bluuebunny/crossref_metadata_2025 huggingface dataset:
Salivary Gland Choristoma of the Middle Ear
Authors: Rinaldo Alessandra , Ferlito Alfio , Devaney Kenneth O.
Published: August 2004

While head and neck surgeons are accustomed to recognizing malignancies in their practices, developmental lesions are much less often encountered, and as such are not as likely to be included amongst other (more aggressive) differential diagnostic considerations. One such developmental lesion is the choristoma, defined as an architecturally normal arrangement of mature tissues found in a location not normally host to such tissues. Choristomas composed of recognizable salivary gland tissue may be found in a variety of locations including the middle ear. Middle ear salivary choristomas are distinctly unusual lesions and typically manifest as unilateral conductive hearing loss; while both adult and pediatric patients have been diagnosed with middle ear choristomas, most patients have been in the first two decades of life. As these are benign, nonprogressive lesions, treatment has been directed toward complete surgical excision whenever feasible, and biopsy for diagnosis with subsequent observation in the case of those lesions which are difficult to remove without endangering the facial nerve. There have been rare instances in which choristomas have been linked to the subsequent development of neoplasms, but in the main choristomas are regarded as self-limited developmental heterotopias.
Management of Chyle Fistula Utilizing Thoracoscopic Ligation of the Thoracic Duct
Authors: Gunnlaugsson Chad B. , Iannettoni Mark D. , Yu Bo , Chepeha Douglas B. , Teknos Theodoros N.
Published: August 2004

Objectives: To document the treatment of refractory chyle leaks using thoracoscopic thoracic duct ligation and provide systematic guidelines to manage chyle leaks. Methods: The medical records of 2 patients with chyle leaks are reviewed, followed by a review of the literature on chyle leaks and their thoracoscopic management. Conclusions: Initial treatment of chyle fistula is aimed at conservative medical management. Persistent high-output fistulas (>500 cm3) should be considered for neck reexploration as conservative management is likely to fail. Thoracoscopic thoracic duct ligation provides a safe and efficient means of treating chyle leaks refractory to repeated surgical and medical intervention. It should also be considered as a primary surgical intervention for patients with: (1) chyle output exceeding 500 cm3/day where prior intraoperative attempts at ligation have failed, (2) severe metabolic and nutritional complications, (3) coexisting chylothorax with respiratory compromise, and (4) low-output fistulas (<500 cm3/day) of long duration (>14 days).
The Reactions of General Practitioners, Nurses and Midwives in Flanders Concerning Breast Cancer Risks in a High-Risk Situation
Authors: Welkenhuysen Myriam , Evers-Kiebooms Gerry
Published: August 2004

Objective: To investigate the reactions of general practitioners (GPs), nurses and midwives concerning the cancer risks in a high-risk family. Methods: Questionnaires were sent to 356 GPs, 881 nurses and 119 midwives. Results: The response rate was 60% for GPs, 58% for midwives and 33% for nurses. The breast cancer risk of an unaffected patient from a high-risk family as well as the risk of her daughter were mostly (>80%) correctly evaluated as increased. The percentage answering ‘increased risk’ dropped to 40% for the daughters of the patient’s brother. Half of the GPs and nurses/midwives explicitly mentioned that a predictive DNA test was available. Less than one third would recommend such a test for a young child. Reluctance was also observed regarding prophylactic mastectomy. Conclusion: These results should be taken into account in genetic education initiatives for GPs, nurses and midwives.
Do Women Understand the Odds? Risk Perceptions and Recall of Risk Information in Women with a Family History of Breast Cancer
Authors: Hopwood Penelope , Howell Anthony , Lalloo Fiona , Evans Gareth
Published: August 2004

