bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of the Manual Mycobacteria Growth Indicator Tube and the Etest with the Method of Proportion for Susceptibility Testing of Mycobacterium tuberculosis
Authors: Fegou E. , Jelastopulu E. , Nicolaou S. , Sevdali M. , Anagnostou S. , Kanavaki S. , Dimitracopoulos G. , Spiliopoulou I.
Published: May 2006

Background: Clinical microbiology laboratories should provide reliable results on susceptibility testing of Mycobacterium tuberculosis to different agents. Methods: The manual Mycobacteria Growth Indicator Tube (MGIT) and Etest were compared to the method of proportion (MOP) for susceptibility testing of 88 clinical isolates of M. tuberculosis against isoniazid (INH), rifampin (RIF), streptomycin (STR) and ethambutol (EMB). Isolates were recovered from different patients and were identified at species level by PCR and hybridization. Results: Resistance to INH was detected in 20.5, 29.5 and 12.5% of the isolates, followed by STR resistance (19.3, 26.1 and 1.1%), RIF (9.1, 4.5 and 5.7%) and EMB (2.3, 11.4 and 2.3%) by the MOP, MGIT and Etest, respectively. Sensitivity of the manual MGIT ranged from 37.5% for RIF resistance to 100% for EMB, while Etest sensitivity ranged from 5.9% for STR to 62.5% for RIF. Conclusions: MOP remains the method of choice, with the manual MGIT showing superior sensitivity at detecting resistance to INH, STR and EMB compared to the Etest.
Potential New Antimalarial Chemotherapeutics Based on Sphingolipid Metabolism
Authors: Pankova-Kholmyansky Irene , Flescher Eliezer
Published: May 2006

The discovery of new antimalarial drugs is mandatory to improve the effectiveness of antimalarial prophylaxis and treatment. In this review, we focused on sphingolipids as potential new targets for antimalarial drugs. Inhibition of sphingomyelin and/or glucosylceramide synthases leads to increased intracellular concentrations of ceramide and results in growth inhibition of Plasmodium falciparum. In mammalian cells, ceramide mediates death by chemotherapeutic drugs. We demonstrated that ceramide mediates the antimalarial effect of artemisinin and mefloquine by depletion of glutathione levels. Furthermore, ceramide and artemisinin activated p38 mitogen-activated protein kinase in P. falciparum, thus inhibiting its growth, apparently by a non-apoptotic mechanism. In summary, we propose novel options of antimalarials based on ceramide cytotoxic activity.
Photoperiod-Independent Changes in Immunoreactive Brain Gonadotropin-Releasing Hormone (GnRH) in a Free-Living, Tropical Bird
Authors: Moore Ignacio T. , Bentley George E. , Wotus Cheryl , Wingfield John C.
Published: May 2006

Timing of seasonal reproduction in high latitude vertebrates is generally regulated by photoperiodic cues. Increasing day length in the spring is associated with changes in the brain that are responsible for mediating reproductive activities. A primary example of this is the increased content of gonadotropin-releasing hormone (GnRH) in the preoptic area of the hypothalamus in birds as they enter the spring breeding season. Increased GnRH activity stimulates the release of luteinizing hormone and follicle-stimulating hormone from the anterior pituitary. These gonadotropins induce growth of the gonads and release of sex steroids which act on the brain to mediate reproductive behaviors. By contrast, seasonal breeding in the tropics can occur in the absence of significant changes in photoperiod. To our knowledge, no studies have investigated whether seasonal breeding in free-living tropical vertebrates is associated with seasonal changes in the GnRH system. We studied two populations of rufous-collared sparrows (Zonotrichia capensis) at the equator, separated by only 25 km, but with asynchronous reproductive phenologies associated with local climate and independent of photoperiodic cues. We collected brains and measured GnRH immunoreactivity (GnRH-ir) during each population’s breeding and non-breeding periods. Breeding males had larger, but not more, GnRH-ir cells than non-breeding birds. The plasticity of the GnRH system was associated with local climate, such that the two populations exhibited asynchronous changes in GnRH-ir despite experiencing identical photoperiod conditions. Our results demonstrate that tropical birds can exhibit neural changes similar to those exhibited in higher latitude birds. However, these tropical populations appear to be using supplementary cues (e.g., rainfall, temperature, food availability) in a similar way to higher latitude species using an initial predictive cue (photoperiod). These results raise questions about the evolution of reliance upon photoperiodism and the strength of reproductive responses to other environmental cues in congeners from higher latitudes. The ability to respond to a multitude of environmental cues might be part of the ancestral condition, and the subsequent obligate photoperiodism in high-latitude congeners could reflect a loss of flexibility in response to environmental signals.
Metabolic Treatment with L-Carnitine in Acute Anterior ST Segment Elevation Myocardial Infarction
Authors: Tarantini Giuseppe , Scrutinio Domenico , Bruzzi Paolo , Boni Luca , Rizzon Paolo , Iliceto Sabino
Published: May 2006

