bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Free Radical Scavenging Activity of Siamese Neem Tree (Azadirachta indica A. Juss var. siamensis Valeton) Leaf Extracts Prepared by Different Methods of Extraction
Authors: Sithisarn Pongtip , Supabphol Roongtawan , Gritsanapan Wandee
Published: May 2006

Objective: The aim of this study was to investigate the antioxidant activity of the aqueous extracts of leaves of Siamese neem tree (Azadirachta indica A. Juss var. siamensis Valeton) from several extracting and drying methods using 2,2-diphenyl-1-picrylhydrazyl (DPPH)-scavenging assay. Materials and Methods: The leaves of Siamese neem tree were extracted using percolation, decoction, maceration, soxhlet extraction, freeze drying or spray drying methods. The extract was tested for antioxidant activity using DPPH-scavenging assay. Thin-layer chromatography of the extract from decoction was also investigated. Results: The freeze drying method gave the highest yield (51.50%, w/w) of crude extract, while decoction gave the most effective DPPH-scavenging activity (EC50: 31.4 µg/ml). Thin-layer chromatography analysis was used to screen the leaf extract obtained using decoction, and the chromatogram showed spots corresponding to quercetin and rutin flavonoids which exhibited antioxidant activities (EC50: 2.29 and 34.67 µg/ml, respectively). Conclusion: Siamese neem tree leaf extracts possessed free radical scavenging activity against the DPPH radical. The most active extract was obtained with the leaf decoction method. It showed antioxidant activity with EC50 of 31.4 µg/ml.
Validity and Reproducibility of Different Combinations of Methods for Occlusal Caries Detection: An in vitro Comparison
Authors: Souza-Zaroni W.C. , Ciccone J.C. , Souza-Gabriel A.E. , Ramos R.P. , Corona S.A.M. , Palma-Dibb R.G.
Published: May 2006

This study assessed the validity and reproducibility of different combinations of occlusal caries detection methods: visual examination (VE), laser fluorescence (LF) and radiographic examination (RE). Intra- and interexaminer reproducibilities were also assessed. Forty-seven extracted human molars were used and 121 sites, either suspected or not to be carious, were chosen. Occlusal surfaces were examined by 8 volunteers, assigned to three groups according to their level of knowledge and clinical experience on dental practice: group I, undergraduate students; group II, postgraduate students; group III, professors. Three combinations of methods were tested: A: VE + LF, B: VE + RE, C: VE + LF + RE. The examiners scored the sites using ranking scales and chose a final score based on their clinical experience. The gold standard was determined by histological examination of the sites. In general, LF and RE yielded poorer results than the combinations of methods. For combination A, group III showed the highest sensitivity, while group II showed the highest specificity. For combination B, group II showed moderate sensitivity whereas groups I and III exhibited low sensitivities; all groups of examiners reached substantial specificity. For combination C, all groups exhibited moderate sensitivity and substantial specificity. Interexaminer reproducibility ranged from fair to moderate for combinations A and C, while for combination B kappa values indicated moderate interexaminer reproducibility. It may be concluded that individual exams presented inferior performance than the conjunction of them. Combination C (VE + LF + RE) resulted in the best accuracy for all groups. The knowledge background of the examiners influenced their ability to detect caries lesions and affected interexaminer reproducibility.
Effects of Various Rinsing Protocols after the Use of Amine Fluoride/Stannous Fluoride Toothpaste on the Acid Production of Dental Plaque and Tongue Flora
Authors: Gerardu V.A.M. , van Loveren C. , Heijnsbroek M. , Buijs M.J. , van der Weijden G.A. , ten Cate J.M.
Published: May 2006

The aim of this clinical study was to evaluate the effect of various rinsing protocols on oral acid production 6 h after tooth brushing with an amine fluoride/stannous fluoride (AmF/SnF2) toothpaste. After a 14-day period of using F-free toothpaste, 30 participants followed three experimental protocols each, followed by F-free washout periods in a randomized crossover trial. They used AmF/SnF2 toothpaste twice daily for 1 week, and after brushing, they either rinsed with tap water, omitted the post-brush rinse, or rinsed with an AmF/SnF2 mouthwash. In the F-free washout periods, the participants brushed their teeth without further instructions. Six hours after the last brushing (± rinsing) of each period, subjects rinsed with 10 ml 10% sucrose solution for 2 min. A tongue film sample and a buccal plaque sample were taken 4 and 8 min after the sucrose challenge, respectively. Metabolic acid ions were determined by capillary electrophoresis. The results show that (1) omitting the post-brush water rinse did not reduce the production of lactic, acetic or minor acids in plaque, nor on the tongue, and that (2) the additional use of AmF/SnF2 mouthwash after brushing reduced the acid production in plaque and tongue samples for at least 6 h. The distributions of acids produced in the plaque or tongue samples were not statistically different between experimental periods. It is concluded that an increase in the antimetabolic effect of AmF/SnF2 toothpaste in between two daily brushing exercises is not achieved by omitting the post-brush water rinse. The additional use of AmF/SnF2 mouthwash after brushing is effective in reducing the acid metabolism in dental plaque and tongue flora.
The Relationship between CYP17 –34T/C Polymorphism and Acne in Chinese Subjects Revealed by Sequencing
Authors: He Li , Yang Zhi , Yu Haijing , Cheng Baoweng , Tang Wenru , Dong Yongli , Xiao Chunjie
Published: May 2006

