bluuebunny/crossref_metadata_2025 huggingface dataset:
In vitro and in vivo Study of Cell Growth Inhibition of Simvastatin on Chronic Myelogenous Leukemia Cells
Authors: Yang Yong-Chang , Huang Wen-Fang , Chuan Liang-Min , Xiao Dai-Wen , Zeng Ya-Li , Zhou Ding-An , Xu Guo-Qiang , Liu Wen , Huang Bo , Hu Qi
Published: October 2008

Background: Statins, a family of 3-hydroxy-3-methylglutaryl CoA (HMG CoA) reductase inhibitors, are being investigated for the therapy and prevention of cancers. Here we aimed to investigate the effects of simvastatin on chronic myelogenous leukemia (CML) cells in vitro and in vivo, and to elucidate the mechanisms. Methods: Cell proliferation and cell cycle were measured after K562 cells were incubated with simvastatin, and differentially expressed genes were determined by oligonucleotide microarray. Changes of 2 genes obtained by oligonucleotide microarray were validated by real-time RT-PCR, and immunohistochemistry was performed to determine expression of proliferating cell nuclear antigen (PCNA). Finally, a xenograft tumor model was constructed to evaluate the effects of simvastatin in vivo. Results: Simvastatin could inhibit K562 cell proliferation, and the inhibition rate was approximately 30% after treatment with 20 µmol/l simvastatin for 48 h. Cell cycle was arrested in G1 phase, as shown by flow cytometry results. Fifteen downregulated, 9 upregulated cell cycle-related genes and decreased PCNA protein were observed in the presence of simvastatin. Furthermore, simvastatin exhibited impairment of xenograft tumor growth in nude mice and also blocked cell cycle in G1 phase. Conclusion: Simvastatin can inhibit CML cell proliferation in vitro and in vivo, and its mechanisms might be involved in cell cycle regulation.
Efficient Inhibition of Ovarian Cancer Growth and Prolonged Survival by Transfection with a Novel Pro-Apoptotic Gene, hPNAS-4, in a Mouse Model
Authors: Yang Fan , Li Zhengyu , Deng Hongxin , Yang Hanshuo , Yan Fei , Qian Zhiyong , Chen Lijuan , Wei Yuquan , Zhao Xia
Published: October 2008

Objective: We transfected ovarian cancer cells and administered recombinant plasmid encoding hPNAS-4 to nude mice bearing ovarian cancer, aiming to evaluate the effect of hPNAS-4 against ovarian cancer in vitro and in vivo. Methods: Ovarian cancer SKOV3 cells were transfected with hPNAS-4-plasmid, and cell proliferation was evaluated by MTT assay; apoptosis was examined by DNA ladder, Hoechst33258 staining and flow-cytometric assays. Nude mice bearing ovarian cancers were treated with hPNAS-4-p/liposome. Tumor growth was determined and survival was recorded. TUNEL assay and microvessel density was assessed to evaluate apoptosis and angiogenesis. Results: Both inhibition of proliferation (p < 0.05) and induction of apoptosis (p < 0.05) were observed in SKOV3 cells transfected with hPNAS-4-p in vitro. In hPNAS-4-p-treated tumor cells in vivo, tumor growth significantly decreased, while the survival time of tumor-bearing mice was prolonged compared with control groups (p < 0.05). Increased apoptosis of tumor cells and decreased angiogenesis in tumor tissue were also observed. Conclusions: Our promising results on the potential antitumor effects of hPNAS-4 on ovarian cancer in vitro and in vivo may be explained, in part, by the induction of apoptosis and inhibition of angiogenesis. Consequently, hPNAS-4 has potential as a new gene therapy for human ovarian cancer.
Prevalence and Outcome of Congenital Left Ventricular Aneurysms and Diverticula in an Adult Population
Authors: Ohlow Marc-Alexander , Secknus Maria A. , Geller Johann C. , von Korn Hubertus , Lauer Bernward
Published: October 2008

Objectives: We sought to investigate the prevalence and clinical outcome of congenital left ventricular aneurysms (LVAs) and diverticula (LVD) in a large adult population. Methods: We retrospectively studied the left ventricular angiograms of 12,271 consecutive patients undergoing cardiac catheterization at our institution and analyzed the medical records of the patients. Results: The overall prevalence of LVA/LVD was 0.76% (94 patients): there were 42 patients with LVA (0.34%) and 52 patients with LVD (0.42%). Men were more likely to have LVA (62 vs. 38%), and women were more likely to have LVD (75 vs. 25%; p = 0.001 for both). The mean time of follow-up was 56 ± 6 months and was focused on clinical events, rehospitalization and survival. Mortality was 6% with no cardiac death. Patients with LVD were significantly more likely to have embolic events (p = 0.04). Patients with LVA and LVD were more likely to have rhythm disturbances compared with controls (p = 0.01 for both). Incidence of syncope was not different in both groups (p = 0.4 and 0.12, respectively). There was no reported incidence of rupture. Conclusion: This large single-center study suggests that the prevalence of LVA/LVD in adults is up to 20-fold higher than previously reported. One third of the affected patients in our series had nonfatal cardiovascular events during follow-up, with a predominance of embolic events in the LVD group.
Single Large Inguinal Lymph Node Metastasis in Human Papillomavirus-Induced Early Invasive Vulvar Cancer of the Anterior Fourchette in Two Young Women
Authors: Hampl Monika , Kueppers Volkmar , Bender Hans Georg
Published: October 2008

