However, the prognostic significance of CD95, CD29 and CD45RO expression in sarcoidosis is not clear. It was hypothesized that expression of CD95 would correlate with spontaneous remission.

Methods:  CD29, CD45, CD45RO and CD95 expression of BAL fluid and peripheral blood (PB) lymphocytes was studied with flow cytometry in 50 patients with sarcoidosis. Results of the 15 chronic patients and 21 patients who remitted spontaneously were compared.

Results:  BAL CD95 (59 vs 8, P = 0.002), and PB CD95 (48 vs 18, P = 0.004) and PB CD45RO (50 vs 41, P = 0.003) expression was significantly higher in patients with chronic disease compared with those with spontaneous remission. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy for these markers were: BAL CD95 (cut‐off: 42.5%) 73.3%, 85.7%, 78.6%, 81.8% and 80.6%; PB CD95 (cut‐off: 25%) 86.7%, 66.7%, 65%, 87.5% and 75%; and PB CD45RO (cut‐off: 44.5%) 80%, 61.9%, 60%, 81.3% and 69.4%, respectively.

Conclusion:  Levels of BAL and PB CD95 and PB CD45RO were unexpectedly elevated in patients with chronic disease and may be useful in predicting prognosis in patients with sarcoidosis. Further studies with more patients are necessary to confirm the prognostic role and cut‐off value for these markers.
Pneumothorax‐associated pleural eosinophilia is tumour necrosis factor‐alpha‐dependent and attenuated by steroids
Authors: KALOMENIDIS Ioannis , MOSCHOS Charalampos , KOLLINTZA Androniki , SIGALA Ioanna , STATHOPOULOS Georgios T. , PAPIRIS Spyros A. , LIGHT Richard W. , ROUSSOS Charis
Published: November 2007

Background and objectives:  The pathogenesis and the optimal treatment of eosinophilic pleural effusions are unknown. We aimed to examine whether pneumothorax‐associated pleural eosinophilia in mice is dependent on tumour necrosis factor (TNF)‐alpha, and whether it is affected by systemic administration of corticosteroids.

Methods:  Mice were injected intrapleurally with 0.4 mL air to create pneumothoraces. Animals were sacrificed 24 or 48 h later, and pleural lavage (PL) was performed. In the first experiment, comparisons were made between wild‐type and TNF‐α knockout mice with pneumothorax. In the second experiment, wild‐type mice were injected intraperitoneally with different doses of dexamethasone (0, 0.25, 0.5 and 1 mg/kg), 5 min before and 24 h after the induction of pneumothorax.

Results:  After induction of a pneumothorax, TNF‐α knockout mice had significantly fewer total number of cells (P = 0.004), mononuclear cells (P = 0.01), neutrophils (P = 0.017) and eosinophils (P = 0.002) in their PL compared with wild‐type animals. TNF‐α was detected in the PL of most of the control mice but not in TNF‐α knockouts. Dexamethasone induced a significant, dose‐dependent reduction of PL total cells (P < 0.001), eosinophils (P < 0.001), mononuclear cells (P = 0.007) and lymphocytes (P = 0.04) at 48 h, and significantly reduced the number of PL total cells (P = 0.045) and eosinophils (P = 0.005) at 24 h. Furthermore, dexamethasone prevented eosinophil infiltration of lung and pleural tissue.

Conclusion:  Pneumothorax‐associated pleural eosinophilia in mice is TNF‐α‐dependent and is significantly attenuated by corticosteroid treatment. In addition, both TNF‐α deficiency and dexamethasone treatment were associated with a significant reduction of other types of inflammatory cells in PL.
Tracheo‐broncho‐bronchiolar lesions in Sjögren's syndrome
Authors: KOBAYASHI Hideo , KANOH Soichiro , MOTOYOSHI Kazuo , AIDA Shinsuke
Published: November 2007

Abstract:  A 53‐year‐old woman reported having a persistent cough and bloody sputum. She did not smoke but had received a diagnosis of Sjögren's syndrome. Chest CT revealed middle lobe syndrome, bronchiectasis and diffuse centrilobular nodular lesions. Bronchoscopy displayed multiple whitish polypoid lesions protruding from the cartilage rings and tracheobronchopathia osteochondroplastica was histologically confirmed by the presence of bony tissue in the tracheo‐bronchial wall. Video‐assisted thoracoscopic biopsy demonstrated lymphocyte aggregation causing follicular broncho‐bronchiolitis. Erythromycin therapy resulted in improvement of the follicular bronchiolitis but not the tracheobronchopathia osteochondroplastica.
Airway responses to salbutamol after exposure to chemical warfare
Authors: BOSKABADY Mohammad H. , ATTARAN Dawood , SHAFFEI Mohammad N.
Published: November 2007

Background and objectives:  Increased airway responsiveness to β‐agonists is noted in asthmatics and smokers. The lung may be exposed to chemical warfare agents such as mustard gas and pulmonary complications of exposure range from no effect to severe bronchial stenosis. There is little understanding of airway hyperresponsiveness to β‐agonist drugs in chemical war victims and this study examined airway responsiveness to salbutamol in victims of chemical warfare.

