bluuebunny/crossref_metadata_2025 huggingface dataset:
Hormonal Therapy with Letrozole for Relapsed Epithelial Ovarian Cancer
Authors: Papadimitriou Christos A. , Markaki Sophia , Siapkaras John , Vlachos Georgios , Efstathiou Eleni , Grimani Irene , Hamilos George , Zorzou Markella , Dimopoulos Meletios-A.
Published: May 2004

Objective: We conducted a phase II trial to evaluate the activity of oral letrozole in women with relapsed or recurrent epithelial ovarian cancer. Methods: Twenty-seven patients were treated with letrozole at a dose of 2.5 mg once a day. Patients with measurable or evaluable disease (n = 21) and those with only increasing CA 125 serum levels (n = 6) were eligible. Paraffin-fixed histological sections from tumor specimens resected at the initial laparotomy were assessed for the presence of estrogen, and progesterone receptors. Results: Among the 21 patients with measurable or evaluable disease who were evaluated for response by WHO criteria, we observed one complete and two partial responses for an objective response rate of 15%. Using criteria for CA 125 response we obtained a marker response in 4 of 27 patients (15%), and the marker remained stable in 5 additional patients (18%). Letrozole treatment was generally well tolerated. No correlation was observed between tumor marker response or stabilization and either estrogen or progesterone receptor expression. Conclusion: The results of our study suggest that the aromatase inhibitor letrozole is an agent with some activity and limited toxicity for relapsed ovarian cancer. As we could not find any association between response and hormonal receptor expression, the underlying mechanisms of letrozole action have to be elucidated.
Effect of Wild-Type and Mutant E-Cadherin on Cell Proliferation and Responsiveness to the Chemotherapeutic Agents Cisplatin, Etoposide, and 5-Fluorouracil
Authors: Fricke Elena , Hermannstädter Christine , Keller Gisela , Fuchs Margit , Brunner Ingrid , Busch Raymonde , Höfler Heinz , Becker Karl-Friedrich , Luber Birgit
Published: May 2004

Objectives: The cell adhesion molecule E-cadherin acts as a tumor and invasion suppressor and regulates cell proliferation. The aim of the present study was to investigate the impact of wild-type (wt) E-cadherin and tumor-derived mutant E-cadherin variants on the proliferation rate of MDA-MB-435S mammary carcinoma cells and the sensitivity of the cells to the chemotherapeutic drugs cisplatin, etoposide and 5-fluorouracil (5-FU) and whether p53 is involved in the chemotherapeutic response. Methods: Proliferation rate was measured by XTT cell viability assay in the presence or absence of chemotherapeutics. Chemosensitivity was also measured by colony formation assay. Expression of p53 was investigated by immunoblot analysis. The mutational hot spot region exon 5–8 of p53 was analyzed for mutations by denaturing high-performance liquid chromatography. Results: The growth rate of MDA-MB-435S cells transfected with wt E-cadherin was reduced as compared with the parental cell line. In contrast, tumor-associated mutations of exons 8 or 9 of the E-cadherin gene interfere with the growth-suppressive function of E-cadherin. Cisplatin sensitivity of wt and mutant E-cadherin-expressing MDA-MB-435S cells was reduced as compared with E-cadherin-negative, parental MDA-MB-435S cells. In contrast, chemosensitivity of parental, wt or mutant E-cadherin-expressing MDA-MB-435S cells measured after etoposide or 5-FU exposure was found to be similar in all tested cell lines. Since p53 influences the sensitivity of cells to chemotherapeutic agents, we investigated whether the p53 expression level or mutation status were different in the nontransfected or E-cadherin-transfected MDA-MB-435S cell lines. We found that the p53 expression pattern and genomic background were similar in all cell lines and not affected by cisplatin. Conclusion: The results obtained in this study suggest that the expression and/or mutation of the E-cadherin gene influence the proliferation rate and drug sensitivity of tumor cells.
Successful Targeted Radiotherapy with 90Y-DOTATOC in a Patient with Merkel Cell Carcinoma
Authors: Meier G. , Waldherr C. , Herrmann R. , Maecke H. , Mueller-Brand J. , Pless M.
Published: May 2004

Merkel cell carcinomas (MCC) belong to the family of neuroendocrine tumors. In addition to other markers, they express somatostatin receptors. They are uncommon, highly malignant skin tumors with an aggressive clinical course. They develop in sun-exposed areas of the skin, mostly in elderly patients. In addition to frequent locoregional recurrences, there is a high incidence of distant metastases. Treatment is stage dependent and consists of operation and chemo- and/or radiotherapy, respectively. The advanced age of patients often impedes adequate therapy. 90Y-DOTATOC is a novel radiolabeled somatostatin analogue containing the active octapeptide of somatostatin. It is very well tolerated and offers the option of treating somatostatin receptor-positive tumors by targeted radiotherapy. We report the case of an 83-year-old woman with recurrent MCC of the left cheek. The primary tumor and several relapses were treated with surgery and locoregional radiotherapy. After the 3rd relapse, she was treated 4 times with 90Y-DOTATOC and two complete remissions were achieved. The fourth administration after the 2nd relapse was ineffective and conventional chemotherapy was started. There were no side effects of the 90Y-DOTATOC. We conclude that due to its good tolerability, 90Y-DOTATOC therapy should be evaluated further as a new therapy for somatostatin receptor-positive MCC.
Increasing Incidence of Critical Liver Disease among Causes of Death in Japanese Hemophiliacs with HIV-1
Authors: Tatsunami Shinobu , Taki Masashi , Shirahata Akira , Mimaya Junichi , Yamada Kaneo
Published: May 2004

