bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment of Idiopathic Pyoderma Gangrenosum with Infliximab: Induction Dosing Regimen or On-Demand Therapy?
Authors: Adışen Esra , Öztaş Murat , Gürer Mehmet Ali
Published: January 2008

Pyoderma gangrenosum is an ulcerative skin disease of unknown origin. Recently tumor necrosis factor α inhibitors have been gaining attention in the treatment of recalcitrant pyoderma gangrenosum. However, there is a lack of an optimal dosing strategy in the published literature about the treatment of idiopathic pyoderma gangrenosum, and this is responsible for substantially different treatment strategies. Therefore, it is necessary to report experiences in this patient population in order to develop an optimal dosing strategy and to clarify whether regularly scheduled or on-demand therapy is suitable for idiopathic pyoderma gangrenosum. Herein we report a recalcitrant case of an idiopathic pyoderma gangrenosum treated successfully with a dosing regimen similar to the one that has been used in psoriasis. By doing so, we were capable of controlling the disease and improving the quality of life in our patient.
Orange Palpebral Spots
Authors: Assouly P. , Cavelier-Balloy B. , Dupré T.
Published: January 2008

We report 27 cases of adults (23 females/4 males, average age 53 years old) presenting yellow-orange pigmented symmetric spots in the internal part of their superior eyelids, different from xanthelasma. Most of them were not aware of their orange palpebral spots (OPS). A systematic observation of adults showed OPS on 15 out of 326 patients. Laboratory investigation carried out in 11 patients did not show particular results except a high level of vitamin E or of total carotenoids in single cases and of β-cryptoxanthin in 5 cases attributed to the high consumption of citrus fruit during winter. In 9 out of the 10 biopsies performed, high-situated fat cells were observed in the reticular dermis, and Fontana pigments (+) in the superficial dermis and sometimes basal keratinocytes. In 1 case yellow-brown autofluorescent microgranular deposits that may correspond to lipofuscin were identified in the superficial dermis. The origin of OPS remains unclear; more than high-situated adipocytes colored by carotenoids, lipofuscin deposit could explain this color, easily visible due to the thinness of the skin in this part of the body. Identifying OPS avoids being mistaken about other pathologies, but further investigations are necessary to understand this entity better.
Infliximab then Efalizumab, the ‘Hit and Run’ Approach Does Not Work
Authors: Barde C. , Thielen A.M. , Saurat J.-H.
Published: January 2008

Background: In a previous paper we described 2 patients treated with a sequential biologic therapy for chronic plaque psoriasis. We used infliximab as an induction treatment followed by efalizumab. We extended this approach to 3 other patients. Objective: The purpose was to show the feasibility of a sequential approach with biologicals. Methods: Five patients received three infusions of infliximab followed by weekly injections of efalizumab from week 10 on. Results: The most important findings, summarized in a table, show that none of the patients continued the treatment for more than a year either because of non-responsiveness or because of spontaneous stopping. Moreover, 4 out of 5 patients did not respond or had serious adverse events on reintroduction of infliximab. Conclusion: Overall, we cannot recommend sequential therapy using infliximab and efalizumab.
Laser Doppler Scanning Study of Axillary Skin before and after Liposuction Curettage in Patients with Focal Hyperhidrosis
Authors: Bechara F.G. , Sand M. , Stücker M. , Georgas D. , Hoffmann K. , Altmeyer P.
Published: January 2008

Background:Minimally invasive surgeries are frequently used in patients suffering from focal axillary hyperhidrosis (FAH). Sweat glands are removed surgically and the axillary skin is thinned out, with skin necrosis being a possible complication due to reduced microcirculation. Although of considerable interest, studies evaluating pre- and postoperative skin perfusion are unavailable. Objective: To evaluate the blood flow of axillary skin in patients with severe focal axillary hyperhidrosis before and after liposuction curettage (LC). Material and Methods: The blood flow in the axillary skin of 11 patients was measured by laser Doppler perfusion imaging before surgery and on days 1, 7 and 28 after LC with a rasping cannula. Skin perfusion was measured in arbitrary units (AU) with measuring points in the axillary center (AC), the operated skin 2 cm from the center (2C) and the surrounding healthy skin (HS). Results: No significant differences of preoperative skin perfusion were found (AC: 0.39 ± 0.08 AU/2C: 0.38 ± 0.07 AU/HS: 0.39 ± 0.07 AU; p > 0.05). On the first and seventh postoperative days, AC (0.2 ± 0.04 AU/0.27 ± 0.81 AU) and 2C (0.2 ± 0.03 AU/0.28 ± 0.06 AU) area were significantly less perfused, whereas the HS showed higher perfusion values (0.59 ± 0.1 AU/0.53 ± 0.09 AU). Twenty-eight days after LC the 2C (0.36 ± 0.07 AU) and HS (0.4 ± 0.06 AU) skin revealed no significant differences compared to preoperative skin perfusion (p > 0.05). The AC perfusion was still slightly reduced (0.37 ± 0.09 AU) without significant difference compared to preoperative findings. Conclusion: LC reduces the axillary skin blood flow with the axillary center being the least perfused area. However, in our collective, no correlation to possible side effects was observed.
National Suicide Rates 1961–2003: Further Analysis of Nordic Data for Suicide, Autopsies and Ill-Defined Death Rates
Authors: Reseland Svein , Le Noury Joanna , Aldred Graham , Healy David
Published: January 2008

