bluuebunny/crossref_metadata_2025 huggingface dataset:
Nonconvulsive Status epilepticus during Cephalosporin Therapy
Authors: Primavera Alberto , Cocito Leonardo , Audenino Daniela
Published: May 2004

Cephalosporins may induce nonconvulsive status epilepticus (NCSE), a potentially reversible condition. Despite the wide use of these antibiotics, there are only few reported cases, because this condition is probably underestimated. We report two new cases of NCSE occurring during treatment with cefepime and ceftazidime, and emphasize the utility of emergent electroencephalogram in patients with an acute altered state of consciousness while receiving treatment with cephalosporins, particularly when there is evidence of impaired renal function.
Glomerular Capillary Tenascin Staining in Renal Allografts and Its Correlation with Capillary Loop ‘Double Contours’, Proteinuria and Graft Outcome
Authors: Fukuda Michio , Morozumi Kunio , Uchida Kazuharu , Oikawa Tadashi , Takeda Asami , Yosida Atsuhiro , Kimura Genjiro
Published: May 2004

Background: Glomerular capillary injuries result in proteinuria, previously reported to be a risk factor for renal allograft dysfunction. According to the Banff 97 Working Classification of Renal Allograft Pathology, ‘double contours’ in glomerular capillary loops (GC-DC) were suggested to be most specific for chronic transplant glomerulopathy. Tenascin-C (TN), a component of extracellular matrix, is known to be overexpressed in various conditions. Methods: TN immunostaining was performed by the labeled streptavidin biotin method. The correlations between glomerular capillary TN (GC-TN) and proteinuria, and between GC-DC and GC-TN, were studied in 27 biopsies showing chronic allograft nephropathy (CAN) lesions. In 14 patients (serum creatinine <2.0 mg/dl at biopsy), graft outcome was studied. Graft function 3 years after biopsy was classified as stable or deteriorated; the term ‘deteriorated’ was used if serum creatinine had increased 20% over baseline, or if the patient required dialysis. Results: In CAN, GC-TN correlated with GC-DC. Proteinuria in patients with intense GC-TN tended to increase during 1 year after biopsy. In graft outcome analysis, GC-TN was significantly lower in stable grafts than in deteriorated ones. Furthermore, all 3 patients demonstrating weak GC-TN without GC-DC returned to dialysis. Conclusion: TN immunostaining is a sensitive method to detect glomerular capillary injury with a predictive value for renal allograft dysfunction.
Usefulness of Microalbuminuria in Cardiovascular Risk Stratification of Essential Hypertensive Patients
Authors: Cerasola Giovanni , Mulè Giuseppe , Nardi Emilio , Cottone Santina , Andronico Giuseppe , Mongiovì Rosalia , Mezzatesta Gianfranco
Published: May 2004

Background/Aims: To evaluate the influence of microalbuminuria (albumin excretion rate – AER) determination and echocardiography (ECHO) on cardiovascular risk stratification, initially performed according the 1999 WHO/ISH guidelines by using only routine diagnostic procedures with or without fundal examination. Methods: 312 essential hypertensives attending our institution were studied retrospectively. Cardiovascular risk was assessed in a semiquantitative way using four categories of absolute cardiovascular disease risk (low, medium, high and very high risk), as proposed by the 1999 WHO/ISH guidelines, on the basis of data on the average 10-year risk of cardiovascular events among participants in the Framingham Study. Results: Without the retinal data, estimating the level of global cardiovascular risk on the basis of routine work-up alone, 14% were classified as low-risk patients, 48% were as medium-risk, 20% as high-risk and 18% at very-high-risk patients. The combined use of AER and ECHO, in line with the newer ESH-ESC guidelines, determined a statistically significant reclassification of the hypertensive patients. Only 10% remained in the low-risk category, 28% were classified in the medium-, 42% in the high- and 20% in the very-high-risk classes. The overall percentage of patients that changed risk stratum (mostly shifting from the medium- to the high-risk class) was significantly different from the proportion of subjects reclassified after the addition of either microalbuminuria or echocardiography alone. No change in the distribution of risk categories was observed when AER assay and ECHO were added to routine procedures including funduscopic examination. Conclusions: Considering the questionable prognostic value of qualitative retinal examination, our results suggest that cardiovascular risk evaluation based only on simple routine work-up, ignoring the information provided by AER determination and ECHO, may underestimate the level of absolute risk.
Effect of Dietary Creatine on Skeletal Muscle Myosin Heavy Chain Isoform Expression in an Animal Model of Uremia
Authors: Taes Youri E.C. , Speeckaert Marijn , Bauwens Evelien , De Buyzere Marc R. , Libbrecht Johan , Lameire Norbert H. , Delanghe Joris R.
Published: May 2004

Background: Chronic renal failure is accompanied with muscle dysfunction and myopathy, characterized by muscle weakness and increased fatigue. Myosin heavy chain (MHC) is the principal structural protein that controls the intrinsic contractile properties of striated muscle. Creatine is widely used as an ergogenic nutritional supplement in sportsmen. This study investigates the effect of creatine supplementation on MHC expression in the setting of uremic myopathy. Methods: Male Wistar rats were either sham operated or subtotally nephrectomized and received a control diet or creatine (2% w/w)-supplemented diet. After 4 weeks of treatment, serum creatinine, creatine, urea and creatinine clearances were determined. MHC isoforms were determined electrophoretically in the extensor digitorum longus and soleus muscles. Results: Creatinine clearances were lower in nephrectomized animals, but similar in creatine-supplemented and control diet animals. Nephrectomized animals had significantly higher MHC IIb and lower MHC IIx isoform expression in the extensor digitorum longus muscle compared to sham-operated animals. In the soleus muscle, MHC IIb expression was increased in nephrectomized animals. Creatine supplementation reversed the MHC transitions observed in uremia in the soleus muscle, but not in the extensor digitorum longus muscle. Conclusion: We observed altered expression of MHC isoforms in uremia. In uremic animals, fast MHC IIb isoforms were increased, whereas MHC I and IIx isoforms predominate in control animals. Dietary creatine supplementation reversed the altered MHC expression during uremia in slow-twitch, but not in fast-twitch muscles.
Selective Expression of TGF-β2 and TGF-β3 Isoforms in Early Mesangioproliferative Glomerulonephritis
Authors: Minto Andrew W. , Wilson Heather M. , Rees Andrew J. , Quigg Richard J. , Brown Paul A.J.
Published: May 2004

