bluuebunny/crossref_metadata_2025 huggingface dataset:
Procalcitonin in Early Detection of Postoperative Complications
Authors: Reith H. Bernd , Mittelkötter Ulrich , Debus E. Sebastian , Küssner Claudia , Thiede Arnulf
Published: April 2003

Background: A prospective clinical study was performed to assess the accuracy of procalcitonin in 70 patients with elective colorectal or aortal surgery and to compare it with inflammatory mediators. Also the early prediction of complications and the outcome of these patients was taken into account. Methods: Laboratory variables and cytokine determination were obtained preoperatively, on the day of operation and postoperatively on a daily basis from day 1 to 5, and on days 7 and 10 in the colorectal group and in the aortal surgery group at different times on the operation day after aortal clamping. The main outcome criteria were early recognition of complications and alterations in the production of procalcitonin and cytokines in order to detect severe infective complications. Results: Procalcitonin was closely related to postoperative complications with significantly elevated levels at day 1 after surgery. The plasma concentrations of IL-6 increase on days 1–3 without a difference in the groups, also C-reactive protein demonstrates no differences. Conclusion: Procalcitonin presents itself as a new parameter of infection and sepsis. In the postoperative period PCT seems to be an interesting marker of early prediction of infective complications when high postoperative levels are found. Under routine conditions procalcitonin is a valid reproducible and detectable parameter.
Spontaneous Rupture of the Pancreaticoduodenal Artery: Three Cases
Authors: Majerus Bernard , Alexandrescu Vlad , Shutsha Etshoko , Timmermans Michel , van Ruyssevelt Christian , Wibin Ernest
Published: April 2003

We report 3 cases of spontaneous rupture of pancreaticoduodenal arteries (PDA). In the first case, an aneurysm of the PDA was demonstrated with stenosis of the celiac trunk; in the second case occlusion of the hepatic artery was shown. In both cases, arterial pancreatic arcades were enlarged and blood flow was retrograde from the superior mesenteric artery. Local high intravascular pressure due to retrograde blood flow through the arterial pancreatic arcades was thought to be the cause of aneurysm development and arterial rupture which necessitated surgical intervention. The third patient presented with a mycotic aneurysm that could be treated by intra-arterial embolization. The characteristics of this rare affliction are discussed, as is the treatment which first entails percutaneous embolization.
Management of Common Bile Duct Stones by Laparoscopic Cholecystectomy and Endoscopic Sphincterotomy: Pre-, Per- or Postoperative Sphincterotomy?
Authors: Meyer Ch. , Vo Huu Le J. , Rohr S. , Thiry L.C. , Bourtoul Ch. , Duclos B. , Reimund J.M. , Baumann R.
Published: April 2003

Background/Aims: The aim of this study was to evaluate the treatment of common bile duct stones (CBDS) by endoscopic sphincterotomy (ES) and laparoscopic cholecystectomy (LC), ES being performed either pre-, per- or postoperatively. Methods: Between January 1990 and June 1997, 386 patients with a median age of 60 (range 18–92) years were treated for suspected or confirmed CBDS. The CBDS were uncomplicated in 264 cases (70%) but associated with a complication in 122 cases (30%), namely, cholangitis (69 cases) or acute pancreatitis (53 cases). ES combined with LC was carried out in 233 cases (60%): ES was preoperative (sequential treatment in two stages) in 197 cases (51%); peroperative in 30 cases (7%), or postoperative in 6 cases (2%). Laparoscopic extraction was performed in 58 cases (15%) and conventional surgery in 82 cases (21%). Results: With respect to sequential treatment, endoscopic retrograde cholangiography showed the presence of CBDS in 117 cases (60%) and preoperative ES allowed the release of the CBDS in 82% of these cases. The complication rate of sequential treatment was 8% (15 cases) after ES and 7% (13 cases) after LC, with 1 death (0.5%). A peroperative ES performed after LC enabled evacuation of the CBDS in 28 cases (93%) without any complications or mortality. Postoperative ES was successful in 100% of cases with residual lithiasis in 16% (1 case) and a complication rate of 16% (1 case). Conclusion: Along with conventional surgery and laparoscopic extraction, ES combined with LC represents an effective alternative in the management of CBDS. Since it can be performed peroperatively, it allows a one-stage, minimally invasive treatment of most uncomplicated CBDS.
Long-Term Results after 75 Anastomoses in the Upper Extraperitoneal Rectum with the Biofragmentable Anastomosis Ring
Authors: Debus E.S. , Sailer M. , Geiger D. , Dietz U.A. , Fuchs K.-H. , Thiede A.
Published: April 2003

Background: Anastomoses in the rectum have a higher risk for complications compared with other gastrointestinal regions. Stapling devices and sophisticated developments in surgical suture materials did not lead to a substantial decrease of local complications. The bioabsorbable anastomosis ring (BAR) is a new alternative technique for creating gastrointestinal anastomoses. Accordingly, the aim of this prospective study was to evaluate the postoperative course and long-term results of patients after anterior rectum resection using BAR. Methods: From 1991 to 1996 75 BAR anastomoses were performed in the upper rectum at the Department of Surgery, University Hospital Würzburg. Thirty-eight patients suffered from malignant, 37 from benign disease. Mean age was 61.4 years with no relevant differences in the gender. Mean follow-up was 31 months (4–63 months). The clinical course was evaluated, a questionnaire completed and/or a 3-monthly reevaluation with endoscopy conducted. Mortality, anastomostic bleeding, leakage and development of anastomotic stenosis were evaluated. Results: Sixty-seven patients could be reexamined. There was no postoperative mortality and no anastomotic bleeding. Six patients (8%) developed an anastomotic leakage, of whom 3 (4%) required reoperation. None of the patients revealed a detectable stenosis in the anastomotic region during follow-up. Conclusion: The BAR procedure is a safe and suitable anastomotic technique after anterior rectum resection.
Increased Risk of Wound Complications and Poor Healing following Laparotomy in HIV-Seropositive and AIDS Patients
Authors: Davis Peter A. , Corless David J. , Gazzard Brian G. , Wastell Christopher
Published: April 2003