Background: Administration of L-carnitine in patients with anterior acute myocardial infarction (AMI) prevents left ventricular remodeling. Current study was aimed to assess the effect of L-carnitine administration on mortality and heart failure in patients with anterior AMI. Methods: CEDIM 2 trial was a randomized, double-blind, multicenter, placebo-controlled trial planned to enroll 4,000 patients with acute anterior AMI. The trial was interrupted after the enrolment of 2,330 patients because of the lower than expected enrolment rate. The primary end point was a composite of death and heart failure at 6 months; 5-day mortality was the secondary end point. Results: During the 6-month follow-up, the primary end-point was not significantly different between the L-carnitine and placebo group (9.2 vs. 10.5%, p = 0.27). A reduction in mortality was seen in the L-carnitine arm on day 5 (secondary end-point) from randomization (HR = 0.61, 95% CI 0.37–0.98, p = 0.041). Conclusions: In CEDIM 2 trial L-carnitine therapy led to a reduction in early mortality (secondary end-point) without affecting the risk of death and heart failure at 6 months in patients with anterior AMI, leading to a non-significant finding with respect to the primary end-point.
The Use of Low-Dose Insulin in Cardiogenic Shock due to Combined Overdose of Verapamil, Enalapril and Metoprolol
Authors: Hasin Tal , Leibowitz David , Antopolsky Meir , Chajek-Shaul Tova
Published: May 2006

We describe a case of severe heart failure due to the combined effect of verapamil and enalapril overdose in a patient treated regularly with metoprolol. The patient was dependent for 2 days on glucagon and dopamine infusion but remained oliguric, with deteriorating renal function. Marked improvement in all hemodynamic parameters was noted a short time after initiation of treatment with low-dose insulin infusion (1–2 units/h), which allowed the prompt withdrawal of glucagon and dopamine. We discuss the efficacy of glucose-insulin treatment in toxic cardiac depression and suggest that a low dose may be beneficial in similar cases.
Decrease in Salivary Secretion by Radiation Mediated by Nitric Oxide and Prostaglandins
Authors: de la Cal Carolina , Lomniczi Alejandro , Mohn Claudia E. , De Laurentiis Andrea , Casal Mariana , Chiarenza Ana , Paz Dante , McCann Samuel M. , Rettori Valeria , Elverdín Juan Carlos
Published: May 2006

Objective: In the present work, we evaluated the effect of exposing the submandibular glands (SMG) to radiation, studying different functional parameters such as salivary secretion, nitric oxide (NO) production, reactive oxygen species formation, prostaglandin (PGE) content and apoptosis. Methods: We irradiated rats in the head and neck region with a single dose of γ-ray radiation of 15 Gy. Two hours after radiation, we measured norepinephrine-induced salivary secretion. After that, the SMG were dissected, and in this tissue, we measured the activity of NO synthase (NOS), the PGE content, the amount of reactive oxygen species, apoptotic cells and mitochondrial inducible NOS (iNOS) expression. Results: We found that radiation decreased salivary secretion when 10 and 30 µg/kg of norepinephrine was administered via the right femoral vein. We observed that iNOS activity was reduced and PGE content increased after radiation in SMG, indicating that NO and PGEs may participate in salivary secretion. The expression of mitochondrial NOS was increased after radiation leading to the formation of large amounts of NO that acts as a proapoptotic signal. In fact, we observed an augmentation in apoptotic cells. In this study, we also observed an increase in lipid peroxidation induced by radiation that may contribute to tissue damage. Conclusions: Our results indicate that radiation induced a decrease in salivary secretion and SMG iNOS activity, meanwhile the PGE content, the lipid peroxidation and apoptosis increased in the tissue. These modifications decrease salivary secretion.
Correction of Endothelial Dysfunction in Diabetic Female Rats by Tetrahydrobiopterin and Chronic Insulin
Authors: Akamine Eliana H. , Kawamoto Elisa M. , Scavone Cristoforo , Nigro Dorothy , Carvalho Maria Helena C. , de Cássia A. Tostes Rita , Britto Luiz R.G. , Fortes Zuleica B.
Published: May 2006

Diabetes-induced vascular dysfunction has mainly been studied in males. However, the mechanisms involved may not correspond to those in females. Here we analyzed the effects of tetrahydrobiopterin (BH4) and chronic insulin on the physiology of mesenteric arterioles of alloxan-diabetic female rats. The parameters studied were the mesenteric arteriolar reactivity (intravital microscopy), nitric oxide synthase (NOS) activity (conversion of L-arginine to L-citrulline), eNOS gene expression (RT-PCR), NO production (diaminofluorescein), reactive oxygen species (ROS) generation (intravital fluorescence microscopy) and Cu/Zn superoxide dismutase (SOD) activity (spectrophotometry) and gene expression (RT-PCR). The reduced endothelium-dependent vasodilation of diabetic females was corrected by both BH4 and insulin. NOS activity was decreased by diabetes, but insulin did not correct it. However, NOS expression was not modified by either diabetes or insulin. Arterioles of diabetic rats exhibited lower NO production, which was fully corrected by BH4 and only partially by insulin. ROS generation was increased in diabetic rats, and both BH4 and insulin normalized it. Diabetes did not change SOD activity and gene expression. However, insulin increased SOD activity but not its expression. Our data suggest that, similarly to males, endothelial dysfunction in female diabetic rats involves an altered ROS/NO imbalance. In contrast to males, however, insulin does not regulate NOS in the microcirculation of diabetic females.
Transcription Factor Ets-1 Regulates Fibroblast Growth Factor-1-Mediated Angiogenesis in vivo: Role of Ets-1 in the Regulation of the PI3K/AKT/MMP-1 Pathway
Authors: Forough Reza , Weylie Brian , Collins Charles , Parker Janet L. , Zhu James , Barhoumi Rola , Watson Dennis K.
Published: May 2006

