bluuebunny/crossref_metadata_2025 huggingface dataset:
Correlation of Tensile Strength with Bursting Pressure in the Evaluation of Intestinal Anastomosis
Authors: Ikeuchi Daisuke , Onodera Hisashi , Aung Tun , Kan Shugen , Kawamoto Kazuyuki , Imamura Masayuki , Maetani Shunzo
Published: April 2003

Background: Although bursting pressure and tensile strength have long been measured to evaluate anastomotic techniques, it has yet to be clarified whether or not they are correlated, what implications they have, and which should be used as a gold standard. Material and Methods: Using an experimental model to estimate pressure and tension in the same colonic anastomosis, the following variables were measured in 48 rats between days 0 and 14: bursting pressure (BP); minimal tensile strength (MITS) necessary to break a part of the anastomosis, and maximal tensile strength (MATS) needed to disrupt the whole anastomosis. Also, circulatory wall tension (CWT) was derived from BP and the anastomotic circumference (AC), and longitudinal wall tension (LWT) from MITS and AC. These variables were compared using correlation and regression analysis. Results: During the lag phase (days ≤4) there was poor correlation between pressure-related and tension-related variables whereas highly significant correlations were noted in the subsequent fibroplastic phase (day ≥5). It was shown by regression lines that positive MITS and MATS were expected when BP was zero. Conclusion: Contrary to the previous assumption, no correlation was found between BP and tensile strength in the critical postoperative period. Based on our present and previous studies, measurement of MITS is recommended to evaluate the healing of colonic anastomosis.
Intraoperative Localization of Right-Sided Small Colonic Lesions: A Novel Use of the Cholangioscope
Authors: Utsunomiya Tohru , Saku Motonori , Emi Yasunori , Ikejiri Kohji , Suzuki Minoru , Saitsu Hideki , Yakabe Shigeru , Nonaka Michiyasu , Muranaka Toru , Yoshida Kohji
Published: April 2003

Background/Aim: We describe a novel use of the cholangioscope to help in the intraoperative localization of small colonic malignancies on the right side of the colon. Methods: A small incision was made at the base of the appendix and a cholangioscope was inserted into the ascending colon through the incised hole of the appendix. Results: The site of the lesion was precisely determined by palpating the distal end of the cholangioscope while observing the area right under it. Conclusion: Our procedure therefore appears to be worthy of consideration in patients with small colonic lesions on the right side of the colon in whom preoperative endoscopic marking techniques might otherwise be required.
Mitotic Index Is the Best Predictive Factor for Survival of Patients with Resected Hepatocellular Carcinoma
Authors: Ouchi Kiyoaki , Sugawara Tohoru , Ono Hidemaro , Fujiya Tsuneaki , Kamiyama Yasuhiko , Kakugawa Yoichiro , Mikuni Junichi , Yamanami Hideaki , Komatsu Satoshi , Horikoshi Akira
Published: April 2003

Background: In patients with hepatocellular carcinoma (HCC), tumor recurrence is not infrequent after resection. It is presumed that characteristics of the tumor such as cellular malignancy might influence the prognosis of the patients in association with tumor stage and radicality of the procedure. Methods: Univariate and multivariate analyses were used to retrospectively determine the clinicopathologic factors potentially related to survival in 40 patients who underwent hepatectomy for HCC. Results: In univariate analysis, tumor stage I or II, mitotic index of 4 or less/10 random high-power fields, solitary tumor, and curative resection were significantly correlated with better survival. In multivariate analysis, the mitotic index and surgical curability were independently significant variables influencing survival of patients, and the mitotic index was the best predictive factor. A highly significant correlation was found between the mitotic index and Ki-67 labeling index. Compared to tumors with a mitotic index of 4 or less, those with a mitotic index of 5 or more had a higher association with multiple tumors and advanced tumor stage, which preclude curative resection. Conclusion: Analysis of the mitotic index is quite simple, and the mitotic index could be a useful factor for predicting the long-term survival of patients with HCC following hepatic resection.
Perforation of Gastric Ulcer Associated with Paraesophageal Hernia Causing Diffuse Peritonitis
Authors: Rakic S. , Hissink R.J. , Schiff B.W.
Published: April 2003

Background/Aims:  Free peritoneal perforation of a gastric ulcer associated with paraesophageal hernia causing diffuse peritonitis is an extremely rare event. Methods: Two new cases of this rare condition and the specificities of management are described. Results: One patient recovered well after surgery, while the other died with signs of persisting sepsis and multiple system organ failure. Conclusion: In the wide spectrum of complications related to paraesophageal hernia, free peritoneal perforation of an associated ulcer seems to be one of the gravest. Early elective repair of the paraesophageal hernia is justified.
Seromuscular Enteric Pedicles andProsthetic Aortic Graf t Complications in a Porcine Abdominal Trauma Model
Authors: Anderson Charles A. , Sawyer Michael A.J. , Cordts Patricia A. , Cordts Paul R. , Demaioribus Christopher A. , Nauschuetz Karen N.
Published: April 2003