Methods:  The threshold concentrations of inhaled salbutamol required for a 20% change in FEV1 as PC20, or a 35% change in specific airway conductance (sGaw) as PC35 were measured in 22 persons exposed to chemical warfare and 15 normal control subjects.

Results:  In 11 of the 22 subjects PC20 salbutamol could be measured and in 15 of the 22 subjects PC35 salbutamol could be measured. This group of patients was the responder group (PC20 = 10.79 and PC35 = 8.55 mg/L) and in them the concentration of salbutamol needed for a response was significantly lower than that required in normal controls (PC20 = 237.68 and PC35 = 88.72 mg/L, P < 0.001). There was a significant correlation between FEV1 and PC20 salbutamol (r = 0.815, P < 0.001).

Conclusions:  These results showed increased airway responsiveness to salbutamol in most subjects exposed to chemical warfare; this was correlated with airway calibre.
Transbronchial needle aspiration accurately diagnoses subcentimetre mediastinal and hilar lymph nodes detected by integrated positron emission tomography and computed tomography
Authors: HSU Li‐Han , KO Jen‐Sheng , YOU Dong‐Ling , LIU Chia‐Chuan , CHU Nei‐Min
Published: November 2007

Objective and background:  Integrated PET and CT (PET/CT) is accurate in detecting hilar‐mediastinal metastases. However, it has a moderate positive predictive value, necessitating pathological verification, especially in situations in which the result would make a difference to treatment. This study aimed to evaluate the performance of transbronchial needle aspiration (TBNA) for hilar‐mediastinal lesions suspicious on PET/CT.

Methodology:  A retrospective study was conducted on 19 patients with a total of 25 positive hilar‐mediastinal lymph nodes localized on PET/CT. Standard TBNA technique with rapid on‐site cytopathology was performed.

Results:  The mean short‐axis diameter of the positive lymph nodes identified on PET/CT was 9.9 ± 3.0 mm. The sensitivity, specificity and diagnostic accuracy of PET/CT‐guided TBNA were 81.8%, 100% and 84%, respectively. The number of needle passes to successful lymph node aspiration or a diagnosis of cancer was 2.36 ± 0.49. Nine of the 25 positive lymph nodes (36%) on PET/CT were smaller than 1.0 cm. The accuracy and sensitivity of TBNA for these subcentimetre nodes was 88.9% and 87.5%, respectively. TBNA replaced surgical sampling in 15 patients (78.9%) with positive lymph nodes on PET/CT. In seven non‐small cell lung cancer patients, diagnosis and staging were possible in the one procedure. No complications were encountered.

Conclusion:  PET/CT can identify small malignant lymph nodes that can then be successfully biopsied by TBNA with on‐site cytopathology.
Better understanding the influence of cigarette smoking and indoor air pollution on chronic obstructive pulmonary disease: A case–control study in Mainland China
Authors: XU Fei , YIN XiaoMei , SHEN HongBing , XU YaoChu , WARE Robert S. , OWEN Neville
Published: November 2007

Background and objective:  Although the association between COPD and smoking status (non‐smoking, ex‐smoking and current smoking) and indoor air pollution in Chinese populations is well established, the link between COPD and the number of cigarettes smoked has not been examined. This study investigated the relationship between the total amount of cigarettes smoked (TACS) and indoor air pollution, with the risk of COPD among urban and rural Chinese adults.

Methods:  A nested case–control study was performed using data collected in a large community survey (N = 29 319) conducted between October 2000 and March 2001 in Nanjing, China. The exposure to indoor respiratory pollutants of cooking and heating materials and to passive cigarette smoke was compared in patients diagnosed with COPD (n = 1743) and controls matched for age, gender and residence (n = 1743).