Background: Concerns about the risk-benefit ratio of treatment with antidepressants in the light of recent evidence pointing to a risk of suicide induction during the course of treatment with antidepressants. These concerns have led to a series of recent studies exploring national rates of suicide and correlating these with data on antidepressant consumption. Methods: We have compared suicide rates in the Nordic countries with autopsy and ill-defined death rates, and antidepressant sales, during the period 1961 through to 2003. Results: There is a close correlation between suicide rates and both autopsy and ill-defined death rates. Conclusions: The role of autopsies and other factors in the registration of a death as a suicide appear to need further clarification.
Randomized Controlled Comparison of Cognitive Behavior Therapy with Rogerian Supportive Therapy in Chronic Post-Traumatic Stress Disorder: A 2-Year Follow-Up
Authors: Cottraux Jean , Note Ivan , Yao Sai Nan , de Mey-Guillard Chantal , Bonasse Françoise , Djamoussian Diane , Mollard Evelyne , Note Brigitte , Chen Yaohua
Published: January 2008

Background: To date, there have been no studies comparing cognitive behavior therapy (CBT) with Rogerian therapy in post-traumatic stress disorder. Method: Sixty outpatients with DSM-IV chronic post-traumatic stress disorder were randomized into two groups for 16 weekly individual sessions of CBT or Rogerian supportive therapy (ST) at two centers. No medication was prescribed. Measures included the Post-Traumatic Stress Disorder Checklist Scale (PCLS), the Hamilton Anxiety Scale, Beck Depression Inventory, and Quality of Life. The general criterion of improvement (GCI) was a score of less than 44 on the PCLS. Results: Forty-two patients were evaluated at post-test, 38 at week 52 and 25 at week 104. At post-test, the rate of patients leaving the trial due to worsening or lack of effectiveness was significantly higher in the ST group (p = 0.004). At this point, no between-group difference was found on the GCI and any of the rating scales. Intent-to-treat analysis found no difference for the GCI, but patients in the CBT group showed greater improvement on the PCLS and Hamilton Anxiety Scale. Naturalistic follow-up showed sustained improvement without between-group differences at weeks 52 and 104. Conclusions: CBT retained significantly more patients in treatment than ST, but its effects were equivalent to those of ST in the completers. CBT was better in the dimensional intent-to-treat analysis at post-test.
Effects of Progressive Muscle Relaxation Training on Anxiety and Depression in Patients Enrolled in an Outpatient Pulmonary Rehabilitation Program
Authors: Lolak Sermsak , Connors Gerilynn L. , Sheridan Michael J. , Wise Thomas N.
Published: January 2008

Background: This prospective, randomized controlled trial examined the effect of progressive muscle relaxation (PMR) training on anxiety and depression in patients with chronic breathing disorders receiving pulmonary rehabilitation (PR). Methods: Eighty-three subjects with chronic breathing disorders entering the 8-week PR program were randomly assigned to a standard care or intervention group. The standard program included 2 days per week of exercise, education and psychosocial support delivered by a multidisciplinary team. The intervention group received additional sessions of PMR training using a prerecorded tape for 25 min/week during weeks 2–8. Primary outcome measures were levels of anxiety and depression evaluated by the Hospital Anxiety and Depression Scale. Results: For anxiety, there was an overall significant improvement within each group over time (p < 0.0001). There was no statistically significant group-time interaction (p = 0.17) and no statistically significant difference between the groups (p = 0.22), despite lower scores for every time point in the PMR group. For depression, there was an overall significant improvement within each group over time (p < 0.0001). Although the difference between the groups (p = 0.09) and group-time interaction (p = 0.07) did not reach statistical significance, the results again favored the PMR group for weeks 5–8. Depression scores were lower for the PMR throughout weeks 1–8. Conclusions: PR is effective in reducing anxiety and depressive level in chronic lung patients. Our findings suggest that adding structured PMR training to a well-established PR program may not confer additional benefit in the further reduction of anxiety and depression in patients receiving PR.
Mitochondrial Localization of Human Recombinant Adenovirus: From Evolution to Gene Therapy
Authors: Alesci Salvatore , Abu-Asab Mones , Perera Shiromi M. , Tsokos Maria , Morris John C. , Pacak Karel
Published: January 2008

Mitochondrial research has influenced concepts in anthropology, human physiology and pathophysiology. We present here direct evidence that human recombinant viruses can localize in mitochondria to disrupt their integrity. This finding, while opening new perspectives in viral gene therapy, may provide new insights into the pathogenesis, prevention and treatment of viral diseases. In addition, it may advance the current understanding of cell evolution.
Risk of Cervical Spine Injury and Other Complications Seen with Skull Fractures in the Setting of Mild Closed Head Injury in Young Children: A Retrospective Study
Authors: Kim Peter D. , Jennings Jennifer S. , Fisher Mariah , Siddiqui Adnan H.
Published: January 2008

We have reviewed records for patients under 2 years of age who presented at our hospital with mild closed head injuries and nondisplaced skull fractures, specifically to examine methods utilized for spine clearance, associated cervical injuries, involvement and findings of child protective services and delayed complications. Of 42 patients included in the series, none were found to have cervical spine injuries. Child protective services were involved in 12 cases with confirmatory findings and subsequent placement occurring in 2 cases. There were no serious delayed complications in this series of patients. AP and lateral plain films of the cervical spine are nonetheless recommended until larger prospective studies suggest otherwise.
Hemispherectomy in a Premature Neonate with Linear Sebaceous Nevus Syndrome
Authors: Winston Ken R. , Kang Jennifer , Laoprasert Pramote , Kleinschmidt-DeMasters B.K.
Published: January 2008

