bluuebunny/crossref_metadata_2025 huggingface dataset:
The Management of T1G3 Bladder Cancer
Authors: Bogdanović Jovo , Marušıć Goran , Djozić Jasenko , Sekulić Vuk , Budakov Pavle , Dejanović Nebojša , Stojkov Jovan
Published: April 2003

Introduction: The treatment of T1G3 bladder cancer is still a controversial issue. Nowadays, intravesical bacillus Calmette-Guérin (BCG) instillation is considered to be the treatment of choice for patients with high-grade superficial bladder tumour after transurethral resection of all visible tumour. The aim of this retrospective study was to determine the effects and results of this approach, recurrence and progression rates in patients with T1G3 superficial bladder tumours. Material and Methods: 43 patients (28 male, 15 female; mean age 65.5 years, range 21–82) with T1G3 TCC (transitional cell carcinoma) bladder tumour underwent transurethral resection and subsequent intravesical BCG according to Morales protocol, in the period 1993–1998 at our institution. The mean follow-up period was 52.5 (range 30–96) months. Results: After one or more initial courses of therapy, 33 patients were disease-free. Twelve patients (27.90%) had recurrent tumour after a median of 7 (range 3–46) months. After a second course of BCG treatment, 6 patients had no evidence of disease, 3 patients had progression and 3 had recurrence. Progression occurred in 7 (16.27%) patients after a median of 19 (range 3–43) months. Five patients underwent radical cystectomy and the remaining 2 underwent bladder-preserving therapies. Two patients died of TCC and 3 due to disease-unrelated conditions. Conclusion: Intravesical BCG instillation can be recommended as treatment modality for responders with T1G3 TCC bladder tumour. The benefit of the second course of intravesical BCG therapy has to be confirmed in further investigations.
Old and New Drug Consumption Habits in Hungary, Romania and Moldova
Authors: Elekes Zsuzsanna , Kovács László
Published: April 2003

The authors present patterns of drug use during the political and social transition periods in Hungary, Romania and Moldova. During the 1990s, each country witnessed major changes in the proliferation of various deviant behaviour patterns. These changes remain rather difficult to interpret and often reveal conflicting tendencies. Available statistical data and research results vary from country to country. On the basis of the information available, we can conclude that the era following the political transitions is characterised by an increase in drug-related problems. Although the extent of illicit drug use is probably much smaller than the extent of many other social problems, the novel nature of the drug problem and its extreme growth in the 1990s make it more of a social issue in all three countries.
Illicit Drug Use and Its Health Consequences in Belarus, Russian Federation and Ukraine: Impact of Transition
Authors: Poznyak Vladimir B. , Pelipas Vadim E. , Vievski Anatoliy N. , Miroshnichenko L.
Published: April 2003

The objective of this paper was to analyze the impact of the transition period on illicit drug use and its health consequences in Belarus, the Russian Federation and Ukraine. Available data were compiled to illustrate the trends and policy responses since 1991, when the countries had become politically independent and implemented radical changes in their social systems, which is particularly prominent in the Russian Federation and Ukraine. The transition period was associated with a rapid and dramatic increase in the supply of drugs combined with an increased demand, which was influenced by a range of social, economic and psychological factors. There was a sharp increase in negative public health consequences too. Inadequate policy responses might have had serious implications for economic and human development in the countries with a total population of more than 200 million people. The role of research to support policy responses is also discussed.
The SCID-hu Mouse Model as a Tool in Dermatopharmacology Research: New Options and a Review of the Literature
Authors: Kappes U.P. , Elsner P.
Published: April 2003

Xenogeneic transplantation of human skin onto severe combined immunodeficiency (SCID) mice lacking functional B and T cells enables the investigation of the human skin organ in vivo by means of an animal carrier. Research on these grafts has yielded a variety of new insights into skin biology and disease. A promising approach is the applicability of this human cutaneous xenograft model for the purpose of drug screening and testing of new therapies. This article reviews the use of the SCID mouse model in terms of dermatotherapy studies and outlines the potential options of this animal model in dermatopharmacology.
Postoperative Hyperprolactinemia Could Predict Longer Disease-Free and Overall Survival in Node-Negative Breast Cancer Patients
Authors: Mandalà Mario , Lissoni Paolo , Ferretti Gianluigi , Rocca Andrea , Torri Valter , Moro Cecilia , Curigliano Giuseppe , Barni Sandro
Published: April 2003

Objectives: Breast manipulation determines a physiological increase in prolactin (PRL) blood levels, but the clinical and biological impact of surgery-induced changes in PRL secretion still has to be clarified. The postoperative hyperprolactinemia has been related to aggressiveness of the tumor, early disease relapse or metastases, and poor overall survival in node-negative breast cancer patients. Surgery-induced hyperprolactinemia may be associated with a longer disease-free survival in both patients with or without node involvement. Methods: One hundred twenty-seven consecutive node-negative breast cancer patients, who were hospitalized from June 1985 to September 1990, were included in this study. The median follow-up was 12 years. To evaluate PRL secretion, venous blood samples were obtained at day 7th after surgery. In order to exclude the influence of stress and gonadal status, GH and estradiol serum levels were measured in the same blood samples. All endocrine examination were made during the morning, starting at 8.00 a.m. after overnight fasting. Hormonal serum levels were determined by the double antibody radioimmunoassay method. Results: Hyperprolactinemia was significantly more frequent in women younger than 50 years compared with the older ones, while the premenopausal status and T1 stage showed only a borderline significant association with hyperprolactinemia. Patients with normal postsurgical prolactinemia had 5- and 10-year disease-free survival rates of 64 and 56%, respectively, and 5- and 10-year overall survival rates of 84 and 70%, respectively. Patients with postsurgical hyperprolactinemia had 5- and 10-year disease-free survival rates of 89 and 81%, respectively, and 5- and 10-year overall survival rates of 94 and 81%, respectively. The difference in overall survival between the hyperprolactinemic and the normoprolactinemic groups, assessed by the log-rank test, was statistically significant (p = 0.02), and the difference in disease-free survival was highly significant (p = 0.0008). Conclusions: Our study shows that postsurgical hyperprolactinemia is associated with a significantly lower recurrence rate and longer disease-free and overall survival in operable node-negative breast cancer patients. Our data suggest that postoperative hyperprolactinemia could be crucial in the development of recurrence in operable breast cancer. Looking at results, the recurrence rate of node-negative patients who did not show postoperative hyperprolactinemia would be, in theory, similar to that of patients with node-positive disease, suggesting that normal postoperative PRL levels could identify a group of node-negative patients at high risk for recurrence.
The Predilection Sites for Chronic Atopic Dermatitis Do Not Show Any Special Functional Uniqueness of the Stratum corneum
Authors: O’goshi Ken-ichiro , Okada Mikiko , Iguchi Makiko , Tagami Hachiro
Published: April 2003