The number of individuals in the UK who are HIV seropositive is increasing as is their presentation with abdominal complications. Poor wound healing following anorectal surgery in HIV-positive patients has been well reported. This study reviews the incidence of wound complications following laparotomy. The hospital records of all HIV-positive patients who underwent laparotomy at a London teaching hospital over a 10-year period were reviewed and compared to an equal number of matched non-HIV patients. Between April 1986 and April 1996, 64 laparotomies were carried out on 53 patients. There was a significantly greater incidence of wound complications (χ2 = 12.75, 1 d.f., p = 0.0003) and wound breakdown (χ2 = 10.45, 1 d.f., p = 0.012) in the HIV group following laparotomy than in the non-HIV control group.
Esophageal Sarcomas: Report of Three Cases
Authors: Kimura Hironobu , Konishi Kohji , Kawamura Taichi , Nojima Naomi , Satou Takahiro , Maeda Kiichi , Yabushita Kazuhisa , Kuroda Yoshitaka , Tsuji Masahiko , Miwa Atsuo
Published: April 2003

Background/Aims:  Sarcomas of the esophagus, including carcinosarcoma, are rare neoplasms. Methods: The clinical and pathologic characteristics of 3 patients with esophageal sarcomas are presented, including the only recorded esophageal carcinosarcoma and 2 patients with leiomyosarcoma. Results: All 3 patients were males who presented with dysphagia or an abnormal shadow of the mediastinum on a plain chest X-ray. Two tumors were in the middle esophagus, and the remaining one was in the distal esophagus. On endoscopic examination, all three tumors were noted to be polypoid. These patients underwent surgical excision. One patient died 7 days following the operation, and the remaining 2 patients died of liver metastasis 10 and 22 months following the treatment. Conclusion: Esophagectomy or esophagogastrectomy is a surgical choice. Even if metastases are present, a palliative resection can still be performed.
A Free Peritoneal Patch Does Not Affect the Leakage Rate but Increases Stricture Formation of a Cervical Esophagogastrostomy
Authors: van Oosterom F.J.T. , van Lanschot J.J.B. , Oosting J. , Obertop H.
Published: April 2003

Background: Healing of a cervical esophagogastrostomy is frequently impaired, resulting in a higher incidence of leakage and stricture formation, as compared to an intrathoracic anastomosis. Lack of mesothelial factors is hypothesized to contribute to this impaired anastomotic healing. The aim of this prospective study was to determine whether a free peritoneal patch around a cervical esophagogastrostomy can improve anastomotic healing. Methods: In 23 consecutive patients a free peritoneal patch was fixed around a cervical esophagogastrostomy. Results were compared to those of a historical control group of 41 patients. Clinical and/or radiographic leakage and stenosis requiring endoscopic dilatation were used as endpoints. Results: Three patients died in the early postoperative period (in-hospital mortality 3/64 = 5%). Leakage rate was 13% (3/23) in the group with a patch and 15% (6/41) in the control group (p = 0.90). At 6-month follow-up, the incidence of stenosis was significantly higher (65%) in the group with a patch, compared to 31% in the control group (p = 0.02). Conclusion: A peritoneal patch does not affect the leakage rate but increases the incidence of postoperative stenosis of a cervical esophagogastrostomy. Therefore, its clinical application is contraindicated.
Laparoscopic Cholecystectomy in Two Patients with Symptomatic Cholelithiasis and Situs inversus totalis
Authors: Demetriades H. , Botsios D. , Dervenis C. , Evagelou J. , Agelopoulos S. , Dadoukis J.
Published: April 2003

Background: Situs inversus viscerum is a rare condition with a genetic predisposition. We report 2 patients with situs inversus totalis and symptomatic cholelithiasis successfully treated via laparoscopic cholecystectomy.  Patients and Methods: The first patient was a 61-year-old female presenting with pain in the left upper quadrant associated with fever, chills, nausea and vomiting. The abdomen was tender with guarding and rebounding pain in the same region. Abdominal ultrasound and CT scan confirmed the diagnosis of gallstones as well as situs inversus with the liver and gallblader on the left side and the spleen on the right. The second patient was a 37-year-old male with known situs inversus who presented with biliary colic due to cholelithiasis. In both patients cholecystectomy was performed laparoscopically in a reverse fashion. Results: Laparoscopic cholecystectomy was carried out successfully despite the reversed anatomic relationships and both patients made a smooth recovery. Conclusion: Cholelithiasis occurring with situs inversus totalis is rare and may present a diagnostic problem. Laparoscopic cholecystectomy can be safely and effectively applied in the setting of situs inversus, although attention must be paid to the details of left-right reversal.
Intraluminal Duodenal Diverticulum Causing Acute Pancreatitis: CT Scan Diagnosis and Review of the Literature
Authors: De Rai Paolo , Castoldi Laura , Tiberio Giorgio
Published: April 2003