A male neonate with seizures, linear sebaceous nevus syndrome and hemimegalencephaly underwent hemispherectomy at 36 weeks’ gestational age. He has had no clinical seizures in the 13 months since surgery but continues to have sharp wave activity over some parts of the intact hemisphere. He has moderate developmental delay and a mild hemiparesis but is making developmental progress.
Congenital Medulloblastoma with Atypical MRI Appearance
Authors: Komatsu Fuminari , Tsugu Hitoshi , Nonaka Masani , Tsutsumi Makoto , Yanai Fumio , Yukitake Kou , Utsunomiya Hidetsuna , Fukushima Takeo
Published: January 2008

A 13-day-old female infant was admitted with hydrocephalus that had been diagnosed on prenatal ultrasound at 33 weeks’ gestation. She was delivered by Caesarean section at 34 weeks with an Apgar score of 10. On admission, she weighed 2,103 g. The head circumference was 32.3 cm, and the fontanelle was tense. T1- and T2-weighted MR images revealed an isointense mass occupying the fourth ventricle with multiple cysts in the vermis. The mass was not enhanced after gadolinium administration. CT showed no definite calcification in the lesion. Preoperatively, vermian tumors, including medulloblastoma, ependymoma, astrocytoma, and hamartomas, were considered in the differential diagnosis. Hamartoma was strongly suspected due to the lack of enhancement on MRI. After a suboccipital midline craniotomy, subtotal resection of a soft grayish tumor with areas of hematoma was carried out. The pathological diagnosis was medulloblastoma. Despite chemotherapy, CSF dissemination resulted in death at 11 months. We report this case of congenital medulloblastoma with atypical MRI findings and discuss the clinical characteristics of this lesion.
Transoral Protrusion of a Peritoneal Catheter: A Rare Complication of Ventriculoperitoneal Shunt
Authors: Berhouma Moncef , Messerer Mahmoud , Houissa Sobhy , Khaldi Moncef
Published: January 2008

Ventriculoperitoneal (VP) shunt surgery is the most used technique for the treatment of hydrocephalus. This procedure is associated with a large amount of complications. Bowel perforation caused by a peritoneal shunt catheter is one of these complications, sometimes fatal, and is usually difficult to recognize, except when protrusion of the peritoneal catheter through a natural orifice occurs. This report presents the case of a 2-year-old boy who had undergone a VP shunt and later presented with protrusion of the peritoneal catheter through his mouth. The shunt device was removed and an external shunt procedure was achieved, using the original ventricular catheter kept in place. The diagnosis of bacterial meningitis was retained and an antibiotic therapy was started. The evolution was fatal in 15 days secondary to a bacterial ventriculitis. Through the reported cases of bowel perforation, many risk factors were individualized, such as age, congenital etiology of the hydrocephalus, silicon allergy or the length of the peritoneal catheter. Bowel perforation is a serious complication of VP shunt surgery, leading sometimes to a fatal outcome.
Autoimmune Pancreatitis Associated with High Levels of Chromogranin A, Serotonin and 5-Hydroxyindoleacetic Acid
Authors: Nobili Elisabetta , Pezzilli Raffaele , Santini Donatella , Campidelli Cristina , Calculli Lucia , Casadei Riccardo , Biasco Guido
Published: January 2008

We report a case of a male patient with autoimmune pancreatitis in whom biochemical examination revealed high plasma chromogranin A concentrations, histological demonstration of a small lymphocytic infiltrate and rapid decrease in size of the pancreatic mass following short-lasting therapy with methylprednisolone. To our knowledge, this is the first patient with autoimmune pancreatitis who had a simultaneous increase of serum chromogranin A levels, circulating and urinary serotonin concentrations and urine 5-hydroxyindoleacetic acid concentrations. This is one of the few cases of mass forming pancreatitis with small lymphocytic infiltrate found in a Caucasian patient and rapid decrease in size of the pancreatic mass following short-lasting therapy with methylprednisolone.
Isolated Hepatic Tuberculosis Presenting as Cystic-Like and Tumour-Like Mass Lesions
Authors: Parsak Cem Kaan , Hanta Ismail , Aslan Ahmet , Alabaz Omer
Published: January 2008

Hepatic tuberculosis is a rare manifestation of extra-pulmonary tuberculosis. Hepatic tuberculous lesions are especially mimicking tumour-like mass or cystic lesions in the liver and so can be misdiagnosed with several diseases. Histopathological examination of the specimen is essential in the diagnosis for hepatic tuberculosis. In this report, two cases with hepatic tuberculosis having cystic solid mass and abscess liver lesions are described.
Clinical Significance of Vibration-Induced Nystagmus
Authors: Park H.J. , Shin J.E. , Lim Y.C. , Shin H.A.
Published: January 2008

The aims of the study were to characterize the vibration-induced nystagmus (VIN) in patients with unilateral vestibular neuritis (VN) and Ménière’s disease (MD), and to clarify the clinical significance of VIN by comparing it with caloric results in patients with VN and MD. We recorded eye movements from 22 VN patients and 24 MD patients using unilateral 100-Hz vibration on the mastoid bone. Eye movements were analyzed and the maximum value of slow-phase eye velocity was obtained during vibration on each mastoid. The average value of slow-phase velocities was calculated. Spontaneous nystagmus was subtracted from the slow-phase velocity, whenever it was present. A canal paresis (CP) greater than 25% was considered pathologic. All but one VN patient showed pathologic CP with the direction of the slow-phase eye movement of VIN toward the lesioned side. Fifteen (63%) out of 24 MD patients showed VIN with the slow-phase eye movement directed to the lesioned side. Pathologic CP was present in 9 (38%) out of 24 MD patients and 8 of them showed slow-phase eye movements of VIN directed to the lesioned side. There were also 8 other MD patients who showed slow-phase eye movement of VIN directed to the intact side. Among them, 3 patients with the slow-phase eye movement more than 5°/s showed CP on the intact side. The amplitude of slow-phase eye velocity showed a significant correlation with CP in patients with either VN or MD. There was no significant difference in the slope of the regression lines between the VN and MD groups. Our results suggest that VIN may probe imbalance of canal responses to low-frequency stimulation similar to the caloric test. It also shows that VIN can help in detecting vestibular imbalance using a stimulation mechanism different from the caloric test. The VIN test can be helpful in determining the lesioned side in patients with VN; however, it has some limitations in localizing the lesioned side in patients with MD.
Speech Recognition Materials and Ceiling Effects: Considerations for Cochlear Implant Programs
Authors: Gifford René H. , Shallop Jon K. , Peterson Anna Mary
Published: January 2008

