bluuebunny/crossref_metadata_2025_split huggingface dataset:
An overview of the pharmacology and clinical efficacy of indapamide sustained release
Authors: Sassard J. , Bataillard A. , McIntyre H. 
Published: November 2005

AbstractThe relationship between blood pressure (BP) and cardiovascular risk is clearly established; hypertension increases the rate of cardiovascular. High systolic blood pressure (SBP) may be the main parameter involved in cardiovascular morbidity and mortality. The benefit of lowering BP, particularly with diuretics has been proven in many outcome studies. Indapamide, a thiazide‐type diuretic, was available for many years at a dosage of 2.5 mg in an immediate release formulation. A new sustained release (SR) formulation has been developed in order to allow the same antihypertensive efficacy with a better acceptability profile. This paper reviews the pharmacology of indapamide 1.5 mg SR from the bench to the bedside. Indapamide has a dual mechanism of action: diuretic effect at the level of the distal tubule in the kidney and a direct vascular effect, both of which contribute to the antihypertensive efficacy of the drug. The SR formulation contains a hydrophilic matrix, which delivers a smoother pharmacokinetic profile. This avoids unnecessary plasma peak concentrations, which may be associated with side effects. Indapamide SR has now been extensively used in hypertensive patients, including those at increased risk, for example elderly or diabetic patients. It has been shown to decrease BP, particularly SBP, with 24‐h efficacy, allowing a once‐daily dosage. Studies have demonstrated BP lowering to be at least as effective as all major therapeutic classes including the more recent antihypertensive drugs. Beyond BP decrease, indapamide SR has also been shown to protect against hypertensive target‐organ damage in the heart and the kidney and to have a favorable metabolic profile. A broad evidence‐base has accumulated to support the benefit of indapamide 1.5 mg SR in hypertensive patients, alone or as part of combination therapy, as recommended by the majority of guidelines.
High expression of eosinophil chemoattractant ecalectin/galectin‐9 in drug‐induced liver injury
Authors: Takahashi Yoshihisa , Fukusato Toshio , Kobayashi Yuko , Akiyama Shuichi , Tamatani Takuya , Shiga Junji , Mori Shigeo 
Published: November 2005

Abstract: Backgound: Ecalectin/galectin‐9 (ECL/GL9) is an eosinophil chemoattractant isolated from T lymphocytes. Drug‐induced liver injury (DILI), often caused by an allergic mechanism, is occasionally accompanied by eosinophilic infiltration. In this study, we intended to determine whether DILI can induce augmentation of ECL/GL9 expression. Further, we investigated whether this augmentation is associated with tissue eosinophilia.Methods: We examined the expression of ECL/GL9 in biopsy specimens of DILI using the immunohistochemical technique. A rabbit anti‐ECL/GL9 antibody was produced by immunizing rabbits with synthetic peptide corresponding to a molecular epitope of ECL/GL9. Thereafter, immunohistochemical staining with the use of this antibody was performed on 16 DILI needle biopsy specimens, and on biopsy specimens of chronic viral hepatitis, liver cirrhosis, and normal liver tissues as controls.Results: In all cases of DILI specimens, but not in control liver specimens, a clear positive staining for ECL/GL9 was observed. Such positive staining was noted on Kupffer cells, fibroblasts, and histiocytes, but not on lymphocytes or hepatocytes. However, the intensity of immunolabeling did not correlate with the extent of eosinophile leukocyte infiltration.Conclusion: High expression of ECL/GL9 is suggested to be a specific finding of DILI. However, tissue eosinophilia in DILI cannot be explained by the augmentation of ECL/GL9 expression.
Laparoscopic findings in patients with nonalcoholic steatohepatitis
Authors: Tanaka Naoki , Ichijo Tetsuya , Okiyama Wataru , Mutou Hidetomo , Misawa Noriko , Matsumoto Akihiro , Yoshizawa Kaname , Tanaka Eiji , Kiyosawa Kendo 
Published: November 2005

