bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Effect of Recalibration of the Roche Cardiac Troponin T Assay
Authors: Gaze David C. , Collinson Paul O.
Published: December 2005

Objective: To assess the effect of recalibration of the Roche 3rd-generation cTnT assay with recombinant human cardiac troponin T (cTnT) standards on clinical decision limits. Materials and Methods: Serum samples from 77 patients (66 ± 16 years) admitted to the coronary care unit were assayed using the 2nd- and 3rd-generation cTnT assays. Results: There was excellent agreement (r = 0.99 Spearman, 95% CI 0.99–1.0; p ≤ 0.0001, n = 153) between the 2nd- and 3rd-generation cTnT assays across the analytical range, but there was a curvilinear relationship between values. There was concordance between the 2nd- and 3rd-generation cTnT values in the range from 0 to 0.2 µg/l. Above 0.2 µg/l, however, there were increasing but predictable differences. Conclusion: There was no statistical difference between the 2nd- and 3rd-generation cTnT assays, demonstrated by a linear relationship below 0.2 µg/l. This confirms that the 3rd-generation assay was calibrated to that of the 2nd-generation assay in the range of 0–0.2 µg/l. The detection limit and upper reference limit of normal will be unaffected by this change in calibration. A non-linear relationship at higher 2nd-generation concentrations (0.2–25.0 µg/l) was observed. Clinical decision limits up to 0.2 µg/l, associated with increased cardiac risk, are unaffected by the assay calibration, but values greater than 0.2 µg/l are affected.
Methicillin Resistance among Staphylococcus aureus Isolates from Saudi Hospitals
Authors: Asghar Atif H. , Momenah Aiman M.
Published: December 2005

Objective: To determine the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) strains among clinical isolates collected from the 4 tertiary hospitals in Makkah, Saudi Arabia, and to test the antimicrobial susceptibility patterns of S. aureus isolates against 9 antimicrobial agents. Materials and Methods: A total of 512 S. aureus clinical isolates were collected during a period of 1 year starting in April 2003 in Al-Noor, King Abdul-Aziz, Hera and King Faisal Hospitals, Makkah, Saudi Arabia. The sensitivity patterns of these isolates were determined using the Kirby-Bauer disk diffusion method. Results: The prevalence of MRSA among S. aureus isolates was 38.9% (199/512). Among 199 MRSA isolates, 78.8% showed multidrug resistance to erythromycin, gentamicin and oxytetracycline. Conclusion: The rate of MRSA resistance in this study was much higher than what had been reported in other areas of Saudi Arabia emphasizing the need for local or country-based surveillance to characterize and monitor MRSA and to develop strategies that will improve MRSA treatment and control.
Epidemiology of Idiopathic Cardiomyopathy in Qatar during 1996–2003
Authors: El-Menyar Ayman A. , Bener Abdulbari , Numan Mohammed T. , Morcos Salwa , Taha Ruba Y. , Al-Suwaidi Jassim
Published: December 2005

Objectives: To report the rates of cardiomyopathies in the population below 50 years of age in Qatar. Subjects and Methods: We conducted a retrospective review of clinical data on patients with cardiomyopathy who were hospitalized in Hamad General Hospital, Doha. Data were collected from medical records during the 1996–2002 period and prospectively from the patients who were hospitalized during the year 2003. All cardiomyopathy patients below 50 years of age who were citizens or permanent residents in Qatar were included in this study. Results: During the study period, a total of 132 cases were recorded with idiopathic cardiomyopathies. Among these, 67.4% were males and 32.6% females; Qatari 31.8%, non-Qatari 68.2%. The consanguinity rate was high among Qatari patients. In the first 7-year study period, 1996–2002, the incidence rate of all types of cardiomyopathies was 2.5/100,000 population per year (95% CI: 1.4–3.5). It increased to 5.2/100,000 population during the year 2003 (95% CI: 3.6–6.7). Dilated cardiomyopathy was most prevalent (75.8%) in all age groups, and the incidence increased remarkably with age. Lower prevalence of hypertrophic cardiomyopathy (13.6%) and left ventricle noncompaction cardiomyopathy (6.1%) was found. In children below 15 years of age, the incidence rate for all types of cardiomyopathies was 2.7/100,000 population. The overall mortality rate was 5.3%. Conclusion: Most cases of cardiomyopathy were identified at an early age: below 15 years and above 35 years of age. Introducing preventive and early diagnosis programs may have an impact on reducing the mortality and morbidity from idiopathic cardiomyopathy.
Demographic and Clinicopathological Characteristics of Nonalcoholic Fatty Liver Disease in the East-Southeastern Anatolia Regions in Turkey
Authors: Bahcecioglu Ibrahim Halil , Koruk Mehmet , Yilmaz Omer , Bolukbas Cengiz , Bolukbas Fusun , Tuncer Ilyas , Ataseven Huseyin , Yalcin Kendal , Ozercan Ibrahim H.
Published: December 2005

Objective: To identify the demographic and clinicopathological characteristics of patients diagnosed with nonalcoholic fatty liver disease (NAFLD) and the risk factors for fibrosis based on histopathological findings in East-Southeastern Anatolia regions in Turkey. Subjects and Methods: The study included a total of 93 patients diagnosed with NAFLD from 5 different centers. Histopathological findings were evaluated by dividing them into four categories using Matteoni classifications. Cases with fibrosis were further evaluated using Brunt classifications. Results: The patients with a nonalcoholic fatty liver were in the 3rd and 4th decade age groups. The mean age was 38 years, 76% of the patients were male, 85% were overweight, 37% were obese, 18% had type 2 diabetes mellitus, and 80.6% had hyperlipidemia. A multiple regression analysis showed that age, type 2 diabetes mellitus, and aspartate aminotransferase (AST) levels were linked with the severity of the disease. Of the 93 patients, 55 (59.1%) had fibrosis, of which 10.8% were classified as severe. The severity of fibrosis was significantly higher in obese patients. Conclusions: The risk factors for severity of NAFLD included advanced age, type 2 diabetes mellitus and serum AST level, while the risk factor for the severity of fibrosis was obesity.
Ethnic Differences in the Management of Coronary Heart Disease Patients: Lessons to Be Learned in Indo-Asians
Authors: Elahi Maqsood , Chetty Govind , Matata Bashir
Published: December 2005