Cochlear implant recipients have demonstrated remarkable increases in speech perception since US FDA approval was granted in 1984. Improved performance is due to a number of factors including improved cochlear implant technology, evolving speech coding strategies, and individuals with increasingly more residual hearing receiving implants. Despite this evolution, the same recommendations for pre- and postimplant speech recognition testing have been in place for over 10 years in the United States. To determine whether new recommendations are warranted, speech perception performance was assessed for 156 adult, postlingually deafened implant recipients as well as 50 hearing aid users on monosyllabic word recognition (CNC) and sentence recognition in quiet (HINT and AzBio sentences) and in noise (BKB-SIN). Results demonstrated that for HINT sentences in quiet, 28% of the subjects tested achieved maximum performance of 100% correct and that scores did not agree well with monosyllables (CNC) or sentence recognition in noise (BKB-SIN). For a more difficult sentence recognition material (AzBio), only 0.7% of the subjects achieved 100% performance and scores were in much better agreement with monosyllables and sentence recognition in noise. These results suggest that more difficult materials are needed to assess speech perception performance of postimplant patients – and perhaps also for determining implant candidacy.
Influence of Vascular Access Type on Outcome Measures in Patients on Maintenance Hemodialysis
Authors: Chand Deepa H. , Teo Boon Wee , Fatica Richard A. , Brier Michael
Published: January 2008

Background: Previous studies postulate that end-stage renal disease (ESRD) patients dialyzed with central venous catheters (CVC) have poorer outcomes compared to patients using arteriovenous fistulae (AVF) or arteriovenous grafts (AVG). Clinical practice guidelines should obviate these differences if access was not important. This study compared clinical measures of adequacy, anemia, and nutrition/inflammation in prevalent hemodialysis patients in 2003 by access type. Methods: Data from The Renal Network Data System were analyzed by univariate analysis of variance to compare Kt/V, URR, albumin, hemoglobin (Hb) and recombinant human erythropoietin (EPO) dose by access type, while adjusting for pertinent factors. Results: 12,501 patients were included. The access type distribution was AVF 36%, AVG 41%, and CVC 23%. CVC patients had lower mean URR, Kt/V, albumin concentration (p < 0.001) than other accesses. Serum Hbs were similar (p = 0.416), however EPO dose (U/kg/week) was higher in those dialyzed with CVC compared to AVF/AVG (p < 0.001). Conclusions: Despite practice guidelines, patients dialyzed via CVC have poorer outcome measures compared to other accesses. This suggests that AVF should be used and/or appropriate adjustments need to be made for those dialyzed with CVC to achieve equal outcomes. Further studies defining barriers need to be conducted.
Homocysteinemia Correlates with Plasma Thiol Redox Status in Patients with End-Stage Renal Disease
Authors: Palleschi Simonetta , De Angelis Sandro , Rossi Barbara , Diana Loretta , Papa Vincenza , Severini Giancarlo , Splendiani Giorgio
Published: January 2008

Background/Aims: In end-stage renal disease (ESRD), hyperhomocysteinemia is a common finding associated with increased cardiovascular risk. However, the pathogenic role of homocysteine is still unclear. In vitro studies show that thiol redox status affects endothelial cell functions. We therefore investigated the possible association between homocysteinemia and plasma thiol redox status in ESRD patients. Methods: Total plasma homocysteine (Hcy), cysteine (Cys) and free thiols (SH) were measured both before and after a dialytic session in 54 ESRD patients receiving (n = 15) or not receiving (n = 39) folate supplementation, and 17 control subjects. Results: High predialysis levels of both Hcy and Cys were found to be negatively correlated with low SH levels both in supplemented (r = –0.680, p < 0.01 and r = –0.624, p < 0.02, respectively) and unsupplemented (r = –0.698, p < 0.001 and r = –0.445, p < 0.01, respectively) patients. Following dialysis, SH values returned to normal and the above correlations were no longer appreciable. Conclusion: A strong, folate therapy-insensitive association between homocysteinemia and plasma free thiol levels was found in ESRD patients. These results support a role for oxidative stress in ESRD-related hyperhomocysteinemia and suggest the plasma thiol redox status alteration as a possible pathogenic mechanism underlying the cardiovascular toxicity of hyperhomocysteinemia in these patients.
A Case-by-Case Protocol of Membranous Nephropathy Treatment with Endovenous Infusion of High Doses of Human Immunoglobulins
Authors: Floccari F. , Cosentini V. , Giacobbe M. , Coppolino G. , Campo S. , Bolignano D. , Tripodo D. , Nostro L. , Buemi M.
Published: January 2008

