bluuebunny/crossref_metadata_2025 huggingface dataset:
Erythropoietin Enhances Long-Term Neuroprotection and Neurogenesis in Neonatal Stroke
Authors: Gonzalez Fernando F. , McQuillen Patrick , Mu Dezhi , Chang Yunsil , Wendland Michael , Vexler Zinaida , Ferriero Donna M.
Published: September 2007

Neonatal stroke leads to mortality and severe morbidity, but there is no effective treatment currently available. Erythropoietin (EPO) has been shown to promote cytoprotection and neurogenesis and decrease subventricular zone morphologic changes following brain injury. The long-term cellular response to EPO has not been defined, and local changes in cell fate decision may play a role in functional improvement. We performed middle cerebral artery occlusion in P10 rats. EPO treatment (5 U/g IP) significantly preserved hemispheric brain volume 6 weeks after injury. Furthermore, EPO increased the percentage of newly generated neurons while decreasing newly generated astrocytes following brain injury, without demonstrating long-term differences in the subventricular zone. These results suggest that EPO may neuroprotect and direct cell fate toward neurogenesis and away from gliogenesis in neonatal stroke.
Perinatal Hypoxic/Ischemic Brain Injury Induces Persistent Production of Striatal Neurons from Subventricular Zone Progenitors
Authors: Yang Zhengang , Levison Steven W.
Published: September 2007

Ischemia-induced production of new striatal neurons in young and adult rodents has been studied. However, it is unclear whether neonatal hypoxic/ischemic (H/I) brain injury-induced neuronogenesis in the striatum is transient or sustained, nor has it been established whether these new neurons arise from progenitors within the striatum or from precursors residing in the adjacent subventricular zone. Here, we report that from 2 weeks to 5 months after H/I there are more doublecortin-positive (Dcx+) cells and Dcx+/NeuN+ cells in the damaged striatum compared to the contralateral striatum. After the S-phase marker 5-bromo-2′-deoxyuridine (BrdU) was injected at both short and long intervals (2 days and 2 months) after H/I to label newly born cells, more BrdU+/Dcx+ and BrdU+/NeuN+ cells were observed in the ipsilateral striatum compared to the contralateral striatum. Retroviral fate-mapping studies demonstrated that these newly born striatal neurons are generated from precursors within the subventricular zone. Altogether, these observations indicate the neonatal brain initiates a prolonged regenerative response from the precursors of the subventricular zone (SVZ) that results in persistent production of new striatal neurons.
Pomegranate Polyphenols and Resveratrol Protect the Neonatal Brain against Hypoxic-Ischemic Injury
Authors: West Tim , Atzeva Madeliene , Holtzman David M.
Published: September 2007

A previous study from our lab has shown that the polyphenol-rich pomegranate juice can protect the neonatal mouse brain against hypoxic-ischemic (H-I) injury when given to mothers in their drinking water. To test the hypothesis that this protection is due to the polyphenols in the juice, we studied the effects of the pomegranate polyphenol extract in the same neonatal H-I model. To further explore the role of a specific polyphenol in neonatal H-I we investigated the effects of resveratrol. The neuroprotective effects of resveratrol have been demonstrated in adult models of stroke, but had not previously been examined in neonates. We show that pomegranate polyphenols and resveratrol reduce caspase-3 activation following neonatal H-I. Resveratrol reduced caspase-3 activation when given before the injury but not when given 3 h after the injury. In addition to preventing caspase-3 activation, resveratrol also reduced calpain activation. Finally, we show that resveratrol can protect against tissue loss measured at 7 days after the injury. These and other recent findings suggest that polyphenols should be further investigated as a potential treatment to decrease brain injury due to neonatal H-I.
Mast Cell Stabilization Limits Hypoxic-Ischemic Brain Damage in the Immature Rat
Authors: Jin Yuxuan , Silverman Ann-Judith , Vannucci Susan J.
Published: September 2007

Perinatal hypoxic-ischemic (HI) brain damage is a major cause of mortality and neurological morbidity in infants and children. Using an established model of unilateral hypoxia-ischemia in neonatal rats, the present study focused on mast cells (MCs), important regulators of inflammatory processes, as potential contributors to HI damage. MCs are present in the pia of the neonatal rat, entering the central nervous system (CNS) during cerebral development along penetrating blood vessels. Following hypoxia-ischemia, MC numbers increased dramatically in the ipsilateral (ischemic) hemisphere (p < 0.01). In animals exposed to hypoxia only, the numbers of MCs were elevated in both hemispheres to an extent equal to that observed in the contralateral hemisphere of HI animals (p < 0.05 vs. control). Within damaged areas (ipsilateral only), MCs were observed in regions of activated microglia and astroglia that characterize the ischemic hemisphere. Using a triple-label paradigm, MCs were observed along elongating blood vessels, some of which express the GLUT1 isoform of the glucose transporter protein, indicative of blood-brain barrier vessels. To determine whether MC activation has a role in HI brain damage, rat pups were treated with the MCs stabilizer, disodium cromoglycate (cromolyn),prior to and/or following hypoxia-ischemia. The cromolyn treatment inhibited MC migration into the CNS (p < 0.05) and limited brain damage more than 50% (p < 0.01) vs. saline controls. These data support the hypothesis that MCs are key contributors to the extent of brain damage due to hypoxia-ischemia in the immature animal.
Gender-Dependent Pathways of Hypoxia-Ischemia-Induced Cell Death and Neuroprotection in the Immature P3 Rat
Authors: Nijboer Cora H.A. , Kavelaars Annemieke , van Bel Frank , Heijnen Cobi J. , Groenendaal Floris
Published: September 2007