Objectives: To examine the impact of ethnicity on the outcome of coronary artery bypass grafting (CABG) for myocardial revascularization. Subjects and Methods: We evaluated retrospectively 7,226 Caucasian (CC) and 650 Indo-Asian (IA) patients who underwent isolated first-time CABG surgery over 5 years. The relationship between ethnicity (IA vs. CC) and 30-day mortality, 6-month mortality and complications were analysed. Results: After adjustment for baseline characteristics, IA and CC patients had similar 30-day [IA/CC odds ratio (OR) 1.07; 95% confidence interval (CI) 0.84–1.35; p = 0.59] and 6-month mortality risk (IA/CC OR 1.10; 95% CI 0.91–1.34; p = 0.31). However, IA patients were more likely to experience complications following surgery (OR 1.28; 95% CI 1.14–1.45; p < 0.01). Conclusion: Ethnicity does not appear to be a strong risk factor for adverse outcomes following CABG surgery in the IA patients. However, future studies are needed to elucidate the specific reasons for higher complication rates in IA patients and to devise strategies to reduce complications following the operation for these patients.
Maxillary Canine with Two Root Canals
Authors: Alapati Subbarayudu , Zaatar Essam I. , Shyama Maddi , Al-Zuhair Nohoud
Published: December 2005

Objective and Importance: To report a case of endodontic retreatment of a maxillary right canine in which an extra canal was located and successfully treated. Clinical Presentation and Intervention:A 35-year-old Asian male reported with pain and lingering discomfort in relation to his maxillary right canine after the conventional root canal therapy. Radiographic examination revealed the presence of another undetected and untreated root canal. Therefore, endodontic retreatment was performed and the patient reported complete relief of pain and found to be asymptomatic after a 3-month, 6-month and 1-year recall period. Conclusion:Forsuccessful endodontic therapy, the clinician should be aware of the variations in the root canal morphology. The science of extra canal is important in endodontics as failure to locate and treat an extra canal(s) is one of the common causes for failure of root canal treatments.
Penetrating Cardiac Injury
Authors: Giurgius Magdy , Al Asfar Fahad , Dhar Piyaray M. , Al Awadi Nema
Published: December 2005

Objectives: To report a case of penetrating cardiac injury with patient’s survival. Clinical Presentation and Intervention: A 23-year-old man stabbed with a knife to the epigastric area just below the right costal margin was brought to the Emergency Room, Al-Adan Hospital, Kuwait, in a state of shock. Aggressive resuscitation was performed, chest X-ray showed no evidence of hemo- or pneumothorax. Exploratory laparotomy was performed revealing a severely congested liver, with no intraperitoneal hemorrhage to explain his being in a state of shock. Left thoracotomy revealed pericardial tamponade with perforation in the right ventricle and hemorrhage. A mattress suture was used to control bleeding from the right ventricle. Postoperative echography revealed a tear in the interventricular septum and papillary muscle. Open-heart surgery was performed to repair the injured tissues. The patient made an uneventful recovery. Conclusion: This report shows that patients with penetrating cardiac injuries and detectable vital signs on arrival at the hospital can be salvaged by prompt surgical intervention.
Development of Two Cancers in the Same Patient after Ileorectal and Ileal Pouch Anal Anastomosis for Familial Adenomatous Polyposis
Authors: Ulaş Murat , Neşşar Gürel , Bostanoğlu Akın , Aydoğ Gülden , Kayaalp Cüneyt , Özoğul Yusuf , Seven Canbek
Published: December 2005

Objective: To report a case of a patient with familial adenomatous polyposis. Clinical Presentation and Intervention: A 36-year-old male patient who suffered from rectal bleeding was treated with colectomy and ileorectal anastomosis for familial adenomatous polyposis (FAP) in 1974. After 19 years, in situ adenocarcinoma was detected in the rectal stump. Completion proctectomy, mucosectomy, and hand-sewn ileal pouch anal anastomosis with protective ileostomy were performed. In 2002, a metachronous cancer was detected at the anastomosis and abdominoperineal resection of the pouch and end ileostomy were performed. Later on, the perineum was excised locally because of cancer recurrence. Conclusion: This case shows that lifetime surveillance of the FAP patients after surgery is crucial.
Safety of Bone Marrow Stem Cell Mobilization Induced by Granulocyte-Colony Stimulating Factor: 30 Days’ Blinded Clinical Results from the Stem Cells in Myocardial Infarction (STEMMI) Trial
Authors: Ripa Rasmus Sejersten , Wang Yongzhong , Jørgensen Erik , Johnsen Hans E. , Grande Peer , Kastrup Jens
Published: December 2005