The treatment of membranous nephropathy is a highly controversial issue. As some patients may have spontaneous remission, in about 50% of cases the risk of treating patients with drugs that may have severe side effects is higher than the potential benefit of arresting disease progression. Some authors therefore propose exclusively symptomatic treatment; other authors use steroids and immunosuppressive drugs, alone or in association with high risk of adverse effects and often uncertain benefits. The intravenous administration of high doses of human immunoglobulins (IVIg) has been also extended to a growing number of kidney diseases including membranous nephropathy. The mechanisms through which IVIg carry out their therapeutic effect are still unclear. The present study is a retrospective and uncontrolled trial, the aim of which was firstly to verify if some patients could respond to extremely short treatment protocols, stopped when they appear to have a stable remission, thereby avoiding expensive continuation of treatment. Secondly, we aimed to verify if some patients, judged as nonresponders to a classical protocol of IVIg therapy, could respond to a more prolonged treatment.
Feasibility of Minocycline and Doxycycline Use as Potential Vasculostatic Therapy for Brain Vascular Malformations: Pilot Study of Adverse Events and Tolerance
Authors: Frenzel Tim , Lee Chanhung Z. , Kim Helen , Quinnine Nancy J. , Hashimoto Tomoki , Lawton Michael T. , Guglielmo B. Joseph , McCulloch Charles E. , Young William L.
Published: January 2008

Background: Tetracyclines may be useful in preventing pathological vascular remodeling, thus decreasing the risk of spontaneous hemorrhage from brain vascular malformations. Methods: Arteriovenous malformation (AVM) and intracranial aneurysm patients undergoing noninvasive management were treated with minocycline or doxycycline (200 mg/day) up to 2 years in a prospective open-label safety pilot trial. The primary outcome was to compare dose-limiting intolerance, defined as treatment-related dose reduction or withdrawal between the agents.Results: Twenty-six patients with AVMs (n = 12) or aneurysms (n = 14) were recruited. Adverse event rates were similar to other reported trials of these agents; 4 of 13 (31%) minocycline and 3 of 13 (23%) doxycycline patients had dose-limiting intolerance (hazard ratio = 3.1, 95% CI = 0.52–18.11, log rank p = 0.70). Conclusions: It is feasible to propose a long-term trial to assess the potential benefit of tetracycline therapy to decrease hemorrhagic risk in brain vascular malformations.
Severity of Carotid Atherosclerosis Unrelated to Chlamydia pneumoniae Infection in Acute Ischemic Stroke Patients: A Clinicopathological Study
Authors: Kónya József , Molnár Sándor , Magyar Mária T. , Szekeres Csilla C. , Kerényi Levente , Csiba László
Published: January 2008

Background: Both clinical and pathological alterations of the carotid arteries were correlated with Chlamydia pneumoniae infection in 67 acute ischemic stroke patients with severe neurological symptoms. Methods: In the clinical study, intima-media thickness (IMT) of the common carotid arteries was determined in vivoby B-mode ultrasound measurement and C. pneumoniae-specific IgG and IgA responses were detected. In the pathological study, the absolute wall thickness of the common, internal and external carotid arteries was measured postmortem in specimens obtained at the autopsy of patients who died due to complications of acute stroke. In the atherosclerotic plaques of the autopsy specimens, C. pneumoniae genomic DNA was detected by polymerase chain reaction amplification. Results: The Spearman’s rho correlation coefficient of IMT with the average wall thickness of the common, internal and external carotid arteries was 0.51 (p = 0.002), 0.34 (p = 0.052) and 0.58 (p < 0.001), respectively. Anti-C. pneumoniae IgG and IgA antibodies were detected in 43 (73%) and 29 (49%) patients, but neither antibody marker correlated with IMT (median: 0.91 mm in IgG positives vs. 0.90 mm in IgG negatives, p = 0.86; 0.88 mm in IgA positives vs. 0.90 mm in IgA negatives, p = 0.53). The presence of C. pneumoniae DNA was detected in the carotid plaques of 21 (54%) of the 39 tested patients, independently of either IMT values or the average wall thickness of all carotid arteries. Conclusions: In acute ischemic stroke patients, C. pneumoniae infection was frequently detected in the arteriosclerotic plaques of the carotid arteries but it did not correlate with the severity of carotid arteriosclerosis.
Caregiver Burden for Impaired Elderly Japanese with Prevalent Stroke and Dementia under Long-Term Care Insurance System
Authors: Muraki Isao , Yamagishi Kazumasa , Ito Yoshinobu , Fujieda Takashi , Ishikawa Yoshinori , Miyagawa Yukiaki , Okada Katsutoshi , Sato Shinichi , Kitamura Akihiko , Shimamoto Takashi , Tanigawa Takeshi , Iso Hiroyasu
Published: January 2008

Background: Limited data are available on caregiver burden for stroke and dementia patients. We examined the associations of prevalent stroke and dementia with family caregiver burden in Japanese general populations. Methods: A total of 916 Japanese home caregivers, whose family members were covered by long-term care insurance, responded to the caregiver burden questionnaire. The questionnaire included the caregiver’s age, sex and employment status, the patient-caregiver relationship, the patient‘s history of stroke, symptoms of dementia, care levels under long-term care insurance and the Zarit Caregiver Burden Interview. Results: The mean total score from the Zarit Caregiver Burden Interview was 12% higher in patients with stroke than in those without (p = 0.02) and 40% higher in those with dementia than in those without (p < 0.001). Compared with nonstroke patients without dementia, the mean total score was 21% higher in stroke patients without dementia (p = 0.01), 49% higher in nonstroke patients with dementia (p < 0.001) and 55% higher in stroke patients with dementia (p < 0.001). After adjustment for the caregiver’s age, sex and employment status, the patient-caregiver relationship, and the patient’s care level and community, the higher scores remained statistically significant for nonstroke patients with dementia and for stroke patients with dementia but not for stroke patients without dementia. Conclusions: Prevalent stroke and, more strongly, dementia were associated with increased family caregiver burden. Among patients with dementia, the presence of stroke did not enhance caregiver burden further.
Risk Factors and Treatment at Recurrent Stroke Onset: Results from the Recurrent Stroke Quality and Epidemiology (RESQUE) Study
Authors: Leoo T. , Lindgren A. , Petersson J. , von Arbin M.
Published: January 2008