Previously, we demonstrated neuroprotection with 2-iminobiotin (2-IB) after cerebral hypoxia-ischemia (HI) in female, but not in male P7 rats. Given the different patterns of brain injury in more immature rats, we examined whether these gender differences could also be observed in P3 rats. HI was induced by unilateral carotid ligation and FiO2 reduction, followed by 2-IB administration. HSP70 protein expression and cytochrome c release from the mitochondria, markers of short-term outcome, were induced by HI to the same extent in male and female animals. However, reduction in HSP70 production and cytochrome c release by 2-IB was seen in female rats only. Long-term cerebral injury after HI, assessed with histology, was similar in male and female P3 rats, but long-term neuroprotection by 2-IB was observed in female rats only. In conclusion, 2-IB provides neuroprotection after cerebral HI in female, but not in male immature P3 rats.
Antioxidant Status Alters Levels of Fas-Associated Death Domain-Like IL-1B-Converting Enzyme Inhibitory Protein following Neonatal Hypoxia-Ischemia
Authors: Payton Kurlen S.E. , Sheldon R. Ann , Mack Devin W. , Zhu Chainglian , Blomgren Klas , Ferriero Donna M. , Northington Frances J.
Published: September 2007

Activation of Fas death receptor (Fas DR) signaling cascade is seen after neonatal hypoxia-ischemia (HI). Cell survival is favored when signaling through the death-inducing signaling complex and cleavage of caspase 8 to its active form is blocked by FLIP, a dominant negative of caspase 8. H2O2 quickly downregulates expression of FLIP. Neonatal mice overexpressing glutathione peroxidase (GPx) have less injury and less H2O2 accumulation compared with neonatal mice overexpressing superoxide dismutase (SOD) or wild-type (WT) littermates. Expression of both FLIPL and FLIPS is increased in GPx-oxerexpressing mice relative to WT mice at 24 h and relative to SOD-overexpressing mice at 2 and 24 h following neonatal HI (ANOVA, p < 0.05). There is an increase in Fas DR expression at 24 h in both WT and GPx-overexpressing mice and significant differences between WT and SOD-overexpressing mice (ANOVA, p < 0.01). There is no difference in FADD expression among the 3 groups 24 h after HI. At 24 h following HI, the ratio of FLIP to Fas DR expression supports a significant negative correlation with injury score (r2 = 0.99, slope = –4.01), and expression of both the active fragment of caspase 8 and caspase 8 activity is increased in SOD overexpressors compared to GPx overexpressors at 24 h after HI (ANOVA, p < 0.05). The overall degree of injury previously seen in these 3 strains correlates well with changes in expression of Fas DR signaling proteins favoring neuroprotection in the GPx-overexpressing mice, i.e. increased FLIP expression and decreased caspase 8 activity compared to SODtg mice. The mechanism by which antioxidant status alters FLIP levels following neonatal HI may be related to the ability to detoxify H2O2 produced following neonatal HI.
Clinical Significance of Platelet Count in Patients with Renal Cell Carcinoma
Authors: Erdemir Fikret , Kilciler Mete , Bedir Selahattin , Ozgok Yasar , Coban Hidayet , Erten Koray
Published: September 2007

Introduction: During the last decades numerous prognostic factors have been studied for predicting survival of renal cell carcinoma (RCC). Platelet count has previously been reported to correlate with prognosis in RCC. The aim of the this study was to evaluate the significance of thrombocytosis in determining prognosis in patients with localized RCC who underwent radical nephrectomy. Patients and Methods: The study included 118 consecutive patients. Patients were divided into a normal platelet count group (group 1) and a thrombocytosis group (group 2) according to the preoperative platelet count. Thrombocytosis was defined as a platelet count greater than 400,000/µl. The data about stage distribution, grade, tumor size, histological subtype, hemoglobin level, Body Mass Index (BMI), age, ECOG score, gender, and survival rate of tumors between these two groups were compared. Survival estimates were compared with the Kaplan-Meier method and multivariate analysis was performed using a Cox model. Results: The mean age of the patients was 61.4 years (range 30–78), and the mean follow-up period was 52.7 ± 19.6 months (range 9–96). Thrombocytosis was present in 23 patients (19.49%). Fourteen (60.86%) of 23 patients with thrombocytosis died of disease progression. Patients with thrombocytosis had a worse prognosis than patients without thrombocytosis (p = 0.001). Thrombocytosis was noted in 8 (10.81%) of 74 patients with stage pT1-pT2 disease and in 15 (34.09%) of 44 patients with stage pT3-pT4 disease (p = 0.004). In univariate analysis, platelet count was correlated with T stage, hemoglobin level, lymph node positivity, ECOG score, and tumor size. Controlling for established prognostic indicators of pathologic stage, tumor size, platelet count, and lymph positivity using Cox’s regression test, the difference in survival between the groups remained significant (p < 0.05). Conclusion: The platelet count can be considered a useful prognostic factor in patients with RCC who undergo radical nephrectomy.
Does Age Affect the Prognosis of Patients with Testicular Germ Cell Tumor?
Authors: Inci Kubilay , Dogan Hasan Serkan , Akdogan Bulent , Ergen Ali , Tasar Celik , Ozen Haluk
Published: September 2007