Background: Mobilization of circulating stem cells from the bone marrow with granulocyte-colony stimulating factor (G-CSF) might promote the repair of myocardial damage after ST-elevation myocardial infarction. However, concern has been raised about the safety of G-CSF. Objective: To determine the short-term (30 days) safety of G-CSF therapy after an ST-elevation myocardial infarction treated with acute percutaneous coronary intervention (PCI). Methods: Patients with an ST-elevation myocardial infarction (treated with PCI <12 h after symptom onset) were enrolled in the STEMMI trial and randomized to G-CSF (10 µg/kg/day) or placebo for 6 days in a double-blind design. Clinical follow-up for this report was done after 1 month. The treatment allocation remains blinded and long-term follow-up is ongoing. Results: Seventy-eight patients (age 56 ± 8.4 years, 80% males, maximal creatine kinase MB 307 ± 193 µg/l) were included. G-CSF treatment was initiated 1 day (range 0–2) after PCI. Three (4%) patients suffered major adverse cardiac events in the first 30 days (1 died in progressive shock, 1 had a subacute stent thrombosis, and 1 developed significant mitral valve regurgitation). No patients had symptoms of early aggressive restenosis, and there were no cases of unstable angina or re-infarction. Eleven patients had minor musculoskeletal pain during the G-CSF treatment period. Conclusion: In this relatively small population of patients there were few major adverse cardiac events and G-CSF treatment after ST-elevation myocardial infarction seemed safe in the short (30 days) term. Further studies of long-term safety will clarify the future role of G-CSF treatment in this setting.
Rationale and Design of the OACIS-LIPID Study That Evaluates Early Use of Pravastatin in Acute Myocardial Infarction
Authors: Sakata Yasuhiko , Sato Hiroshi , Kinjo Kunihiro , Fujii Kenshi , Kodama Kazuhisa , Tanouchi Jun , Mishima Masayoshi , Kusuoka Hideo , Nakatani Daisaku , Mizuno Hiroya , Shimizu Masahiko , Hori Masatsugu
Published: December 2005

We conduct a prospective randomized study, the OACIS-LIPID, to determine whether early use of pravastatin can prevent secondary cardiac events in patients with acute myocardial infarction (AMI) and hyperlipidemia (HL). Three hundred and fifty Japanese patients with AMI and mild to moderate HL are randomly assigned to receive or not to receive pravastatin in an open-labeled fashion. The primary dose of pravastatin is 10 mg per day, which is a standard dose for the Japanese population. Both groups receive dietary counseling. Over a 9-month follow-up period, the combination of the endpoints (death, nonfetal myocardial infarction, unstable angina, noncardiac rehospitalization, revascularization and nonfetal stroke) will be evaluated. The results of the OACIS-LIPID study will determine the utility of a practical dose of hydroxymethylglutaryl coenzyme A reductase as an early intervention in AMI.
Hyperlipemia and Oxidation of LDL Induce Vascular Smooth Muscle Cell Growth: An Effect Mediated by the HLH Factor Id3
Authors: Taylor Angela M. , Li Feng , Thimmalapura Pushpa , Gerrity Ross G. , Sarembock Ian J. , Forrest Scott , Rutherford Sarah , McNamara Coleen A.
Published: December 2005

Hyperlipemia and oxidized LDL (ox-LDL) are important independent cardiovascular risk factors. Ox-LDL has been shown to stimulate vascular smooth muscle cell (VSMC) proliferation. However, the effects of hyperlipemia and the molecular mechanisms mediating hyperlipemia and ox-LDL effects on VSMC growth are poorly understood. The helix-loop-helix (HLH) transcription factor, Id3, is a redox-sensitive gene expressed in VSMC in response to mitogen stimulation and vascular injury. Accordingly, we hypothesize that Id3 is an important mediator of ox-LDL and hyperlipemia-induced VSMC growth. Aortas harvested from hyperlipemic pigs demonstrated significantly more Id3 than normolipemic controls. Primary VSMC were stimulated with ox-LDL, native LDL, sera from hyperlipemic pigs, or normolipemic pigs. VSMC exposed to hyperlipemic sera demonstrated increased Id3 expression, VSMC growth and S-phase entry and decreased p21cip1 expression and transcription. Cells stimulated with ox-LDL demonstrated similar findings of increased growth and Id3 expression and decreased p21cip1 expression. Moreover, the effects of ox-LDL on growth were abolished in cells devoid of the Id3 gene. Results provide evidence that the HLH factor Id3 mediates the mitogenic effect of hyperlipemic sera and ox-LDL in VSMC via inhibition of p21cip1 expression, subsequently increasing DNA synthesis and proliferation.
Endothelial Urocortin Has Potent Antioxidative Properties and Is Upregulated by Inflammatory Cytokines and Pitavastatin
Authors: Honjo Tomoyuki , Inoue Nobutaka , Shiraki Rio , Kobayashi Seiichi , Otsui Kazunori , Takahashi Motonori , Hirata Ken-ichi , Kawashima Seinosuke , Yokozaki Hiroshi , Yokoyama Mitsuhiro
Published: December 2005

Background: Urocortin, a neuropeptide discovered in the midbrain, is a member of the corticotropin-releasing factor family and is expressed in heart tissues. Urocortin exerts potent cardioprotective effects under various pathological conditions including ischemia/reperfusion. However, the regulation and function of vascular urocortin are unknown. Methods and Results: Immunohistochemistry showed definitive expression of urocortin in endothelial cells of coronary large arteries and microvessels from autopsied hearts. RT-PCR confirmed the expression of urocortin in human umbilical vein endothelial cells (HUVECs). Urocortin (10–8M) potently suppressed the generation of angiotensin II-induced reactive oxygen species (ROS) in HUVECs. Tumor necrosis factor-α and interferon-γ increased the urocortin mRNA levels and its release from HUVECs. Incubation with pitavastatin (0.1–3.0 µM) significantly increased the urocortin mRNA levels and its release from HUVECs. Furthermore, treatment with pitavastatin (2 mg/day) for 4 weeks increased the serum urocortin level from 11.0 ± 6.5 to 16.4 ± 7.3 ng/ml in healthy volunteers. Conclusion: Endothelial urocortin was upregulated by inflammatory cytokines and pitavastatin and suppressed ROS production in endothelial cells. Treatment with pitavastatin increased the serum urocortin level in human subjects. Thus, endothelial urocortin might protect cardiomyocytes in inflammatory lesions. Urocortin might partly explain the mechanisms of various pleiotropic effects of statins.
Therapeutics in Renal Disease: The Road Ahead for Antiproliferative Targets
Authors: Nelson Peter J. , Shankland Stuart J.
Published: December 2005