Background/Aims: Abdominal vascular trauma may require prosthetic grafting despite peritoneal contamination by concurrent visceral injury. This study tested the use of vascularized, seromuscular enteric pedicles (VSEP) against the development of vascular prosthetic complications, in a porcine abdominal trauma model. Methods: Eight pigs underwent aortic transection and reconstruction with a Dacron interposition graft (DIG). A standard bacterial inoculum soaked the DIG in situ. An enteric segment was isolated on its mesenteric pedicle, and the mucosa stripped. This VSEP was wrapped around the DIG and oversewn. Animals received antibiotics for 5 days. Endpoints were 2-week survival, or evidence of sepsis. The animals underwent explantation of the DIG, VSEP, and native aorta for the purposes of histological, and microbiological analyses, and scanning electron microscopy (SEM). Outcome measures were graft infection, graft thrombosis, tissue incorporation, and anastomotic integrity. Results: Two pigs were excluded for perioperative death. All study group animals (n = 6), survived 2 weeks. Infection and thrombosis were found in 0/6 (0%). Incorporation and anastomotic integrity were evident in 6/6 (100%). VSEP had intact blood supplies. SEM demonstrated viable muscle, microcirculation, and fibroplasia in VSEP. Conclusion: We conclude that VSEP may help prevent prosthetic graft complications in the contaminated setting.
Recurrent Idiopathic Perforations of the Small Intestine
Authors: Losanoff Julian E. , Kjossev Kirien T.
Published: April 2003

Background/Aims: Idiopathic perforation of the small intestine is extremely rare. The definition depends on the absence of any detectable pathology that could be responsible for the perforation. This study was undertaken to outline the criteria for determination of the condition. Methods: Case report and review of the literature. Results: A 50-year-old male patient underwent surgery including laparostomy and planned reexplorations for multiple recurrent small intestinal perforations of unknown origin; the patient made an uneventful recovery. Extensive investigations were carried out to search for any pathology that could explain the occurrence of perforations, but yielded no results. Conclusions: Further studies will possibly give more information concerning idiopathic perforation of the small intestine, provided that judicious criteria for its determination are applied.
Intermittent Activity-Induced Hemobilia Caused by Liver Hemangioma
Authors: Birth M. , Ortlepp J. , Bontikous S. , Amthor M. , Weiser H.-F. , Bruch H.-P.
Published: April 2003

Background: Intestinal bleeding of unknown origin can lead to a difficult workup. Abdominal colic, melena/hematemesis, and jaundice represent the pathognomonic triad for hemobilia, but clinical presentation and etiology of this entity are varying. Seldom all of these symptoms are present, and rarely does hemobilia cause melena or hematemesis. Often the correct diagnosis is missed. Patients frequently have a long history of complaints and inadequate therapy. Case Report: We report on a patient who complained of repeated, severe epigastric pain and massive melena induced by exercise activity. After 2 years of complaints and an unnecessary operation, ultrasound detected a liver hemangioma. It was supposed that the hemangioma was causing hemobilia during strenuous physical activity. The patient underwent a partial liver resection to eliminate the hemangioma. All complaints resolved, and the patient remained asymptomatic postoperatively. Conclusions: Physicians should be aware of hemobilia as a rare cause of upper gastrointestinal bleeding, especially if esophagogastroduodenoscopy cannot demonstrate any bleeding source. Ultrasound is able to visualize many diseases leading to hemobilia and should be integrated into the early workup of unclear intestinal bleedings.
Electrocoagulation of Perianal Warts: A Word of Caution
Authors: Ammori Basil J. , Ausobsky John R.
Published: April 2003

Background: Perianal warts are common, and may be extensive. Electrocoagulation is a recognised management option. Method: A 20-year-old male underwent electrocautery of extensive perianal warts. He presented 3 months postoperatively with constipation and inability to defecate. Examination revealed severe perianal stricture, which necessitated a defunctioning colostomy. Result: A gradual and spontaneous resolution of the stricture was observed over the following 18 months. Closure of the colostomy was followed by satisfactory anal function. Conclusion: Electrocautery of extensive perianal warts should be used with caution. Preservation of healthy skin bridges between lesions is essential if perianal stricture is to be avoided, and may best be achieved by sharp scissors dissection.
Intrahepatic Biliary Cystadenoma Causing Luminal Common Bile Duct Obstruction
Authors: Sutton C.D. , White S.A. , Berry D.P. , Dennison A.R.
Published: April 2003

Background: Biliary cystadenomas are rare cystic tumours that arise in the liver or less frequently in the extrahepatic biliary system. They are commoner in middle-aged women, their most favoured site is the right hepatic lobe. Methods: Case report and review of the literature. Results: We present only the second case of an intrahepatic cystadenoma causing luminal obstruction of the common bile duct. Clinical presentation is often non-specific and can prove to be a diagnostic challenge. Conclusion: Wide local excision of biliary cystadenomas is recommended, with regular radiological follow-up.
Esophageal Leiomyomatosis in a Woman with a History of Vulvar Leiomyoma and Barrett’s Esophagus
Authors: Compagnoni Gia M. , Talamonti Mark S. , Joob Axel , Ergun Gulchin A. , Rao Sam
Published: April 2003

Background: The diagnosis and treatment of esophageal pathology remains a challenge despite advances in preoperative endoscopy, radiographic staging, and perioperative care. Case Report: In this article, we present an interesting case of esophageal leiomyomatosis in a woman with a history of vulvar leiomyoma and Barrett’s esophagus. This paper represents the first reported simultaneous occurrence of these three pathologic entities in the English literature. Conclusions: The clinical presentation and characteristic pathologic findings in patients with esophageal leiomyomatosis are reviewed. Diagnostic and therapeutic approaches to esophageal masses are discussed including the indications for esophageal resection.
Lymphoepithelial Cyst in the Pancreas
Authors: Anagnostopoulos Petros V. , Pipinos Iraklis I. , Rose William W. , Elkus Robert
Published: April 2003