The functional deficiencies of the stratum corneum (SC) have been well documented in the skin of atopic dermatitis (AD) patients. AD tends to affect certain predilection areas chronically such as the face, neck and the flexural folds of the extremities. From the paucity of the information about the functional characteristics of the SC in such skin areas, we conducted biophysical measurements at the predilection sites of AD, i.e. the cheek, anterior surface of the neck, nape, antecubital fossa and popliteal fossa and relatively uninvolved sites such as the elbow, mid volar forearm, knee and mid calf in 34 AD patients and in 40 normal individuals. Reflecting the great interlocation variations in the SC noted even in the normal individuals, we found location-dependent as well as severity-dependent changes of SC function in the AD patients. Thus, the values of transepidermal water loss (TEWL) obtained on the cheek and, unexpectedly, the elbow were quite high, whereas those on the poplieal fossa were very low; even those values recorded on the lesional skin of the latter of the AD patients were significantly lower than those of the cheek of normal healthy individuals (p < 0.05). Moreover, the TEWL values measured at the nonlesional skin of AD patients were much closer to those of the normal healthy skin than to those of the lesional skin in most areas. Similarly, the SC hydration state that is influenced by the amount of skin surface lipids showed prominent location-dependent changes in addition to a severity-dependent change. It was much higher even in the lesional skin of the face and neck than in the normal skin of the extensor surface of the limbs. The corneocyte size, which inversely correlates with the turnover rate of the SC, was larger even on the lesional skin of the extremities than that of the normal cheek. It is only in skin surface pH that such location dependency was not demonstrable; it uniformly revealed higher values in the lesional and nonlesional skin of AD patients regardless of the sites. From these comparative data obtained at the predilection sites and relatively unaffected sites of AD, we think that those functional abnormalities of the SC reported in AD patients simply reflect the severity of underlying inflammatory changes rather than inherently defective SC functions.
Investigation of the Localization of Nerves in the Uterosacral Ligament: Determination of the Optimal Site for Uterosacral Nerve Ablation
Authors: Fujii Miho , Sagae Satoru , Sato Toshio , Tsugane Mizuyo , Murakami Gen , Kudo Ryuichi
Published: April 2003

We select surgical treatment for cases for which severe dysmenorrhea persists following medical treatment. Many reports have described the use of neurectomies by cutting off pain conducting nerve pathways using laparoscopic surgery. Laparoscopic uterosacral nerve ablation (LUNA) has been associated with a high success rate for pain control, but there are few reports of anatomical studies in the uterosacral ligament. Using an immunohistochemical method, we examined the number and types of nerve fiber bundles in the uterosacral ligaments and its surrounding tissue in cadavers. The greatest number of nerve fiber bundles was found at a distance of 16.5–33 mm and at a depth of 3–15 mm distal to the site of attachment of the uterosacral ligament to the uterine cervix. Furthermore, there were many more sympathetic and parasympathetic nerve fiber bundles than sensory ones in the uterosacral ligament and its surrounding tissue. These results show the appropriate site of transection of uterosacral ligaments when performing LUNA.
Laparoscopic Treatment of Endometrioma-Associated Infertility and Pregnancy Outcome
Authors: Takuma Naoyuki , Sengoku Kazuo , Pan Bochen , Wada Keiko , Yamauchi Tomofumi , Miyamoto Toshinobu , Ohsumi Daisuke , Ishikawa Mutsuo
Published: April 2003

Ovarian endometriomas do not respond well to medical treatment with hormonal suppression, and surgical removal of the endometriomas is usually required. In this study, we attempt to identify the optimal laparoscopic procedures in laparoscopic treatment of ovarian-endometrioma-associated infertility. Among cases in which patients received no IVF-ET after the laparoscopic treatment, the pregnancy rate after complete cystectomy of endometriomas was statistically lower than that after fenestration with electrocoagulation of the cyst wall. Among cases in which patients received IVF-ET, there was no difference in ovarian response between patients that had complete cystectomy and fenestration with electrocoagulation of the cyst wall. However, the pregnancy rate in patients who had aspiration alone was statistically lower than that in patients who had aspiration followed by ethanol fixation. Thus, it appears that for patients who do not require follow-up IVF-ET, fenestration with electrocoagulation of the cyst wall is suitable, whereas for patients who need follow-up IVF-ET, ethanol fixation may be a better choice.
Current Thinking on the Pathogenesis of Endometriosis
Authors: Donnez Jacques , van Langendonckt Anne , Casanas-Roux Françoise , van Gossum Jean-Paul , Pirard Céline , Jadoul Pascale , Squifflet Jean , Smets Mireille
Published: April 2003