Background: Although many arguments have been raised on the role of heredity in the etiology of acne, the relevant genetic elements in the pathogenesis of the disease are not well established. Objective: The aim of our study was to evaluate the association between a genetic polymorphism in the promoter region of the CYP17 gene and the development of acne. Methods: 206 acne patients and 200 controls were included in the study. A polymerase chain reaction (PCR) sequencing technique was used to reveal a CYP17 gene polymorphism in its promoter region. A χ2 test was used for data analysis. Results: CYP17 –34T/C polymorphism was found and the frequency distribution of the C/C homozygotes and C allele in the male patients with severe acne (33.3 and 60.9%, respectively) were statistically significantly different from those of the control samples (18.2 and 46.6%; p < 0.05). No significant difference was observed between the female patients, mild + moderate male patients and their controls, respectively. Conclusion: The CYP17 –34C/C homozygote Chinese men are at a significantly increased risk of developing severe acne.
Reticular Erythematous Mucinosis Occurring in a Brother and Sister
Authors: Caputo Ruggero , Marzano Angelo V. , Tourlaki Athanasia , Marchini Maurizio
Published: May 2006

Reticular erythematous mucinosis (REM) is a rare, primary cutaneous mucinosis clinically characterized by a persistent reticular erythema on the mid chest and mid-upper back, and histologically by a mononuclear cell infiltrate and deposits of mucin in the dermis. To our knowledge, the present report of REM occurring in a Caucasian man and his sister is the first reported case of familial REM. Since a host-specific immune response to unknown antigens may be involved in the pathogenesis of this entity, human leukocyte antigen typing was determined and compared to those reported in autoimmune diseases.
The Need for New Therapies for Acute Ischaemic Stroke
Authors: Millán Mónica , Dávalos Antoni
Published: May 2006

Stroke creates the fourth highest burden of disease worldwide, and is the leading cause of adult long-term disability in developed countries. These factors mean that stroke has a high associated cost for healthcare systems, and a potentially devastating effect on family and carers. One of the main reasons why patients have such a poor prognosis is a lack of treatment options. Recombinant tissue plasminogen activator (rt-PA) is the only treatment currently licensed to treat selected patients with acute ischaemic stroke. However, only 1–8.5% of hospitalised patients receive treatment with rt-PA due to the short time window for administration (within 3 h of symptom onset), risk of intracerebral haemorrhage, need for a computed tomography scan, and exclusions due to other specific criteria. For acute ischaemic stroke, well-tolerated treatments that offer an extended therapeutic window are urgently needed to decrease disability, aid neurological recovery and improve patient prognosis. Neuroprotective agents potentially offer benefit to stroke patients without the associated haemorrhagic risk of thrombolytic therapy. Such agents target the ischaemic penumbra and aim to reduce the risk of brain injury and long-term disability by disrupting the cellular, biochemical, and metabolic consequences of infarction following exposure to ischaemia. Future directions should involve developing a neuroprotective compound that is safe, well tolerated and effective in a broad range of patients.
Optimising Clinical Trial Design for Proof of Neuroprotection in Acute Ischaemic Stroke: The SAINT Clinical Trial Programme
Authors: Davis Stephen
Published: May 2006

The development of effective therapies for acute ischaemic stroke has proven to be a challenging task. The only approved therapy for acute ischaemic stroke remains intravenous recombinant tissue plasminogen activator initiated within 3 h of stroke onset, following a CT scan to exclude intracerebral haemorrhage. Many other therapies have been evaluated in Phase III clinical trials, including more than 50 neuroprotective agents, but the results have either been inconclusive or negative. These trials have provided valuable lessons for the design of future studies in acute ischaemic stroke, including the importance of adequate testing in preclinical studies, time to treatment from symptom onset, target dose, patient selection, sample size and the outcome measures used. These key criteria have been captured in the Stroke Therapy Academic Industry Roundtable (STAIR) recommendations for the preclinical and clinical development of acute stroke therapies. NXY-059 is a novel free radical-trapping neuroprotectant that reduces infarct size and preserves brain function in animal models of acute ischaemic stroke. It is one of the first compounds to have progressed to Phase III clinical trials, having fulfilled the STAIR recommendations for the preclinical development of neuroprotective agents. The efficacy and safety of NXY-059 in patients with acute ischaemic stroke is currently being evaluated in the Stroke Acute Ischaemic NXY-059 Treatment (SAINT) clinical trial programme, which was designed in accordance with the STAIR clinical recommendations. The final results from the first of these studies, SAINT I, have recently been reported.
Structure-Function Relationships of C-Type Lectin-Related Proteins
Authors: Morita Takashi
Published: May 2006

The structural and functional studies of the first identified C-type lectin-like protein (CLP), blood coagulation factor IX/factor X-binding protein (IX/X-bp), have been instrumental in defining how new functionally heterodimeric CLPs are generated from monomeric carbohydrate recognition domain in C-type lectins by three-dimensional domain swapping. The crystal structures of γ-carboxyglutamic acid domains of coagulation factors X and IX have recently been clarified in structural studies of complexes between the γ-carboxyglutamic acid domain of factors X and X-bp (a venom CLP) and between the γ-carboxyglutamic acid domain of factors IX and IX-bp (a venom CLP).
Comparison of Textilinin-1 with Aprotinin as Serine Protease Inhibitors and as Antifibrinolytic Agents
Authors: Flight Simone , Johnson Lambro , Trabi Manuela , Gaffney Patrick , Lavin Martin , de Jersey John , Masci Paul
Published: May 2006