Background: Lymphoepithelial cysts of the pancreas constitute a rare clinicopathologic entity. Case Report: We report a case of lymphoepithelial cyst of the pancreas and review the world literature. Results: Lymphoepithelial cysts are true pancreatic cysts lined by squamous epithelium and surrounded by mature lymphoid tissue. The cyst arises typically in middle aged men, and is usually asymptomatic or causes nonspecific abdominal complaints. There is no specific serologic marker for this entity. None of its radiologic characteristics can help differentiate it from other cystic lesions of the pancreas. Fine-needle aspiration cytology may be able to suggest its benign nature and identify it as a true cyst of the pancreas. The outcome after surgical excision is uniformly good with good symptom control and no recurrences. Recommendations: In the symptomatic patient or the asymptomatic patient with acceptable surgical risk a simple cyst excision should be performed after verification of the diagnosis with frozen section. In the asymptomatic patient with a high surgical risk, in whom fine-needle aspiration suggests the diagnosis of a lymphoepithelial cyst, observation of the lesion is recommended. When simple cyst excision is technically not possible, extensive resections/reconstructions should be avoided and drainage/bypass procedures may be considered.
Effects of N-Acetylcysteine on Pulmonary Macrophage Activity after Intestinal Ischemia and Reperfusion in Rats / with Invited Commentaries
Authors: Börjesson Anna , Wang Xiangdong , Sun Zhengwu , Wallén Rita , Deng Xiaoming , Johansson Eric , Andersson Roland
Published: April 2003

Background/Aims: Intestinal ischemia and reperfusion (I/R) is considered to be a critical and triggering event in the development of distal organ dysfunction after a variety of insults. It appears that activated leukocytes, especially polymorphonuclear granulocytes (PMNs), and reactive oxygen species are important mediators in the process. In the present study, the aim was to evaluate the behavior of pulmonary macrophages, acute lung injury and pulmonary endothelial permeability after intestinal I/R, together with potential alterations in pulmonary endothelial and epithelial ultrastructure and cellular membrane system integrity. Methods: Intestinal ischemia for 40 min was followed by reperfusion for 12 h in the rat. Macrophage uptake of radiolabeled bacteria, levels of pulmonary blood content assessed by radiolabeled red blood cells and pulmonary endothelial permeability of radiolabeled albumin, as well as pulmonary endothelial and epithelial ultrastructure and cellular membrane system integrity by the use of scanning electron microscopy and a tracer was evaluated after 12 h reperfusion. Treatment with the free radical scavenger N-acetylcysteine (NAC) administered prior to reperfusion was evaluated. Results: Overactivation of pulmonary macrophages was noted after intestinal I/R, as was a significant decrease in pulmonary blood content. No increase in pulmonary albumin leakage or increase in pulmonary water content was found after intestinal I/R as compared to controls. Treatment with NAC prevented against intestinal I/R-induced overactivation of pulmonary macrophages and a decrease in pulmonary blood content. Conclusion: Reactive oxygen species may be involved in the regulation of pulmonary macrophage function and pulmonary circulation after intestinal I/R.
Biliary Stricture due to Hypertrophied Liver Rotation after Right Hepatic Lobectomy
Authors: Tekin Ahmet , Perek Sadık
Published: April 2003

Background: After partial hepatectomy, liver regeneration occurs with the hepatocyte mass to its almost previous size. Biliary stricture due to hypertrophied liver rotation following partial hepatectomy is uncommon and its management still remains controversial. We encountered extrahepatic biliary stricture due to hypertrophied left lobe rotation in 2 patients who had right hepatic lobectomy for liver trauma. Herein, we present our experience with the modified Longmire procedure for the management of this complication. Results: There were no complications during the early postoperative period in either of the patients. After the Longmire procedure, the first patient was followed for 5 months with some elevation in liver enzymes and the other was followed for 14 months with normal liver function tests. Both of the patients are completely symptom free postoperatively. Conclusion: The present experience suggests that the modified Longmire procedure is the most promising surgical approach to the management of biliary stricture due to hypertrophied left lobe rotation after right hepatic lobectomy.
Pseudo-Meigs’ Syndrome Caused by Secondary Ovarian Tumors from Gastrointestinal Cancer
Authors: Nagakura Shigenori , Shirai Yoshio , Hatakeyama Katsuyoshi
Published: April 2003

Background: Pseudo-Meigs’ syndrome is a condition characterized by nonmalignant ascites and/or pleural effusion caused by pelvic tumors other than solid benign ovarian tumors. This syndrome has only rarely occurred in association with gastrointestinal cancers. Method: We treated a 53-year-old woman who developed this syndrome due to ovarian metastasis from colon cancer. Diagnostic work-up for abdominal distension disclosed a sigmoid colon cancer and bilateral ovarian masses. Ultrasonography demonstrated massive ascites and a right pleural effusion. Repeated cytologic examinations of both effusions revealed no malignant cells. Laparotomy disclosed no peritoneal dissemination. A radical sigmoidectomy and hysterectomy with bilateral salpingo-oophorectomy were performed. Results: Histologic examination confirmed ovarian metastases from the colonic primary tumor. After resection, both effusions disappeared promptly, confirming a diagnosis of pseudo-Meigs’ syndrome caused by sigmoid colon cancer. The patient remains alive with disease after 52 months. Conclusion: Among 6 reported occurrences with gastrointestinal tumors including our case, the primary site was the colon or rectum in 5 and the stomach in 1. Two cases were due to Krukenberg tumors. Three patients with documented outcomes were alive 108, 52, and 12 months after resection. Clinicians should note that gastrointestinal cancers, especially colorectal tumors, rarely may cause pseudo-Meigs’ syndrome and resection may provide long-term palliation.
Promotion of Evaluation as a Strategy towards an Effective Substance Prevention
Authors: Ostaszewski Krzysztof
Published: April 2003