Abstract: Background/Aims: Laparoscopic observation of the liver is important to diagnose liver conditions accurately. However, the laparoscopic findings of nonalcoholic steatohepatitis (NASH) have not been characterized. The aim of this study was to clarify the laparoscopic characteristics of NASH.Methods: Twenty‐four patients were enrolled. The degrees of hepatomegaly, color and irregularity of the liver surface, and the presence of depressions, patches, and vesicles were investigated. These laparoscopic findings were compared among NASH, alcoholic liver disease (ALD), and autoimmune hepatitis (AIH).Results: Mild hepatomegaly, dullness of the liver edge, increased fat accumulation of the round ligament, and whitish markings were found in most of the patients with NASH. Small depressions were observed in approximately 70% of the patients. As fibrosis developed, the liver surface became whiter and more uneven. Compared with patients with ALD and AIH, increased fat accumulation of the round ligament and dullness of the liver edge were observed more frequently in those with NASH. However, coarse and groove‐like depressions were rare in NASH patients.Conclusions: Several findings, including mild hepatomegaly, increased fat accumulation of the round ligament, rounded liver edge, whitish markings, and small depressions were common in patients with NASH. However, coarse and groove‐like depressions were rare. These findings may be helpful for confirming a diagnosis of NASH.
Prognostic analysis in chronic hepatitis B patients: a retrospective study of 216 cases about Scheuer scores, in situ expression of viral antigens and tissue hepatitis B virus DNA levels
Authors: Zhu Rong , Huang Hai , Zhang Huiping , Wang Zhen , Hu Xiqi , Zhai Weirong , Lin Yuqin , Wang Jiyao , Zhu Hongguang 
Published: November 2005

Abstract: Background: Most of the previous studies of patients with chronic hepatitis B virus (HBV) infection concentrated on serum samples. Liver biopsy specimens for HBV have not been systematically analyzed. This study was performed to analyze some histopathological indicators (Scheuer scores, the expression of HBV antigens in situ, HBV DNA quantification) in the biopsy samples and showed the relationship among them and the prognosis of chronic hepatitis.Methods: A total of 216 consecutive chronic HBV‐infected patients were followed up by clinical and laboratory data and classified into two groups at first: carcinogenesis and non‐carcinogenesis. The non‐carcinogenesis also included two groups: cirrhosis and non‐cirrhosis. The non‐cirrhosis was still divided into fluctuation and normalization at last. Histological activity index was described by Scheuer scores. Two‐step immunohistochemical staining showed the expression of viral antigens in situ. Tissue HBV DNA levels were determined by fluorescence quantitative real‐time PCR.Results: Regression analysis revealed significant positive correlations between the expression of hepatitis B e antigen (HBeAg) and grading, as well as between hepatitis Bx (HBx) protein and grading or staging of Scheuer scores. Positive correlations between grading or staging and prognosis were statistically significant. The expressions of HBeAg and HBx protein were higher in patients with cirrhosis than those without cirrhosis. Scheuer score was the most important indicator of prognosis.Conclusions: HBeAg and HBx protein can be used as indicators of hepatitis activity and their positive expressions increase the risk for cirrhosis remarkably. In addition to be a marker of liver damage, Scheuer score is the most reliable indicator of the prognosis.
Design‐based stereological estimation of hepatocyte number, by combining the smooth optical fractionator and immunocytochemistry with anti‐carcinoembryonic antigen polyclonal antibodies
Authors: Marcos Ricardo , Monteiro Rogério A. F. , Rocha Eduardo 
Published: November 2005

Abstract: Background/Aims: Hepatocytes (HEP) have been the major target for structural quantification in the liver, but an estimation of their total number (N), their percentage in relation to the global number of liver cells and the evaluation of the percentage of binucleated hepatocytes (BnHEPs) have never been performed with modern design‐based stereological techniques. The establishment of sound technical guidelines and baseline quantitative data in non‐pathological conditions are relevant to properly evaluate HEP hyperplasia and BnHEP responses.Methods: In this study, we combined immunocytochemistry with sound design‐based stereology for estimating the N of HEP and the N of non‐hepatocytic cells (NHCs). For obtaining systematic uniform random sections (30 μm thick), a smooth fractionator sampling scheme was applied to the liver of five male Wistar rats (3 month old). Those sections were immunostained with polyclonal antibodies against carcinoembryonic antigen. Because biliary canaliculi were then marked, an unequivocal counting of mononucleated hepatocytes (MnHEP) and BnHEP was allowed.Results: The N of HEP was estimated to be 1.93 × 109, with a coefficient of error (CE) of 0.02, corresponding to 129 × 106 HEP/g of liver. BnHEP represented 26% of total HEP number. The N of NHC was estimated as 1.31 × 109 (CE=0.02).Conclusion: The strategy here presented provides a reliable method for accessing the N of HEP (distinguishing MnHEP from BnHEP) in situations in which these parameters are relevant, namely for evaluating the magnitude of an hyperplastic liver response from its very early onset.
DLPC and SAMe combined prevent leptin‐stimulated TIMP‐1 production in LX‐2 human hepatic stellate cells by inhibiting H2O2‐mediated signal transduction
Authors: Cao Qi , Mak Ki M. , Lieber Charles S. 
Published: November 2005

