bluuebunny/crossref_metadata_2025 huggingface dataset:
Stressinkontinenz der Frau: Theorien und moderne Operationstechniken im Vergleich
Authors: Perucchini D. , Fink D.
Published: April 2003

Eine ganze Reihe von Faktoren sind für die reibungslose Schliessfunktion des unteren Harntraktes wichtig. Für die Entstehung einer Stressinkontinenz kann nicht eine einzelne Ursache verantwortlich gemacht werden. Durch Geburtsschädigung, Alterung und Überlastung kann es zu multiplen Schädigungen kommen, und diese können sich klinisch als Senkungszustände und/oder als Inkontinenz manifestieren. In den letzten Jahren konnten interessante neue Einblicke in den Mechanismus der Stressinkontinenz gewonnen werden. Die vereinfachte anatomische Vorstellung, durch die Korrektur des urethrovesikalen Winkels Kontinenz zu erreichen, wird zunehmend zu Gunsten von komplexen, ganzheitlichen Theorien verlassen. Dabei sind das suburethrale Widerlager nach De Lancey und eine schlechte Verankerung diverser Muskeln und Bänder nach Ulmsten und Petros von Bedeutung. Gemäss der Integraltheorie wird die primär «schlaffe» Vagina wie ein Trampolin im kleinen Becken «gleichmässig ausgespannt». Zur operativen Standardtherapie der Harninkontinenz gehörten während mehr als 50 Jahren die Kolposuspensionsverfahren. Mit der Einführung des «tension-free vaginal tape» kam es zu einem Paradigmenwechsel. Die spannungsfreien Schlingenverfahren stellen eine echte Innovation dar und haben sich innert Kürze im Alltag etabliert. Mit zunehmender Dynamik drängen neue Varianten von Schlingentechniken auf den Markt. Diese werden im Sinne einer kurzen Übersicht vorgestellt.
Malignant Struma ovarii: Report of a Case and Review of the Literature
Authors: Kostoglou-Athanassiou I. , Lekka-Katsouli I. , Gogou L. , Papagrigoriou L. , Chatonides I. , Kaldrymides P.
Published: April 2003

Malignant struma ovarii is a very rare disease and therefore there is neither common agreement on treatment regimens nor sufficient follow-up experience. The case of a 38-year-old woman with malignant struma ovarii is described. The patient presented with a clinically silent ovarian neoplasm discovered incidentally during investigations for metrorrhagia. The ovarian mass was resected and the tumor was found to be a teratoma. Within the teratoma a papillary thyroid carcinoma of the follicular variant was found. Subsequently, in order to make follow-up of the patient possible by thyroglobulin measurement and radioiodine whole body scintigraphy, near-total thyroidectomy was performed and the thyroid was found to be normal on histology. Whole body radioiodine scintigraphy with 131I and ablation of the thyroid remnant by the administration of 80 mCi 131I was performed. The patient recovered uneventfully and is now well.
Superoxide Anion Production by Granulocytes Incubated with HeLa 229 Cells Persistently Infected with Influenza Virus B/Lee/40
Authors: Hayase Yukiharu , Tobita Kiyotake
Published: April 2003

Objective: The purpose of this study was to determine whether granulocytes can be primed to produce superoxide anion by incubation with cells persistently infected with influenza viruses. Methods: The effect of in vitro incubation with HeLa 229 cells persistently infected with influenza virus B/Lee/40 (He/Le cells) on the generation of superoxide anion by human granulocytes was examined by a cytochrome c reduction assay. Results: Generation of superoxide anion from granulocytes, preincubated with He/Le cells in the productive phase and stimulated with formyl-methionine-leucine-phenylalanine, was significantly enhanced compared with granulocytes preincubated with uninfected HeLa 229 cells. He/Le cells in the productive phase were positive for viral proteins by immunofluorescence and for viral particles by scanning electron microscopy. The priming effects were concentration-dependently inhibited by polyclonal antibodies to the virus. He/Le cells in the latent phase, negative for viral proteins and viral particles, did not prime granulocytes. Culture supernatants of the productive phase did not prime granulocytes. Conclusion: Unreleased influenza viruses on He/Le cells in the productive phase primed granulocytes to produce excessive amounts of superoxide anion, suggesting that cytotoxicity by hyperresponsive granulocytes could take place in persistent influenza infection as well as in acute infection.
Accurate Prediction of Response to Interferon Therapy by Repeated Measurement of Hepatitis C Virus Core Protein in Patients with Chronic Hepatitis C
Authors: Nishiguchi Shuhei , Enomoto Masaru , Tanaka Motoharu , Fukuda Katsuhiko , Tamori Akihiro , Habu Daiki , Takeda Tadashi , Shiomi Susumu , Tanaka Takashi , Yano Yoshihisa , Otani Shuzo
Published: April 2003

Objective and Methods: Serum levels of hepatitis C virus (HCV), a predictor of the response to interferon (IFN) therapy, can fluctuate widely in patients with chronic hepatitis C, even without antiviral therapy. In order to increase the accuracy of predicting the response to therapy, serum samples from 134 patients with chronic hepatitis C were collected twice: 1.0–4.5 months before and just before the start of IFN therapy, and were tested for HCV core protein by a fluorescent enzyme immunoassay. Results: Forty-one (31%) patients had a complete response to IFN and 93 (69%) had no response. The most useful cutoff value between high and low viral loads for predicting the response to therapy was 40 pg/ml of HCV core protein. A complete response was obtained more frequently in 32 of 45 patients with persistently low viral loads than in those with persistently high viral loads (7 of 71) (p < 0.0001). In 2 of 18 patients with a low viral load at one time point but a high viral load at another, the rate of complete response was similar to that in patients with persistently high viral loads. Conclusion: Prediction of the response to IFN therapy based on HCV core protein measurement at two time points before therapy is more reliable than that based on HCV core protein measurement at only one time point.
Molecular Evaluation of the Prevalence of Oncogenic Human Papillomavirus Genotypes in Cervical Acetowhite Lesions
Authors: Rocha-Zavaleta Leticia , Garcia-Carranca Alejandro , Lira de la Cruz Angeles , Barrios Tonatiuh , Valdespino Victor , Cruz-Talonia Fernando
Published: April 2003