Critical liver diseases are now major causes of death in HIV-1-infected patients after the remarkable improvement in the clinical status resulting from highly active antiretroviral therapy. We report the results of an analysis on causes of deaths related to liver diseases based on our surveillance of hemophiliacs infected with HIV-1 up until May 31, 2002. A total of 1,405 patients (hemophilia A, 1,084, and hemophilia B, 321) were registered. The cumulative number of deaths was 534 (hemophilia A, 414, and hemophilia B, 120) by May 31, 2002. Hepatic disease due to HCV infection was found in 29.8% (95% confidence interval: 20.3–40.7%) of the total cases with known causes of death after 1997, whereas this value was 14.0% (95% confidence interval: 10.8–17.7%) before 1997 (p < 0.01). We observed an increasing incidence of critical hepatic diseases among HIV-1-infected hemophiliacs, thus suggesting that treatment of HCV infection is essential for HIV-1-infected hemophiliacs.
Molecular Analysis of Beta-Thalassemia and Sickle Cell Anemia in Antalya
Authors: Keser I. , Sanlioglu A.D. , Manguoglu E. , Guzeloglu Kayisli O. , Nal N. , Sargin F. , Yesilipek A. , Simsek M. , Mendilcioglu I. , Canatan D. , Luleci G.
Published: May 2004

We have studied 918 chromosomes for mutations leading to β-thalassemia and sickle cell anemia, which are the two most frequently found monogenic disorders in Antalya, Turkey. Three hundred and seventy-seven postnatal and 82 prenatal cases were studied between 2000 and May 2003 in our center using reverse dot blot hybridization (RDBH) with 22 probes specific for Mediterranean populations. In this study, IVSI-110 (G→A) appeared to be the most common mutation with an occurrence rate of 44.4% among the 16 different mutations found to be associated with β-thalassemia. Heterozygosity for IVSI-110 was the most prevalent combination, whereas 34 of our 377 postnatal cases showed homozygosity for this mutation, a genotype leading to β-thalassemia major. The total percentage of postnatal patients clinically diagnosed as β-thalassemia major was 18.6%, whereas 5% of the cases were diagnosed clinically as β-thalassemia intermedia. One new Hb variant, Hb Antalya, and one new mutation, Cod 3 (+T) were found. HbS accounted for 10.3% of all mutations; homozygosity was found in 1.9% of all cases. Of the 82 cases analysed prenatally for β-globin gene mutations and by cytogenetic techniques for possible chromosomal abnormalities, 21 fetuses were found to be affected with β-globin gene mutations. One of these fetuses was also found to have a 45,X karyotype, and 1 had a 46,XY/47,XY,+22 karyotype. Quite a high rate of consanguineous marriages in Antalya (35.17%) renders mutation screening, genetic counseling, and educational programs held by our Thalassemia Unit essential. This study was the first to be performed specifically in our region where hemoglobinopathies are most frequent as a consequence of migrations of racially and culturally distinct groups to the area in the distant past.
Hematologic Manifestation of Childhood Celiac Disease
Authors: Fisgin Tunc , Yarali Nese , Duru Feride , Usta Belgin , Kara Abdurrahman
Published: May 2004

We wanted to describe the hematologic manifestations of celiac disease (CD) in childhood. This study included 22 children with CD in whom the disease remained undiagnosed until they had presented with hematological abnormalities, such as anemia, thrombocytopenia, leukopenia or prolonged prothrombin time (PT) and activated partial thromboplastin time (APTT). Anemia was present alone in 19 (86.3%) patients, and leukopenia coexisted with anemia in 2 (9%) patients. Thrombocytopenia was found alone in 1 (4.5%) patient. Twelve patients had an iron deficiency anemia. Iron deficiency coexisted with zinc and vitamin B12 deficiency in 3 patients, copper and vitamin B12 deficiency in two, vitamin B12 deficiency in two, zinc deficiency in two and one patient had combined iron, zinc, and copper deficiency. Males had significantly lower values of hemoglobin (p < 0.05) and MCV (p < 0.05) compared to the females. In conclusion CD should be included in the differential diagnosis in children who present with anemia, leukopenia, thrombocytopenia or prolonged PT and APTT, especially in geographical areas where the prevalence of the CD is high.
T Cell Receptor δ-Chain Gene Rearrangement in a Novel Case of Adult NK Cell Leukemia
Authors: Stagno Fabio , Guglielmo Patrizia , Lo Nigro Luca , Santonocito Annamaria , Giustolisi Rosario
Published: May 2004

Malignancies arising from natural killer (NK) cells are being increasingly recognized as distinct clinicopathological entities. We here report the characteristics of a peculiar case of NK-cell acute leukemia with unusual agranular morphology and rearrangement of the T-cell receptor (TCR) δ-chain gene.
Dialysis-Related Hypotension as a Cause of Progressive Frontal Lobe Atrophy in Chronic Hemodialysis Patients: A 3-Year Prospective Study
Authors: Mizumasa Tohru , Hirakata Hideki , Yoshimitsu Takahiro , Hirakata Eriko , Kubo Michiaki , Kashiwagi Minoru , Tanaka Hiroshi , Kanai Hidetoshi , Fujimi Satoru , Iida Mitsuo
Published: May 2004