Abstract: Background/Aims: Both dilinoleoylphosphatidylcholine (DLPC) and S‐adenosylmethionine (SAMe) have antioxidant properties and antifibrogenic actions. Because H2O2 mediates signal transduction‐stimulating liver fibrogenesis, we investigated whether DLPC and SAMe attenuate the production of tissue inhibitor of metalloproteinase (TIMP)‐1 by inhibiting H2O2 formation.Methods: LX‐2 human hepatic stellate cells were treated with leptin with or without DLPC, SAMe or various inhibitors.Results: Leptin‐stimulated TIMP‐1 mRNA and its protein were diminished by DLPC or SAMe alone, and the response was fully prevented by the combination of DLPC and SAMe. H2O2 was increased while glutathione was decreased; these changes were prevented by AG490, suggesting a Janus kinases (JAK)‐mediated process. Up‐regulation of leptin receptor and activation of JAK1 and 2 were not affected by DLPC+SAMe, whereas phosphorylation of ERK1/2 and p38 was blocked by DLPC+SAMe or catalase, suggesting an H2O2‐dependent mechanism. These treatments also suppressed leptin‐stimulated TIMP‐1 promoter activity and decreased TIMP‐1 mRNA stability, contributing to TIMP‐1 mRNA down‐regulation. PD098059, an ERK1/2 inhibitor, suppressed TIMP‐1 promoter activity, whereas SB203580, a p38 inhibitor, decreased TIMP‐1 message stability; both resulted in a partial reduction of TIMP‐1 mRNA.Conclusion: As decreased TIMP‐1 production may enhance collagen deposition, the combined administration of DLPC+SAMe should be considered for the prevention of H2O2‐mediated signaling and the resulting fibrosis.
Photosensitivity in Idiopathic Generalized Epilepsies
Authors: Covanis Athanasios 
Published: November 2005

Summary:  Photosensitivity is an abnormal visual sensitivity of the brain in reaction to flickering light sources or patterns and is expressed in the electroencephalogram as generalized spike‐and‐wave discharge and in more susceptible individuals as clinical seizures. The most common types of seizures are generalized tonic‐clonic, followed by myoclonic and absence. The photosensitive epilepsies are classified as pure photosensitive, where seizures occur only with the flickering light source/pattern or during intermittent photic stimulation (IPS) in the laboratory, and epilepsy with photosensitivity, where spontaneous seizures also occur. Positive response to IPS in idiopathic epilepsy syndromes, which are included in the International Classification or are in development, is reported to range from 7.5% in juvenile absence epilepsy to 100% in pure photosensitive epilepsy.The treatment of photosensitivity and pure photosensitive epilepsy with rare seizures includes general and specific protective measures. For most patients, however, combination treatment with antiepileptic drugs is necessary. Valproic acid monotherapy has a success rate of 73–86%. Levetiracetam appears to be a new alternative therapeutic option. Clobazam, lamotrigine, ethosuximide, and topiramate also have been recommended as second‐choice therapies.
Properties of Antiepileptic Drugs in the Treatment of Idiopathic Generalized Epilepsies
Authors: Patsalos Philip N. 
Published: November 2005

Summary:  Although valproate is considered to be the drug of first choice for the treatment of idiopathic generalized epilepsies (IGEs), other antiepileptic drugs (AEDs), both old (ethosuximide, clobazam, and clonazepam) and new (lamotrigine, levetiracetam, topiramate, and zonisamide) are also available. These AEDs do not appear to have a common mechanism of action in that both inhibitory gamma‐aminobutyric acid (GABA; e.g., clobazam, clonazepam, and valproate) and excitatory glutamate (e.g., lamotrigine and topiramate) mechanisms are involved. Ethosuximide primarily acts by blocking T‐type voltage‐gated calcium channels in thalamic neurones while topiramate and zonisamide have multiple mechanisms of action. In contrast, levetiracetam is unique in that it may act via a specific binding site in the brain.In terms of their pharmacokinetic characteristics, all eight AEDs are rapidly absorbed after oral ingestion with peak blood concentration being achieved within 1–4 hours. Bioavailability is 100% with the exception clonazepam (90%) and topiramate (81–95%). Plasma protein binding is variable with valproate (90%), clobazam (85%) and clonazepam (86%) showing substantial binding, lamotrigine (55%) and zonisamide (50%) intermediate binding, and levetiracetam (0%), ethosuximide (0%) and topiramate (10%) being minimally bound. However, the binding by zonisamide is complicated by its binding to erythrocytes as well as albumin. All AEDs, with the exception of lamotrigine and levetiracetam, undergo elimination as a result of extensive metabolism by hepatic cytochrome P450 enzymes, which are highly amenable to induction and inhibition by other drugs and therefore susceptible to pharmacokinetic interactions. Lamotrigine metabolism is via hepatic glucuronidation, a process that is also susceptible to induction and inhibition by concurrent drugs. Levetiracetam is minimally metabolized (by hydrolysis in blood), is excreted predominantly unchanged in urine, and to date has not been associated with any clinically significant pharmacokinetic interactions. Using a semiquantitative pharmacokinetic rating system, based on 16 pharmacokinetic characteristics, a direct comparison between AEDs is possible. Thus valproic acid, regarded as the drug of first choice in the treatment of IGEs, rates lowest with respect to favorable pharmacokinetic characteristics, mostly because of its nonlinear pharmacokinetics, extensive hepatic metabolism, and its high propensity to interact both with other AEDs and non‐AEDs. Levetiracetam rates highest with topiramate in second place.
Comorbidity Profile of Dementia Patients in Primary Care: Are They Sicker?
Authors: Schubert Cathy C. , Boustani Malaz , Callahan Christopher M. , Perkins Anthony J. , Carney Caroline P. , Fox Christopher , Unverzagt Frederick , Hui Siu , Hendrie Hugh C. 
Published: November 2005