Background/Aim: Evidence from ex vivo glomerular analysis has implicated overexpression of transforming growth factor (TGF) beta 1 in progressive renal disease. The roles of TGF-β2 and TGF-β3 are less clear. The purpose of this study was to define the temporal expression and abundance of TGF-β isoforms in both acute and progressive Thy-1 glomerulonephritis during the crucial initiation phase of these models. Methods: Acute Thy-1 glomerulonephritis was induced by a single injection of OX7, while the progressive model was induced by two injections, 7 days apart. Results: Cellular infiltration of glomeruli consisted of transient increases of neutrophils and ED1+ macrophages. The distribution of TGF-β1, TGF-β2, and TGF-β3 revealed distinct differences in normal and nephritic rats. No changes in TGF-β1 staining were observed within glomeruli of either model. In marked contrast, in the one-shot model, TGF-β2 and TGF-β3 stainings increased rapidly, yet transiently, throughout affected glomeruli, followed by more sustained staining in glomerular epithelial cells. Diffuse, transient staining was absent in two-shot glomerulonephritis, but an increase in epithelial cell staining mirrored that seen in the one-shot model. Conclusion: Based on these results, we propose that the effects, formerly thought of as solely due to a single entity, TGF-β1, may be the result of an interplay between individual TGF-β isoforms.
Successful Gene Transfer Using Adeno-Associated Virus Vectors into the Kidney: Comparison among Adeno-Associated Virus Serotype 1–5 Vectors in vitro and in vivo
Authors: Takeda Shin-ichi , Takahashi Masafumi , Mizukami Hiroaki , Kobayashi Eiji , Takeuchi Koichi , Hakamata Yoji , Kaneko Takashi , Yamamoto Hisashi , Ito Chiharu , Ozawa Keiya , Ishibashi Kenichi , Matsuzaki Toshiyuki , Takata Kuniaki , Asano Yasushi , Kusano Eiji
Published: May 2004

Background/Aim: Gene transfer into the kidney has great potential as a novel therapeutic approach. However, an efficient method of gene transfer into the kidney has not been established. We explored the transduction efficiency of renal cells in vitro and in vivo using adeno-associated virus (AAV) serotype 1–5 vectors encoding the β-galactosidase gene. Methods: In the in vitro study, rat kidney epithelial cell line NRK52E cells were transfected with AAV serotype derived vectors. In the in vivo study, AAV serotype derived vectors were selectively injected into the kidney using a catheter-based gene delivery system in rats and mice mimicking the clinical procedure. The efficiency of gene expression was histologically evaluated on the basis of the β-galactosidase expression. Results: AAV serotype 1, 2, and 5 vectors transduced in rat kidney epithelial cell line NRK52E cells in vitro, whereas AAV serotype 3 or 4 vectors showed no transduction. In addition, the kidney-specific injection of AAV serotype 2 vectors successfully transduced in tubular epithelial cells, but not in glomerular, blood vessel, or interstitial cells in vivo, whereas the rest of the serotypes showed no transduction. Conclusion: Since kidney-specific gene delivery via the renal artery by catheterization is highly feasible in humans, these findings provide useful information for promising strategies in renal gene therapy.
A New Method of Color Doppler Perfusion Measurement via Dynamic Sonographic Signal Quantification in Renal Parenchyma
Authors: Scholbach Thomas , Dimos Ingo , Scholbach Jakob
Published: May 2004

Objective: Perfusion quantification of tissues is an important goal to evaluate the state of blood supply of an organ. We developed a method to quantify tissue perfusion via color Doppler signal quantification from sonographic videos and applied this to describe renal parenchymal perfusion in healthy kidneys. Method: Color Doppler sonographic videos of renal perfusion from both kidneys of 87 healthy children (age 2 weeks to 16 years) were recorded under defined conditions. Perfusion data (color hue, color area) were measured in a standardized region of interest automatically. Signal intensity was calculated as whole ROIs (regions of interest) mean flow velocity (cm/s) encoded by color Doppler signals during one full heart cycle. Results: Normal signal intensity values are: 1.86 cm/s in the region encompassing central 50% of the renal cortex and 0.56 cm/s in the peripheral 50% of the renal cortex. These differences are significant. Signal intensity of both kidneys did not differ. Conclusion: Signal intensity of cortical tissue in healthy kidneys was quantified noninvasively from color Doppler signal data in an easily accomplishable manner with new measurement software. Normal values for this technique have been calculated. Possible further applications might be all situations, where perfusion changes could be expected like inflammation, renal insufficiency, vascular diseases and tumors.
Oxidative Stress Influences CC-Chemokine Levels in Hemodialyzed Patients
Authors: Pawlak Krystyna , Pawlak Dariusz , Mysliwiec Michal
Published: May 2004