Background/Aim: Brain atrophy is known to develop more rapidly in hemodialysis (HD) patients than other individuals. The present study was designed to examine the role of HD-related hypotension in brain atrophy in patients on chronic HD. Methods: By using magnetic resonance imaging, whole brain atrophy was assessed by the ventricular-brain ratio (VBR; ventricular area/whole brain area). Frontal brain atrophy was assessed by the frontal atrophy index (FAI; frontal brain area/intracranial frontal space). The number of lacunae was also counted. We studied 32 HD patients without symptomatic neurological abnormalities or diabetes mellitus: male/female ratio 19/13; mean age ± SD 53 ± 10 (range 28–77) years; mean HD duration ± SD 11 ± 6 (range 1–22) years. Magnetic resonance imagings were taken in 1995 and 1998. All dialysis-related hypotension episodes during the same period were identified from the medical records and counted. Results: The VBR ranged from 8.8 to 18.7% in 1995 (12.8 ± 2.2%) and was not different in 1998 (13.1 ± 2.7%). However, the VBR increased by more than 5% in 14 patients, and their HD duration of 13 ± 6 years was significantly longer than that of 18 patients with stable VBR (p < 0.05). The FAI in 1995 was 62.2 ± 4.2% (range 55.8–71.3%) and decreased significantly to 59.7 ± 4.7% (range 50.2–70.9%) in 1998 (p < 0.05). The change in FAI correlated significantly with both the total number of dialysis-related hypotension episodes (r = 0.45, p < 0.05) and the increase in number of lacunae (r = 0.42, p < 0.05). Conclusion: Our results suggest that dialysis-related hypotension plays a role in progressive frontal lobe atrophy in HD patients.
Association between Mast Cells and Bladder Carcinoma
Authors: Serel T. Ahmet , Soyupek Sedat , Çandir Özden
Published: May 2004

Introduction: The aim of this study was to determine whether there are quantitative variations in the numbers of mast cells (MCs) in bladder carcinoma tissue associated with the histopathological grading of tumours. Materials and Methods: Specimens of 56 bladder carcinomas were stained with toluidine blue and histologically staged using the Mostofi system. The MC counts were assessed within tumour tissue and lamina propria of the bladder. The MCs in the adjacent ‘normal bladder tissue’ of 14 specimens from patients who underwent cystectomy and of 10 specimens from patients having interstitial cystitis were also determined. The results were analyzed by using the Student t test, the Wilcoxon signed-rank test, and the Spearman correlation (rs). Results: The mean MC concentration was 0.57 within the tumour tissue and 3.36 in the lamina propria. The difference between the two MC groups was statistically significant (p < 0.0001); there were no correlations between mean MC counts in tumour tissue and histopathological tumour grade and between mean MC counts in lamina propria and histopathological tumour grade. Statistically significant differences were also observed between tumour group and interstitial cystitis group (p = 0.029) and between tumour group and normal ‘adjacent’ tissue group (p = 0.037). Conclusions: Our findings suggest that MCs aggregate in small numbers in the lamina propria of bladder carcinomas and that the MC count is related to tumour differentiation. The number of MCs may be a useful prognostic indicator in patients with bladder carcinoma.
Seminal Plasma Prostate-Specific Antigen Level in Benign Prostatic Hyperplasia
Authors: Şenkul Temuçin , Narin Yavuz , İşeri Cüneyt , Şen Bülent , Karademir Kenan , Erden Doǧan
Published: May 2004

Introduction: We evaluated the role of the seminal plasma PSA level in the prediction of the response to α-blocker treatment in patients with benign prostatic hyperplasia. Materials and Methods: 18 male patients with lower urinary tract symptoms were enrolled in the study. After their blood was sampled for PSA, ejaculates of all the subjects were obtained. Serum and seminal plasma PSA levels were calculated by Active PSA IRMA kit. Patients were given 4 mg/day doxazosin for a period of 6 weeks, following which their International Prostate Symptom Score (IPSS) evaluation was repeated. The correlation between serum PSA, seminal plasma PSA and PSA density levels and the percentage improvement in IPSS was investigated. Results: The mean serum PSA level, the mean PSA density and the mean seminal PSA level of the patients were 2.7 ± 1.2 ng/ml, 0.05 ± 0.02 ng/ml/cm3 and 0.7 ± 0.39 g/l, respectively. The percentage improvement in IPSS varied from 26.9 to 53.5%. Serum PSA and serum PSA density were not useful in the prediction of the response to α-blocker treatment, but the seminal PSA levels correlated with the percentage improvement in the IPSS (p = 0.017). Conclusions: Seminal plasma PSA has been found to be a better predictor of the response to α-blocker treatment when compared to serum PSA and PSA density.
The Experimental Model of Hydatidosis in Rabbit Testis
Authors: Verit Ayhan , Ozbilge Hatice , Yeni Ercan , Unal Dogan , Ozardali Ilyas , Ciftci Halil , Ozbilge Mustafa
Published: May 2004

Objectives: Although no part of the human anatomy is invulnerable to hydatid disease, it has been reported to occur mostly in vital organs such as liver, lungs and brain. Hydatid disease of the urinary tract is uncommon accounting for only 2% of all such cases. Testes are extremely rare sites for echinococcosis. To our knowledge there are only 3 cases of testicular hydatid cyst described. In this animal model, we studied echinococcosis in rabbit testis. Methods: We directly infected the unilateral testis of 4 male rabbits with infective protoscolices via intratesticular injection and housed them under pathogen-free conditions for 10 weeks. All rabbits survived during the follow-up period and then, at the 10th week, all testes were removed for histopathologic investigation. Results: Despite of the direct infection of the rabbit testes with Echinococcus granulosus, there was no demonstrable hydatid cyst after a 10-week period except from some fibrosis in the injection tract of the testicular tissue in 1 case. Conclusion: The testes are extremely rare anatomic locations for echinococcosis infection. The mechanism of this resistance should be another reason apart from blood-testicular barrier. We think that low temperature in the scrotum or different properties of the testicular tissue may be the reasons of this defense mechanism. If this hypothesis clarifies with the further studies, new treatment options may be defined in the medical literature for the hydatid cyst.
Delayed Life-Threatening Haematuria from a Renal Pseudoaneurysm Caused by Blunt Renal Trauma Treated with Selective Embolization
Authors: Giannopoulos Aris , Manousakas Theodoros , Alexopoulou Efthymia , Brountzos Elias , Papadoukakis Stefanos , Kelekis Dimitrios
Published: May 2004