The incidence of human papillomavirus (HPV)-induced vulvar cancer in young women is increasing and often presents as microinvasive or early invasive tumors in a grade 3 vulvar intraepithelial neoplasia. So far, the risk of lymph node metastases in early invasive vulvar carcinoma (depth of invasion 1.1–2.0 mm) is reported to be less than 8%. We present 2 cases of young women with early invasive vulvar cancers (depth of invasion 1.5 and 2.0 mm) induced by HPV 16 and 42. In both cases, the cancers are located between the clitoris and urethra and are each accompanied by one groin macro-metastatic lymph node. This case report highlights the necessity for complete inguinofemoral lymphadenectomy and/or adequate radiation therapy of the groin in early invasive tumors in young women to prevent cancer recurrence in the groin. Additionally, the indication for a sentinel node procedure in these specific cases requires particular caution.
A Treatment Selection Protocol for Recurrent Ovarian Cancer Patients: The Role of FDG-PET/CT and Staging Laparoscopy
Authors: Fagotti A. , Fanfani F. , Rossitto C. , Lorusso D. , De Gaetano A.M. , Giordano A. , Vizzielli G. , Scambia G.
Published: October 2008

Objective: To investigate the best diagnostic and staging strategy for recurrent ovarian cancer. Methods: The negative predictive value, specificity, positive predictive value, sensitivity, and accuracy rates of the fluorine-18-fluorodeoxyglucose positive emission tomography computed tomography (FDG-PET/CT) and staging laparoscopy in identifying surgically treatable/untreatable patients are assessed in a consecutive series of 70 recurrent ovarian cancer cases. Moreover, the diagnostic performance of each staging procedure in the evaluation of the number of nodules is analyzed. Results: The negative predictive value of the FDG-PET/CT was 83.3%, whereas the positive predictive value was 76.9%. Specificity was 55.6%, whereas sensitivity was 93.0%. Accuracy rate was 78.6%. Negative predictive value, specificity, positive predictive value, sensitivity, and accuracy rate of staging laparoscopy were 88.9, 64.0, 80.8, 95.0 and 83.1%, respectively. Combined radiological and laparoscopic evaluation showed a negative predictive value of 88.9%, a specificity of 59.3%, a positive predictive value of 78.8%, a sensitivity of 95.3%, and an accuracy rate of 81.4%. The number of nodules identified by FDG-PET/CT corresponded in only 23 patients (40.3%) at laparotomy, whereas 15 of 30 patients were correctly diagnosed (50.0%) by staging laparoscopy. Conclusions: The combination of FDG-PET/CT and staging laparoscopy has a significant effect on the multimodal approach to the population of patients with recurrent ovarian cancer. Such techniques should be considered complementary, because of the potential of each one to identify a different setting of the disease.
Role of AIB1 for Tamoxifen Resistance in Estrogen Receptor-Positive Breast Cancer Cells
Authors: Su Qingbo , Hu Sanyuan , Gao Haidong , Ma Rong , Yang Qifeng , Pan Zhenhua , Wang Tiantian , Li Feng
Published: October 2008

Objectives: The p160 nuclear receptor coactivator, AIB1 (amplified in breast cancer 1), is frequently overexpressed in human breast cancer and has been shown to be associated with tamoxifen resistance. The present study aimed to investigate the role of AIB1 in tamoxifen resistance of breast cancer cells. Methods: We reconstructed the RNA interference expression vector, pGenesil-1-U6, specially targeting AIB1 mRNA, and it was stably transfected into the human breast cancer cell line BT474. Cell proliferation and cell cycle distribution were assessed in the cells transfected with scramble control shRNA (BT474/shControl) and AIB1 shRNA (BT474/shAIB1) to explore the possible functions of AIB1 in breast cancer progression. The expression of AIB1, ERα, HER2 and pS2 was analyzed in the presence of 17β-estradiol or 4-hydroxytamoxifen (Tam) by Western blot analysis. Results: Compared with the parental BT474 and the BT474/shControl cells, the levels of AIB1 mRNA and protein were significantly reduced in BT474/shAIB1 cells. A knockdown of AIB1 levels restored the inhibitory effect of tamoxifen on cell proliferation. Conclusions: Tam behaves like an estrogen agonist in ER-positive breast cancer cells that express high levels of AIB1 and HER2, resulting in de novo resistance. Knockdown of AIB1 can eliminate this cross talk and restore the antitumor effects of tamoxifen.
Gender Differences in Treatment Outcomes among Patients with Non-Small Cell Lung Cancer Given a Combination of Carboplatin and Paclitaxel
Authors: Yamamoto Harukaze , Sekine Ikuo , Yamada Kazuhiko , Nokihara Hiroshi , Yamamoto Noboru , Kunitoh Hideo , Ohe Yuichiro , Tamura Tomohide
Published: October 2008

Objectives: It was the aim of this study to investigate gender differences in the outcomes of carboplatin and paclitaxel chemotherapy in patients with unresectable stage IIIB-IV non-small cell lung cancer (NSCLC). Methods: Gender, age, performance status, histology, hematological toxicity, tumor responses and survival parameters obtained retrospectively by medical chart review were analyzed. Results: A total of 227 patients (147 males and 80 females) were included. The median lowest leukocyte count was 2,900 (range 1,200–12,400)/µl in males and 2,200 (range 600–6,500)/µl in females (p < 0.001). Grade 3–4 leukopenia was noted in 15% of male and in 39% of female patients (p < 0.001). In both genders, the response rate in evaluable patients was 39%. The median progression-free survival was 4.4 months for men and 5.3 months for women (p = 0.0081). After progression of the disease, gefitinib was administered in 64 (44%) male and 45 (56%) female patients, with a median treatment of 35 and 144 days, respectively. The median survival time was 11.9 months for men and 22.2 months for women (p < 0.001). Conclusion: Female gender was associated with a favorable prognosis in patients with NSCLC who received carboplatin and paclitaxel chemotherapy, although the response rates did not differ between the genders. Of note, hematological toxicity was more severe in female patients.
Effects of Human Growth Hormone on Haematopoietic Recovery of Rats Receiving Chemotherapy
Authors: Zhang Yi , Chen Jiayong , Liang Daoming , Yuan Yong , Wu Xiaoting
Published: October 2008