Background: Increased oxidative stress (SOX) has been reported in hemodialyzed (HD) patients, but its influence on CC-chemokine levels remains unknown. Methods: The levels of 3 distinct SOX markers (Cu/Zn superoxide dismutase (Cu/Zn SOD), total lipid peroxide, and autoantibodies against oxidized LDL (OxLDL-Ab)), as well as those of 4 CC-chemokines (monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory proteins (MIP-1α, MIP-1β), regulated upon activation, normal T cell expressed and secreted (RANTES), and tumor necrosis factor-α (TNF-α)) were measured pre- and post-HD session in 15 HD patients with cardiovascular disease (CVD) and 12 HD patients without CVD (pre- and post-HD session) and 17 controls. Results: Cu/Zn SOD levels were elevated in HD patients (both before and after HD) compared to controls (p < 0.001). Total lipid peroxide levels were similar in the controls in pre-dialysis samples, but were increased after a HD session (p < 0.001). Pre-dialysis OxLDL-Ab levels were increased only in the HD group with CVD compared to controls (p < 0.05). The pre-dialysis plasma levels of TNF-α (p < 0.001), MCP-1 (p < 0.001) and MIP-1β (p < 0.01) were increased both in all HD patients and subgroups with CVD when compared to the controls, and remained significantly elevated when measured after HD. Dialysis increased MCP-1 (p < 0.05) and MIP-1β (p < 0.001) levels as compared to the controls as well as in patients without CVD. Plasma RANTES was significantly lower before HD (p < 0.05) and after HD (p < 0.001) in patients with CVD. Patients without CVD and all HD patients also had lower RANTES before and after HD when compared to controls (all p < 0.001). A positive correlation was observed between plasma pre-dialysis Cu/Zn SOD levels and the other SOX markers (all p < 0.05), age (p < 0.05) and duration of hemodialysis (p < 0.001). A positive relationship existed between plasma Cu/Zn SOD levels and those of MCP-1, MIP-1β and TNF-α (all p < 0.001). RANTES levels negatively correlated with Cu/Zn SOD (p < 0.0001).TNF-α positively correlated with age (p < 0.05), total lipid peroxide (p = 0.010), MCP-1 (p < 0.01) and MIP-1β levels (p < 0.01). An identifiable association exists between MCP-1 and MIP-1β levels (p < 0.01), whereas both MCP-1 and MIP-1β were inversely correlated with RANTES (both p < 0.05). Conclusion: Our data indicate for the first time a probable functional relationship between oxidative stress and CC-chemokine levels in hemodialyzed patients, particularly in those with cardiovascular disease. This relationship may represent one of the mechanisms involved in the progression of atherosclerosis in these patients.
Intestinal Absorption and Biliary Secretion of Zinc in Rats with Chronic Renal Failure
Authors: Chen Shu-Ming , Liao Jyh-Fei , Kuo Cheng-Deng , Ho Low-Tone
Published: May 2004

Background/Aims: In chronic renal failure (CRF), zinc deficiency is partially attributed to decreased intestinal zinc absorption, but the mechanism of this decrease in intestinal zinc absorption is obscure. Therefore, the objective of this study was to investigate the cause of decreased intestinal zinc absorption in a uremic rat model using an in vivo perfusion technique as well as to evaluate the effect of intestinal zinc perfusion on the secretion of biliary zinc in normal and CRF rats. Methods: CRF was induced by five-sixths nephrectomy (Nx). During zinc sulfate perfusion, absorption of zinc in the small intestine and the response of plasma zinc level were measured. After intestinal zinc perfusion for 80 min, the concentrations of zinc and metallothionein (MT) in the intestinal mucosal and liver tissue were assayed. The secretion of biliary zinc and the excretion of urinary zinc were also determined before and after zinc sulfate perfusion. The results were compared with those obtained from 10 sham-operated normal rats. Results: The CRF rats showed a significant decrease in the rate of intestinal zinc absorption and in the response of plasma zinc levels during intestinal zinc perfusion. They also had significantly higher levels of mucosal zinc and MT than sham-operated normal rats, but their contents of liver zinc were significantly lower than those of sham-operated normal rats after zinc sulfate perfusion. CRF rats showed a low plasma zinc level and a high urinary zinc excretion in baseline levels, but had similar output of basal biliary zinc as compared with sham-operated normal rats. Zinc sulfate perfusion in the small intestinal was not found to increase the secretion of biliary zinc and the excretion of urinary zinc, either in normal or CRF rats. Conclusion: In the CRF rat, the reduction of intestinal zinc absorption may result from reduced mucosal zinc efflux from the basolateral membrane into plasma. These data also suggest that the absorbed zinc from the gastrointestinal tract is mostly taken up by the liver or other tissues, and is less excreted in bile juice and urine.
Human Cortical Fibroblast Responses to High Glucose and Hypoxia
Authors: Qi Weier , Poronnik Philip , Young Barbara , Jackson Chris J. , Field Michael J. , Pollock Carol A.
Published: May 2004