Introduction: In this study, the effect of age on the prognosis of testicular germ cell tumors in patients over 40 was investigated. Materials and Methods: Ninety-three patients with testicular germ cell tumor who were 40 years old and over were identified in our germ cell tumor database. Patients were grouped according to their age with those between 40 and 44, 45 and 49 and 50 and over constituting groups I, II and III, respectively. Results: Only 15% of the patients of group III had localized disease (p = 0.002). Group III patients had a significantly lower response rate to initial chemotherapy and a higher disease progression rate during therapy (complete response rate: 33.3%, progression rate: 44.4%, p = 0.035). The multivariate analysis revealed that advanced stage was the only independent prognostic factor for survival (p = 0.0011). Conclusion: Testicular germ cell tumor patients over 50 years old presented with a more advanced stage and had higher disease progression and disease mortality rates.
Does Lower-Pole Caliceal Anatomy Predict Stone Clearance after Shock Wave Lithotripsy for Primary Lower-Pole Nephrolithiasis?
Authors: Talas Halit , Kilic Ozcan , Tangal Semih , Safak Mut
Published: September 2007

Aim: In order to have an idea about the success rates after extracorporeal shock wave lithotripsy (SWL) in patients with lower-pole stones, we reviewed the caliceal anatomy of the patients treated in our clinic. Patients and Methods: One hundred and ninety-eight patients having at least a 3-month follow-up period, with a single stone located in the lower pole, were included. Lower infundibulopelvic angle (LIP-A), infundibular width, and infundibular length were measured from standard intravenous urograms taken before initial ESWL. Results: One hundred and thirty patients (65%) were male, and 68 patients (35%) were female. We found no impact of age, sex, and affected side on the results of ESWL. The overall stone-free rate was 61.1% after 3 months of follow-up. The stone-free rates were 47.8 and 81.4% in patients with an acute (<70°) and an obtuse (≧70°) LIP-A, respectively (p = 0.007). Taking the infundibular width into consideration, the stone-free rates were 85.4 and 43.2% for favorable and unfavorable angles and widths (p = 0.003). However, infundibular length and stone sizes were not found to have important effects on a stone-free status (p = 0.546 and p = 0.283). Conclusion: We conclude that LIP-A (≧70°) has the greatest impact on the clearance of residual fragments produced by SWL.
Is Antegrade Endopyelotomy Really Less Invasive than Open Pyeloplasty?
Authors: Dobry E. , Usai P. , Studer U.E. , Danuser H.
Published: September 2007

Objective: We investigated the invasiveness of antegrade endopyelotomy and open pyeloplasty in two consecutive series of patients with ureteropelvic junction obstruction. Patients and Methods: 98 patients were treated by open pyeloplasty from 1980 to 1991, and 137 patients by antegrade endopyelotomy from 1991 to 1999. Diagnosis of ureteropelvic junction obstruction was made by excretory urogram and/or antegrade pyelography, diuretic renography and retrograde pyelography. Invasiveness was evaluated by the postoperative need for analgesics, the complication rate and the residual long-term symptoms after surgery. Results: The postoperative need for opiate analgesics was significantly higher in patients after open pyeloplasty than after antegrade endopyelotomy. Ten percent of the patients complained of problems with the lumbotomy scar after open pyeloplasty, which was not encountered after endopyelotomy. Complications after open pyeloplasty occurred in 24% and were more severe than the 11% seen after endopyelotomy. The primary success rate after open pyeloplasty was 98 and 89% after antegrade endopyelotomy. The long-term success rate, ≧24 month postoperatively, was 96% (median follow-up 37 (24–196) months) and 76% (median follow-up 32 (24–73) months), respectively. Conclusion: Open pyeloplasty and endopyelotomy both have a high success rate with better patency results after open pyeloplasty. Open pyeloplasty is more invasive and has a higher morbidity. Endopyelotomy is a minimally invasive procedure with faster recovery, fewer and minor complications, significantly less need for peri- and postoperative analgesics, less residual pain due to the access, and no functional and esthetic sequelae of lumbotomy.
Cytomegalovirus and Clostridium difficile Ischemic Colitis in a Renal Transplant Recipient: A Lethal Complication of Anti-Rejection Therapy?
Authors: Veroux Massimiliano , Puzzo Lidia , Corona Daniela , Buffone Antonino , Tallarita Tiziano , Murabito Paolo , Veroux Pierfrancesco
Published: September 2007

Intestinal ischemia is reported to be the most common gastrointestinal complication of renal transplantation and a potential cause of morbidity and mortality. The recent use of more potent immunosuppressive drug regimens has reduced the incidence of acute rejection, increasing the incidence of potentially fatal infectious complications, such as clinically important cytomegalovirus (CMV) infection. A 42-year-old kidney transplant recipient experienced on postoperative day 10 a dehiscence of the ureterovesical anastomosis, associated with a 7-cm longitudinal tear graft on the lower pole of the kidney and an ureteral ischemia. A graft biopsy demonstrated a mild acute rejection for which the patient received an unsuccessful administration of steroids, with progression of the rejection, so that 1 mg/kg/day antithymocyte globulin was administered. Two days later the patient presented with fever (39.5°C), diffuse abdominal pain with tenderness and bloody diarrhea, and diagnosis of CMV colitis was achieved; rectal samples were taken for histologic examination, and Clostridium difficile toxin was isolated. A subtotal colectomy with Hartmann’s procedure was performed, but the patient died 13 days later of a multiple organ failure. The risk of lethal CMV colitis is increased in patients being treated with anti-rejection therapy for severe acute rejection; the occurrence of simultaneous infection, such as pseudomembranous colitis, usually characterized by a favorable prognosis, increases the mortality rate in these patients.
Increased Serum Levels of Circulating CD40 Ligand in Patients with Bullous Pemphigoid: Preliminary Results
Authors: Watanabe R. , Ishiura N. , Nakashima H. , Yazawa N. , Kuwano Y. , Tada Y. , Okochi H. , Fujimoto M. , Tamaki K.
Published: September 2007