OBJECTIVES: To compare the medical comorbidity of older patients with and without dementia in primary care.DESIGN: Cross‐sectional study.SETTING: Wishard Health Services, which includes a university‐affiliated, urban public hospital and seven community‐based primary care practice centers in Indianapolis.PARTICIPANTS: Three thousand thirteen patients aged 65 and older attending seven primary care centers in Indianapolis, Indiana.MEASUREMENTS: An expert panel diagnosed dementia using International Classification of Diseases, 10th Revision, criteria. Comorbidity was assessed using 10 physician‐diagnosed chronic comorbid conditions and the Chronic Disease Score (CDS).RESULTS: Patients with dementia attending primary care have on average 2.4 chronic conditions and receive 5.1 medications. Approximately 50% of dementia patients in this setting are exposed to at least one anticholinergic medication, and 20% are prescribed at least one psychotropic medication. After adjusting for patients' age, race, and sex, patients with and without dementia have a similar level of comorbidity (mean number of chronic medical conditions, 2.4 vs 2.3, P=.66; average CDS, 5.8 vs 6.2, P=.83).CONCLUSION: Multiple medical comorbid conditions are common in older adults with and without dementia in primary care. Despite their cholinergic deficit, a substantial proportion of patients with dementia are exposed to anticholinergic medications. Models of care that incorporate this medical complexity are needed to improve the treatment of dementia in primary care.
Outcome of Critically Ill Oldest‐Old Patients (Aged 90 and Older) Admitted to the Intensive Care Unit
Authors: Rellos Konstantinos , Falagas Matthew E. , Vardakas Konstantinos Z. , Sermaides George , Michalopoulos Argyris 
Published: November 2005

OBJECTIVES: To compare the outcomes of critically ill oldest‐old patients (≥90) with those of younger patients.DESIGN: Prospective cohort study.SETTING: General intensive care unit (ICU) of a tertiary care hospital in Athens, Greece.PARTICIPANTS: The oldest‐old and younger patients.MEASUREMENTS: In‐hospital and ICU mortality and stay, demographics, comorbidity, and complications.RESULTS: Of 5,505 consecutive patients admitted to the ICU, 60 (1.1%) were in the oldest‐old group (aged 90–98). Their mean length of ICU and hospital stay±standard deviation was 5.3±6.8 and 23.3±35.7 days, respectively. ICU mortality was 20%. Total in‐hospital mortality was 40%, compared with 8.9% (P=.001) in younger patients. Acute Physiology and Chronic Health Evaluation II score was independently associated with in‐hospital mortality (odds ratio=1.18, 95% confidence interval=1.05–1.33). Of 24 oldest‐old patients who died, 22 (91.7%) died in the ICU or in the ward within 30 days after ICU discharge.CONCLUSION: All‐cause in‐hospital mortality was higher in the oldest‐old group than in younger patients, but the mortality of this cohort of patients did not seem to reach a figure that would make physicians, relatives, and healthcare administrators decide against ICU care in this population.
Functional disability of mental disorders and comparison with physical disorders: a study among the general population of six European countries
Authors: Buist‐Bouwman M. A. , De Graaf R. , Vollebergh W. A. M. , Alonso J. , Bruffaerts R. , Ormel J. ,   the ESEMeD/MHEDEA 2000 investigators
Published: November 2005