This manuscript is a review of new ideas regarding the pathogenesis of peritoneal endometriosis, ovarian endometriosis, and retroperitoneal adenomyosis. Peritoneal endometriosis, the different aspects of which (black, red and white) represent distinctive steps in the evolutionary process, can be explained by the transplantation theory. Red lesions are the most active and most highly vascularized lesions and are considered to be the first stage of peritoneal endometriosis. The retroperitoneal nodule is an adenomyotic nodule whose histopathogenesis is not related to the implantation of regurgitated endometrial cells but to metaplasia of Müllerian remnants located in the rectovaginal septum. Metaplastic changes of Müllerian rests into adenomyotic glands involving the rectovaginal septum and the retroperitoneal space are responsible for the striking proliferation of the smooth muscle, creating an adenomyomatous appearance similar to that of adenomyosis in the endometrium.
B-Type Natriuretic Peptide Is Related to Left Ventricular Mass in Hypertensive Patients but Not in Athletes
Authors: Almeida Susana S. , Azevedo Ana , Castro Alice , Friões Fernando , Freitas João , Ferreira António , Bettencourt Paulo
Published: April 2003

A positive correlation has been previously documented between B-type natriuretic peptide (BNP) levels and left ventricular mass index (LVMI) in hypertensive patients. We evaluated 8 cycling athletes, 8 healthy age-matched controls; 17 hypertensive patients and 7 age-matched controls. LVMI was significantly higher in athletes and hypertensive patients than in their controls. Plasma levels of BNP in hypertensive patients were significantly higher than in athletes and their age-matched controls. No significant difference was found between athletes and their controls. Cycling athletes had significantly larger LVMI than hypertensive patients and controls, without elevated BNP levels. These results suggest that BNP levels are elevated in patients with increased LVM due to hypertension but not in physiologically increased LVM. Whether elevated BNP levels in athletes is a sign of structural heart disease merits further investigation.
Anaerobic Threshold and Maximal Oxygen Uptake in Patients with Coronary Artery Disease and Stable Angina before and after Percutaneous Transluminal Coronary Angioplasty
Authors: Barmeyer A. , Meinertz T.
Published: April 2003

In this study, we investigated the effect of percutaneous transluminal coronary angioplasty (PTCA) on functional exercise capacity, oxygen uptake at anaerobic threshold (VO2AT) and maximal oxygen uptake (VO2max) in patients with coronary artery disease (CAD). Twenty-five patients with CAD and stable angina pectoris underwent spiroergometry before and after PTCA. All patients had reduced functional capacity with Weber class B in 5, class C in 16 and class D in 4 patients with mean VO2AT of 9.4 ± 1.5 ml·kg–1·min–1 and mean VO2max of 13.3 ± 3.3 ml· kg–1·min–1. After PTCA, VO2max (15.8 ± 3.1 ml·kg–1· min–1) increased significantly (p < 0.001) compared to before PTCA. Subgroup analysis revealed that patients with low functional capacity before PTCA (VO2max <15 ml· kg–1· min–1) had the most benefit from PTCA with an increase in VO2AT from 8.7 ± 1.0 to 9.6 ± 1.4 ml·kg–1· min–1 (p < 0.05) and of VO2max from 11.3 ± 2.2to 14.8 ± 3.5 ml·kg–1·min–1 (p < 0.001) whereas in patients with VO2max >15 ml·kg–1·min–1, VO2AT (p = 0.9) and VO2max (p = 0.2) did not improve significantly. In conclusion, there is reduced functional capacity and VO2max which improved after PTCA in CAD patients. In patients with low VO2max before PTCA, functional capacity, VO2AT and VO2max significantly improved after PTCA, suggesting reversible myocardial impairment induced by intermittent myocardial ischemia. Patients with higher VO2max had no significant benefit from PTCA with respect to functional capacity, VO2max and VO2AT.
The Influence of Consanguineous Marriage on Infant and Child Mortality among Palestinians in the West Bank and Gaza, Jordan, Lebanon and Syria
Authors: Pedersen J.
Published: April 2003

Objectives: The purpose of this paper is to explore the characteristics of mortality differences associated with consanguineous marriage among Palestinians in the Middle East. Methods: The data came from five surveys of Palestinians living in the West Bank and Gaza, Syria, Jordan and Lebanon, conducted during the period 1995–2000. Infant and child mortality was estimated for the offspring of consanguineous and non-consanguineous parents using the synthetic cohort method. Results: The data showed an increase in infant mortality of 15.0 additional deaths per 1,000 births among the offspring of first cousins, and a corresponding increase of 6.1 deaths per 1,000 for the progeny of parents from the same patrilineal clan. Conclusion: In populations where marriage within kin groups is common, both first cousin marriage and intra-group marriage carries an added risk of infant and child mortality.
G-Protein Beta-3-Subunit and eNOS Gene Polymorphism in Transplant Recipients with Long-Term Renal Graft Function
Authors: Viklický Ondřej , Hubáček Jaroslav A. , Vítko Štefan , Heemann Uwe W. , Vasarhelyi Barna , Kohnle Mathias , Teplan Vladimír , Lácha Jiří , Szabó Attila J.
Published: April 2003