Pseudo-aneurysms complicating blunt renal traumas, although very rare, represent significant causes of secondary haematuria, potentially life-threatening. Initial surgical repair of the injured kidney does not preclude the presence of an obscure pseudo-aneurysm that could become evident later on. We herein present a patient with a grade III blunt renal trauma initially treated surgically. Thirty days after the trauma, he developed secondary haematuria caused by a renal pseudo-aneurysm located far from the oversewed area. This vascular lesion was successfully treated using selective arterial embolization.
Kidney Transplants from LivingRelated Donors Having Double Inferior Vena cava
Authors: Nakatani Tatsuya , Kim Taku , Naganuma Toshihide , Uchida Junji , Takemoto Yoshiaki , Sugimura Kazunobu
Published: May 2004

We performed four living related kidney transplantations from donors with double inferior vena cava (D-IVC), in which the left kidney was selected in two cases and the right in two cases. By dissecting the right internal iliac vein and isolating the right external iliac vein, the surgical procedure of the recipient side was so devised as to avoid any complications. In one patient, the surgical procedure of the donor side was modified to extend the donor left renal vein by anastomosis of part of the donor IVC to the renal vein. In the other case, no special treatment was necessary due to the patient’s slender physique. In all four cases, transplants were successfully performed. The following conclusions can be made from these results: If the donor has D-IVC, it is essential to carefully conduct pre-operative examinations including angiography and venography to investigate other possible anomalies and blood flow of the renal vein. In addition, the graft must be carefully selected so that it is not disadvantageous to the donor. If there is no disadvantage to the donor as to which kidney is selected, the kidney with the longer renal vein should be transplanted.
Diagnostic Levels in Dental Public Health Planning
Authors: Ismail Amid
Published: May 2004

This concept paper discusses the rationale for using different diagnostic criteria for dental caries in public health programs. The author contends that epidemiological data or needs assessment surveys should collect data to provide information on the epidemiology of different stages of the caries process in order to enable planners to design tailored programs to prevent dental caries. In a rapidly progressing caries environment, conventional approaches to delivering preventive measures may not work. The author also contends that dental public health programs should expand their vision to influence how dentists are detecting, diagnosing and managing dental caries. Dentists’ restorative decisions have significant impact on the oral health status of a nation. Henceforth, detecting the early or noncavitated caries level and preventing these lesions from progressing to the cavitated stage (or being restored) could have a significant impact on the oral health status around the world. There is a need for more research on the best methods to detect, prevent and treat early carious lesions.
A Caries Vaccine?
Authors: Russell Michael W. , Childers Noel K. , Michalek Suzanne M. , Smith Daniel J. , Taubman Martin A.
Published: May 2004

Studies performed in numerous laboratories over several decades have demonstrated the feasibility of immunizing experimental rodents or primates with protein antigens derived from Streptococcus mutans or Streptococcus sobrinus against oral colonization by mutans streptococci and the development of dental caries. Protection has been attributed to salivary IgA antibodies which can inhibit sucrose-independent or sucrose-dependent mechanisms of streptococcal accumulation on tooth surfaces according to the choice of vaccine antigen. Strategies of mucosal immunization have been developed to induce high levels of salivary antibodies that can persist for prolonged periods and to establish immune memory. Studies in humans show that salivary antibodies to mutans streptococci can be induced by similar approaches, and that passively applied antibodies can also suppress oral re-colonization by mutans streptococci. Progress towards practical vaccine development requires evaluation of candidate vaccines in clinical trials. Promising strategies of passive immunization also require further clinical evaluation.
Are We Ready to Move from Operative to Non-Operative/Preventive Treatment of Dental Caries in Clinical Practice?
Authors: Pitts N.B.
Published: May 2004

This review focuses on the clinical interactions between patients and the dental team, not on caries prevention at a public health level. Many dentists no longer take a narrow surgical view seeking to apply interventive treatment as a one-off event at a certain trigger point of disease severity and the evidence that caries is an initially reversible, chronic disease with a known multi-factorial aetiology is being appreciated more widely. The caries process should be managed over time in an individualized way for each patient. Very few individuals can be considered to be truly ‘caries free’ when initial lesions as well as more advanced dentine lesions are considered. It is now very clear that, by itself, restorative treatment of the disease does not ‘cure’ caries. The caries process needs to be managed, in partnership with patients, over the changing challenges of a lifetime. The answer to the question posed in the title should be, in many cases, that we are ready to move to non-operative/preventive care (if we have not done so already). However, this should be for appropriate stages of lesion extent and in patients who respond to advice on recall frequency and preventive behaviours.
Mineralo- and Glucocorticoid Receptor mRNAs Are Differently Regulated by Corticosterone in the Rat Hippocampus and Anterior Pituitary
Authors: Hügin-Flores Mirza E. , Steimer Thierry , Aubert Michel L. , Schulz Pierre
Published: May 2004