Discovery into the molecular basis of renal disease is occurring at an unprecedented rate. With the advent of the NIH Roadmap, there is a greater expectation of translating this knowledge into new treatments. Here, we review the therapeutic strategy to preserve renal function in proliferative renal diseases by directly inhibiting the mitogenic pathways within renal parenchymal cells that promote G₀ to G1/S cell-cycle phase progression. Reductionist methodologies have identified several antiproliferative molecular targets, and promising preclinical testing of leading small-molecule drugs to modulate these targets has now led to landmark clinical trials. Yet, this advancement into targeted therapy highlights important differences between the therapeutic goals of molecular nephrology versus molecular oncology and, by extension, the poorly understood role of alternative target activity in drug efficacy. Systems research to clarify these issues should accelerate the development of this promising therapeutic strategy.
The Frequency and Determinants of Calcification in Intracranial Arteries in Chinese Patients Who Underwent Computed Tomography Examinations
Authors: Chen Xiang-yan , Lam Wynnie W.M. , Ng Ho Keung , Fan Yu-hua , Wong Ka Sing
Published: December 2005

Background: Intracranial artery calcification is common but the prevalence and determinants are not well established. We aim to describe the prevalence and location of calcification in intracranial arteries according to brain multi-detector-row computed tomography (MDCT) images, and to investigate its correlation with potential risk factors. Methods: We studied consecutive men and women referred for brain CT in December 2004. All patients received a questionnaire regarding their medical history related to atherosclerosis, including traditional risk factors of atherosclerosis, serum chemistry values and inflammatory markers. All CT examinations were done with a 16-slice MDCT and the severity of intracranial artery calcification was categorized. Results: Four hundred and ninety patients aged 1.4–101 years (62.92 ± 19.04; mean ± SD) were included in our study. There were 340 patients (69.4%) who had intracranial artery calcification. The highest prevalence of intracranial artery calcification was seen in the internal carotid artery (60%), followed by vertebral artery (20%), middle cerebral artery (5%) and basilar artery (5%). Patients with calcification were significantly older than those without calcification (p < 0.001). A significantly higher prevalence of calcification was present among patients with hypertension (p < 0.001), diabetes (p < 0.001), renal failure (p < 0.05), atrial fibrillation (p < 0.05), smoking (p < 0.05), hyperlipidemia (p < 0.001), ischemic heart disease (p < 0.05) and ischemic stroke (p < 0.001). Mean values of serum phosphate, serum urea and CRP level were also significantly higher in patients with intracranial artery calcification (p < 0.05, respectively), and there was a trend that patients with intracranial calcification had a higher white blood cell count (p = 0.070). Stepwise multiple logistic regression showed age (RR = 2.795 per 10 years), a history of ischemic stroke (RR = 3.915), and white blood cell count (RR = 1.107) to be independently associated with intracranial artery calcification. Conclusions: Calcification of the intracranial arteries is associated with age, history of ischemic stroke and white blood cell count. Further prospective studies to investigate the clinical significance of intracranial artery calcification are needed.
Dipyridamole Decreases Protease-Activated Receptor and Annexin-V Binding on Platelets of Poststroke Patients with Aspirin Nonresponsiveness
Authors: Serebruany Victor , Malinin Alex , Ziai Wendy , Atar Dan , Pokov Alex , Jilma Bernd , Hanley Dan
Published: December 2005

Background: Although controversial, the phenomenon of aspirin resistance (AR) has been correlated in some small studies with poor clinical outcomes in patients with coronary artery disease. Even less is known regarding the role of AR in the poststroke population. The reason for and the underlying mechanism of AR is unknown. We hypothesized that excessive formation of thrombin on the platelet surface may contribute to this phenomenon and assessed how dipyridamole affects multiple platelet and thrombin generation biomarkers in AR patients after ischemic stroke. Methods: Whole blood samples from 20 poststroke AR patients were pretreated with dipyridamole, simulating the therapeutic range, and then incubated for 45 min at 37°C. Platelet characteristics were assessed by aggregometry, cartridge-based analyzer, and receptor expression by flow cytometry. Markers of thrombin generation were measured in the autologous plasma by ELISA. Results: Pretreatment of blood with dipyridamole resulted in 22–26% diminished expression of intact PAR-1 receptor (p = 0.021 and p = 0.024) and 28–31% decrease of annexin V binding (p = 0.031 and p = 0.02) after incubation with 2 µg/ml and 4 µg/ml of dipyridamole, respectively. Platelet aggregation and thrombin generation markers were not affected in vitro by dipyridamole. Conclusions: Dipyridamole may be capable of overcoming increased prothrombinase complex formation and be in part able to compensate for AR in patients with moderate carotid stenosis. This phenomenon may explain the clinical advantages of Aggrenox®, known to reduce ischemic events in poststroke patients as proven in clinical trials, though an additional antithrombotic benefit beyond the platelet inhibition by aspirin alone.
Effect of the Glycine Antagonist Gavestinel on Cerebral Infarcts in Acute Stroke Patients, a Randomized Placebo-Controlled Trial: The GAIN MRI Substudy
Authors: Warach Steven , Kaufman David , Chiu David , Devlin Thomas , Luby Marie , Rashid Ajaz , Clayton Linda , Kaste Markku , Lees Kennedy R. , Sacco Ralph , Fisher Marc
Published: December 2005