We previously demonstrated that a modified secreted form of fibroblast growth factor 1 (FGF-1), a prototypic member of the FGF family, has the ability to stimulate angiogenesis in an in vivo model of angiogenesis, the so-called chick chorioallantoic membrane assay or CAM. We recently defined the importance of the phosphatidylinositol 3-kinase/AKT pathway in FGF-1-mediated angiogenesis in this model using specific pharmacological inhibitors. In our continuing efforts to define the molecular signaling pathway regulating FGF-1-induced angiogenesis in vivo, we utilized a transcription factor activity assay and identified transcription factor Ets-1 as a critical effector of FGF-1-induced angiogenesis. Both activity and mRNA expression levels of the Ets-1 molecule were increased in response to FGF-1 overexpression in CAMs, as documented by electrophoretic mobility shift assay (gel shift) and reverse transcription real-time PCR techniques, respectively. Furthermore, the delivery of Ets-1 antisense (AS) into CAM tissues effectively reduced angiogenesis in the CAM assay. In addition, both Ets-1 AS-treated chicken CAMs and cultured endothelial cells exhibited a reduction in matrix metalloproteinase 1 gene expression levels. The Ets-1 AS-treated endothelial cells also demonstrated a reduction in migration. These data suggest that Ets-1 activation is a requisite for FGF-1-mediated angiogenesis in vivo. Therefore, Ets-1 might be a potential target for the generation of inhibitor drugs for the treatment of FGF-dependent pathological angiogenesis such as metastatic tumors, rheumatoid arthritis and diabetic retinopathy.
Theoretical and Numerical Analysis of Different Adequacy Indices for Hemodialysis and Peritoneal Dialysis
Authors: Waniewski Jacek , Debowska Malgorzata , Lindholm Bengt
Published: May 2006

Background: Apart from KT/V, equivalent urea clearance (EKR) and fractional solute removal (FSR) can also be used to assess the dialysis adequacy. Our objective was to analyze the relationships between these indices for different dialysis modalities and schedules, using urea kinetic modeling. Methods: EKR and FSR were calculated for HD (three or six times per week), automatic nightly PD (ANPD) and CAPD using the following reference values of urea concentration and mass in the body: peak, peak average, time average and treatment time average. Results: The standard KT/V approach is related to the treatment time average, whereas the standard EKR is related to the time average reference values. In spite of KT/V = 3.5 (K meaning dialyzer clearance or peritoneal diffusive mass transport coefficient), EKR and FSR were lower for ANPD and CAPD than for HD. The ratio of EKR to FSR was essentially the same for the different treatment modalities (range 3.48–4.07 ml/min). This could be explained by the theoretical analysis which predicts the value of EKR/FSR = V/Tc, independent of the treatment modality and schedules (V is a solute distribution volume, Tc is the time of the full dialysis cycle). Conclusion: Whereas the index KT/V in its standard form cannot be used to compare different dialysis regimens, EKR and FSR provide very similar evaluation of different dialysis modalities and schedules, and may be considered as equivalent measures for comparative studies of dialysis adequacy.
Efficacy and Safety of Fluvastatin-Extended Release in Hypercholesterolemic Patients: Morning Administration Is Equivalent to Evening Administration
Authors: Scharnagl Hubert , Vogel Monika , Abletshauser Claudia , Freisinger Franz , Stojakovic Tatjana , März Winfried
Published: May 2006

Background: Flexibility in the time of administration of statin therapy is likely to improve patient compliance. This study compared the efficacy and tolerability of morning and evening administration of the extended-release formulation of fluvastatin (fluvastatin XL). Methods: In this prospective, double-blind, multicenter, multiple dose study, 236 patients with type IIa/b hypercho lesterolemia were randomized to receive fluvastatin XL, 80 mg, in the morning or evening for 8 weeks. Results: At 8 weeks, low-density lipoprotein cholesterol levels were reduced by 34.5 and 35.0% in the morning and evening treatment groups, respectively (p = 0.0118 for non-inferiority of morning administration). There were no statistically significant differences between the morning and evening treatment groups in the changes in total cholesterol (p = 0.56), high-density lipoprotein cholesterol (p = 0.21), triglycerides (p = 0.13), apolipoprotein B (p = 0.66) and apolipoprotein AI (p = 0.88) at 8 weeks. The frequency of adverse events was slightly lower in the morning treatment group compared with the evening treatment group (27.4 vs. 35.5%). Conclusions: The efficacy and safety profiles of fluvastatin XL are equivalent for morning and evening administration.
Blood Pressure Management in Acute Stroke: A Long-Standing Debate
Authors: Spengos Konstantinos , Tsivgoulis Georgios , Zakopoulos Nikolaos
Published: May 2006

Although elevated blood pressure (BP) levels are a common complication of acute stroke, whether of ischaemic or haemorrhagic type, a long-standing debate exists regarding the management of post-stroke hypertension. In the absence of solid, randomised data from controlled trials, the current observational evidence allows different approaches, since theoretical arguments exist for both lowering BP in the setting of acute stroke (reduce the risk of stroke recurrence, of subsequent oedema formation, of rebleeding and haematoma expansion in patients with cerebral bleeding) as well as leaving raised BP levels untreated (avoid reduction in cerebral perfusion pressure and blood flow to viable ischaemic tissue in the absence of normal autoregulation). The present review will summarize the evidence for and against the therapeutic manipulation of BP in acute stroke provided by the currently available observational studies and randomised trials, consider the ongoing clinical trials in this area and address the present recommendations regarding this conflicting issue.
Neuropsychological Changes in Patients with Carotid Stenosis after Carotid Endarterectomy
Authors: Fukunaga Shinya , Okada Yasushi , Inoue Tooru , Hattori Fumitada , Hirata Koichi
Published: May 2006