Background: Autoimmune bullous diseases are characterized by autoantibodies against specific adhesion molecules of the skin and/or mucous membrane. While these autoantibodies are known to play a primary role in the disease manifestation, it remains unknown how disease-specific autoreactive B cells and autoantibodies are induced. Recent studies have indicated the importance of the CD40 and CD40 ligand (CD40L) receptor-ligand pair in the immunopathogenesis of autoimmune diseases. CD40L circulates in soluble form, and some reports suggest that serum soluble CD40L (sCD40L) levels are increased in various autoimmune diseases. Objectives: To determine serum sCD40L levels in patients with pemphigus vulgaris (PV) and bullous pemphigoid (BP), and to determine their correlation with clinical findings and laboratory findings. Patients and Methods: Sera from 10 PV patients, 35 BP patients and 12 normal controls were subjected to ELISA assays to measure serum levels of sCD40L, anti-desmoglein-3 antibody and anti-BP180 antibody. Results and Conclusions: Circulating sCD40L levels were significantly elevated in BP patients, but not in PV patients. Serum sCD40L levels increased in the early stage of disease onset and recurrence in BP patients. In conclusion, circulating sCD40L levels may be a useful marker for early activation of autoimmune diathesis and, furthermore, an effective therapeutic target in patients with BP.
Neurological Disorders in Patients with Bullous Pemphigoid
Authors: Cordel Nadège , Chosidow Olivier , Hellot Marie-France , Delaporte Emmanuel , Lok Catherine , Vaillant Loïc , Bernard Philippe , D’Incan Michel , Roujeau Jean Claude , Joly Pascal
Published: September 2007

Background: Unexpected cases of bullous pemphigoid (BP) have been reported in adult patients with various neurological disorders suggesting a possible relationship between these diseases. Objectives: (1) To determine the prevalence and types of neurological disorders in patients with BP, (2) to assess patients’ functional impairment, and (3) to compare the clinical and biological findings as well as prognosis of BP patients presenting with or without neurological disorders. Methods: BP patients with neurological disorders were selected in a series of 341 consecutive BP patients treated in 20 French Dermatology Departments. Functional impairment was prospectively assessed using the Karnofsky score which is a measure of patients’ general condition. Results: At least one neurological disorder was present in 123 of the 341 BP patients (36%). They primarily consisted of dementia (n = 68; 20%; 95% CI: 16–25%), cerebral stroke (n = 52; 15%; 95% CI: 4–19%), and/or Parkinson’s disease or parkinsonism (n = 32; 9%; 95% CI: 7–13%). BP patients with neurological disease were older than patients without neurological disease (83.8 ± 7.5 years vs. 79.3 ± 10.3 years, p < 10–4). They also had a lower Karnofsky score (47 ± 19% vs. 74 ± 20%, p < 10–4). One-year overall survival rates of the two groups were 50.8% (95% CI: 41.8–59.7) and 78.7% (95% CI: 73.0–84.2), respectively (p < 10–4). In contrast, the number of bullae and main biological features at baseline were not different between the two groups of patients. Conclusion: This study demonstrated a high frequency of neurological disorders, particularly dementia, in BP patients. Most of these patients had a severe functional impairment and a poor prognosis.
S-100B and FDG-PET/CT in Therapy Response Assessment of Melanoma Patients
Authors: Strobel Klaus , Skalsky Jeannine , Steinert Hans C. , Dummer Reinhard , Hany Thomas F. , Bhure Ujwal , Seifert Burkhardt , Pérez Lago Marisol , Joller-Jemelka Helen , Kalff V.
Published: September 2007

Objective: To compare the value of the tumor marker S-100B protein and fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in patients treated for melanoma metastases. Methods: In 41 patients with proven melanoma metastases, S-100B measurements and FDG-PET/CT were performed before and after therapy. The change of S-100B levels (ΔS-100B) was assessed. In all patients, therapy response was assessed with PET/CT using visual criteria and change of maximal standard uptake value (ΔSUVmax.) or total lesion glycolysis (ΔTLG). Results: In 15 of 41 patients (37%), S-100B values were not suitable because they were normal before and after therapy. In 26 patients, S-100B was suitable for therapy response assessment. PET/CT was suitable for response assessment in all patients. Correlations between ΔS-100B and ΔTLG (r = 0.850, p < 0.001) and between ΔS-100B and ΔSUVmax. (r = 0.818, p < 0.001) were both excellent. A complete agreement between S-100B and PET/CT response assessment was achieved in 22 of 26 patients. In 4 patients, therapy response differed between the S-100B and PET/CT findings, but subsequent S-100B measurements realigned the S-100B results with the later PET/CT findings. Conclusion: In a third of our patients with metastases, the S-100B tumor marker was not suitable for therapy assessment. In these patients, imaging techniques remain necessary, and FDG-PET/CT can be used for response assessment.
Pain and Photodynamic Therapy
Authors: Lindeburg Katrine E.K. , Brogaard Henriette M.V. , Jemec Gregor B.E.
Published: September 2007