Human growth hormone (hGH) is a pleiotropic cytokine targeting a variety of tissues. Its protective effects on haematopoiesis during treatment with chemotherapeutic drugs were investigated. Sprague-Dawley rats were intraperitoneally administered with both carboplatin and 5-fluorouracil together with or without recombinant hGH (rhGH) at a dose of 1 IU/kg/day. Body weight, full blood count, bone marrow differential count and expression of proliferating cell nuclear antigen (PCNA) in bone marrow were measured weekly for 4 weeks in chemotherapy-treated (CT) or chemotherapy plus rhGH-treated (CT+GH) animals. During the first week, body weight, white blood cell count, haematopoietic count and reticulocyte count were decreased in the CT group as well as in the CT+GH group, but to a lesser extent in the latter group (CT vs. CT+GH group, p < 0.05). Further decreases were also prevented in the CT+GH group. Myeloid cells were extremely hypoplastic in the CT group, while in the CT+GH group, myeloid cells recovered from obviously hypoplastic to excessively hyperplastic in the first 2 weeks, and the myeloid karyocyte count increased significantly (CT+GH vs. CT group, p < 0.05). PCNA-positive cell count in the CT+GH group was also significantly higher than in the CT group (CT+GH vs. CT group, p < 0.05). Thus, rhGH showed a promising protective effect on body weight loss and haematopoietic recovery of chemotherapy-treated rats, which may be useful in clinic to reduce the side effects of chemotherapy.
4-Diazopyrazole Derivatives as Potential New Antibiofilm Agents
Authors: Schillaci Domenico , Maggio Benedetta , Raffa Demetrio , Daidone Giuseppe , Cascioferro Stella , Cusimano Maria Grazia , Raimondi Maria Valeria
Published: October 2008

Background: The recognition that chronic infections and infections associated with medical devices are biofilm related has been the impulse for investigating the antibiofilm properties of some diazopyrazoles biologically active as antimicrobials. Methods: The susceptibility of staphylococcal biofilms was determined at concentrations ranging from 25 to 1.5 µg/ml using crystal violet and methylthiazotetrazolium (MTT) staining. In the case of Candida albicans, we first assessed the anti-germ tube formation effect of 4-NO2 (compound 1c) and then we evaluated its antibiofilm activity at concentrations ranging from 100 to 6.2 µg/ml. Results: All the compounds were active against reference staphylococcal biofilm strains at the maximum tested concentration of 25 µg/ml; despite its remarkable activity as germ tube inhibitor, compound 1c showed weak activity against C. albicans biofilms at 100 µg/ml. Conclusion: 4-Diazopyrazoles represent an interesting source of antimicrobial compounds in the development of new antibiofilm agents.
Nevirapine Toxicity in Non-HIV Cancer Patients
Authors: Landriscina Matteo , Fabiano Annarita , Lombardi Valentina , Santodirocco Michele , Piscazzi Annamaria , Fersini Alberto , De Vis Koen , Barone Carlo , Cignarelli Mauro
Published: October 2008

Background: Nevirapine (NVP) is a nonnucleoside reverse transcriptase inhibitor used in HIV patients and recently evaluated as a differentiating and antiproliferative agent in human malignancies. However, while NVP is a safe treatment in immunocompromised patients, NVP-containing regimens have been associated with severe immune-mediated toxicities in non-HIV individuals. Methods and Results: We describe the toxicity profile of single-agent NVP in 6 non-HIV cancer patients treated for a median period of 7.3 months (range 1–24), reporting only a reversible grade III increase in glutamyl transpeptidase and glutamic pyruvic transaminase serum values. Interestingly, NVP treatment correlates with either a decrease in CD8+ T cell counts or a parallel increase in CD4/CD8 ratio, antithyroglobulin and antithyroid peroxidase autoantibody titers. Conclusions: These results, although obtained in a small cohort of patients, suggest that the toxicity profile of single-agent NVP may be worth testing in a phase I/II study in non-HIV cancer patients and that NVP toxicity may depend on its capacity to trigger autoimmune responses in susceptible individuals.
Endogenous Hepatocyte Growth Factor Attenuates Inflammatory Response in Glycerol-Induced Acute Kidney Injury
Authors: Homsi Eduardo , Janino Patricia , Amano Mariane , Saraiva Camara Niels Olsen
Published: October 2008

Background: Hepatocyte growth factor (HGF) is overexpressed after acute kidney injury (AKI). The aim of this study was to evaluate the role of endogenous HGF in the progression of the inflammatory response in glycerol-induced AKI (Gly-AKI) in rats. Methods: Renal and systemic HGF expressions were evaluated during the development of Gly-AKI. Subsequently, the blockade of endogenous HGF was analyzed in rats treated with anti-HGF antibody concomitant to glycerol injection. Apoptosis, cell infiltration and chemokine and cytokine profiles were investigated. Results: We detected an early peak of renal and plasma HGF protein expressions 3 h after glycerol injection. The pharmacological blockade of the endogenous HGF exacerbated the renal impairment, the tubular apoptosis, the renal expression of monocyte chemoattractant protein-1 and the macrophage, CD43+, CD4+ and CD8+ T lymphocytes renal infiltration. The analysis of mRNA expressions of Th1 (t-bet, TNF-α, IL-1β) and Th2 (gata-3, IL-4, IL-10) cytokines showed a Th1-polarized response in Gly-AKI rats that was aggravated with the anti-HGF treatment. Conclusion: Endogenous HGF attenuates the renal inflammatory response, leukocyte infiltration and Th1 polarization after glycerol injection. The control of cellular immune response may partly explain the protective effect of endogenous HGF in the development of Gly-AKI.
Caries Ecology Revisited: Microbial Dynamics and the Caries Process
Authors: Takahashi N. , Nyvad B.
Published: October 2008