A growing number of European initiatives focusing on the evaluation and monitoring of substance abuse prevention is observed. At the beginning of the 90s a team from the Institute of Psychiatry and Neurology in Warsaw, Poland, began a project designed for the promotion of evaluation in the field of substance abuse prevention. The project included outcome studies on popular school-based programs and development of teaching materials and publications to popularize the concept and methods of evaluation. As results of the project several outcome studies were completed, several scales for evaluating alcohol prevention programs were developed, a number of articles and a handbook on evaluation were published.
West German Drinking Patterns in 1984 and 1990
Authors: Bloomfield Kim
Published: April 2003

Basic drinking patterns are examined with regard to sociodemographic correlates for the years 1984/1986 and 1990/1992 by a secondary analysis of data from representative samples of the former West German general population. Data come from the National Health Survey of the German Cardiovascular Prevention Study in which the former West German non-institutionalized general population aged 25–69 years was sampled through multistage probability methods. In 1984, 91% of West Germans were drinkers, 16% were daily drinkers, and 8% consumed a mean of 60 g or more of ethanol per day. These figures decreased slightly but significantly by 1990. Despite a downward trend in consumption between 1984 and 1990, Germany remains a ‘wet’ culture.
Outpatient Opiate Detoxification Treatment with Buprenorphine
Authors: Diamant K. , Fischer G. , Schneider C. , Lenzinger E. , Pezawas L. , Schindler S. , Eder H.
Published: April 2003

In an open study design, 50 opioid-dependent subjects (DSM-IV: 304.0) were investigated in a gradual detoxification treatment with buprenorphine. The study was performed at the drug addiction outpatient clinic of the Department of General Psychiatry at the University of Vienna. Subjects had to contact the outpatient clinic on a daily basis and buprenorphine was administered according to their clinical status. Withdrawal symptoms were evaluated by applying the WANG scale. Urine samples were screened for drug toxicology to exclude additional consumption. In this investigation buprenorphine was applied sublingually in a free dosage scheme aimed at completing detoxification treatment within 10 days by reducing buprenorphine on a daily basis. A mean daily dosage of 2.3 mg buprenorphine was required by patients on day 1 of the treatment period. The highest mean daily buprenorphine dosage was given on day 2, followed by a daily reduction over the study period. The result of this open study design revealed that a gradual daily reduction of buprenorphine might be a successful alternative outpatient detoxification treatment in opioid-dependent subjects. Compliance was 70%, the reported and evaluated withdrawal symptoms during the study period were moderate.
Treatment Outcome in Alcoholism – A Comparison of Self-Report and the Biological Markers Carbohydrate-Deficient Transferrin and γ-Glutamyl Transferase
Authors: Mundle Götz , Ackermann Klaus , Günthner Arthur , Munkes Jörg , Mann Karl
Published: April 2003

The primary source for evaluating treatment outcome in alcoholism is usually verbal self-report. Because the validity of self-report is often doubted, more objective markers for treatment outcome are needed. In this study, we compared self-report data from 238 male alcohol-dependent patients participating in a combined 6-week inpatient followed by a 1-year outpatient treatment program with the biological markers carbohydrate-deficient transferrin (CDT) and γ-glutamyl transferase (GGT). According to self-report, over 70% of the patients had a positive treatment outcome (57% abstinence, 16% intermediate relapse). These results are supported by the general reduction of CDT and GGT during the treatment period (p < 0.001). When we performed a cross-sectional analysis at 6 months during the outpatient program, there was a high consistency of self-report data with the biological markers (CDT 93%, GGT 91%, CDT/GGT 85%). Our results support the hypothesis that in abstinence- oriented treatment programs, self-reports are valid and can be used as the basis of measurement for treatment outcome.
Drug Treatment in Contemporary Anthropology and Sociology
Authors: Hunt Geoffrey , Barker Judith C.
Published: April 2003

The relatively slim social science literature on drug treatment is reviewed. Attention is paid to the institutionalization of treatment at the meso (local community or clinic) level and the micro (client) level rather than to the more commonly examined macro (societal or national) level. The inter-penetration across these levels of ideologies and practices around drugs is revealed through discussion of the targeting of certain populations for treatment, methods of client control in treatment settings, and the client’s view of treatment. In the literature, drug users are often presented as passive individuals, subject to various forms of restrictive social control in therapeutic settings. Their perspective on the processes or efficacy of treatment is rarely sought. The concept of drug treatment as necessarily beneficial to clients is questioned in this paper.
Platelet Monoamine Oxidase Activity in Alcoholics with and without a Family History of Alcoholism
Authors: Soyka Michael , Bondy Brigitta , Benda Ellen , Preuss Ulrich , Hegerl Ulrich , Möller Hans-Jürgen
Published: April 2003

