bluuebunny/crossref_metadata_2025 huggingface dataset:
Transthoracic Ultrasound of Lung and Pleura in the Diagnosis of Pulmonary Embolism: A Novel Non-Invasive Bedside Approach
Authors: Reissig Angelika , Kroegel Claus
Published: December 2003

The diagnosis of pulmonary embolism (PE) presents a considerable challenge and requires a high index of clinical suspicion from the attending physician. In addition, diagnosing PE may require the use of one or more direct and indirect diagnostic methods. Here, transthoracic sonography (TS) provides an alternative and attractive bedside approach which is based on (1) detecting alterations in the lung parenchyma, (2) involvement of the pleura and (3) peripheral perfusion characteristics associated with thromboembolism. Using a 5 MHz or 3.5 MHz convex scanner, occasionally supplemented by a 7.5 MHz linear scanner or colour-flow Doppler mode, the intercostal areas are systematically examined by TS. Most of the PE-related lesions are localised in the lower lobes of the lung and are often associated with an area of pleuritic chest pain. The characteristic sonographic findings of TS in PE are multiple, hypoechoic, pleural-based parenchymal lesions which adopt a wedge-shape. In addition, a central echo may occasionally be detectable within the lesion. Another regular sonographic feature is the involvement of the pleura manifesting as either localised effusion, basal effusion or both. However, several differential diagnoses such as pneumonia, bronchogenic carcinoma, metastases of extra-pulmonary malignancies, and simple pleurisy need to be excluded. Since localisation of PE-associated lesions may occasionally escape sonographic detection, an inconspicuous sonographic result does not fully exclude PE. As detection of PE-associated lesions using chest ultrasonography has a high specificity and sensitivity, can be rapidly performed, is widely available, non-invasive, cost-effective, and avoids transport of critically ill patients to the investigation site, the technique may prove a valuable tool in the diagnosis of PE at bedside facilitating immediate treatment decision. Further, because the method focuses on detection of peripheral lesions it complements other diagnostic techniques employed when PE is suspected.
Fourteen-Year Trend of Tuberculosis Dynamics in the Northwest of Turkey
Authors: Kart Levent , Akduman Deniz , Altin Remzi , Tor Meltem , Unalacak Murat , Begendik Fusun , Erdem Funda , Alparslan Umit
Published: December 2003

Background: The incidence of tuberculosis (TB) in different countries as estimated by the World Health Organization (WHO) vary from 23/100,000 and less in industrialized countries, 191/100,000 in Africa and 237/100,000 in South East Asia. Objectives: The aim of this study was to analyze the dynamics of TB in the northwest of Turkey, between 1988 and 2001. Methods: All pulmonary TB cases reported to the National Tuberculosis Center by local TB dispensaries during 1988–2001 were analyzed. The number of new and relapsed TB cases were documented and classified according to age and type of TB (standard classification of TB patients according to disease type: pulmonary, new, smear positive; pulmonary, smear negative; relapse, and extrapulmonary). We recorded information about the prevalence of TB in different patient groups (patients with a contact history, patients who were detected in active community screening or passive case finding), TB trends in different age groups, type of TB, patients who had relapses, percentage of patients who were lost to follow-up. Results: A total number of 288,996 patients were examined at Zonguldak Tuberculosis Dispensary between 1988 and 2001. Case notification rates of TB decreased over the study period. Respiratory TB was the most commonly encountered form of disease (>90%). The percentage of TB decreased in the 0- to 14-, 15- to 24-year-olds and increased in the 25- to 44- and 45- to 64-year-olds. Conclusion: Properly designed disease surveillance systems are critical for monitoring the TB trends so that each country can identify its own high-risk groups and target interventions to prevent, diagnose, and treat the disease.
Overproduction of MUC5AC Core Protein in Patients with Diffuse Panbronchiolitis
Authors: Kaneko Yukihiro , Yanagihara Katsunori , Miyazaki Yoshitsugu , Hirakata Yoichi , Mukae Hiroshi , Tomono Kazunori , Okada Yoshio , Kadota Jun-ichi , Kohno Shigeru
Published: December 2003

Background: The genetic identities of mucins secreted in the airways of patients with diffuse panbronchiolitis (DPB) have not been previously investigated, although hypersecretion is a common feature of this disease. Objective: The purpose of this study was to determine the production of MUC5AC, a major core protein of mucin in airway secretion, and the effect of macrolide treatment on such production in patients with DPB. Method: We performed Western blot analysis for MUC5AC of bronchoalveolar lavage fluid patients. Cases consisted of four groups including patients with DPB, idiopathic pulmonary fibrosis (IPF), and sarcoidosis, and healthy volunteers. Results:MUC5AC was detected in DPB patients but not in other groups. Macrolide treatment tended to inhibit such production in DPB patients. Conclusions: Our results suggest that overproduction of MUC5AC plays an important role in the pathogenesis of DPB.
Increased Lung Uptake of Technetium-99m Hexamethylpropylene Amine Oxime in Diffuse Infiltrative Lung Disease
Authors: Hang L.-W. , Shiau Y.-C. , Hsu W.-H. , Tsai J.J.-P. , Yeh J.-J. , Kao A.
Published: December 2003