We investigated changes in neuropsychological function in patients with carotid stenosis following carotid endarterectomy (CEA) in relation to cerebral hemodynamics. The subjects were 24 patients who underwent CEA and 17 healthy controls matched by age, educational level, gender and handedness. Cerebral angiography, single-photon emission computed tomography (SPECT) and neuropsychological tests were performed approximately 1 week before and 3 weeks after CEA in all patients. In the patient group, the categories achieved in the new modified Wisconsin Card Sorting Test (WCST) improved significantly after CEA (4.0 ± 2.0; before CEA: 2.3 ± 2.1, p < 0.01). The perseverative errors of Nelson in the WCST improved significantly (before CEA: 9.1 ± 6.9, after CEA: 3.3 ± 3.4, p < 0.01). The difficulty maintaining set in the WCST improved significantly (before CEA: 2.3 ± 1.9, after CEA: 1.3 ± 1.7, p < 0.05). In the control group, none of the test scores showed significant improvement between the first and second tests. Moreover, frontal lobe function improved significantly in those patients with baseline carotid artery diameter of more than 70% of normal, or whose preoperative cerebral perfusion reserve was reduced by less than 15% of a response to acetazolamide. Our results suggest that CEA improves frontal lobe function in patients with severe carotid stenosis or reduced cerebral perfusion reserve.
Prematurity – Another Example of Perinatal Metabolic Programming?
Authors: Hofman P.L. , Regan F. , Cutfield W.S.
Published: May 2006

Low birth weight is associated with both later adult diseases such as type 2 diabetes mellitus and a number of metabolic abnormalities, the foremost of which is insulin resistance. Indeed the link between an adverse perinatal environment, manifested by low birth weight, and adult life pathology may be an early, permanent reduction in insulin sensitivity. A reduction in insulin sensitivity has been demonstrated in small for gestational age (SGA), term subjects from childhood through to adulthood. Less is known about children born premature into an adverse neonatal environment. We present data demonstrating that premature infants also have metabolic abnormalities similar to those observed in term, SGA children and that these occur irrespective of whether they are SGA or appropriate for gestational age (AGA).
Cerebral White Matter Hyperintensities on MRI: Current Concepts and Therapeutic Implications
Authors: Ovbiagele Bruce , Saver Jeffrey L.
Published: May 2006

Background: White matter hyperintensities (WMH) are commonly observed MRI abnormalities in the elderly, which generally reflect covert vascular brain injury. WMH cumulatively produce substantial neurologic, psychiatric, and medical morbidity. This review provides an overview of current knowledge on vascular WMH, and describes some pharmacological agents that may have a role in mitigating this condition. Summary of Review: This review has two main focus areas. The first is a discussion of currently available knowledge regarding the public health burden, pathogenesis, and various risk factors associated with the presence of vascular white matter lesions noted on brain MRI. The second section of the article details the mechanistic and clinical basis for promising pharmacological treatment modalities that could potentially prevent progression of ischemic cerebral white matter brain injury. Many of these therapies are already of proven efficacy in preventing recurrent stroke. Conclusions: Individuals with vascular white matter lesions on MRI may represent a potential target population likely to benefit from secondary stroke prevention therapies.
A Randomised, Controlled Pilot Study to Investigate the Potential Benefit of Intervention with Insulin in Hyperglycaemic Acute Ischaemic Stroke Patients
Authors: Walters M.R. , Weir C.J. , Lees K.R.
Published: May 2006

Background: Hyperglycaemia on presentation with acute ischaemic stroke (AIS) is associated with poor outcome, but intervention is unproven. We investigated the safety and tolerability of one method of glycaemic control. Methods: Patients within 24 h of AIS and plasma glucose 8–20 mmol/l were randomised to receive either rigorous glycaemic control (RC) or standard management (SM) for 48 h. RC comprised i.v. insulin at a variable rate adjusted for target glucose concentration of 5–8 mmol/l, and intravenous crystalloid. The SM group received intravenous crystalloid alone in an open-label design. Results: Thirteen patients were randomised to RC and 12 to SM (age 75 ± 6.2 years; 40% male; 20% lacunar stroke; time to treatment 8 ± 6.1 h; plasma glucose 10.6 ± 0.9 mmol/l; known diabetes 52%; NIHSS 8, range 2–28). The glucose concentration-time curve was reduced in the RC group (AUC 324 ± 15 versus 385 ± 28 h·mmol/l, p = 0.04). By 48 h, plasma glucose in both groups was 6.8 ± 1.1 and 7.5 ± 1.3 mmol/l respectively, but mean hourly insulin requirements in the RC group had dropped from 3.25 ± 0.32 units to 1.25 ± 0.5 units (p < 0.01). One transient episode of hypoglycaemic symptoms occurred in the RC group. Conclusion: Glycaemic control with sliding scale insulin for 48 h is feasible and well-tolerated after AIS. Treatment after 48 h may be unnecessary.
High Blood Pressure and Inflammation Are Associated with Poor Prognosis in Lacunar Infarctions
Authors: Blanco Miguel , Castellanos Mar , Rodríguez-Yáñez Manuel , Sobrino Tomás , Leira Rogelio , Vivancos José , Lizasoain Ignacio , Serena Joaquín , Dávalos Antonio , Castillo José
Published: May 2006