Background: Despite new immunosuppressive drugs, only a minority of graft survive over 15 years. The aim of our study was to determine the influence of gene polymorphisms in the G-protein-β3 subunit (Gβ3) and endothelial nitric oxide synthase (eNOS) on the long-term outcome of kidney grafts. Methods: Using PCR, corresponding genotypes in Gβ3 (C825T) and eNOS (G894T) gene polymorphism were evaluated in patients with preserved graft function over 15 years and in a control group of transplant recipients. Results: There were no differences in allele and genotype distributions of both polymorphisms between groups. In Gβ3 polymorphism, the 825T allele carriers had a significantly lower body mass index while in eNOS polymorphism there were no links between genotypes, renal function and atherosclerosis risk factors. Conclusions: Our data suggest that these gene polymorphisms have only a minor influence on long-term renal graft function.
Controversies in Management of Diabetes in Patients with Coronary Heart Disease
Authors: Abdella N.A.
Published: April 2003

A global epidemic of type 2 diabetes exists and in the near future it may be closely associated with an epidemic of cardiovascular disease. Since the diabetic population is at risk of developing cardiovascular disease, diabetes management should target tight glycaemic control. Two controversial issues in the management of diabetics with coronary heart disease (CHD) are discussed in this review. Firstly, exogenous insulin administration and increased risk of cardiovascular disease, and, secondly, the effect of sulphonylurea treatment on potassium ATP channels and risk of myocardial ischaemia. The consensus of opinion is that high circulating serum insulin level is simply a marker of an insulin-resistant state and therefore does not have a direct role in the pathogenesis of atherosclerosis in diabetic patients. However, overwhelming evidence exists for the linear association between worsening glycaemic control and increased risk for coronary heart disease. The United Kingdom Prospective Diabetes Study reported intensive blood glucose control decreased the risk of myocardial infarction by 16%. The benefits of tight glycaemic control outweighs the theoretical concept of hyperinsulinaemia being atherogenic. Safety concerns about sulphonylureas date back to 1970. The mechanism of action of sulphonylureas by closure of potassium ATP channels identified in pancreatic beta cells, cardiomyocytes and vascular smooth muscle cells caused great concern about safety because of the risk of developing myocardial ischaemia. Brief episodes of cardiac ischaemia render the heart more resistant to subsequent ischaemic events, this phenomenon is called ‘ischaemic preconditioning’. Activation of potassium ATP channels completely mimicked the preconditioning phenomena; moreover, blocking these channels with some of the sulphonylurea compounds abolished this protective effect. The concept of selectivity of sulphonylurea compounds therefore emerged and the choice of drug should be based on this fact. Every compound should be studied individually for its efficacy and safety vis-à-vis the relevant end points for type 2 diabetes, i.e. cardiovascular morbidity and mortality.
Human Herpesvirus 8 Investigations: A Role in the Clinical Management of Kaposi’s Sarcoma?
Authors: Simonart T. , Hermans P. , van Vooren J.P.
Published: April 2003

Kaposi’s sarcoma (KS) is a vascular tumour associated with infection by human herpesvirus 8 (HHV-8). Most of the recent studies on KS have focused on the epidemiology and molecular biology of HHV-8. However, the contribution of virological investigations into HHV-8 to the clinical management of KS has been poorly evaluated so far. From a diagnostic point of view, HHV-8 currently appears as a useful tool for distinguishing KS from its mimics. Seroconversion to antibodies against HHV-8 may predict the development of KS in susceptible individuals, and reduction of HHV-8 viraemia is associated with therapies effective against KS. Further prospective studies are still required to determine the role of serological or genotypic investigations into HHV-8 in the prevention of KS and in KS response to therapy.
Trichogerminoma: A Rare Cutaneous Adnexal Tumor with Differentiation toward the Hair Germ Epithelium
Authors: Kazakov D.V. , Kutzner H. , Rütten A. , Dummer R. , Burg G. , Kempf W.
Published: April 2003

In 1992, Sau and colleagues described 14 cases of a rare cutaneous adnexal tumor with differentiation toward the hair germ epithelium. All cases in their study displayed a unique constellation of histological features which allowed the authors to consider the neoplasm to be a distinct entity and to designate it as ‘trichogerminoma’ (TG). We present a case of an adnexal tumor identical to that described as TG and report the immunophenotypical features of this neoplasm for the first time. A biopsy from a 41-year-old man revealed a well-demarcated epithelial tumor composed of multiple lobules located in the deep dermis without connection to the overlying epidermis and surrounded by a fibrous pseudocapsule. The tumorous lobules were composed of uniform basophilic cells with vesicular nuclei, dispersed chromatin and prominent nucleoli showing no prominent peripheral palisading. Some of the lobules had the appearance of densely packed ‘cell balls’ with peripheral condensation of the tumor cells. The stroma showed a moderate number of fibroblasts and mast cells. Reticulum staining revealed fine reticulum fibers surrounding the tumor aggregates with accentuation of the ‘cell balls’. Immunohistochemically, the tumor cells expressed AE1/AE3, CK5/8, CK5/6, CAM5.2 and stained negatively for CK20, CK7, calretinin, Lu-5 and Thomsen- Friedensreich antigen. There was no increase in the numbers of CK20-positive Merkel cells in the epidermis overlying the tumor; however, a few Merkel cells were scattered in some tumor lobules. In addition, we stained 6 trichoblastomas (TBs) and found a particular pattern of calretinin expression in this tumor which was not observed in our case of TG. We conclude that pathological features allow the delineation of TG as a distinct adnexal neoplasm. Histological differential diagnosis includes basal-cell carcinoma (pilar type), large nodular TB, trichoblastic fibroma, trichoepithelioma, tricholemmoma, pilomatricoma and matrical carcinoma.
A New Calcipotriol/Betamethasone Dipropionate Formulation (DaivobetTM) Is an Effective Once-Daily Treatment for Psoriasis vulgaris
Authors: Kaufmann R. , Bibby A.J. , Bissonnette R. , Cambazard F. , Chu A.C. , Decroix J. , Douglas W.S. , Lowson D. , Mascaro J.M. , Murphy G.M. , Stymne B.
Published: April 2003