In most cell lines and animal tissues, glucocorticoid receptors undergo downregulation after exposure to corticosterone. However, corticosterone treatment has not shown a consistent effect on mineralocorticoid (MR) and glucocorticoid receptors (GR) in the hippocampus, and it has been rarely assessed in the anterior pituitary. In this study we investigated dose-dependent effects of corticosterone on MR and GR mRNAs in the hippocampus and anterior pituitary. Adrenalectomized rats substituted with corticosterone in drinking fluid were injected subcutaneously with vehicle or 1, 10, 50, 100, or 200 mg of corticosterone, and sacrificed 4 h later. In the hippocampus we found a progressive decrease in MR and GR mRNAs with increasing doses of corticosterone. This was significant with 50 and 100 mg corticosterone for MR mRNA and with 10–200 mg corticosterone for GR mRNA at plasma corticosterone levels above 30 µg/dl. The anterior pituitary did not show significant changes at any dose. A time-course with 2 mg of corticosterone (non-response dose range at 4 h) revealed a significant decrease in MR and GR mRNAs in the hippocampus 8 h after the subcutaneous injection. In the anterior pituitary both mRNAs showed an increase that was significant 24 h after injection for MR and from 8 to 24 h for GR. In the hippocampus, adrenalectomy (absence of corticosterone) induced a significant increase in MR and GR mRNAs on day 3, but not on days 1, 8 and 21 after adrenalectomy. In the anterior pituitary there were no significant changes at any time after adrenalectomy. In summary, we have found an in vivo corticosterone dose- and time-dependent downregulation of MR and GR mRNAs in the hippocampus, whereas anterior pituitary MRs and GRs seem relatively insensitive to the excess or the absence of corticosterone, suggesting the lack of an autoregulatory effect in this tissue. Significant mRNA changes appearing later in time could suggest a secondary response via a glucocorticoid-induced gene product. Corticosteroid receptor downregulation in the hippocampus could prevent overstimulation or tissue damage when plasma corticosterone is high, while increased corticosteroid receptors in the anterior pituitary could buffer the excessive brain drive on the pituitary during chronic stress or pathological conditions associated with increased plasma glucocorticoids, such as depression.
Protein Kinase Cδ as Gonadotropin-Releasing Hormone Target Isoenzyme in the αT3-1 Gonadotrope Cell Line
Authors: Maccario Hélène , Junoy Brice , Poulin Benoit , Boyer Bénédicte , Enjalbert Alain , Drouva Sophia V.
Published: May 2004

We investigated the kinetics of gonadotropin-releasing hormone (GnRH)-induced activation of the protein kinase C (PKC) δ isoform in αT3-1 gonadotrope cells. Results were evaluated in subcellular fractions and whole-cell lysates using specific antibodies recognizing either non- or (trans- and auto-)phosphorylated forms of the kinase at Thr505 and Ser643 residues modulating stability and/or activation of the enzyme. Under basal conditions, and in contrast to PKC Ε, PKC δ was mainly associated with the membrane compartment. GnRH (10–7M) elicited further and rapid membrane translocation and time-dependent phosphorylation at both sites of PKC δ. The neuropeptide’s effects did not show a refractory period after short but successive GnRH stimulation and were abolished by the GnRH antagonist, antide. Sustained GnRH stimulation (2–6 h) provoked rapid down-regulation of PKC δ. Antide, by inhibiting the initial processes (translocation, phosphorylation), counteracted the degradation of the enzyme. Proteolytic processing of PKC δ was shown to mainly involve proteasome activity. Indeed, specific proteasome inhibitors prevented GnRH-elicited kinase depletion and induced membrane accumulation of the enzyme in a phosphorylated (Thr505, Ser643) form. Thus, GnRH may regulate time-dependent cell responses by modulating the phosphorylation/activation state of its signal transduction effector proteins, and by maintaining their appropriate expression balance via proteolytic processes involving the proteasome system.
Preclinical Memory Profile in Alzheimer Patients with and without Allele APOE-epsilon4
Authors: Estévez-González Armando , García-Sánchez Carmen , Boltes Anunciación , Otermín Pilar , Baiget Montserrat , Escartín Antonio , del Rio Elisabeth , Gironell Alex , Kulisevsky Jaime
Published: May 2004

To investigate the association between APOE-Ε4 allele and memory phenotype in the preclinical stage of Alzheimer’s disease (AD). We compared an extensive preclinical memory profile at the baseline evaluation of 2 AD genotype groups: APOE-Ε4 allele carriers and patients with APOE-Ε3 homozygosity. Baseline memory performance was carried out at least 2 years (interval of 27.7 ± 4 months) before AD diagnosis was established, and analysis included different modalities of working memory (visuoperceptive, visuospatial, digit span and processing speed), of declarative memory (recent, verbal learning, prospective and semantic) and of nondeclarative memory (procedural, incidental and priming). We found no significant differences: memory performance was similar in both genotype groups. The presence of the APOE-Ε4 allele does not seem to be sufficient to cause a distinctive preclinical memory phenotype in AD patients.
Congenital Insensitivity to Pain with Anhidrosis in Taiwan: A Morphometric and Genetic Study
Authors: Guo Yuh-Cherng , Liao Kwong-Kum , Soong Bing-Wen , Tsai Ching-Piao , Niu Dau-Ming , Lee Hsiang-Ying , Lin Kon-Ping
Published: May 2004

