bluuebunny/crossref_metadata_2025 huggingface dataset:
Myofascial Pain, Fibromyalgia or Fibrositis?
Authors: Pearce J.M.S.
Published: July 2004

The terms myofascial pain, fibromyalgia and fibrositis are critically examined. They constitute diagnostic labels for non-specific musculoskeletal aches and pains. Analysis of the evidence shows that none of these labels is substantiated by hard physical signs or by laboratory evidence of consistent pathological or biochemical abnormality. What is the objective evidence for disorder(s) of muscle, fascia or fibrous tissues, so clearly indicated by these diagnostic names? Alternative terms such as ‘regional pain syndrome’ or ‘chronic pain syndrome’ merely redefine the clinical problem without providing a mechanism or basis for diagnosis. Despite different diagnostic criteria, these conditions, along with chronic fatigue syndrome, have many demographic and clinical similarities, most notably tender trigger points. Indeed, the terms are often used interchangeably. There are few differences in the symptoms, physical findings, laboratory tests, functional status, psychosocial features and psychiatric disorders. This paper seeks not to deny the existence of aches and pains, but to critically examine the utility of these terms. The only claimed physical sign is the presence of tender trigger points over muscles or muscle attachments. Research suggests that tender points are a measure of general distress related to pain complaints but separately associated with fatigue and depression. They are present in some normal subjects and are variable in occurrence in time in the same individual. They reflect no demonstrable pathology. It is therefore argued that none of these commonly used diagnoses represent distinct disease entities. A possible but unproven alternative hypothesis is that such symptoms relate to neural pain with both peripheral and central components, and in some instances psychological or wilful embellishment.
Normal CSF Hypocretin-1 (Orexin A) Levels in Dementia with Lewy Bodies Associated with Excessive Daytime Sleepiness
Authors: Baumann Christian R. , Dauvilliers Yves , Mignot Emmanuel , Bassetti Claudio L.
Published: July 2004

Excessive daytime sleepiness, hallucinations and REM sleep behavior disorder are symptoms reported in both dementia with Lewy bodies (DLB) and narcolepsy. Considering the demonstration of low hypocretin-1/orexin A levels in the cerebrospinal fluid (CSF) of most patients with narcolepsy, we hypothesized the presence of a deficient hypocretinergic transmission in DLB. Hypocretin-1 was tested in the CSF of 10 DLB patients. Levels were found to be in the normal range (mean 521 pg/ml, range 382–667) when compared to controls (n = 20, mean 497 pg/ml, range 350–603) and Alzheimer’s disease patients (n = 7, mean 474 pg/ml, range 333–564). In DLB, excessive daytime sleepiness, hallucinations and REM sleep behavior may occur in the absence of a detectable hypocretin deficiency.
White Matter Loss in the Splenium of the Corpus callosum in a Case of Posterior Cortical Atrophy: A Diffusion Tensor Imaging Study
Authors: Yoshida Tomokatsu , Shiga Kensuke , Yoshikawa Kenji , Yamada Kei , Nakagawa Masanori
Published: July 2004

There have been several functional imaging studies using PET and SPECT to investigate posterior cortical atrophy (PCA). These studies have suggested dysfunction of corticocortical connections which is consistent with the occipitoparietal stream. However, there are no reports suggesting disturbance of the white matter that interconnects the temporal, parietal and occipital cortices. We measured fractional anisotropy (FA) in the genu and splenium of the corpus callosum and created color maps using diffusion tensor imaging (DTI), which is a relatively new MRI technique that allows visualization of the directionality of water diffusion, in a patient with PCA and compared these findings with those in 5 typical Alzheimer disease (AD) patients. The PCA patient was a 75-year-old man presenting with progressive complex visual disorder who satisfied the clinical diagnostic criteria for PCA. In 5 typical AD patients, the FA index in the splenium was higher than that in the genu; however, in the PCA patient, the FA index in the splenium was significantly lower than that in the genu. A DTI-based color map of the PCA patient showed reduction of anisotropy and fiber volume in the splenium. These findings suggest that the splenium of the corpus callosum secondarily degenerated due to neuronal degeneration of the temporal, parietal and occipital cortices and suggest that reduction of the FA in the splenium is one of the characteristics of PCA.
Evidence for the Benefits of the Low-Molecular-Weight Heparin Dalteparin in ‘High-Risk’ Patients with Acute Coronary Syndromes
Authors: Husted Steen , Ziegler Birgitte
Published: July 2004

Acute coronary syndrome (ACS) is a clinical emergency that requires urgent assessment. ACS encompasses a variety of clinical symptoms of varying severity, and risk stratification is essential to enable triage of patients to the optimum level of care and specific therapy. The medical treatment of ACS is directed primarily at the dissolution of developing intracoronary thrombi by antiplatelet (e.g. aspirin and clopidogrel) and anticoagulant [e.g. low-molecular-weight heparin (LMWH) and unfractionated heparin] therapy. Recent data from clinical trials have shown that LMWH is at least as effective and safe as unfractionated heparin. Additionally, elevation of biochemical cardiac markers and ST segment changes provide powerful risk stratification tools. Data from the Fragmin during Instability in Coronary Artery Disease and Fragmin and Fast Revascularisation during Instability in Coronary Artery Disease studies have demonstrated that prolonged treatment with the LMWH dalteparin provides significant benefit in clinical outcome in patients stratified as ‘high risk’ by troponin measurement and ST monitoring. While an early invasive strategy is recommended in ‘high-risk’ patients with ACS, dalteparin treatment is also effective and safe for up to 45 days in patients awaiting revascularization, or in those for whom an early invasive treatment is not possible. This paper is a review of the evidence for the use of dalteparin in ACS.
Galanin-Like Peptide mRNA Alterations in Arcuate Nucleus and Neural Lobe of Streptozotocin-Diabetic and Obese Zucker Rats
Authors: Shen Jun , Gundlach Andrew L.
Published: July 2004