A number of studies point at platelet monoamine oxidase (MAO) activity being reduced in alcoholics with a family history of drinking, this being a possible vulnerability marker for alcoholism. To test this hypothesis, we examined a group of recently detoxified alcoholics with high (n = 25) and low genetic loading for alcoholism (n = 28) and a group of healthy controls (n = 21). Clinical assessments were made using the SCID II interview for psychiatric disorders, the Family History Assessment Module and the Semi-Structural Assessment of Genetics in Alcoholism, a questionnaire especially designed for genetic studies. Platelet MAO activity with and without ethanol stimulation and the percentage of MAO activity with ethanol did not differ between groups. The only significant difference was a lower inhibition of MAO activity with ethanol in alcoholics both with and without a family history compared to controls. In patients with antisocial personality traits, platelet MAO activity was also not found to be different from other alcoholics. Our findings question the hypothesis of reduced platelet MAO activity to be a possible vulnerability marker for alcoholism.
Inequity in the Hospital Care of Patients with Alcoholism and Medication Addiction
Authors: Maylath Esther , Seidel Jochen , Schlattmann Peter
Published: April 2003

In a psychiatric/ecological study, the authors investigated which aspects of a town district would provide an explanation to the fact that alcoholics are treated above average in addiction-psychiatric wards in a given city district, while in other districts treatment is carried out in internal medical wards. The research was based on data collected between 1988 and 1994 from approximately 77% of all patients suffering from alcohol and legal drug abuse (n = 15,473) in 41 hospitals in Hamburg. It was established that in somatic departments, mainly internal medicine, 70% of male and 67% of female patients were admitted for alcohol and legal drug abuse. The results of a geographical analysis of hospitalization risks showed that the addiction-psychiatric facilities of psychiatric wards are mainly utilized by inhabitants from nearby districts. Risks of above-average hospitalization for alcoholics and legal drug abusers in internal wards, as well as insufficient addiction-psychiatric care, are to be expected in town districts where a shortage of psychiatrists exists, and where the unemployment rate is high. In these crucial areas, addiction-specific facilities, such as qualified programs for detoxication or techniques for short intervention, should be established within the framework of an addiction-specific liaison service in general hospitals.
HLA class I (A, B) and II (DR, DQ) Gene and Haplotype Frequencies in Blood Donors from Wales
Authors: Darke C. , Guttridge M.G. , Thompson J. , McNamara S. , Street J. , Thomas M.
Published: April 2003

Accurate estimates of HLA-A, B, DR and DQ phenotype, gene and haplotype frequencies (HF) in the normal population are of importance in, for example, disease susceptibility studies, platelet transfusion support and transplantation. HLA population genetics studies have been performed on numerous groups, however, no major studies have been carried out on the population of Wales. As part of the validation process for our routine HLA-A and B typing by PCR using sequence-specific primers (PCR-SSP) we examined 1,798 normal, unrelated Caucasoid blood donors living in Wales and recruited onto the Welsh Bone Marrow Donor Registry (WBMDR). Typing was performed by serology (HLA-A, B) and PCR-SSP at low resolution (HLA-A, B, DR, DQ) resulting in a particularly rigorous level of HLA specificity assignment. Four discrepancies were found between the HLA-A and B serological and PCR-SSP specificity assignments: (1) two instances of HLA-A2 by serology were undetected by PCR-SSP and were a new HLA-A2 allele – A*0224; (2) one example of HLA-B*15 by PCR-SSP failed to react by serology, and remained undetectable by serology in subsequent samples, and (3) one example of HLA-B45 by serology was identified as HLA-B*5002 by PCR-SSP. Hardy-Weinberg and homozygosity analysis showed that the goodness-of-fit was excellent (p > 0.05), for both phenotype distribution and the number of homozygotes identified, for all four loci. The phenotype and gene frequencies for the 18 HLA-A, 34 -B, 15 -DR and 8 -DQ specificities identified and two- and three-locus HF, linkage disequilibrium and related values for HLA-A/B, B/DR, DR/DQ and HLA-A/B/DR and B/DR/DQ were essentially typical of a northern European population. HLA-A2, B44, DR4 and DQ2 were the highest frequency phenotypes and HLA-A2403, A34, A74, B42, B75, B2708, B48, B67 and B703 occurred once only. There were no examples of: A36, A43, A69, A80, B46, B54, B59, B73, B76, B77, B7801, B8101 or DR18 specificities. DR17, DQ2 and A1, B8, DR17 were the highest frequency two- and three-locus haplotypes identified. Diverse HLA-A, B, DR phenotypes were identified in 87.0% (1,564) of subjects. When HLA-DQ was also considered, different four locus phenotypes were identified in 89.1% (1,602) of subjects. This frequency information will be beneficial as a high-quality reference control for disease susceptibility studies and in calculating the chances of identifying a bone marrow donor in a patient’s extended family. This process was successful for the validation of our HLA-A and -B PCR-SSP typing procedure and the findings suggest an accurate level of specificity assignment of WBMDR panel donors who had previously been typed by serology alone.
Plasma α1,3-Fucosyltransferase Deficiency in Schizophrenia
Authors: Yazawa Shin , Tanaka Susumu , Nishimura Toyo , Miyanaga Kazuo , Kochibe Naohisa
Published: April 2003