In this essay we propose an extension of the caries ecological hypothesis to explain the relation between dynamic changes in the phenotypic/genotypic properties of plaque bacteria and the demineralization/remineralization balance of the caries process. Dental plaque represents a microbial ecosystem in which non-mutans bacteria (mainly non-mutans streptococci and Actinomyces) are the key microorganisms responsible for maintaining dynamic stability on the tooth surface (dynamic stability stage). Microbial acid adaptation and subsequent acid selection of ‘low-pH’ non-mutans bacteria play a critical role for destabilizing the homeostasis of the plaque by facilitating a shift of the demineralization/remineralization balance from ‘net mineral gain’ to ‘net mineral loss’ (acidogenic stage). Once the acidic environment has been established, mutans streptococci and other aciduric bacteria may increase and promote lesion development by sustaining an environment characterized by ‘net mineral loss’ (aciduric stage). Hence, high proportions of mutans streptococci and/or other aciduric bacteria may be considered biomarkers of sites of particularly rapid caries progression. This cascade of events may change the surface texture of caries lesions from smooth to rough (enamel) or hard to soft (dentin). These clinical surface features can be reversed at any stage of lesion development provided that the acidogenic/aciduric properties of the biofilm are resolved. From an ecological point of view it is therefore not only important to describe which bacteria are involved in caries, but also to know what the bacteria are doing.
Effects of Sucrose on the Extracellular Matrix of Plaque-Like Biofilm Formed in vivo, Studied by Proteomic Analysis
Authors: Paes Leme A.F. , Bellato C.M. , Bedi G. , Del Bel Cury A.A. , Koo H. , Cury J.A.
Published: October 2008

Previous studies have shown that sucrose promotes changes in the composition of the extracellular matrix (ECM) of plaque-like biofilm (PLB), but its effect on protein expression has not been studied in vivo. Therefore, the protein compositions of ECM of PLB formed with and without sucrose exposure were analyzed by two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). For this purpose, a crossover study was conducted during two phases of 14 days each, during which a volunteer wore a palatal appliance containing eight enamel blocks for PLB accumulation. In each phase, a 20% sucrose solution or distilled and deionized water (control) were extraorally dripped onto the blocks 8×/day. On the 14th day, the PLB were collected, the ECM proteins were extracted, separated by two-dimensional gel electrophoresis, digested by in-gel trypsin and MALDI-TOF MS analyzed. In the ECM of PLB formed under sucrose exposure, the following changes compared with the control PLB were observed: (1) the presence of upregulated proteins that may be involved in bacterial response to environmental changes induced by sucrose and (2) the absence of calcium-binding proteins that may partly explain the low inorganic concentration found in ECM of PLB formed under sucrose exposure. The findings showing that sucrose affected the ECM protein composition of PLB in vivo provide further insight into the unique cariogenic properties of this dietary carbohydrate.
Streptococcus mutans and Streptococcus sanguinis Colonization Correlated with Caries Experience in Children
Authors: Ge Y. , Caufield P.W. , Fisch G.S. , Li Y.
Published: October 2008

The aim of this study was to examine the colonization of Streptococcus mutans and Streptococcus sanguinis in the oral cavity and the association with severe early childhood caries (S-ECC). Saliva and plaque samples were collected from 14 S-ECC children and 8 caries-free (CF) children. All S-ECC children were S. mutans positive; 100% of CF children and 93% of S-ECC children were S. sanguinis positive. The children’s caries severity was positively correlated with levels of S. mutans (p < 0.001), total oral streptococci (p < 0.01), total cultivable oral bacteria (p < 0.05), and children’s age (p < 0.05). Logistic regression analysis showed that the interaction of S. sanguinis with S. mutans was a significant factor associated with the caries status in children, suggesting that the relative levels of these two microorganisms in the oral cavity play an important role in caries development.
Protection Against Dryness of Facial Skin: A Rational Approach
Authors: Proksch E.
Published: October 2008

Facial skin is unique in that it gets far more exposure to the external environment than skin on other areas of the body and paradoxically, because it contains the thinnest epidermis and stratum corneum, especially on the eye lid. Environmental attacks contribute to drying of facial skin and damage to the stratum corneum. In recent years, there has been an explosion of new products that contain ingredients that claim to benefit facial skin and protect against environmental damage. This review critically examines the scientific basis, rationale and evidence for inclusion of these ingredients in products for protection of facial skin.
Seasonal Effects on the Nasolabial Skin Condition
Authors: De Paepe K. , Houben E. , Adam R. , Hachem J.-P. , Roseeuw D. , Rogiers V.
Published: October 2008

In the present work, nasolabial skin condition and the influence of seasonal changes during autumn and winter were studied in 16 healthy female volunteers. Apart from visual scoring of erythema and skin scaliness, transepidermal water loss (TEWL), skin hydration, apparent skin pH, skin colour and skin desquamation were biophysically measured. The study results showed that nasolabial TEWL was significantly higher during wintertime than in autumn. Also skin colour measurements and squamometry scorings revealed higher values, indicating a more reddish and scaly nasolabial skin during winter compared to autumn. Results from tape stripping and skin surface lipid analysis by high-performance thin-layer chromatography demonstrated significant differences for triglycerides and cholesterol esters, indicating a functionally inferior hydrolipidic layer during the winter season.
Differential Frontal Activation during Exogenous and Endogenous Orientation of Visuospatial Attention
Authors: Takahashi Masaharu , Ikegami Masanaga
Published: October 2008