Background: Topical corticosteroids and calcipotriol have been used separately for many years to treat psoriasis. A new combination ointment has been formulated, which contains both calcipotriol and the corticosteroid betamethasone dipropionate. Objective: To compare the combination ointment with betamethasone dipropionate ointment, calcipotriol ointment and ointment vehicle in patients with psoriasis vulgaris. Methods: 1,603 patients were randomised to one of the 4 double-blind treatments used once daily for 4 weeks. Results: Themean percentage change in the PASI at the end of treatment was –71.3 (combination), –57.2 (betamethasone), –46.1 (calcipotriol) and –22.7 (vehicle). The mean difference of combination minus betamethasone was –14.2 (95% CI: –17.6 to –10.8, p < 0.001), of combination minus calcipotriol –25.3 (95% CI: –28.7 to –21.9, p < 0.001) and of combination minus vehicle –48.3 (95% CI: –53.2 to –43.4, p < 0.001). 6.0% of patients (combination) reported local adverse reactions compared to 4.9% (betamethasone), 11.4% (calcipotriol) and 13.6% (vehicle). Conclusion: Calcipotriol/betamethasone dipropionate combination ointment used once daily is well tolerated and more effective than either active constituent used alone.
Measures of Perception of Bronchoconstriction and Clinical and Functional Data Are Not Interrelated in Asthma
Authors: Grazzini M. , Ottanelli R. , Duranti R. , Stendardi L. , Ronchi M.C. , Romagnoli I. , Scano G.
Published: April 2003

Background: Sensitivity and absolute perceptual magnitude characterize the perception of bronchoconstriction (PB). Objectives: To define whether clinical and functional characteristics and level of bronchial hyperresponsiveness (BHR) correlate with these two PB indexes during bronchial challenge in asthma. Methods: PB on both the Borg scale and the visual-analogue scale (VAS) was assessed in 45 consecutive asthmatics during a methacholine-induced decrease in forced expiratory volume in 1 s (FEV1) and specifically quantified as Borg and VAS slope, as a measure of sensitivity, whereas scores at a 20% FEV1 decrease (PB20) were assessed as a measure of absolute perceptual magnitude. Clinical score and BHR were also assessed. Results: PB20 related to slope on both the Borg scale and the VAS (p < 0.0001). PB20 and slope related neither to clinical score nor to baseline functional data on both scales. The relationship between the level of BHR and PB20 on either scale was of questionable clinical significance (r2 = 7%). Conclusions: Irrespective of the scale employed, our data indicate the need for directly assessing PB rather than deriving it from clinical and functional data and level of BHR.
The Cholinergic Deficiency Syndrome and Its Therapeutic Implications
Authors: Lemstra Afina W. , Eikelenboom Piet , van Gool Willem A.
Published: April 2003

Cholinesterase inhibitors are licensed for treatment of dementia in Alzheimer’s disease. However, the effects of these drugs on the cognitive symptoms of dementia are very small. We suggest that symptoms like impairment of attention and concentration, anxiety, restlessness and hallucinations, delineate a specific central cholinergic deficiency syndrome (CDS), that may be a much better target for such treatment. Changes in the quantitative electroencephalogram, muscarinic subtype radioimaging and serum anticholinergic activity may potentially help to diagnose the CDS. CDS is suggested to occur in various neurodegenerative diseases like Alzheimer’s disease, Lewy body dementia and Parkinson’s disease and to respond well to cholinesterase inhibitor therapy.
Overexpression of Human Tumor-Associated Antigen, RCAS1, Is Significantly Linked to Dedifferentiation of Thyroid Carcinoma
Authors: Ito Yasuhiro , Yoshida Hiroshi , Nakano Keiichi , Kobayashi Kaoru , Yokozawa Tamotsu , Hirai Keisuke , Matsuzuka Fumio , Matsuura Nariaki , Kuma Kanji , Miyauchi Akira
Published: April 2003

Objective: Counterattack by RCAS1 on carcinoma to cytotoxic T cells and natural killer (NK) cells has been suggested as a contribution to carcinoma progression, because RCAS1 can inhibit their proliferation and induce apoptosis. In this study, we examined RCAS1 expression in various thyroid neoplasms in order to clarify its clinical significance. Methods: We studied RCAS1 expression by means of immunohistochemistry using a mouse monoclonal antibody against RCAS1 for normal thyroid epithelium, follicular adenoma, follicular carcinoma, papillary carcinoma and undifferentiated (anaplastic) carcinoma. Results: Normal epithelium and follicular adenoma did not express or only faintly expressed RCAS1. In thyroid carcinomas. RCAS1 overexpression was more frequently observed in anaplastic (undifferentiated) carcinomas than papillary (p < 0.0001) and follicular carcinomas (p = 0.0018). In follicular carcinoma, the widely invasive type more frequently overexpressed RCAS1 than the minimally invasive type (p = 0.0488). Furthermore, the incidences of RCAS1 overexpression increased with carcinoma dedifferentiation (p < 0.0001). Conclusion: These results suggest that RCAS1 may contribute to the progression of thyroid carcinoma with high biological aggressiveness.
Fluoride Intake in Japanese Children Aged 3–5 Years by the Duplicate-Diet Technique
Authors: Murakami T. , Narita N. , Nakagaki H. , Shibata T. , Robinson C.
Published: April 2003