Background: Intraluminal duodenal diverticulum is a rare congenital anomaly. First described by Boyd in 1845, no more than 100 cases have been reported up to now: only 17 are associated with acute pancreatitis. Methods: A new case of intraluminal duodenal diverticulum with acute pancreatitis is reported and the literature about this association reviewed. Results: The diagnosis was made by helical CT scan. The pathogenesis of pancreatitis was possibly due to a pure duodenal content reflux through the papilla of Vater. The patient was successfully treated by surgery. Conclusions: Intraluminal duodenal diverticulum is a rare but curable cause of pancreatitis, usually affecting young people. We describe, for the first time, its unusual helical CT imaging with two-dimensional reformations.
Association of Transjugular Intrahepatic Portosystemic Shunt with Embolization in the Treatment of Bleeding Duodenal Varix Refractory to Sclerotherapy
Authors: Illuminati Giulio , Smail Allaoua , Azoulay Daniel , Castaing Denis , Bismuth Henri
Published: April 2003

Background: Bleeding from duodenal varices are often severe (mortality as high as 40%), and more difficult to sclerose than esophageal varices. We report a patient with a bleeding duodenal varix, refractory to sclerotherapy, successfully treated by the association of portosystemic shunt placement and varix embolization, via the same transjugular intrahepatic route. Methods: A 40-year-old Black male underwent emergency TIPS and duodenal varix embolization after failure of endoscopic sclerotherapy. The portosystemic pressure gradient droped from 16 to 9 mm Hg following TIPS. At 5 months from TIPS, the patient is well, with a patent shunt at Doppler ultrasound. Conclusion: The present report of successful control of duodenal varix, actively bleeding and refractory to sclerotherapy, by means of combined TIPS and embolization, supports the role of TIPS and suggests that its association to embolization can be valuably considered in the difficult setting of portal hypertension with bleeding duodenal varices.
Drug Policies and Harms: A Conceptual Framework
Authors: Longshore Douglas , Reuter Peter , Derks Jack , Grapendaal Martin , Ebener Patricia
Published: April 2003

Existing indicators of drug-related policies and harms – official statistics, treatment data, and so on – are difficult to interpret and to compare across jurisdictions. We propose a conceptual framework including key dimensions of policy and harm. The framework is designed to guide creation of a new dataset in which existing empirical data can be used to assign city-specific scores on policy and harm dimensions. By an interpretive process involving local experts and a coordinating body, we believe that existing data can be evaluated and synthesized to derive these scores. We also propose a cumulative case-study method of querying the dataset to test hypotheses regarding relationships between policies and harms.
Drug Misusers and Their Treatment in the Czech Republic: Changing Problems and Changing Structures
Authors: Csémy Ladislav
Published: April 2003

This paper reviews recent developments in treatment of drug-related disorders in the Czech Republic after the socio-political changes in 1989. In the first part, a profile of drug users is given. In the second part, changes in the inpatient and outpatient treatment facilities are discussed.
The Pompidou Group Treatment Demand Protocol: The First Pan-European Standard in the Field
Authors: Stauffacher Michael , Kokkevi Anna
Published: April 2003

There have been many efforts to collect drug treatment demand data in the last decades, but only few organisations worked on international comparable instruments. This paper describes such an attempt organised under the auspices of the Council of Europe in the late 80s, beginning of the 90s. Both the developed protocol as well as its implementation in various European cities are presented. Between 1993 and 1999, a comparative research project to annually compile data and trends on European level was carried out. Data quality issues and methodological problems are highlighted. The paper notes the value and success of the treatment demand indicator, but claims for further improvements and a combined use with other indicators and qualitative information. Some spin-off and follow-up projects are summarised.
Sharp Increase in Illicit Drug Use in Greece: Trends from a General Population Survey on Licit and Illicit Drug Use
Authors: Kokkevi A. , Loukadakis M. , Plagianakou S. , Politikou K. , Stefanis C.
Published: April 2003

The study aims to follow trends in the prevalence of licit and illicit substance use between 1984 and 1998 in the Greek general population. Data are drawn from two nationwide cross-sectional household surveys. Probability samples consisted of 4,297 (1984) and 3,759 (1998) 12- to 64-year-old respondents. Regular tobacco smoking in the total sample increased in women and decreased in men while alcohol consumption remained at similar levels. The use of illicit drugs showed a 3-fold increase since 1984 reaching a lifetime prevalence of 19% in males and 6% in females. In contrast, a significant decrease was noted in the unprescribed use of psychoactive medicines, especially among women. Trends in licit and illicit substance use can be explained by sociocultural and policy changes in Greece in the last 15 years.
Stage of Change of Cigarette Smoking in Alcohol-Dependent Patients
Authors: Zullino Daniele , Besson Jacques , Schnyder Christiane
Published: April 2003

Despite the heavy burden of tobacco-related problems in alcohol-dependent patients, little effort has been directed toward reducing the prevalence of smoking in these patients. It seems reasonable to develop nicotine addiction treatments for alcohol-dependent patients based on the smoker’s stage of change. To assess the stage of change for tobacco consumption and possible quitting barriers in alcohol-dependent patients, 88 consecutively admitted inpatients of a Swiss university-affiliated alcohol withdrawal clinic were interviewed with a semistructured schedule. More than half of the alcohol-dependent smokers (50.7%) considered the possibility of smoking cessation or had already decided to stop, although the majority (83.1%) were highly dependent smokers. Positive reinforcers were factors influencing motivation both to stop smoking as well as to continue smoking, whereas negative reinforcers had no influence. As recovering alcoholic patients are often interested in smoking cessation and the introduction of nicotine treatment interventions has been shown not to jeopardize the outcome of alcohol treatment, alcohol treatment programs should include counseling for smoking cessation. Education and training for staff is essential, as their beliefs and habits remain an important barrier.
In vivo and in vitro Modulation of Immune Stimulatory Capacity of Primary Dendritic Cells by Adenovirus-Mediated Gene Transduction
Authors: Sonderbye Lene , Feng Sandy , Yacoubian Shahan , Buehler Hans , Ahsan Nasimul , Mulligan Richard , Langhoff Erik
Published: April 2003

