bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Anesthesia on Plasma and Kidney ANG II Levels in Normotensive and ANG II-Dependent Hypertensive Rats
Authors: Husková Zuzana , Kramer Herbert J. , Thumová Monika , Vaňourková Zdenka , Bürgelová Marcela , Teplan Vladimír , Malý Jan , Červenka Luděk
Published: May 2006

Background: Previous studies have implicated that normotensive rats with normal renal renin activity respond to anesthesia and surgery with greater increases in plasma and kidney angiotensin II (ANG II) concentrations than ANG II-dependent hypertensive rats with intrarenal renin depletion. In the present study, we therefore compared plasma and kidney ANG II levels in anesthetized and conscious normotensive and ANG II-dependent hypertensive rats. Methods: Salt-replete Hannover-Sprague-Dawley rats (HanSD) served as controls. As models of ANG II-dependent hypertension we used: 1st, transgenic rats harboring the Ren-2 renin gene (TGR); 2nd, two-kidney, one-clip (2K1C) Goldblatt hypertensive rats, and, 3rd, ANG II-infused hypertensive rats. As additional model with enhanced renin-angiotensin system (RAS) activity, salt-depleted HanSD and TGR were employed. Results: In anesthetized salt-repleted HanSD, plasma and kidney ANG II levels were higher than in salt-repleted TGR, ANG II-infused and 2K1C rats. Salt depletion caused marked increases in ANG II levels in HanSD but did not alter them in TGR. In contrast, in conscious animals immediately after decapitation plasma and kidney ANG II levels were similar in salt-repleted and salt-depleted TGR, in ANG II-infused rats, in the clipped kidney of 2K1C rats and in salt-depleted HanSD and in all these groups they were significantly higher than in salt-repleted HanSD. Conclusions: These findings indicate that anesthesia increases plasma and kidney ANG II levels in HanSD to a greater degree than in ANG II-dependent models of hypertension. Therefore, the results from studies employing anesthetized animals must be interpreted with caution.
Salt Sensitivity and Hypertension after Menopause: Role of Nitric Oxide and Angiotensin II
Authors: Hernandez Schulman Ivonne , Raij Leopoldo
Published: May 2006

Hypertension is a major risk factor for cardiovascular disease and renal disease. After menopause, the incidence of hypertension increases in women to levels that equal or exceed that in men, suggesting a protective role of female sex hormones. Salt sensitivity of blood pressure is associated with an increased risk for development of hypertension and cardiovascular disease. We and others have demonstrated that after menopause, the prevalence of salt sensitivity increases, suggesting that female sex hormones influence renal sodium handling and blood pressure regulation. A homeostatic balance between the counteracting effects of nitric oxide (NO) and angiotensin (Ang) II on pressure natriuresis, renal hemodynamics, tubular sodium reabsorption, and oxidative stress plays an important role in modulating salt sensitivity as well as hypertensive end-organ injury. Estrogens modulate the activity and expression of NO and Ang II. We infer that after menopause, estrogen deficiency promotes an unbalance between NO and Ang II, resulting in disturbed renal sodium handling, oxidative stress, and hypertension, particularly in genetically prone women. A better understanding of the mechanisms underlying the development of postmenopausal hypertension and associated cardiovascular and renal diseases should provide insights into preventive and therapeutic strategies.
Delta-Sleep-Inducing Peptide Potentiates Anticonvulsive Activity of Valproate against Metaphit-Provoked Audiogenic Seizure in Rats
Authors: Hrnčić Dragan , Stanojlović Olivera , Živanović Dragana , Šušić Veselinka
Published: May 2006

The effect of delta-sleep-inducing peptide (DSIP) on the anticonvulsive activity of a nonprotective valproate (VPA) dose in a metaphit model of generalized, reflex audiogenic seizures in adult Wistar rats was studied. The animals that received metaphit (10 mg/kg) were exposed to audiogenic stimulation (100 ± 3 dB, 60 s) at hourly intervals. Metaphit-treated rats displaying seizures in 8 previous tests were i.p. injected with VPA (50 mg/kg) or DSIP (1.0 mg/kg) or their combination. Latency to seizure was behaviorally assessed. The EEGs and power spectra were recorded and analyzed. Neurotoxicity was evaluated by the chimney test. DSIP or VPA alone expressed no significant effect on the latency duration, but their combination significantly prolonged latency to seizure during 6 h after injection, while inducing no significant motor impairment. Neither the applied drugs nor their combination abolished metaphit-provoked EEG epileptiform activity. The results show that DSIP potentiated anticonvulsive effects of a nonprotective VPA dose in a metaphit model of audiogenic seizures without influencing its neurotoxicity.
Expression of Polo-Like Kinase 1 (PLK1) Protein Predicts the Survival of Patients with Gastric Carcinoma
Authors: Kanaji Shingo , Saito Hiroaki , Tsujitani Shunichi , Matsumoto Sachiko , Tatebe Shigeru , Kondo Akira , Ozaki Mitsuhiko , Ito Hisao , Ikeguchi Masahide
Published: May 2006