Aims: The aim was to measure the prefrontal cortical activity involved in shifting spatial attention to visual stimuli in the left or right visual field using near-infrared spectroscopy. Methods: Eleven participants performed a simple vigilance task, an endogenous attention task and an exogenous attention task. In the endogenous task, the left or the right side of the center diamond brightened, indicating the side for subsequent target appearance (controlled shift of attention). In the exogenous task, the peripheral squares brightened, indicating the appearance of target in those squares (reflexive shift of attention). Results: Stimuli at validly cued locations were responded to faster than stimuli at invalidly cued locations. Increases in oxyhemoglobin (oxy-Hb) were observed in the right prefrontal cortex throughout the 3 tasks, and in the left prefrontal cortex during the vigilance and the exogenous tasks. In the exogenous task, marked decreases in oxy-Hb were observed in the bilateral ventrolateral prefrontal cortex. Conclusions: These results suggest that the left and the right prefrontal cortices mediate distinct cognitive processes during the performance of visuospatial attentional tasks.
Diagnosis, Treatment, Observation and Outcome of Fetal Supraventricular Tachycardia in a Twin Pregnancy
Authors: Schiermeier Sven , van Leeuwen Peter , Reinhard Joscha , Grönemeyer Dietrich , Hatzmann Wolfgang
Published: October 2008

Background: Magnetocardiography and M-mode fetal echocardiography are non-invasive techniques capable of identifying fetal arrhythmias. The STAN®-fetal scalp electrode system can record the fetal echocardiogram in labor. Case: A patient was admitted to hospital with preterm contractions and cervical insufficiency at 28 weeks of gestation. After treatment with a β-sympathomimetic drug (Partusisten®) one fetus developed supraventricular tachycardia. After terminating the Partusisten medication, there was no effect on the fetal arrhythmia and flecainide therapy was initiated. Maintenance dosages controlled the condition thereafter. Cardiac time intervals of a fetus in labor can be presented, which did not change significantly throughout the first stage of labor. Conclusion: Flecainide is an effective therapy for supraventricular tachycardias in a twin pregancy. Analyzing the cardiac time intervals during pregnancy can improve perinatal outcome.
Mollaret’s Meningitis
Authors: Pearce J.M.S.
Published: October 2008

Pierre Mollaret is mainly known for his contributions to infectious diseases and their prevention. He also described benign, recurrent endothelio-leukocytic meningitis in three patients who had short-lived recurrent attacks of fever, headache and vomiting caused by sterile meningitis, with ‘fantomes cellulaires’ (cell ghosts) in the cerebrospinal fluid. Identical symptoms are caused by Herpes simplex virus-2 and other viruses. The term Mollaret’s meningitis should be restricted to idiopathic recurrent aseptic meningitis. This paper briefly outlines the syndrome and its discoverer.
Agreement between Multidetector-Row CT Angiography and Ultrasound Echo-Color Doppler in the Evaluation of Carotid Artery Stenosis
Authors: Saba Luca , Sanfilippo Roberto , Montisci Roberto , Mallarini Giorgio
Published: October 2008

Purpose: Stroke is a leading cause of severe disability in the western world. A correct diagnostic procedure to stratify risk is necessary in order to rapidly plan the most efficient therapy. The purpose of this work was to evaluate the agreement between ultrasound echo-color Doppler (US-ECD) and multidetector-row CT angiography (MDCTA) in determining the degree of carotid stenosis. Methods and Materials: From January 2004 to February 2007, 187 patients who had previously undergone both US-ECD and MDCTA were studied retrospectively. For each patient, stenosis degree was measured by applying the North American Symptomatic Carotid Endarterectomy Trial criteria. Data derived from MDCTA and US-ECD were then compared to calculate the inter-technique variability by using Cohen ĸ statistics. For all plaque types (fatty, mixed and calcified), inter-technique variability was assessed. The Wilcoxon signed-rank test was used to highlight differences between the procedures, and scatterplots were also calculated. As a gold standard, reference surgical comparisons were performed in 50 patients. Results: The percentage of observed agreements in the evaluation of stenosis degree was 72.19% with a ĸ value of 0.659 (95% confidence interval: 0.604–0.715) and a weighted ĸ of 0.789. After the evaluating stenosis degree in fatty, mixed and calcified plaques, the percentages of observed agreements were 79.31, 74.58 and 64.29%, respectively, with ĸ values of 0.738, 0.691 and 0.565. Conclusion: A good agreement between US-ECD and MDCTA in the evaluation of stenosis degree was observed, together with a remarkable difference between the 2 techniques in the assessment both of calcified plaques and of plaques showing a predominant calcific component.
Actigraphic Measurement of Motor Deficits in Acute Ischemic Stroke
Authors: Gebruers N. , Truijen S. , Engelborghs S. , Nagels G. , Brouns R. , De Deyn P.P.
Published: October 2008