Results:  The smoking rate among COPD patients was significantly higher than that among the controls. After controlling for possible confounders, the adjusted odds ratios for COPD increased across TACS tertiles: from lower (OR = 1.40, 95% confidence interval (CI): 1.09–1.79), to middle (OR = 1.55, 95% CI: 1.21–1.99), and upper (OR = 1.77, 95% CI: 1.37–2.29). Among smokers, women were significantly more likely to develop COPD than men (OR = 1.20, 95% CI: 1.02–1.41). There were no significant associations between COPD and domestic fuels used, kitchen ventilation or passive smoking. Heating in winter with coal was weakly but positively linked with COPD among non‐smokers overall, among women non‐smokers, and specifically for women living in urban as well as rural areas.

Conclusions:  A clear dose–response relationship exists between cigarette smoking and COPD; compared with men, women smokers were more susceptible to COPD. Exposure to other respiratory pollutants in the home was not significantly associated with the diagnosis of COPD.
Management of multidrug‐resistant tuberculosis: Update 2007
Authors: YEW Wing Wai , LEUNG Chi Chiu
Published: November 2007

Abstract:  Multidrug‐resistant tuberculosis (MDR‐TB) with bacillary resistance to at least isoniazid and rifampicin in vitro is a worldwide phenomenon. Hot spots of the disease are found scattered in different continents. Prevention of its development through good tuberculosis control programmes operating under the directly observed therapy, short‐course (DOTS) strategy is of paramount importance. However, with established MDR‐TB, treatment with alternative and specific chemotherapy is necessary to achieve a beneficial outcome. Such an approach on a programme basis is currently known as the ‘DOTS‐Plus’ strategy. Second‐line (reserve) drugs utilized in the treatment of MDR‐TB are generally less potent and more toxic, perhaps with the notable exceptions of some fluoroquinolones and injectable agents. Surgery has a distinct adjunctive role for the management of MDR‐TB in selected patients. The emergence of extensively drug‐resistant tuberculosis (XDR‐TB), that is, MDR‐TB with additional bacillary resistance to the fluoroquinolones and injectables, has provided a very alarming challenge to global health, as the disease currently has a low cure rate and high mortality. In order to combat XDR‐TB, strengthening of DOTS and DOTS‐Plus programmes is mandatory, especially in the face of surging HIV infection. Furthermore, more attention needs to be focused on developing new drugs with potent bactericidal and sterilizing activities and low side‐effects, and above all, drugs that are affordable for communities worldwide.
Association of Helicobacter pylori infection with gastroduodenal disease, epidemiologic factors and iron‐deficiency anemia in Turkish children undergoing endoscopy, and impact on growth
Authors: SÜOGLU ÖZLEM DURMAZ , GÖKÇE SELIM , SAGLAM ASLI TOROS , SÖKÜCÜ SEMRA , SANER GÜNAY
Published: November 2007

Background: The purpose of the present paper was to investigate the relationship between Helicobacter pylori infection and clinical symptomatology, breast‐feeding and socioeconomic level. The relationship between H. pylori and iron‐deficiency anemia (IDA) and the effect of H. pylori infection on growth were also investigated.

Methods: The subjects consisted of 70 patients aged 4–16 years who underwent upper gastrointestinal endoscopy for recurrent abdominal pain, nausea, vomiting, and dyspeptic complaints during a 2 year period. Patients were divided into two groups according to presence of histological evidence of H. pylori infection (group 1, H. pylori positive; group 2, H. pylori negative) and groups were compared with respect to epidemiologic characteristics, gastrointestinal complaints, height and weight SD scores and IDA.

Results: Thirty‐five (50%) of the 70 patients participating in the study were H. pylori positive. The mean age of group 1 was significantly higher than that of group 2. There were similar characteristics and symptomatology between groups. The majority of the patients in group 1 belonged to low socioeconomic class (class I and II; P < 0.05). The number of the patients exclusively breast‐fed for ≥4 months was significantly higher in group 2 than in group 1. Gastritis was significantly more frequent in group 1. Mean hemoglobin, serum Fe and ferritin levels were 11.6 ± 1.7 g/dL, 45.0 ± 23.2 μg/dL and 11.9 ± 8.4 μg/dL, respectively, for group 1 and 12.2 ± 0.7 g/dL, 79.3 ± 26.4 μg/dL and 42.1 ± 31.8 μg/dL, respectively, for group 2. The mean serum Fe and ferritin levels of group 2 were significantly higher than those of group 1. IDA was observed in 20 (57.1%) and six (17.1%) patients in groups 1 and 2, respectively. IDA was significantly more frequent in group 1. Helicobacter pylori infection was found to be the only variable that had significant effect on IDA. Mean SD height and weight for group 1 were lower than those of the group 2. When the patients were evaluated in four groups according to H. pylori and IDA status, mean height SD score of patients with both H. pylori infection and IDA was significantly lower than that of the patients negative for H. pylori and IDA concomitantly.