The actual prevalence of cancer-related human papillomavirus (HPV) genotypes in cervical acetowhite lesions has not been established. In this work, the presence of oncogenic types of HPV in cervical acetowhite tissue was evaluated by molecular means. The presence of HPV DNA was determined in a group of women with and without cervical acetowhite lesions by a polymerase chain reaction (PCR) using the MY09/MY11 primers. The presence of 13 oncogenic HPV types was evaluated using the Hybrid Capture II test, and the prevalence of HPV type 16 (HPV16) was studied using an HPV16-specific PCR. HPV DNA was detected in 85.9% patients with acetowhite lesions; oncogenic HPV types were found in 83.7% of them; HPV16 was identified in 51.1% of the cases. HPV DNA was detected in 87.3% of the patients without acetowhite changes. Interestingly only 16.8% were infected by oncogenic genotypes and 2.5% were positive for the presence of HPV16. In conclusion, subclinical infection by oncogenic HPV genotypes is associated with the presence of acetowhite cervical tissue (p < 0.0005). Therefore, women showing acetowhite lesions might be at risk of developing cervical cancer.
Cyclophosphamide-Immunodepressed FVB/N Mice: Potentiating the Effects of Testicular Cytomegalovirus Infection
Authors: Tebourbi L. , Emile J.F. , Cerutti I.
Published: April 2003

The aim of this study was to investigate the effect of cyclophosphamide (CY) immunosuppression on the infection of germinal cells following testicular inoculation of male FVB/N mice with murine cytomegalovirus (MCMV). We used CY to modulate the immune status in order to mimic iatrogenic immunosuppression in humans (organ transplantation) as closely as possible. We show that viral pathological manifestations observed in mice treated with this CY-MCMV combination were severer than those observed in immunocompetent male mice infected with MCMV alone. As previously reported, the typical MCMV cellular inclusions were present in interstitial spaces; however, the spermatogenic cells were never directly infected. Nonetheless, at the end of our observation, we obtained definitive necrosis of the testes. These results suggest that germline cell necrosis induces sterility in immunodepressed infected male mice indirectly. In the case of organ transplantation, particular attention should be accorded to male patients receiving CY.
Hospital Management of Children with Acute Asthma Exacerbations in Kuwait: Adherence to International Guidelines
Authors: Hijazi Z. , Abdulmalek A.K. , Al-Taweel F. , Al-Shareda S.
Published: April 2003

Objectives: To evaluate the in-patient management of children with acute exacerbation of bronchial asthma and its adherence to international guidelines. Subjects and Methods: Medical records of 100 consecutive admissions for acute exacerbation of asthma to the paediatric wards at Mubarak Al-Kabeer Hospital, Kuwait, from October through December 1999 were retrieved. Data relevant to asthma symptoms, severity, treatment regimens and discharge plan were collected and evaluated. The mean age of patients was 4.3 years, ranging from 2 to 12 years. Admissions totalled 82 males and 18 females, with hospital stays ranging from 1 to 11 days (mean = 2.6 days). Results: There were no fatalities. Reported episodes were severe (17%), moderate (11%) and mild (9%); degree of severity was not documented in 63 cases. Pulse, respiratory rate, colour and use of accessory muscles were not documented in 48, 48, 47 and 63% of the patients, respectively. Arterial blood gas was checked in 16 patients and pulse oximetry in 71. Full blood count, serum urea and electrolytes were obtained in 86 patients and chest radiographs in 76. All patients received nebulized salbutamol. However, some received additional medications: ipratropium bromide (79%), steroids (95%), intravenous aminophylline (5%) and antibiotics (43%). Two children were shifted to an intensive care unit, 1 of whom needed intubation. On discharge, there was no documentation of follow-up arrangements, or prophylactic anti-inflammatory drugs or other medications in 52, 81 and 32 patients, respectively. Conclusion: Patient management showed deficits, and documentation was inadequate. Areas of particular concern were assessment of patients, unnecessary investigations and use of antibiotics, and lack of post-discharge planning and prophylaxis with steroids. Adherence to the international guidelines was partial.
Radiotherapy for Early Stage of Hodgkin’s Disease at Kuwait Cancer Control Center, Kuwait
Authors: Al-Shemmari Salem H. , Al-Humood Salah A. , Muralidharan K.C. , Varghese V.A.
Published: April 2003

Objective: To evaluate the outcome of using radiotherapy (RT) alone to treat patients with early-stage Hodgkin’s disease (HD). Method: The records of 28 patients with HD treated with RT alone at Kuwait Cancer Control Center between 1980 and 1998 were reviewed. Results: Twenty-three patients had stage I HD and 5 stage II. Two patients had B symptoms, 12 (42.9%) patients lymphocyte-predominant histology, 9 (32.1%) nodular sclerosis and 7 (25%) mixed cellularity. Overall survival and relapse-free survival at 10 years were 100 and 83%, respectively. Conclusion: Our data indicate that the use of RT alone for treatment of early stages of HD appears to be effective.
Effects of Fat, Beef and Fiber in Diets on Activities of Sphingomyelinase, Ceramidase and Caspase-3 in Rat Colonic Mucosa
Authors: Yang Liping , Mutanen Marja , Cheng Yajun , Duan Rui-Dong
Published: April 2003