Background: This study aimed to investigate the use of actigraphy (accelerometry) to measure disuse of the impaired arm in acute stroke patients. We correlated the National Institute of Health Stroke Scale (NIHSS) and the Fugl-Meyer Assessment arm section (FMA) findings with actigraphic data as a measure of validity. Methods: Thirty-nine acute ischemic stroke patients were included within 1 week after stroke onset. At inclusion, motor deficits were assessed by the NIHSS, FMA and 48-hour actigraphic recordings of both wrists were performed. Results: Moderate but highly significant correlations (Spearman’s rho) between actigraphic recordings and total NIHSS (ratio r = –0.59 and activity of impaired arm r = –0.75; p < 0.001) and FMA (ratio r = 0.54 and activity of impaired arm r = 0.69; p < 0.001) scores were found. Based on actigraphic motor activity scores, ROC curves were calculated following dichotomization of the population based on NIHSS = 7 and FMA = 45, showing good sensitivity and specificity, with negative predictive value of 100% and positive predictive value of 91% for the ratio variable. Conclusions: Moderate but highly significant correlations were found between actigraphy and the stroke scales NIHSS and FMA. Actigraphy was able to reliably discriminate less impaired from more impaired stroke patients with excellent sensitivity and specificity values. Actigraphy is a simple, valid, objective and reliable clinical research tool that can be used to determine motor impairment of the upper limb in stroke patients.
Frequency and Clinical Significance of Acute Bilateral Cerebellar Infarcts
Authors: Hong Ji Man , Bang Oh Young , Chung Chin-Sang , Joo In Soo , Huh Kyoon
Published: October 2008

Background: Unlike acute unilateral cerebellar infarct (UCI), acute bilateral cerebellar infarcts (BCI) have attracted little attention. To evaluate the clinical significance of BCI, we compared UCI and BCI and analyzed potentially prognostic factors. Methods: Patients who were consecutively admitted at a university hospital over a 4-year period with acute cerebellar infarcts, proven by diffusion-weighted imaging, were studied. Cerebellar infarcts were topographically classified, and divided into 2 groups: UCI and BCI. The demographics, involved territories, concomitant lesions outside the cerebellum (CLOC), bilateral involvement, infarct volume, hospital courses, and mechanisms were analyzed. We performed multiple regression analysis to predict the poor outcome at discharge [≧3 on the modified Rankin Scale (mRS)]. Results: Among 162 patients with acute cerebellar infarcts, 31% (n = 50) were BCI. Territorial infarcts were 74% (n = 120) and non-territorial infarcts 26% (n = 42) of the total. Posterior inferior cerebellar artery infarcts were the most common, and combined-territorial infarcts were the rarest. Baseline demographics were not significantly different between UCI and BCI, except for initial stroke severity (modified NIH Stroke Scale and infarct volume) and diabetes. Large-artery atherosclerosis was significantly higher in BCI, whereas undetermined causes were higher in UCI (p = 0.028). By multiple regression analysis, BCI was the only independent radiological factor for poor prognosis (odds ratio, 6.96; 95% CI, 1.80–26.92), and represented a significantly more unstable hospital course, longer hospital stay, worse mRS at discharge, and higher mortality. Conclusions: In acute cerebellar infarcts, bilateral involvement is common and appears to be a superior determinant for early prognosis rather than territories involved or CLOC.
The Role of High-Sensitivity C-Reactive Protein in Asymptomatic Intra- and Extracranial Large Artery Diseases
Authors: Takahashi Wakoh , Ohnuki Tomohide , Ohnuki Yohichi , Kawada Shiaki , Takagi Shigeharu
Published: October 2008

Background: It remains unclear whether high-sensitivity CRP (hs-CRP) is predictive of atherosclerosis in the intracranial artery. The aim of this study is to assess the role of hs-CRP in asymptomatic intracranial artery occlusive diseases. Methods: Of the 3,366 apparently healthy subjects who received a brain checkup, 138 with ≧25% intracranial artery stenosis on magnetic resonance angiography, 267 with ≧25% extracranial carotid artery stenosis on B-mode ultrasonography and 435 without intracranial artery or extracranial carotid artery stenosis (age-matched controls) were selected for this study. Results: The mean CRP concentration in the subjects with intracranial artery stenosis was not significantly different from that in the control subjects, and the differences of mean CRP concentrations among the subgroups with 25–49, 50–74 and 75% or greater stenosis in the intracranial artery were not significant. The odds ratios of hs-CRP for extracranial carotid artery stenosis tended to increase with increasing CRP concentrations, but those of hs-CRP for intracranial artery stenosis showed no significant difference. Conclusion: The degree of atherogenic inflammation in asymptomatic intracranial artery stenosis may be less than that in extracranial carotid artery stenosis.
Hydrops Fetalis, Thickened Placenta and Other Sonographic Findings in a Low-Level Trisomy 21 Mosaicism: A Case Report
Authors: Sifakis S. , Koukoura O. , Mantas N. , Velissariou V. , Koumantakis E.
Published: October 2008

We report a case of trisomy 21 mosaicism detected upon amniocentesis in a 36-year-old woman. Ultrasound examination at 23weeks’ gestation showed a fetus with hydrops, pulmonary hypoplasia, oligohydramnios, thickened placenta, and intrauterine growth retardation. Cytogenetic analysis revealed low-percentage (6%) mosaicism for trisomy 21. Hydrops fetalis and thickened placenta are uncommon findings in fetuses affected by trisomy 21 mosaicism. A short review of the literature is given regarding the sonographic findings associated with trisomy 21 mosaicism, and the genetic counseling in such cases.
Insulin Modulation of Luteinizing Hormone Secretion in Normal Female Volunteers and Lean Polycystic Ovary Syndrome Patients
Authors: Moret Mallory , Stettler Rodrigue , Rodieux Frederique , Gaillard Rolf C. , Waeber Gérard , Wirthner Daniel , Giusti Vittorio , Tappy Luc , Pralong Francois P.
Published: October 2008