Background: Photodynamic therapy (PDT) is increasingly used in the treatment of various skin diseases. The main adverse effect in PDT treatment is pain. Each lesion is generally treated twice, and clinical experience suggests that the 2nd treatment causes more pain than the 1st and thus becomes a therapy-limiting factor. Objectives: To investigate the intrapatient variation in the experience of pain, between 1st and 2nd PDT treatments. Methods: We registered patients treated with PDT by using a mechanical visual analogue scale (VAS). Patients were tested immediately after the 1st and 2nd PDT treatments. Intrapatient comparison was made comparing 1st and 2nd treatments. Results: A total of 38 patients were included. The median VAS score increased significantly according to the Wilcoxon matched-pairs signed-ranks test (p < 0.02) from 4 after the 1st PDT (range 0–8) to 4.75 (range 1–10) after the 2nd PDT treatment. The VAS score of pain was increased in the 2nd treatment for 21 patients, remained unchanged in 6 patients and was reduced in 11 patients who reported less pain after the 2nd treatment. Patients who scored low (VAS <5) after the 1st treatment experienced an increase in mean VAS score of 1.4 at the 2nd PDT treatment. In contrast, subjects with a high VAS score (>5) after the 1st PDT had a mean decrease in the VAS score of 0.26 at the 2nd PDT treatment. The difference (p = 0.005) suggests that the pain at the 1st PDT treatment may be predictive of future pain. Conclusion: The 2nd treatment of PDT was significantly more painful than the 1st, although some patients experienced reduced pain on the 2nd treatment. The pain experienced at the 1st PDT treatment may be predictive of the pain at subsequent treatments.
Pimecrolimus 1% Cream in Non-Specific Inflammatory Recurrent Balanitis
Authors: Georgala S. , Gregoriou S. , Georgala C. , Papaioannou D. , Befon A. , Kalogeromitros D. , Rigopoulos D.
Published: September 2007

Background: Non-specific balanitis is a common inflammatory dermatosis with frequent relapses and considerable impact on male sexual life. Objective: To evaluate the efficacy and safety of pimecrolimus 1% cream in recurrent non-specific balanitis. Methods: Twenty-six patients with recurrent flares of non-specific balanitis were randomly assigned to 1 group applying pimecrolimus cream 1% and 1 group applying placebo on the glans twice daily for 7 days. The patients were assessed on day 14. They were instructed to continue applying the agent whenever symptoms initialized for the following 90 days and take account of the cumulative days with symptoms. Results: Seven out of the 11 (63.6%) patients in the pimecrolimus group and 1 out of 11 (9%) in the control group were free of all symptoms and lesions after 14 days, 3 (27.3%) in both groups reported improvement, while 1 (9.1%) in the pimecrolimus and 7 (63.6%) in the control group remained unaffected. (χ2 = 9.0, d.f. = 2, p = 0.011). Days with symptoms during the 90-day follow-up period were 7.50 ± 3.02 for the pimecrolimus and 17.62 ± 4.40 for the control group (p = 0.000064). Conclusions: Pimecrolimus 1% cream is promising in relieving symptoms and signs of non-specific balanitis during flares and controlling the disease during long-term follow-up.
Borrelia burgdorferi-Associated Primary Cutaneous Marginal-Zone B-Cell Lymphoma: A Case Report
Authors: Monari P. , Farisoglio C. , Calzavara Pinton P.G.
Published: September 2007

An association between Borrelia burgdorferi with primary cutaneous B-cell lymphoma (PCBCL) has long been suspected but just recently, thanks to a polymerase chain reaction technique, it had been possible to demonstrate B. burgdorferi-specific DNA in skin lesions of patients with different PCBCL subtypes. Locating cases of PCBCL that are related to B. burgdorferi infection could be really important for therapeutic implications; in fact, there are several reports of PCBCL responding to antibiotic therapy against B. burgdorferi. We report a case of B. burgdorferi-associated primary cutaneous marginal-zone B-cell lymphoma that, after specific antimicrobial therapy, did not show any clinical regression. We can conclude that additional studies are necessary in order to establish the use of antimicrobial therapy in B. burgdorferi-associated PCBCL.
Thalidomide in the Treatment of Kaposi’s Sarcoma
Authors: Rubegni Pietro , Sbano Paolo , De Aloe Giovambattista , Flori Maria Laura , Fimiani Michele
Published: September 2007

Background: Kaposi’s sarcoma (KS) is a lymphangioproliferative tumour. Therapy of KS depends on the characteristics of the disease, especially area and growth rate of lesions, and patient condition. Currently symptomatic resectable lesions are excised, whereas more advanced disease and unresectable lesions are treated with radiotherapy. If a large area or internal organs are affected or other treatments fail, chemotherapy is used. Recently some authors have reported their encouraging experience in the use of thalidomide in patients with AIDS-related KS. Objective: To evaluate the efficacy of thalidomide in 3 patients with non-AIDS-related KS. Methods: Two patients with classic widespread cutaneous and 1 with iatrogenic cutaneous and visceral KS were treated with thalidomide (100 mg/day) for 12 months. Results: In all 3 patients partial remission was evident after 4 months of thalidomide therapy; in 2 out of 3 complete remission was achieved after 12 months of treatment. Conclusions: Our results seem to confirm the utility of thalidomide in the treatment of non-AIDS-related KS.
Dermoscopic Appearance of Juvenile Xanthogranuloma
Authors: Palmer Antony , Bowling Jonathan
Published: September 2007

Juvenile xanthogranuloma (JXG) is the commonest form of non-Langerhans cell histiocytosis and manifests as asymptomatic yellow-red papulonodules that usually occur in childhood and spontaneously regress within a year of formation. The diagnosis may be made by clinical examination alone and confirmed by histology in cases of diagnostic doubt. Here we report the use of dermoscopy in evaluating skin lesions suggestive of JXG. Three patients diagnosed as having JXG in our dermatology department over the last year showed a characteristic orange-yellow ‘setting sun’ appearance on dermoscopy. We therefore feel that the use of dermoscopy can be extended to include the examination of non-pigmented skin lesions, particularly in paediatric patients.
HPV-2 Isolates from Patients with Huge Verrucae Vulgaris Possess Stronger Promoter Activities
Authors: Lei Yan-Jun , Wang Chen , Gao Chen , Jiang Hui-Ying , Chen Jian-Ming , Han Jun , Yuan Yu-Kang , Dong Xiao-Ping
Published: September 2007