Objective: The present study investigates the activity changes of sphingomyelinase (SMase), ceramidase and caspase-3 in colonic mucosa of rats induced by high fat and red meat diets. Method: For a period of 3 weeks, rats were fed protein without fat (control), high fat only, high fat with beef, and high fat with fiber (cellulose) diets. The fat content (22.4%) was constant in the three high fat diets. Then, the colonic mucosae were scraped and homogenized and the activities of SMase, ceramidase and caspase-3 determined. Results: Compared to the control diet, the fat diet and fat with beef diet reduced intestinal alkaline SMase by 80 and 84%, respectively; ceramidase activity by 60 and 92%, respectively, and caspase-3 activity by 40 and 75%, respectively. The activities of acid and neutral SMases were also decreased by fat and fat with beef diets but to a smaller extent than those of alkaline SMase. Supplement of fiber in the fat diet had no effect on the changes of alkaline SMase activity but prevented fat-induced decreases in acid and neutral SMase activities and partially prevented those of ceramidase and caspase-3 activities. The activity of intestinal alkaline phosphatase was not changed by any of the diets. Conclusion: Fat, beef and fiber significantly affect the enzymes responsible for sphingomyelin metabolism and apoptosis in the colon. The effects may have implications in colonic tumorigenesis related to dietary factors.
Bronchoesophageal Fistulae Secondary to Tuberculosis
Authors: Lado Lado F.L. , Golpe Gómez A. , Cabarcos Ortíz de Barrón A. , Antúnez López J.R.
Published: April 2003

An elderly patient with a bronchoesophageal fistula secondary to tuberculosis and a 3-month history of cough and dysphagia worsening with deglutition was admitted to hospital. Radiological examination and CT of the thorax revealed mediastinal adenopathy. Bronchoscopy, esophagoscopy and esophagraphy confirmed the presence of a bronchoesophageal fistula. Histological examination of the esophagus and bronchial biopsy specimens revealed nonnecrotic granulomas, and the acid-fast bacilli tested positive for Mycobacterium tuberculosis in respiratory secretions. Antituberculous treatment was started after diagnosis of intrathoracic lymph node tuberculosis with bronchoesophageal fistulization. A month and a half after initiating treatment, paroxistic coughing during deglutition persisted. An esophagoscopy was performed, and the orifice was closed with a fibrin tissue. After 9 months of treatment, the patient was asymptomatic and in good health.
Transbronchial Needle Aspiration in the Diagnosis of Intrathoracic Lymphadenopathy
Authors: Cetinkaya Erdogan , Yildiz Pinar , Kadakal Figen , Tekin Ali , Soysal Fusun , Elibol Senem , Yilmaz Veysel
Published: April 2003

Background: Transbronchial needle aspiration (TBNA) of intrathoracic lymph nodes has been shown to be useful in the diagnosis and staging of bronchogenic carcinoma. The usefulness of TBNA has not been widely investigated in benign disease other than sarcoidosis. Objectives: We investigated the diagnostic value of TBNA in consecutive patients who were referred to Yedikule Hospital of Chest Disease and Thoracic Surgery because of mediastinal and/or hilar adenopathy. Methods: A total of 29 TBNA procedures were performed in 28 patients who had mediastinal or hilar adenopathy identified by computed tomography of the chest. TBNA of enlarged lymph nodes was performed using a flexible bronchoscope (BF 30T, Olympus) and a 19-gauge needle capable of obtaining core biopsy specimens (MW-319 Mill-Rose Laboratories, Mentor, Ohio, USA) from endobronchial or endotracheal locations. All patients had at least three examinations of sputum smears for acid-fast bacilli prior to bronchoscopy and the results of sputum smears were found to be negative. Results: Adequate lymph node samplings were obtained by TBNA in 23 of 29 (79%) procedures. Diagnostic samples were obtained by TBNA in 20 of 29 (69%) procedures. We were able to make a diagnosis in 20 of 23 (87%) patients in whom adequate lymph node samples were obtained by TBNA. TBNA was the only means of diagnosis in 13 of 28 (46%) patients. The diagnoses provided using TBNA were tuberculosis in all of 10 patients (100%), sarcoidosis in 7 of 8 patients (87.5%), lymphoma in 1 of 2 patients (50%), small cell carcinoma in 1 patient and nonspecific lymphadenitis in 1 patient. No complication was observed and there was only minimal bleeding. Conclusions: We conclude that TBNA, using 19-gauge histologic needles through a flexible bronchoscope, is a valuable tool in the diagnosis of intrathroracic adenopathy, particularly in patients with tuberculosis and sarcoidosis. TBNA should be considered in the diagnosis of intrathoracic adenopathy before other invasive procedures.
Anticholinergics in the Treatment of Chronic Obstructive Pulmonary Disease
Authors: Beeh Kai-Michael , Welte Tobias , Buhl Roland
Published: April 2003

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality in the world. In the majority of cases, the disease is the result of years of cigarette smoking. Contributing factors leading to bronchial obstruction in COPD include mucus hypersecretion and an increase in bronchial muscle tone, which is triggered mainly by cholinergic mechanisms. Anticholinergic bronchodilators reduce vagal cholinergic tone, the main reversible component of COPD; hence they are the first-line treatment for bronchial obstruction in COPD. In addition to improving lung function, anticholinergics improve dyspnea, quality of life and exercise tolerance, and they reduce exacerbations. When compared with other bronchodilators, anticholinergics show at least equivalent bronchodilator potency, but with fewer side effects. In addition, due to their unique site of action, anticholinergics can be effectively combined with other bronchodilators. The introduction of new, long-acting anticholinergics is a promising addition to the treatment of COPD and is expected to lead to improved treatment outcomes and improved patient compliance.
A Model of Isolated Autologously Hemoperfused Porcine Slaughterhouse Kidneys
Authors: Grosse-Siestrup Christian , Unger Volker , Fehrenberg Claudia , v. Baeyer Hans , Fischer Axel , Schäper Frank , Groneberg David A.
Published: April 2003