Levels of plasma α1,3-fucosyltransferase (α1,3FT) were assayed in 44 patients with schizophrenia and in 50 healthy controls. Significantly reduced enzyme activities were observed in patients (p < 0.05) and 4 unrelated patients were found, for the first time in Japan, to be deficient in the enzyme activity. Two point mutations in the coding region of the FUT6 gene encoding plasma α1,3FT that were responsible for the inactivation of the enzyme activity were detected in those patients. Genotyping of the Le gene (FUT3) in these patients demonstrated that 2 of them were also FUT3 deficient and were grouped as Lewis– individuals whereas the rest were Lewis+.
HLA-DMA Alleles Are Possible New Markers of Rheumatoid Arthritis: Study of a Corsican Group
Authors: Cucchi-Mouillot P. , Lai S. , Carcassi C. , Silicani-Amoros P. , Floris L. , Amoros J.-P. , Genetet B. , Haras D. , Contu L.
Published: April 2003

The HLA-DMA gene, along with the HLA-DMB gene, encodes the not classical class II molecule. This molecule catalyzes the class-II-associated invariant-chain peptide (CLIP)-antigen peptide exchange in classical class II molecule peptide-binding groove. As such, the DM heterodimer is an antigen presentation regulator and may be linked to immune system deficiencies such as those observed in autoimmune diseases. The study of DMA gene polymorphism seems be a reasonable approach to provide an answer to this question. Thanks to PCR-derived methods, the relationship between DMA gene polymorphism and rheumatoid arthritis (RA) was demonstrated in the present study. The DMA*0101 allele was observed to confer a significant predisposition to RA while the DMA*0102 allele significantly protected from this disease. Polymorphism experiments with the HLA-DRB1 gene revealed that this relationship between DMA polymorphism and RA is not a consequence of a linkage disequilibrium with the HLA-DRB1 alleles implicated in this pathology. The study of the DMA gene could therefore prove to be very useful in the early diagnosis of RA.
How Cytotoxic is Nitric Oxide?
Authors: Gordge M.P.
Published: April 2003

Nitric oxide (NO) shows an unusual divergence of action, being utilised both as a physiological signalling molecule, and as a toxic mediator. NO-mediated cellular injury may arise by a variety of mechanisms, including disruption of mitochondrial respiration, enzyme inhibition, lipid peroxidation and genetic mutation. Toxicity is largely mediated via intermediates such as N2O3 and peroxynitrite, arising from the reaction of NO with either molecular oxygen or reactive oxygen species. In general, such reactions become significant only when high concentrations of NO are generated by the induction of nitric oxide synthase.
Insights from Mathematical Modeling of Renal Tubular Function
Authors: Weinstein Alan M.
Published: April 2003

Mathematical models of proximal tubule have been developed which represent the important solute species within the constraints of known cytosolic concentrations, transport fluxes, and overall epithelial permeabilities. In general, model simulations have been used to assess the quantitative feasibility of what appear to be qualitatively plausible mechanisms, or alternatively, to identify incomplete rationalization of experimental observations. The examples considered include: (1) proximal water reabsorption, for which the lateral interspace is a locus for solute-solvent coupling; (2) ammonia secretion, for which the issue is prioritizing driving forces – transport on the Na+/H+ exchanger, on the Na,K-ATPase, or ammoniagenesis; (3) formate-stimulated NaCl reabsorption, for which simple addition of a luminal membrane chloride/formate exchanger fails to represent experimental observation, and (4) balancing luminal entry and peritubular exit, in which ATP-dependent peritubular K+ channels have been implicated, but appear unable to account for the bulk of proximal tubule cell volume homeostasis.
Inducible Nitric Oxide Synthase Induction in Thy 1 Glomerulonephritis Is Complement and Reactive Oxygen Species Dependent
Authors: Mosley Karen , Waddington Simon N. , Ebrahim Hatim , Cook Terence , Cattell Victoria
Published: April 2003

Thy 1 glomerulonephritis (GN) is a rat model of complement-dependent immune mesangial injury with induced glomerular nitric oxide (NO) synthesis. To examine mechanisms of inducible nitric oxide synthase (iNOS) induction, we studied the effects of treatment with the antioxidant N-acetyl-cysteine (NAC) and soluble complement receptor 1 (sCR1). Thy 1 GN was induced by intravenous anti-Thy 1 antibody. Glomeruli were isolated and kidney tissue taken from 30 min to 24 h after induction. Nitrite (NO–2) synthesis, luminol chemiluminescence for reactive oxygen species (ROS), and iNOS and cytokine mRNA were assayed in isolated glomeruli. Mesangial injury (mesangiolysis) and leucocyte infiltration were quantitated on tissue sections. NAC (i.p. 1,000 mg/kg, 1 h prior to anti-Thy 1) reduced glomerular NO–2 synthesis (3.5 ± 0.66 vs. untreated 8.2 ± 1.1, p = 0.02), and iNOS mRNA expression, and abolished enhanced chemiluminescence. In vitro incubation of nephritic glomeruli with 20 mM NAC also suppressed nitrite production (4.7 ± 0.8 vs. untreated 12.2 ± 0.7 nmol NO–2/2,000 glomeruli/48 h, p = 0.003), and chemiluminescence. In NAC-treated animals, neutrophil infiltration (0.5 ± 0 vs. untreated 9.6 ± 1.6 glomerulus, p = 0.0005), and macrophage infiltration (1.7 ± 0.4 vs. untreated 12.0 ± 0.1, p = 0.006) were abolished, and mesangiolysis was significantly reduced (45.9 ± 1.3 vs. untreated 34.4 ± 2.1 cells/glomerulus, p = 0.009). NAC did not inhibit anti-Thy 1 antibody deposition. C1q was unaffected, but C3 was reduced. sCR1 treatment prevented iNOS mRNA induction, the enhanced chemiluminescence, and the neutrophil infiltration at 1 h. IL-1β and TNFα mRNAs were not affected by either NAC or sCR1. These results show that NAC inhibits iNOS induction and NO synthesis in this model, and suppresses ROS synthesis and injury. They suggest that complement-dependent ROS generation is the critical initiating event that follows fixation of anti-Thy 1 antibody.
Glowing Podocytes in Living Mouse: Transgenic Mouse Carrying a Podocyte-Specific Promoter
Authors: Imai Enyu , Akagi Yoshitaka , Isaka Yoshitaka , Ikawa Masahito , Takenaka Masaru , Hori Masatsugu , Okabe Masaru
Published: April 2003