Objectives: To assess the influences of the mutations within the long control region (LCR) and E2 open reading frame (ORF) of the human papillomavirus-2 (HPV-2) isolates from patients with extensive verrucae vulgaris with cutaneous horns in the activities of the viral early promoters. Methods: A PCR method was applied for screening HPV DNA in the lesion specimens and the complete HPV-2 genomes was analyzed. Recombinant CAT-reporter plasmids containing various HPV-2 LCRs and mammalian expression plasmids containing E2 ORF were constructed. The promoter activity was evaluated by transient transfection. Results: The whole HPV-2 genomes were obtained from both patients. Several mutations in LCR and mutations leading to alterations of amino acids in E2 protein were identified in isolate-1, while a few point mutations in LCR were seen in isolate-2. Under the control of LCRs, the viral early promoter activities of isolate-1 and isolate-2 were increased 3- and 2-fold, respectively. Alterations of amino acids in E2 protein of isolate-1 partially abolished its promoter repressive activity. Compared with that of prototype HPV-2, the promoter activity of isolate-1 in the presence of its E2-expressing plasmid was significantly increased. Conclusions: The increased promoter activities might be linked, at least partially, to the clinical phenotypes of the uncommon huge verrucae vulgaris.
Newer N-Phthaloyl GABA Derivatives with Antiallodynic and Antihyperalgesic Activities in Both Sciatic Nerve and Spinal Nerve Ligation Models of Neuropathic Pain
Authors: Yogeeswari Perumal , Ragavendran Jegadeesan Vaigunda , Sriram Dharmarajan , Kavya Ramkumar , Vanitha Kaliappan , Neelakantan Harshini
Published: September 2007

Background: There is considerable research evidence supporting a palliative role for γ-aminobutyric acid (GABA)-ergic neurotransmission and voltage-gated sodium channel blockade in neuropathic pain conditions. Hence, the present study was undertaken to assess the peripheral analgesic, antiallodynic and antihyperalgesic activities of the synthesized structural analogues of GABA. Methods: The screening study included acute tissue injury, chronic constriction injury (CCI), and spinal nerve ligation (SNL) models of neuropathic pain. Results: All of the tested compounds sup-pressed the acetic acid-induced writhing response significantly in comparison to the control. In particular, compound JVP-8 was observed to be the most active compound with percent inhibition greater than that of the standard drug aspirin (97.8% inhibition of writhing response as against 97.0% shown by aspirin). In neuropathic pain studies, compound JVP-5 (100 mg/kg i.p.) emerged as the most active compound affording maximum protection against dynamic allodynia and mechanical hyperalgesia in the CCI model, and against spontaneous pain and mechanical hyperalgesia in SNL rats. Conclusion: In this study, we have demonstrated that combining phthalimide pharmacophore with GABA has evolved compounds effective for the treatment of neuropathic pain.
Selection of Anticoagulants for Leukocytapheresis Therapy in Cases of Active Ulcerative Colitis
Authors: Kanke Kazunari , Hoshino Mina , Tominaga Keiichi , Nakano Michiko , Terano Akira , Hiraishi Hideyuki
Published: September 2007

Background and Aim: Leukocytapheresis (LCAP) is an extracorporeal leukocyte removal therapy that removes immunocompetent leukocytes from the peripheral blood. Nafamostat mesilate (NM) is the most commonly used anticoagulant for LCAP due to various benefits associated with its use, such as a reduced likelihood of bleeding and minimization of adverse reactions caused by contact between blood and the LCAP device. However, adverse reactions have also been reported with NM administration. We reviewed the safety of anticoagulants other than NM, from the perspective of bradykinin production and the consequent drop in blood pressure during treatment. Methods: For each of 10 patients with ulcerative colitis, we used four types of anticoagulants sequentially [NM (30–50 mg), heparin, low-molecular-weight heparin (LMWH) and NM (1 mg), and LMWH] for LCAP. We then examined the changes in the blood bradykinin concentrations from the perspective of adverse reactions during LCAP. Results: The bradykinin production levels from Cellsorba EX varied, depending on the type of anticoagulant used. NM alone (30–50 mg) or LMWH + NM (1 mg) inhibited bradykinin production, whereas heparin alone or LMWH alone significantly accelerated it. However, an excessive fall of blood pressure was not noted in any of the cases. Use of LMWH alone was frequently associated with pressure elevations in the column. Conclusions: Given the significant benefits of minimized adverse reactions of LCAP and of continuation of LCAP, we suggest that an appropriate selection of the anticoagulant(s) may allow safer execution of LCAP.
Dietary Lupin Protein Lowers Triglyceride Concentrations in Liver and Plasma in Rats by Reducing Hepatic Gene Expression of Sterol Regulatory Element-Binding Protein-1c
Authors: Spielmann Julia , Shukla Anjali , Brandsch Corinna , Hirche Frank , Stangl Gabriele I. , Eder Klaus
Published: September 2007