Background: Diffuse infiltrative lung disease (ILD) is a heterogeneous group of disorders which predominantly affect the lung parenchyma and spare the airway. Objective: To assess pulmonary vascular endothelium damage in ILD, the lung uptake of technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) was determined. Methods: In 20 ILD patients and 25 controls without ILD, the lung uptake of 99mTc-HMPAO was measured. Anterior lung imaging, including a large part of the liver, was made 10 min after intravenous injection of 20–25 mCi of 99mTc-HMPAO. Regions of interest covered the liver and lung to calculate the lung/liver uptake ratios. The 20 ILD patients included 10 patients with clinically manifest pulmonary disease (group 1) and 10 asymptomatic patients (group 2). All of the study subjects had normal pulmonary function test results. Results: The mean lung/liver uptake ratio in the 25 controls without ILD (0.36 ± 0.10) was significantly lower than that in the 20 ILD patients (0.97 ± 0.61). In addition, the mean lung/liver uptake ratio in the 10 ILD patients with clinically manifest pulmonary disease (1.45 ± 0.51) was higher than that of the other 10 asymptomatic ILD patients (0.49 ± 0.09). Conclusions: Our results indicated that determining the lung/liver uptake ratio on 99mTc-HMPAO lung imaging should be an objective method to assess subclinical pulmonary damage in ILD patients.
Spirometry Reference Values for Women and Men Aged 65–85 Living in Southern Europe: The Effect of Health Outcomes
Authors: Pistelli Riccardo , Bellia Vincenzo , Catalano Filippo , Antonelli Incalzi Raffaele , Scichilone Nicola , Rengo Franco
Published: December 2003

Background: Spirometry is more and more frequently used for the diagnosis of respiratory diseases in the elderly people. Unfortunately, reliable predictive values for the spirometric variables in the elderly are lacking. Objectives: Data obtained from 429 subjects participating in the multicenter Italian study SARA on respiratory health in the elderly were analyzed in order to derive reference values for spirometry in the age range of 65–85 years. The second aim of this study was to assess the influence of variables describing many dimensions of the health status on the prediction of spirometric variables in that age range. Methods: Subjects were recruited as consecutive outpatients referred during the study period to 24 geriatric or respiratory institutions distributed throughout Italy. Spirometries were performed using the same equipment by specifically trained and certified personnel supervised by a real-time quality control program. In addition to the standard anthropometric variables, covariates describing the affective, mental, and general health conditions were investigated through standardized questionnaires, to improve the modeling of spirometric outcomes. Results: Reliable predictive values for forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were produced (coefficient of determination, for FVC: R2 = 0.64; for FEV1: R2 = 0.54). The effect of general health conditions on spirometric outcomes accounted for the most part of the between-gender difference in the ageing-dependent decrease in lung function. Conclusions: We suggest that a multidimensional approach to health problems should be used for a better interpretation of spirometric results in the elderly.
Abnormalities of the Respiratory Function and Control of Ventilation in Patients with Anorexia nervosa
Authors: González-Moro J.M.R. , de Miguel-Díez J. , Paz-González L. , Buendía-García M.J. , Santacruz-Siminiani A. , de Lucas-Ramos P.
Published: December 2003

Background: Anorexia nervosa is a good model to study the effects of malnutrition on the respiratory system, since it excludes the consequences that some chronic diseases can have on the lung. Objective: The objective of this study was to assess pulmonary function and alterations in the respiratory system in patients with anorexia nervosa. Methods: Twenty-two women, 12 with anorexia nervosa and 10 healthy volunteers, were studied. Anthropometric data were gathered for all the participants. In every case, an arterial blood gas test and functional respiratory study, that included spirometry, plethysmography, measure of maximum muscular respiratory pressure and study of the ventilatory pattern at baseline and after hypercapnic stimulation, were performed. Results: No significant differences were found in mean age and height in both groups of patients but there was a difference in body mass index (p < 0.05). In pulmonary function tests, an increase in residual volume (RV), RV/total lung capacity (TLC) ratio and functional residual capacity and a decrease in maximum respiratory pressure were found in patients with anorexia nervosa compared to the control group (p < 0.05). Differences were also found in the ventilatory pattern, with a reduction in minute ventilation and occlusion pressure as well as a decreased response of these parameters to hypercapnic stimulation (p < 0.05) in the patients with anorexia nervosa. Conclusion: In patients with anorexia nervosa, a significant elevation in RV, in the RV/TLC ratio and in functional residual capacity and a decrease in the maximum respiratory pressure were noted. In addition, they present an alteration in the central respiratory drive and a response of the respiratory system to hypercapnic stimulation. Although these alterations have no repercussion on the maintenance of gas exchange in baseline conditions, they may have in extreme situations.
Bronchial Hyperresponsiveness and Quality of Life in Asthmatics
Authors: Riccioni G. , D’Orazio N. , Di Ilio C. , Della Vecchia R. , Ballone E. , Menna V. , Guagnano M.T.
Published: December 2003

Background: Quality of Life (QoL) measurements are more responsive to clinically significant changes that are not evaluated by conventional clinical measures. Objective: The objective of this study is to examine the relationship between bronchial hyperresponsiveness (BHR) and QoL in asthmatic patients. Patients and Methods: 394 patients underwent clinical follow-up, pulmonary function tests and the methacholine challenge test (MCHt), and completed the Asthma Quality of Life Questionnaire (AQLQ). Results: 200 patients had a positive MCHt and in 194 it was negative. For all 32 items, asthmatic patients had a median value of 4.7 (4.2–5.9) compared to 5.6 (4.7–6.3) in patients with negative MCHt (p < 0.01). For physical activities, patients with positive MCHt showed a median value of 5.0 (4.5–6.0) compared to 5.7 (4.8–6.3) in patients with negative MCHt (p < 0.05). Median scores of 12 items of symptoms and 5 items of emotions were significantly lower in patients with positive MCHt [4.5 (3.7–5.8) and 5.1 (4.2–6.1)] than in patients with negative MCHt [5.5 (4.4–6.1) and 6.3 (5.2–6.9), respectively, (p < 0.01)]. For items of environmental stimuli the median score was 4.7 (3.7–5.9) in patients with positive MCHt, being significantly lower than in patients with negative MCHt [5.4 (4.2–6.4), p < 0.05]. Patients with positive MCHt had lower values of QoL than patients with negative MCHt. Conclusions: QoL changes may be more sensitive than evaluation of BHR. The measurement of Qol may be important because it enables us to characterize patients who could be candidates eventually to a pharmacological treatment for BHR because they have an impaired QoL.
Mediastinal Lymph Node Staging by FDG-PET in Patients with Non-Small Cell Lung Cancer: Analysis of False-Positive FDG-PET Findings
Authors: Konishi Jun , Yamazaki Koichi , Tsukamoto Eriko , Tamaki Nagara , Onodera Yuya , Otake Toshiyuki , Morikawa Toshiaki , Kinoshita Ichiro , Dosaka-Akita Hirotoshi , Nishimura Masaharu
Published: December 2003