Green fluorescence protein (GFP) has been utilized as a marker of gene expression due to the great advantage in its simple and quick detectability. We generated transgenic mice carrying a GFP cDNA under the control of a β-actin/β-globin promoter (CX promoter) and cytomegalovirus enhancer. The green luminescence derived from GFP was apparent in skeletal muscle, pancreas, heart and kidney, but not in other tissues. The GFP expression in the kidney was localized in podocytes. Moreover, in situ hybridization of GFP showed that the transcriptional level was highly active in the podocytes. These results suggested that the glowing green fluorescence would be a useful in vivo marker of podocyte in these transgenic lines in the physiological and pathophysiological state, and that the CX promoter could allow a podocyte-specific expression of a molecule of interest in kidney.
Nuclear Protein Transport Pathways
Authors: Köhler Matthias , Haller Hermann , Hartmann Enno
Published: April 2003

Nuclear proteins like transcription factors and ribosomal proteins are synthesized in the cytoplasm and have to be transported into the nucleus to fulfill their functions. The transport of proteins >20–60 kD through the nuclear pore complex (NPC) into the nucleus is an active, energy-requiring process. Transport substrates are recognized by their transport proteins via certain signals. The best-characterized protein import pathway is the ‘classical’ nuclear localization signal-dependent pathway with importin α and β carrying the substrate to the NPC. The transport of the importin-substrate complex into the nucleus is regulated by the small GTPase Ran/TC4. During the last years more than ten proteins have been discovered which have already been proven or are very likely to be nuclear transport factors of distinct import pathways: members of the importin α protein family are very similar and transport in complex with importin β nuclear localization signal-bearing proteins into the nucleus. Members of the Ran-binding protein family show some weak similarity to importin β. Sharing a common domain at the amino terminus, they are able to bind RanGTP, a prerequisite for their function as nuclear import or export factors for distinct proteins or RNAs. However, Ran/TC4 seems to play a key regulatory role in all nuclear transport pathways described so far, although the molecular mechanism of the translocation step through the NPC is still unclear.
Hypoxia-Induced Changes in Extracellular Matrix Metabolism in Renal Cells
Authors: Norman J.T. , Orphanides C. , Garcia P. , Fine L.G.
Published: April 2003

The mechanisms underlying the progressive fibrosis that characterises end-stage renal disease in vivo remain to be established but hypoxia, as a result of microvascular injury and loss, has been suggested to play an important role. In support of this hypothesis, in vitro studies show that hypoxia (1% O2) induces a fibrogenic phenotype in human renal tubular endothelia, interstitial fibroblasts and microvascular endothelial cells, simultaneously increasing extracellular matrix (ECM) production and decreasing turnover via effectors on matrix-degrading enzymes and their inhibitors. The effects of hypoxia on ECM metabolism are independent of hypoxia-induced growth factors and are mediated by a haem-protein sensor and activation of both protein kinase C- and tyrosine kinase-mediated signal transduction pathways. De novo gene transcription is regulated by both hypoxia-inducible factor-1-dependent and -independent mechanisms. Further understanding of the molecular mechanisms by which decreased oxygen alters expression of genes involved in ECM metabolism in renal cells may provide new insights into the pathogenesis of fibrosis and identify novel avenues for intervention.
Animal Models of Alport Syndrome: Advancing the Prospects for Effective Human Gene Therapy
Authors: Heikkilä Pirkko , Tryggvason Karl , Thorner Paul
Published: April 2003

Several animal models for Alport syndrome have been described. These are available for studies on the pathogenetic mechanisms of the disease, as well as for the development of new technologies for gene therapy in this progressive hereditary kidney disease. This review summarizes current knowledge on the molecular basis of Alport syndrome, and on the animal models which all remarkably well resemble the human disease. Recent work aimed at the development of gene therapy, including hurdles and progress are discussed.
Pathogenesis of Renal Failure in Rhabdomyolysis: The Role of Myoglobin
Authors: Holt Steve , Moore Kevin
Published: April 2003

Rhabdomyolysis causes renal dysfunction associated with renal vasoconstriction, tubular toxicity and luminal obstruction. There is now accumulating evidence that renal injury, caused by lipid peroxidation, is important in the pathogenesis of renal failure. The proposed central role of free iron in this process is examined. Current data have shown that the heme center of myoglobin can initiate lipid peroxidation and renal injury without invoking release of free iron, and this process is due to redox cycling of the heme group from ferrous to ferric and to ferryl oxidation states. Alkaline conditions prevent myoglobin-induced lipid peroxidation by stabilizing the reactive ferryl myoglobin complex. This review explores the evidence for each of these mechanisms.
Role of Intrarenal Endothelin 1, Endothelin 3, and Angiotensin II Expression in Chronic Cyclosporin A Nephrotoxicity in Rats
Authors: Ramírez César , Olmo Asunción , O’Valle Francisco , Masseroli Marco , Aguilar Mariano , Gómez-Morales Mercedes , Revelles Francisco , García-Chicano María José , Arrebola Francisco , Reguero María Eugenia , del Moral Raimundo G.
Published: April 2003