Objective: To assess the prognostic value of polo-like kinase 1 (PLK1), an important regulator of cell cycle progression, in patients with gastric carcinoma. Methods: PLK1 expression was determined in 160 gastric carcinoma patients by immunohistochemistry and compared with p53 expression and the proliferating cell nuclear antigen-labeling index (PCNA-LI) to evaluate the effect of PLK1 on tumor progression. Furthermore, PLK mRNA expression was determined in 26 advanced gastric cancer patients by reverse transcription-polymerase chain reaction (RT-PCR). Results: PLK mRNA expression was detected in 25 (96.2%) patients by RT-PCR. Immunohistochemical staining revealed PLK1 expression in 84 (52.5%) patients. There were no significant relationships between PLK1 expression and various clinicopathological factors. PLK1 expression was significantly correlated with the PCNA-LI, but not p53 expression. The prognosis of patients with PLK1-positive tumors was significantly worse than that of patients with PLK1-negative tumors (p < 0.05). Moreover, multivariate analysis revealed that PLK1 expression was an independent prognostic factor. Patients with PLK1-positive and high PCNA-LI tumors showed a significantly poorer prognosis than patients with PLK1-negative and/or low PCNA-LI tumors. Furthermore, the prognosis of patients with PLK1- and p53-positive tumors was significantly worse than that of patients with PLK1- and p53-negative or PLK1-negative and p53-positive tumors. Conclusion: PLK1 expression may be a critical indicator of a poor prognosis in patients with gastric carcinoma.
Zoledronic Acid (Zometa®) Enhances the Cytotoxic Effect of Gemcitabine and Fluvastatin: In vitro Isobologram Studies with Conventional and Nonconventional Cytotoxic Agents
Authors: Budman Daniel R. , Calabro Anthony
Published: May 2006

Objectives: To identify synergistic combinations of clinically available agents with zoledronic acid which would enhance antitumor activity as measured by median effect isobologram analysis and apoptosis assays in vitro. Methods: The interaction of zoledronic acid as a doublet with either carboplatin, cisplatin, 5′DFUR, docetaxel, epirubicin, fluvastatin, gemcitabine, imatinib, paclitaxel, trastuzumab, or vinorelbine was studied in a 72-hour in vitro system using defined human cancer cell lines grown as a monolayer in exponential phase. Drug effect on growth was measured by a standard MTT assay. Median effect isobologram analysis was applied to the results to determine the presence of synergism, additive effects, or antagonism of drug combinations. Synergistic combinations were also assayed by a cytoplasmic histone-associated DNA fragmentation apoptosis assay to verify that the effect was not cytostatic. Results: Zoledronic acid with gemcitabine demonstrated global cytotoxic synergy across 7 of 8 cell lines. Clinically achievable concentrations of fluvastatin with zoledronic acid also demonstrated synergy in 7 of 8 cell lines. All the breast cancer cell lines were sensitive. Zoledronic acid and epirubicin were antagonistic in all 4 breast cell lines studied. Conclusions: Combinations of zoledronic acid with either gemcitabine or fluvastatin may have a therapeutic role in treatment of bone metastasis of selected malignancies.
Decreased Phosphoactive ERKs and JNKs in Malachite-Green-Transformed Syrian Hamster Embryo Fibroblasts Are Associated with Increased Phosphoactive p38 Kinase: Possible Therapeutic Importance
Authors: Bose Bipasha , Gour Rekha R. , Motiwale Leena , Rao K.V.K.
Published: May 2006

Background: Malachite green (MG), consisting of green crystals with a metallic lustre, is highly soluble in water, cytotoxic to various mammalian cells and also acts as a liver tumor promoter. In view of its industrial importance and possible exposure of human beings, MG poses a potential environmental health hazard. We have earlier reported the malignant transformation of Syrian hamster embryo (SHE) cells by MG. Methods: Cell transformation assays were carried out as described in the literature. Western blotting and flow cytometry were carried out by standard methods. Results: In this study, we have studied the role of all three isoforms of mitogen-activated protein (MAP) kinases, i.e. extracellular regulated kinases (ERKs), Jun N-terminal kinases (JNKs) and p38 kinase in the MG-transformed SHE fibroblasts compared to controls. Our results showed that transformed cells were associated with decreased expression of ERKs and JNKs as evidenced by Western blotting studies. However, the p38 MAP kinase was found to be upregulated. Flow cytometric DNA histogram analysis indicated an increase in the expression of S phase cells in the transformed cell line as compared to their control counterparts. Conclusions: The present studies indicate that decreased phosphoactive ERKs and JNKs and increased phosphoactive p38 kinase are associated with increased S phase cells during transformation of SHE cells by MG.
Validation of a Calibrated Prediction Model for Response to Growth Hormone Treatment in an Independent Cohort
Authors: de Ridder Maria A.J. , Stijnen Theo , Drop Stenvert L.S. , Blum Werner F. , Hokken-Koelega Anita C.S.
Published: May 2006

Background: Prediction models, e.g. for prediction of response to growth hormone treatment, need validation in appropriate independent cohorts, comparing predicted and observed outcomes. In a previous validation of a model for predicting the first-year response to growth hormone treatment in children with idiopathic growth hormone deficiency, overfitting was observed. We modified the prediction formula and now report validation of this modified model. Patients and Methods: The modified and original prediction models were applied to a group of patients selected from Lilly’s GeNeSIS database using the same inclusion and exclusion criteria as for the original model. For both prediction methods, observed first-year height velocity was plotted vs. predicted height velocity in a calibration plot. For a valid prediction, the regression line should correspond to the line of identity (observed outcome is equal to predicted outcome); the regression lines for each prediction model were tested for significant differences from this line of identity. Results: The number of patients fulfilling the criteria was 226. The regression line in the calibration plot of the modified model was not significantly different from the line of identity (p = 0.43), in contrast to the original model (p < 0.001). For the modified model the mean (SD) prediction error was –0.11 (2.05) cm/year and for the original model 0.28 (2.11) cm/year. Conclusion: The modified prediction method, obtained after calibration of the original model, performs well in an independent patient sample and gives more accurate predictions than the original model.
Association of Advanced Glycoxidation End Products and Inflammation Markers with Thrombosis of Arteriovenous Grafts in Hemodialysis Patients
Authors: Cai Weijing , Zhu Li , Chen Xue , Uribarri Jaime , Peppa Melpomeni
Published: May 2006