This study was conducted to determine the fluoride intakes in 94 preschool children aged 3, 4 and 5 (n = 30, 30, 34, respectively) residing in Yokkaichi, Mie Prefecture (< 0.16 ppm F water supply). The parents duplicated all the diets that their children ingested on 3 separate days during a 1-year period. The acid-diffusible fluoride in the diet was isolated by the acid-diffusion technique and measured with a fluoride electrode. The mean daily fluoride intakes from diet alone by children aged 3, 4 and 5 were 0.30 mg (n = 29, SD 0.19), 0.28 mg (n = 30, SD 0.19) and 0.30 mg (n = 34, SD 0.19), respectively. The total estimated mean values from diet and dentifrice were 0.35 mg (n = 29, SD 0.22, range 0.13–1.00), 0.33 mg (n = 30, SD 0.19, range 0.13–0.86) and 0.39 mg (n = 34, SD 0.18, range 0.18–1.01), respectively. It was concluded that the mean (±SD) total fluoride from diet and dentifrice in 3- to 5-year-old Japanese children was 0.35 ± 0.19 mg/day (0.021 ± 0.012 mg/kg body weight).
Fourteen chromosomal localizations and an update of the cytogenetic map of the rabbit
Authors: Zijlstra C. , de Haan N.A. , Korstanje R. , Rogel-Gaillard C. , Piumi F. , van Lith H.A. , van Zutphen L.F.M. , Bosma A.A.
Published: April 2003

In order to improve the informativeness of the cytogenetic map of the rabbit genome, fourteen markers were regionally mapped to individual chromosomes. The localizations comprise eleven gene loci (PRLR, GHR, HK1, ACE, TF, 18S+28S rDNA, CYP2C4, PMP2, TCRB, ALOX15 and MT1) and three microsatellite loci (Sat13, Sol33 and D1Utr6). Five of the genes contain known microsatellite sequences. To achieve these localizations, homologous and heterologous small insert clones, and clones from a rabbit Bacterial Artificial Chromosome (BAC) library were used as probes for fluorescence in situ hybridization experiments. Results indicate that especially BAC clones are a valuable tool for cytogenetic mapping. Some of the genes were selected for mapping on the basis of human- rabbit comparative painting data, to achieve localizations on gene-poor rabbit chromosomes. Our data are, in general, in agreement with the human-rabbit comparative painting data. By mapping microsatellite sequences that have also been used in linkage studies, links are provided between the genetic and physical maps of the rabbit genome. Linkage groups I, VI and XI could be assigned to chromosomes 1, 5 and 3 respectively. Moreover, in this paper we give an overview of the current status of the rabbit cytogenetic map. This map now comprises 62 physically mapped genes, which are scattered over all autosomes, except chromosome 2, and the X chromosome.
Identification of a haplosufficient 3.6-Mb region in human chromosome 11q14.3→q21
Authors: Li L. , Moore P. , Ngo C. , Petrovic V. , White S.M. , Northrop E. , Ioannou P.A. , McKinlay Gardner R.J. , Slater H.R.
Published: April 2003

Cytogenetic deletions are almost always associated with phenotypic abnormality and are very rarely transmitted. We have located a hitherto undescribed, familial deletion involving the region 11q14.3→q21 in five individuals in a three-generation kindred. Four of the deletion carriers show no phenotypic abnormality; the other, who is the proband, was investigated for short stature and poor academic progress. In view of the apparent innocuous nature of this genetic imbalance, the deletion was investigated in detail to determine its size (3.6 Mb) and location with reference to molecular markers and genetic content. The deleted region is described by a contig of 37 BACS including the flanking regions, which we have assembled. Several possible contributory factors are considered, which might explain the lack of clinical significance of this large deletion. It is notable that there are few genes in this region and none have known functions. All most likely have copies elsewhere in the genome and a number of other hypothetical genes appear to be members of certain gene families, i.e. none is unique. Part of the region (1 Mb) is also duplicated at the pericentromeric region 11p11. Given the very low proportion of the genome occupied by single copy genes and their uneven distribution, regions such as this, which appear to be functionally haplosufficient, may be more common than hitherto recognised.
Steroid Receptor Coactivator SRC-1 Exhibits High Expression in Steroid-Sensitive Brain Areas Regulating Reproductive Behaviors in the Quail Brain
Authors: Charlier Thierry D. , Lakaye Bernard , Ball Gregory F. , Balthazart Jacques
Published: April 2003

The steroid receptor coactivator SRC-1 modulates ligand-dependent transactivation of several nuclear receptors, including the receptors for sex steroid hormones. Reducing the expression of SRC-1 by injection of specific antisense oligonucleotides markedly inhibits the effects of estrogens of the sexual differentiation of brain and behavior in rats and inhibits the activation of female sexual behavior in adult female rats. SRC-1 thus appears to be involved in both the development and activation of sexual behavior. In the Japanese quail brain, we amplified by RT-PCR a 3,411-bp fragment extending from the HLH domain to the activating domain-2 of the protein. The quail SRC-1 is closely related to the mammalian (m) SRC-1 and contains a high proportion of GC nucleotides (62.5%). Its amino acid sequence presents 70% identity with mammalian SRC-1 and contains the three conserved LXXLL boxes involved in the interaction with nuclear receptors. In both males and females, RT-PCR demonstrates a similarly high level of expression in the telencephalon, diencephalon, optic lobes, brain stem, spinal cord, pituitary, liver, kidney, adrenal gland, heart, lung, gonads and gonoducts. Males express significantly higher levels of SRC-1 in the preoptic area-hypothalamus than females. In both sexes, lower levels of expression are observed in the cerebellum and muscles. In situhybridization utilizing a mixture of four digoxigenin-labeled oligonucleotides confirms at the cellular level the widespread distribution of SRC-1 mRNA in the brain and a particularly dense expression in steroid-sensitive areas that play a key role in the control of male sexual behavior. These data confirm the presence and describe for the first time the SRC-1 distribution in the brain of an avian species. They confirm its broad, nearly ubiquitous, distribution in the entire body including the brain as could be expected for a coactivator that regulates to the action of many nuclear receptors. However this distribution is heterogeneous in the brain and sexually differentiated in at least some areas. The very dense expression of SRC-1 in limbic and mesencephalic nuclei that are associated with the control of male sexual behavior is consistent with the notion that this coactivator plays a significant role in the activation of this behavior.
Eine jungianische Perspektive der Menopause: Nicht nur für Frauen1
Authors: Culbert-Koehn JoAnn
Published: April 2003