Background: The rapidly evolving field of transplantation research with a focus on ischemic and reperfusion injuries has gained importance since the methodology of organ preservation significantly limits graft survival. Numerous models of isolated perfused kidneys have been established in the past years but limitations such as organ size, perfusate and ethical standards have restricted a widespread research in this area. Methods: A model of hemoperfused isolated porcine slaughterhouse kidneys was established which encompasses the advantages of autologous blood as optimal perfusate and a reduction of animal experiments. Results: The size and geometry of the porcine kidney is more comparable to human conditions and various renal functions, blood parameters and morphology can easily be accessed in the present model. Stable organ function can be maintained over 2 h with an amount of 500–1,000 ml of autologous blood which is metabolically controlled via a dialysis system. Conclusion: In summary, the present model describes a new and economic approach for targeting renal function in transplantation models by combining autologous blood as optimal perfusate with a well-defined organ geometry and function and slaughterhouse animals as a source.
Site of Methylguanidine Production and Factors That Influence Production Levels
Authors: Yokozawa Takako , Muto Yasuko , Wakaki Kunihiko , Kashiwagi Hiroshi
Published: April 2003

The site of methylguanidine (MG) production in the kidney was investigated using animal models of renal disease and cultured renal epithelial cells. In rats with proximal tubular injury induced by adenine, the blood and urinary levels of MG increased as the severity of injury increased. In contrast, in cases of glomerular injury, there were no such changes in MG levels. Thus, it was apparent that proximal tubular injury served to promote MG production. In addition, a marked increase was observed in the intensities of bands attributable to 5,5-dimethyl-1-pyrroline-N-oxide (DMPO)-OH in the electron spin resonance spectrum of the kidney in the rats given adenine. In these rats, the activity of the radical-scavenging enzymes superoxide dismutase, catalase, and glutathione peroxidase was decreased. This suggests that the formation of excessive radicals and deterioration of defense mechanisms that contribute to the development of oxidative stress underlie the enhanced MG production. The experiments using cultured cells revealed that an oxide of adenine, 2,8-dihydroxyadenine (DHOA), directly induced renal tubular injury. These findings indicate that the accumulation of creatinine due to DHOA, combined with oxidative stress, resulted in increased MG production.
Reciprocal Expression of Vascular Endothelial Growth Factor and Nitric Oxide Synthase by Coronary Arterial Wall Cells during Chronic Inhibition of Nitric Oxide Synthesis in Rats
Authors: Sakamoto Hironosuke , Nakamura Tetsuya , Akuzawa Nobuhiro , Masuda Hiroaki , Sumino Hiroyuki , Saito Yuichiro , Ohyama Yoshio , Kurashina Toshiaki , Tamura Junichi , Kurabayashi Masahiko
Published: April 2003

Chronic inhibition of nitric oxide (NO) synthesis by oral administration of NG-nitro-L-arginine methyl ester (L-NAME) causes hypertension and produces arteriosclerosis in rats. Balloon injury induces upregulation of vascular endothelial growth factor (VEGF) in medial smooth muscle cells of the rat arterial wall, and NO secreted by a restored endothelium acts as the negative feedback mechanism that downregulates VEGF expression to basal levels. In this study, we tested the hypothesis that a reciprocal relation between VEGF and NO would be established in a rat model of chronic NO blockade. Male Wister rats received plain drinking water (n = 10) or L-NAME (0.5 mg/ml) in the drinking water (n = 11) for 6 weeks. After 6 weeks, the wall-to-lumen ratios and perivascular fibrosis in the coronary arteries were greater in the L-NAME group than in the control group. NO synthase-positive cells in the intima were abundantly observed in the control group, whereas no such cells were seen in the L-NAME group. In contrast, the number of VEGF-positive smooth muscle cells in the media was greater in the L-NAME group than in the control group. These findings strongly suggest a reciprocal relation between VEGF and NO even in a rat model of chronic NO blockade.
Home Hemodialysis
Authors: Piccoli Giorgina Barbara , Bermond Francesca , Mezza Elisabetta , Quaglia Marco , Pacitti Alfonso , Jeantet Alberto , Segoloni Giuseppe Paolo
Published: April 2003

Background: Home hemodialysis is usually considered a superior therapy, whose decline is related to demographic, social, psychological and financial factors as well as to competition with renal transplantation and PD. Methods: A home hemodialysis program was started in November 1998 in the University of Torino, Italy (200–210 patients on dialysis). Its main features are the tailoring of dialysis schedules and the acceptance of patients with comorbidity. Nurses assist home sessions in case of short-term problems, while the training center ensures follow-up for long-term clinical and logistic problems. Results: The program started in November 1998 on a previous one (active from 1970 to 1998; 6 patients on treatment in November 1998). Since then, 25 more patients joined the program. Out of 31 patients followed since November 1998, 4 were grafted, 2 died, and 2 dropped out from training. In June 2001, 15 patients were on home hemodialysis, 8 on training. Dialysis schedules and controls are flexible and tailored; in June 2001, range of dialysis time was 1.20–5 h; sessions: 2–6; 8 patients were on thrice-weekly dialysis, 7 on daily dialysis; all patients reached target EKRc >10 ml/min (median 15, range 11–24 ml/min). Conclusion: Tailored, flexible schedules allowed home hemodialysis in over 10% of our patients, confirming that there is still room for this treatment in our setting.
Heminephrectomy Causes the Progression of Glomerulosclerosis and Apoptosis in High IgA Strain ddY Mice
Authors: Kusano Hitoshi , Muso Eri , Ono Takahiko , Nogaki Fumiaki , Nomura Keiko , Takeda Toshiya , Miyawaki Shigeki , Matsumori Akira , Yoshida Haruyoshi , Sasayama Shigetake
Published: April 2003