Background and Purpose: Gavestinel, GV150526, is a selective antagonist at the glycine site of the N-methyl-D-aspartate receptor. The safety and efficacy of GV150526 were studied in two phase III randomized placebo-controlled clinical trials of acute ischemic stroke patients within 6 h from onset [The Glycine Antagonist in Neuroprotection (GAIN) International and GAIN Americas Trials]. A planned MRI substudy within these trials investigated the effect of gavestinel on infarct volume. Methods: Patients enrolled in the GAIN trials at designated MRI substudy sites were eligible if they had a pretreatment acute cortical lesion on diffusion-weighted MRI of at least 1.5 cm diameter or 5 cm3. Final lesion assessment was performed on T2-weighted MRI at month 3. Blinded image analysis was performed centrally. The primary hypothesis was that gavestinel would attenuate lesion growth from baseline relative to placebo. Results: A total of 106 patients were eligible, 75 (34 gavestinel, 41 placebo) of whom had month 3 scans (primary analysis population). No effects of gavestinel on infarct volume were observed in the primary or other analyses. However, significant associations of lesion volume to clinical severity and outcomes were observed. Ischemic lesion volume decrease was predictive of substantial clinical improvement. Conclusion: Consistent with the clinical outcomes in the GAIN trials, no effects of gavestinel on ischemic infarction was observed. Concordance of results of the clinical outcome trials with those of this infarct volume substudy as well the associations of infarct volume to clinical outcomes further support the potential role of infarct volume as a marker of outcome in dose finding and proof of principle acute stroke trials.
Correlation of Coronary and Cerebral Atherosclerosis: Difference between Extracranial and Intracranial Arteries
Authors: Bae Hee-Joon , Yoon Byung-Woo , Kang Dong-Wha , Koo Ja-Seong , Lee Seung-Hoon , Kim Ki-Bong , Lee Juneyoung , Roh Jae-Kyu
Published: December 2005

Background: A difference with regard to the correlation with coronary atherosclerosis (CAS) between extracranial carotid atherosclerosis (ECAS) and intracranial cerebral atherosclerosis (ICAS) has been assumed but not proven clearly by direct comparison within the same population. Methods: A consecutive series of 246 patients undergoing coronary artery bypass graft surgery were reviewed. The severity of CAS was estimated as a CAS score based on coronary angiography. The presence of ECAS and ICAS was screened by transcranial Doppler and carotid duplex sonography, and confirmed by magnetic resonance angiography. Results: The CAS scores in patients with ECAS were observed to be higher than those in patients without ECAS (10.62 ± 4.80 vs. 9.45 ± 4.25; p = 0.054 on the Mann-Whitney U test). The difference in CAS scores was smaller between patients with and without ICAS (10.41 ± 4.44 vs. 9.66 ± 4.49; p = 0.201). Similar patterns were observed on comparing the correlation of ECAS and ICAS with a quartile of the CAS score. An advanced CAS, which was generated by collapsing the quartiles of the CAS score into 75th percentile or less and more than the 75th percentile, was significantly associated with ECAS, but not with ICAS. These associations remained unchanged after adjustments had been made for age, sex, hypertension, diabetes mellitus, hyperlipidemia, smoking and a history of stroke or transient ischemic attack. Conclusions: This study suggests that the correlation of CAS with ECAS is stronger than that of CAS with ICAS, and this difference is independent of the classic risk factors for atherosclerosis.
Diazepam to Improve Acute Stroke Outcome: Results of the Early GABA-Ergic Activation Study In Stroke Trial
Authors: Lodder J. , van Raak L. , Hilton A. , Hardy E. , Kessels A.
Published: December 2005

Background: We tested whether diazepam, a GABA-ergic drug that also inhibits brain nitric monoxide formation, improves acute stroke prognosis. Methods: 880 patients, randomized within 12 h of acute stroke, received diazepam 10 mg or placebo by rectiole, as soon as possible, followed by 10-mg tablets twice daily for 3 days. Primary outcome was independence (Rankin score <3) at 3 months; secondary outcome was complete recovery (Barthel index ≧95 or Rankin score ≤1). Results: Intention-to-treat analyses on all 849 patients with full follow-up (50.4% on diazepam): odds ratio (OR) 1.14, 95% CI 0.87–1.49 for primary endpoint, and an OR of 1.26 (0.90–1.76) for complete recovery, both favoring diazepam. Adjusted analyses for all stroke patients (843): OR 1.20 (0.87–1.65), and 1.25 (0.89–1.74), respectively, and for all infarct patients (748): OR 1.31 (0.93–1.85), and 1.46 (1.02–2.09; p = 0.037), respectively. Analyses restricted to cardioembolic infarct patients (200) showed treatment benefit for the primary outcome: OR 2.26, 95% CI 1.07–4.76, p = 0.032, and complete recovery: OR 2.65, 95% CI 1.06–6.59, p = 0.037. About one third of ischemic stroke patients had ‘any adverse event’, without any difference between treatment groups. In 95 intracerebral hemorrhage patients, frequency of pneumonia and death were higher in the diazepam group than in the placebo group: 35 and 10%, 22 and 12%, respectively. Conclusions: Although point estimates favored diazepam treatment in various analyses, our data did not confirm our primary hypothesis. Diazepam treatment seems beneficial in cardioembolic infarct patients, is safe in acute ischemic stroke, but may better be avoided in intracerebral hemorrhage.
Thai Stroke Patient Caregivers: Who They Are and What They Need
Authors: Jullamate Pornchai , de Azeredo Zaida , Pául Constança , Subgranon Rachaneeporn
Published: December 2005