Objectives: To describe and compare women’s risk perceptions and recall of breast cancer risk information in a cohort of first-time attendees at a family history clinic. Methods: We conducted a 1-year prospective study of 158 women aged 18–45 years with a confirmed lifetime risk of breast cancer of 1 in 6 or greater. Risk perception and recall were assessed using a self-report questionnaire, completed pre-counselling and 3, 6, 9 and 12 months post-counselling, and through interviews conducted at 3 and 12 months. Results: The proportion of women with accurate personal risk perceptions based on ‘gambling’ odds (‘1 chance in x’) significantly improved after risk counselling from 12% pre-counselling to 67% 3 months post-counselling (p < 0.001), which was maintained for 1 year. This was the method of reporting perceived risk associated with the best level of risk accuracy and the women’s preferred format for describing risk, but the concept of lifetime risk was understood by only 44% of women. Qualitative risk categories (‘high’, moderate’ or ‘low’) correlated significantly with women’s self-reported odds values, but each category comprised a wide range of women’s perceived numeric risks. Describing risk as the ‘likelihood of breast cancer’ resulted in a broad and somewhat inaccurate reporting of risk, compared with numeric ratings made at the same time. There was an increase of up to 4-fold in the proportion of women who failed to recall their risk value over time, and women were unable to accurately put the breast cancer risk in context compared with other health threats. Conclusions: All methods of describing risk have limitations, but the results of the present study provide good support for women’s accurate recall of numeric risk values and their preference for use of these ‘gambling’ odds. This may have been influenced by consistency of the use of this method both in risk communication and in personal summary letters. Descriptive risk formats reflected higher levels of perceived vulnerability to breast cancer, and genetic counsellors need to be aware of these different perceptions.
Information-Seeking Behaviour and Psycho-Social Interactions during the Genetic Testing Process
Authors: Cypowyj C. , Eisinger F. , Morin M. , Mogoutov A. , Sobol H. , Julian-Reynier C.
Published: August 2004

Objectives: The first aim of this study was to investigate the information-seeking behaviour (ISB) of women attending cancer genetic consultations at which the possibility of BRCA testing is considered. We focused here specifically on ISB apart from the cancer genetic consultation, i.e. on what complementary sources of information about genetic testing were consulted and what factors were involved in this behaviour. The second aim was to study the role of the social network used by the patients to collect various opinions on which to base their decisions about being tested. Methods: A prospective cohort study (2000–2002) was therefore carried out on all women attending a single cancer genetic clinic in France after a BRCA1/2 analysis had been proposed. Closed questionnaires were administered before and after the second cancer genetic consultation. The purpose of this consultation was to confirm the patient’s decision to be tested. Results: Results were analysed in 108 subjects (mean age 47 years, SD 11 years; 74% affected by breast/ovarian cancer). Prior to the 2nd consultation, 35.2% of the women had actively looked for information about BRCA1/2 testing, as compared to 25.0% afterwards. After multivariate adjustment by logistic regression, the pre-consultation ISB was found to be associated with greater satisfaction with the information about the psycho-social consequences of genetic testing [adjusted odds ratio (ORadj) 1.03, 95% confidence interval (CI) 1.01–1.06] (scale from 0 to 100) and about the certainty of being a gene carrier (ORadj 3.04, 95% CI 1.16–7.98). Those who actively looked for complementary information were also more often accompanied at the consultation by a family member (ORadj 4.82, 95% CI 1.85–12.56). The other variables tested (depression, coping, socio-demographic and medical characteristics) were not significant (p > 0.05). The role of the social network in the decision making process was perceived as being less helpful when the persons consulted tended to have neutral or unfavourable opinions about genetic testing. Conclusions: Few women actively sought complementary information about BRCA genetic testing in addition to the cancer genetic consultation. Those who did so differed from the others in terms of their social network and their satisfaction with the consultation. The cancer geneticist is the key actor in women’s decision making about genetic testing.
Psychological Distress and Breast Self-Examination Frequency in Women at Increased Risk for Hereditary or Familial Breast Cancer
Authors: van Dooren S. , Rijnsburger A.J. , Seynaeve C. , Kriege A. , Duivenvoorden H.J. , Bartels C.C.M. , Essink-Bot M.L. , de Koning H.J. , Tibben A.
Published: August 2004

Background: The Magnetic Resonance Imaging Screening study evaluates the efficacy and psychological impact of a surveillance program for women at increased risk for hereditary or familial breast cancer in the Netherlands. Surveillance consists of biannual physical examination, annual mammography, annual MRI and monthly breast self-examination (BSE). Objective: To examine the association between psychological distress and reported BSE frequency. Methods: Two months prior to surveillance demographics, BSE frequency, general distress (Hospital Anxiety and Depression Scale and the somatic scale of the Symptom Checklist-90) and breast cancer-specific distress (Impact of Event Scale) were assessed in 316 women (mean age 40.5 years, range 21–63 years). Results: The majority (57%) reported performing monthly BSE. Ten percent reported never performing BSE, 20% less frequently than once a month and 13% at least once a week. Women below the age of 40 who examined their breasts more frequently than recommended (i.e. at least once a week) were shown to be significantly more distressed than the other women in the sample (p = 0.03). These women represented 15% of all the women below the age of 40 years in our study sample. Conclusion: Higher breast cancer-specific distress scores were observed among younger women who examined their breasts at least once a week. It is important for physicians to be aware of this hypervigilant behaviour, especially since it is correlated with breast cancer-specific distress.
Women’s Experiences of Undergoing BRCA1 and BRCA2 Testing: Organisation of the German Hereditary Breast and Ovarian Cancer Consortium Survey and Preliminary Data from Münster
Authors: Nippert Irmgard , Schlegelberger Brigitte
Published: August 2004