Background: Much effort has been made to study first-ever stroke patients. However, recurrent stroke has not been investigated as extensively. It is unclear which risk factors dominate, and whether adequate secondary prevention has been provided to patients who suffer from recurrent stroke. Also, the different types of recurrent stroke need further evaluation. Methods: The study included patients with recurrent stroke admitted to twenty-three Swedish stroke centers. The type of previous and recurrent stroke was determined, as well as evaluation (when applicable) of recurrent ischemic stroke according to the TOAST classification. Presence of vascular risk factors was registered and compared to the type of stroke. Also assessed was ongoing secondary prevention treatment at recurrent stroke onset. Results: A total of 889 patients with recurrent stroke (mean age 77) were included in the study. Of these, 805 (91%) had ischemic stroke, 78 (9%) had intracerebral hemorrhage and 6 (<1%) stroke of unknown origin. The most frequent vascular risk factors were hypertension (75%) and hyperlipidemia (56%). Among the 889 patients, 29% had atrial fibrillation. Of the patients in the ischemic group with cardiac embolism, only 21% were on anticoagulation treatment. The majority of the patients (75%) had their most recent previous stroke >12 months before admission. Conclusions: Few patients had a recurrent stroke shortly after the previous stroke in this study. This indicates that it is meaningful to prevent a second event with an adequate long-term treatment strategy for secondary prevention after first-ever stroke. There also seems to be a clear potential for improving secondary prevention after stroke.
Involvement of PI3K/Akt Pathway in TGF-β2-Mediated Epithelial Mesenchymal Transition in Human Lens Epithelial Cells
Authors: Yao Ke , Ye Pan Pan , Tan Jian , Tang Xia Jing , Shen Tu Xing Chao
Published: January 2008

Background: Epithelial mesenchymal transition (EMT) of postoperative remnants of lens epithelial cells (LECs) can lead to posterior capsule opacification. This study was designed to determine the effect of signaling pathways that contribute to TGF-β2-mediated EMT in human lens epithelial B-3 cells (HLEB-3 cells). Methods: The HLEB-3 cells were cultured and stimulated with TGF-β2 at different concentrations for an indicated time. The effect of TGF-β2 on cell cycle distribution was measured by flow cytometry. Western blot and immunofluorescence were used to analyze changes in connexin 43, fibronectin, desmin and integrin β1 protein expression associated with EMT in HLEB-3 cells. Activation of phosphatidylinositol-3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways was also detected by Western blot. Results: The cell cycle progression of HLEB-3 cells was limited, and the cells underwent morphological alteration after treatment with TGF-β2. Stimulation of HLEB-3 cells with TGF-β2 suppressed connexin 43 protein expression, increased fibronectin, desmin and integrin β1 protein expression. TGF-β2 activated PI3K/Akt in a time-dependent manner, but not extracellular signal-regulated kinase and p38 MAPK. The activation of PI3K/Akt was necessary for the TGF-β2-stimulated downregulation of connexin 43, which in turn was necessary for TGF-β2-induced EMT in HLEB-3 cells. Conclusions: TGF-β2 is a potent growth factor for LEC EMT. TGF-β2-induced EMT in LECs is mediated by the downregulation of connexin 43, which is regulated through the PI3K/Akt pathway.
Intracellular Effects of NSAIDs/ASA in Oxidatively Stressed Human Lens Epithelial Cells in Culture
Authors: Petersen A. , Carlsson T. , Karlsson J.-O. , Zetterberg M.
Published: January 2008

The aim of the study was to examine the effects of nonsteroidal anti-inflammatory drugs (NSAIDs)/acetylsalicylic acid (ASA) on human lens epithelial cells (HLECs) during oxidative stress. HLECs were exposed to H2O2 in the absence or presence of indomethacin, diclofenac, celecoxib (NSAIDs) or ASA for 24 h. HLECs were assayed for changes in superoxide and peroxide production and for variations in glutathione. Mitochondrial depolarization was measured using the membrane potential-sensitive dye JC-1. The results of the study include reduction in superoxide and peroxide production as well as reduction in glutathione depletion in oxidatively stressed HLECs incubated with low concentrations of NSAIDs/ASA. However, no protection against H2O2-induced mitochondrial depolarization by NSAIDs/ASA could be seen. In conclusion, NSAIDs/ASA display reactive oxygen species-scavenging properties in H2O2-exposed HLECs in culture.
Plasma Membrane Ca2+-ATPase Isoform Expression in Human Cataractous Lenses Compared to Age-Matched Clear Lenses
Authors: Marian Moazez J. , Mukhopadhyay Partha , Borchman Douglas , Paterson Christopher A.
Published: January 2008

The plasma membrane calcium ATPase (PMCA) pump is the major mechanism by which calcium is removed from the lens. The aim of this study was to determine if mRNA and proteins levels of PMCA isoforms changed with age or lens opacity. mRNA was quantified using a quantitative real-time reverse transcription polymerase chain reaction assay (RT-PCR). PMCA protein levels were quantified using Western blot analysis. No PMCA mRNA or proteins were detected in human lens fiber cells. The mRNA and protein levels of PMCA1, 3 and 4 in the epithelium of cataractous lenses were similar to those of epithelium from age-matched clear lenses and were also the same in younger lenses. PMCA2 mRNA and protein levels were 1.6–2.5 times higher, respectively, in cataractous lenses compared to age-matched clear lenses. Elevated PMCA2 expression in cataractous lenses might be a compensatory mechanism to overcome higher intracellular calcium levels in cataract.
Choroidal Sclerosis in Localized Scleroderma (Morphea en Plaque)
Authors: Milenkovic S. , Petrovic L. , Risimic D. , Kosanovic-Jakovic N. , Jaksic V. , Djakovic Z. , Stojkovic M. , Risovic D. , Ivankovic Lj. , Ivancevic-Milenkovic M.
Published: January 2008