Background/Aims: Endocrine features of polycystic ovary syndrome (PCOS) include altered ovarian steroidogenesis, hyperinsulinemia and abnormal luteinizing hormone (LH) secretion. This study was undertaken to further evaluate the role of insulin to modulate LH secretion in lean PCOS patients with normal insulin sensitivity and normal volunteers. Methods: The study was performed in five nonobese patients diagnosed with PCOS on the basis of amenorrhea and a polycystic morphology at ovarian ultrasound, and 5 normal controls in early to mid-follicular phase and matched for weight and age. All subjects were phenotyped, and then admitted for 12 h of frequent (q 10’) blood sampling on two separate occasions, once for a baseline study and the other time for a hyperinsulinemic and euglycemic clamp study. LH was measured in samples obtained throughout each admission in order to perform LH pulse analysis. Results: Baseline LH secretion in PCOS subjects was significantly different from controls: they had higher LH levels, higher LH/FSH ratios as well as a faster LH pulse frequency than normal women. Insulin administration did not affect the pattern of LH secretion of PCOS patients, whereas it significantly increased the LH pulse frequency while decreasing the LH interpulse intervals in the controls. Conclusions: These data confirm that an abnormal pattern of LH secretion characteristic of PCOS can be observed in lean patients, and appears independent of peripheral insulin levels. Furthermore, our results in lean controls provide the first direct evidence that peripheral insulin can modulate the activity of hypothalamic gonadotropin-releasing hormone (GnRH) neurons in the human.
Selective Depletion of Alveolar Macrophages in Polymicrobial Sepsis Increases Lung Injury, Bacterial Load and Mortality but Does Not Affect Cytokine Release
Authors: Traeger Tobias , Kessler Wolfram , Hilpert Anne , Mikulcak Marlene , Entleutner Markus , Koerner Pia , Westerholt Alexandra , Cziupka Katharina , van Rooijen Nico , Heidecke Claus-Dieter , Maier Stefan
Published: October 2008

Background: Resident tissue macrophages exert important functions during severe systemic infection and contribute to changes in local as well as systemic immune responses. Alveolar macrophages (AM) play a crucial role in airway diseases and in the defense against microorganisms invading the body via the bronchopulmonary tract. It has been postulated that AM are involved in the development of acute local disorders as a consequence of extrapulmonary stimuli like pancreatitis, peritonitis, or trauma. Objective: The aim of this study was to analyze the local and systemic role of AM during sepsis using selective AM depletion in the murine colon ascendens stent peritonitis (CASP) model of polymicrobial sepsis. Methods: 48 h prior to CASP surgery, AM of female C57BL/6 mice were selectively depleted by intratracheal application of clodronate liposomes (Lipo-clod). For control purposes, phosphate-buffered saline (PBS) liposomes (Lipo-PBS) were used. Results: CASP led to significantly elevated levels of local and systemic cytokines independent of the presence of AM. In contrast, levels of gut-derived bacteria in bronchoalveolar lavage and lung of septic mice were significantly higher in Lipo-clod-treated animals compared to Lipo-PBS-treated animals. After CASP-induced sepsis, local barrier dysfunction in the lung was detected; AM depletion resulted in severely enhanced development of acute lung injury. Consequently, Lipo-clod-treated animals showed strongly reduced survival rates after CASP. Conclusions: Contrarily to other macrophage populations, AM do not significantly contribute to local and systemic cytokine release during polymicrobial abdominal sepsis. AM have important protective functions for local clearance of gut-derived bacteria and attenuation of lung injury.
Pituitary Changes Involved in Prolactin Secretion Induced by Mifepristone and Naloxone during Late Pregnancy
Authors: Villegas Gabutti Carlos , Ezquer Marcelo , Deis Ricardo , Maldonado Cristina , Soaje Marta
Published: October 2008

Background/Aims: The antiprogesterone mifepristone facilitates prolactin release, an effect enhanced by administration of the opioid antagonist naloxone. The present study explores ultrastructural changes in lactotropes after mifepristone and naloxone administration, correlating them with the expression of pituitary prolactin. Methods/Results: Rats were sacrificed at 18:00 h on day 19 of pregnancy. Prolactin immunoelectron microscopy of lactotropes from control rats showed characteristics of quiescent cells with numerous small and spherical secretory granules. Naloxone administration did not modify lactotrope morphology or prolactin expression in terms of mRNA or protein abundances. Mifepristone treatment induced lactotrope activation with development of the rough endoplasmic reticulum and Golgi complex with prolactin immunoreactive small newly formed and large mature secretory granules. Mifepristone increased prolactin mRNA and protein expression. Naloxone administration to mifepristone-treated rats potentiated lactotrope activation compared with mifepristone alone showing exocytotic images of prolactin granules and some cells with evident signs of involution. Conclusions: (1) Blockade of progesterone action by mifepristone activated the lactotrope, increased significantly prolactin mRNA and protein expression and prepared the pituitary for naloxone action. (2) The high serum prolactin levels induced by mifepristone and naloxone may regulate negatively lactotrope activity as suggested by the presence of regressing cells neighboring the actively secreting cells.
‘Bowenoid Wart’: Wart with Bowenoid Histological Changes?
Authors: Corbalan-Velez R. , Ruiz-Macia J.A. , Brufau C. , Martinez-Escribano J. , Ara-Martín M. , Carapeto F.J.
Published: October 2008

Introduction: Cases of lesions that simulate Bowen’s disease have been previously described in the literature. Case Report: Nine exophytic verruca-like lesions with histological findings of Bowen’s disease (BD) are described. All cases had a rapid growth, and were located on the face and neck of elderly patients with chronic solar skin damage. We carried out p16 immunohistochemical staining using the immunoperoxidase technique, which was negative in all cases. Discussion: We think that these 9 lesions are only histologically mimicking BD, and could be a subtype of verruca (‘bowenoid wart’). These lesions could be provoked by nononcogenic human papillomavirus (HPV), as in other cases previously described. The p16 staining was negative in all cases, in contrast with most BD cases. It would be interesting to study whether positive p16 staining is related to oncogenic HPV, whereas negative p16 staining could be associated with low or nononcogenic HPV; thus, more studies are needed.
Prognosis and Natural History in the Cardiomyopathies
Authors: Oakley C.M.
Published: October 2008