Textilinin-1 (Q8008) was isolated from the venom of the Pseudonaja textilis and has a 47% sequence identity to the antihaemorrhagic therapeutic agent aprotinin. When equimolar concentrations of enzyme and aprotinin were pre-incubated, plasmin was inhibited 100%, plasma kallikrein 58%, and tissue kallikrein 99%. Under the same conditions, textilinin-1 inhibited plasmin 98%, plasma kallikrein 16% and tissue kallikrein 17%. Whole blood clot lysis was inhibited strongly by both aprotinin and textilinin-1, as shown by thrombelastography. At 2 µM inhibitor lysis initiated by t-PA was greater than 99% inhibited by aprotinin (LY60 = 0.4 ± 0.1) whereas textilinin-1, inhibited lysis by 91% (LY60 = 8.9 ± 0.7). The same trend was found with the lysis of euglobulin fractions. From these data textilinin-1 appears to be a more specific plasmin inhibitor than aprotinin but aprotinin inhibits clot lysis to a greater extent.
Identification and Localization of Heparin-Binding Region of Snake Venom VEGF and Its Blocking of VEGF-A165
Authors: Tokunaga Yuko , Yamazaki Yasuo , Morita Takashi
Published: May 2006

Vascular endothelial growth factor (VEGF-A165) displays diverse effects through binding to its receptor, KDR (kinase domain-containing receptor). Heparan sulfate/heparin-like molecules greatly contribute to their interaction. Indeed, the mitogenic potency of VEGF-A165 lacking the C-terminal heparin-binding region is less than 1% compared with intact VEGF-A165. We previously found novel heparin-binding VEGFs, designated VEGF-F that specifically recognizes KDR in snake venoms. VEGF-Fs almost completely lack the C-terminal heparin-binding region compared with VEGF-A165, despite their heparin-binding potential. In this study, we attempted to identify the heparin-binding region of VEGF-F using synthetic peptides. We have demonstrated that the heparin-binding site of VEGF-F is located in its C-terminal region, particularly localized on the N-terminal portion of this region. Furthermore, a synthetic peptide of this region blocks the biological activity of VEGF-A165 in vitro and in vivo.
The Use of Snake Venom-Derived Compounds for New Functional Diagnostic Test Kits in the Field of Haemostasis
Authors: Schöni Reto
Published: May 2006

Pentapharm Ltd. has a long tradition of producing and proceeding snake venom components as APIs and tools in pharmaceutical and diagnostic applications, beginning with the snake venom-derived product Reptilase® about 60 years ago. In recent years diagnostic test kits in the field of haemostasis have been developed, like Pefakit® APC-R Factor V Leiden and Pefakit® PiCT®, which make use of one or more snake venom compounds as key reactants. The venom-derived compounds are responsible for many outstanding properties of these tests and account for their top ranking performance qualities confirmed in non-clinical and clinical studies. Both tests are on the market in Europe. Pefakit® APC-R Factor V Leiden is also marketed in the US since January 2005. Research on snake venom-derived compounds for diagnostic and pharmaceutical use is ongoing.
Vagal-Accessory-Hypoglossal Syndrome: Schmidt’s or Jackson’s?
Authors: Pearce J.M.S.
Published: May 2006

Paralysis of the vagal-accessory-hypoglossal nerves has many eponyms. Many cases were caused by injuries in the First World War. Confusion arose because of the varied anatomical sites and varied extent of tissues damaged. Hughlings Jackson’s name is justified by historical precedence, but descriptive terms of axial and extra-axial lesions are preferred.
Barriers to Autopsy: Creutzfeldt-Jakob Disease in New York State
Authors: Lillquist Patricia P. , Thomas Nadia , Belay Ermias D. , Schonberger Lawrence B. , Morse Dale
Published: May 2006

Surveillance of Creutzfeldt-Jakob disease (CJD) monitors trends and ensures timely identification of variant CJD and other emergent prion diseases. Brain tissue is needed to definitively diagnose these diseases. A survey of neurologists and pathologists in New York State was conducted to understand neurologists’ and pathologists’ views on autopsy and CJD. Neurologists reported using autopsy rarely or never. Over half of the pathologists worked in facilities that did not perform autopsies when CJD was suspected. Barriers to autopsy included family reluctance, infection control concerns, and local facilities unable to perform brain autopsy. More accurate, complete recognition of CJD and variant forms depends on physician awareness of the manifestations of CJD and its diagnosis, access to pathologists and facilities willing and able to perform brain biopsies and autopsies, and family acceptance of such procedures.
Trends in Risk of Stroke in Patients with a Hospital Diagnosis of Nonvalvular Atrial Fibrillation: National Cohort Study in Denmark, 1980–2002
Authors: Frost Lars , Vukelic Andersen Ljubica , Vestergaard Peter , Husted Steen , Mortensen Leif Spange
Published: May 2006

Aim: We examined trends in incidence of stroke of any nature (ischemic and/or hemorrhagic) in subjects with a hospital diagnosis of nonvalvular atrial fibrillation or flutter in Denmark from 1980 to 2002 by sex, age and conditions of comorbidity. Methods: We identified all individuals, aged 40–89 years, with an incident hospital diagnosis of atrial fibrillation or flutter and no history of stroke or heart valve disease in the Danish National Registry of Patients, and subjects were followed in the Danish National Registry of Patients for occurrence of an incident diagnosis of stroke of any nature (ischemic and/or hemorrhagic) and in the Danish Civil Registration System (emigration and vital status). We used multivariate Cox proportional hazard regression analysis to estimate trends in incidence of stroke. Results: Nonvalvular atrial fibrillation or flutter was diagnosed in 141,493 subjects (75,126 men and 66,367 women), and during follow-up 15,964 subjects had an incident diagnosis of stroke. The hazard ratios for stroke in the last 3-year period compared to the first 5-year period, adjusted for 10-year age group, conditions of comorbidity, and general stroke trend in the Danish population were 0.78 (95% CI 0.70–0.86) in men, and 0.80 (95% CI 0.72–0.88) in women. The reduction in risk of stroke by calendar year was most prominent in patients aged 40–74 years. Conclusion: We observed a modest decrease in risk of stroke in subject with atrial fibrillation in Denmark during calendar years 1980–2002. However, we could not control for any changes in diagnostic performance, admission practice, and medical management of patients with atrial fibrillation.
Differences in Risk Factors for Dementia with Neurodegenerative Traits and for Vascular Dementia
Authors: Wehr H. , Bednarska-Makaruk M. , Łojkowska W. , Graban A. , Hoffman-Zacharska D. , Kuczyńska-Zardzewiały A. , Mrugała J. , Rodo M. , Bochyńska A. , Sułek A. , Ryglewicz D.
Published: May 2006