Dendritic cells (DCs) are potent antigen-presenting cells which are key leukocytes in the initiation of cell-mediated organ graft rejection, antiviral immunity, and antitumor responses. In this study we demonstrate that genetic modification of primary human and mouse DCs by adenoviral gene transfer is an effective means of induction and modulation of antigen presentation by DCs. An adenovirus vector (AdLacZ) was used to express an intracellular model antigen β-galactosidase (β-gal) in DCs. Our results show that 30–40% of precursor dendritic cells (PDCs) derived from human umbilical cord blood and circulating mature blood DCs express high levels β-galactosidase (β-gal) after infection with AdLacZ with no cytopathic effect observed. In vitro, AdLacZ transduced PDCs and DCs demonstrated a 10- to 20-fold higher mixed lymphocyte reaction (MLR) stimulatory capacity as compared to that of monocytes. In vivo, immunization with AdLacZ transduced mouse DCs resulted in more potent cytotoxic T lymphocyte (CTL) responses against the predicted H-2 restricted β-gal epitope as compared to CTL responses obtained by β-gal peptide pulsed DCs. Modulations of the MLR stimulatory capacity of DCs were examined by expression of mouse B7 and CTLA-4Ig. The results show that expression of mouse B7 by a recombinant adenoviral vector (Ad7) significantly enhances the MLR stimulatory capacity of human DCs. In contrast, expression of CTLA-4Ig (AdCTLA-4Ig) reduces the MLR stimulatory capacity of the transduced cells. We conclude that recombinant adenovirus can readily be used for genetic modulation DC-induced immune responses in vivo and in vitro. DCs targeted for induction of specific antigen responses or for modulation of the immune stimulatory capacity may have a potential use in the control of transplantation rejection or viral infections.
Terminal Complement Component Deficiencies in Japan
Authors: Fukumori Yasuo , Horiuchi Takahiko
Published: April 2003

From the serological screening for complement component deficiencies, we found 2 subjects with inherited C5 deficiency (C5D), 4 with C6D, 6 with C7D, 4 with C81 (α-γ subunit) D and 138 with C9D among 145,640 healthy Japanese blood donors. Recently, the genetic bases of some of the C6D, C7D, C81D and C9D Japanese individuals were elucidated using an exon-specific PCR-SSCP method followed by direct sequencing of the target exons.
HLA-A, -B, -C, -DRB1, DRB3, DRB4, DRB5 and DQB1 Polymorphism Detected by PCR-SSP in a Semi-Urban HIV-Positive Ugandan Population
Authors: Krausa P. , McAdam S. , Bunce M. , Whitworth J. , Biryahwaho B. , French N. , Tugume B. , Gilks C. , Gotch F.
Published: April 2003

PCR-SSP was used to HLA-type a cohort of Ugandan HIV-positive individuals. The results represent a more comprehensive description of HLA in an African population than previously described and are in concordance with data from a general Black population. Substantial differences exist between this population and Caucasoid populations in which immunological responses to HIV have been investigated; this emphasises that the main HLA-restrictive elements for HIV-specific cytotoxic T lymphocytes will most likely be different for each population.
Novel Polymorphism in the Coding Region of the IL-13 Receptor Alpha’ Gene: Association Study with Atopic Asthma in the Japanese Population
Authors: Ahmed Saifuddin , Ihara Kenji , Sasaki Yuka , Nakao Futoshi , Nishima Sankei , Fujino Tokihiko , Hara Toshiro
Published: April 2003

Interleukin (IL)-4 and IL-13 play key roles in the development of atopic asthma. The IL-13 receptor (R) α′ chain is a component of both IL-4R and IL-13R complexes. By screening the whole coding region of the IL-13Rα′ gene for polymorphisms, we identified a new polymorphism at nucleotide position 1050 from the ATG start codon. The allelic frequency of the C/T polymorphism in the Japanese population was found to be 0.97:0.03. Because of the low frequency of the T allele, the association study failed to indicate any significant association between this polymorphism and atopic asthma in the Japanese population. Further studies are required in other racial groups with higher frequencies of this polymorphism to elucidate the association.
Oral Supplementation of L-Arginine Prevents Chronic Cyclosporine Nephrotoxicity in Rats
Authors: Yang Chul Woo , Kim Yong Soo , Kim Jin , Kim Young Ok , Min So Youn , Choi Euy Jin , Bang Byung Kee
Published: April 2003