Background/Aims: Intimal hyperplasia at the venous anastomosis of arteriovenous dialysis grafts (AVGs) is a common and costly complication in hemodialysis (HD) patients. Previous studies have shown significant accumulation of advanced glycation end products (AGEs) within the lesions, suggesting a pathogenic role for these compounds in this condition. Methods: We retrospectively analyzed data from 139 HD patients, including 58 subjects with AVGs, to determine any relationship between serum AGEs and other circulating markers, e.g. C-reactive protein (CRP), tumor necrosis factor (TNF-α), vascular cell adhesion molecule-1 (VCAM-1), plasminogen activator inhibitor type 1 and vascular endothelial growth factor, with the presence of graft thrombosis, an index of venous intimal hyperplasia. Results: Patients with previously thrombosed AVGs exhibited significantly higher levels of serum AGEs (42 ± 18 vs. 28± 8 U/ml), CRP (1.4 ± 1.1 vs. 0.6 ± 0.4 mg/dl) and VCAM-1 (3,172 ± 696 vs. 2,447 ± 1,101 ng/ml) than those with uncomplicated AVGs, variances that were mostly attributed to diabetes difference. There was no difference regarding the levels of the parameters studied between patients with AVGs and other forms of vascular access. Conclusions: These results support an association between circulating AGEs, markers of inflammation and endothelial function and intimal hyperplasia at the venous anastomosis of AVGs in HD patients. The implication is that there may be a therapeutic role for anti-AGE interventions in the management of this common clinical condition.
Enhanced External Counterpulsation Reduces Lung/Heart Ratio at Stress in Patients with Coronary Artery Disease
Authors: Lee Chii-Ming , Wu Yen-Wen , Jui Hsiang-Yiang , Chen Ming-Fong , Lee Yuan-Teh , Soran Ozlem
Published: May 2006

Enhanced external counterpulsation (EECP) is a recently approved treatment modality for patients with angina and heart failure. However, the efficacy of EECP on left ventricular (LV) function has not been well established.The study was aimed to determine whether EECP leads to an improvement in objective parameters of LV function. Patients with coronary artery disease (n = 10) who showed evidence of stress-induced myocardial ischemia despite conventional medical or surgical therapies were enrolled and received EECP therapy for a total of 35 h. The therapeutic effects of EECP were examined by thallium-201 single-photon emission computed tomography (201Tl-SPECT). Compared with baseline, the lung/heart ratio at stress decreased significantly from 0.40 ± 0.08 to 0.35 ± 0.08 (p= 0.001) at 1 month and 0.33 ± 0.10 (p = 0.03) at 6 months following EECP treatment. LV ejection fraction marginally improved from 56.7 ± 7.7% to 57.6 ± 5.9% (p = 0.382) at 1 month and to 60.1 ± 8.6% (p = 0.062) at 6 months after EECP therapy, although not statistically significant. We concluded that EECP improved LV function, shown as the reduction of lung/heart ratio at stress, in patients with coronary artery disease, up to 6 months after EECP treatment.
Chronic Deep Brain Stimulation of the Subthalamic Nucleus for Parkinson’s Disease: Effects on Cognition, Mood, Anxiety and Personality Traits
Authors: Castelli L. , Perozzo P. , Zibetti M. , Crivelli B. , Morabito U. , Lanotte M. , Cossa F. , Bergamasco B. , Lopiano L.
Published: May 2006

Objective: To evaluate modifications occurring in cognitive functions and behavioural aspects in a group of 72 consecutive patients with Parkinson’s disease (PD) 15 months after bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN). Methods: 72 consecutive PD patients bilaterally implanted for DBS of the STN were evaluated before and after surgery with a mean follow-up of 15 months. A neuropsychological assessment was performed to evaluate reasoning (Raven Colour Matrices), memory (Bisyllabic Word Repetition Test, Corsi’s Block-Tapping Test, Paired-Associate Learning) and frontal executive functions (Trail Making Test Part B, Nelson Modified Card Sorting Test, phonemic and category verbal fluency tasks). Mood and suicidal ideation were evaluated using the Beck Depression Inventory (BDI). Anxiety was measured by means of the State-Trait Anxiety Inventory and personality traits were evaluated with the Structured Clinical Interview for the DSM-III-R Axis II Disorders (SCID-II). Assessment of thought disorders and apathy was based on subitems of the Unified Parkinson’s Disease Rating Scale. Results: The comparisons between pre- and postoperative neuropsychological test scores showed a significant worsening only in phonemic and semantic verbal fluency tasks, while fewer errors were found in the Nelson Modified Card Sorting Test. Globally, behavioural assessment evidenced a small improvement in mood, as assessed by the BDI, in obsessive-compulsive and paranoid personality traits (SCID-II). Thought disorders worsened while suicidal ideation, anxiety and apathy showed no postoperative modifications. The analysis of individual outcomes (±1 SD criterion) evidenced a relevant postoperative cognitive decline in 3 patients out of 65 (4.5%). Moreover, following implantation, 1 patients exhibited psychosis (1.5%), 2 patients experienced a clinically relevant worsening of depressive symptoms (3%), 7 patients showed an increase in anxiety (12%) and 3 patients a worsening in depression and anxiety symptoms (3%). On the contrary, 12 patients (20%) showed a relevant improvement in mood and 14 patients (23%) a relevant reduction of anxiety symptoms after the surgery. Conclusions: The present study confirms that STN DBS is cognitively safe since the only relevant change observed was a mild decrease in verbal fluency tasks. Globally, a small postoperative improvement was found in the BDI, and in two SCID-II subscales concerning obsessive-compulsive and paranoid personality traits, even though postoperative behavioural disturbances can occur in individual patients.
Subclinical Hypothyroidism in HIV-Infected Patients Is Not an Autoimmune Disease
Authors: Beltran S. , Lescure F.-X. , El Esper I. , Schmit J.-L. , Desailloud R.
Published: May 2006