Congenital insensitivity to pain with anhidrosis (CIPA) is characterized by insensitivity to pain, anhidrosis, recurrent hyperpyrexia, mild mental retardation, and self-mutilating behavior. We report 2 brothers, aged 20 and 18 years, who suffered from phenotypes of CIPA. Both brothers had a branch site mutation in intron 7 (IVS7-33 T→A) of the neurotrophic tyrosine kinase receptor type 1 gene. The electrophysiological studies showed no significant abnormal findings in sensory evoked potentials, motor evoked potentials to transcranial magnetic stimulation, or heart rate variations; sympathetic skin responses were absent. Morphometric study of their sural nerve histopathology revealed normal myelinated fiber density, 8,082 fibers/mm2 and 5,637 fibers/mm2 (normal 6,141 ± 421); decreased unmyelinated fiber density, 2,537 fibers/mm2 and 2,211 fibers/mm2 (normal 28,578 ± 8,669); increased axon size, 4.41 ± 1.59 µm and 5.33 ± 1.48 µm (normal 3.73 ± 1.45), and increased axon diameter (A)/myelin thickness (M) ratio (A/M), 3.47 ± 1.42 and 2.70 ± 1.07 (normal 2.49 ± 0.93). Scatterplot analysis of the G ratio (axon diameter:fiber diameter) did not show consistent results in the relationship between axon size and myelin thickness. In conclusion, the neuropathy of our CIPA patients included a marked reduction of small myelinated and unmyelinated fibers and a relatively increased axon size. This is the first CIPA family encountered in Taiwan.
Apolipoprotein E and Alpha-1-Antichymotrypsin Polymorphisms in Sporadic Inclusion Body Myositis
Authors: Gossrau G. , Gestrich B. , Koch R. , Wunderlich C. , Schröder J.M. , Schroeder S. , Reichmann H. , Lampe J.B.
Published: May 2004

Sporadic inclusion body myositis (s-IBM) is a progressive muscle disease of unknown aetiology. Characteristically, intracellular amyloid deposits are detectable, including β-amyloid precursor protein, phosphorylated tau, α1-antichymotrypsin (α1-ACT) and apolipoprotein E (ApoE). Polymorphisms and mutations of the encoding genes have been identified in a variety of neurodegenerative diseases including Alzheimer’s disease (AD). Beside other factors, polymorphisms may lead to protein accumulation in both diseases. In particular, polymorphisms within the ApoE and α1-ACT gene have been implicated in the aetiology of AD and s-IBM. We analysed ApoE and α1-ACT gene polymorphisms in 35 s-IBM patients. We could not identify any statistical significant correlation between distinct ApoE and α1-ACT genotypes and the risk of developing s-IBM. Additionally, ApoE and α1-ACT genotypes seem not to influence the onset age of s-IBM. A combination of different α1-ACT and ApoE genotypes appears not to enhance the risk of developing s-IBM. Therefore, allelic variations of α1-ACT and ApoE are unlikely to be genetic key factors in the aetiology of s-IBM.
Cardiac Cephalalgia
Authors: Chen Shih-Pin , Fuh Jong-Ling , Yu Wen-Chung , Wang Shuu-Jiun
Published: May 2004

We report a patient with cardiac cephalalgia and review reported cases from the English-language literature based on the new diagnostic criteria published in the International Classification of Headache Disorders, ed 2. Twenty-two patients, including ours, with headaches of cardiac origin were reviewed. The cases fit three of the four new criteria well: Criteria B (acute myocardial ischemia has occurred, 100%), C (headache developed concomitantly with acute myocardial ischemia, 100%), and D (headache resolved and does not recur after effective medical or surgical treatment for myocardial ischemia, 83%). The cases in which we had exceptions were to the proposed headache features (criterion A), which were generally not fulfilled, with nausea as the least frequent finding (27%); this criterion might not be mandatory for diagnosis.
Mixed Medullary-Follicular Thyroid Carcinoma
Authors: Kostoglou-Athanassiou I. , Athanassiou P. , Vecchini G. , Gogou L. , Kaldrymides P.
Published: May 2004

Objective: The aim was to describe the case of a female patient with a mixed medullary-follicular thyroid carcinoma. Methods: The patient underwent thyroidectomy for the treatment of multinodular goiter. A tumor was found which exhibited the features of a mixed medullary-follicular thyroid carcinoma. Immunohistochemistry was performed. Results: Immunohistochemistry was positive in the area of the carcinoma for calcitonin and thyroglobulin. She developed extensive metastatic deposits in the bones of the pelvis and in the calvarium causing hyperthyroidism. Conclusion: A patient with a mixed medullary-follicular thyroid carcinoma is described, who had elevated levels of both calcitonin and thyroglobulin and developed metastatic deposits, which could produce thyroid hormones.
Asperger Syndrome, Obsessive-Compulsive Disorder, and Major Depression in a Patient with 45,X/46,XY Mosaicism
Authors: Fontenelle Leonardo F. , Mendlowicz Mauro V. , Bezerra de Menezes Gabriela , dos Santos Martins Rosa Rita , Versiani Marcio
Published: May 2004

Background: Although previous reports have described the association of autism, mental retardation, and schizophrenia with a missing Y chromosome, we are not aware of any case showing an association between this particular chromosomal abnormality and Asperger syndrome. Method: We report the case of a male patient with a combination of Asperger syndrome, obsessive-compulsive disorder and 45,X/46,XY mosaicism. During the follow-up, this individual has also developed a severe episode of major depression, which was successfully treated with electroconvulsive therapy. Results: To the best of our knowledge, this is the first case in which a 45,X/46,XY mosaicism was described in association with Asperger syndrome, either alone or associated with other psychiatric disorders. Diagnostic and therapeutic aspects of this unique case are presented and discussed. Conclusions: Our findings suggest that a missing Y chromosome may play an etiological role in some cases of Asperger syndrome.
Deficit of Executive Functions in Schizophrenia: Relationship to Neurological Soft Signs and Psychopathology
Authors: Bersani Giuseppe , Clemente Roberta , Gherardelli Simona , Pancheri Paolo
Published: May 2004