Galanin-like peptide (GALP) is a 60-amino-acid peptide with structural similarities to galanin and a high affinity for galanin receptors. GALP is expressed by a discrete population of neurons in the arcuate nucleus (ARC) and median eminence of the hypothalamus of several species, including the rat. GALP neurons express leptin receptors and GALP mRNA levels are decreased slightly in fasted rats and stimulated significantly by acute leptin treatment in combination with fasting. In studies to further explore the leptin dependence of GALP expression, we examined GALP mRNA levels in the hypothalamus of obese Zucker and streptozotocin-induced diabetic (STZ-DM) rats. In leptin receptor-deficient obese Zucker rats, with 75% higher body weight than lean littermates, GALP mRNA levels in the ARC were decreased by 75%, while neuropeptide Y (NPY) mRNA levels were increased 7-fold (n = 5, p < 0.001), consistent with earlier reports. In hypoleptinemic diabetic rats with 4.5-fold higher blood glucose and 15% lower body weight than controls, GALP mRNA levels in the ARC were decreased by 90%, while NPY mRNA levels were increased 9-fold (n = 5, p < 0.001). GALP is also expressed by pituicytes in the neural lobe of the rat pituitary gland and GALP expression is increased by osmotic stimulation such as dehydration and salt loading. Thus, in STZ-DM rats that are in a hyperosmotic state with elevated plasma vasopressin levels, GALP mRNA levels were increased by ∼20-fold in the neural lobe relative to control (n = 4, p < 0.001). The current findings are consistent with a strong tonic influence of leptin receptor signalling on hypothalamic GALP expression under normal conditions, and possible abnormalities in GALP neuronal signalling and their putative targets, thyrotropin-releasing hormone and gonadotropin hormone-releasing hormone neurons, under pathophysiological conditions such as diabetes and obesity. Our data in STZ-DM rats also clearly demonstrate that GALP gene expression is differentially regulated in neurons and pituicytes.
Food Consumption Patterns in a Mediterranean Region: Does the Mediterranean Diet Still Exist?
Authors: Tur Josep A. , Romaguera Dora , Pons Antoni
Published: July 2004

Aims: To assess the food consumption patterns in the adult population of a Mediterranean region: the Balearic Islands (BI). Methods: A cross-sectional nutritional survey was carried out in the BI between 1999 and 2000. A random sample (n = 1,200) of the adult population (16–65 years) was interviewed. Dietary habits were assessed by means of 24-hour recall during 2 non-consecutive days, the first in the warm season and the second in the cold season, and a quantitative food frequency questionnaire. Anthropometric measurements were also obtained. Results: Current food patterns in the BI are characterized by a prominent consumption of dairy products, vegetables, fruit, bread, soft drinks and meat. According to the dietary guidelines for the Spanish population, only appropriate consumption of olive oil and other fats, dairy products, nuts, and soft drinks have been achieved. Intakes of fruit, vegetables, fish, eggs, pulses, cereals and potatoes are below desirable levels. On the other side, intakes of sugary products, sweets and cakes are higher than desirable. Alcohol intake, in the context of the Mediterranean diet, can be considered as acceptable. Conclusions: The dietary patterns observed among the BI population are in harmony with the actual dietary trends in Spain and other Mediterranean countries. Mediterranean dietary habits still exist, but a progressive departure from the traditional Mediterranean diet is being observed mainly in younger generations. It would be desirable to increase the consumption of fish, vegetables, fruit, cereals and pulses and decrease the intake of food sources containing saturated fat.
Relevance of Lunar Periodicity in Human Spontaneous Abortions
Authors: Valandro Luca , Zordan Mauro , Polanska Marta , Puricelli Paolo , Colombo Lorenzo
Published: July 2004

The effect of the moon on human reproduction has been scarcely investigated and with controversial results. The present analysis describes a significant effect of extreme perigeal lunar positions on the number of hospitalized spontaneous abortions (n = 1,329) recorded at two university clinics and a public hospital at Padova, Italy, during the years 2000–2003. Spectral analysis evidenced a 205-day period which appears to be correlated with the 206-day periodicity in extreme lunar distances. Circa-septan and circa-annual periodicities were also observed. Peak significances were determined by a Monte Carlo approach (circa-septan and 205-day periodicities: p < 0.001; circa-annual periodicity: p < 0.05). Our study indicates that the occurrence of human abortions displays suggestive periodicities that may be of relevance for gynecological and obstetrical practice.
N-Acetylcysteine in the Prevention of Radiocontrast-Induced Nephropathy: Clinical Trials and End Points
Authors: Hoffmann Ute , Banas Bernhard , Fischereder Michael , Krämer Bernhard K.
Published: July 2004

N-acetylcysteine (NAC) has been suggested to prevent radiocontrast-induced nephropathy (RCIN) in patients with a reduced renal function. However, clinical studies have not been demonstrating this effect consistently. Also, reviews and meta-analyses dealing with the question of prevention of RCIN by NAC have been controversial. Nearly all investigators used serum creatinine as surrogate end point of their trials, and changes in serum creatinine concentrations are thought to reflect the extent of renal injury as primary outcome. In a recent study, an effect of NAC on creatinine values and estimated glomerular filtration rate without any effect on cystatin C levels has been shown in volunteers with a normal renal function. Therefore, before renal protective effects of NAC in RCIN are proposed, any direct effects of NAC on creatinine, urea, and estimated glomerular filtration rate should be addressed. In future trials, the glomerular filtration rate should preferentially be measured directly, or at least additional markers of the renal function (e.g., serum cystatin C) have to be assessed. Furthermore, additional ‘hard’ end points, i.e., hospital morbidity, mortality, or dialysis dependency, should be considered in the design of future studies of RCIN.
Free Reactive Oxygen Species and Nephrotoxicity of Contrast Agents
Authors: Haeussler Ulla , Riedel Martin , Keller Frieder
Published: July 2004