Background and Purposes: Primary informal caregivers play a significant role in providing care to stroke survivors after having been discharged from the hospital. Our aims were to describe the characteristics of Thai stroke caregivers and to explore their needs while providing care to their stroke relatives. Methods: Using open-ended questions, we individually interviewed 20 caregivers of stroke survivors to identify their characteristics and their own needs. Additional field notes were made during all interviews. Results: Our findings revealed that the majority of Thai informal stroke caregivers in this study were female, mostly daughters, with the exception of 2 Thai primary stroke caregivers found to be nieces. The majority of caregivers provided care to their stroke relatives 24 h per day. The four major categories of informal rehabilitation were: physical, psychological, social, and spiritual rehabilitation activities. Assistance, information and social support were the three main needs of the caregivers. Conclusion: Based on these findings, appropriate nursing information and assistance focusing on rehabilitation and stroke caregivers’ needs should be provided to Thai stroke caregivers performing informal care to ensure that both patients and caregivers have the best possible quality of life.
Comparative Study of Antibiotic-Containing Polymethylmetacrylate Capsules and Beads
Authors: Börzsei László , Mintál Tibor , Horváth Aranka , Koós Zoltán , Kocsis Béla , Nyárády József
Published: December 2005

Background: This study aimed at making local antibiotic therapy wider in cases of chronic suppurations by administering antibiotics which previously could not be given in this way through the conventional polymethylmetacrylate (PMMA) carrier techniques. Capsules from this material were produced with a pressing machine designed and laid out by us. The characteristics of antibiotic penetration from this novel carrier were compared to those of PMMA beads. Methods: The time-dependent outflow of amikacin, clindamycin, pefloxacin, piperacillin + tazobactam, amoxicillin + clavulanic acid and cefotaxime was examined from the capsules and the beads with standard microbiological techniques using the Micrococcus luteus ATCC9341 test strain. The diameter of the inhibitory zones was measured after 24 h incubation at 37°C and converted to µg/ml antibiotic concentrations. Results and Conclusions: Our results revealed that all antibiotics showed longer-lasting and higher concentration outflow from the PMMA capsules than from the beads. Therefore, these capsules can provide a more promising new opportunity for specific local antimicrobial treatment in cases of chronic suppurative bone and soft tissue injuries. In these cases the polymerization has already been completed and the heat does not influence the structure of the antibiotics; therefore, it can be inserted into the capsules in powder or solution form.
Comparative Randomized Pilot Study of Azithromycin and Doxycycline Efficacy and Tolerability in the Treatment of Prostate Infection Caused by Ureaplasma urealyticum
Authors: Škerk Višnja , Mareković Ivana , Markovinović Leo , Begovac Josip , Škerk Vedrana , Baršić Neven , Majdak-Gluhinić Vida
Published: December 2005

A total of 1,442 patients with symptoms of chronic prostatitis were examined over a 4-year period at the Outpatient Department for Urogenital Infections, University Hospital for Infectious Diseases Dr. Fran Mihaljević, Zagreb, Croatia. The inclusion criteria for chronic prostatitis caused by Ureaplasma urealyticum were the presence of clinical symptoms, presence of U. urealyticum in expressed prostatic secretion (EPS) or voided urine collected immediately after prostatic massage (VB3), absence of U. urealyticum in urethral swabs and absence of other possible pathogens of chronic prostatitis in EPS or VB3. A total of 63 patients with prostate infection caused by U. urealyticum were available for this pilot study. The patients were randomized according to a computer randomization list to receive a total dose of 4.5 g of azithromycin given as a 3-day therapy of 1 × 500 mg weekly for 3 weeks or doxycyline 100 mg b.i.d. for 21 days. Patients’ sexual partners were treated at the same time. Clinical efficacy and tolerability of the administered drug as well as possible adverse events were evaluated during, at the end and 4–6 weeks after completion of therapy. Bacteriological efficacy was evaluated 4–6 weeks after completion of therapy. Treatment groups did not differ regarding age, distribution of urethral, prostatic, sexual and other symptoms, or digitorectal prostatic examination. Five patients treated with doxycycline had nausea. In the group of patients with prostate infection caused by U. urealyticum, the eradication rate was not significantly different with regard to the administered azithromycin (25/32) or doxycycline (23/31). Clinical cure did not significantly differ with regard to the administered azithromycin (22/32) or doxycycline (21/31).
Long-Term Remission in a Patient with Carcinoma of Unknown Primary Site
Authors: Jentsch-Ullrich K. , Kalinski T. , Roessner A. , Franke A. , Mohren M.
Published: December 2005

Background: Cancer of unknown primary site also designated as CUP syndrome usually presents as metastatic disease with a poor prognosis and low remission as well as survival rates. Case: We report a 46-year-old male with para-aortal and left-sided cervical lymph node metastases. Histological examination of a cervical lymph node revealed papillary carcinoma. Despite thorough investigation, no primary tumor was found. The patient was empirically treated with six courses of the FACP regimen (5-fluorouracil, Adriamycin, cyclophosphamide and cisplatin) combined with radiotherapy (40 Gy) and has remained in complete remission for 124 months. Conclusion: This case indicates that treatment of a patient with cancer of unknown primary site may be rewarded by a benign course. However, complete cure remains a very rare event in CUP. Remission can be achieved with a platinum-containing regimen combined with radiotherapy.
What Is the Best Sequence of Chemotherapy in Advanced Colorectal Cancer? Final Results of a Five-Arm Study
Authors: Popov Ivan , Jelic Svetislav , Krivokapic Zoran , Micev Marjan , Babic Dragana , Zdrale Zdravko
Published: December 2005