Aims and Methods: A study of 350 HIV+ patients in our region showed that 16% suffered from hypothyroidism. Twenty-two HIV+ hypothyroid patients (10 with subclinical hypothyroidism, 12 with low FT4 levels (LT4) (confirmed by a dialysis equilibrium assay) and 22 HIV+ euthyroid controls receiving highly active anti-retroviral therapy were included in an additional study. Results: No goiter or anti-thyroid antibodies were detected. Use of stavudine was more frequent in the LT4 subgroup (p < 0.01) and subclinical hypothyroidism group (p = 0.04). Use of didanosine (OR, 12.5, p < 0.01) and ritonavir (OR, 33.0, p < 0.01) was more frequent in the LT4 subgroup, with a greater didanosine cumulative dose (616.7 mg [180.0, 1,260.0] vs. 263.7 [63.0, 948.0], p = 0.01). Reverse T3, binding protein levels, the TSH response to thyrotropin-releasing hormone, urinary iodine, plasma selenium and thiocyanate levels did not differ. IFNγ levels were lower in the subclinical hypothyroidism group (pg/ml) (9.1 [0.0, 22.7] vs. 19.5 [0.0, 40.9], p = 0.03). Conclusion: None of the investigated mechanisms are able to explain the occurrence of hypothyroidism in HIV patients receiving highly active anti-retroviral therapy except the anti-retroviral treatment. In light of the absence of autoimmunity, the normal adenohypophysis and thyroid responses to thyrotropin-releasing hormone, central hypothyroidism is suspected and could explain LT4 and high TSH levels. Underlying mechanisms need further exploration.
Inflammatory Markers in Adults with Prader-Willi Syndrome before and during 12 Months Growth Hormone Treatment
Authors: Höybye Charlotte
Published: May 2006

Background: In Prader-Willi syndrome (PWS) obesity and partial growth hormone (GH) deficiency are frequently observed. The risks of cardiovascular diseases and early death are increased. We examined inflammatory markers in adult PWS, before and during 12 months of GH treatment. Method: Twelve PWS adults, median age 23.5 years (17–37) and median BMI 33.8 kg/m2 (21.2–50.4), participated. Serum interleukin-6, tumour necrosis factor α, high sensitive protein C-reactive protein (HCRP), cholesterol, triglycerides, leptin, adiponectin, glucose, insulin, insulin-like growth factor I and body composition were measured at baseline and after 6 and 12 months of GH treatment. Results: Median and range at baseline for interleukin-6 was 9.87 ng/l (1.76–10.72), for tumour necrosis factor α 2.39 ng/l (1.00–3.26) and for HCRP 7.64 mg/l (0.41–41.1) (normal values < 5 ng/l, < 8 ng/l and<5 mg/l, respectively). At baseline correlations between inflammatory markers and age, anthropometry, body composition and the metabolic parameters were non-significant; only positive associations were found between tumour necrosis factor α and body weight (r = 0.617, p = 0.033) and between HCRP and BMI (r = 0.594, p = 0.041). GH treatment non-significantly decreased the levels of the inflammatory markers. Conclusion: In this pilot study, levels of interleukin-6 and HCRP were increased, and GH intervention did not significantly reduce the levels. Chronic inflammation might contribute to the increased cardiovascular morbidity and mortality in PWS.
Impact of Implantable Defibrillators and Resynchronization Therapy on Outcome in Patients with Left Ventricular Dysfunction – A Meta-Analysis
Authors: Abdulla Jawdat , Haarbo Jens , Køber Lars , Torp-Pedersen Christian
Published: May 2006

Background: The clinical benefits of cardiac resynchronization therapy (CRT) and primary prophylactic implantable cardioverter defibrillator (ICD) in patients with left ventricular systolic dysfunction (LVSD) are debated. Objective: To evaluate by a meta-analysis the effect of CRT and prophylactic ICD therapy in patients with LVSD. Methods: Eligible trials evaluating the effect of CRT vs. no-CRT, ICD vs. no-ICD and adding ICD to CRT vs. no-ICD were selected and meta-analyzed. The outcomes were: all cause mortality, cardiac mortality, hospitalization for heart failure and change in exercise tolerance and New York Heart Association class. Results: Implantation of CRT reduced all cause mortality odds ratio (OR) = 0.73 (0.60–0.89) p = 0.002 and hospitalization for heart failure OR = 0.60 (0.45, 0.80) p = 0.001, increased peak oxygen consumption by 1.77 (0.32–3.22) ml/kg/min p = 0.017 and improved New York Heart Association class by at least one class with OR = 1.52 (1.30, 1.77) p < 0.0001. Implantation of ICD reduced all-cause mortality OR = 0.75 (0.59–0.96) p = 0.025 and cardiac mortality OR = 0.63 (0.48, 0.82) p = 0.001. Adding ICD to CRT reduced all cause mortality OR = 0.69 (0.53–0.91) p = 0.008. Conclusion: Selective patients with LVSD benefit from CRT, ICD or both. Further investigations are necessary to clarify which patients benefit most from a single or combined device implantation.
Migraine and Patent Foramen Ovale: A Residual Coincidence or a Pathophysiological Intrigue?
Authors: Piechowski-Jozwiak B. , Devuyst G. , Bogousslavsky J.
Published: May 2006