Background: In order to promote safe and effective testing for BRCA1 and BRCA2 mutations in clinical practice, a network of expert centres in hereditary breast and ovarian cancer (‘Verbundprojekt familiärer Brust- und Eierstockkrebs’; German Consortium on Hereditary Breast and Ovarian Cancer) has been established by the Deutsche Krebshilfe (German Cancer Aid). To improve practice, evaluations based upon the views of patients who have undergone testing concerning the impact of the genetic diagnosis and the quality of the services they receive and require are undertaken. Methods: Herein, we first describe the protocols for interdisciplinary pre- and post-test counselling and for molecular diagnostics, then the feedback from the patients undergoing testing. Women and men who had obtained their test results at least 6 months earlier were interviewed using a questionnaire including open and standardised questions at 11 participating centres in 2002–2003. Reported here are the survey protocol and preliminary data from interviews with women conducted by the centre based at the University of Münster’s Medical School in 2002 (n = 46). Results: Compared to international guidelines, the Consortium’s protocols provide more specifically outlined indications based on the mutation frequencies observed in the German population for families that should be offered interdisciplinary counselling and genetic testing. The data from the Münster survey suggest that there is little regret regarding the decision to undergo testing and that the vast majority of women would undergo the test again. However, women with positive findings experienced more problems than women with negative results. They were less prone to recommend the test and to communicate the tests results in their family compared to women with negative test results. Communication of test results within the family was characterised by preferential information of female family members. Conclusion: BRCA1/2 testing should be provided within a framework that ensures harmonisation and standardisation of services and that protects users. Women and men with positive test results may need special support from counsellors on how to handle test results in their families. Strategies need to be developed and evaluated on how to help stimulate and facilitate the dissemination of information within families without potentially ‘overstraining’ the ‘messenger patient’, at least when a mutation has been identified.
Effects of Sexual Arousal on Lymphocyte Subset Circulation and Cytokine Production in Man
Authors: Haake Philip , Krueger Tillmann H.C. , Goebel Marion U. , Heberling Katharina M. , Hartmann Uwe , Schedlowski Manfred
Published: August 2004

Objective: Sexual arousal and orgasm induce an increase in sympathetic activity as well as in catecholamine and prolactin plasma concentrations. However, the effects of sexual arousal and orgasm on immune functions in man are unknown. Thus, this study investigated the effects of masturbation-induced orgasm on lymphocyte circulation and cytokine production in healthy young males. Methods: In a crossover design, 11 volunteers completed an experimental condition in which they were asked to masturbate until orgasm and to participate in a control condition without sexual activity. Blood was drawn continuously for determination of endocrine parameters. In addition, leukocyte and lymphocyte subsets were analyzed via flow cytometry, and the production of lipopolysaccharide-induced interleukin 6 and tumor necrosis factor alpha was measured before and then 5 and 45 min after the orgasm. Results: The results confirmed transient increases in adrenaline and prolactin plasma concentrations. Sexual arousal and orgasm increased the absolute number of leukocytes, in particular natural killer cells (CD3–CD16+CD56+), in the peripheral blood. In contrast, T cell (CD3+) and B cell (CD3–CD20+) subpopulations as well as the production of interleukin 6 and tumor necrosins factor alpha remained unaffected by sexual activity. Conclusion: These findings demonstrate that components of the innate immune system are activated by sexual arousal and orgasm.
5-HT1A and β-Adrenergic Receptors Regulate Proliferation of Rat Blood Lymphocytes
Authors: Sempere Telésfora , Urbina Mary , Lima Lucimey
Published: August 2004