Background: Recently, it has been shown that dietary lupin protein lowers plasma triglyceride concentrations in rats. In this study, we investigated the hypothesis that this effect is due to a downregulation of sterol regulatory element-binding protein (SREBP)-1c, a transcription factor that regulates the expression of lipogenic enzymes in the livers of rats. Methods: Two groups of 12 rats each were fed semisynthetic diets containing 200 g/kg of either casein (control group) or lupin protein from Lupinus albus for 22 days. Results: Rats fed the diet containing lupin protein had lower concentrations of triglycerides in the liver, plasma and VLDL + chylomicrons (p < 0.05). The concentration of protein in VLDL + chylomicrons was also lower in rats fed lupin protein than in rats fed casein (p < 0.05). The mRNA concentrations of SREBP-1c and fatty acid synthase in the liver were lower in rats fed lupin protein than in rats fed casein (p < 0.05). The mRNA concentrations of lipoprotein lipase in the liver did not differ between both groups of rats. Conclusion: This study confirms that a protein isolated from L. albus is strongly hypotriglyceridemic in rats. It is shown for the first time that this effect is at least in part due to a downregulation of SREBP-1c in the liver which in turn leads to a reduction in hepatic fatty acid synthesis.
From Mitochondria to Disease: Role of the Renin-Angiotensin System
Authors: de Cavanagh E.M.V. , Inserra F. , Ferder M. , Ferder L.
Published: September 2007

Mitochondria are energy-producing organelles that conduct other key cellular tasks. Thus, mitochondrial damage may impair various aspects of tissue functioning. Mitochondria generate oxygen- and nitrogen-derived oxidants, being themselves major oxidation targets. Dysfunctional mitochondria seem to contribute to the pathophysiology of hypertension, cardiac failure, the metabolic syndrome, obesity, diabetes mellitus, renal disease, atherosclerosis, and aging. Mitochondrial proteins and metabolic intermediates participate in various cellular processes, apart from their well-known roles in energy metabolism. This emphasizes the participation of dysfunctional mitochondria in disease, notwithstanding that most evidences supporting this concept come from animal and cultured-cell studies. Mitochondrial oxidant production is altered by several factors related to vascular pathophysiology. Among these, angiotensin-II stimulates mitochondrial oxidant release leading to energy metabolism depression. By lowering mitochondrial oxidant production, angiotensin-II inhibition enhances energy production and protects mitochondrial structure. This seems to be one of the mechanisms underlying the benefits of angiotensin-II inhibition in hypertension, diabetes, and aging rodent models. If some of these findings can be reproduced in humans, they would provide a new perspective on the implications that RAS-blockade can offer as a therapeutic strategy. This review intends to present available information pointing to mitochondria as targets for therapeutic Ang-II blockade in human renal and CV disease.
Recent Advancement of Understanding Pathogenesis of Type 1 Diabetes and Potential Relevance to Diabetic Nephropathy
Authors: Ichinose Kunihiro , Kawasaki Eiji , Eguchi Katsumi
Published: September 2007

Type 1 diabetes mellitus is an autoimmune disease characterized by progressive destruction of pancreatic beta cells by genetic and environmental factors which leads to an absolute dependence of insulin for survival and maintenance of health. Although the majority of mechanisms of beta cell destruction remain unclear, many molecules, including proinflammatory cytokines and chemokines such as tumor necrosis factor alpha and monocyte chemoattractant protein-1, are implicated in the development of beta cell damage. Furthermore, beta cell destruction is enhanced by the Th1 and Th17 subsets of CD4+ T cells. In contrast, there are mechanisms involved in the maintenance of peripheral tolerance by regulatory T cells, the function of which depends on the pleiotropic cytokine transforming growth factor beta. Development and progression of renal injuries in patients with diabetic nephropathy are also associated with several growth factors and proinflammatory cytokines, including tumor necrosis factor alpha, insulin-like growth factor-1, monocyte chemoattractant protein-1, vascular endothelial growth factor, and transforming growth factor beta. Although the pathogenic mechanisms underlying type 1 diabetes and diabetic nephropathy are principally different, i.e., autoimmunity and inflammation, some common factors, including susceptibility genes and proinflammatory cytokines, are involved in both mechanisms, including infiltrating cell recruitment, upregulation of other cytokines and chemokines, or apoptosis.
Early versus Late Local Recurrences after Conservative Treatment of Breast Carcinoma: Differences in Primary Tumor Characteristics and Patient Outcome
Authors: Courdi A. , Largillier R. , Ferrero J.-M. , Lallement M. , Raoust I. , Ettore F. , Peyrottes I. , Chamorey E. , Balu-Maestro C. , Chapellier C.
Published: September 2007

Objectives: To investigate whether some aspects of patient or tumor characteristics influence the timing of local recurrence (LR) in breast cancer treated conservatively, and to assess the impact of the timing of LR on patient outcome. Methods: A retrospective analysis was conducted on patients treated with conservative breast surgery followed by radiotherapy for breast carcinoma who developed LR. Out of 2,008 cases treated in our Institute between 1977 and 2002, 180 ipsilateral LR were observed. Of these, 46 LR were observed within 36 months after treatment, called early local recurrence (ELR), 44 developed between 37 and 60 months, called medium local recurrence (MLR), and 90 occurred after 60 months, called late local recurrence (LLR). Patient and tumor characteristics were analyzed in the 2 groups and compared. Results: Primary tumors >20 mm were more frequently found in patients with ELR (31%) than in patients with LLR (17%, p = 0.047). Grade 3 tumors were more often encountered in patients with ELR than in patients with LLR (27 versus 7%, p = 0.0002). Patients with ELR more frequently had tumors with negative estrogen receptors than patients with LLR (37% versus 6%, p < 0.0001). There was no statistically significant difference in the axillary lymph node (LN) status between patients with ELR and those with LLR (35 and 23% of positive LN, respectively, p = 0.24). Tumor size, grade, LN status, hormone receptors and the timing of LR affected the specific survival (SS) from initial surgery. On multivariate analysis, only LN status and the timing of LR retained an independent prognostic value, with an odds ratio of 6.7 for ELR. After LR, the SS was also influenced by all of the above factors, and on multivariate analysis, LN status, hormone receptors and the timing of LR were independent predictors with an odds ratio of SS of 2.50 in case of ELR (p = 0.006). The 5-year SS after LR for ELR, MLR and LLR were 55.8, 74.8 and 79.5%, respectively. Conclusions: Unfavorable tumor characteristics such as big size, high grade, lack of hormone receptors, but not LN status, were associated with ELR. These findings suggest that patients with such aggressive tumor characteristics who do not recur early will have a lower risk of LLR than patients with more favorable factors.
Silver-Stained Nucleolar Organizer Regions in Normal and Dysplastic Cervical Lesions: Correlation with DNA Ploidy and S-Phase Fraction by Flow Cytometry
Authors: Singh Madhulika , Prasad Sahdeo , Kalra Neetu , Singh Uma , Shukla Yogeshwer
Published: September 2007