Migraine is one of the most common neurological disorders and one of the most frequent primary headaches. It imposes a significant burden on the affected individuals, society and health care system. As the etiology and pathophysiology of migraine are not well understood, treatment is largely symptomatic. Patent foramen ovale is a remnant of a fetal circulation and is highly prevalent in the general population. Its presence was linked to several disorders including migraine. The aim of this review was to search in the available data the answer to the question whether the link between migraine and patent foramen ovale is coincidental or whether they represent a pathophysiological entity.
Progression of Unilateral Moyamoya Disease: A Clinical Series
Authors: Kelly Michael E. , Bell-Stephens Teresa E. , Marks Michael P. , Do Huy M. , Steinberg Gary K.
Published: May 2006

Background: The natural history of unilateral moyamoya disease (MMD) in adult patients is not clearly described in the literature. We present a series of 18 patients with unilateral MMD and analyze the risk factors for progression to bilateral disease. Methods: A retrospective review of 157 MMD patients treated at Stanford University Medical Center from 1991 to 2005 identified 28 patients with unilateral MMD (defined as none, equivocal or mild involvement on the contralateral side). Results: Eigh teen patients (5 males and 13 females) were identified with unilateral MMD and angiographic follow-up of ≧5 months. Mean radiologic follow-up (± standard error of the mean) was 19.3 ± 3.4 months and mean clinical follow-up was 24.5 ± 3.7 months. Five patients had childhood onset MMD and 13 patients had adult onset disease. Angiographic progression from unilateral to bilateral disease was seen in 7 patients (38.9%) at a mean follow-up of 12.7 ± 2.4 months. Four of the 7 patients had significant clinical and radiologic progression requiring surgical intervention. Five of 7 patients that progressed had adult onset MMD. The presence of equivocal or mild stenotic changes of the contralateral anterior cerebral artery (ACA), middle cerebral artery (MCA) or internal carotid artery (ICA) was an important predictor of progression (p < 0.01); 6 of 8 patients (75%) with equivocal or mild contralateral disease progressed, whereas only 1 of 10 patients (10.0%) with no initial contralateral disease progressed to bilateral MMD. One patient had mild or equivocal MCA, ICA and ACA stenosis at the time of initial diagnosis and this patient progressed. Conclusions: Contralateral progression in the adult form occurs more commonly than previously reported. The presence of minor changes in the contralateral ACA, intracranial ICA and MCA is an important predictor of increased risk of progression. Patients with a completely normal angiogram on the contralateral side have a very low risk of progression.
ICAM-1 and VCAM-1 Expression following Aneurysmal Subarachnoid Hemorrhage and Their Possible Role in the Pathophysiology of Subsequent Ischemic Deficits
Authors: Rothoerl Ralf Dirk , Schebesch Karl-Michael , Kubitza Marion , Woertgen Chris , Brawanski Alexander , Pina Ana-Luisa
Published: May 2006

Background: The pathophysiology of ischemic cerebral lesions following aneurysmal subarachnoid hemorrhage (SAH) is poorly understood. There is growing evidence that inflammatory reactions could be involved in the pathogenesis of such delayed occurring ischemic lesions. The aim of this study was to evaluate adhesion molecules with regard to these lesions following SAH. Methods: Serum and cerebrospinal fluid (CSF) samples were taken daily from 15 patients up to day 9 after SAH and evaluated for intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1). Results: CSF and serum samples correlated well during nearly the whole time course (p < 0.0001). A secondary increase in ICAM-1 and VCAM-1 in the serum and CSF correlated with an increase in flow velocity in the transcranial Doppler (p > 0.0001 and p < 0.007) but not to a delayed lesion in the CT scan. Conclusion: We believe that inflammatory processes are involved in the pathogenesis of cerebral vasospasm but they might only be a part of a multifactorial pathogenesis.
Dissection of Cervical Arteries: Long-Term Follow-Up Study of 130 Consecutive Cases
Authors: Arauz Antonio , Hoyos Leticia , Espinoza Carlos , Cantú Carlos , Barinagarrementeria Fernando , Román Gustavo
Published: May 2006

Background and Purpose: We describe the natural history, functional prognosis and long-term recurrences of patients with dissection of cervical arteries (DCA) in a sequential observational study. Methods: We describe 130 patients with angiographically-proven DCA admitted to the Neurology Institute in Mexico City (Mexico), and analyzed clinical and neuroimaging data, treatment and outcome. Treatment with either anticoagulation or aspirin was decided by the primary physician. Primary outcome measures were recurrence (stroke and death) and clinical outcome at 6 months. Follow-up studies were performed to determine recanalization. Results: Mean age was 35.4 years; 4 patients died (3%) and 126 were followed for 3,906 person/years; 17 patients (13%) had a heralding ischemic cerebral event (6 strokes, 11 TIAS) about 8 days before the diagnosis of DCA. After diagnosis, recurrent ischemic stroke occurred in 6 patients (4.8%) within the 2 first weeks (1.5 persons/1,000 follow-up years). No significant differences were found between aspirin and anticoagulation. Recanalization was more frequent in vertebral dissections. Complete recanalization of vertebral dissections was associated with a favorable prognosis [OR 3.2 (95% CI 1.1–8.8; p = 0.02)]. Conclusions: In Mexico, DCA affects young adults and may present with a heralding stroke or TIA. We found rare, early ischemic recurrences. Vertebral territory dissections had better prognosis than carotid ones, particularly in patients with demonstrated complete recanalization.
Lobar Brain Hemorrhages and White Matter Changes: Clinical, Radiological and Laboratorial Profiles
Authors: Maia Luís F. , Vasconcelos Cristiana , Seixas Susana , Magalhães Rui , Correia Manuel
Published: May 2006