Background/Aims: Approximately 30% of individuals with diabetes mellitus are susceptible to diabetic nephropathy, whereas ischemic injury uniformly induces renal impairment. As matrix accumulation correlates with progressive renal disease we assessed parameters associated with matrix turnover in response to high glucose ± hypoxia in human cortical fibroblasts (CF). Methods: CF were grown to confluence and exposed to media containing 5 or 25 mmol/l D-glucose for 72 h with or without a superimposed hypoxic insult. Results: High glucose increased cellular protein content (p < 0.05). Combined high glucose and hypoxia induced a further increase in cellular protein content (p < 0.005), suggestive of a synergistic hypertrophic effect. MMP secretion corresponded inversely with changes in TIMP expression. In cell cultures derived from 2/3 of patients, high glucose increased MMP-9 (p < 0.0005) and MMP-2 (p < 0.005) while TIMP-1 was reduced (p = 0.05). In the remaining cell cultures derived from 1/3 of patients, MMP-2 was reduced (p < 0.0001) while TIMP-1 and TIMP-2 were both increased (p < 0.05). In contrast, hypoxia induced uniform reductions in MMP-9 and MMP-2 in both normal and high glucose conditions. High glucose increased the expression of PAI-1 mRNA (p < 0.05) in all patients independent of changes in the MMP-TIMP axis. Conclusions: In summary, variability was observed in the MMP-TIMP axis following exposure to high glucose. In contrast, high glucose uniformly induces PAI-1 expression. Hypoxic insults uniformly reduce matrix breakdown independent of the prevailing glucose conditions.
Bilateral Stimulation of the Subthalamic Nucleus in Parkinson’s Disease: Surgical Efficacy and Prediction of Outcome
Authors: Jaggi Jurg L. , Jaggi Jurg L. , Umemura Atsushi , Umemura Atsushi , Hurtig Howard I. , Hurtig Howard I. , Siderowf Andrew D. , Siderowf Andrew D. , Colcher Amy , Colcher Amy , Stern Matthew B. , Stern Matthew B. , Baltuch Gordon H. , Baltuch Gordon H.
Published: May 2004

Objective: Over the last decade neurosurgery has reemerged as a valid therapy for patients with advanced Parkinson’s disease. Previously, we have addressed safety and efficacy of subthalamic nucleus (STN) deep brain stimulation (DBS). In this study, we extended these observations and analyzed factors that affect surgical outcome and its predictive value. Methods: Thirty-nine patients were enrolled in an open-label prospective protocol designed to evaluate safety and efficacy of bilateral STN DBS in patients with advanced Parkinson’s disease between January 1999 and July 2002. Electrodes were stereotactically implanted with electrophysiological conformation of the target location. All patients were evaluated in the medication ‘off’ and ‘on’ state preoperatively and at 3, 6, and 12 months after surgery in medication ‘on’ and ‘off’ as well as in the stimulation ‘off’ and ‘on’ state. Tests included Unified Parkinson’s Disease Rating Scales (UPDRS) as well as timed tests. All data was analyzed by means of Analysis of Variance. For outcome prediction, correlation and linear regression analyses were utilized. Stimulation produced significant improvements in all ‘off’ mediation conditions, resulting in a 42% improvement in UPDRS III score at 12 months compared to the preoperative status. Stimulation in conjunction with medication did not produce any significant change when compared to the preoperative medication ‘on’ state. Dyskinesia, motor fluctuations, and duration of ‘off’ periods were significantly reduced with stimulation. Significant outcome predictor variables were age, preoperative percent change of UPDRS III score from medication ‘off’ to medication ‘on’ state, and the duration of disease. Conclusions: Bilateral STN DBS produces robust improvements in parkinsonian motor symptoms. Surgical outcome can reliably be predicted.
Low-Molecular-Weight Heparin in Acute Coronary Syndromes
Authors: O’Donnell Martin , Turpie A.G.G.
Published: May 2004

Acute coronary syndrome (ACS) may be divided into two distinct conditions on the basis of the electrographical presence or absence of significant ST-segment elevation. Coronary arterial plaque rupture with subsequent thrombus formation is usually responsible for the development of ACS. A number of antithrombotic therapies have been developed to inhibit key steps in the sequential process of thrombus formation. Thrombin generation is of critical importance in the creation of intracoronary thrombosis. Heparins, in therapeutic doses, reduce the risk of death and myocardial infarction by about 50% in aspirin-treated patients presenting with ACS with non-ST-segment elevation. Low-molecular-weight heparin (LMWH) primarily targets the inhibition of factor Xa (and to a lesser extent thrombin) by binding with antithrombin. A number of well-designed, large randomized controlled trials have shown that LMWHs have at least comparable efficacy and safety to unfractionated heparin, but their superior practical advantages have made them a mainstay therapy in the treatment of ACS with non-ST-segment elevation. More recently, the role of LMWH in the treatment of ACS with ST elevation has been evaluated in a large randomized trial.
Acupuncture and Moxibustion in the Treatment of Active Crohn’s Disease: A Randomized Controlled Study
Authors: Joos Stefanie , Brinkhaus Benno , Maluche Christa , Maupai Nathalie , Kohnen Ralf , Kraehmer Nils , Hahn Eckhart G. , Schuppan Detlef
Published: May 2004

Background: Acupuncture has traditionally been used in the treatment of inflammatory bowel disease in China and is increasingly being applied in Western countries. The purpose of this study was to investigate the efficacy of acupuncture in the treatment of active Crohn’s disease (CD). Methods: A prospective, randomized, controlled, single-blind clinical trial was carried out to analyze the change in the CD activity index (CDAI) after treatment as a main outcome measure, and the changes in quality of life and general well-being, serum markers of inflammation (α1-acid glycoprotein, C-reactive protein) as secondary outcome measures. 51 patients with mild to moderately active CD were treated in a single center for complementary medicine by three trained acupuncturists and randomly assigned to receive either traditional acupuncture (TCM group, n = 27) or control treatment at non-acupuncture points (control group, n = 24). Patients were treated in 10 sessions over a period of 4 weeks and followed up for 12 weeks. Results: In the TCM group the CDAI decreased from 250 ± 51 to 163 ± 56 points as compared with a mean decrease from 220 ± 42 to 181 ± 46 points in the control group (TCM vs. control group: p = 0.003). In both groups these changes were associated with improvements in general well-being and quality of life. With regard to general well-being, traditional acupuncture was superior to control treatment (p = 0.045). α1-acid glycoprotein concentration fell significantly only in the TCM group (p = 0.046). Conclusions: Apart from a marked placebo effect, traditional acupuncture offers an additional therapeutic benefit in patients with mild to moderately active CD.
Effect of Intraduodenal Administration of Ursodeoxycholic Acid on Interdigestive Interaction between Gallbladder Motility, Pancreatic Secretion and Endocrine Activity
Authors: Neubrand M.W. , Dominguez-Munoz J.E. , Reichel C. , Kampmann S. , Eschmann K. , von Falkenhausen M. , Bregulla M. , Malfertheiner P. , Sauerbruch T.
Published: May 2004