Background: Accurate staging of mediastinal and hilar lymph nodes is a critical factor determining operability in patients with non-small cell lung cancer (NSCLC). Positron emission tomography with 2-[18F] fluoro-2-deoxy-D-glucose as a tracer (FDG-PET) has recently been reported to be more effective in detecting tumor involvement in mediastinal and hilar lymph nodes than computed tomography (CT). Objective: In this study, we analyzed the accuracy of FDG-PET in mediastinal and hilar lymph node staging in patients with NSCLC and the factors associated with false-positive or false-negative FDG-PET findings in mediastinal and hilar lymph node staging. Methods: Fifty-four patients with NSCLC who underwent preoperative analysis including chest CT and whole-body FDG-PET were evaluated retrospectively. Using FDG-PET, lesions were considered to be positive if a definite, localized area of higher uptake, excluding physiologic uptake, than in surrounding normal tissue was present. On CT findings, lymph nodes were considered to be positive if they were >10 mm in short-axis diameter, except subcarinal lymph nodes (#7), which were considered to be positive if they were >15 mm in short-axis diameter. All patients underwent surgical resection of primary tumors and mediastinal and hilar lymph nodes between 1999 and 2001 in our institute. Resected lymph nodes were histologically examined for the existence of tumor cells. Results: A total of 306 lymph nodes were resected and used for analysis. The sensitivity, specificity, positive predictive value and negative predictive value of FDG-PET were 73, 98, 70 and 98%, while those of CT were 55, 96, 55 and 96%, respectively. When pre-operative nodal staging was compared with post-operative histopathological staging, 44 patients (81%) were correctly staged, 7 (13%) were overstaged and 3 (6%) were understaged by FDG-PET, while 39 patients (72%) were correctly staged, 8 (15%) were overstaged and 7 (13%) were understaged by CT. All 7 overstaged patients by FDG-PET had other pulmonary complications, including interstitial pneumonitis (n = 2), previous pulmonary tuberculosis (n = 3), silicosis (n = 1) and emphysema (n = 1), although they were not in the active stage. In 3 understaged patients by FDG-PET, lymph nodes were also undetectable by CT. Conclusion: FDG-PET is superior to CT in mediastinal and hilar lymph node staging of patients with NSCLC. However, care should be taken in lymph node staging for patients who have other pulmonary complications, including interstitial pneumonitis, previous pulmonary tuberculosis and silicosis.
Electromagnetic Navigation during Flexible Bronchoscopy
Authors: Schwarz Yehuda , Mehta Atul C. , Ernst Armin , Herth Felix , Engel Ahuva , Besser Doron , Becker Heinrich D.
Published: December 2003

Background: Flexible bronchoscopy is routinely utilized in the diagnosis and treatment of various lung diseases. Nondiagnostic bronchoscopy leads to more invasive interventions, such as transthoracic needle aspiration, mediastinoscopy or even thoracotomy. Electromagnetic navigation is a novel technology that facilitates approaching peripheral lung lesions, which are difficult to sample by conventional means. The navigation system involves creating an electromagnetic field around the chest and localizing an endoscopic tool using a microsensor overlaid upon previously acquired CT images. Objectives: To determine the practicality, accuracy and safety of real-time electromagnetic navigation, coupled with previously acquired 3D CT images, in locating artificially created peripheral lung lesions in a swine model. Methods: Peripheral lung lesions were created in four swine models by insertion of a metal tube (1 × 10 mm) via a transthoracic approach. An electromagnetic field was created by placing the animal on an electromagnetic location board. A position sensor incorporated into the distal tip of a dedicated tool was used to navigate to the various target lesions. Information gathered in real time during bronchoscopy was presented on a monitor simultaneously by displaying previously acquired CT images. Upon reaching the target lesion, biopsies were performed and the functionality and safety of the superDimension/Bronchus System was observed and documented. Results: The registration accuracy expressed by the fiducial target registration error, expressing both the registration quality and the stability of fiducial (registration) points, was 4.5 mm on average. No adverse effects, such as pneumothorax or internal bleeding, were encountered in any of the animals in this study. Conclusions: Real-time electromagnetic positioning technology coupled with previously acquired CT images is an accurate technology added to standard bronchoscopy to assist in reaching peripheral lung lesions and performing biopsies.
Stability of Glutathione in Induced Sputum: Impact of Freezing
Authors: Beier J. , Beeh K.M. , Kornmann O. , Buhl R.
Published: December 2003