Background: The nephrotoxicity induced by contrast media remains a serious clinical problem, and the underlying mechanism has not been completely understood. Experimental and clinical investigations suggest that reactive oxygen species (ROS) are critical determinants of radiocontrast nephropathy (RCN), and that antioxidants can prevent this damage. Methods: Cultured human proximal renal tubule cells (HK-2) were exposed to hydrogen peroxide (H2O2) at different concentrations. H2O2-induced tubular DNA damage was examined in the presence of the antioxidant MESNA (sodium-2-mercaptoethane sulphonate). The induction of DNA damage was measured with the alkaline comet assay (single cell gel electrophoresis). We also studied 12 patients with stable renal impairment (median baseline creatinine 296 µmol/l; range: 203–495 µmol/l) undergoing cardiac catheterization/intervention prospectively. Patients received 800 mg MESNA intravenously 30 min before exposure to the contrast agent in addition to 0.9% saline hydration. Results: In the cell cultures, oxidative stress on HK-2 cells induced increased DNA migration in the comet assay. Treatment of tubular cells with the antioxidant MESNA prior to the addition of H2O2 significantly reduced DNA migration in the comet assay. In the clinical study, treatment of the patients with MESNA prevented the adverse renal effect of contrast media (median serum creatinine 293; range: 187–433 µmol/l) 48 h after coronary angiography/intervention. Conclusion: Both the in vivo and the in vitro studies suggest that the ROS-mediated renal injury could be inhibited by a potent antioxidant such as MESNA.
New AUC-Based Method to Estimate Drug Fraction Removed by Hemodialysis
Authors: Czock David , Rasche Franz Maximilian
Published: July 2004

Background: A supplemental dose is often necessary after hemodialysis depending on the amount of drug removed by hemodialysis. However, there are different methods of estimating this amount, and most methods ignore drug rebound after hemodialysis. In this report we present a new area under the concentration curve (AUC)-based method that provides an estimate of the drug fraction removed by hemodialysis including drug rebound. Methods: Valganciclovir, the oral prodrug of ganciclovir, was administered to 6 patients with end-stage renal disease. Hemodialysis was performed after 32 h. The fraction of ganciclovir removed by hemodialysis was estimated using the new AUC-based method, a classical method (using the slope on and off hemodialysis), the back-extrapolation method, and a reference model (a two-compartment model with zero-order input and first-order elimination). Results: The AUC-based method and the back-extrapolation method provided accurate estimates of the fraction of ganciclovir removed by hemodialysis (47 ± 6 and 46 ± 5%, respectively) compared to the reference model (49 ± 3%). The classical method, which does not account for the rebound of ganciclovir concentrations after hemodialysis, overestimated the removed fraction by 9% (58 ± 3%). Conclusions: The new AUC-based method and the back-extrapolation method accurately estimate the drug fraction removed by hemodialysis for drugs with a rebound after hemodialysis. The AUC-based method is more robust and as efficient compared to the back-extrapolation method.
Impact of Different Immunosuppressive Regimens on Antigen-Presenting Blood Cells in Kidney Transplant Patients
Authors: Scherberich Juergen E. , Estner Heidi , Segerer Wolfgang
Published: July 2004

Background: Alloantigen-specific and unspecific immune processes contribute to chronic renal graft dysfunction. Despite ‘optimized immunosuppressive therapy’ (IS), the role of chronic cell activation still remains open. Methods: 69 kidney transplant recipients (NTX) were assessed for monocyte surface antigens CD14 (LPS receptor) and CD16 (Fc-γ-III receptor) by flow cytometry including the percentage amount of the proinflammatory CD14+CD16+ subset. 14 non-dialysis patients with chronic renal failure (CRF) and 24 healthy persons served as controls. Results: All 14 patients suffering from CRF revealed higher CRP serum levels compared to healthy controls (p = 0.01). NTX patients had a (not significant) tendency to higher CRP concentrations (p > 0.05). The mean expression of CD14 on monocytes (mCD14) was lower in patients with CRF and in NTX patients (p = 0.024 – p = 0.026). NTX patients revealed low expression of monocytic CD14 with no difference between the single IS therapy groups. The proinflammatory monocyte subpopulation positive for CD14 and CD16 was elevated both in uremic and NTX patients (p < 0.002), despite long-lasting IS therapy. Conclusions: Continuing IS therapy, even under ‘optimized’ drug-monitoring conditions, does not sufficiently prevent or suppress a microinflammatory (and potential fibrotic growth-promoting) status in NTX patients.
Low-Dose Sirolimus in Combination with Mycophenolate Mofetil Improves Kidney Graft Function Late after Renal Transplantation and Suggests Pharmacokinetic Interaction of Both Immunosuppressive Drugs
Authors: Renders Lutz , Steinbach Reiko , Valerius Thomas , Schöcklmann Harald O. , Kunzendorf Ulrich
Published: July 2004