This study was performed to evaluate the effect of L-arginine (L-Arg) on the prevention of chronic cyclosporine (CsA) nephrotoxicity in rats. Rats pair-fed a low-salt diet (0.05%) were given CsA (15 mg/kg/day s.c.), CsA and L-Arg (L-Arg group, 1.25 g/l water), CsA and N-nitro-L-arginine methyl ester (L-NAME group, 70 mg/l water) or vehicle. After 28 days, the L-Arg group had a higher glomerular filtration rate compared to the CsA (0.42±0.05 vs. 0.31±0.06 ml/min/100 g, p < 0.05) and the L-NAME groups (vs. 0.19± 0.04 ml/min/100 g, p < 0.05) and a significantly lower serum creatinine level compared to the CsA (0.70±0.06 vs. 0.92±0.12 mg/dl, p < 0.05) and the L-NAME groups (vs. 1.21±0.17 mg/dl, p < 0.05). The L-Arg group had less fibrosis, tubular injury (TI), and arteriolopathy than the CsA (fibrosis 0.39±0.14 vs. 0.74±0.15; TI 1.3±0.3 vs. 2.0±0.1; arteriolopathy 33±7 vs. 48±17, p < 0.05, respectively) and the L-NAME groups (fibrosis vs. 1.67±0.32, TI vs. 2.6±0.3, arteriolopathy vs. 63±10, p < 0.05, respectively). Plasma renin activity in the L-Arg group was less than in the CsA (18±2 vs. 23±3 ng Ang I/ml/h, p < 0.05) and the L-NAME groups (vs. 30±3 ng Ang I/ml/h, p < 0.05). Nitric oxide production in L-Arg group was higher than in the CsA (24.2±1.7 vs. 11.1±1.5 µmol/24 h, p < 0.05) and the L-NAME groups (vs. 8.4±1.0 µmol/24 h, p < 0.05). In conclusion, the nitric oxide pathway is associated with the pathogenesis of chronic CsA nephrotoxicity, and exogenous L-Arg supplementation is effective in reducing chronic CsA nephrotoxicity in rats.
Mechanical Stretch/Relaxation Stimulates a Cellular Renin-Angiotensin System in Cultured Rat Mesangial Cells
Authors: Becker B.N. , Yasuda T. , Kondo S. , Vaikunth S. , Homma T. , Harris R.C.
Published: April 2003

Angiotensin II (Ang II) may play a significant role mediating intraglomerular hypertension and glomerular sclerosis. Therefore, we investigated whether a model of pressure-induced stress, mechanical stretch/relaxation, affected the renin-angiotensin system (RAS) in cultured rat mesangial cells. Type 1 Ang II receptor (AT1R) expression was assessed by 125I-Ang II binding and quantitative reverse-transcription polymerase chain reaction. Stretch/relaxation increased steady-state AT1R mRNA levels as well as specific [125I]Ang II binding. Increased AT1R expression was associated with altered AT1R signaling. Ang II (100 nM) increased total phosphoinositide hydrolysis in control cells (186 ± 25%, n = 6; p < 0.025 vs. no treatment). However, stretch/relaxation for 48 h further augmented AT1R-mediated PI hydrolysis (293 ± 38%, n = 6; p < 0.025 vs. Ang II treatment alone). We examined other RAS components in mesangial cells subjected to stretch/relaxation. Angiotensinogen, determined by radioimmunoassay of Ang I generation in conditioned media, increased with stretch/relaxation, and reverse-transcription polymerase chain reaction demonstrated increased angiotensinogen gene expression in stretch/relaxation-treated cells. However, renin activity and angiotensin-converting-enzyme-like activity were unaffected by stretch/relaxation. Thus, mesangial cells maintain a local RAS similar to those described in other tissues, and AT1R expression and angiotensinogen production in this cellular RAS are increased by stretch/relaxation. It is likely that mesangial cells in vivo, exposed to variations in intraglomerular pressure, may regulate their responses via a local RAS.
Evidence for Atrial Natriuretic Factor Induced Natriuretic Peptide Receptor Subtype Switching in Rat Proximal Tubular Cells during Culture
Authors: Mistry Sanjay K. , Chatterjee Prabal K. , Weerackody Roshan P. , Hawksworth Gabrielle M. , Knott Rachel M. , McLay James S.
Published: April 2003

Culture and natriuretic peptide dependent changes in the expression of the natriuretic peptides atrial natriuretic factor (ANF), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) and the natriuretic peptide receptors A, B, and C in primary cultures of rat proximal tubular cells were demonstrated using polymerase chain reaction analysis and cyclic guanosine monophosphate response to ANF and CNP. Freshly isolated cells expressed mRNA coding for the natriuretic peptide receptor C only, with no expression of the natriuretic peptides or the natriuretic peptide receptors A or B. At confluence natriuretic peptide receptor C expression was lost, while mRNA transcripts for both ANF and BNP and the A and B receptors became apparent. The appearance of mRNA transcripts for the natriuretic peptide receptors A and B during cell growth correspond with a significant increase in the cyclic guanosine monophosphate respone to both ANF and CNP, confirming the presence of functionally active guanylate cyclase linked A and B natriuretic peptide receptors. The observed changes in peptide receptor expression during culture were preceded by changes in natriuretic peptide mRNA expression, suggesting the possibility that natriuretic peptide receptor subtype switching may be under the control of endogenous peptide release. Incubation of freshly isolated proximal tubular cells with ANF, BNP, or CNP for 3 h induced similar changes in receptor expression. Incubation with ANF induced expression of the natriuretic peptide receptor B and CNP while inhibiting natriuretic peptide receptor C. Incubation with BNP induced expression of the natriuretic peptide receptor B and CNP. Incubation with CNP induced expression of the natriuretic peptide receptors A and B and CNP. These results suggest that primary cultures of rat proximal tubular cells may experience natriuretic peptide and natriuretic peptide receptor subtype switching as they approach confluence under the control of endogenously expressed natriuretic peptides.
Podocyte Phenotypes as Defined by Expression and Distribution of GLEPP1 in the Developing Glomerulus and in Nephrotic Glomeruli from MCD, CNF, and FSGS
Authors: Sharif Kaveh , Goyal Meera , Kershaw David , Kunkel Robin , Wiggins Roger
Published: April 2003