Background: Oxidative stress has repeatedly been linked to the pathogenesis of pulmonary disorders like asthma and chronic obstructive pulmonary disease. Measuring glutathione (GSH) in induced sputum (IS) offers a noninvasive tool to study oxidative stress in airway diseases. Objectives: This study assessed the stability of GSH in sputum supernatant under varying conditions. Methods: GSH in IS of 14 (7 healthy, 4 chronic obstructive pulmonary disease, 3 allergic rhinitis) nonsmoking subjects was quantified spectrophotometrically. The stability of GSH in supernatant was analyzed over 24 h under different ambient conditions (room temperature and cooling at 4°C). Reproducibility of GSH measurements in immediately processed and frozen supernatant (+72 h) was expressed by intraclass correlation coefficient (Ri) and coefficient of repeatability (CR). Results: GSH recovery in supernatant decreased in a time- and temperature-dependent manner. Samples stored at 4°C and room temperature showed a rapid decline of stability after 2 h. Mean GSH concentrations in IS after freezing (–20°C) and thawing after 72 h were not significantly different from GSH values measured immediately after processing of the samples (immediate processing: 17.9 ± 13.9 µM; 72 h freezing: 16.4 ± 12.9 µM, p = 0.2). The reproducibility between immediately processed and frozen samples was excellent (Ri = 0.97; CR = 5.7 µM). Conclusions: Storage of sputum supernatant at room temperature or 4°C leads to a rapid decline of GSH recovery compared with baseline values. Immediate freezing of samples is a suitable and valid alternative to rapid processing and allows collection and shipment of samples for subsequent analysis.
Miliary Tuberculosis as a Cause of Acute Empyema
Authors: Runo James R. , Welch Derek C. , Ness Erik M. , Robbins Ivan M. , Milstone Aaron P.
Published: December 2003

Adult respiratory distress syndrome (ARDS) and sepsis are known, life-threatening complications of miliary tuberculosis. This report describes a patient with miliary tuberculosis who rapidly developed an acute tuberculous empyema. She had a fulminant course culminating in ARDS, sepsis and subsequent death. This case highlights the rare association of acute empyema with miliary tuberculosis.
Pulmonary Infection due to Mycobacterium szulgai
Authors: Sánchez-Alarcos José M.F. , de Miguel-Díez Javier , Bonilla Ignacio , Sicilia Juan J. , Álvarez-Sala José L.
Published: December 2003

A 75-year-old man was admitted with cough, purulent sputum, fatigue and weight loss of 10 kg of some months’ duration. His chest radiograph showed poorly defined opacities in the right lung. Eleven years before admission an epidermoid carcinoma of the right lung had been diagnosed and a right bilobar resection had been performed. The patient remained asymptomatic for 8 years. Cultures of 4 consecutive sputum samples were positive for mycobacteria that were identified as Mycobacterium szulgai by gas chromatography. A 6-month regimen of rifampin, isoniazid and pyrazinamide resulted in complete eradication of the mycobacterium. M. szulgai is an unusual pathogen in humans. In the English literature, only 35 cases of pulmonary disease have been reported. Its clinical and radiological characteristics are similar to tuberculosis but in contrast to the rest of the non-tuberculous mycobacteria, M. szulgai has shown in vitro and in vivo susceptibility to most primary antituberculosis drugs.
Three Unusual Cases where Cardiopulmonary Bypass Was Used in Thoracic Surgery
Authors: Doğan Rıza , Öç Mehmet , Özkan Murat , Güvener Murat , Çöplü Lütfü , Demircin Metin
Published: December 2003

Cardiopulmonary bypass (CPB) is a technique which is commonly performed without any problem in cardiac surgery. CPB can also be used in patients with a tumoral mass adherent to the great vessels, in patients with critically narrowed airway, if cross-table intubation of the distal trachea is not feasible and in patients necessitating re-do surgery with extensive adhesions because it allows extensive mobilization of the heart and great vessels without compromising their function. It also allowed the central pulmonary artery to be controlled without comprising oxygenation and complete resection of a tumor localized in the A-P window. Herein we report such patients operated with CPB without any problem.
Multiple Lung Nodules in a Woman with a History of Melanoma
Authors: Taylor Jennifer L. , Quiñones Maymí Desirée M. , Sporn Thomas A. , McAdam H. Page , Wahidi Momen M.
Published: December 2003

A 61-year-old Caucasian female presented with a 6-week history of dry persistent cough. She had no shortness of breath, chest pain, fever, chills, or weight loss. She had been diagnosed with melanoma on the left thigh 6 months earlier. It was a spindle cell variant, Clark’s grade III, with maximal thickness of 0.5 mm. At the time of diagnosis of melanoma, there was no evidence of metastasis on chest radiographs or computed tomography (CT) of the abdomen and pelvis. Treatment of her melanoma was limited to surgical excision with no subsequent radiation or chemotherapy. Other significant past medical history included hypertension, hypothyroidism, and bilateral breast augmentation. She had a 40 pack-year history of smoking.
Pulmonary Alveolar Microlithiasis
Authors: Castellana Giuseppe , Lamorgese Vito
Published: December 2003

Pulmonary alveolar microlithiasis (PAM) is a rare idiopathic disease with unknown etiology and pathogenesis. The present work updates the world literature on PAM up to the end of 2001 by means of a full review, including minor reports in local languages (not English). Excluding secondary cases, a total of 424 cases have been reported worldwide, 269 of which were sporadic and showed a prevalence of the male sex and 155 of which were familial cases and prevalently affected the female sex. The highest number of cases has been reported in Europe, followed by Asia, especially Asia Minor, while the single nations with the greatest number of reported cases are Turkey, then Italy and the USA. The salient clinical features of PAM as described in the literature are analyzed: family history, clinical course, association with other diseases, presence of calcification in other organs. In the first cases, reported in the 60s and 70s, diagnosis was primarily made at autopsy, whereas nowadays diagnostic investigation is made above all by transbronchial biopsy and bronchoalveolar lavage. Radiological imaging is sufficient in cases where other family members are known to be affected, diagnosed by means of invasive techniques. There is no known treatment to date, while lung transplantation is performed in the severest cases. A better knowledge of the epidemiological characteristics of this rare disease could help to diagnose a larger number of cases and to gain insight into its etiology and pathogenesis, which are still unknown.
Long-Term Results of the Immunosuppressive Treatment of Patients with Severe Acquired Aplastic Anemia: A Single Institution Study
Authors: Ruiz-Argüelles Guillermo J. , Gómez-Rangel J. David
Published: December 2003