Background: White matter changes have several histopathologic correlates including cerebral amyloid angiopathy (CAA). The aim of this study was to characterize the clinical, laboratorial and neuroradiological profile of a CAA-related lobar hemorrhages case series. Methods: A cohort of 50 consecutive patients with cerebral lobar hemorrhages was studied and clinical, radiological data and ApoE polymorphisms were analyzed. White matter changes were graded and microbleeds were characterized according to number and location using T2* MRI. Results: A statistically significant association was found between the prestroke cognitive performance and poststroke dementia and between hemorrhage volume and mortality. More severe white matter changes were found in probable CAA when comparing to possible CAA. The most prominent white matter lesions are associated with the presence and the number of microbleeds. The frequency of APOE υ2 and υ4 alleles was higher in this cohort when compared to a Northern Portuguese population. Conclusion: White matter changes are frequent in lobar hemorrhage patients and are associated with cortical microbleeds, the radiological hallmark of CAA. Therefore, white matter changes may be the sole phenotype of CAA and, potentially, involved in the pre-stroke cognitive impairment presented by the patients, which are genetically distinct from the population in general.
Histamine Type 1 Receptor Deficiency Reduces Airway Inflammation in a Murine Asthma Model
Authors: Miyamoto Kenichi , Iwase Michiko , Nyui Miki , Arata Satoru , Sakai Yasushi , Gabazza Esteban C. , Kimura Hiroshi , Homma Ikuo
Published: May 2006

Background: Histamine plays an important role in immediate and late immune responses. The histamine type 1 (H1) receptor is expressed on several immune cell populations, but its role in a murine model of asthma remains unclear. The present study evaluated the role of histamine H1 receptors in airway allergic inflammation by comparing the development of bronchial asthma in histamine H1 receptor gene knockout (H1RKO) and wild-type mice. Methods: H1RKO and wild-type mice were sensitized by intraperitoneal injection of ovalbumin (OVA) or saline, and then challenged with aerosolized OVA or saline. Ventilatory timing in response to inhaled methacholine was measured, and samples of blood, bronchoalveolar lavage, and lung tissues were taken 24 h after the last OVA challenge. Results: OVA-treatedwild-type mice showed significantly increased airway eosinophilic infiltration, and airway response to methacholine compared to OVA-treated H1RKO mice. The serum level of immunoglobulin E and levels of interleukin (IL)-4, IL-5, IL-13, and TGF-β1 in bronchoalveolar lavage fluid were lower in OVA-treated H1RKO mice than in OVA-treated wild-type mice, but there was no significant difference in interferon-γ expression. Overall, deletion of histamine H1 receptors reduced allergic responses in a murine model of bronchial asthma. Conclusion: Histamine plays an important role via H1 receptors in the development of T helper type 2 responses to enhance airway inflammation.
Expression of Fas Ligand and CTLA4 in Adenoids Has a Predictive Value for Allergic Rhinitis Development in Children
Authors: Zakrzewska Anna , Gryczyńska Danuta , Kobos Józef , Górski Paweł
Published: May 2006

Background: The balance of CD28/CTLA4-derived signals and Fas-dependent apoptosis activity is determined by the peripheral defense mechanisms and might play a role in the pathogenesis of allergy. Objectives: The aim of the study was to investigate the expression of costimulatory and pro- and antiapoptotic molecules in adenoid T cells of children suffering from allergic rhinitis and to find out which of these molecules have a predictive value in the development of allergic rhinitis. Methods: The adenoids of 60 children, removed because of nasal obstruction, chronic rhinitis and recurrent respiratory infection, were evaluated. Patients were divided into two groups: group 1, suffering from chronic allergic rhinitis, and group 2, suffering from chronic rhinitis, where no specific IgE was detected, including children with a positive family history of allergy (group 2a) and children with neither a personal nor a family history of allergy (group 2b). For immunohistochemical stainings anti-CD3, anti-CD19, anti-CD4, anti-CD8, anti-CD25, anti-CD28, anti-CTLA4 (CD152), anti-bcl-2, anti-Fas, and anti-FasL antibodies were used. The number of cells expressing these molecules was identified in adenoid interfollicular spaces. The results were then analyzed in allergic and nonallergic children. During a 24-month follow-up children were re-examined for allergy and results were compared to previous immunohistochemical evaluations. Results: The expression of CD4, CD25, CD28, FasL, and CTLA4 was significantly increased in group 1 compared to group 2 (p < 0.05). However, the discriminant analysis confirmed that only CTLA4 and FasL expression fully discriminated allergic subjects from the others. During a 24-month period of observation 8 children from group 2a were also diagnosed with allergic rhinitis. All of them, especially those sensitized to mites, had an increased number of FasL+ and CTLA4+ in previously removed adenoids. Conclusion: An increased number of cells with intracellular expression of FasL and CTLA4, in interfollicular spaces of adenoids, seems to be a predictive factor of the development of allergic rhinitis.
Outcome and Treatment of Bucillamine-Induced Nephropathy
Authors: Hoshino Junichi , Ubara Yoshifumi , Hara Shigeo , Suwabe Tatsuya , Sawa Naoki , Tagami Tetsuo , Katori Hideyuki , Takemoto Fumi , Hara Shigeko , Takaichi Kenmei
Published: May 2006