Glomerular epithelial protein 1 (GLEPP1) is a podocyte receptor membrane protein tyrosine phosphatase located on the apical cell membrane of visceral glomerular epithelial cell (VGEC) foot processes. Double label immunofluorescence, immunoelectron microscopy, and peroxidase immunohistochemistry were used to map the GLEPP1 distribution in the developing glomerulus and in minimal-change nephropathy (MCN), congenital nephrotic syndrome of the Finnish type, and focal-segmental glomerulosclerosis (FSGS). In MCN GLEPP1 was shifted away from the glomerular basement membrane on the apical cell membrane of effaced foot processes. These data are compatible with the previously suggested concept that MCN can be considered a form of dedifferentiation of the podocyte phenotype. Similarly, changes seen in congenital nephrotic syndrome of the Finnish type can be considered a consequence of failure to complete normal podocyte development. In FSGS glomeruli GLEPP1 was frequently absent from VGECs, even when no sclerosis was detectable in that glomerulus. Therefore, in FSGS, VGECs may lose GLEPP1, and this loss appears to occur in the absence of scarring and may, therefore, precede the scarring process. We speculate that a changed VGEC phenotype that does not express GLEPP1 might have properties similar to the early undifferentiated VGEC developmental phenotype. GLEPP1 distribution pattern and absence from glomeruli of individuals with nephrotic syndrome may, therefore, represent a useful phenotypic marker.
Renal Hemodynamic Response to Erythropoietin-Induced Polycythemia in 5/6 Nephrectomised Rats Is Different from Normal Rats
Authors: Paixão Ana D.O. , Ferreira Alice T. , Oshiro Maria E.M. , Razvickas Clara V. , Boim Mírian A. , Schor Nestor
Published: April 2003

The effects of recombinant human erythropoietin (rHuEPO)-induced polycythemia on renal function and glomerular hemodynamics were evaluated in Munich-Wistar rats (MW+EPO) before and after infusion of indomethacin; the rHuEPO effects on total renal function were also evaluated in 5/6 nephrectomized (CRF) MW and spontaneously hypertensive rats (MW-CRF+EPO and SHR-CRF+EPO, respectively). In normal MW rats, rHuEPO (300 IU/kg BW, 3×/week, during 2 weeks) induced elevation in MAP, with maintenance of GFR, paralleled by superficial vasodilatation and elevation in SNGFR, suggesting cortical blood redistribution. These hemodynamic alterations induced by rHuEPO were blunted by indomethacin, suggesting a participation of the vasodilator prostaglandins in the renal compensatory mechanism of polycythemia. Elevation in MAP and reduction in GFR occurred in the MW-CRF+EPO group compared with the group receiving vehicle. In contrast, the SHR-CRF+EPO presented a reduction in MAP and maintenance of GFR, suggesting different rHuEPO effects depending on previous renal function and/or hypertensive state.
Furosemide Compounds Enhance Urinary Excretion of Active Kallikrein Independently of Their Effects on Urinary Electrolyte Excretion
Authors: Bulmer Bronwyn , Penschow Jennifer D.
Published: April 2003

The chemical and diuretic effects of furosemide on the excretion and activation of urinary prokallikrein were investigated in rats by treatment with furosemide compounds with a range of diuretic activity or amiloride hydrochloride or the vehicle. Diuresis occurred with furosemide and benzyl furosemide, but not with isofurosemide, amiloride hydrochloride, or the vehicle. The urinary excretion rate of active kallikrein was significantly elevated above controls throughout the 72 h of treatment with all of the drugs tested, regardless of the level of diuresis or the rate of urinary electrolyte excretion. In contrast, the urinary excretion rate of total kallikrein (prokallikrein + active kallikrein) was unchanged in all groups. These data indicate that furosemide derivatives increase the activation, but not the excretion, of urinary prokallikrein and that these effects are unrelated to the chemical structure or diuretic activity of the compounds or to overall changes in urinary electrolyte excretion rates.
Applications of Capillary Electrophoresis in Nephrology
Authors: Stocking Christopher J. , Slater Jonathan M. , Simpson C.F.
Published: April 2003

Capillary electrophoresis has recently emerged as a powerful technique for separating components in biological samples. A family of separation methods capable of handling a diverse range of samples has been developed, the sample volumes required are very small and a wide range of specialised detectors can be employed. This review examines some methods with particular application to the analysis of urine and tubular fluid samples and references relevant applications.
Transgenic Models in Renal Tubular Physiology
Authors: Jaisser Frederic , Beggah Ahmed T.
Published: April 2003

Animal transgenesis has proven to be useful for physiological as well as physiopathological studies. Besides the classical approach based on the random integration of a DNA construct in the mouse genome, gene targeting can be achieved using totipotent embryonic stem (ES) cells for targeted transgenesis. Transgenic mice are then derived from the transgenic ES cells. This allows the introduction of null mutations in the genome (so-called knock-out) or the control of the transgene expression by the endogenous regulatory sequences of the gene of interest (so-called knock-in). Development of these transgenic animals leads to a better understanding of the cellular function of many genes or to the generation of animal models for human diseases. The purpose of this short review is to describe animal models in renal tubular physiopathology. Recent progresses will allow the generation of animal models with conditional expression of the transgene of interest or with a conditional gene mutation. This permits spatial and temporal control of the expression of the transgene or of the mutation. This should allow the generation of models suitable for physiological analysis or closer to disease state.
Tubule Function in Transgenic Mice
Authors: Wang Tong , Giebisch Gerhard
Published: April 2003