In México, only few patients can afford adequate treatment for aplastic anemia. In a single institution 61 individuals with severe aplastic anemia (SAA) were identified; of these, 33 were followed for at least 3 months, 26 could be treated with immunosuppression (IS), 20 with antithymocyte globulin and cyclosporin A (ATG + CyA) and 6 with CyA, whereas 7 individuals were given only anabolic androgens. In the patients treated with IS a complete remission was achieved in 12 and a partial remission in 6, the overall response rate being 69%. The 5,729-day overall survival (SV) was 54%; it was superior for the patients who received both ATG and CyA (58 vs. 50%). These data contrast with those of the patients who were given only androgens: 14% SV at 5,510 days. Within the group of patients who received IS, one developed acute myelogenous leukemia, another paroxysmal nocturnal hemoglobinuria and another a primary Sjögren’s syndrome-associated low-grade, B cell, non-Hodgkin’s lymphoma. Two individuals who received IS were allografted from HLA-identical siblings and survived 70 and 413 days after the allograft. On the other hand, we also found that, for several reasons, mainly economic ones, only 41% of individuals with SAA finally benefited from the best immunosuppressive therapeutic approach. IS was a good therapeutic choice for some patients with SAA, clearly better than androgen treatment.
Splenectomy for Massive Splenic Infarction Unmasks Paroxysmal Nocturnal Hemoglobinuria
Authors: Tsatalas Costas , Margaritis Dimitris , Pantelidou Despina , Kotsianidis Ioannis , Karayiannakis Anastasios J. , Spanoudakis Emanuel , Kartasis Zafiris , Kaloutsi Vasiliki , Polychronidis Alexandros , Manavis Ioannis , Bourikas George
Published: December 2003

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disorder characterized by pancytopenia, hemolysis, and thrombosis. Abdominal vein thrombosis is a life-threatening manifestation of this disease. We present a patient with complete spleen necrosis due to thrombosis of the splenic vessels. After splenectomy, other causes of thrombophilia were excluded and the diagnosis of PNH was established. The patient was put on anticoagulation but despite the prophylactic international normalized ratio maintained over the last 18 months of follow-up, he had another episode of intrahepatic thrombosis which was treated with tissue plasminogen activator thrombolysis.
Effect of Stobadine on Leukocyte Free Radical Generation in Streptozotocin-Diabetic Rats: Comparison with Vitamin E
Authors: Demiryürek A. Tuncay , Karasu Çimen , Stefek Milan , Stolc Svorad
Published: December 2003

We investigated a possible alteration in the ability of leukocytes to produce reactive oxygen species by stobadine, a pyridoindole antioxidant, in streptozotocin-diabetic rats. The production of free radicals from whole blood was assessed by luminol-enhanced chemiluminescence after stimulation by phorbol myristate acetate. The effects of vitamin E treatment were also evaluated and compared with the effects of combined treatment with stobadine. Diabetes was induced by streptozotocin (55 mg/kg i.p.). Some of diabetic rats and their age-matched controls were treated orally with a low dose of stobadine (24.7 mg/kg/day), vitamin E (400–500 IU/kg/day), or stobadine plus vitamin E for 10 weeks. Stobadine and vitamin E separately produced, to a similar degree, a reduction in diabetes-induced hyperglycemia. The phorbol myristate acetate stimulated chemiluminescence signal was markedly depressed in both moderate and severe diabetic rats. Stobadine treatment prevented this depression of the chemiluminescence response. Vitamin E treatment also eliminated the depression of the chemiluminescence signal in diabetic rats, and the combination with stobadine did not produce further improvement in leukocyte function. These results suggest that stobadine treatment alone is able to produce beneficial effects on leukocyte function and to maintain leukocyte free radical release during diabetes.
Inhibition of Guinea Pig Intestinal Peristalsis by the Flavonoids Quercetin, Naringenin, Apigenin and Genistein
Authors: Gharzouli Kamel , Holzer Peter
Published: December 2003

Flavonoids are known to relax precontracted intestinal smooth muscle and to delay intestinal transit. We therefore investigated the effects of quercetin, naringenin, apigenin and genistein on intestinal peristalsis in vitro. Peristalsis in fluid-perfused segments of the guinea pig small intestine was recorded through the intraluminal pressure changes associated with the peristaltic waves. Alterations of distension sensitivity were reflected by changes in the peristaltic pressure threshold and alterations of peristaltic performance by changes in the maximal acceleration, amplitude and residual baseline pressure of the peristaltic waves. Quercetin, naringenin, apigenin and genistein (10–300 µmol/l) depressed intestinal peristalsis in a structure- and concentration-dependent manner. The flavonoid-evoked changes in peristalsis parameters made it possible to distinguish between two patterns of peristaltic motor inhibition: a decrease in distension sensitivity and peristaltic performance (apigenin and genistein) and a decrease in distension sensitivity without a major change in peristaltic performance (quercetin and naringenin). The antiperistaltic effect of quercetin was partially prevented by apamin (0.5 µmol/l), N-nitro-L-arginine methylester (100 µmol/l) and naloxone (0.5 µmol/l), whereas the effect of genistein was hardly affected by these drugs. Peristaltic motor activity suppressed by quercetin (300 µmol/l), but not genistein (100 µmol/l), was partially restored by apamin. In contrast, neostigmine (0.3 µmol/l) caused a significant recovery of peristalsis from blockade by genistein but failed to reverse peristaltic motor blockade due to quercetin. These observations suggest that naringenin and quercetin inhibit peristalsis by facilitating inhibitory enteric pathways, whereas apigenin and genistein interfere with muscle excitation or excitation-contraction coupling.
Differential Induction of the Expression of GST Subunits by Geniposide in Rat Hepatocytes
Authors: Kuo Wu-Hsien , Wang Chau-Jong , Young Shun-Chieh , Sun Yuan-Chang , Chen Yi-Jun , Chou Fen-Pi
Published: December 2003