One hundred and ninety-three patients were assigned to receive 5-FU/LV, irinotecan and oxaliplatin in five different sequential treatment groups: Mayo Clinic Regimen (MCR) + LV5FU2 (group A); MCR + irinotecan (350 mg/m2) (group B); MCR + FOLFIRI (group C); MCR + FOLFOX4 (group D); FOLFIRI + FOLFOX4 (group E). The results were as follows: group A (32 patients), median overall survival (OS) 14 months, median time to progression (TTP1) 6 months, median TTP2 5 months, response rate (RR1) 22%, RR2 25%; group B (27 patients), OS 11 months, TTP1 6 months, TTP2 3 months, RR1 22%, RR2 19%; group C (43 patients), OS 14 months, TTP1 5 months, TTP2 5 months, RR1 12%, RR2 19%; group D (45 patients), OS 15 months, TTP1 5 months, TTP2 4 months, RR1 18%, RR2 20%; group E (46 patients), OS 19 months, TTP1 9 months, TTP2 5 months, RR1 39%, RR2 25%. There was a significant difference in OS (p < 0.005) between groups E vs. B and A, D vs. B. Sequential therapy with 3 active drugs (FOLFIRI + FOLFOX4) was the most efficacious combination in comparison with any other two drug combinations applied in our study.
Synergistic Inhibitory Effects of Curcumin and 5-Fluorouracil on the Growth of the Human Colon Cancer Cell Line HT-29
Authors: Du Boyu , Jiang Liping , Xia Quan , Zhong Laifu
Published: December 2005

The synergistic effect of combination treatment with COX-2 inhibitors and chemotherapy may be another promising therapy regimen in the future treatment of colorectal cancer. Curcumin, a major yellow pigment in turmeric which is used widely allover the world, inhibits the growth of human colon cancer cell line HT-29 significantly and specifically inhibits the expression of COX-2 protein. However, the worldwide exposure of populations to curcumin raised the question of whether this agent would enhance or inhibit the effects of chemotherapy. In this report, we evaluated the growth-inhibitory effect of curcumin and a traditional chemotherapy agent, 5-FU, against the proliferation of a human colon cancer cell line (HT-29). The combination effect was quantitatively determined using the method of median-effect principle and the combination index. The inhibition of COX-2 expression after treatment with the curcumin-5-FU combination was also evaluated by Western blot analysis. The IC50 value in the HT-29 cells for curcumin was 15.9 ± 1.96 µM and for 5-FU it was 17.3 ± 1.85 µM. When curcumin and 5-FU were used concurrently, synergistic inhibition of growth was quantitatively demonstrated. The level of COX-2 protein expression was reduced almost 6-fold after the combination treatment. Our results demonstrate synergism between curcumin and 5-FU at higher doses against the human colon cancer cell line HT-29. This synergism was associated with the decreased expression of COX-2 protein.
Comparison of Efficacy of Oral Valacyclovir and Topical Acyclovir in the Treatment of Herpes Simplex Keratitis: A Randomized Clinical Trial
Authors: Sozen Engin , Avunduk Avni Murat , Akyol Nurettin
Published: December 2005

Thirty eyes of 28 patients with herpetic disease were included in the study. Group 1 patients (15 eyes of 15 subjects) received topical acyclovir (ACV) ointment. Oral valacyclovir (VACV) was prescribed to group 2 (15 eyes of 13 patients). The anterior segment of each eye was carefully examined by slit lamp and scored. Each patient was also instructed to grade his/her subjective symptoms. The corneal lesion healed significantly faster in the group 2 eyes compared to the group 1 eyes. Photophobia score on day 3 and slit-lamp score on day 10 were at significantly lower levels in group 2 compared to group 1. In herpetic keratitis, oral VACV can be a good alternative to ACV ointment therapy.
A Mathematical Model for Capillary Formation and Development in Tumor Angiogenesis: A Review
Authors: Pamuk Serdal
Published: December 2005

Background: Angiogenesis is a morphogenic process whereby new blood vessels are induced to grow out of a preexisting vasculature. Endothelial cells (EC) form the lining of all blood vessels. Following tumor angiogenic growth factors, EC in neighboring normal capillaries are activated to secrete proteases. These then degrade the basal lamina and permit the EC to migrate into the extracellular matrix. Methods: We use mechanisms to produce protease, inhibitors, and fibronectin. Results: This article reviews a mathematical model originally presented by Levine et al. [Bull Math Biol 2001;63:801–863] and some results of Pamuk [Math Models Methods Appl Sci 2003;13/1:19–33; Math Biosci 2004;189/1:21–38]. Conclusions: We obtained a very good computational agreement with the rabbit cornea experiments of Folkman [Sci Am 1976;234:58–64]. We also introduce angiostatin to the model for therapeutic case as studied by Ulukaya et al. [Chemotherapy 2004;50/1:43–50].
Synergistic in vitro Interactions between (22S,23S)-3β-Bromo-5α,22,23-Trihydroxystigmastan-6-one and Acyclovir or Foscarnet against Herpes simplex Virus Type 1
Authors: Talarico Laura B. , Castilla Viviana , Ramirez Javier A. , Galagovsky Lydia R. , Wachsman Mónica B.
Published: December 2005

The replication of herpes simplex virus (HSV) type 1 in Vero cells is inhibited in the presence of (22S,23S)-3β-bromo-5α,22,23-trihydroxystigmastan-6-one (6b), a synthetic brassinosteroid derivative. Since a late step of virus multiplication is hindered by 6b, we performed studies of drug-drug combination with acyclovir (ACV) and foscarnet (FOS). It was determined that 6b would act synergistically with low concentrations of ACV and moderate concentrations of FOS against HSV. The best drug combination tested in this study resulted in an increase of 29.3 and 47.2% in antiviral activity for ACV (0.036 µM) and FOS (37.5 µM) in the presence of 14.8 and 6.9 µM of 6b, respectively.
Thyroid Tuberculosis: Diagnosis and Treatment
Authors: El Malki H.O. , Mohsine R. , Benkhraba K. , Amahzoune M. , Benkabbou A. , El Absi M. , Ifrine L. , Belkouchi A. , Balafrej S.
Published: December 2005