Background: Gastroduodenal motorfunction, gallbladder motility, and pancreatic secretion are closely related during the interdigestive state. The extent to which application of ursodeoxycholic acid (UDC) influences this process is only partly understood. Aim: As UDC is widely used for the therapy of gallbladder stones and of cholestatic liver disease, we wanted to define the immediate effect of UDC on interdigestive gallbladder and antroduodenal motility, biliary-pancreatic secretion and hormone release in man. Methods: Interdigestive gastrointestinal function in 10 healthy males (26–35 years) was studied twice after 12-hour fasting on 2 different days. Antroduodenal motility was continuously recorded manometrically over a complete interdigestive migrating motor complex (MMC) cycle. Gallbladder volume was evaluated sonographically in 5- to 7-min intervals during the MMC cycle. Pancreatic and biliary secretion was determined by a standard duodenal perfusion technique measuring chymotrypsin, amylase, lipase and bile salts in duodenal aspirates every 15 min. Plasma levels of pancreatic polypeptide (PP) and motilin were determined by radioimmunoassay in 15-min intervals. On 2 separate days, 7–10 days apart, each subject received intraduodenally either 10 mg/kg UDC (pH 8) or placebo 30 min after the first recorded duodenal MMC cycle phase III. Results: With placebo, the fasting gallbladder volume decreased slightly from phase I (32 ± 8 ml) to the end of phase II (24 ± 13 ml), but increased significantly from 31 ± 14 ml (phase I) to 46 ± 11 ml (phase III) after intraduodenal UDC application (p < 0.01). Pancreatic secretion was significantly reduced after UDC application at the end of phase II (secretion of chymotrypsin 10 ± 3 U/min vs. 5 ± 2 U/min, p < 0.01). Serum levels of PP were also reduced by UDC during the entire MMC cycle. This reached statistical significance at the end of phase II (84 ± 8 pg/ml vs. 57 ± 14 pg/ml; p < 0.05) and during phase III (86 ± 19 pg/ml vs. 64 ± 22 pg/ml; p < 0.05), while motilin slightly increased during the MMC cycle after UDC application. UDC instillation did not affect antroduodenal motility. Conclusion: UDC exerts significant inhibitory effects on interdigestive gallbladder contractility, pancreatic secretion, and PP release. Whether these inhibitory effects are mediated by cholinergic pathways or other mechanisms requires further investigation.
Effect of IgG Therapy on Lymphocyte Subpopulations in the Peripheral Blood of Kuwaiti Women Experiencing Recurrent Pregnancy Loss
Authors: Mahmoud F. , Diejomaoh M. , Omu A. , Abul H. , Haines D.
Published: May 2004

Intravenously administered polyspecific IgG is being increasingly used as an immunomodulating therapy with controversial beneficial outcome. The aim of this study was to evaluate the effects of IgG infusion on peripheral T-cell subpopulations in women with recurrent pregnancy loss (RPL). Fifteen women with a history of three previous RPL between 6 and 22 weeks of gestation and positivity for the antiphospholipid antibody syndrome (APS) were randomized to one of two treatment groups: (a) an intravenous immunoglobulin therapy group (RPL-IVIg; 7 patients), 500 mg IVIg/kg/month and (b) a placebo-treated group given multivitamins (8 patients). Control groups comprised either normal pregnant women without APS (10 patients) or non-pregnant women. The T-cell markers were characterized using a monoclonal antibody panel including CD3, CD4, CD8, CD25, CD29, CD38, CD45RA, CD45RO, CD54 and HLA-DR. Analysis was performed with a two-color fluorescent-activated flow cytometer. In the first trimester, the percentage of CD4+CD25+, CD4+CD45RO+, CD8+HLA-DR+, and CD8+CD38+ populations were reduced in the multivitamin group compared to normal pregnant women (p < 0.05) while in the RPL-IVIg group only CD4+CD25+ cells were reduced (p < 0.05). By the second trimester, CD3+CD16+CD56+ was significantly higher in multivitamin- than in IVIg-treated women (p < 0.05). The percentage of CD4+HLA-DR+ was significantly higher in the two RPL groups compared to normal pregnant women (p < 0.05). IVIg therapy in women with RPL was associated with a significant reduction in CD3+CD16+CD56+ and CD4+CD25+. This may contribute to the suppression of immune-mediated processes contributing to premature abortion.
Pretransplant Mixed Lymphocyte Culture Still Has an Impact on Graft Survival
Authors: El-Agroudy Amgad E. , Ismail Amani M. , El-Chenawy Farha A. , Shehab El-Din Ahmed B. , Ghoneim Mohamed A.
Published: May 2004