Geniposide, an iridoid glycoside isolated from the fruit of Gardenia jasminoides Ellis, has the biological capabilities of detoxication, antioxidation, and anticarcinogenesis. In this study, the mechanism of geniposide affecting the GST (glutathione S-transferase) system was investigated. Primary cultured rat hepatocytes were treated with geniposide and examined for total GST activity and expression of GST subunits. The results showed that the geniposide-induced GST activity was dose and time dependent. Western blotting data demonstrated that geniposide induced increased protein levels of GSTM1 and GSTM2 (∼1.7- and 1.8-fold of control, respectively), but did not increase those of GSTA1. The corresponding transcripts levels were confirmed by RT-PCR. Using PD98059, the effect of geniposide was verified to be via the MEK pathway. The results suggest that geniposide possesses a potential for detoxication by inducing GST activity via increasing the transcription of GSTM1 and GSTM2.
Pharmacokinetics and the Cardiovascular Effects of Irbesartan in Aortic Coarctated Rats
Authors: Höcht Christian , Opezzo Javier A. W. , Taira Carlos A.
Published: December 2003

A pharmacokinetic-pharmacodynamic study of irbesartan (IRB) was performed in anesthetized sham-operated (SO) and aortic coarctated (ACo) rats. Anesthetized Wistar rats were used 7 days after ACo procedure or SO. A vascular shunt probe was inserted into the carotid artery for the study of plasma pharmacokinetics. In a separate experiment, a concentric probe was placed into the anterior hypothalamus for the study of the IRB distribution in the central nervous system. IRB (10 mg·kg–1 i.v.) induced a rapid decrease of the heart rate (HR) in the ACo animals (ΔHR –19.2 ± 2.0 bpm, n = 6; p < 0.05 vs. basal HR), but not in the SO rats (ΔHR –6.7 ± 5.1 bpm, n = 6). Moreover, IRB reduced the mean arterial blood pressure in the animals of both experimental groups, but the hypotensive effect lasted longer in ACo rats than in SO animals. Analysis of blood samples showed a lower constant of elimination of IRB in ACo rats (Ke 0.67 ± 0.28 h–1, n = 5; p < 0.05) than in SO rats (Ke 1.72 ± 0.30 h–1, n = 6). Also, a greater distribution of IRB in the anterior hypothalamus was seen in the ACo rats (area under the curve32 ± 4 ng·ml–1·h–1, n = 6; p < 0.05) than in the SO rats (area under the curve 12 ± 1 ng·ml–1·h–1). The protein binding of IRB was similar in both experimental groups (SO rats 7.1 ± 1.2%, n = 6; ACo rats 7.7 ± 1.5%, n = 6). In conclusion, ACo reduces the plasma elimination of IRB, increasing the distribution in the central nervous system. The longer hypotensive effect of IRB observed in ACo animals could be explained by the slowest elimination of the drug in ACo rats. On the other hand, the effect of IRB on the HR suggested that angiotensin II modulates this parameter in ACo animals at an early stage of hypertension.
Evidence for the Mechanisms Underlying the Effects of Pimaradienoic Acid Isolated from the Roots of Viguiera arenaria on Rat Aorta
Authors: Tirapelli Carlos R. , Ambrosio Sergio R. , da Costa Fernando B. , de Oliveira Ana M.
Published: December 2003

The present study examines the effects of the diterpene ent-pimara-8(14),15-dien-19-oic acid (PA) on rat thoracic aorta. PA (10–5, 3 × 10–5 and 10–4 mol/l) caused concentration-dependent inhibition of phenylephrine (Phe)-induced contraction in either endothelium-intact or endothelium-denuded aortic rings. PA attenuated the contraction induced by CaCl2 in Ca2+-free solution containing Phe (10–7 mol/l) or KCl (30 mmol/l). This diterpene did not interfere with Ca2+ release from intracellular stores mediated by either Phe (10–6 mol/l) or caffeine (30 mmol/l). PA (10–6 to 3 × 10–4 mol/l) concentration dependently relaxed Phe-pre-contracted rings with intact (92.64 ± 7.60%) or denuded endothelium (98.82 ± 1.56%). Pre-incubation of denuded aortic rings with NG-nitro-L-arginine methyl ester (10–4 mol/l), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (10–6 mol/l) or indomethacin (10–5 mol/l) reduced PA-induced relaxation (percentage of relaxation: 77.50 ± 3.95, 78.56 ± 2.81, 77.11 ± 6.22, respectively). However, the relaxant responses induced by PA on Phe-pre-contracted rings were unaffected by tetraethylammonium (1 and 5 mmol/l). PA also relaxed KCl-pre-contracted rings with intact (97.44 ± 3.66%) or denuded endothelium (95.95 ± 3.72%). Collectively, these results support the notion that the effects elicited by PA on vascular smooth muscle are endothelium-independent and involve extracellular Ca2+ influx blocked. In addition, PA effects are partly dependent on the release of nitric oxide from the vascular smooth muscle through an activation of guanylyl cyclase-dependent mechanism and are related to the release of metabolites derived from the arachidonic acid pathway. Finally, our results demonstrated that the PA relaxant action is not related with the opening of potassium (K+) channels.
Amlodipine Increases Endothelial Nitric Oxide by Dual Mechanisms
Authors: Berkels Reinhard , Taubert Dirk , Bartels Henning , Breitenbach Thomas , Klaus Wolfgang , Roesen Renate
Published: December 2003