Many transporters involved in renal electrolyte transport have recently been identified and cloned. The availability of genetically manipulated mice, especially transgenic knockout and overexpression models, has made it possible to examine ion transport in kidney tubules in the absence of specific transporters whose function in defined tubule segments is well known. Such selective alterations in transport functions are also useful to investigate adaptive mechanisms by which the kidney compensates for specific transport lesions. Examples of mouse models displaying altered renal transport function include targeted disruption of genes encoding the Na-H exchanger isoforms NHE2 and NHE3, the thiazide-sensitive Na-Cl cotransporter TSC, CFTR, and the colonic isoform of the H,K-ATPase. Moreover, mice with null mutation in the Na-H exchanger isoform NHE1 have been also identified. In addition, a strain of mice with enhanced H,K-ATPase expression due to a defective endocytosis signal has been developed. Other transporter knockout models will soon become available. In this review we focus on the physiological characterization of renal tubule transport in animals with well-defined genetic transport lesions.
Combined in vivo and in vitro Approaches to Analysis of Renal Tubule Function
Authors: Malnic Gerhard
Published: April 2003

The study of renal tubule function obtained its first impulse with whole kidney approaches, such as the clearance technique, and is presently centered on cellular analysis involving intracellular ion activities and on molecular studies describing the structure of transporter molecules and the function of their subunits and constitutional building blocks as well as their distribution along the nephron and within individual cells. Between these extremes a number of successful techniques have dominated the field, including the micropuncture methods which were pioneered by Richards, Walker and others in the late 1920s and 1930s, and were revived and perfectioned in the following decades leading to complex in vivo and in vitro micromethods that for an important period of time have been the center of scientific progress in this area. In the present paper, some of the methods in this field are shortly reviewed, specifically from the point of view of acid-base physiology applied to the renal tubule.
Sodium Balance and Hypertension: Rare Genetic Disorders Expose Pathogenic Mechanisms
Authors: Burnier Michel
Published: April 2003

The importance of sodium in the pathophysiology of hypertension has been revealed by several sources, including large epidemiological analyses, interventional trials, and a large body of experimental and clinical evidence. According to Guyton’s hypothesis, a shift of the pressure-natriuresis curve has been described in all forms of hypertension, suggesting that the ability of the kidney to excrete sodium must be altered in hypertension. Yet, the intrarenal mechanism responsible for the abnormal salt excretion remains unknown. In recent years, the discovery of the molecular mechanisms involved in the pathogenesis of some rare forms of hypertension, i.e., Liddle’s syndrome, glucocorticoid-remediable hypertension, and apparent mineralocorticoid excess, has revived the interest in salt-induced hypertension, since the reported genetic defects decrease the ability of the kidneys to excrete sodium. This review presents the pathogenic mechanisms revealed by these rare disorders and discusses the possible implication of these discoveries for the understanding of the pathophysiology of essential hypertension.
Effect of Radiocontrast Agents on Intrarenal Nitric Oxide (NO) and NO Synthase Activity
Authors: Heyman Samuel N. , Goldfarb Marina , Carmeli Fanni , Shina Ahuva , Rahmilewitz Daniel , Brezis Mayer
Published: April 2003

Background/Aims: Contrast media (CM) induce a biphasic renal hemodynamic response, with late prominent cortical vasoconstriction and marked outer medullary vasodilation. The objective of the study was to explore a possible role for altered nitric oxide (NO) production or bioavailability in these hemodynamic responses. Methods: We explored the impact of CM (sodium iothalamate) upon rat renal NO synthase (NOS) activity (citrulline recovery) and NO (using a NO electrode). Results: The cortical NOS activity following CM was 11.5 ± 1.0 versus 13.8 ± 1.1 nmol/gww/min (gww = gram wet weight) in controls (p = 0.16, NS). In rats pretreated with the nonselective endothelin antagonist bosentan, CM reduced the cortical NOS activity to 8.5 ± 1.2 nmol/gww/min (p < 0.005 vs. controls). Cortial NO readings declined over 30 min following CM by 13 ± 8% (p < 0.05, Anova), in parallel with the decline in cortical blood flow. The outer medullary NOS activity was not affected by CM (5.2 ± 1.5 vs. 5.5 ± 1.3) nmol/gww/min in controls) or bosentan. Nevertheless, the outer medullary NO reading increased by 36 ± 23% (p < 0.05), with a concomitant increase in regional blood flow. Conclusion: In the cortex, CM might reduce the NOS activity (an effect blunted by endothelin release). This may potentiate the effect of endothelin to induce regional vasoconstriction. In the outer medulla, the vasodilatory response to CM does not seem to be mediated by enhanced NOS activity and might reflect increased local NO bioavailability as the result of regional hypoxia.
Targets for Endothelin in the Diseased Kidney: Clues for Therapeutic Intervention
Authors: Rohmeiss P. , Birck R. , Braun C. , Kirchengast M. , van der Woude F.J.
Published: April 2003

The endothelin system has been implicated in various renal diseases. This review focuses on the involvement of endothelin-1 in pathogenesis and pathophysiology of acute and chronic renal failure with regard to its hemodynamic and nonhemodynamic effects. Future developments concerning the use of endothelin receptor antagonists and the role of endothelin in the kidney transplantation setting are discussed.
The Proximal Tubule Phenotype and Its Disruption in Acute Renal Failure and Polycystic Kidney Disease
Authors: Witzgall Ralph
Published: April 2003