Lacunar infarction has long been considered to be associated with good prognosis, however a significant percentage of these patients remain functionally dependent. In this study we sought to investigate the factors associated with poor outcome in patients with lacunar infarction. Subjects and Methods: We have performed a secondary study in 113 patients with lacunar infarctions admitted within the first 24 h of symptom onset (mean age 70 years, 57.5% men). Blood pressure, body temperature, serum glucose levels, neurotransmitters and pro-inflammatory markers were measured at admission and during the first 72 h. Stroke severity was assessed by the Canadian Stroke Scale (CSS). Neuroimaging evaluation was performed at admission and between days 4 and 7. Poor functional outcome was considered as a Barthel index <85 at 3 months. Results: 36 patients (31.9%) had poor outcome. Older age (p = 0.009), history of hypertension (p = 0.005), higher body temperature (p < 0.0001), systolic blood pressure (SBP) (p = 0.010), serum glucose (p = 0.002) and interleukin-6 (IL-6) (p < 0.0001) levels, as well as lower CSS score at admission (p < 0.0001) were all predictive factors of poor outcome in bivariate analyses. SBP at admission (OR 2.07, CI 95% 1.04–3.28, p = 0.015) was the only clinical predictor on multivariate analysis. When the logistic model was further adjusted for biomarkers of inflammation and excitotoxicity, IL-6 levels (OR 1.09, CI 95% 1.01–1.26, p = 0.003), but not SBP, was independently associated with poor outcome. This association persisted even after adjusting for potential predictors recorded during the first 72 h of hospitalization. Conclusion: High SBP and IL-6 levels on admission may predict poor outcome in patients with lacunar infarction.
Subtypes and One-Year Survival of First-Ever Stroke in Chinese Patients: The Nanjing Stroke Registry
Authors: Liu Xinfeng , Xu Gelin , Wu Wentao , Zhang Renliang , Yin Qin , Zhu Wusheng
Published: May 2006

Background: Morbidity and mortality of stroke have been investigated extensively in Western populations, while data concerning case fatality and cause of death after stroke are very limited in mainland China. This study aimed to analyze the 1-year survival and predictors of case fatality in Chinese patients with first-ever stroke. Methods: Subjects are patients registered in the Nanjing Stroke Registry Program. Information concerning cardiovascular risk factors and stroke characteristics were collected, and patients were followed after registration. Ischemic strokes were classified according to TOAST criteria as large-artery atherosclerosis (LAA), cardiac embolism stroke (CES), small-vessel stroke (SVS), or other determined and undetermined causes (UND). One-year case fatality was analyzed by the Kaplan-Meier method, and predictors of case fatality were evaluated by the Cox proportional hazards model. Results: A total of 752 patients with first-ever stroke were included, of which 142 (18.9%) were identified as intracerebral hemorrhage (ICH), 120 (16.0%) as LAA, 123 (16.4%) as SVS, 160 (21.3%) as CES and 216 (28.7%) as UND. The overall survival rate was 86.4% at the end of the 1-year follow-up. Patients with SVS have the highest survival rate (92.7%), followed by UND (89.4%), CES (88.1%) and LAA (84.2%). Patients with ICH have the lowest survival rate (76.8%). Survival rates of patients with different subtypes of stroke presented a significant difference (χ2 = 19.3, p < 0.001). For patients deceased during the first year after the index stroke, 33.3% of deaths were caused by the first stroke, 18.6% by recurrent stroke, 16.7% by cardiovascular comorbidities, 14.7% by nonvascular conditions and 16.7% died of undetermined causes. Advanced age, hypertension, hyperlipidemia, diabetes mellitus (DM), atrial fibrillation (AF), history of transient ischemic attack and cigarette smoking were associated with an increased risk of death 1 year after stroke. Conclusions: The case fatality rate and predictors for mortality of Chinese patients with first-ever stroke are similar to those reported for other populations. The significant influence of cardiovascular disease on the first-year survival rate emphasizes the importance of acute stroke management and control of hypertension, DM, AF and other predictors for decreasing case fatality and improving prognosis.
A Longitudinal Study of Health-Related Quality of Life of First Stroke Survivors’ Close Relatives
Authors: Schlote A. , Richter M. , Frank B. , Wallesch C.W.
Published: May 2006

Background and Purpose:Mental and social burdens of stroke patients’ relatives have been investigated repeatedly, but there is little information about their quality of life (QoL). The purpose of the study was to describe the health-related QoL of stroke patients’ relatives at 3 points in time after the stroke. Method: Sixty-four closest relatives of patients suffering from a disabling stroke were questioned at admission to inpatient rehabilitation as well as 6 months and 1 year after discharge with the SF36 (short form 36-item questionnaire) and about probable covariates. Results: During inpatient rehabilitation relatives’ perception of their physical role as well as of all mental health scales was significantly lower than the normative data. We found improvements in all scales except physical functioning between inpatient rehabilitation and 6 months after discharge. Deteriorations between 6 months and 1 year occurred in physical functioning, role physical, social functioning, role emotional and mental health. Conclusions: Changes in perceived health-related QoL indicate that relatives go through different stages while coping with the chronic illness of their family member during rehabilitation and in the first year after discharge. These findings may aid support and counseling.
The Skin Allergenic Properties of Chemicals May Depend on Contaminants – Evidence from Studies on Coumarin
Authors: Vocanson M. , Goujon C. , Chabeau G. , Castelain M. , Valeyrie M. , Floc’h F. , Maliverney C. , Gard A. , Nicolas J.F.
Published: May 2006