Background: The reduction in nephrons in IgA nephropathy is critical to the prognosis of this disease. However, the immunopathological mechanism of the modifications seen in glomerular lesions is not clear. We thus investigated the influence of nephron reduction by heminephrectomy on renal lesions in a high immunoglobulin A inbred strain of ddY mouse (HIGA mouse), which shows progressive mesangial sclerosis with elevated renal expression of transforming growth factor (TGF)-β. Methods: Five-week-old HIGA mice were heminephrectomized (Nx), and were evaluated in comparison with a sham-operated group (S) at 40 weeks old. Histological findings, immunoglobulin depositions (IgG, IgA, and IgM), and expressions of cytokine and extracellular matrix proteins (TGF-β, fibronectin, collagen type I and IV) were analysed. PCNA and TUNEL stainings were performed with electron microscopic detection of apoptosis. Tissue renin-angiotensin systems (RAS) were also investigated by real-time quantitative RT-PCR. Results: In the Nx group, the glomerular tuft area and ratio of mesangial matrix area per tuft were significantly increased, and the glomerular cell count per tuft area was significantly decreased. Glomerular immunoglobulin deposits of IgG, IgA, and IgM in Nx were all significantly expanded in the paramesangium. The glomerular expressions of TGF-β and the extracellular matrix proteins were significantly increased in Nx mice. In contrast to the significant decrease of PCNA-positive cells, TUNEL-positive cells were significantly increased in Nx. Angiotensin-converting enzyme (ACE) was significantly increased in the renal cortex of Nx. Conclusion: Simple heminephrectomy, other than 5/6 renal ablation, of HIGA mice may be a potential model for research into the progressive glomerulosclerosis of human IgA nephropathy. The pathological role of apoptosis is apparently involved in these disease processes, possibly through upregulated RAS.
Lipid-Lowering Drugs: Are Adverse Effects Predictable and Reversible?
Authors: Muscari Antonio , Puddu Giovanni M. , Puddu Paolo
Published: April 2003

Most of the currently available statins and fibric acid derivatives have been implicated in causing complications either in monotherapy or in combination therapy. Adverse events occur more often with the statins that are metabolized via the CYP enzyme system and its 3A4, 2C9 or 2C19 paths. All compounds interfering with the same cytochrome system may either impair or enhance the elimination of statins. Other factors predisposing to adverse effects are age, female sex, renal insufficiency, electrolyte disturbances, infections and trauma. Complications chiefly concern the hepatic function, skeletal muscles and peripheral nerves. The major adverse effect is myopathy, up to rhabdomyolysis with ensuing acute renal insufficiency. Fibrates bind to peroxisome proliferator-activated nuclear receptors α, with subsequent stimulation of fatty acid oxidation and reduction in the rate of hepatic lipid generation. Fibrates are associated with a number of adverse effects, including liver enzyme elevations, gastrointestinal side effects and rhabdomyolysis. The combination of statins with fibrates may cause serious complications and should be avoided when possible. In order to prevent or minimize adverse clinical outcomes, patients should be closely monitored and informed of the most common symptoms.
The Influence of Node-Fibril Morphology on Healing of High-Porosity Expanded Polytetrafluoroethylene Grafts
Authors: Miura H. , Nishibe T. , Yasuda K. , Shimada T. , Hazama K. , Katoh H. , Watanabe S. , Okuda Y. , Kumada T.
Published: April 2003

Purpose: To manufacture high-porosity expanded polytetrafluoroethylene (ePTFE) vascular grafts with the same internodal distance but different node-fibril morphology, and to evaluate their biologic behaviors in a canine carotid artery implantation model. Materials and Methods: Several types of high-porosity ePTFE vascular grafts with the same inside diameter (4 mm) and wall thickness (650 µm) were manufactured under different heating, stretching conditions. The luminal surface and cross section of the grafts were photographed by scanning electron microscopy and the node-fibril structure was examined. Two typical types of high-porosity ePTFE vascular grafts were then selected and proceeded to an animal study. The test grafts were explanted after an interval of 12 weeks and subjected to histomorphometric analyses. Results: The following two types of high-porosity ePTFE vascular grafts were selected; one had a through-pore structure extending from the outer to the inner surface and the other had a random-node architecture with tortuous path channels extending from the outer to the inner surface. The histomorphometric analyses of thrombus-free surface, thickness of pseudointima, cellular ingrowth, capillary ingrowth, and cellular proliferation revealed no significant differences between the grafts. Conclusion: In high-porosity ePTFE vascular grafts, graft healing enhanced by transmural tissue ingrowth may be not largely dependent on node-fibril morphology. This knowledge will be helpful to design a new type of high-porosity ePTFE vascular grafts available for clinical use.
Prenatal Diagnosis of Pial-Superficial Arteriovenous Malformation
Authors: Reyal Fabien , Vuillard E. , Sibony Olivier , Magnier Suzelle , Oury Jean-Francois , Luton Dominique
Published: April 2003