Background/Aim: Mixed lymphocyte culture (MLC) is an important in vitro test for studying allograft reaction. The recipient-donor MLC reflects donor specific hypo- or hyperimmune response. The various studies have been correlated donor-specific MLC reactivity with graft survival in cadaver kidney transplantation. This retrospective study reports the relationship between of MLC hyper-responsiveness and graft survival in living-donor kidney transplantation. Methods: The study included 477 patients who underwent live-donor kidney transplantation between Marsh 1976 and January 2002. They were divided according to the relative response (RR) of pre transplant one way MLC into hypo responders (RR <4) and hyper responders (RR >4). The demographic and follow-up data for both groups were recorded. The duration of follow-up ranged from 44 to 84 months. Results: The two groups were homogenous regarding age, sex, donor source, HLA-A, B-and -DR mismatches, number of blood transfusion and type of 3 primary immunosuppressions. Acute rejection (AR) episodes were seen in 182 (44.8%) patients in the hypo-responders group, of whom 10 were steroid resistant, while in the hyper-responder recipients, AR episodes occurred in 33 patients (46.5%) of whom 5 patients (15.2%) were steroid resistant (p < 0.05). Chronic allograft nephropathy occurred in 14.5% and 27.3% and the actuarial 5-year graft survival was 79% and 60% (p = 0.03).in the hypo- and hyper-responder groups, respectively. Conclusions: It is concluded that MLC reaction may predict high-risk patients for immunological graft failure and that more potent immunosuppression should be considered in MLC hyper-responders.
Arteriolar Endothelial Dysfunction Is Restored in Ischaemic Muscles by Chronic Electrical Stimulation
Authors: Kelsall C.J. , Brown M.D. , Kent J. , Kloehn M. , Hudlicka O.
Published: May 2004

Chronic intermittent electrical stimulation (15 min on, 85 min off, seven times per day) eliminated endothelial dysfunction of pre-capillary arterioles in ischaemic rat ankle flexor muscles. Responses to acetylcholine were restored from constriction to dilation, and the reduced dilation to bradykinin was corrected by 1 week of stimulation. Administration of the NOS inhibitor Nω-nitro-L-arginine for 1 week impaired arteriolar reactivity in a similar way to ischaemia, and dilator function was likewise restored by chronic stimulation. This suggests that nitric oxide production in the microcirculation is depressed by chronic ischaemia and that chronic electrical stimulation can specifically reverse this deficit. Stimulation applied to ischaemic muscles for 2 weeks also increased the numbers of microvessels immunostained for α-smooth muscle actin and the numbers of eNOS-positive microvessels and capillaries. These findings help to elucidate the mechanism of the beneficial effect of exercise in the treatment of peripheral vascular diseases by showing that muscle activity can improve both function and structural capacity of the microvasculature.
Protective Effect of Quercetin on the Evolution of Cisplatin-Induced Acute Tubular Necrosis
Authors: Francescato Heloísa D. Coletta , Coimbra Terezila M. , Costa Roberto S. , Bianchi Maria de L.P.
Published: May 2004

Background: The mechanism of cisplatin-induced nephrotoxicity is unknown, but has been associated with renal lipid peroxidation. The bioflavonoid quercetin may be a potential alternative to reduce cisplatin-induced nephrotoxicity. The aim of this study was to evaluate the effect of quercetin on the evolution of cisplatin-induced acute tubular necrosis. Methods: One hundred and three male Wistar rats were injected with cisplatin (5 mg/kg, i.p.), 43 of them received quercetin (50 mg/kg, by gavage) before cisplatin injection. Blood and urine were collected 5 and 20 days after the injection for the determination of plasma creatinine, urine volume and osmolality. The kidneys were removed for the determination of renal malondialdehyde (MDA) and for histological and immunohistochemical studies. The renal expression of fibronectin, α-smooth muscle actin, vimentin, Jun N-terminal kinase, nuclear factor-ĸB, and macrophages during the evolution of the acute tubular necrosis induced by cisplatin and the histological changes observed in the kidneys were analyzed. Results: Cisplatin-treated rats presented a transitory increase in plasma creatinine levels, tubular cell necrosis and increased immunostaining for vimentin, α-SM-actin, fibronectin, ED1, NF-ĸB, and p-JNK in the renal cortex and outer medulla. These alterations were less intense in animals treated with quercetin. Conclusion: Quercetin treatment attenuated the functional, histological and immunohistochemical alterations induced by cisplatin.
Radial Artery Bypass Grafts Have an Increased Occurrence of Angiographically Severe Stenosis and Occlusion Compared With Left Internal Mammary Arteries and Saphenous Vein Grafts
Authors: Khot Umesh N. , Friedman Daniel T. , Pettersson Gosta , Smedira Nicholas G. , Li Jianbo , Ellis Stephen G.
Published: May 2004

Background—

The radial artery has been increasingly used in CABG. However, angiographic outcome data have been limited.

Methods and Results—

We reviewed all coronary angiography procedures from February 1996 to October 2001 and selected patients with a radial artery bypass graft. Angiographic outcomes were divided into groups as (1) occluded, (2) severe disease (≥70% stenosis, or string sign), or (3) patent (<70% stenosis). Multivariable analyses determined predictors of severe disease or occlusion. A total of 310 patients had a radial artery graft. Mean follow-up after coronary artery bypass grafting was 565±511 days. Radial artery grafts had a patency rate of 51.3%, which was significantly lower than that for left internal mammary arteries (90.3%,
P
<0.0001) or saphenous vein grafts (64.0%,
P
=0.0016). Radial artery grafts had an occlusion rate of 33.7%, compared with 4.8% for left internal mammary arteries (
P
<0.0001), and had a severe stenosis rate of 15.1%, compared with 5.9% for saphenous vein grafts (
P
=0.0003) and 4.8% for left internal mammary arteries (
P
<0.0001). Women had a worse overall radial artery patency rate than men (38.9% versus 56.1%,
P
=0.025). A radial artery graft was the most powerful multivariable predictor of severe stenosis or occlusion (χ
2
=28.87,
P
<0.0001). Because of diseased radial artery grafts, 58 patients required subsequent percutaneous intervention, and 26 patients required repeat CABG.