Aims: Chronic allograft nephropathy and/or calcineurin inhibitor toxicity are common problems after organ transplantation. The aim of this study was to examine the safety and efficacy of switching from a calcineurin inhibitor-based to a calcineurin inhibitor-free immunosuppressive regimen consisting of sirolimus and mycophenolate mofetil (MMF) late after renal transplantation. Methods: Kidney biopsies were performed in renal-transplanted patients with increasing serum creatinine levels at least 6 months after transplantation (mean time ± SD after renal transplantation: 76.4 ± 50.4 months). Patients with no signs of acute rejection were switched to MMF (500–2,000 mg/day) in combination with a low dose of sirolimus (1 mg/day). Renal function, serum chemistry, blood trough levels of sirolimus and MMF, and blood pressure were monitored. Results: 13 patients were investigated. During our observation period (mean observation time ± SD: 11.2 ± 5.9 months), an improvement in renal function was observed in 10/13 patients. In 3/13 patients, renal function deteriorated further and hemodialysis was initiated in 2 patients within the next 6 months. However, a serum creatinine concentration above 3.5 mg/dl was measured in 2 of those 3 patients prior to the switch of the immunosuppressive protocol. Administration of a low dosis of sirolimus (1 mg/day) led to relevant sirolimus (4.16 ± 1.85 ng/ml) and MMF blood trough levels (month 1: 6.8 ± 3.46; month 3: 4.67 ± 1.78 mg/l). The following adverse events were observed: borderline acute rejection (1/11 patients), anemia responding to higher dosage of erythropoietin (3/11), hyperlipidemia (1/11), and urinary tract infections (4/11). Conclusions: Low-dose sirolimus therapy in combination with concentration-adjusted MMF therapy leads to improvement of organ function late after renal transplantation. The follow-up of those patients should include assessments of blood cell counts, serum lipids and urinalysis to recognize the possible side effects.
Sirolimus Dosage during and after Conversion from Calcineurin Inhibitor Therapy to Sirolimus in Chronic Kidney Transplant Patients
Authors: Diekmann Fritz , Fritsche Lutz , Neumayer Hans-Hellmut , Budde Klemens
Published: July 2004

Sirolimus (SRL) is an alternative to calcineurin inhibitors (CNI) in kidney transplant patients with chronic allograft dysfunction. Methods: 33 patients were converted to SRL receiving a single loading dose of 15 mg and initial maintenance dose of 5 mg/day. CNI was reduced by 50% on day 1 and tapered during 4–6 weeks after achieving SRL target (8–12 ng/ml). Concomitant immunosuppressive therapy remained unchanged. Results: Patient survival was 100% and graft survival was 85% after 1 year. Mean SRL dose decreased from 5 mg/day initially to 2.8 ± 1.3 mg/day. SRL dose-adjusted trough concentration did not change significantly over time. Dose-adjusted trough concentrations of CNI before conversion and of SRL after 1 year did not correlate. We observed no severe infections, however, one rejection Banff Ia occurred 7 months after conversion associated with subtherapeutic SRL trough concentration. Adverse events were anemia, dyslipidemia, epistaxis, stomatitis, and bronchiolitis obliterans which occurred mainly during the conversion phase. Conclusion: Overlapping conversion from CNI to SRL in chronic kidney transplant patients is possible and safe. However, further studies are necessary with shorter overlap and lower SRL loading and initial maintenance dose which might lead to a decrease in the high number of adverse events in the overlap phase.
Effects of Parathyroidectomy on Renal Allograft Survival
Authors: Lee Patricia Pui , Schiffmann Leif , Offermann Gerd , Beige Joachim
Published: July 2004

Background: Hyperparathyroidism is a common problem secondary to renal insufficiency and is often not entirely resolved after renal transplantation (TX). Methods: In this retrospective analysis, the effects of parathyroidectomy (PTX) on allograft function were evaluated and the risk factors involved in allograft deterioration in patients after PTX will be discussed. Results: The rise in creatinine was steeper 1 year after PTX compared to 2 years before PTX in the majority (13 of 22) of patients. Compared to a cohort without PTX, graft survival was significantly decreased by 60% in 6 years (p < 0.0001). After multivariate adjustment, risk factors attributed to graft function included baseline creatinine (p = 0.02), baseline systolic blood pressure (p = 0.04) and time between TX and PTX, but not PTX itself. The peri-PTX drop in serum calcium was significantly more accentuated in patients exhibiting a worsening of graft function after PTX (p = 0.04). Conclusions: In patients requiring PTX, graft function is in danger of worsening. Since many factors contribute to this negative correlation and no association with parathyroid hormone (PTH) levels before PTX has been observed, we do not recommend prophylactic PTX on the basis of PTH levels only. However, appropriate management of peri-PTX risk factors is highly important. If the clinical situation, e.g. progressive renal osteodystrophy, requires removal of parathyroid glands, the procedure should be performed, if possible, in the presence of stable graft function.
One for All – A Multi-Use Dialysis System for Effective Treatment of Severe Thallium Intoxication
Authors: Kielstein J.T. , Linnenweber S. , Schoepke T. , Fliser D.
Published: July 2004

Guided by the idea of providing a stable electrolyte composition of the dialysate, the late Bernd Tersteegen designed a machine ingeniously combining the advantages of a closed tank hemodialysis system with the efficacy and bacteriological safety of a single-pass system. Several thousand dialysis sessions have been performed with this system in the chronic hemodialysis population. Recently, highly efficient (i.e. high volume) dialysis systems have been successfully introduced for the treatment of critically ill patients in the intensive care unit as extended dialysis. Furthermore, they can also be a safer, more effective and less costly alternative to traditional extracorporeal techniques in the treatment of severe intoxication. In a case-based approach, we review the increasing use of such a system.
Lithium Acetate Therapy in a Maintenance Hemodialysis Patient
Authors: Walcher Judith , Schoecklmann Harald , Renders Lutz
Published: July 2004