Objectives: To investigate the prognostic significance of DNA ploidy and silver-stained nucleolar organizer regions (AgNOR), their relation to the cytological grades of cervical dysplasia and correlation of cells in the S-phase of the cell cycle and DNA ploidy with AgNOR count. Methods: Multiparametric DNA flow-cytometric analysis and AgNOR count were performed on cervical smear samples, cytologically diagnosed as normal (n = 196), atypical squamous cells of unknown significance (ASCUS, n = 98) and various grades of cervical dysplasia (n = 127). Results: Among the cytological grade, aneuploid cases from low-grade squamous intraepithelial lesion (mild) and high-grade squamous intraepithelial lesion (moderate and severe) groups were showing high AgNOR counts (ranges 4.33–5.86 and 5.91–7.42, respectively). Aneuploid cases from the ASCUS group also presented high AgNOR (range 3.72–4.93). The high percentage of cells in the S-phase (>12%) correlated with these 2 parameters in the ASCUS and dysplasia groups. After grouping the cases into those with high (>4.0) and low (<4.0) AgNOR counts, significant correlations in the group with high AgNOR count with DNA ploidy, S-phase and cytological grade were recorded (p < 0.001). Results obtained from follow-up study revealed that cases with aneuploidy, high AgNOR count and S-phase fraction presented with a progressive trend of disease. Conclusions: Thus, the study shows that high AgNOR count, S-phase fraction and aneuploid DNA have prognostic significance in the early detection of cervical cancer.
Laparoscopic versus Open Total Mesorectal Excision: A Comparative Study on Short-Term Outcomes
Authors: Veenhof A.A.F.A. , Engel A.F. , Craanen M.E. , Meijer S. , de Lange-de Klerk E.S.M. , van der Peet D.L. , Meijerink W.J.H.J. , Cuesta M.A.
Published: September 2007

Background: Laparoscopic total mesorectal excision (TME) is being used in rectal cancer more frequently. The aim of this study was to analyze the differences in short-term outcomes between open and laparoscopic TME. Methods: In this nonrandomized consecutive study, the short-term outcomes of 100 patients undergoing TME for proven rectal cancer were analyzed. Results: Two groups of 50 patients underwent an open or laparoscopic TME for rectal cancer. Both groups were comparable. Laparoscopic surgery took longer to perform (250 vs. 197.5 min, p < 0.01), but was accompanied by less blood loss (350 vs. 800 ml, p < 0.01). Enteric function recovered sooner after laparoscopy. The numbers of major and minor complications were comparable between both groups, although fewer patients had major complications in the laparoscopic group (6 vs. 15 patients, p = 0.03). Hospital stay was shorter for patients who underwent a laparoscopic abdominoperineal resection (10 vs. 12 days, p = 0.04). Median follow-up was 17 months for the laparoscopic group and 22 months for the open group. Survival analyses between the groups showed no statistical difference in disease-free and overall survival. Conclusion: This study shows that laparoscopic TME for rectal cancer is a safe and feasible technique with some short-term benefits over open TME.
The Post-Surgical Inflammatory Response Provokes Enhanced Tumour Recurrence: A Crucial Role for Neutrophils
Authors: van den Tol M.P. , ten Raa S. , van Grevenstein W.M.U. , van Rossen M.E.E. , Jeekel J. , van Eijck C.H.J.
Published: September 2007

Background/Aims: Peritoneal trauma activates a cascade of peritoneal defence mechanisms responsible for postoperative intra-abdominal tumour recurrence. After peritoneal trauma, inflammatory cells and soluble factors are present in the abdominal cavity and can be captured in lavage fluids. The present study evaluated which component enhances intra-abdominal tumour recurrence. Furthermore, we evaluated which inflammatory cells are present and studied the influence of anti-neutrophil serum (ANS) on peritoneal tumour recurrence. Methods: In a peritoneal trauma model in rats, postoperative lavage fluids were collected and separated into cellular and supernatant components. Both components were injected in naïve rats together with CC531s colon carcinoma cells. In a second experiment, rats were treated with one or three doses of ANS. Results: Intraperitoneal injection of naïve recipients with inflammatory cells or supernatant resulted in significant tumour recurrence. Severe peritoneal trauma provoked significant intra-abdominal neutrophil influx which could be prevented by ANS. Treatment with one dose did not affect blood cell counts and significantly reduced tumour recurrence. Treatment with three doses of ANS decreased blood lymphocytes, monocytes, and neutrophils and induced tumour load. Conclusions: Neutrophils play a crucial role in postoperative adhesion and growth of spilled tumour cells after surgical peritoneal trauma. Prevention of peritoneal neutrophil influx reduces local tumour recurrence.