Conclusion: Low socioeconomic status seems to be an important risk factor for H. pylori infection. Exclusive breast‐feeding at least for 4 months can have a protective role against H. pylori infection. Increased frequency of growth retardation and IDA in H. pylori‐infected patients in the present study supports similar findings in the literature, although there is still need for detailed studies to clarify the causative mechanisms.
Factors affecting oral health habits among children with cerebral palsy: Pilot study
Authors: SUBASI FERYAL , MUMCU GONCA , KOKSAL LEYLA , CIMILLI HALE , BITLIS DEMET
Published: November 2007

Background: The aim of the present study was to investigate the factors affecting the oral health habits of children with spastic‐type cerebral palsy (CP).

Methods: A total of 35 children with CP and their mothers were randomly selected for this cross‐sectional study. Data regarding their sociodemographic characteristics and their oral health habits were collected during face‐to‐face interviews.

Results: Logistic regression analysis indicated that mothers’ irregular brushing habits were a risk factor for their children’s lack of regular brushing habits (odds ratio: 6.4, P = 0.048). Additionally, a significant association was observed between the mother’s length of time between dental visits and the length of time between children’s dental visits (R2= 0.11, P = 0.046).

Conclusions: Mothers’ oral health habits, including brushing habits and frequency of dental visits, are important factors in promoting healthy and beneficial oral health habits in children with CP in Turkey.
Therapeutic efficacy of sequential and simultaneous treatments with interferon‐α and lamivudine in children with chronic hepatitis B
Authors: AKMAN SEZIN ASIK , OKCU SABRIYE COKCEKEN , HALICIOĞLU OYA , SUTCUOGLU SUMER , ANIL MURAT , KIZILGUNESLER ASLI , BAKILER ALI RAHMI
Published: November 2007

Background: Interferon (IFN)‐α and lamivudine (LAM), a nucleoside analog, are frequently used drugs for the treatment of chronic hepatitis B (CHB), and their combined therapy has been shown to be effective. The purpose of the present study was to examine the therapeutic efficacy of sequential and simultaneous combination therapies of IFN‐α and LAM in children with CHB.

Methods: A total of 45 children with CHB, whose antibody status was positive for hepatitis B surface antigen (HBsAg), hepatitis B envelope antigen (HBeAg), and HBV‐DNA at least for 6 months; who had alanine aminotransferase (ALT) levels 1.5‐fold higher than normal and hepatic activity index scores higher than 6, were allocated to two groups. The first group included 24 children who were given standard dose IFN‐α (5 MU/m2 s.c., thrice weekly) for 6 months, followed by LAM (4 mg/kg per day per oral, maximum 100 mg/day) for an additional 6 months (sequential therapy group). The second group included 21 children who were given IFN‐α and LAM therapy simultaneously for 6 months and who continued with LAM alone for another 6 months (simultaneous therapy group). Partial response was defined as normalization of ALT and eradication of HBV‐DNA. Complete response was defined as normalization of ALT, eradication of HBV‐DNA and e seroconversion. Non‐responders were defined as having positive HBV‐DNA and abnormal ALT levels. Sustained response was defined as absence of HBsAg and presence of hepatitis B surface antibody (anti‐HBs).

Results: The mean age of the sequential therapy group was 12.7 ± 4.1 years, and 16 (66.7%) of the patients were male. The mean age of the simultaneous therapy group was 14.8 ± 4.6 years, and 15 (71.4%) were male. In the first group, 13 patients (54.2%) were non‐responders; partial response was observed in five patients (20.8%), and complete response was seen in six patients (25%). Despite the occurrence of e seroconversion, normalization of ALT was not achieved in one case. In the second group, which consisted of 21 patients, 11 subjects (52.4%) were non‐responders; partial response was observed in one case (4.8%), and complete response was seen in seven (33.3%). Sustained response was found in two patients (9.5%). There were no significant differences between the groups (P > 0.05).

Conclusion: When the therapeutic efficiency of two different treatment regimens applied for 1 year was evaluated in childhood CHB therapy, it was remarkable that there was a sustained response and a higher complete response in group 2, although there was no considerable difference between the therapy results of both groups.