Background/Aims: Single cases of lithium carbonate dosing in hemodialysis patients have been published. We investigate the dose-serum level relationship after single and multiple lithium acetate dosing in a hemodialysis patient and review the literature. Methods: Lithium acetate was administered orally over a period of 11 months in a patient with major depressive episodes after being placed on hemodialysis three times a week. The serum trough levels of lithium before and after hemodialysis were analyzed. The data were compared with those reported in the literature, and potential drug interactions and the importance of the residual renal function are discussed. Results: No adverse events due to the lithium therapy were documented. Steady state levels of between 0.6 and 0.8 mmol/l of lithium acetate were achieved 17 days after initiating the therapy, using 24 mmol/l of lithium three times a week, in a patient with a residual diuresis of about 400 ml/day. In contrast, data reported in the literature implicate that only 9.6–14.4 mmol/l of lithium (450–600 mg of lithium carbonate) is sufficient to achieve adequate serum levels. Conclusions: The residual renal function can be important for lithium clearance. The creatinine clearance does not reflect this point.
Peritoneal Closure vs. Non-Closure: Estimation of Pelvic Fluid by Transvaginal Ultrasonography after Abdominal Hysterectomy
Authors: Al-Inany Hesham
Published: July 2004

Objective: To determine the volume of pelvic fluid and febrile morbidity after hysterectomy in which the peritoneum was or was not closed. Design: Prospective single-center study. Participants: Fifty-four women undergoing abdominal hysterectomy were enrolled in the study. Patients were randomized into two groups according to peritoneal closure: group I (n = 28) in which the peritoneum was closed, and group II (n = 26) in which the peritoneum was left open. All participants had early postoperative transvaginal ultrasound. Outcome Measures: Volume of pelvic fluid accumulated after hysterectomy, total leukocytic count before and after hysterectomy, body temperature over the first 24 h, and wound healing. Results: There was a statistically significant difference between both groups regarding the volume of pelvic fluid collection, the duration of the operation and number of ampoules needed (p < 0.05). There was no statistically significant difference regarding body temperature, TLC, and wound complications. Conclusion: Peritoneal non-closure does not increase short-term morbidity, however it does cause an increase in peritoneal pelvic fluid. The impact of this on long-term sequelae as adhesions should be investigated.
Idarubicin Administered during Pregnancy: Its Effects on the Fetus
Authors: Matsuo Koji , Shimoya Koichiro , Ueda Shuji , Wada Kazuko , Koyama Masayasu , Murata Yuji
Published: July 2004

Acute myeloblastic leukemia, subtype M1, was diagnosed in a 39-year-old G2P1 Japanese woman at 21 weeks’ gestation. Remission-induction polychemotherapy, including daunorubicin, performed for one cycle, did not lead to remission. Second-line chemotherapy, including idarubicin, performed for one cycle, was administrated during the early third trimester of pregnancy. Septic shock occurred due to severe myelosuppression. An emergent cesarean section was performed in response to a nonreassuring pattern of the fetal heart rate and a rapid decrease in fetal amniotic fluid. The neonate delivered at 32 weeks’ gestation showed no signs of cardiac failure but did show signs of transient myelosuppression, hepatopathy, and elevated creatine kinase. Complete remission was established with idarubicin including chemotherapy.
Cerebral Ultrasound Findings in Neonatal Lupus Syndrome
Authors: Zuppa A.A. , Gallini F. , De Luca D. , Luciano R. , Frezza S. , de Turris P.L. , Tortorolo G.
Published: July 2004

A prospective study was performed enrolling 11 newborns with neonatal lupus syndrome (NLS) and 22 control newborns to investigate cerebral ultrasound (US) anomalies and their relationship with clinical neurological signs and laboratory findings. Cerebral US detected a significantly higher incidence in the study group of both subependymal pseudocysts (SEPC) and subependymal hemorrhage (SEH), neither of which correlated to autoantibody levels. All infants had completely normal neurological examinations both at birth and follow-up. The etiopathogenesis of central nervous system findings in NLS is discussed. US evaluation identified minimal anomalies compatible with favorable outcome: further studies are necessary to investigate the possible long-term sequelae, pathogenesis and spectrum of cerebral US findings.
Changes of Fatty Acid Composition of Human Milk during the First Month of Lactation: A Day-to-Day Approach in the First Week
Authors: Minda Hajnalka , Kovács Andrea , Funke Simone , Szász Mária , Burus István , Molnár Szilárd , Marosvölgyi Tamás , Decsi Tamás
Published: July 2004