In 229 patients with dementia and in 144 control subjects, polymorphisms of apolipoprotein E (ApoE), low-density-lipoprotein (LDL)-receptor-related protein, α2-macroglobulin, interleukin (IL) 1β, angiotensin-converting enzyme and of methylene tetrahydrofolate reductase genes were investigated. In plasma, antibodies against Chlamydia pneumoniae and lipids were determined. Dementia was classified as probable Alzheimer’s disease (AD), probable dementia of vascular origin (VaD) and mixed dementia (MD). An association of the disease with ApoE and IL-1β polymorphism and increased levels of LDL cholesterol were observed in AD and in MD but not in VaD.
Is Gastrin Partially Responsible for Body Weight Reduction after Gastric Bypass?
Authors: Stenström Björn , Zhao Chun-Mei , Tømmerås Karin , Arum Carl-Jørgen , Chen Duan
Published: May 2006

Background: The rationale for bariatric surgery is to reduce food intake by gastric restriction and/or malabsorption by intestinal bypass. Unlike ghrelin, gastrin is released in response to food intake. Here we studied the possible role of gastrin in the reduction of body weight after gastric bypass surgery. Methods: Rats were divided into four experimental groups and were subjected to different treatments: sham operation, gastric bypass, sham operation + gastrin infusion, and gastric bypass + gastrin infusion. The gastric bypass was done by anastomosing the esophagus to the duodenal bulb without bypassing the intestine. Gastrin-17 was infused continuously for 2 months via subcutaneously implanted osmotic minipumps. Body weights were recorded; serum gastrin and ghrelin levels were measured, and the stomachs were analyzed morphologically. Results: Gastric bypass resulted in reducing the body weight, stomach weight, thickness of the oxyntic mucosa, serum gastrin concentration, and activity of the ECL cells. Gastrin infusion prevented mucosal atrophy and ECL cell inactivation, and attenuated the body weight reduction that occurred following gastric bypass. Circulating ghrelin and ghrelin-producing A-like cells in stomachs that had undergone gastric bypass were unchanged with or without gastrin infusion and are thus unlikely to be responsible for the reduced body weight. Conclusion:We suggest that hypogastrinemia and impaired ECL cell function in the oxyntic mucosa of the stomach might be partially responsible for the reduction in body weight that occurs after gastric bypass.
Gene Expression of the Na+–Ca2+ Exchanger, SERCA2a and Calsequestrin after Myocardial Ischemia in the Neonatal Rabbit Heart
Authors: Seehase Matthias , Quentin Thomas , Wiludda Elke , Hellige Gerhard , Paul Thomas , Schiffmann Holger
Published: May 2006

Background: Neonatal hearts are less susceptible to developing myocardial dysfunction after hypoxia and/or ischemia than adult hearts. Differences in intracellular calcium homeostasis may be responsible for reduced calcium overload of the immature myocardium leading to the observed protection against ischemia. Objective: To assess differences in baseline and post-ischemic gene expression of calcium handling proteins after ischemia in neonatal and adult rabbit hearts. Methods: We used isolated antegrade perfused rabbit hearts (age 2 days, 28 days, n = 32), which were exposed to ischemia and hypothermia simulating myocardial stunning comparable to neonatal asphyxia. Gene and protein expression of the sodium–calcium exchanger (NCX), the sarco-endoplasmatic reticulum Ca2+-ATPase 2a (SERCA) and calsequestrin (CSQ) were measured using quantitative real-time PCR and Western blotting. Results: After ischemia and reperfusion in neonatal and adult hearts, a significant decrease in myocardial performance was recorded. At the mRNA level, significant differences in the baseline expression of NCX, SERCA and CSQ between neonatal and adult hearts were observed. In neonatal post-ischemic hearts, NCX and CSQ expression were significantly higher at the mRNA level than in controls. In contrast, SERCA expression remained unchanged in neonatal hearts and decreased in adult hearts compared to the non-ischemic controls. Conclusion: These findings suggest that changes in gene expression of calcium handling proteins may be involved in the different susceptibility of neonatal compared to adult hearts to developing myocardial dysfunction after ischemia.
Does the Hyperfiltration of Minoxidil Result in Increased Proteinuria and Loss of Renoprotection Conferred by Angiotensin Inhibition?
Authors: Diskin Charles J. , Stokes Thomas J. , Dansby Linda M. , Radcliff Lautrec , Carter Thomas B.
Published: May 2006