Several experimental and clinical studies have demonstrated the antiatherogenic profile of the long-acting calcium antagonist amlodipine. Given the pivotal role of endothelial (dys)function during atherogenesis, we investigated the influence of amlodipine on endothelial nitric oxide (NO) bioavailability. Acute addition of amlodipine to segments of porcine coronary arteries resulted in a significant increase in NO release which could be blocked by the NO synthase inhibitor L-NMMA (N-monomethylarginine). This effect was mirrored by a rise in intracellular cGMP levels in porcine endothelial cell cultures. Long-term (24 h) treatment of porcine endothelial cell cultures with amlodipine (0.1–10 µmol/l) significantly enhanced the basal NO formation in a concentration-dependent manner which was abrogated in the presence of L-NMMA (0.1 mmol/l). In EA.hy 926 endothelial cells, amlodipine treatment for 24 h significantly increased the endothelial NO synthase protein expression. To evaluate whether the observed increase in NO was additionally due to an antioxidative protection of NO, we examined the influence of amlodipine in different in vitro models. In a cell-free system, amlodipine quenched superoxide anions (hypoxanthine/xanthine oxidase assay) at high concentrations (150 µmol/l). Addition of artificial membrane preparations (dimyristoylphosphatidylcholine) to mimic a physiological environment significantly enhanced this antioxidative effect. In a more physiological model of hyperglycemia (30 mmol/l, 20 min) induced formation of reactive oxygen species from native endothelial cells of porcine coronary arteries, amlodipine concentration dependently attenuated the reactive oxygen species release (>60%; 10 µmol/l). We conclude, that amlodipine increases the endothelial NO bioavailability, firstly via enhanced NO formation and secondly by prolonging the half-life of NO through antioxidative properties. This may result in an improved endothelial function.
Pertussis Toxin-Sensitive G Protein but Not NO/cGMP Pathway Mediates the Negative Inotropic Effect of Carbachol in Adult Rat Cardiomyocytes
Authors: Sandirasegarane Lakshman , Diamond Jack
Published: December 2003

Previous studies have shown that muscarinic inhibition of cardiac contractility is mediated by either activation of nitric oxide (NO)/guanosine 3′,5′-cyclic monophosphate (cGMP) pathway or stimulation of inhibitory G protein (Gi). However, it still remains controversial as to whether NO/cGMP pathway or Gi protein or both mediate(s) the negative inotropic effect of muscarinic agonists in adult ventricular myocytes. In the present study that involves the use of adult rat ventricular myocytes, the muscarinic agonist, carbachol, inhibited β-adrenergic (isoproterenol) stimulation of contractility (cell shortening) by 82% and increased cGMP levels by 49% within 6 min. Pretreatment of myocytes with soluble guanylyl cyclase inhibitor (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, ODQ) or NO synthase inhibitor (NG-monomethyl-L-arginine, L-NMMA) for 30 min blocked carbachol-induced increases in cGMP levels. However, neither ODQ nor L-NMMA pretreatment had any effect on carbachol inhibition of isoproterenol-induced contractility. In addition, carbachol did not attenuate increases in myocyte contractility induced by forskolin (a direct activator of adenylyl cyclase) or 8-(4-chlorophenylthio)-adenosine 3′,5′-cyclic monophosphate (a cell-permeable cAMP analog which activates cAMP-dependent protein kinase). Pretreatment of myocytes with Gi protein inhibitor, pertussis toxin (PTX, 1 µg/ml), for 18–20 h abolished carbachol inhibition of isoproterenol-induced contractility. Furthermore, in ventricular myocytes isolated 3 days after in vivo treatment of rats with PTX (3 µg/100 g, i.p.), there was a complete loss of the negative inotropic effect of carbachol. These data indicate that pertussis toxin-sensitive G protein but not NO/cGMP pathway is required for muscarinic inhibition of β-adrenoceptor-mediated increases in contractility in adult rat ventricular myocytes.
Effects of Oxytocin Outside Pregnancy
Authors: Lippert Theodor H. , Mueck Alfred O. , Seeger Harald , Pfaff Andreas
Published: December 2003

For a long time, oxytocin was regarded as a pregnancy hormone released by the hypophysis to stimulate labour and milk ejection. In the present survey, data have been collected from the literature to show the spectrum of the hitherto known functions of oxytocin outside pregnancy. It is now known that oxytocin receptors can occur almost ubiquitously in the organism, that oxytocin is also formed outside of the brain and that oxytocin has functions in a number of organs. In the first part of the survey, stimuli that contribute to an increase in oxytocin release are compiled. In the second part, details are given on the individual oxytocin targets. Although the majority of findings are based on the results of animal experiments, there are already a number of studies that indicate similar effects of oxytocin in humans. According to the current state of knowledge, oxytocin appears to be involved in functions in the following organs: male and non-pregnant female reproductive tract, pancreas, cardiovascular system, kidney, brain and breast. There are indications that oxytocin may also have actions in other organs. There continues to be a considerable need for research into oxytocin in order to better understand the physiological and pathophysiological actions and to be able to derive possible therapeutic uses. Further light on the spectrum of functions of oxytocin may be cast by the possibility of the use of oxytocin antagonists.
Extremely Short Stature: Influence of Each Parent’s Height on Clinical-Biological Features
Authors: Giacobbi V. , Trivin C. , Lawson-Body E. , Fonseca M. , Souberbielle J.-C. , Brauner R.
Published: December 2003