Lymphocytes possess serotonin 5-HT1A and β-adrenergic receptors, which have been related to cell proliferation. In the present report, lymphocytes of rat blood were isolated by Ficoll-Hypaque gradients and differential adhesion to plastic. They were cultured in RPMI medium for 72 h in the presence of the mitogens lipopolysaccharide concanavalin A and anti-CD3 antibody. The latter two stimulated the proliferation of lymphocytes, but not the first. Serotonin (0.1–100 µM) was added alone or in the presence of suboptimal concentrations of concanavalin A (2 µg/ml) or anti-CD3 antibody (0.4 µg/ml). The 5-HT1A receptor agonists, 8-hydroxy-2-(di-n-propylamino)tetralin and buspirone (0.1–100 µM) were also tested in the cultures. Serotonin, 8-hydroxy-2-(di-n-propylamino)tetralin and buspirone neither had any effect by themselves, nor modified the proliferation induced by the mitogens. Noradrenaline (25–1,000 µM) and the β-adrenergic receptor agonist, isoproterenol (5–100 µM), produced a reduction of the activation induced by concanavalin A or anti-CD3 antibody in a dose-dependent manner. Increasing serotonin concentrations reduced the inhibitory effect of noradrenaline (300 µM). Variable concentrations of 8-hydroxy-2-(di-n-propylamino)tetralin or buspirone also reduced the inhibition produced by isoproterenol (100 µM). The antagonist of 5-HT1A receptors, WAY-100,478 (0.1–100 µM), inhibited concanavalin A- or anti-CD3 antibody-induced proliferation. Serotonin (0.1–100 µM) impaired the inhibitory effect of the 5-HT1A antagonist (10 µM). The inhibitor of tryptophan hydroxylase, p-chlorophenylalanine (50–1,000 µM), decreased the stimulatory effect of concanavalin A, serotonin (0.5–100 µM) and 8-hydroxy-2-(di-n-propylamino)tetralin (1–100 µM) reverted the effect of p-chlorophenylalanine (1,000 µM). The serotonin reuptake blockers zimelidine, imipramine and clomipramine decreased concanavalin A-induced proliferation. The concentrations of serotonin and noradrenaline increased in lymphocytes cultured in the presence of concanavalin A, probably as a mechanism for modifying the final effect on proliferation. The present results indicate that 5-HT1A receptors play a stimulatory role on rat blood lymphocytes, and they interact in a parallel and opposite manner with β-adrenergic receptors. Furthermore, endogenous serotonin is relevant in displaying its stimulatory effect.
Evidence for Daily Rhythms of the Expression of Proopiomelanocortin, Interleukin-1-Beta and Interleukin-6 in Adenopituitaries of Male Long-Evans Rats: Effect of Adjuvant Arthritis
Authors: Šereš Janette , Herichová Iveta , Roman Olha , Bornstein Stefan , Jurčovičová Jana
Published: August 2004

Objective: Several interleukins (ILs) including IL-1β and IL-6 are produced in the anterior pituitary (AP) where they probably participate in the local regulation of hormone production. Immune challenge brings about the dysregulation of immune-endocrine interaction and enhanced the expression of pituitary IL-1β and IL-6. Little is known about regulation of their production, and therefore the purpose of the present work was to describe the relationship between circulating corticosterone and the mRNA expression of proopiomelanocortin (POMC), IL-1β and IL-6 in the AP during a 24-hour cycle in normal rats and rats with acute adjuvant arthritis (AA). Methods: Groups of intact male Long-Evans rats and rats 23 days after induction of AA kept on a 12-hour light/dark cycle (light on at 6:00 a.m.) were killed at 4-hour intervals starting at 2:00 p.m. Trunk blood was used for corticosterone determination by radioimmunoassay. Adenopituitaries were extracted for total RNA and the message of interest was quantitated by real-time PCR using specific primers and TaqMan probes. Parameters of rhythms were evaluated by cosinor analysis. Results: In normal rats, serum corticosterone showed a circadian rhythm with the peak at 6:00 p.m. and the nadir in the morning hours (p < 0.001). POMC mRNA in AP also showed a circadian rhythm (p < 0.05) which was inversely related to corticosterone levels. IL-1β and IL-6 expression in normal rats showed clear-cut daily rhythms (p < 0.001) with the nadirs in the dark period, in contrast to the corticosterone peak in plasma. In arthritic rats, rhythmic corticosterone secretion was suppressed with a plateau pattern of the rhythm. The mean POMC expression was higher than in controls, and the rhythm failed to be significant. IL-1β expression was suppressed by AA (p < 0.001) but the rhythm was still present (p < 0.05). The rhythmic pattern of IL-6 expression was similar to that of controls, but with higher mesor values (p < 0.05). Conclusion: These results suggest a regulatory relationship between circulating corticosterone and the expression of POMC, IL-1β and IL-6 in AP of normal rats. Arthritis induced a higher expression of POMC and IL-6 in the AP and a suppression of IL-1β mRNA during the 24-hour cycle which suggests the involvement of different regulatory mechanisms compared to normal conditions.
Influence of Chronic Interleukin-2 Infusion and Stressors on Sickness Behaviors and Neurochemical Change in Mice
Authors: Sudom Kerry , Turrin Nicolas P. , Hayley Shawn , Anisman Hymie
Published: August 2004