Background: Fatty acid composition of human milk (HM) is known to change considerably during lactation. However, we were unable to find data on changes of fatty acid composition of HM during the very early phase of lactation, i.e. in the first week of life. Subjects and Methods: HM samples were obtained from 18 healthy lactating women every day during the first week and thereafter on the 14th and 28th days of lactation. Fatty acid composition of colostrum and mature HM samples was determined by high-resolution capillary gas-liquid chromatography. Results: Values of the n-6 essential fatty acid, linoleic acid, in HM did not change significantly during the first month of lactation, whereas values of the n-3 essential fatty acid, α-linolenic acid, showed significant increases during the first 2 weeks of lactation (1st day: 0.49 [0.12], % weight/weight, median [ranges from the 1st to the 3rd quartile], 14th day: 0.69 [0.31], p < 0.05). In contrast, values of the n-6 long-chain metabolites, eicosadienoic-, dihomo-γ-linolenic- and arachidonic acid, as well as the values of the n-3 long-chain metabolites, eicosatrienoic-, and eicosapentaenoic acid exhibited significant decreases during the entire period investigated. The principal n-3 long-chain metabolite, docosahexaenoic acid, showed a significant increase between the 3rd and 14th days, but a significant decrease between the 14th and 28th days (3rd day: 0.15 [0.13], 14th day: 0.28 [0.11], p < 0.05, 28th day: 0.19 [0.12], p < 0.01). There were statistically significant positive correlations between arachidonic and docosahexaenoic acid values on the 1st (r = 0.67, p < 0.01), 5th (r = 0.56, p < 0.05) and the 6th (r = 0.53, p < 0.05) days of lactation. Conclusion: Fatty acid composition of HM changes significantly even during the first week of lactation. The lack of positive correlation between essential fatty acids and their long-chain metabolites suggests that it is not only the availability of essential fatty acids that influences the fatty acid composition of human colostrum.
Increased Frequency of Bacterial Vaginosis and Chlamydia trachomatis in Pregnant Women with Human Papillomavirus Infection
Authors: da Silva Cléber Sérgio , Adad Sheila Jorge , Hazarabedian de Souza Maria Azniv , Macêdo Barcelos Ana Cristina , Sarreta Terra Ana Paula , Candido Murta Eddie Fernando
Published: July 2004

The aim of this study was to verify the presence of bacterial vaginosis (BV), Candida sp, Chlamydia trachomatis, Neisseria gonorrhoeae, to determine the prevalence of tobacco use and measure vaginal pH (VpH) in pregnant women with (n = 26) and without (n = 26) human papillomavirus (HPV) infection, and make comparisons between these 2 groups. HPV, C. trachomatis and N. gonorrhoeae were diagnosed using hybrid capture, BV using clinical criteria, and Candida sp via cultures. A digital pH meter was used to measure VpH. The frequencies of Candida sp were 19.2 and 23.1% (p = 1), and VpH was 4.4 ± 0.4 and 4.3 ± 0.4 (p = 0.23), in the HPV-positive and HPV-negative groups, respectively. Compared to the group of pregnant women without HPV infection, those with HPV infection had a significantly higher prevalence of tobacco use (50 vs. 11.5%; p = 0.006), BV (53.8 vs. 15.4%; p = 0.007), and C. trachomatis (34.6 vs. 7.7%; p = 0.039). No case of N. gonorrhoeae was diagnosed. All cases of C. trachomatis and BV had high-grade HPV infection.
Effects of Ibuprofen and Hypoxia on Neutrophil Apoptosis in Neonates
Authors: Hanna Nazeeh , Graboski Sarah , Laskin Debra L. , Weinberger Barry
Published: July 2004

Background: Ibuprofen is a cyclooxygenase inhibitor that is effective in treating patent ductus arteriosus in preterm infants. However, recent trials have suggested that it may increase the risk of developing necrotizing enterocolitis and chronic lung disease. Apoptosis of neutrophils is impaired in newborns, leading to reduced clearance of activated cells and possibly contributing to the susceptibility of infants to these inflammatory diseases. Objectives: In the present studies, we investigated the hypothesis that ibuprofen reduces neonatal neutrophil apoptosis in the setting of hypoxia or lipopolysaccharide (LPS). Methods: Neutrophils and peripheral blood mononuclear cells were isolated from adult and cord blood and cultured in the presence or absence of ibuprofen (1.5 mM), hypoxia (<5% O2), and bacterial LPS (100 ng/ml). Apoptosis was quantified by measuring binding of FITC-Annexin V using flow cytometry. Cytokine concentrations in cell supernatants were measured by ELISA. Results: After 24 h, 20% of adult and 14% of neonatal neutrophils were apoptotic. Apoptosis was reduced by hypoxia in both adult and neonatal cells. Ibuprofen further reduced neutrophil apoptosis, but only when the cells were cultured in the presence of mixed leukocytes. This suggests that the effects of ibuprofen on apoptosis are dependent on soluble products secreted by peripheral blood mononuclear cells. We found that production of tumor necrosis factor (TNF)-α by neonatal leukocytes was significantly increased by ibuprofen, and was further increased following exposure to ibuprofen in the presence of LPS and hypoxia. In contrast, production of macrophage inflammatory protein (MIP)-1α was not affected by treatment with ibuprofen, and ibuprofen blocked induction of this chemokine by LPS. Conclusion: We conclude that the net effect of ibuprofen on neutrophils is antiapoptotic, especially in the presence of hypoxia or LPS. This effect may be mediated, in part, by increased production of TNF-α by peripheral blood mononuclear cells. These data suggest that treatment of infants with ibuprofen, in the presence of infection and/or tissue hypoperfusion/hypoxia, may contribute to the development of inflammatory diseases.
Down Syndrome Candidate Region 1,a Downstream Target of VEGF, Participa tes in Endothelial Cell Migration and Angiogenesis
Authors: Iizuka Masashi , Abe Mayumi , Shiiba Kenichi , Sasaki Iwao , Sato Yasufumi
Published: July 2004