Almost 200 patients with cardiomyopathy have been studied at the Royal Postgraduate Medical School London over the last 8 years. Roughly half fell into the hypertrophic class without left ventricular dilation. Epidemiological survey has shown a familial incidence in about one third of these and a dominant mode of inheritance. Inflow restriction and sudden death predominated in this group. The sporadic cases more often showed left ventricular outflow tract obstruction and a primary role for mitral regurgitation in the genesis of this outflow obstruction has been postulated. In the sporadic group a translation from outflow to inflow obstruction sometimes occurs but seems to represent a late phase of the disorder in contrast to the familial cases in which this may be an early or sole feature. In the congestive cardiomyopathies with left ventricular dilatation a correlation between cavity dilatation and wall thickness aided assessment of prognosis the outlook being worse in those with high cavity wall thickness ratios. Coronary angiography estimations of myocardial blood flow and myocardial biopsy has been carried out in some of the patients from both groups of cardiomyopathies and the further information gained from these studies was discussed in conjunction with the physiological hemodynamic and angiographic findings in the whole series of patients with cardiomyopathy.
Familial Cardiomyopathy
Authors: Kariv I.
Published: October 2008

The diagnosis of primary myocardial disease or cardiomyopathy is made by definition in patients with clinical radiological and electrocardiographic signs of heart disease which cannot be included in one of the well-defined nosological entities such as congenital rheumatic or coronary heart disease. Neither is the heart affection secondary to any systemic disease such as collagen diseases progressive muscular dystrophy or amyloidosis. Familial cardiomyopathy was first described by Evans in 1949. The familial characteristic depends upon finding a number of offspring affected in one family. This report deals with 11 families collected during the last 7 years. Of the 98 members examined 47 were found affected. The clinical features radiological and electrocardiographic findings and serum enzyme alterations are presented. The clinical features include a history of dizziness or loss of consciousness cardiac arrhythmias and the possibility of sudden death. The electrocardiogram indicates atrioventricular conduction defects with in a few cases complete AV block and Adams-Stokes attacks ventricular hypertrophy mostly leftintraventricular block and sometimes the pattern of the Wolff-Parkinson-White syndrome. The heart is usually enlarged on X-ray or has an ‘unusual’ shape. The necessity of a complete examination of all the members of the patient’s family is stressed. The genetic aspects are discussed and appear to conform to genetic transmission by an autosomal dominant gene with high penetrance.
Pulmonary Emphysema in Ibadan, Nigeria: A Preliminary Report on a Pathological Study of 114 Unselected Necropsies
Authors: Alli A.F.
Published: October 2008

A large scale survey of the incidence of pulmonary emphysema in necropsy material in Ibadan is in progress. The present report concerns the findings in the 114 lungs so far analyzed. This series consists of lungs from 59 males and 55 females. Ignoring traces of emphysema and considering both sexes only 7 (6.1%) of the 114 lungs showed emphysema. If trace amounts are included 22 (19.3%) of 114 lungs showed evidence of emphysema. Only 7 (12.7%) of 55 lungs from females showed emphysema and only 1 of the 7 lungs with emphysema showed up to 18.9% involvement. The remaining 6 lungs showed much less than 10% involvement most showing 1% or less. Of 59 lungs of males 15 (25.4%) showed evidence of emphysema. One of these lungs showed 94.9% involvement 3 lungs showed 25-33% involvement 6 lungs showed between 3% and 16% involvement while the remaining 5 lungs showed l% or less involvement. Emphysema is thus more common and more severe in males than in females in Ibadan. Compared with London Edingburgh Cardiff Boston and some other centers emphysema is of low incidence and the lesion is very mild in Ibadan. This is most probably due to the lack of heavy industries and therefore the lack of air pollution in Ibadan.
Histochemical Studies of Tissue Forms and of Perifungal Substance in Subcutaneous Phycomycosis
Authors: Bader G. , Grueber H.L.E.
Published: October 2008

A histochemical study of phycomyces hyphae of a case of subcutaneous phycomycosis from India showed that the protoplast consists of PAS-positive polysaccharides and a small amount of RNA containing proteins. The cell wall is laminated and it is suggested that cellulose and hemicellulose compounds, as well as other polysaccharides but no proteins are present. Special attention was paid to the perihyphal substance. Adsorption of anti-human gamma globulin suggests the presence of host antibodies among the proteins present in precipitate. PAS-positive polysaccharides in this substance are probably products of the fungus. Thus, the perifungal substance of phycomyces may be considered as an immune precipitate, which is of a different nature to that of the capsular substance as produced by Cryptococcus neoformans and by spores of Rhinosporidium seeberi.
Conidial Discharge in Protomycopsis thirumalacharii
Authors: Pavgi M.S. , Haware M.P.
Published: October 2008

Mechanism and occurrence of conidial discharge in Protomycopsis thirumalacharii Pavgi, causing the purple leaf spot of Sesbania grandiflora Pers. was studied in detail. The conidia were ‘shot off’ violently from the conidiophores only in dry atmosphere at a temperature range of 15-30°C. Field observations also corroborated the mode of pathogenic infection on the host leaves.
Pulmonale und zerebrale Kryptokokkose bei chronischer Lymphadenose
Authors: Bankl H. , Minauf M.
Published: October 2008

A secondary Cryptococcus neoformans-infection in a case of chronic lymphadenosis treated with cytostatics, X-ray and corticosteroids is described. The autopsy diagnosis was based on the morphologic features of Cryptococcus neoformans in a toruloma of the lung and a granulomatous meningoencephalitis. The clinical symptoms and roentgenographic observations makes probable that infection takes place about 8 months before death.