Die jungianische Psychologie hat etwas zu bieten, das für Frauen in der Menopause von besonderem Interesse ist, denn die jungianische Psychologie legt nachdrückliches Gewicht auf Besonderheiten, Wachstum und Entwicklung in der zweiten Lebenshälfte. Darüber hinaus beschäftigen sich die Jungianer seit vielen Jahren sowohl auf einer persönlichen wie auf einer archetypischen Ebene mit Fragen der weiblichen Entwicklung. In der vorliegenden Arbeit wird die vorhandene Literatur gesichtet, und es werden zehn psychologische Fragestellungen behandelt, die für den Übergangsprozess während der Menopause eine besondere Rolle spielen. Es werden zwei Beispiele angeführt: das einer Frau in der Menopause und das einer Frau nach der Menopause. Schliesslich greift die Autorin zur Veranschaulichung des Überganges zur Menopause auf eine Erzählung der Athabasken-Indianer zurück.
Molecular Complexes Formed with Polycystins
Authors: Lakkis Montaha , Zhou Jing
Published: April 2003

Polycystins are a family of novel transmembrane proteins with at least six members already identified in humans. Defects in polycystins-1 and -2 are responsible for nearly all cases of autosomal-dominant polycystic kidney disease (ADPKD), a major cause of end-stage renal failure. With the progress made in elucidating the genetic basis of ADPKD, the challenges are to understand the functions of polycystins and to delineate the biochemical and cellular mechanisms of cyst development and progression. In this review, we summarize the recent advances in our knowledge of the functions of polycystins with emphasis on the molecular composition of polycystin protein complexes in the kidney.
Towards Understanding the Polycystins
Authors: Kaletta Titus , van der Craen Marc , van Geel Anton , Dewulf Nathalie , Bogaert Thierry , Branden Michael , King Kevin V. , Buechner Matthew , Barstead Robert , Hyink Deborah , Li Hsi-Ping , Geng Lin , Burrow Christopher , Wilson Patricia
Published: April 2003

Autosomal dominant polycystic kidney disease (ADPKD) is a very common inherited disease caused by mutations in PKD1 or PKD2 genes characterized by progressive enlargement of fluid-filled cysts and loss of renal function [1]. Previous studies proposed a role for human polycystin-1 in renal morphogenesis acting as a matrix receptor in focal adhesions and for polycystin-2 as a putative calcium channel [2, 3]. The genome of Caenorhabditis elegans contains 2 new members of the polycystin family: lov-1, the homolog for PKD1; and pkd-2, the homolog for PKD2 [4; this paper]. Mutation analysis in C. elegans showed similarly compromised male mating behaviors in all single and double lov-1 and pkd-2 mutants, indicating their participation in a single genetic pathway. Expression analysis localized LOV-1 and PKD-2 to the ends of sensory neurons in male tails and to the tips of CEM neurons in the head, consistent with functions as chemo- or mechanosensors. Human and C. elegans PKD1 and PKD2 homologs, transfected into mammalian renal epithelial cells, co-localized with paxillin in focal adhesions suggesting function in a single biological pathway. Based on the role of polycystins in C. elegans sensory neuron function and the conservation of PKD pathways we suggest that polycystins act as sensors of the extracellular environment, initiating, via focal adhesion assembly, intracellular transduction events in neuronal or morphogenetic processes.
Dietary Citrate Treatment of Polycystic Kidney Disease in Rats
Authors: Tanner George A. , Tanner Judith A.
Published: April 2003

Progression of autosomal-dominant polycystic kidney disease (ADPKD) in the heterozygous male Han:SPRD rat is dramatically slowed by ingestion of potassium or sodium citrate. This study examined the efficacy of delayed therapy with sodium citrate, the effect of sodium citrate therapy on kidney cortex levels of transforming growth factor-β (TGF-β), and the response to calcium citrate ingestion. Rats were provided with citrate salts in their food, and renal clearance, blood pressure, blood chemistry, and survival determinations were made. Sodium citrate therapy was most effective when started at age 1 month, and delay of therapy until age 3 months produced no benefit. Kidney cortex TGF-β levels were elevated in 3- and 8-month-old rats with ADPKD, but not in 6-week-old rats. Sodium citrate treatment, started at age 1 month, lowered TGF-β levels to normal in 3-month-old rats, but this is probably not the primary mechanism of citrate’s beneficial effect. Calcium citrate had only a modest effect in preserving glomerular filtration rate. Effective treatment of ADPKD in this rat model requires early administration of a readily absorbed alkalinizing citrate salt. Existing data on ADPKD patients on vegetarian diets or with kidney stones should be studied in light of these findings.
Power and Sample Size Calculations for Case-Control Genetic Association Tests when Errors Are Present: Application to Single Nucleotide Polymorphisms
Authors: Gordon Derek , Finch Stephen J. , Nothnagel Michael , Ott Jürg
Published: April 2003