In the newborn, cerebral pial arteriovenous malformation has been recognized as a cause of congestive heart failure. Prenatal diagnosis allows early medical treatment of cardiac failure and increases the chance of successful neuroradiological intervention. This paper highlights the importance of careful prenatal cerebral examination in cases of cardiac ventricle enlargement.
The Influence of Family History of Stuttering on the Onset of Stuttering in Young Children
Authors: Buck Suzanne M. , Lees Roberta , Cook Frances
Published: April 2003

Content analysis was undertaken of the case records of 61 children who stuttered who were attending a specialist centre for children who stutter. The subjects were divided into two groups, on the basis of family history of stuttering. Positive family histories of stuttering were reported for 44 children and 17 had negative family histories. The two groups were compared in terms of gender ratios, the age of onset and the type of onset (gradual vs. sudden) of stuttering. Those with positive family histories began stuttering earlier than those with no reported family history of stuttering, though this difference was not statistically significant. The type of onset of stuttering was not related to the presence or absence of a family history of stuttering. The findings are discussed in terms of the practicability of this method of data collection.
Effect of Cleft Type on Overall Speech Intelligibility and Resonance
Authors: van Lierde K.M. , De Bodt M. , van Borsel J. , Wuyts F.L. , van Cauwenberge P.
Published: April 2003

The main purpose of this study was to measure and compare the effect of an unilateral cleft lip and palate (UCLP) and a bilateral cleft lip and palate (BCLP) on overall speech intelligibility, nasalance and nasality. An additional objective was to compare the nasalance and nasality patterns of cleft palate children with the available normative data for normal children. The subjects were 37 children with an UCLP (19/37) or a BCLP (18/37) with normal cognitive and motor functions and normal hearing levels. All subjects had a non-syndromic cleft, followed the same surgical protocol and did not undergo secondary pharyngeal surgery. To measure and compare the effect of cleft type, objective and subjective assessment techniques were used. For the objective assessment of nasal resonance the nasometer and the mirror-fogging test were used. Nasalance scores were obtained, while patients produced sounds, read three standard passages or repeated sentences focusing on specific consonants. A perceptual evaluation of speech, the Gutzmann (1913) test and the tests of Bzoch (1989) were used as subjective assessment techniques. The perceptual assessment of the overall speech intelligibility was based on the spontaneous speech and reading or repeating of the nasometric sentences. These samples were judged by three speech pathologists using a 4-category nominal scale. A subjective test (Morley, 1945) was used to evaluate the velopharyngeal mechanism. The findings of the present study show no statistically significant differences for nasalance values, nasality and overall speech intelligibility between the UCLP and BCLP children. Significant differences were found between the data of the normal group and the cleft palate children. These differences included nasalance values as well as nasality data and overall speech intelligibility.
n–3 Fatty Acids and Cardiovascular Disease
Authors: Westphal Sabine , Luley Claus
Published: April 2003

During 3 decades considerable knowledge on n–3 fatty acids has accumulated, showing that they are not only an essential nutrient but that they favorably influence coronary heart disease. The paradigm that n–3 fatty acids act exclusively by lipid reduction has been challenged. n–3 fatty acids have a potent antiarrhythmic action, inhibit thrombogenesis, improve endothelial reactivity, lower blood pressure and reduce proinflammation. Epidemiologic studies showed an inverse correlation between the consumption of fish or other sources of dietary n–3 fatty acids and cardiovascular events. Strong confirmation of their protective effects came from randomized clinical trials all of which reported relevant benefits for patients with preexistent coronary heart disease.
Carpal Bone Maturation Assessment by Image Analysis from Computed Tomography Scans
Authors: Canovas F. , Banegas F. , Cyteval C. , Jaeger M. , DiMéglio A. , Bonnel F. , Sultan Ch.
Published: April 2003

Bone maturation is the only reliable indicator of growth and its radiologic assessment with or without automated systems is a qualitative method. Image processing allows the study of bone maturation with quantitative data. Carpal bone maturation was studied in 20 children (13 boys and 7 girls, ages ranging from 4 to 15 years) without any clinical evidence of endocrine disease by image analysis from computed tomography (CT) scans. Each wrist CT scan was processed in order to extract the carpal bones and to measure quantitative data regarding volume, axes of inertia and density for each bone. The volumes and the length of the inertia axes were significantly correlated with age. Whatever the age, there were strong correlations between the volume or the length of the main inertia axis of one carpal bone and that of all others. The decrease in the carpal bone volume measured from the processing procedure compared with the theoretical volume of bone defined from the length of the three inertia axes indicated a change in bone shape during growth. Although the mean density was constant, there was an increase in the standard deviation of density with age. Skeletal maturity assessment with image analysis from CT scans seems to be a good complementary investigation to determine bone age in children.
Thyroid Function and Obesity in Children and Adolescents
Authors: Stichel H. , l’Allemand D. , Grüters A.
Published: April 2003

The aim of this retrospective study was to investigate the frequency of thyroid dysfunction as assessed by TSH, T3 and T4 in a large cohort of 290 obese and 280 healthy children. In addition, thyroid autoantibodies were measured in random subgroups of 123 obese and 80 control children, iodine excretion in 50 and thyroid volume in 23 of the obese children. Elevated TSH levels (>4 U/l) were found in 22 obese children (7.5%), but only in one control (0.3%). The medians of TSH and T3 concentrations were normal, but significantly higher in the obese group than in the controls, while T4 levels did not differ. The prevalence of positive thyroid autoantibodies was increased in the obese children, for the most part in those with elevated TSH. There was no evidence for iodine deficiency as a cause of the average increase of TSH. We conclude that in childhood obesity TSH and T3 levels are significantly increased; in most cases, however, these increases are not accounted for by thyroid autoimmunity or iodine deficiency. As a consequence, TSH elevations with normal thyroid hormone levels in obese children don’t need any thyroxine treatment, if thyroid disorders were definitely excluded beforehand.
The Effects of Growth Hormone Deficiency and Growth Hormone Replacement Therapy on Bone
Authors: Cowell Christopher T. , Wüster Christian
Published: April 2003