Vascular endothelial growth factor (VEGF) is a principal stimulator of angiogenesis. However, the downstream targets of VEGF in endothelial cells (ECs) are not entirely clarified. Survey of downstream targets of VEGF in human ECs identified a number of genes, including Down syndrome candidate region 1 (DSCR1). Here, we confirmed the inducible expression of DSCR1 in ECs by Northern and Western blottings. Moreover, VEGF-stimulated induction of DSCR1 was blocked by anti-VEGF receptor-2 monoclonal antibody (mAb), or the specific calcineurin inhibitors cyclosporin A and FK506. The expression of DSCR1 in ECs of neovessels was further shown by immunohistochemical analysis. We therefore examined whether DSCR1 played any roles in angiogenesis. The specific downregulation of DSCR1 expression by antisense oligonucleotide (AS-ODN) inhibited VEGF-stimulated migration of ECs as well as angiogenesis in vivo. AS-ODN inhibited the spreading of ECs on vitronectin, as well as on the immobilized anti-αvβ3 mAb, but not on anti-αvβ5 mAb. Moreover, AS-ODN inhibited tyrosine phosphorylation of focal adhesion kinase when ECs were plated on a vitronectin-coated dish. Immunoprecipitation followed by Western blotting showed the coimmunoprecipitation of DSCR1 and integrin αvβ3. These results suggest that DSCR1 is involved in angiogenesis by regulating adhesion and migration of ECs via the interaction with integrin αvβ3.
Specific Functional Effects of Memantine Treatment in Patients with Moderate to Severe Alzheimer’s Disease
Authors: Doody R. , Wirth Y. , Schmitt F. , Möbius H.J.
Published: July 2004

Treatment of Alzheimer’s disease (AD) that combats progressive functional deterioration can improve the patient’s quality of life and reduce caregiver burden. Memantine, a moderate affinity N-methyl-D-aspartate receptor antagonist, reduces global deterioration in AD patients and provides cognitive and functional benefits relative to placebo. Two previous studies reported statistically significant benefits of memantine for overall functional ability on the Alzheimer Disease Cooperative Study Activities of Daily Living Inventory modified for severe dementia (ADCS-ADL19), Functional Assessment Staging, and G2 scale. The present study reports a single-item analysis of the ADL scales from the two trials and shows that patients treated with memantine demonstrated a numerical advantage over placebo on all items assessed. These results help to translate the positive effects of memantine into specific aspects of functional ability, information that is relevant to AD patients and their families as well as to researchers interested in the assessment of functional ability in AD clinical trials.
Cortisol and Its Relation to Insulin Resistance before and after Weight Loss in Obese Children
Authors: Reinehr Thomas , Andler Werner
Published: July 2004

Background: Insulin resistance occurs both in obesity and in Cushing’s syndrome suggesting a pathogenetic role of cortisol in insulin-resistant obese subjects. Methods: We examined serum cortisol in 81 insulin-resistant (homeostasis model assessment (HOMA) >4) obese children (age in median 12 years) and 151 obese children without insulin resistance (HOMA ≤4) (age in median 10 years) and compared these to cortisol of 83 healthy children of normal weight (age in median 12 years). Multivariate linear regression analysis was conducted for the dependent variable insulin resistance (HOMA), including weight status (BMI), age, gender, pubertal stage and cortisol concentration as independent variables. Furthermore, we analyzed cortisol and insulin resistance in 45 obese children with significant weight loss (reduction in SDS-BMI ≧0.5) and in 109 obese children without significant weight loss (reduction in SDS-BMI <0.5) over the time period of 1 year. Results: Cortisol was significantly (p = 0.006) higher in obese insulin-resistant children (median 14.6 µg/dl) compared to those of normal weight (median 11.4 µg/dl) or obese without insulin resistance (median 11.7 µg/dl). Insulin resistance was significantly influenced by weight status (BMI), age and cortisol using multivariate linear regression analysis. A reduction in overweight showed a significant decrease in cortisol (p = 0.005) and insulin resistance (p = 0.002) in insulin-resistant children, whilst there were no significant changes in children not reducing their overweight and in non-insulin-resistant children. Conclusions: Cortisol was moderately increased in insulin-resistant, obese children and related to insulin resistance. Weight reduction led to a decrease in cortisol and insulin resistance. These facts point to an association between cortisol and insulin resistance in obesity.
Peptide YY Directly Inhibits Ghrelin-Activated Neurons of the Arcuate Nucleus and Reverses Fasting-Induced c-Fos Expression
Authors: Riediger Thomas , Bothe Christine , Becskei Csilla , Lutz Thomas A.
Published: July 2004

The hypothalamic arcuate nucleus (Arc) monitors and integrates hormonal and metabolic signals involved in the maintenance of energy homeostasis. The orexigenic peptide ghrelin is secreted from the stomach during negative status of energy intake and directly activates neurons of the medial arcuate nucleus (ArcM) in rats. In contrast to ghrelin, peptide YY (PYY) is released postprandially from the gut and reduces food intake when applied peripherally. Neurons in the ArcM express ghrelin receptors and neuropeptide Y receptors. Thus, PYY may inhibit feeding by acting on ghrelin-sensitive Arc neurons. Using extracellular recordings, we (1) characterized the effects of PYY on the electrical activity of ghrelin-sensitive neurons in the ArcM of rats. In order to correlate the effect of PYY on neuronal activity with the energy status, we (2) investigated the ability of PYY to reverse fasting-induced c-Fos expression in Arc neurons of mice. In addition, we (3) sought to confirm that PYY reduces food intake under our experimental conditions. Superfusion of PYY reversibly inhibited 94% of all ArcM neurons by a direct postsynaptic mechanism. The PYY-induced inhibition was dose-dependent and occurred at a threshold concentration of 10–8M. Consistent with the opposite effects of ghrelin and PYY on food intake, a high percentage (50%) of Arc neurons was activated by ghrelin and inhibited by PYY. In line with this inhibitory action, peripherally injected PYY partly reversed the fasting-induced c-Fos expression in Arc neurons of mice. Similarly, refeeding of food-deprived mice reversed the fasting-induced activation in the Arc. Furthermore, peripherally injected PYY reduced food intake in 12-hour fasted mice. Thus the activity of Arc neurons correlated with the feeding status and was not only reduced by feeding but also by administration of PYY in non-refed mice. In conclusion, our current observations suggest that PYY may contribute to signaling a positive status of energy intake by inhibiting Arc neurons, which are activated under a negative status of energy intake by signals such as ghrelin.
Center Median-Parafascicular Complex and Pain Control
Authors: Weigel Ralf , Weigel Ralf , Krauss Joachim K. , Krauss Joachim K.
Published: July 2004