Conclusions—

In patients predominantly presenting with signs and symptoms of myocardial ischemia after CABG, radial artery grafts have lower patency rates than left internal mammary artery and saphenous vein grafts. Selective use of the radial artery is warranted, particularly in women.
Depression: International intervention for a global problem
Authors: Crawford Mike. J.
Published: May 2004

Since 1948 the World Health Organization has had the challenging task of trying to achieve ‘the attainment by all peoples of the highest possible level of health’ (World Health Organization, 1946). A central part of this work has involved assessing the extent of health-related problems in different parts of the world and advocating for the implementation of effective strategies to address these problems. For many years the World Health Organization has expressed concerns about the relatively low level of funding assigned to mental health services in many countries. Estimates based on data collected in 2000 show that in most of sub-Saharan Africa and South-East Asia there are fewer than one mental health nurse and one psychiatrist per 100 000 people (World Health Organization, 2001). Two papers produced with the support of the World Health Organization and published in this issue of the Journal strengthen the argument for additional funding for mental health services. In the first paper, üstün and colleagues (2004, this issue) summarise data on the relative impact of common health-related problems in different regions of the world, and in an accompanying paper Chisholm and others (2004, this issue) estimate the cost-effectiveness of different interventions for depression in these different areas.
Foetal origins of schizophrenia: Testable hypotheses of genetic and environmental influences
Authors: Abel Kathryn M.
Published: May 2004

Although four-fifths of the variance in schizophrenia is attributable to genes, the locus of genetic defect remains elusive. Moreover, genetic investigation provides little detail, beyond suggesting that the contribution of genes is complex, probably polygenic and unlikely to be sufficient in most cases to allow expression of the syndrome (Vincente & Kennedy, 1997). Some apparently genetic effects also need explanation in a more complex model. Population studies show that schizophrenia is more likely to be inherited from an affected mother than from an affected father (Byrne et al, 2002), and increasing paternal age confers increased risk (Malaspina et al, 2001). Other effects are difficult to explain in conventional genetic terms: season of birth, urbanicity and migration are consistently reported to affect rates of schizophrenia in adulthood (Mortensen et al, 1999; Cantor-Graae et al, 2003), as is prenatal exposure to famine (Susser & Lin, 1992). Hypotheses of schizophrenia must be able to account for this interplay of genetic and environmental risk factors.
Global burden of depressive disorders in the year 2000
Authors: Üstün T. B. , Ayuso-Mateos J. L. , Chatterji S. , Mathers C. , Murray C. J. L.
Published: May 2004

Background

The initial Global Burden of Disease study found that depression was the fourth leading cause of disease burden, accounting for 3.7% of total disability adjusted life years (DALYs) in the world in 1990.

Aims

To present the new estimates of depression burden for the year 2000.

Method

DALYs for depressive disorders in each world region were calculated, based on new estimates of mortality, prevalence, incidence, average age at onset, duration and disability severity.

Results

Depression is the fourth leading cause of disease burden, accounting for 4.4% of total DALYs in the year 2000, and it causes the largest amount of non-fatal burden, accounting for almost 12% of all total years lived with disability worldwide.

Conclusions

These data on the burden of depression worldwide represent a major public health problem that affects patients and society.
Reducing the global burden of depression
Authors: Chisholm Dan , Sanderson Kristy , Ayuso-Mateos Jose Luis , Saxena Shekhar
Published: May 2004

Background

International evidence on the cost and effects of interventions for reducing the global burden of depression remain scarce.

Aims

To estimate the population-level cost-effectiveness of evidence-based depression interventions and their contribution towards reducing current burden.

Method

Primary-care-based depression interventions were modelled at the level of whole populations in 14 epidemiological subregions of the world. Total population-level costs (in international dollars or I) and effectiveness (disability adjusted life years (DALYs) averted) were combined to form average and incremental cost-effectiveness ratios.

Results

Evaluated interventions have the potential to reduce the current burden of depression by 10–30%. Pharmacotherapy with older antidepressant drugs, with or without proactive collaborative care, are currently more cost-effective strategies than those using newer antidepressants, particularly in lower-income subregions.

Conclusions

Even in resource-poor regions, each DALYaverted by efficient depression treatments in primary care costs less than 1 year of average per capita income, making such interventions a cost-effective use of health resources. However, current levels of burden can only be reduced significantly if there is a substantial increase in treatment coverage.
Focal changes in brain energy and phospholipid metabolism in first-episode schizophrenia
Authors: Jensen J. Eric , Miller Jodi , Williamson Peter C. , Neufeld Richard W J. , Menon Ravi S. , Malla Ashok , Manchanda Rahul , Schaefer Betsy , Densmore Maria , Drost Dick J.
Published: May 2004

Background

Membrane phospholipid and high-energy abnormalities measured with phosphorus magnetic resonance spectroscopy (31P-MRS) have been reported in patients with schizophrenia in several brain regions.

Aims

Using improved imaging techniques, previously inaccessible brain regions were examined in patients with first-episode schizophrenia and healthy volunteers with 4.0 T 31P-MRS.

Method

Brain spectra were collected in vivo from 15 patients with first-episode schizophrenia and 15 healthy volunteers from 15 cm3 effective voxels in the thalamus, cerebellum, hippocampus, anterior/posterior cingulate, prefrontal cortex and parieto-occipital cortex.