Objective:  To examine the association of mental and physical disorders with multiple domains of functioning and compare the two.Method:  Data were derived from the European Study of the Epidemiology of Mental Disorders, a general population study in which adults (n > 21 000) from Belgium, France, Germany, Italy, the Netherlands and Spain were assessed using the Composite International Diagnostic Interview (mental disorders), World Health Organization Disability Assessment Schedule second edition (functional disability) and self‐report (physical disorders). Means in different groups were compared using the Mann–Whitney U‐test and multiple regression analyses.Results:  Mental disorders were related to disability in all domains of functioning: anxiety disorders the most, followed by mood disorders, and finally alcohol disorders. The findings suggest that mental disorders are associated with similar or higher levels of disability in all domains, except getting around, than arthritis and heart disease.Conclusion:  Mental disorders are associated with a similar or higher negative impact on daily functioning than arthritis and heart disease.
Pattern of health service utilization and predictors of readmission after a first admission for psychosis: a 2‐year follow‐up study
Authors: Cougnard A. , Parrot M. , Grolleau S. , Kalmi E. , Desage A. , Misdrahi D. , Brun‐Rousseau H. , Verdoux H. 
Published: November 2005

Objective:  To explore the pattern of health service utilization over 2 years following a first admission for psychosis and the baseline characteristics predicting readmission.Method:  Patients included in a cohort of first‐admitted subjects with psychosis (n = 84) were assessed at the end of a 2‐year follow‐up using multiple sources of information.Results:  At the end of the follow‐up, one of three subjects had no contact with any mental health professional, and 38% of subjects had no contact with a psychiatrist. Half of the patients were readmitted over the 2‐year follow‐up. The baseline characteristics independently predicting psychiatric readmission were a high number of helping contacts before first admission and persistence of psychotic symptoms at discharge.Conclusion:  Decreasing the frequency of readmission in the early course of psychosis is a public health priority. Development of psychotherapeutic programs for subjects with early psychosis who have enduring psychotic symptoms at first discharge should be promoted.
Antifertility Effect of Passive Administration of Antibodies to 80kDa Human Sperm Antigen and its Synthetic Peptides in Male and Female Rats
Authors: Bandivdekar Atmaram H. , Vernekar Vandana J. , Kamada Masaharu , Raghavan Vijaya P. 
Published: November 2005

ProblemA human sperm antigen of molecular size of about 80kDa (80kDa HSA) has been reported to be sperm‐specific, conserved and responsible for inducing immunological infertility. The partial N‐terminal amino acid sequence of 80kDa HSA (peptide NT) and its peptides obtained by enzymatic digestion with endoproteinase Lys‐C (peptides 1–4) and with endoproteinase Glu‐C (peptides 5 and 6) did not show sequence homology with any of the proteins of the GenBank. The peptides NT, 1, 2, 3 and 4 were synthesized, conjugated to keyhole limpet hemocyanin and used as an immunogen to raise the antibodies in rabbits. Peptide 3 did not elicit significant antibody titer while peptides NT, 1, 2 and 4 elicited significant antibody titer and immunobiologically mimicked the native protein.Method of studyEffects of passive administration of two injections each of 200 μL of antibodies or 10 and 40 μg purified immunoglobulins to 80kDa HSA, peptides NT, 1, 2 and 4 on fertility in male and female rats were investigated.ResultsPassive administration of antibodies to 80kDa HSA and its peptides NT, 1, 2 and 4 resulted in agglutination of epididymal spermatozoa with loss of motility but had no effect on sperm count or weights of the reproductive organs. These animals failed to impregnate normal female rats. Passive administration of these antibodies to female rats also resulted in infertility. The presence of antibodies was detected by enzyme‐linked immunosorbent assay in uterine secretions of animals treated with antipeptide antibody. The presence of agglutinated spermatozoa was observed in the post‐coital vaginal smears of these animals. The immunized females were found to be ovulating normally and the number of corpora lutea were unaltered. Of the four antipeptide antibodies studied, antibodies to peptides NT and 1 were most effective in inhibiting fertility both in male as well as female rats. Hence, the antifertility studies were further confirmed by passive administration of 10 and 40 μg of purified immunoglobulins of antibodies to NT and 1, which resulted in a dose‐dependent inhibition of fertility in male and female rats.ConclusionsThe study demonstrated that the synthetic peptides of 80kDa HSA immunobiologically mimicked the native protein and impaired fertility following passive administration of antipeptide antibodies and hence, suggested the suitability of synthetic peptides of 80kDa HSA as candidates for development of antifertility vaccine.