Objective: It was the aim of this study to report clinical characteristics and treatment of thyroid tuberculosis (TT). Methods: During 16 years, 2,426 patients have been operated on the thyroid in the surgical department ‘A’ in Ibn Sina Hospital, Rabat, Morocco. Anatomopathological results of the removed thyroid were analyzed for evidence of tuberculosis. Results: Eight cases of TT were diagnosed. Five patients had a goiter and 3 patients had an isolated nodule of the thyroid. In one case, fine-needle aspiration cytology gave the diagnosis of TT. This patient had a complete drainage of the abscess. In all other patients, the diagnosis was given after surgery. All patients received additional antituberculous drugs for 6 months, and follow-up was satisfactory. Conclusion: TT does not have any consistent symptoms. Fine-needle aspiration is the best method for diagnosis and can result in the avoidance of surgery.
Chloroquine Accumulation by Purified Plasma Membranes from Plasmodium falciparum
Authors: Elandaloussi Laurence M. , Smith Peter J.
Published: December 2005

Resistance of Plasmodium falciparum to chloroquine (CQ) has been associated with a decrease in CQ accumulation by parasitized erythrocytes. This study aimed at investigating the role of parasite plasma membranes (PPM) in the mechanism of CQ accumulation. CQ accumulation capabilities of membranes were determined using tritiated CQ. PPM isolated from chloroquine-sensitive parasites were found to accumulate less CQ than those isolated from chloroquine-resistant parasites. However, CQ accumulation was found to be ATP-independent suggesting that this accumulation results from binding rather than transport.
Megakaryocytic cells synthesize and platelets secrete α5-laminins, and the endothelial laminin isoform laminin 10 (α5β1γ1) strongly promotes adhesion but not activation of platelets
Authors: Nigatu Ayele , Sime Wondossen , Gorfu Gezahegn , Geberhiwot Tarekegn , Andurén Ingegerd , Ingerpuu Sulev , Doi Masayuki , Tryggvason Karl , Hjemdahl Paul , Patarroyo Manuel
Published: December 2005

Following vascular injury, basement membrane (BM) components of the blood vessels are exposed to circulating cells and may contribute to hemostasis and/or thrombosis. Laminins 8 (LN-8) (α4β1γ1) and 10 (LN-10) (α5β1γ1) are major laminin isoforms of the endothelial BM, and LN-8 is also secreted by activated platelets. In the present study, we demonstrate synthesis of α5-laminins LN-10 and LN-11 (α5β2γ1) by megakaryocytic cells, and intracellular expression of these laminin isoforms in blood platelets. In contrast to platelet LNα4 chain that had an apparent molecular weight of 180 kDa and associated mostly to LNβ1 chain, platelet LNα5 consisted of 300/350 kDa polypeptides and associated mainly to LNβ2. Both α4– and α5-laminins were secreted by platelets following stimulation. When compared to recombinant human (rh) LN-8, rhLN-10 was much more adhesive to platelets, though adhesion to both proteins was largely mediated via α6β1 integrin. In spite of their adhesive properties, rhLN-8 and rhLN-10 induced neither P-selectin expression nor cell aggregation, two signs of platelet activation. This study demonstrates synthesis/expression of heterotrimeric α5-laminins in hematopoietic/blood cells, and provides evidence for the adhesive, but not activating, role of endothelial laminin isoforms in platelet biology.
Circulating platelet-derived microparticles in systemic lupus erythematosus
Authors: Alfaro Gino , Goycoolea Manuela , Quiroga Teresa , Ocqueteau Mauricio , Massardo Loreto , Pérez Carol , Sáez Claudia , Panes Olga , Matus Valeria , Mezzano Diego , Pereira Jaime
Published: December 2005

The risk for thrombosis is significantly increased in systemic lupus erythematosus (SLE), affecting both venous and arterial vessels. Activated platelets are known to participate in thrombus formation and growth. A general feature of activated cells is the shedding of microparticles (MP) which support coagulation by exposure of negatively charged phospholipids and possibly tissue factor (TF). In this work we characterized circulating MP in patients with SLE and their relationship with a procoagulant state. Thirty patients with SLE (aged 15–72 years, mean age 38 years) and 20 healthy controls (aged 22–54 years, mean age 34 years) were studied; patients fulfilled 4 revised criteria for SLE. The number and cellular source of circulating MP were determined by flow cytometry using double labeling with specific monoclonal antibodies and annexin V. Thrombin generation was measured as the endogenous thrombin potential (ETP) without the addition of exogenous phospholipids and TF; under these conditions the generation of thrombin depended directly on the number of MP present in plasma. Thrombin anti-thrombin (TAT) and plasmin-antiplasmin (PAP) complexes were measured by ELISA. Compared to the controls, circulating MP were significantly elevated in the patient group (1218 ± 136 vs 653 ± 74 x103/ml plasma, p: 0.0007). In both groups, most of these MP were of platelet origin (927± 131 vs 517 ± 72 x103/ml plasma, p:0.009 ). ETP was higher among patients as compared to the controls (804± 64 vs 631 ± 37 nM thrombin, p: 0.025). Plasma levels of TAT in patients and controls were 3.4 ± 0.8 and 1.4 ± 0.5 µg/L, respectively (p:0.04), and of PAP complexes were 62.5 ± 14 and 24.05± 2.5 µg/ml, respectively (p: 0.014).The number of platelet-derived MP correlated significantly with thrombin generation (r: 0.42; p: 0.038) and TAT levels (r: 0.40; p: 0.035).We did not find an association of circulating MP with disease activity nor with the presence of antiphospholipid antibodies. The increased number of circulating platelet-derived microparticles and their association with high ETP and activation of the coagulation system suggest that these microparticles play an important role in the pathogenesis of the prothrombotic state in SLE patients.