Background/Aims: Positive patch tests are considered representative of a contact allergy to the tested chemical. However, contaminants and derivatives rather than the suspected chemical itself could be responsible for the allergic skin reactions. Here, we tested the importance of contaminants in the sensitizing and allergenic properties of coumarin in mice and humans. Coumarin, an ingredient in cosmetics and fragrances, was chosen as the reference chemical since conflicting results have been obtained regarding its ability to induce contact allergy. In some chemical preparations, this could be explained by the presence of coumarin derivatives endowed with allergenic properties. Methods: In mice, three different coumarin preparations were tested in the local lymph node assay. In humans, we assessed the irritant and allergenic properties of highly pure coumarin in nonallergic and fragrance-allergic patients. Results: Pure coumarin did not exhibit irritant or sensitizing properties in the local lymph node assay. In contrast, two other commercially available coumarins and three contaminants that were detected in these coumarin preparations were identified as weak and moderate sensitizers, respectively. In humans, pure coumarin was extremely well tolerated since only 1 out of 512 patients exhibited a positive patch test to the chemical. Conclusions: These results indicate that coumarin cannot be considered as a common contact allergen and further emphasize that purity of chemicals is mandatory for the assessment of their allergenicity.
Response of Respiratory Flour Allergics in an Ingested Flour Challenge May Involve Plasmacytoid Dendritic Cells, CD25+ and CD152+ T Cells
Authors: Hoffmann Hans Jürgen , Skjold Tina , Raithel Martin , Adolf Katja , Hilberg Ole , Dahl Ronald
Published: May 2006

Background: A number of occupational respiratory allergens are food related, and little is known about the responses these allergens elicit in sensitized persons that ingest them. Methods: Nine respiratory flour-allergic volunteers were exposed in a double-blind placebo-controlled food challenge with flour. Responses were monitored by spirometry, acoustic rhinometry, determination of urinary methyl histamine and tryptase and flow cytometric evaluation of basophil, dendritic and T cell numbers and markers. Results: Significant increases in serum tryptase (compared with placebo post-exposure levels) and methyl histamine and a coordinated decrease in blood basophils and nasal volume after ingestion of allergen compared with placebo suggest an allergic response to ingested allergen. There was no change in forced expiratory volume in 1 s. The number of blood plasmacytoid dendritic cells (DC), but not of myeloid DC, decreased after exposure (p = 0.001). DC HLA DR was reduced after both exposures (p < 0.001). Expression of CXCR4 on DC was reduced after allergen (p = 0.033) but not after placebo exposure. CD4+ T cell expression of CD25 was elevated after placebo (p = 0.021) but reduced after allergen provocation. The reduction in CD25 expression after allergen compared with placebo was significant (p = 0.024). CD152 was downregulated on these cells after allergen (p = 0.039) but less so after placebo exposure. Conclusion: Persons with respiratory allergy respond after ingestion of the relevant allergen. Response to this allergen challenge may selectively recruit plasmacytoid DC through CXCR4 and T cells expressing CD25 and CD152, which may be a regulatory phenotype.
Assessment of Health-Related Quality of Life in Chronic Dialysis Patients with the COOP/WONCA Charts
Authors: Martín-Díaz Francisco , Reig-Ferrer Abilio , Ferrer-Cascales Rosario
Published: May 2006

Background: The aim of the present work was to determine the health-related quality of life (HRQOL) of our patients on hemodialysis using the COOP/WONCA charts. A further aim was to explore its psychometric characteristics. Methods: The present study included all patients attending the hemodialysis unit of our hospital. The comparative study of the results was conducted with other population groups in which this questionnaire has been applied previously (primary-care patients, their accompanying persons, pregnant women, Alzheimer patient carers and drug addicts). The dimensional structure of the questionnaire was explored by factorial analysis of principal components, and internal consistency was evaluated with the Cronbach α factor. Concurrent validity was determined by comparative analysis of the results of the COOP/WONCA charts with those of another questionnaire, the 36-item short form of the Quality of Life Score (SF-36). To do so, 60 randomly chosen patients completed both questionnaires. Results: 98.9% of patients completed the COOP/WONCA charts in their entirety. The mean scores of all the charts, with the exception of overall health, are in the range of what could be called ‘favorable area of quality of life’ (below 3). With respect to the rest of the groups, the dialysis patients had the best scores on the ‘feelings’ and ‘social activities’ charts and none of the worst ones. The joint factorial analysis revealed that the questionnaire has a 3-factor structure: factor 1 or daily functioning, factor 2 or quality of life and health, factor 3 or the psychosocial factor. The Cronbach α value for the 9 charts was 0.766. All the correlations between equivalent dimensions of questionnaires COOP/WONCA and SF-36 were statistically significant (p < 0.01). The convergent validity mean was 0.57 and the discriminant validity mean was 0.22, appreciably lower than convergent validity. Conclusions: This study shows that the process of psychological adaptation to problems deriving from dialysis is satisfactory. Moreover, the COOP/WONCA charts are a useful instrument for the determination of the HRQOL in hemodialysis patients without losing psychometric quality.
Efficacy of Darbepoetin in Doxorubicin-Induced Cardiorenal Injury in Rats
Authors: Noiri Eisei , Nagano Nobuo , Negishi Kosuke , Doi Kent , Miyata Sonoe , Abe Megumi , Tanaka Tamami , Okamoto Koji , Hanafusa Norio , Kondo Yasushi , Ishizaka Nobukazu , Fujita Toshiro
Published: May 2006