The objective of the present study was to retrospectively examine whether the addition of minoxidil to patients who were already treated with maximum doses of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers but who had not achieved target blood pressures, has any detrimental effect on proteinuria or renal function or whether its effect on blood pressure prove salutary. The clinical records of the patients seen at the Hypertension, Nephrology, Dialysis and Transplantation Clinic from June 1982 through May 2005 were reviewed to identify 54 patients (78% men, 82% African-American) who had taken minoxidil (with and without angiotensin inhibition and blockade) and who had documented 24-hour urines for creatinine clearance and quantification of proteinuria before the initiation of minoxidil and after the blood pressure had stabilized on its final dose. The study was done at the Hypertension, Nephrology, Dialysis and Transplantation Clinic, the regional referral center for renal problems in eastern Alabama, USA. Minoxidil, whether alone or in combination with maximum doses of ACEIs and ARBs, was very successful in reduction of mean arterial pressure, but there was a tendency towards an increase in proteinuria. When minoxidil was given alone, patients demonstrated a trend towards reduction of proteinuria associated with blood pressure reduction; however, when minoxidil was added after the maximal doses of ACEIs and ARBs had been reached there was a significant increase in proteinuria (p = 0.017) on paired comparison in the same patients whose proteinuria had already demonstrated a significant decrease (p = 0.02) on the ACEI and ARB alone despite further significant reduction of blood pressure with the minoxidil (p = 0.003). Renal function deterioration to end stage renal disease correlated with increase in proteinuria (p = 0.03). We conclude that minoxidil was very effective in lowering systemic blood pressure but when given to patients already on maximum doses of ACEI and ARBs, there was an increase in proteinuria which could be interpreted as a detrimental effect having in mind that the blood pressure was significantly lowered.
Multicenter Phase II Study of Gemcitabine and Oxaliplatin (GEMOX) as Second-Line Chemotherapy in Colorectal Cancer Patients Pretreated with 5-Fluorouracil plus Irinotecan
Authors: Ziras N. , Potamianou A. , Varthalitis I. , Syrigos K. , Tsousis S. , Boukovinas I. , Tselepatiotis E. , Christofillakis C. , Georgoulias V.
Published: May 2006

Purpose: To evaluate the efficacy and tolerance of the gemcitabine/oxaliplatin (GEMOX) combination as second-line chemotherapy for patients with advanced colorectal cancer (CRC) pretreated with an irinotecan (CPT-11)/5-fluorouracil (5-FU)/leucovorin (LV) regimen. Patients and Methods: Patients with documented disease progression during or after first-line treatment with CPT-11 and 5-FU/LV were enrolled. Gemcitabine (1,000 mg/m2 days 1 and 8) and oxaliplatin (100 mg/m2 day 1) were administered every 3 weeks. Results: Partialresponses were observed in 6 of the 34 (17.7%) patients enrolled (intention-to-treat analysis; overall response rate: 17.7%; 95% confidence interval 4.8–30.5%). Eight (23.5%) patients experienced disease stabilization and 20 (59%) disease progression (tumor growth control rate = 41.2%). The median duration of response was 5.5 months, and the median time to tumor progression 2.7 months. The median overall survival was 9.1 months (1-year survival rate: 44.0%). Grade 3 neutropenia and thrombocytopenia occurred in 18 and 15% of the patients, respectively. Other severe non-hematologic toxicities were rare. Conclusion: The interesting tumor growth control rate and the favorable toxicity profile of the GEMOX regimen in pretreated patients with advanced CRC strongly suggest that this regimen may provide an alternative therapeutic option for this group of patients.
The Current and Future State of Interventional Cardiology: A Critical Appraisal
Authors: Meier Bernhard
Published: May 2006

After 75 years of invasive and over 50 years of interventional cardiology, cardiac catheter-based procedures have become the most frequently used interventions of modern medicine. Patients undergoing a percutaneous coronary intervention (PCI) outnumber those with coronary artery bypass surgery by a factor of 2 to 4. The default approach to PCI is the implantation of a (drug-eluting) stent, in spite of the fact that it improves the results of balloon angioplasty only in about 25% of cases. The dominance of stenting over conservative therapy or balloon angioplasty on one hand and bypass surgery on the other hand is a flagrant example of how medical research is digested an applied in real life. Apart from electrophysiological interventions, closure ot the patent foramen ovale and percutaneous replacement of the aortic valve in the elderly have the potential of becoming daily routine procedures in catheterization laboratories around the world. Stem cell regeneration of vessels or heart muscle, on the other hand, may remain a dream never to come true.
Microbleeds in Alzheimer Disease Are More Related to Cerebral Amyloid Angiopathy than Cerebrovascular Disease
Authors: Nakata-Kudo Yuriko , Mizuno Toshiki , Yamada Kei , Shiga Kensuke , Yoshikawa Kenji , Mori Satoru , Nishimura Tunehiko , Nakajima Kenji , Nakagawa Masanori
Published: May 2006

Cerebral amyloid angiopathy (CAA) is one of the cardinal pathological features in the vascular components of Alzheimer’s disease (AD). CAA itself results in disrupted microvasculature, mainly in the cerebral cortex, eventually leading to a brain cortical or subcortical hemorrhage in a population of elderly people, but clinically overt brain hemorrhages are not so frequent in AD patients. Here we assessed 50 AD patients and 26 controls to detect latent brain hemorrhages with gradient-echo T2*-weighted images, a sensitive magnetic resonance imaging technique to detect hemosiderin components in the brain. Microbleeds, demarcated as low-intensity spots in T2*-weighted images, were detected in 16.7% of AD patients without cerebrovascular disease (CVD) and in 12.5% of those with CVD, while no microbleeding was detected in the control subjects. No significant difference was observed between the microbleed-positive group and the microbleed-negative counterpart in their clinical background, such as hypertension, the use of antiplatelet drugs and smoking. In addition, white matter high intensities in the T2-weighted image were significantly more confluent in the microbleed-positive AD group than its negative counterpart. In conclusion, our evaluation of AD brains revealed that latent microbleeds in AD patients are more frequent than in normal controls. Microbleeds not being related to common hemorrhagic risk factors, but being significantly related to white matter pathologies suggested that microbleeds in AD may be associated with CAA, but not with hypertension or CVD.
Renal Function in Patients with Abdominal Aortic Aneurysm
Authors: Nakamura Satoko , Yoshihara Fumiki , Kamide Kei , Horio Takeshi , Nakahama Hajime , Inenaga Takashi , Nishigami Kazuhiro , Fukuchi Kazuki , Ogino Hitoshi , Kawano Yuhei
Published: May 2006