The purpose of this work is to quantify the effects that errors in genotyping have on power and the sample size necessary to maintain constant asymptotic Type I and Type II error rates (SSN) for case-control genetic association studies between a disease phenotype and a di-allelic marker locus, for example a single nucleotide polymorphism (SNP) locus. We consider the effects of three published models of genotyping errors on the chi-square test for independence in the 2 × 3 table. After specifying genotype frequencies for the marker locus conditional on disease status and error model in both a genetic model-based and a genetic model-free framework, we compute the asymptotic power to detect association through specification of the test’s non-centrality parameter. This parameter determines the functional dependence of SSN on the genotyping error rates. Additionally, we study the dependence of SSN on linkage disequilibrium (LD), marker allele frequencies, and genotyping error rates for a dominant disease model. Increased genotyping error rate requires a larger SSN. Every 1% increase in sum of genotyping error rates requires that both case and control SSN be increased by 2–8%, with the extent of increase dependent upon the error model. For the dominant disease model, SSN is a nonlinear function of LD and genotyping error rate, with greater SSN for lower LD and higher genotyping error rate. The combination of lower LD and higher genotyping error rates requires a larger SSN than the sum of the SSN for the lower LD and for the higher genotyping error rate.
Cerebellar Regulation of Sensorimotor Activity in Brown Trout
Authors: Roberts B.L. , Dean J.A. , Paul D.H.
Published: April 2003

Evoked field potentials were recorded from the mesencephalic (‘optic’) tectum, cerebellar corpus, midline rhombencephalon, and spinal cord of decerebrated brown trout in response to single electrical shocks given to an optic nerve. Evoked responses were also recorded from the rhombencephalon and spinal cord following stimulation (singly and with trains) to the optic tectum and to the cerebellar corpus. The potentials recorded from the tectum in response to optic nerve stimulation were similar in form to those reported by other workers from other species of teleost. The rhombencephalic responses to optic nerve and tectal stimulation were complex and comprised presumed pre- and post-synaptic events. Cerebellar stimulation evoked no detectable responses in these brain regions, but when given prior to tectal stimulation (by up to 10 ms), tectally-evoked spinal cord responses were reduced in amplitude by as much as 85%. After cerebellar ablation, there was no difference from controls in the latency, form or amplitude of any response, even when tested with paired pulse stimulation. However, when the cerebellum was ablated, rhombencephalic and spinal responses to optic nerve and tectal stimulation were markedly enhanced (by 200–300%). These clear-cut complimentary consequences of cerebellar ablation or stimulation emphasize the gain-setting role of the cerebellum and indicate, at least in relation to optically evoked motor activity, that cerebellar regulation acts at the level of the supraspinal drive to spinal motor circuits and not within the sensory centers.
New Possibilities for Stereotaxis
Authors: Iseki Hiroshi , Muragaki Yoshihiro , Taira Takaomi , Kawamata Takakazu , Maruyama Takashi , Naemura Kiyoshi , Nambu Kyojiro , Sugiura Madoka , Hirai Nobuyuki , Hori Tomokatsu , Takakura Kintomo
Published: April 2003

Information-guided stereotaxis, assisted by visualization of medical information, will become the next generation of neurosurgical systems. We performed 76 open MRI surgeries at Tokyo Women’s Medical University between March 3, 2000 and April 12, 2001. Of them, comparisons of pre- and post-operative MR images for malignant gliomas in 21 cases revealed an average resection rate of 90.3% (the maximum 100%, the minimum 55%). In this article we describe real time updated navigation, augmented reality navigation, three-dimensional navigation, chemical navigation, information-guided navigation system (High definition visual Computer Aided Surgery System: HivisCAS), and open MRI-guided surgery that we are developing.
Stereotactic Neuroendoscopic Management of Hydrocephalus: A Three-Year Follow-Up and Analysis of Malaysian Children with Aqueduct Stenosis
Authors: Abdullah J. , Ariff A.R. , Ghazaime G. , Naing N.N.
Published: April 2003

The beneficial effects of stereotactic third ventriculostomy versus ventriculoperitoneal shunt were evaluated in 62 paediatric patients and analysed in relation to age, sex, clinical history, presence of meningomyelocele, magnetic resonance imaging measurements of hydrocephalus and third ventricle floor size. The third ventriculostomy were done on 50 patients using the Richard-Wolf® Caemaert Endoscope and the Leksell Stereotactic Frame Model G. These patients were operated using the 4-French Fogarthy catheter to open the base of the third ventricle. During the same period of study 12 paediatric patients with aqueduct stenosis who were managed by ventriculoperitoneal shunt were included. Both surgical procedures were compared. Statistically univariate analysis revealed that those patient with an age group of more than six months undergoing ventriculostomy had good outcome. Multivariate analysis revealed that past history of haemorrhage and/or meningitis were predictors of poor outcome. Sex, size of lumbar meningocele at birth, abnormal ventricular anatomy or narrow third ventricular floor size were non predictors of bad outcome in these patients. There was no difference in outcome in both the shunt or ventriculostomy group.
Radiosurgery for Vestibular Schwannomas: Preliminary Results of the Adelaide Experience
Authors: Lee G.Y.F. , Roos D.E. , Brophy B.P.
Published: April 2003

We present the preliminary results of our experience with Linear Accelerator (LINAC) radiosurgery for unilateral vestibular schwannomas. The treatment outcomes of 42 patients with a minimum follow-up of 12 months are reported. An excellent rate of tumour control was achieved with a relatively low complication rate. The current results compare favourably with other reported studies in the literature.