The center median-parafascicular (CM-Pf) complex, which constitutes the major portion of the intralaminar thalamus in man, has long been known to be involved in the processing of pain under normal and pathological conditions. Yet, these ‘forgotten’ nuclei with their rich connectivity to other thalamic nuclei, the basal ganglia and cortical areas have received only relatively little attention over the past two decades. With regard to the recent reinterest in functional stereotactic neurosurgery as a treatment option for chronic refractory pain, the CM-Pf complex has been reconsidered as a target. This review provides a systematic overview on the current knowledge about the anatomy and connectivity of the CM-Pf complex, neurophysiological studies, and on concepts of its role in pain processing under various conditions. We also review the previous experience with ablative surgery and deep brain stimulation of the CM-Pf complex. Studies in men and experimental animals indicate that the CM-Pf complex is part of a medial pain system, which appears to be involved primarily in affective and motivational dimensions of pain. Single-unit recordings from the CM-Pf complex have shown that the activity of CM-Pf cells is modified by painful stimuli. Under pathological conditions, bursting firing patterns and altered discharge rates were found. Thalamotomies targeting at the CM-Pf complex yielded beneficial results for chronic pain, but interpretation of the results is limited. With bifocal deep brain stimulation, short-term effects of CM-Pf stimulation were superior to those of somatosensory thalamic stimulation in neuropathic pain. There is evidence, that the CM-Pf complex might also be involved in the mediation of the beneficial effects of somatosensory thalamic stimulation and periventricular grey stimulation.
Long-Lasting Microthalamotomy Effect after Temporary Placement of a Thalamic Stimulating Electrode
Authors: Kondziolka Douglas , Lee John Y.K.
Published: July 2004

Essential tremor can be surgically treated by thalamotomy or deep brain stimulation. During the surgical procedure for both of these procedures, a transient microthalamotomy effect has been observed. This benefit is usually short-lived and appears to be predictive of patient outcome. This report describes a patient who underwent a temporary placement of a stimulating electrode within the ventral intermediate nucleus of the motor thalamus. The procedure was aborted intraoperatively and the patient demonstrated a microthalamotomy effect. This microthalamotomy effect has remained persistent for 24 months, and the patient remains tremor free. This case report lends evidence to the idea that the volume of motor thalamus responsible for tremor may be small and precise. By recognizing the benefit obtained from small lesions with minimal tissue manipulation, surgeons can continue to refine the target for movement disorder surgery.
Differential Expression of Connective Tissue Growth Factor in Inflammatory Bowel Disease
Authors: di Mola Fabio F. , Di Sebastiano Pierluigi , Gardini Andrea , Innocenti Paolo , Zimmermann Arthur , Büchler Markus W. , Friess Helmut
Published: July 2004

Inflammatory bowel disease consists of Crohn’s disease (CD) and ulcerative colitis (UC). A major clinical problem in some patients is to differentiate clearly between these entities, which is important when planning appropriate medical and surgical treatment. Connective tissue growth factor (CTGF), a novel peptide involved in fibrotic disorders, was analyzed in the present study in CD and UC patients to evaluate its possible role in these two disorders. Twenty-five normal human intestinal tissue samples were obtained through an organ donor program. CD tissues were obtained from 28 individuals undergoing partial intestinal resection (17 small bowel; 11 large bowel) due to complications of the disease. UC tissue samples were obtained from 16 patients undergoing colectomy due to complications of the disease. Expression of CTGF was studied by Northern blot analysis. In situ hybridization was used to localize mRNA moieties in the tissue samples. Northern blot analysis revealed an average 5-fold increase in CTGF mRNA expression in 89% (25/28) of CD tissue samples by comparison with normal controls (p < 0.0001). In contrast, in UC samples CTGF mRNA levels were comparable to those of normal controls. However, UC tissue samples exhibited enhanced TGF-β1 mRNA levels (4-fold; p < 0.05). In situ hybridization in CD samples showed CTGF mRNA localized especially in fibroblasts within the submucosal layer, around lymph follicles and in some areas of intense damage in the proximity of the luminal surface, whereas inflammatory cells were devoid of any CTGF mRNA signal. The present data indicate that CTGF plays a different role in IBD and might be useful, especially in those cases with unusual disease presentation, to better differentiate UC and CD. In addition, our data indicate a crucial role for CTGF in CD, where fibrosis and stenosis are frequent complications that require surgery.
Quality of Life and Illness Costs in Irritable Bowel Syndrome
Authors: Simrén Magnus , Brazier John , Coremans Georges , Dapoigny Michel , Müller-Lissner Stefan A. , Pace Fabio , Smout André J.P.M. , Stockbrügger Reinhold W. , Vatn Morten H. , Whorwell Peter J.
Published: July 2004

Quality of life is reduced in patients with irritable bowel syndrome, and the costs for this disease are substantial to society. During a meeting in London, UK, the IBiS club reviewed the literature on these subjects. Drawbacks and advantages with existing instruments to assess quality of life and costs were discussed and the clinical and scientific relevance of the current knowledge was assessed. A summary from the meeting is presented in this paper.