Aims: Renal dysfunction occurs occasionally after the repair of abdominal aortic aneurysm (AAA), and preoperative renal function is considered as one of the potential causes. The present study was designed to evaluate and compare renal function and risk factors of AAA patients with those of hypertensive patients. Methods: We prospectively examined 95 patients with AAA and 72 patients with essential hypertension (HT) without other cardiovascular diseases (CVD). Renal function, urinary albumin excretion (UAE) and renal scintigraphy were compared. Kidney size was calculated using ultrasonography. Results: Serum creatinine and creatinine clearance in AAA patients was worse than in HT patients. Smoking status was more apparent in AAA patients. Renal artery stenosis occurred in 8 patients with AAA. Renal scintigraphy showed normal function in 19%, hypofunction in 69% and severe dysfunction in 12% of the AAA patients, and normal function in 42% and hypofunction in 58% of the HT patients (p < 0.0001). Multivariate linear regression analysis showed that renal function was related to age, UAE, CVD, smoking status and kidney size for all patients, UAE, CVD, smoking status and kidney size for AAA patients, and age and kidney size for HT patients. Conclusion: Renal function of AAA patients was worse than HT patients without other CVD. The risk factors for renal dysfunction were different between AAA and HT patients. These preoperative conditions may relate to the postoperative renal dysfunction seen in AAA patients.
Angiotensin-Converting Enzyme Gene Polymorphism in Children with Idiopathic Nephrotic Syndrome
Authors: Tsai I-Jung , Yang Yao-Hsu , Lin Yen-Hung , Wu Vin-Cent , Tsau Yong-Kwei , Hsieh Fon-Jou
Published: May 2006

Aims: To investigate the genetic polymorphism of angiotensin-converting enzyme (ACE) insertion/deletion (I/D) in children with idiopathic nephrotic syndrome (INS), as well as its relationship with patient’s clinical response to steroid therapy. Methods: Fifty-nine patients with INS were recruited and divided into 2 groups according to their clinical response to steroids: steroid-sensitive (SS) with 19 patients and non-SS with 40 patients, which was further divided into steroid-dependent (SD) and steroid-resistant (SR) groups with 35 and 5 patients, respectively. Seventy-nine children without previous renal diseases and negative proteinuria were enrolled as a control group. The genotypes for ACE I/D polymorphism, including DD, ID, and II, were analyzed. Results: The distribution of ACE DD, ID, and II genotypes in INS patients were 52.5, 10.2 and 37.3%, respectively; the corresponding numbers for the control group were 2.5, 25.3 and 72.2%, respectively. Patients with INS had a significantly higher percentage of DD genotype (p <0.001) than the control group. This higher incidence of the DD genotype was observed in both the SS and non-SS groups. A higher percentage of the DD genotype in the non-SS group and in the SD group as compared to the SS group (both p < 0.05) was also noted. Conclusion: Our data shows that INS is associated with a higher incidence of the DD genotype, especially in non-SS patients. This finding suggests that the DD genotype may be a risk factor for INS and play a role in the clinical response to steroids.
Pretreatment Serum Levels of Cytokines and Cytokine Receptors in Patients with Non-Small Cell Lung Cancer, and Correlations with Clinicopathological Features and Prognosis
Authors: Kaminska Janina , Kowalska Maria , Kotowicz Beata , Fuksiewicz Malgorzata , Glogowski Maciej , Wojcik Ewa , Chechlinska Magdalena , Steffen Jan
Published: May 2006

Objectives: Cytokines are potential new serum markers, especially desirable for malignancies with poor prognosis like non-small cell lung cancer (NSCLC). Methods: Cytokines, tumor necrosis factor α (TNFα), interleukin (IL)-6 and IL-8, soluble TNF (sTNF) RI, sTNF RII, soluble IL-2 receptor-α, IL-1 receptor antagonist (IL-1ra), IL-10, vascular endothelial growth factor, basic fibroblast growth factor, and macrophage (M-CSF) and granulocyte colony-stimulating factor, as well as tumor markers – carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC) and CYFRA 21.1 – were assessed in the sera of 103 untreated NSCLC patients, and these cytokines and tumor markers were refered to clinical parameters of the disease and to the overall survival of patients evaluated during a 6-year follow-up. Results: Most of the factors analyzed were found to be elevated in the sera of NSCLC patients, and increases in IL-6, IL-8 and sTNF RI were noted in the greatest proportion of stage I patients. Most cytokine/cytokine receptor levels revealed higher sensitivity than the standard tumor markers; IL-6 and IL-1ra levels were significantly different in patients with squamous cell versus adenocarcinoma; IL-6 and IL-10 were related to the tumor size, while IL-6 and M-CSF levels significantly increased with disease progression. A significant prognostic value of pretreatment serum M-CSF and CEA levels in NSCLC patients has been shown, but only M-CSF proved to be an independent prognostic factor. Conclusions: Increased pretreatment serum M-CSF level is a significant independent predictor of poor survival in patients with NSCLC.
A Phase II Study of Irinotecan with 5-Fluorouracil and Leucovorin in Patients with Pretreated Gastroenteropancreatic Well-Differentiated Endocrine Carcinomas
Authors: Ducreux M.P. , Boige V. , Leboulleux S. , Malka D. , Kergoat P. , Dromain C. , Elias D. , de Baere T. , Sabourin J.C. , Duvillard P. , Lasser P. , Schlumberger M. , Baudin E.
Published: May 2006