Idiopathic extremely short stature probably has several causes. Objective: To evaluate the influence of each parent’s height on clinical-biological features. Methods: 57 patients without intrauterine growth retardation seen at 7.9 ± 0.4 years for height ≤–3 SD were classified according to the difference between their target height and actual height: <2 SD in familial short stature (FSS, n = 28) and >2 SD in non-FSS (n = 29). Results: Height decreased from –0.5 ± 0.1 SD at birth to –2 ± 0.2 SD at 1 year and –2.7 ± 0.1 SD at 3 years, but the changes in the two groups were similar. FSS children were shorter than non-FSS children both at birth (p = 0.03) and as adults after growth hormone (GH) treatment (p < 0.05), but their plasma insulin-like growth factor I concentrations and GH peaks were similar. The FSS children fathers’ heights were more frequently below –2 SD (64%) than the mothers’ heights (35%) and were correlated with height at first evaluation (p < 0.05). For the whole population, the mothers’ heights were correlated with birth weight (p < 0.05) and with height at first evaluation (p < 0.03). Conclusion: This study confirms the influence of the mother’s height on birth weight and shows how of the father’s height influences idiopathic extremely short stature.
Clinical Characteristics and Molecular Analysis of PIT1, PROP1,LHX3, and HESX1 in Combined Pituitary Hormone Deficiency Patients with Abnormal Pituitary MR Imaging
Authors: Kim Sung-Su , Kim Youngho , Shin Young-Lim , Kim Gu-Hwan , Kim Tae-Ue , Yoo Han-Wook
Published: December 2003

Background/Aims: Many genes encoding pituitary transcription factors involved in the formation of the pituitary gland are identified. Different mutations in these genes have been reported in patients with familial combined pituitary hormone deficiency (CPHD). This study was undertaken to analyze PIT1, PROP1, LHX3, and HESX1 in 12 CPHD patients with abnormal pituitary magnetic resonance imaging (MRI). Since embryonic development of the pituitary requires the coordinated expression of specific transcription factors, we postulated the presence of mutations in PIT1, PROP1, LHX3, and HESX1 genes. Methods: Anterior pituitary function was evaluated. Each gene was PCR amplified exon by exon, and subsequently sequenced. Results: In all cases, MRI examination showed abnormal pituitary gland development featuring ectopic neurohypophysis, hypoplastic anterior lobe, empty sella, and septo-optic dysplasia. Endocrinologically, all patients revealed multiple pituitary hormone deficiency including growth hormone, thyroid stimulating hormone, luteinizing hormone, follicular stimulating hormone and adrenocorticotropin. They were all sporadic cases without a positive family history. None of disease-causing specific mutations were identified in PIT1, PROP1, LHX3, and HESX1 genes of 12 sporadic CPHD patients with abnormal pituitary imaging. However, 2 novel polymorphisms were found in PROP1 gene: IVS1+3 A→G and 27 T→C (Ala9Ala) in exon 1. Their allele frequencies in patients and normal controls were not statistically different. Overall, allele frequencies of these polymorphisms were as follows: for the IVS1+3 A→G polymorphism, the allele frequency of A was 54%, and 46% for G, with 58% of an A/G heterozygosity. For the 27 T→C (Ala9Ala) polymorphism, the allele frequency of T was 46%, and 54% for G, with 42% of a T/C heterozygosity. Conclusions: Mutations of PIT1, PROP1, LHX3, and HESX1 genes are very rare in sporadic CPHD patients with abnormal pituitary MRI.
Annual Changes in Bone Mineral Content and Body Composition during Growth
Authors: Braillon P.M.
Published: December 2003

Objectives: To compute the annual changes in total bone mineral content (BMCt), lean tissue mass and fat mass (LTM and FM) during growth. Methods: Whole body DXA data were used to calculate the annual changes of the parameter P (P = BMCt, LTM or FM), as a percentage, as ΔP% = 100 × (Pi+1 – Pi) / Pi; with Pi and Pi+1 the values for P at age i and age (i+1). Smoothed curves were then obtained from ΔP% values plotted against age. Results: Changes in FM were different in males and females. A peak velocity was marked for the three tissues at age 6.5 in boys, and at age 6.5–7.5 in girls; a pubertal peak spurt appeared at age 12 in girls and between age 13 and 14 in boys. This latter peak was followed by an exponential decrease, and no significant changes were found for the three components after age 20 in girls and age 21–22 in boys. Conclusion: Changes in tissue accretion during growth are easy to follow when expressed in percentages. Fat changes, especially, should be around 17% in girls and 15% in boys at the age of puberty.
Metabolic Effects of Growth Hormone Therapy in an Alström Syndrome Patient
Authors: Tai Tsai-Sung , Lin Shih-Yi , Sheu Wayne Huey-Herng
Published: December 2003

Aim: To investigate the metabolic effects of recombinant human growth hormone (rhGH) in an Alström syndrome patient with growth hormone deficiency. Methods: A 15-year-old Alström syndrome boy with growth hormone deficiency received rhGH therapy for 1 year. Biochemical parameters, including hepatic enzyme levels, lipid profiles, and insulin sensitivity, were measured. Body composition analysis and computed tomography scans of the liver were performed. Results: After 1 year of rhGH treatment, body fat mass, fat infiltration in the liver, and serum lipid profiles had all decreased. Insulin sensitivity and acanthosis nigricans improved. Conclusion: rhGH therapy might have beneficial effects on body composition, liver fat content, lipid profiles, and insulin resistance in Alström syndrome patients, with improvement of the glucose homeostasis.