Results

People with first-episode schizophrenia showed increased levels of glycerophosphocholine in the anterior cingulate. Inorganic phosphate, phosphocreatine and adenosine triphosphate concentrations were also increased in the anterior cingulate in this group.

Conclusions

The increased phosphodiester and high-energy phosphate levels in the anterior cingulate of brains of people with first-episode schizophrenia may indicate neural overactivity in this region during the early stages of the illness, resulting in increased excitotoxic neural membrane breakdown.
Somatic symptoms in depression: Evaluation of their diagnostic weight in an African setting
Authors: Okulate G. T. , Olayinka M. O. , Jones O. B. E.
Published: May 2004

Background

Somatic symptoms are extremely common features of depression and other mental disorders in African countries such as Nigeria, buttheir weight in the diagnosis of depression is not certain.

Aim

To determine what weight should be assigned to these symptoms in comparison with other well-known symptoms in the diagnosis of depression.

Method

A sample of 829 persons completed the Patient Health Questionnaire which was earlier modified by the inclusion of the somatic symptoms being studied. Using principal component analysis and a logistic regression model, the contributions of these symptoms in comparison with others were determined.

Results

Core depressive symptoms accounted for most of the total variance for depression. The somatic symptoms studied loaded separately from the core depressive symptoms and were not as good predictors of depression. A cognitive factor emerged as well as some somatic factors.

Conclusions

Although somatic symptoms may be florid among patients with depression, they have considerably less weight than core depressive symptoms in the diagnosis of depression. The emerging cognitive factor could be similar to that described by previous authors.
Ethnic variation among adolescent psychiatric in-patients with psychotic disorders
Authors: Tolmac Jovanka , Hodes Matthew
Published: May 2004

Background

There is strong evidence that the rates of psychiatric admission for psychosis in the UK are elevated for the Black adult population compared with the White population. Black adults also have a higher rate of involuntary psychiatric admissions. There have been no studies in this country investigating links between ethnic background and psychiatric admission in the adolescent population.

Aims

To investigate whether Black compared with White adolescents from London are over represented in psychiatric in-patient settings and whether they are more likely to be detained under the Mental Health Act 1983.

Method

Cross-sectional survey of London adolescents aged 13–17 years, who were in-patients in psychiatric units.

Results

Adolescents from the Black group (Black African, Black Caribbean, Black British) were over represented among those admitted with a diagnosis of a psychotic disorder when compared with adolescents from the White group (White British/White Irish, White Other): odds ratio=3.7,95% C12.0–6.7. They were also more likely to be detained on admission and more likely to be born outside the UK and have refugee background.

Conclusions

The possible impact of various background factors influencing admission is discussed.
Relationship between alcohol use disorders and suicidality in a psychiatric population
Authors: McCloud Annie , Barnaby Ben , Omu Nicola , Drummond Colin , Aboud Andy
Published: May 2004

Background

Alcohol misuse is a risk factor in suicide and parasuicide.

Aims

To measure the prevalence of alcohol use disorders in a cohort of psychiatric admissions using the Alcohol Use Disorders Identification Test (AUDIT), and the relationship between the AUDIT score and suicidality.

Method

Consecutive psychiatric admissions were interviewed with a lifestyle survey that included the AUDIT, and admission case notes were reviewed.

Results

Out of 200 subjects, 48.5% scored 8 or more (indicating hazardous or harmful alcohol use) and 22.5% scored 16 or more (indicating significant alcohol dependence) on the AUDIT. There were no significant gender differences. Alcohol misuse was strongly associated with suicidality.

Conclusions

The AUDIT questionnaire should be incorporated into psychiatric assessments when risk of self-harm is being evaluated. Further research is warranted to examine the impact of interventions for alcohol use disorders in psychiatric settings on self-harm and suicidal ideation.
Prematurity at birth and adolescent depressive disorder
Authors: Patton George C. , Coffey Carolyn , Carlin John B. , Olsson Craig A. , Morley Ruth
Published: May 2004

Association between prematurity/low birthweight and adolescent depressive disorder studied using a case–control design within a prospective cohort study of 2032 adolescents. Odds for depressive disorder were 11-fold (95% C12–62) higher for the premature/low-birthweight participants after regression adjustment for major confounding factors. For premature/low-birthweight females, cumulative rates of depressive disorder over 30 months were 15.2% (95% C111.1–20.5) v. 1.8% (95% C11.6–2.1) in those with normal deliveries. Physiological adaptations in utero before full term may be implicated causally in some cases of depression in adolescence.
Computer-aided self-help for phobia/panic via internet at home: A pilot study
Authors: Kenwright Mark , Marks Isaac M. , Gega Lina , Mataix-Cols David
Published: May 2004

In an open study, ten people with phobia or panic disorder who could not travel repeatedly to a therapist accessed a computer-aided exposure self-help system (Fear Fighter) at home on the internet with brief therapist support by telephone. They improved significantly, and their outcome and satisfaction resembled those in patients with similar disorders who used Fear Fighter in clinics with brief face-to-face therapist support.
Mental health in the enlarged European Union: Need for relevant public mental health action
Authors: Marušič Andrej
Published: May 2004

On 1 May 2004 ten new countries will join the European Union (EU), which as a result will comprise 25 culturally quite different countries. Each enlargement of the EU so far has been a difficult experience for both the existing member states and the new entrants, since each membership change has altered the structure and the sharing of costs and benefits of membership. Furthermore, each new member brings its own traditions, preferences, strengths and weaknesses, including the mental health of its population and its psychiatric services. Are we ready for the changes to come?