Cognitive deficits and neurological soft signs (NSS) have frequently been reported in schizophrenic patients and they both appear related to prominent negative symptoms. The aim of the present study was to examine the relationship between deficit of executive functioning, assessed by the Wisconsin Card Sorting Test (WCST), NSS and psychopathological dimensions of schizophrenia in order to address the issue of whether a typology of schizophrenic patients may be identifiable by clinical, neurological and neuropsychological features. A sample of 26 male schizophrenic patients was divided, on the basis of the performance on the WCST, into two subgroups (‘good performers’ and ‘poor performers’) that were compared for the prevalence and severity of NSS, assessed by the Neurological Evaluation Scale (NES), and for the psychopathological features, assessed using the Positive and Negative Syndrome Scale (PANSS). To test for between-group differences, ANOVA was conducted. The ‘poor performers’ group showed greater severity of NSS: significant differences emerged for the NES total score and for the ‘sequencing of complex motor acts’ score. However, no significant differences between the groups emerged for any PANSS score. These findings seem to indicate that a common neurobiological abnormality could underlie cognitive deficits, especially concerning executive functioning, and subtle neurological abnormalities often present in schizophrenia, but they appear to deny that such dysfunctional correlates of schizophrenia are related to a prominent negative symptomatology.
α4β1 Integrin (VLA-4) Blockade Attenuates both Early and Late Leukocyte Recruitment and Neointimal Growth following Carotid Injury in Apolipoprotein E (–/–) Mice
Authors: Barringhaus Kurt G. , Phillips J. William , Thatte Jayant S. , Sanders John M. , Czarnik Ann C. , Bennett Daniel K. , Ley Klaus F. , Sarembock Ian J.
Published: May 2004

Background: The α4β1 integrin (VLA-4) supports rolling and firm adhesion of leukocytes to inflamed tissues via ligation of VCAM-1 or fibronectin expressed on the activated endothelium. We tested the hypothesis that VLA-4 mediates leukocyte recruitment and neointimal growth after arterial injury in the atherosclerosis-prone apolipoprotein E (ApoE)-deficient mouse. Methods: ApoE (–/–) mice fed a Western diet underwent air desiccation injury, and the expression patterns of VLA-4 and VCAM-1 were determined by immunohistochemistry (IHC). To determine the effect of targeted VLA-4 blockade on leukocyte recruitment and neointimal growth, ApoE (–/–) mice received an intraperitoneal injection of a VLA-4 neutralizing monoclonal antibody (PS/2) at the time of injury alone or over a prolonged administration course. Additional mice received an isotype control antibody. Results: IHC demonstrated a marked increase in VLA-4 expression 7 days following injury. Prolonged administration of PS/2 resulted in a 72% reduction (p < 0.02) in neointimal growth 28 days following injury. IHC revealed a marked 95% reduction in neutrophil recruitment at 7 days and a 48% reduction in macrophage recruitment 28 days following injury with prolonged PS/2 administration. Conclusions: Prolonged VLA-4 blockade reduces leukocyte recruitment and neointimal growth following air desiccation injury in ApoE (–/–) mice. These findings demonstrate an important role for VLA-4 in the response to arterial injury.
Jean Fautrier's Jolies Juives
Authors: Perry Rachel E.
Published: May 2004

There is in the words “a beautiful Jewess” a very special sexual signification, one quite different from that contained in the words “beautiful Rumanian,” “beautiful Greek,” or “beautiful American,” for example. This phrase carries an aura of rape and massacre with it. The “beautiful Jewess” is she whom the cossacks under the czars dragged by her hair through the streets of her burning village. And the special works which are given over to accounts of flagellation reserve a place of honor for the Jewess. But it is not necessary to look into esoteric literature. From the Rebecca of Ivanhoe up to the Jewess of “Gilles” … the Jewess has a well-defined function in even the most serious novels. Frequently violated or beaten, she sometimes succeeds in escaping dishonor by means of death, but that is a form of justice; and those who keep their virtue are docile servants or humiliated women in love with indifferent Christians who marry Aryan women. I think nothing more is needed to indicate the place the Jewess holds as a sexual symbol in folklore.
Of the Public Born: Raymond Hains and La France déchirée
Authors: Feldman Hannah
Published: May 2004

Le peuple constitue ses propres archives. —Michel Foucault, 1974
Le grand jasaq de Gengis-khan, l'empire, la culture mongole et la shari'a
Authors: Aigle Denise
Published: May 2004