Plaque morphea is a superficial type of morphea (localized scleroderma) which is characterized by various fibrotic areas of the dermis without systemic features. We present a 63-year-old man with morphea en plaque. The skin on his forearms and feet was taut, thickened and hidebound with scattered telangiectatic changes. Autoantibody profile was obtained and only ANA were positive (1:80). The patient had a decreased vision in the only functional, left eye. Our case is specific because the patient negated any kind of health problem, meaning the morphea and visual deterioration were of outstanding importance for him. Choroidal sclerosis and fundus appearance was extremely impressive and, to our knowledge, this is the first report of such unique case of ocular involvement in the literature.
Pemphigus Vulgaris after Coxsackievirus Infection and Cephalosporin Treatment: A Paraviral Eruption?
Authors: Ruocco E. , Lo Schiavo A. , Baroni A. , Sangiuliano S. , Puca R.V. , Brunetti G. , Ruocco V.
Published: January 2008

Pemphigus is an autoimmune disease that results from the interaction between predisposing genetic factors and exogenous agents, mainly drugs and viruses. Herein we report the case of a 66-year-old woman referred to our department for the onset of painful oral erosions and bullous lesions on the torso. Clinical, laboratory and histopathological investigations led to the diagnosis of pemphigus vulgaris. Two weeks before the outbreak of the lesions, the patient had suffered from a viral pharyngitis, subsequently diagnosed as herpangina, and had been taking an oral cephalosporin (cefixime) for 1 week to prevent possible bacterial complications. A relationship between the onset of pemphigus and coxsackievirus infection or cefixime administration or both was supposed. The case may represent a peculiar paraviral eruption, where a predisposing pemphigus-prone genetic background paved the way for the acantholytic autoimmune disorder as a consequence of the combined effect of the coxsackievirus infection and the cephalosporin treatment.
Plasma DNA: A Molecular Marker of Surgical Insult and Postoperative Recovery in Esophageal Cancer
Authors: Banki F. , Mason R.J. , Hagen J.A. , DeMeester S.R. , Lipham J.C. , Danenberg K. , Danenberg P. , DeMeester T.R.
Published: January 2008

Aim: To assess plasma DNA changes intraoperatively, to relate plasma DNA to the magnitude of the surgical insult and to monitor the changes during the postoperative recovery period. Material and Method: Prospective study of 35 patients with esophageal cancer who had esophagectomy of different magnitudes: 19 esophagectomy without thoracotomy and 16 esophagectomy with thoracotomy. The plasma DNA was measured prior to surgery, throughout the course of the operation on four different intervals, and on postoperative days 1, 3, 5, and 7. Results: A significant difference was seen in the median plasma DNA intraoperatively between the two groups: esophagectomy without thoracotomy, 507 ng/ml/min (range 211–2,708), esophagectomy with thoracotomy, median 1,098 ng/ml/min (range 295–22,284; p = 0.014). Postoperative complications were identified in 6 patients who demonstrated a significant elevation in plasma DNA on postoperative days 5 and 7. Conclusion: Plasma DNA increases during surgery as a result of cell damage and the rise correlates with the magnitude of surgery. The descent of plasma DNA postoperatively correlates with surgical recovery. Elevation of the plasma DNA during the postoperative period correlates with postoperative complications. Plasma DNA is an objective molecular marker of surgical insult and can be used to monitor postoperative recovery after esophagectomy.
Nigella sativa Oil for Prevention of Chronic Cyclosporine Nephrotoxicity: An Experimental Model
Authors: Uz Ebru , Bayrak Omer , Uz Efkan , Kaya Arif , Bayrak Reyhan , Uz Burak , Turgut Faruk Hilmi , Bavbek Nuket , Kanbay Mehmet , Akcay Ali
Published: January 2008

Nephrotoxicity is the main secondary effect of cyclosporine A (CsA) treatment. The antioxidant action of Nigella sativa oil (NSO) may explain the protective effect of these agents against various hepatotoxic and nephrotoxic models in vivo and in vitro. This study was designed to investigate the possible protective effects of NSO, in prevention of chronic CsA-induced nephrotoxicity in rats. Animals were randomly divided into four experimental groups: the control group received sunflower oil, the other groups were treated with CsA (25 mg/kg/day b.w. orally) or NSO (2 ml/kg orally) or CsA + NSO, respectively. Urine and serum creatinine levels, tissue superoxide dismutase, glutathione peroxidase and catalase enzyme activities, and nitric oxide and malondialdehyde levels were measured, and histological examination was performed. In our study, CsA caused a significant deterioration in the renal function, morphology and gave rise to severe oxidative stress in the kidney. NSO significantly improved the functional and histological parameters and attenuated the oxidative stress induced by CsA. In conclusion, our study demonstrated for the first time that NSO protects kidney tissue against oxygen free radicals, preventing renal dysfunction and morphological abnormalities associated with chronic CsA administration.
Maternal Footprints of Southeast Asians in North India
Authors: Thangaraj Kumarasamy , Chaubey Gyaneshwer , Kivisild Toomas , Selvi Rani Deepa , Singh Vijay Kumar , Ismail Thanseem , Carvalho-Silva Denise , Metspalu Mait , Bhaskar L.V.K.S. , Reddy Alla G. , Chandra Sarat , Pande Veena , Prathap Naidu B. , Adarsh Niharika , Verma Abhilasha , Jyothi Inaganti Amara , Mallick Chandana Basu , Shrivastava Nidhi , Devasena Ragala , Kumari Babita , Singh Amit Kumar , Dwivedi Shailendra Kumar Dhar , Singh Shefali , Rao Geeta , Gupta Pranav , Sonvane Vartika , Kumari Kavita , Basha Afsar , Bhargavi K.R. , Lalremruata Albert , Gupta Arvind Kumar , Kaur Gurukamal , Reddy K.K. , Rao A.Papa , Villems Richard , Tyler-Smith Chris , Singh Lalji
Published: January 2008