In light of recent developments in the fields of genetics, molecular, cell and developmental biology, the kidney is receiving increasing attention as a model system for organ development and human diseases. Gene disruption experiments have provided evidence for the essential role of a number of proteins in the earliest phase of nephron development, but very little is known about the identity of such proteins in more advanced stages. This minireview will focus on the proximal tubule and its role in the pathology of ischemic acute renal failure and polycystic kidney disease. Like all other nephron segments, the proximal tubule develops from the metanephrogenic mesenchyme. So far the only genetic model which affects the function of the proximal tubule is a strain of knockout mice with an inactivation of the HNF1 gene. After ischemic renal damage the proximal tubule responds with a different genetic program than the distal tubule. Evidence from human polycystic kidney disease and several animal models of polycystic kidney disease suggests that proximal tubules are affected differently by polycystic kidney disease than distal tubules and collecting ducts.
Thrombin: A Novel Renal Growth Factor
Authors: Grandaliano Giuseppe , Gesualdo Loreto , Schena Francesco P.
Published: April 2003

Glomerular fibrin deposition is a common histopathological finding in a variety of glomerular diseases and suggests the intraglomerular activation of the coagulation system. The activation of thrombin is the last step in the coagulation cascade. On the basis of its ability to modulate several cell functions through the activation of different receptors and intracellular-signaling pathways, thrombin could be considered as a growth factor more than as a simple coagulation factor. Indeed, this multifunctional serine protease may represent the link between the activation of the coagulation cascade and the inflammatory and profibrotic response at the glomerular level. This review will focus on the potential role of thrombin in the pathogenesis of glomerular damage and on the mechanisms underlying the cellular effects of this serine protease.
mRNA Differential Display Analysis of Nephrotic Kidney Glomeruli
Authors: Haltia Anni , Solin Marja-Liisa , Luimula Pauliina , Kretzler Matthias , Holthöfer Harry
Published: April 2003

Background: Differential display RT-PCR (DDRT-PCR) is a new powerful technique for identification and characterization of altered gene expression in eukaryotic cells and tissues. We studied here changes in kidney glomerular gene expression in patients with congenital nephrotic syndrome of the Finnish type (CNF), an inherited kidney disease with heavy proteinuria already in utero. Methods: Using the DDRT-PCR approach and isolated glomeruli from removed human kidneys, we compared the gene expression patterns of normal human and CNF glomeruli. Differential expression of candidate genes was verified by Northern blotting, and the corresponding PCR fragments were sequenced and compared to known sequences in databanks. Results: We found several genes and sequence tags with altered expression in nephrotic glomeruli including fragments with close homologies to cytochrome c oxidase subunit I, integrin-linked kinase, insulin-like growth factor II receptor and eotaxin, and also clones resembling anchyrin and cadherin-like consensus sequences. Conclusion: All the sequences identified are of interest in respect to pathogenesis of proteinuria. Furthermore, this study reveals potentially new members to known gene families with tissue and cell type-specific expression.
Progressive Renal Disease: Fibroblasts, Extracellular Matrix, and Integrins
Authors: Norman Jill T. , Fine Leon G.
Published: April 2003

Progressive renal disease is characterized by expansion of the tubulo-interstitium and accumulation of extracellular matrix within this tissue compartment. Interstitial fibroblasts are the primary producers of the interstitial matrix, and in the evolution of tubulo-interstitial fibrosis these cells undergo changes, namely increased proliferation, differentiation to myofibroblasts, and altered extracellular matrix metabolism, all of which, in other cell types, have been shown to be regulated by the major family of extracellular matrix receptors, the integrins. In the normal kidney, interstitial fibroblasts express α1, α4, α5, and β1 integrins, and fibrosis is associated with increased expression of α1, α2, α5, αv, and β1 integrins. In particular, α5, β1, and αv are suggested to be linked with the fibrotic process. In vitro, renal fibroblasts express a similar range of integrins, and ligation of selected receptors is associated with specific functions. Ligation of α6 stimulates proliferation, while α5 promotes expression of myofibroblastic phenotype, and β1 integrin has been implicated in cell contraction. Recent studies suggest that renal fibroblasts also express the non-integrin matrix receptors, discoidin domain receptors, and that changes in activation of these receptors may be associated with fibrogenic events. Thus the current, albeit limited, data suggest an important role for receptors for extracellular matrix molecules in the pathogenesis of progressive renal fibrosis.
Cell Cycle Regulatory Proteins in Glomerular Disease
Authors: Shankland Stuart J. , Al’Douahji Mouhannad
Published: April 2003

The growth response of resident glomerular cells is determined by the underlying disease. Thus glomerular cells can proliferate, fail to proliferate, hypertrophy or apoptose. Cell growth is controlled by cell cycle regulatory proteins, and cell proliferation requires that cyclin-dependent kinases (CDK) be activated by partner cyclins. Inhibiting CDK2 reduces mesangial cell proliferation. Mesangial cell proliferation also requires that levels of specific cyclin kinase inhibitors (CKI) decrease. In contrast, the visceral glomerular epithelial cells’ inability to proliferate may be due to increased levels of CKI. Moreover it is becoming increasingly clear that mesangial cell hypertrophy in diabetes requires increased CKI expression. Finally, apoptosis, which is often linked to proliferation, may also be due to the increased activity of CDK2. Thus, identifying specific cell cycle regulatory proteins following injury may provide future targets for therapy in glomerular disease.