Only a few drugs are active in the treatment of well-differentiated endocrine carcinomas (WDEC). We evaluated the combination of the so-called ‘de Gramont schedule’ and irinotecan in these tumors in a phase II study. Methods: 20 patients were enrolled in the study. The combination regimen included irinotecan, 180 mg/m2 on day 1, followed by 200 mg/m2 folinic acid in a 2-hour infusion, an intravenous 10-min bolus of 400 mg/m2 5-fluorouracil (5FU) and finally 600 mg/m2 5FU in a 22-hour infusion. Folinic acid and 5FU were repeated on day 2. Clinical, biological and morphological parameters were assessed by CT every 8 weeks. The site of the primary tumor was the pancreas in 10 cases, the lung in 3 cases and other sites in 7 cases. Sixteen patients had previously received chemotherapy, and 6 of them had had two lines of treatment. Six patients had previously been treated with chemoembolization. Results: The median number of cycles administered was 8. Grade 3–4 neutropenia was observed in 8 patients, and 1 patient experienced febrile neutropenia. There was no toxicity-related death. No complete symptomatic response was observed in 7 evaluable patients; 4 patients had an objective biological response. One patient achieved a morphological objective response, stabilization was observed in 15, but progression occurred in 3 patients. Median survival was 15 months. Conclusion: The above-mentioned combination of LV5FU2 + irinotecan does not yield major activity in heavily pretreated unresectable metastatic gastroenteropancreatic WDEC, and significant toxicity was observed.
Reduced Incidence of Severe Palmar-Plantar Erythrodysesthesia and Mucositis in a Prospective Multicenter Phase II Trial with Pegylated Liposomal Doxorubicin at 40 mg/m2 Every 4 Weeks in Previously Treated Patients with Metastatic Breast Cancer
Authors: Al-Batran Salah-Eddin , Meerpohl Hans-Gerd , von Minckwitz Gunter , Atmaca Akin , Kleeberg Ulrich , Harbeck Nadia , Lerbs Werner , Hecker Detlef , Sehouli Jalid , Knuth Alexander , Jager Elke
Published: May 2006

Purpose: The aim of this study was to assess whether the reduction in the total dose of pegylated liposomal doxorubicin (PLD) per cycle from 50 mg/m2 every 4 weeks to 40 mg/m2 every 4 weeks can effectively lower the incidence of treatment-related palmar-plantar erythrodysesthesia (PPE) and mucositis. Methods: Patients received PLD 40 mg/m2 every 4 weeks, and were evaluated for toxicity prior to each treatment and for response every 8 weeks. Results: All patients were previously treated with at least one chemotherapy regimen for metastatic disease, and 72% of the patients had a prior exposure to an anthracycline. Forty-six evaluable patients received a median of four PLD cycles, with a median dose intensity of 10 mg/m2/week and a median cumulative dose of 160 mg/m2. No National Cancer Institute Common Toxicity Criteria (NCI-CTC) grade 3 or 4 PPE was observed in these patients. NCI-CTC grade 3 or 4 mucositis occurred in 4.3% of patients, only. Response rates and survival results observed here were comparable to those observed with PLD 50 mg/m2 every 4 weeks in a matched patient population. However, patients treated with PLD 40 mg/m2 every 4 weeks experienced less PPE and mucositis and required clearly less dose reductions and treatment delays. Conclusion: The favorable safety profile observed in this study leads us to recommend the use of PLD 40 mg/m2 every 4 weeks for patients with advanced breast cancer.
Sympathectomy Causes Aggravated Lesions and Dedifferentiation in Large Rabbit Atherosclerotic Arteries without Involving Nitric Oxide
Authors: Kacem Kamel , Sercombe Christine , Hammami Mohamed , Vicaut Eric , Sercombe Richard
Published: May 2006

Previously [Histochem J 1997;29:279–286], we found that sympathectomy induced neointima formation in ear but not cerebral arteries of genetically hyperlipidemic rabbits. To clarify the influence of sympathetic nerves in atherosclerosis, and whether their influence involves vascular NO activity, we studied groups of normocholesterolemic intact (NI) and sympathectomized (NS), and hypercholesterolemic intact (HI) and sympathectomized (HS) rabbits (diet/6-hydroxydopamine for 79 days). Segments of basilar (BA) and femoral (FA) arteries were studied histochemically, to evaluate differentiation (anti-desmin, anti-vimentin, anti-h-caldesmon, and nuclear dye), by confocal microscopy, and by in vitro myography. In BAs, staining of NI and NS groups was similar. In hypercholesterolemic groups, a small neointima developed, more frequently in HS segments where smooth muscle cells (SMCs) positive for all antibodies appeared to be migrating into the neointima. In FAs, SMCs stained for the three antibodies in the NI group, but we observed desmin- and h-caldesmon-negative, vimentin-positive cells in some external medial layers of the NS, HI and HS groups, identical to adventitial fibroblasts. Large neointimas of the HS group contained vimentin-positive and largely desmin- and h-caldesmon-negative cells. Relaxation of BA or FA segments to acetylcholine was not decreased by sympathectomy. Sympathectomy increased the contraction of resting FAs to nitro-L-arginine (p = 0.0379). Thus, sympathectomy aggravates the tendency for FA SMCs to migrate and dedifferentiate, increasing atherosclerotic lesions, without decreasing NO activity, but has only minor effects on BAs.
The Prevalence of Endometriosis in Women with Chronic Pelvic Pain
Authors: Guo Sun-Wei , Wang Yuedong
Published: May 2006