Mongol law, the jasaq, has provided the basis for a long tradition of studies which were inaugurated by Petis de la Croix in 1710. He was the first to define a list of precepts of the jasaq, but without taking into consideration either the chronology or their origins. Most subsequent scholars dealing with the question revived this same vision of the jasaq. Debate was especially focused on whether or not the Mongols possessed a written code of laws. But, until now, little discussion has taken place concerning what the jasaq represented for the Mongols themselves and how this Mongol law was perceived by Mediaeval authors who, on the whole, confused the imperial edicts (jasaq) with customs (yosun). The present article is an attempt to clarify these issues. The author examines the jasaq in its politico-cultural context and, in particular, the analysis of the precepts takes into consideration shamanism, the Mongol system of representations. Reasons for the lack of understanding by Muslims of certain customs in disharmony with Islam are thereby highlighted, reasons which led them to see, in the jasaq, an equivalent of the sharī'a: a Mongol order imposed on populations which had fallen under their domination. La loi mongole, le jasaq, a donné lieu à une longue tradition d'études qui fut inaugurée par Petis de la Croix au XVIIe siècle. Il fut le premier à dresser une liste des préceptes du jasaq, sans tenir compte de la chronologie des sources et de leur provenance. Les chercheurs qui se sont penchés par la suite sur cette question ont repris, pour la plupart d'entre eux, cette vision du jasaq. Le débat s'est surtout focalisé sur l'existence ou non d'un code de loi écrit chez les Mongols. Mais, jusqu'à présent, il a été peu discuté de ce que le jasaq représentait pour les Mongols eux-mêmes et comment cette loi mongole a été perçue par les auteurs médiévaux qui confondaient, la plupart du temps, les édités impériaux (jasaq) et les coutumes (yosun). Cet article fait le point sur ces questions. L'auteur examine le jasaq dans son contexte politico-culturel et, en particulier, il prend en compte, dans l'analyse des préceptes, le système de représentations des Mongols, le chamanisme. Il met ainsi en lumière les raisons de l'incompréhension, de la part des musulmans, de certaines coutumes en désaccord avec l'islam, ce qui les a conduits à voir dans le jasaq l'équivalent de la sharī'a: un ordre mongol imposé aux populations tombées sous leur domination.
Psychometric properties of the sensory scale of the Fugl-Meyer Assessment in stroke patients
Authors: Lin Jau-Hong , Hsueh I-Ping , Sheu Ching-Fan , Hsieh Ching-Lin
Published: May 2004

Objective: To examine the psychometric properties of the sensory scale of the Fugl-Meyer Assessment (FMA-S) in stroke patients with a broad range of neurological and functional impairment at times from 14 to 180 days after stroke.

Subjects: A total of 176 first stroke patients consecutively admitted to a university based medical centre.

Design: This prospective, longitudinal investigation was based on data collected at 14, 30, 90 and 180 days after stroke.

Main outcome measures: Reliability (inter-rater reliability and internal consistency), validity (convergent and predictive validity) and responsiveness of the FMA-S were examined.

Results: The inter-rater agreement of the total score of the FMA-S was excellent, with an intraclass correlation coefficient of 0.93. The Cronbach's alphas of the FMA-S at four time points after stroke ranged from 0.94 to 0.98, indicating excellent internal consistency. However, the FMA-S showed a significant ceiling effect (more than 44.4% of the subjects achieving the highest score), poor to moderate inter-rater reliability for light touch items (weighted kappa ranging from 0.30 to 0.55), low to moderate validity (Spearman's rho ranging from 0.29 to 0.53), and low to moderate responsiveness (standardized response mean ranging from 0.27 to 0.67) at different post-stroke stages of recovery.

Conclusions: The psychometric properties of the FMA-S in measuring sensory function do not support its clinical use in stroke patients. Further studies on methods to improve the psychometric properties of the FMA-S are needed.
Rehabilitation outcomes after brain injury: disability measures or goal achievement?
Authors: Liu Clarence , McNeil Jane E , Greenwood Richard
Published: May 2004

Background: The outcome of rehabilitation interventions following brain injury is commonly rated by disability scales. Goal-setting and achievement are important in inpatient rehabilitation, but seldom assessed as outcomes.

Objective: To compare the information acquired from using disability ratings and goal attainment/variances as outcome measures in brain injury rehabilitation.

Setting: An inpatient regional neurological rehabilitation unit.

Subjects: One hundred and seventy-seven patients admitted after single incident brain injury over a three-year period.

Main measures: (1) Disability outcomes by the Barthel Index and the Functional Independence Measure, (2) goal achievement and variance distribution, and (3) the influence of diagnosis and demographics on these measures.

Results: Patients improved significantly on all disability scales employed (p < 0.0001), with the baseline admission scores being inversely correlated with changes in dependency by discharge (rho∼0.4). The median attainment rate of long-term goals was 75% per patient. Nonachievement was most frequently due to cognitive problems (38%), followed by behavioural difficulties and physical limitations (18% each). Goal achievement correlated poorly with disability outcome at discharge (rho∼0.3). Patients who accomplished all their goals tended to be less disabled at admission. Diagnostic groups and demographic factors had little influence on either disability or goal achievement outcomes.

Conclusions: The use of a simple goal achievement and variance coding scheme has been relatively straight forward to incorporate into the daily practice of the unit. It provides useful information on rehabilitation process and outcome after brain injury that is complementary to the utilization of disability measures.
Natural history of primary progressive multiple sclerosis
Authors: Ebers George C
Published: May 2004

The relationship of primary progressive multiple sclerosis (PPMS) to relapsing -remitting MS (RRMS) and secondary progressive MS (SPMS) remains unclear. Natural history data from a population-based cohort of patients with PPMS followed for approximately 25 years demonstrate remarkable similarities in the progressive phases of PPMS and SPMS. Immunogenetic and magnetic resonance imaging studies in large numbers of patients also fail to differentiate between the two MS categories. PPMS thus resembles SPMS without the relapses, although the two forms do differ with respect to sex ratio. A n unfavourable outcome in PPMS is predicted by rapid early progression of disability and involvement of three or more systems. Natural history studies provide information on likely long-term outcomes and can be used in the design and interpretation of clinical trials in PPMS. The evidence that PPMS is distinct remains weak.