This study was intended to elucidate the efficacy of an erythropoietin analog in cardiorenal dysfunction syndrome using a rodent model. Cardiorenal dysfunction was induced using doxorubicin hydrochloride (DXR). Lower doses (3 µg/kg) and higher doses (30 µg/kg) of darbepoetin alfa (DA) were used for intervention. Blood examinations for creatinine, blood urea nitrogen, iron, and hemoglobin were performed until 11 weeks after starting DA administration. Urine collection was performed 10 weeks after starting DA, and protein, iron, and N-acetyl-β-D-glucosaminidase levels and antioxidation capacity of DA were determined. The dry left ventricular heart weight was measured, when the animals were sacrificed 11 weeks after starting DA administration. Histological analyses were performed for interstitial fibrotic changes and iron deposition in the kidney. Administration of DA markedly improved anemia to the normal control level and significantly alleviated DXR-induced increases of creatinine, blood urea nitrogen, renal interstitial fibrosis, renal iron deposition, and dry left ventricular weight, but serum and urinary iron and urinary protein and N-acetyl-β-D-glucosaminidase levels were unchanged. The urinary total radical-trapping antioxidant capacity was improved to the normal control level in DA-treated animals. DA reduced the DXR-induced cardiorenal injury. This improvement was achieved, when anemia was corrected to the normal control level.
The Bioactivity of Plasma Factors in Focal Segmental Glomerulosclerosis
Authors: Marszal Joanna , Saleem Moin A.
Published: May 2006

Focal segmental glomerulosclerosis (FSGS) is a devastating form of nephrotic syndrome, often leading to end-stage renal failure after the failure of a succession of highly toxic therapies. It has long been thought to be caused by a circulating factor(s) that may be produced by cells of the immune system. Much research has focused on identifying such factor(s), including the development of a promising in vitro assay, which estimates glomerular permeability based on the swelling of isolated glomeruli in response to patients’ plasma. This assay has also been used as the basis of testing plasma fractions for permeability activity, with no specific factor yet identified. Other studies have attempted to replicate proteinuria in whole animals, by injecting plasma or plasma fractions from focal segmental glomerulosclerosis patients, with inconsistent results. More recently there has been evidence that there may be either inhibitory or missing factor(s) in plasma, with respect to permeability. An additional major biological advance is a growing appreciation of the podocyte as the target cell in this disease, and an understanding of the key molecules involved. Putting together this knowledge, with the latest technological advances in protein identification, provides promising avenues towards finally solving the basis of this enigmatic disease.
Hyperbaric Oxygen Treatment Augments the Efficacy of a Losartan Regime in an Experimental Nephrotic Syndrome Model
Authors: Yilmaz Mahmut Ilker , Korkmaz Ahmet , Kaya Ayper , Sonmez Alper , Caglar Kayser , Topal Turgut , Eyileten Tayfun , Yenicesu Mujdat , Acikel Cengizhan , Oter Sukru , Yaman Halil , Aktug Hüseyin , Oguz Yusuf , Vural Abdulgaffar , Ikizler T. Alp
Published: May 2006

Background/Aims: Proteinuria is associated with oxidant stress and inflammation. Hyperbaric oxygen (HBO) treatment has anti-inflammatory and anti-oxidant effects. The aim of the study was to investigate the benefits of HBO treatment on an experimental nephrotic syndrome model. Methods: 50 male Sprague-Dawley rats weighing 255 ± 39 g were housed. Forty rats were injected 6 mg/kg adriamycin into tail veins under anesthesia to induce nephrosis, while 10 rats were spared as sham control. After the stabilization of proteinuria at the sixth week, the rats were treated for 6 weeks by losartan (n = 10, 30 mg/kg/day), HBO (n = 10, 2.8 atmosphere absolute, 90 min/day), HBO + losartan (n = 10) and vehicle (n = 10). Protein carbonyl (PCO), superoxide dismutase (SOD) and glutathione peroxidase (GPx) were analyzed from tissue specimens. Biochemical markers were studied from venous samples and 24-hour urine was collected for proteinuria. The surviving animals at 12 weeks (vehicle group (n = 6), HBO (n = 6), losartan (n = 8), HBO + losartan (n = 10) were sacrificed. Glomerular sclerosis, tubulointerstitial and blood vessel changes were determined by semiquantitative scoring. Results: The PCO levels increased (p < 0.001), and the GPx and SOD levels decreased (p < 0.001 for both) in the nephrotic rats. In losartan and HBO groups GPx levels increased (p = 0.001, p = 0.002 respectively), but PCO and SOD levels did not change. The combination of HBO with losartan significantly increased the GPx and SOD levels (p = 0.001 for both) and decreased PCO levels (p = 0.005). HBO but not losartan significantly reduced proteinuria (p < 0.001). The combination of HBO and losartan reduced proteinuria better than the single losartan regime (p < 0.001). The effect of the combination was also noticed on the histological examination of the kidneys. The activities, appetites, weight gains, and improvement of edema were better in the HBO combined with losartan regime. Conclusions: These results indicate that the addition of HBO therapy to a conventional regime, angiotensin receptor blockers, has significant benefits in the management of proteinuria. Future clinical studies are needed to elucidate the role of HBO and other antioxidant strategies in the treatment of proteinuria.
Nephrotoxicity due to Combination Antibiotic Therapy with Vancomycin and Aminoglycosides in Septic Critically Ill Patients
Authors: Malacarne Paolo , Bergamasco Stefano , Donadio Carlo
Published: May 2006

The aim of this prospective observational study was to evaluate the incidence of nephrotoxicity due to combination therapy with vancomycin and aminoglycosides in septic critically ill patients admitted to the intensive care unit. Methods: Thirty consecutive critically ill patients were treated with vancomycin concurrent with aminoglycosides for sepsis. Inclusion criteria were: the need for mechanical ventilation and the presence of severe infection due to bacteria susceptible to vancomycin and aminoglycosides. Exclusion criteria were: age <18 years, impaired renal function (24-hour creatinine clearance <90 ml/min) or previous adverse reaction to either drug. Serum creatinine and urea concentrations, creatinine clearance, 24-hour urinary excretion of proteins, β2-microglobulin and enzymes were measured immediately before starting therapy and at different times thereafter. Results: Eleven of the 30 patients had a transient and modest increase in serum urea, 15 patients presented with urinary excretion of β2-microglobulin and tubular enzymes, and 14 patients had urinary proteins.In the only patient with severe acute renal failure (serum creatinine 8.2 mg/dl), the clinical course was complicated by prolonged hypotension. Conclusion: Concurrent administration of vancomycin and aminoglycosides to critically ill septic patients with normal renal function at baseline induced mainly slight and transient toxic tubular effects. The only clinically significant nephrotoxic event occurred in a patient with septic shock.
Renal Vascular Resistance in Sepsis
Authors: Langenberg Christoph , Bellomo Rinaldo , May Clive N. , Egi Moritoki , Wan Li , Morgera Stanislao
Published: May 2006