Background: The 2004 American College of Obstetrics and Gynecology clinical management guideline states that the prevalence of endometriosis is approximately 33% in women with chronic pelvic pain (CPP). This estimate came from a review showing that 28% of adult women with CPP were found to have endometriosis. The prevalence of 28% in adult women was arrived based on a compilation of 11 published studies. Yet even within the 11 studies, the reported prevalence of endometriosis varies wildly, ranging from 2 to 74%. Such an astounding variation or heterogeneity raises the question whether it is appropriate to use a single prevalence of endometriosis for all women with CPP. Methods: We sought to identify possible sources of heterogeneities in the estimation of prevalence of endometriosis in women with CPP. We included more studies that reported prevalence estimates than the review, and examined the effect of sample size and the year of publication on the heterogeneity. Results: The year of publication is positively associated with the prevalence estimate, which may indicate an increasing awareness of various appearances of endometriosis, or the prevalence of endometriosis may have increased among women with CPP. An alternative analysis with removal of four studies reporting highest prevalence estimates indicated that sample size is negatively associated with the prevalence estimates while the year of publication became only marginally significant. Conclusions: There are identifiable sources of heterogeneity in prevalence estimates, with the year of publication, sample size, and difference in evaluation of CPP being three apparent sources. Having a single prevalence estimate for all women with CPP may be too simplistic at best. The true prevalence is very likely to be higher than 33%.
Highly Active Antiretroviral Therapy-Associated Metabolic Syndrome and Cardiovascular Risk
Authors: Barbaro Giuseppe , Barbarini Giorgio
Published: May 2006

The introduction of highly active antiretroviral therapy (HAART) has significantly modified the course of human immunodeficiency virus (HIV) disease, with longer survival and improved quality of life of HIV-infected subjects. However, HAART regimens, especially those including protease inhibitors, have been shown to cause in a high proportion of HIV-infected patients a metabolic syndrome (lipodystrophy/lipoatrophy, dyslipidemia, type 2 diabetes mellitus, insulin resistance) that may be associated with an increased risk of cardiovascular disease (coronary artery disease and stroke). A careful stratification of the cardiovascular risk and cardiovascular monitoring of patients under HAART is needed according to the most recent clinical guidelines.
Prospective Study of Empiric Monotherapy with Ceftazidime for Low-Risk Grade IV Febrile Neutropenia after Cytotoxic Chemotherapy in Cancer Patients
Authors: Chernobelski Pnina , Lavrenkov Konstantin , Rimar Doron , Riesenberg Klaris , Schlaeffer Francisc , Ariad Samuel , Mermershtain Wilmosh
Published: May 2006

Purpose: It was the aim of this study to evaluate the results of a prospective study in a single medical center using ceftazidime monotherapy in cancer patients with chemotherapy-induced grade IV febrile neutropenia and a low risk for gram-negative bacteremia. Subjects and Methods: Thirty-eight patients were admitted with low-risk grade IV febrile neutropenia after chemotherapy for solid tumors. The median patient age was 57 years (range 18–74). Sixteen patients (42%) developed febrile neutropenia after the first cycle of current chemotherapy line, 9 patients (24%) received 2–3 cycles and 13 patients (34%) received more than 3 chemotherapy cycles before manifesting febrile neutropenia. Five patients were treated with prophylactic granulocyte colony-stimulating factor commenced 24 h after completion of the chemotherapy cycle. Empiric monotherapy with intravenous ceftazidime was started on admission and administered 2 g every 8 h. Results: The mean polymorphic nuclear cell count on admission was 231 cells/mm3. Ceftazidime therapy was well tolerated. Twenty-five (66%) patients responded with clinical improvement and complete resolution of fever within 48 h after initiation of ceftazidime therapy. Thirty-two (84%) patients were afebrile after 72 h of therapy. Thirty-three patients (87%) remained on unmodified ceftazidime therapy throughout their hospitalization. Five patients (13%) subsequently required modification of the treatment regimen for various reasons. Mean duration of fever and neutropenia were 2 (1–10) days and 4 (1–11) days, respectively. None of the patients discontinued therapy because of adverse effects. No positive blood cultures were obtained. No events of septic shock were observed. Mean duration of hospitalization was 6 days (range 3–12). Conclusion: In our series, monotherapy with intravenous ceftazidime appears safe and effective in cancer patients with low-risk grade IV febrile neutropenia after cytotoxic chemotherapy and may appreciably reduce antibiotics costs.
Measuring Heart Rate Variability with Wavelet Thresholds and Energy Components in Healthy Subjects and Patients with Congestive Heart Failure
Authors: Lin Jou-Wei , Hwang Juey-Jen , Lin Liang-Yu , Lin Jiunn-Lee
Published: May 2006

Background: Analysis of wavelet thresholds and energy components can be used to differentiate patients with congestive heart failure (CHF) from healthy subjects and to demonstrate the improvement of heart rate variability after treatment with beta-blockers in the patient group. Methods: Nine patients with CHF without concurrent beta-blocker therapy and 15 healthy volunteers were recruited and received 24-hour Holter recording. Wavelet thresholds and energy components were calculated. The patients with CHF were then treated with atenolol for 3 months. Another Holter recording was repeated and associated wavelet parameters were estimated. Results: Wavelet thresholds were statistically higher in normal subjects than those derived from patients with CHF (62.40 ± 20.65 vs. 16.90 ± 9.72, p < 0.001). The difference was still significant after control of heart rate and the total number of heart beats (74.85 ± 22.68 vs. 32.51 ± 18.73, p < 0.001). The energy component of HRV in the finest wavelet domain was also significantly higher in the normal subjects (243.01 ± 237.69 × 10–6 vs. 40.65 ± 39.65 × 10–6, p = 0.001). These two measures increased after treatment with beta-blockers in the patients with CHF, but not to the extent of those of normal subjects. Conclusion: Analysis of wavelet thresholds and energy components has provided robust and accurate measurements for background HRV.