Recently, several reports have described the effects of growth hormone (GH) deficiency (GHD) on bone and the associated potential benefits of GH therapy. Not all of these reports have, however, been consistent and the results are debated. Some of the contention surrounding this issue reflects disagreement about which bone parameters are the best indicators of bone strength and fracture risk. In November 1999, a meeting was held in Taormina, Italy, to discuss the assessment of bone in patients with GHD and the effects of GH therapy on the skeleton. The participants included endocrinologists, orthopaedists and biophysicists from around the world. During the meeting, the advantages and disadvantages of the various indicators of bone strength were defined. In considering GH therapy, the delegates agreed that it had beneficial effects on bone in adults with GHD, but that further studies were needed in GH-deficient children. Finally, the participants stressed the need for more data to clarify which indicator of bone strength is the most appropriate to use in adults and children with GHD, and to define fully the role of GH therapy in bone metabolism. It was recognized that pharmacoepidemiological surveys, such as KIGS (Pharmacia International Growth Database) and KIMS (Pharmacia International Metabolic Database), are valuable sources of such data, and are, therefore, important in the development of evidence-based medicine.
Possible Roles of Insulin-Like Growth Factor in Regulation of Physiological and Pathophysiological Liver Growth
Authors: Skrtic Stanko , Wallenius Kristina , Sjögren Klara , Isaksson Olle G.P. , Ohlsson Claes , Jansson John-Olov
Published: April 2003

Background/Aims: Almost all circulating insulin-like growth factor-1 (IGF-1) is produced and secreted from the liver. However, the possible role of IGF-1 in local regulation of liver functions including liver growth is unclear. In the present study, we investigated the role of IGF-1 on liver growth in vivo and in hepatic stellate cell function in vitro. Results: Liver-specific knock-out of the IGF-1 gene by use of the cre-loxP system caused enhanced liver growth, possibly reflecting increased growth hormone (GH) secretion due to decreased negative feedback by IGF-1. Studies on cultured rat hepatic stellate cells (HSC) showed that IGF-1 and hepatocyte-conditioned medium (PCcM) time- and dose-dependently increased hepatocyte growth factor (HGF) mRNA and HGF immunoreactivity. IGF-1 and PCcM also enhanced DNA synthesis in the HSC cultures. The PCcM did not contain bioactive IGF-1 and was also able to stimulate proliferation when prepared under serum- and hormone-free conditions. Conclusion: In vivo results show that IGF-1 is not essential for normal growth of the intact liver. The in vitro results indicate that both IGF-1 and IGF- 1-independent factor(s) from hepatocytes can stimulate HGF production by HSC. It remains to be investigated whether these effects are of importance for liver regeneration or pathological conditions.
Insulin Resistance and Insulin-Like Growth Factors in Children with Intrauterine Growth Retardation
Authors: Canfarani Stefano , Geremia Caterina , Germani Daniela , Scirè Giuseppe , Maiorana Arianna , Boemi Sergio
Published: April 2003

Aims: To investigate (a) the prevalence of insulin resistance in children with intrauterine growth retardation (IUGR); (b) whether catch-up growth is associated with a higher risk of insulin resistance; (c) the insulin-like growth factor (IGF) system status. Methods: 49 children with IUGR aged 9.1 ± 3.3 years underwent anthropometric measurements, and assessment of insulin resistance and IGF system parameters. A fasting glucose/insulin ratio (G/I) <6 was chosen as suggestive of insulin resistance. Results: 11/49 (22%) children had a G/I <6. Postnatal growth closely correlated with birth size and actual body mass index (BMI). None of the insulin resistance parameters was related to linear growth and BMI. Liver function markers were significantly related to insulin sensitivity status. The IGF system status was normal and did not correlate with insulin resistance indicators. Conclusions: (a) Children with IUGR have a high prevalence of reduced insulin sensitivity; (b) postnatal catch-up growth is related to intrauterine growth and actual nutritional status; (c) insulin sensitivity status is not related to postnatal growth but to liver function; (d) IGF system is normal and not related to the insulin resistance parameters during childhood.
Insulin-Like Growth Factor -I Deficiency
Authors: Camacho-Hübner Cecilia , Savage Martin O.
Published: April 2003

The insulin-like growth factor (IGF) system composed of two ligands, their receptors and regulatory proteins (acid-labile subunit and IGF-binding proteins) plays a central role in the regulation of growth and development in mammals. In addition to its key role in the stimulation of cellular proliferation and growth, IGF-I has important effects on carbohydrate, protein and bone metabolism. The molecular biology and physiology of the IGF system are complex, resulting in many potential mechanisms of IGF deficiency. Briefly, IGF-I deficiency may result from a primary defect in the IGF-I gene, its promoters, or may be secondary to a defect outside the gene itself. It may also result as a consequence of growth hormone (GH) deficiency, GH receptor/post-receptor abnormalities or abnormalities of the IGF-I receptor. The purpose of this presentation is to review the different types of IGF-I deficiency using the well-characterized clinical conditions with its associated biochemical and molecular defects. The clinical consequences in terms of phenotype-genotype, linear growth and body composition in patients with primary and secondary IGF deficiency will be presented, together with results from recombinant human (rh)IGF-I replacement therapy. Finally, as primary IGF-I deficiency is associated with insulin resistance, some of the metabolic actions of IGF-I will be briefly discussed.
SHOX in Short Stature Syndromes
Authors: Blaschke Rüdiger J. , Rappold Gudrun A.
Published: April 2003