We have analyzed 7,137 samples from 125 different caste, tribal and religious groups of India and 99 samples from three populations of Nepal for the length variation in the COII/tRNALys region of mtDNA. Samples showing length variation were subjected to detailed phylogenetic analysis based on HVS-I and informative coding region sequence variation. The overall frequencies of the 9-bp deletion and insertion variants in South Asia were 1.9 and 0.6%, respectively. We have also defined a novel deep-rooting haplogroup M43 and identified the rare haplogroup H14 in Indian populations carrying the 9-bp deletion by complete mtDNA sequencing. Moreover, we redefined haplogroup M6 and dissected it into two well-defined subclades. The presence of haplogroups F1 and B5a in Uttar Pradesh suggests minor maternal contribution from Southeast Asia to Northern India. The occurrence of haplogroup F1 in the Nepalese sample implies that Nepal might have served as a bridge for the flow of eastern lineages to India. The presence of R6 in the Nepalese, on the other hand, suggests that the gene flow between India and Nepal has been reciprocal.
Selecting Predictive Markers for Pharmacogenetic Traits: Tagging vs. Data-Mining Approaches
Authors: Sabbagh Audrey , Génin Emmanuelle , Darlu Pierre
Published: January 2008

Objective: The tagging approach appears as a promising tool to test the association of genetic variants with complex traits such as disease susceptibility or drug response. However, since tag markers are selected only on the basis of inter-marker LD properties, regardless of any phenotypes, it remains unclear to what extent they can be useful to predict variable drug responses, once typed in clinical material. We undertook a study to provide further insights into the usefulness of the tagging approach for selecting phenotype-associated markers relevant to drug response. Methods: Several tagging methods were applied to the genotyping data of two drug-metabolizing enzymes, NAT2 and CYP2D6, and the ability of the selected tagging markers to predict the individual metabolizer status was empirically evaluated. We also assessed the impact of LD levels, tagging thresholds and allele frequencies on tagging efficiency. Results: We found that the functional variation was adequately represented by the selected tagging markers, these latter providing a classification accuracy for the individual metabolizer status close to the maximal 100% value observed with the entire set of polymorphisms. Conclusion: The tagging approach is an interesting approach to select candidate gene markers predictive of drug response in pharmacogenomic studies.
Computation of the Posterior Probability of Linkage Using ‘High Effect’ Genetic Model Priors
Authors: Logue M.W. , Li Y.
Published: January 2008

Objectives: The posterior probability of linkage, or PPL, directly measures the probability that a disease gene is linked to a marker. By placing a Bayesian prior on the elements of the genetic model, it allows for an unknown genetic model without the inflationary effects of maximization. The standard technique uses essentially uniform priors over the elements of the penetrance vector. However, much of the parameter space corresponds to models that seem unlikely to yield substantial evidence for linkage: for example, models with very high phenocopy rates. Methods: A new class of priors on the elements of the genetic model is examined both theoretically and in simulations. These priors place 0% probability over models with low sibling relative risk, λs. Results: Focusing the prior probability on high λs models does tend to increase the mean PPL for linked markers, and to decrease the mean PPL for unlinked markers. However, the power to detect linkage remains virtually unchanged. Moreover, under these priors, the PPL occasionally yields unacceptably high values under no linkage. Conclusions: It appears important to retain prior probability over apparently ‘uninformative’ genetic models to accurately characterize the amount of evidence for linkage represented by the data.
Meta-Analysis of 23 Type 2 Diabetes Linkage Studies from the International Type 2 Diabetes Linkage Analysis Consortium
Authors: Guan Weihua , Pluzhnikov Anna , Cox Nancy J. , Boehnke Michael
Published: January 2008

Background: The International Type 2 Diabetes Linkage Analysis Consortium was formed to localize type 2 diabetes predisposing variants based on 23 autosomal linkage scans. Methods: We carried out meta-analysis using the genome scan meta-analysis (GSMA) method which divides the genome into bins of ∼30 cM, ranks the best linkage results in each bin for each sample, and then sums the ranks across samples. We repeated the meta-analysis using 2 cM bins, and/or replacing bin ranks with measures of linkage evidence: bin maximum LOD score or bin minimum p value for bins with p value <0.05 (truncated p value). We also carried out computer simulations to assess the empirical type I error rates of these meta-analysis methods. Results: Our analyses provided modest evidence for type 2 diabetes-predisposing variants on chromosomes 4, 10, and 14 (using LOD scores or truncated p values), or chromosome 10 and 16 (using ranks). Our simulation results suggested that uneven marker density across studies results in substantial variation in empirical type I error rates for all meta-analysis methods, but that 2 cM bins and scores that make more explicit use of linkage evidence, especially the truncated p values, reduce this problem. Conclusion: We identified regions modestly linked with type 2 diabetes by summarizing results from 23 autosomal genome scans.