Endothelin 1 (Et1) is widely expressed in the kidney and is related to several functions and to pathological conditions with progression towards sclerosis. The function of endothelin 3 (Et3) at the renal level is debatable, but it could have an important regulatory function in the reabsorption of water through its action on tubular type B receptors. Angiotensin II has recently been implicated as the principal factor responsible for the progression of interstitial fibrosis induced by cyclosporin A (CsA). We investigated this relationship in vivo and analyzed the modifications induced by CsA toxicity in Sprague-Dawley rats treated with 25 mg/kg/day of CsA for 28 and 56 days. Immunohistochemical methods and molecular analysis were used to study the expression of Et1 and Et3 and immunohistochemistry alone to determine the intrarenal expression of angiotensin II. Rats treated with CsA developed chronic nephrotoxicity lesions; semiquantitative analyses of hyaline arteriolopathy revealed that the passage of time affected the extent of this lesion and led to the diminution of the total glomerular area. Immunohistochemical results showed that chronic CsA treatment induced moderate secretion of Et1 and Et3 at tubular and glomerular levels and that the local expression of angiotensin II in the treatment groups was more evident than in control animals. Besides, the mRNA levels of preproEt3 showed a dramatic increase from 28 days after CsA treatment (control group 0.07 ± 0.11 vs. CsA group 0.48 ± 0.11, p < 0.01), while the mRNA levels of preproEt1 increased from 56 days (control group 0.15 ± 0.05 vs. CsA group 0.34 ± 0.09, p < 0.05). At 28 days, renal lesions correlated strongly with the mRNA levels of Et3 (r > 0.50, p < 0.01). However, at 56 days, the key finding was the strong correlation of the most important analytical, histological, and immunohistochemical parameters of CsA nephrotoxicity with Et1 mRNA levels (r > 0.50, p < 0.01). These results support the hypothesis that the clinical and morphological phenomena linked with CsA nephrotoxicity are related to hypersecretion of endothelins and local expression of angiotensin II in the outer medulla and medullary rays; Et3 and angiotensin II are the first to act, followed subsequently by Et1.
Doppler Study on Pulmonary Venous Flow in the Human Fetus
Authors: Hong Y. , Choi J.
Published: April 2003

Objectives: The fetal pulmonary circulation is different from the postnatal circulation: the flow is small. The arterial pressure is almost systemic, and the vascular resistance is high. Moreover, lungs are collapsed in the fetus. However, the pulmonary venous flow in the fetus has not been studied. The aims of this study were to look at flow patterns of pulmonary venous system in the fetus and to see whether there are any changes in Doppler parameters with fetal growth. Methods: The pulmonary venous flow velocity was analyzed in 56 normal human fetuses. The fetal gestational age ranged from 17 to 37 weeks. Pulsed-Doppler echocardiography was used to investigate the right upper pulmonary vein in four-chamber view. After the pulmonary venous signal was obtained, by enlarging the sample size, the pulmonary arterial signal was superimposed for timing. Heart rate velocities at systolic peak (S), at diastolic peak (D), at nadir between S and D (O), and at nadir between D and the next S (X) and velocity-time integral were measured. Results: The pulmonary venous signal showed basically continuous flow from pulmonary vein toward left atrium through all the cardiac cycles, and it had biphasic peaks: one during the systolic and the other during the diastolic phase. The systolic peak of pulmonary vein occurred slightly earlier or later than the systolic upstroke of pulmonary arterial waveforms. The systolic peak of pulmonary vein was higher than the diastolic peak in 45 out of 56 cases. Velocities of systolic and diastolic peaks and velocity-time integral of the pulmonary vein have significantly increased with fetal growth. Conclusions: In the fetus, the flow pattern of the pulmonary vein was similar to that of the postnatal pattern with the exception of absence of atrial reversal. Lower velocities may reflect a decreased pulmonary flow volume.
In utero Repair of Myelomeningocele: A Comparison of Endoscopy and Hysterotomy
Authors: Bruner Joseph P. , Tulipan Noel B. , Richards William O. , Walsh William F. , Boehm Frank H. , Vrabcak Eileen K.
Published: April 2003

Objective: To compare endoscopic coverage of myelomeningocele with a maternal split-thickness skin graft in utero to definitive neurosurgical closure through a hysterotomy. Methods: Four fetuses with isolated myelomeningocele underwent endoscopic coverage of the defect with a maternal split-thickness skin graft in a CO2 environment at 22–24 weeks’ gestation. Subsequently, 4 fetuses underwent standard neurosurgical closure of their myelomeningoceles at 28–29 weeks’ gestation. Results: The mean operating time for the endoscopic procedures was 297 ± 69 min. Two fetal losses occurred as a result of chorioamnionitis and placental abruption, respectively. A third baby delivered at 28 weeks’ gestation after prolonged disruption of the membranes. The 2 survivors required standard closure of the myelomeningocele after delivery. The mean operating time for the hysterotomy procedures was 125 ± 8 min. No mortality occurred, and all the infants delivered between 33 and 36 weeks with well-healed myelomeningocele scars. At present, the functional levels of all infants approximate the anatomical levels of the lesions. Conclusion: With current technology, in utero repair of congenital myelomeningocele through a hysterotomy appears to be technically superior to procedures performed endoscopically.