Background: Bucillamine (BCL), a treatment for rheumatoid arthritis, occasionally causes proteinuria. Renal specimens are reported to show segmental granular deposition of immunoglobulin G, associated with membranous nephropathy. Long-term course and optimal treatment have remained unknown, and were investigated here. Methods: We examined clinical records of 400 patients treated with BCL for rheumatoid arthritis, at our hospital from 1998 to 2003, finding 17 with proteinuria and biopsy-proven BCL-induced nephropathy. Results: In all 17 patients, proteinuria resolved without loss of renal function between 3 and 85 months after discontinuing BCL (14.1 ± 3.4). The only factor influencing time to remission was pathologic stage of membranous nephropathy (stage I vs. stage II or III: 11.5 ± 4.8 vs. 21.6 ± 3.3 months; p = 0.02). Maximal proteinuria, total amount of BCL, BCL exposure time, and use of prednisolone or other immunosuppressant agents did not significantly influence time until remission. Conclusion: The most important therapeutic step in treating BCL-induced nephropathy is to discontinueBCL. Prednisolone or other immunosuppressant agents might not be effective.
Angiotensin-Converting Enzyme Inhibitors as a Risk Factor for Contrast-Induced Nephropathy
Authors: Cirit Mustafa , Toprak Omer , Yesil Murat , Bayata Serdar , Postaci Nursen , Pupim Lara , Esi Ertap
Published: May 2006

Background/Aims: The aim of the present study was to assess the influence of chronic angiotensin-converting enzyme (ACE) inhibitor administration on the development of contrast-induced nephropathy (CIN) in patients undergoing coronary angiography. Methods: A total of 230 patients with renal insufficiency and age ≧65 years were divided into two groups according to prior use of ACE inhibitors (ACE inhibitor group, n = 109; control group, n = 121). CIN was defined as an increase of ≧25% in creatinine over the baseline value within 48 h of angiography. Results: CIN occurred in 17 patients (15.6%) in the ACE inhibitor group and 7 patients (5.8%) in the control group (p = 0.015). Serum creatinine level increased from 1.34 ± 0.20 to 1.53 ± 0.27 mg/dl in the ACE inhibitor group and from 1.33 ± 0.18 to 1.45 ± 0.19 mg/dl in the control group (p < 0.001). Chronic ACE inhibitor administration was a risk indicator of CIN [odds ratio 3.37; 95% confidence interval 1.14–9.94; p = 0.028]. Multi-vessel coronary involvement (p = 0.001), hypoalbuminemia (p = 0.005), diabetes mellitus (p = 0.006), GFR ≤40 ml/min (p = 0.010), and congestive heart failure (p = 0.024) were other risk indicators of CIN. Conclusion: Chronic ACE inhibitor administration is a risk for developing CIN in elderly patients with renal insufficiency.
Immediate Effect of Shakuyaku-kanzo-to on Muscle Cramp in Hemodialysis Patients
Authors: Hyodo Toru , Taira Takayasu , Takemura Toru , Yamamoto Sumiko , Tsuchida Mayumi , Yoshida Kazunari , Uchida Toyoaki , Sakai Tadasu , Hidai Hideo , Baba Shiro
Published: May 2006

We administered 2.5 g of Shakuyaku-kanzo-to granule to 61 patients who had muscle cramp during hemodialysis (HD) sessions and examined its immediate effects. We selected 10 patients who wanted to take the drug at home, out of cases, for whom the drug was effective on the study described above and had them take the drug in the same way at the beginning of muscle cramp at home examined the effects. In the study during HD sessions, muscle cramp and its associated pain disappeared in 5.3 ± 3.9 min on average in 54 out of 61 cases. In the study of patients who took the drug at home, muscle cramp disappeared within 10 min in all cases. Shakuyaku-kanzo-to is thought to be very useful for muscle cramp during HD sessions of hemodialized patients because it has immediate effects by its oral administration on the occasion of cramp. With regard to the muscle cramp, which appears at home after HD sessions, the patients can cope with it by taking the drug by themselves. This is an epoch-making therapy, for it was impossible to cope with muscle cramp except in hospitals because the therapy of muscle cramp was limited to intravenous infusion of hypertonic solutions of dextrose, mannitol, and saline during HD sessions.
Coronary Artery Calcification, Systemic Inflammation Markers and Mineral Metabolism in a Peritoneal Dialysis Population
Authors: Ammirati Adriano Luiz , Dalboni Maria Aparecida , Cendoroglo Miguel , Draibe Sérgio Antonio , Fernandes Canziani Maria Eugênia
Published: May 2006

Aims: To assess the prevalence of coronary artery calcification (CAC) in peritoneal dialysis (PD) patients and to determine whether comorbidities such as inflammation, dyslipidemia and mineral metabolism disorders correlate with its development. Methods: Forty-nine PD patients (45% male; median age, 52 years) were submitted to multislice computed tomography. Inflammatory markers, anti-oxidized LDL antibody, calcium–phosphate balance and lipid profiles were assessed. Results: Twenty-nine patients (59.2%) presented CAC (median calcium score, 234.7 Agatston units). Patients with CAC were older than those without, more frequently presented a history of coronary artery disease or hypertension and had lower HDL cholesterol levels, as well as presenting higher levels of osteoprotegerin and LDL oxidation. The logistic regression revealed that the independent determinants of CAC were age (odds ratio = 1.12; p = 0.006) and number of prescribed anti-hypertensive drugs (odds ratio = 2.38; p = 0.048). When the population was stratified by calcium score quartile, soluble Fas levels were significantly higher in patients with severe calcification. In patients younger than 45, CAC correlated positively with phosphorus levels (r = 0.52; p = 0.04). Conclusion: In PD patients, CAC is highly prevalent. Our results indicate that conditions such as inflammation and mineral disturbances are associated with its development.
Vitamin B6 Deficiency and Dietary Fats: Effects on Lipid Composition and Glutathione Peroxidase Activity in Rat Liver
Authors: Bordoni Alessandra , Cabrini Luciana , Marchetti Mario , Danesi Francesca , Bochicchio Davide , Biagi Pier L. , Maranesi Magda
Published: May 2006