Linear growth is a multifactorial trait that is influenced and regulated by a combination of environmental and internal factors. Among the intrinsic determinants of final body height, genetic factors have become more and more prominent, and the list of genes involved in growth-related processes has been extended accordingly. One of the most exciting additions to this list is represented by the discovery of the pseudoautosomal gene SHOX. Originally described as a gene responsible for idiopathic short stature, it has become clear that SHOX mutations can also cause mesomelic short stature and Madelung deformity in Léri-Weill syndrome. In addition, recent studies implicate SHOX haploinsufficiency in a variety of somatic Turner syndrome stigmata.
Cushing’s Disease in Childhood: Presentation, Investigation, Treatment and Long-Term Outcome
Authors: Savage M.O. , Lienhardt A. , Lebrethon M.-C. , Johnston L.B. , Huebner A. , Grossman A.B. , Afshar F. , Plowman P.N. , Besser G.M.
Published: April 2003

Seventeen patients with Cushing’s disease (CD) were treated from 1978 to 2000. There were 11 males and 6 females aged 6.8–18.8 years (mean age 13.0 ± 5.9 years). Presenting features were: weight gain (100%); growth failure (71%); hirsutism (53%); striae (53%); hypertension (47%). Mean age of patients with striae was 15.2 ± 2.3 years, without striae 10.3 ± 3.3 years. Median height SDS was –1.81 (range –0.28 to –4.17), 53% having height SDS < –1.8. The height velocity in 6 subjects was subnormal (0.9–3.8 cm/year). Median BMI SDS was 2.29 (range 1.72–5.06). Cushing’s disease was confirmed by detectable serum ACTH, median 28 ng/l (range 12–99, NR <10–50) (n = 15); loss of cortisol circadian rhythm values at midnight ranging from 216 to 1,080 nmol/l (NR <50) (n = 15); lack of cortisol suppression (NV < 50 nmol/l) during low-dose dexamethasone suppression test (LDDST) (0.5 mg 6-hourly × 8) (n = 14); and >50% suppression of cortisol compared with the basal value during high-dose dexamethasone suppression test (HDDST) (2 mg 6-hourly × 8) (n = 14). A CRH test (1 µg/kg i.v.) showed an increase of cortisol from 12 to 217% (median 73.5%) (n = 16). Pituitary imaging (CT/MRI) showed an image consistent with microadenoma in 6/17 patients, but there was concordance between pituitary imaging and surgical findings in 1/11 patients (9%). Inferior petrosal sinus sampling (IPSS) for ACTH after CRH was performed in 11 subjects (age 10.7–18.8 years). Central to peripheral ACTH ratios were >2 (2.5–157.2) in 10/11 patients. The inter-petrosal sinus ACTH gradient was >1.4 in 10 patients (2.1–20.8), indicating lateralization of ACTH secretion. In 10 patients (91%), the side of the tumour on IPSS was predictive of findings at surgery. Therapy consisted of transsphenoidal microadenomectomy (TSS) in 16 patients and bilateral adrenalectomy (1978) in 1. Following TSS alone, 7 patients were cured (cortisol <50 nmol/l) and 2 were in remission (cortisol <300 nmol/l), i.e. 56%. Seven had persisting hypercortisolaemia and underwent pituitary irradiation (4,500 cGy). Therapeutic outcome for a median of 8 years (0.5–24 years) resulted in cure of CD in 14/17 patients (82%) and remission in 1. Linear growth after TSS ± pituitary irradiation in 10 subjects showed no short-term catch-up growth, with peak growth hormone (GH) 0.5–20.9 mU/l to insulin tolerance test (ITT)/glucagon. Eight patients were treated with human growth hormone (hGH) (14 U/m2/week) combined in 3 with GnRH analogue. The mean final (n = 6) or latest (n = 4) height SDS was –1.36. The difference between final/latest height SDS and target height SDS was 0.93 ± 1.13, i.e. less (p = 0.005) than the difference between height SDS and target height SDS at presentation, i.e. 1.72 ± 1.26, indicating long-term catch-up growth.
Investigating Familial Endocrine Neoplasia Syndromes in Children
Authors: Johnston L.B. , Chew S.L. , Lowe D. , Reznek R. , Monson J.P. , Savage M.O.
Published: April 2003

Familial endocrine neoplasia syndromes multiple endocrine neoplasia (MEN) type 1, MEN type 2 and von Hippel Lindau (VHL) can now be diagnosed genetically in childhood. Paediatric endocrinologists must therefore be prepared to investigate and manage these children. This paper provides an overview of the major features of these syndromes and suggests protocols for regular screening of children known to be at risk of developing these disorders.
Metabolic Syndromes in Human Immunodeficiency Virus Infection
Authors: Macallan Derek C.
Published: April 2003

Infection with human immunodeficiency virus (HIV) is associated with marked disturbance of metabolism affecting the metabolism of carbohydrates, fats and proteins. In the first decade of clinical experience of HIV, the primary clinical manifestation of such disturbed metabolism was wasting. Such wasting was often severe and contributed significantly to the morbidity and mortality of AIDS. Mechanistic studies demonstrated that in addition to the effects of altered intermediary metabolism, reduced food intake played a major role in the causation of AIDS-related wasting. More recently, potent anti-retroviral drugs have dramatically changed the clinical consequences of HIV infection. Wasting has become far less frequent among infected patients and occurs in only a small percentage of subjects on effective anti-retroviral therapy. However, a new constellation of metabolic syndromes has become apparent characterized by altered body fat distribution (‘lipodystrophy’), lactic acidosis and evidence of mitochondrial dysfunction. The mechanistic basis for such syndromes is currently unclear, but is the subject of ongoing research.