Aims: To assess changes in renal vascular resistance (RVR) in human and experimental sepsis and to identify determinants of RVR. Methods: We performed a systematic interrogation of two electronic reference libraries using specific search terms. Subjects were animals and patients involved in experimental and human studies of sepsis and septic acute renal failure, in which the RVR was assessed. We obtained all human and experimental articles reporting RVR during sepsis. We assessed the role of various factors that might influence the RVR during sepsis using statistical methods. Results: We found no human studies, in which the renal blood flow (and, therefore, the RVR) was measured with suitably accurate direct methods. Of the 137 animal studies identified, 52 reported a decreased RVR, 16 studies reported no change in RVR, and 69 studies reported an increased RVR. Consciousness of animals, duration of measurement, method of induction of sepsis, and fluid administration had no effect on the RVR. On the other hand, on univariate analysis, size of the animals (p<0.001), technique of measurement (p = 0.017), recovery after surgery (p = 0.004), and cardiac output (p <0.001) influenced the RVR. Multivariate analysis, however, showed that only cardiac output (p = 0.028) and size of the animals (p = 0.031) remained independent determinants of the RVR. Conclusions: Changes in RVR during sepsis in humans are unknown. In experimental sepsis, several factors not directly related to sepsis per se appear to influence the RVR. A high cardiac output and the use of large animals predict a decreased RVR, while a decreased cardiac output and the use of small animals predict an increased RVR.
FGF-23 and sFRP-4 in Chronic Kidney Disease and Post-Renal Transplantation
Authors: Pande Sangeeta , Ritter Cynthia S. , Rothstein Marcos , Wiesen Karen , Vassiliadis John , Kumar Rajiv , Schiavi Susan C. , Slatapolsky Eduardo , Brown Alex J.
Published: May 2006

Background: The phosphatonins fibroblast growth factor-23 (FGF-23) and FRP-4 are inhibitors of tubular phosphate reabsorption that may play a role in the hyperphosphatemia associated with chronic kidney disease (CKD) or in the hypophosphatemia associated with renal transplants. Methods: Plasma FGF-23, FRP-4, phosphorus and parathyroid hormone were measured in patients at all stages of CKD. Phosphate regulation of FGF-23 and secreted frizzled related protein-4 (sFRP-4) was examined in end-stage renal disease patients in the presence and absence of therapeutic phosphate binder usage. In renal transplant patients, plasma FGF-23, sFRP-4 and phosphorus concentrations were determined before and 4–5 days after transplantation. Results: Plasma FGF-23 correlated with creatinine clearance (r2 = –0.584, p < 0.0001) and plasma phosphorus (r2 = 0.347, p < 0.001) in CKD patients and with plasma phosphorus (r2 = 0.448, p < 0.001) in end-stage renal disease patients. Phosphate binder withdrawal increased FGF-23 levels. In kidney transplant patients, dramatic decreases in FGF-23 (–88.8 ± 5.4%) and phosphorus (–64 ± 10.2%) were observed by 4–5 days post-transplantation. In patients with post-transplant hypophosphatemia, FGF-23 levels correlated inversely with plasma phosphorus (r2 = 0.661, p < 0.05). sFRP-4 levels did not change with creatinine clearance or hyperphosphatemia in CKD or end-stage renal disease patients, and no relation was noted between post-transplant sFRP-4 levels and hypophosphatemia. Conclusions: In CKD, FGF-23 levels rose with decreasing creatinine clearance rates and increasing plasma phosphorus levels, and rapidly decreased post-transplantation suggesting FGF-23 is cleared by the kidney. Residual FGF-23 may contribute to the hypophosphatemia in post-transplant patients.
Novices in Surgery Are the Target Group of a Virtual Reality Training Laboratory
Authors: Hassan Iyad , Maschuw Katja , Rothmund Matthias , Koller Michael , Gerdes Berthold
Published: May 2006

Background: This study aims to establish which physicians represent the suitable target group of a virtual training laboratory. Methods: Novices (48 physicians with fewer than 10 laparoscopic operations) and intermediate trainees (19 physicians who performed 30–50 laparoscopic operations) participated in this study. Each participant performed the basic module ‘clip application’ at the beginning and after a 1-hour short training course on the LapSim®. The course consisted of the tasks coordination, lift and grasp, clip application, cutting with diathermy and fine dissection at increasing difficulty levels. The time taken to complete the tasks, number of errors, and economy of motion parameters (path length and angular path) were analyzed. Results: Following training with the simulator, novices completed the task significantly faster (p = 0.001), demonstrated a greater economy of motion [path length (p = 0.04) and angular path (p = 0.01)]. In contrast, the intermediate trainees showed a reduction of their errors, but without reaching statistical significance. They showed no improvement in economy of motion and completed the task significantly slower (p = 0.03). Conclusion: Novices, in comparison to intermediate trainees, tend to benefit most during their first exposure to a laparoscopy simulator.