Dietary selenium, vitamin B6 and fatty acids modulate both tissue acyl composition by regulating polyunsaturated fatty acid metabolism and antioxidant defences by influencing glutathione peroxidase activity. Alteration in the intake of one of them could therefore lead to different results depending on the intake of the others. To clarify this complex relationship, in the present study we have evaluated the modifications occurring in fatty acid composition and glutathione peroxidase activity in total liver and liver microsomes of rats fed diets containing the same amount of selenium, but different vitamin B6 content and fatty acid composition. Our data indicate that both acyl composition and glutathione peroxidase activity are greatly influenced not only by vitamin B6 deficiency, but also by the diet unsaturation degree. This study underlines that not only selenium availability but also other nutrients can modulate glutathione peroxidase activity.
DNA-Spermine and DNA-Lipid Aggregate Formation Visualized by Fluorescence Correlation Spectroscopy
Authors: Kral Teresa , Langner Marek , Hof Martin
Published: May 2006

Background: Fluorescence correlation spectroscopy (FCS) can be used for the determination of diffusion coefficients of single molecules. Since diffusion coefficients are correlated with size and shape of the labeled species, FCS provides information on conformational changes in plasmids aggregates. Methods: A 10-kbp plasmid stained with PicoGreen® was condensed by spermine or liposomes formulated from cationic lipid and egg phosphatidylcholine. Results: The diffusion coefficient of DNA increases from 1.0 × 10–12 m2/s to 3.2 × 10–12 m2/s by the addition of spermine, whereas the addition of cationic liposomes leads to complexes characterized by diffusion coefficients with values ranging from 1.7 to 1.9 × 10–12 m2/s. Conclusions: FCS experiments allow determining the diffusion coefficients of DNA-containing aggregates which provide information regarding the topology and homogeneity of the aggregate.
Allergic and Anaphylactic Response to Sesame Seeds in Mice: Identification of Ses i 3 and Basic Subunit of 11s Globulins as Allergens
Authors: Navuluri Lalitha , Parvataneni Sitaram , Hassan Hanem , Birmingham Neil P. , Kelly Caleb , Gangur Venu
Published: May 2006

Background: Allergy to sesame seeds is an emerging food allergy of a serious nature due to a high risk of systemic anaphylaxis. Although a mouse model to study sesame anaphylaxis is desirable, currently it is not available. Here, using a transdermal exposure model system, we tested the hypothesis that sesame seed elicits IL-4-associated IgE antibody response with consequent clinical sensitization in mice. Methods: Groups of BALB/c mice were exposed to sesame seed extract or saline or a control food (vanilla bean extract) by transdermal applications. Systemic IgE, IgG1 and IgG2a antibody responses were examined using preoptimized ELISA. Type 2 and type 1 cytokine responses were evaluated by ex vivo antigen-mediated activation of spleen cells. Clinical response to oral sesame challenge was studied. Western blot and N-terminal amino acid sequence analyses were performed to identify the sesame allergens. Results: Transdermal exposure to sesame elicited robust IgE and IgG1 but very little IgG2a antibody responses. IgE response to transdermal exposure in two high-IgE responder mice strains with disparate MHC confirmed the intrinsic allergenicity of sesame seed. Transdermal sensitization was associated with activation of IL-4 but not IFN-γ. Furthermore, oral exposure to sesame resulted in clinical signs of systemic anaphylaxis. Western blot and sequence analysis identified four allergens including Ses i 3 and the basic subunit of 11s globulins. Conclusion: These data argue that transdermal exposure to sesame seed can result in IL-4 activation, IgE response and clinical sensitization for systemic anaphylaxis.
Sphincterolysis: A Novel Approach towards Chronic Anal Fissure
Authors: Gupta Pravin J.
Published: May 2006

Background and Aims:The surgical approach in chronic anal fissure is often found associated with disturbed anal continence as well as recurrence. This report describes the author’s approach of ‘sphincterolysis’ or fragmentation of the fibers of the internal sphincter on the left lateral anal wall. Patients and Methods:132 patients with chronic anal fissures were treated with this technique. Pre- and postoperative anal manometry was recorded. The postoperative course and early and 1-year follow-up results were recorded. Results: Early complications included ecchymosis, hematoma, and pain. Fissure healing and relief of symptoms observed in 97% of patients. A transient, variable degree of incontinence occurred in 23 patients and persistent incontinence to flatus and soiling in 5. Conclusion: Internal anal sphincterolysis is a safe, effective procedure for the treatment of chronic anal fissure.
Active Influenza Immunization in Hemodialysis Patients: Comparison between Single-Dose and Booster Vaccination
Authors: Song Joon Young , Cheong Hee Jin , Ha Seok Hoon , Kee Sae Yoon , Jeong Hye Won , Kim Woo Joo
Published: May 2006

Background/Aims: Hemodialysis (HD) patients are recommended to be immunized against influenza annually, but the immune response after vaccination is known to be weakened in these patients. We intended to compare the efficacy of influenza vaccines in HD patients with that in healthy people, and we also evaluated the additive effect of a booster vaccination in HD patients. Methods: During the 2003–2004 influenza season, 100 patients on HD and 50 age-matched healthy controls were recruited from the Korea University Guro Hospital. The HD patients were divided into two groups: single-dose group (50 patients) and booster group (50 patients). Eight weeks following the influenza vaccination, the serum antibody responses were compared. Results: Although the antibody response of the HD patients was impaired in comparison with that of healthy controls, more than 90% of the HD patients showed protective antibody levels. Booster vaccination did not significantly increase the immune response in HD patients. Conclusions: Influenza vaccination in HD patients should be encouraged, but the immune response was comparatively impaired in subpopulations, including patients with a long-term HD history (>2.5 years), with a higher urea reduction rate, or with underlying diabetes. There was no effect of a booster vaccine dose on the antibody titers.