Objectives: Major depression is associated with increased circulating interleukin-2 (IL-2) levels, and IL-2 immunotherapy may provoke depressive symptoms, leading to the suggestion that this cytokine may contribute to the evolution of affective disorders. Although depression is a relatively chronic condition, and immunotherapy involves repeated cytokine administration, animal studies have typically assessed the consequences of acute cytokine treatment. The present investigation assessed several behavioral and neurochemical effects of chronic IL-2 infusion. Methods: Behaviors reflecting anhedonia and/or anorexia, sickness behavior, plasma corticosterone and norepinephrine (NE) activity in the paraventricular nucleus (PVN) of the hypothalamus were assessed following continuous infusion of IL-2 over 7 days in CD-1 mice. Results: The cytokine treatment reduced the consumption of a highly favored palatable substance (chocolate milk) and reduced locomotor activity monitored over the course of the 7-day period. Although sickness behaviors were also increased significantly by the treatment, the degree of sickness behavior was actually modest. While a chronic, variable stressor also affected consumption of the palatable food, this treatment did not enhance the effects of IL-2. Furthermore, in contrast to acute and chronic stressors that increased plasma corticosterone levels and the utilization of NE within the PVN of the hypothalamus, IL-2 did not promote such effects and did not modify the impact of the stressors. Conclusion: While IL-2 may induce anorexia or anhedonia, the effects of this treatment are distinguishable from those elicited by stressors and those typically elicited by proinflammatory cytokines. The data are related to findings suggesting a link between IL-2 and depressive illness.
Phase 2 Trial of Interferon-Beta as Second-Line Treatment of Ovarian Cancer, Fallopian Tube Cancer, or Primary Carcinoma of the Peritoneum
Authors: Markman Maurie , Belinson Jerome , Webster Kenneth , Zanotti Kristine , Morrison Bei , Jacobs Barbara , Borden Ernest , Lindner Daniel
Published: August 2004

Objective: The protocol was designed to examine the biological effects and clinical activity of interferon-β in patients with platinum/taxane-resistant ovarian cancer. Methods: Patients with resistant ovarian and fallopian tube cancers and primary peritoneal carcinoma were treated with recombinant human interferon-β (Rebif®, Serono International) at doses ranging from 6 to 24 million international units (MIU)/day, based on their tolerance to therapy. Levels of IP-10, an interferon-inducible protein, were measured in the serum to evaluate the biological effects of the drug. Also, the peripheral blood mononuclear cells and serum were examined for the induction of previously described novel regulators of interferon-induced death. Results: Eighteen patients were treated, of whom 9 (50%) could be treated at the highest dose level (24 MIU). The major toxicities were fever, chills and fatigue. The median duration of therapy was 6 weeks (range 1–22). No objective responses were observed. IP-10 levels were significantly increased, compared with baseline, at 2, 4, and 6 weeks after initiation of therapy (p < 0.01). Conclusions: Recombinant human interferon-β produced a definite biological effect in the serum of treated patients, but this outcome was not translated into any clinically observable or meaningful impact on the disease process.
Phase II Study of Weekly Paclitaxel in Patients with Non-Small Cell Lung Cancer Who Have Failed Previous Treatments
Authors: Yasuda Kazuhito , Igishi Tadashi , Kawasaki Yuji , Kato Kazuhiro , Matsumoto Shingo , Katayama Satoru , Sako Takanori , Shigeoka Yasushi , Suyama Hisashi , Sugitani Akinori , Yamamoto Mistunobu , Hitsuda Yutaka , Shimizu Eiji
Published: August 2004

Objective: New effective therapy is desirable for patients with non-small cell lung cancer (NSCLC) who have failed previous treatments. Fractionated administration of paclitaxel may be less toxic and more active against NSCLC. The aim of this study was to evaluate the activity and toxicity of weekly paclitaxel therapy for NSCLC in a second-line setting. Methods: Patients with pathological or cytological diagnosis of NSCLC, measurable lesions, and one or more prior therapies were enrolled. We administered weekly infusions of 80 mg/m2 paclitaxel 3 times in a 4-week cycle. In the absence of progressive disease or intolerable toxicity, each patient was treated for a minimum of 4 cycles. Results: Of 39 patients enrolled, 1 patient achieved complete response and 11 patients achieved partial response (response rate, 31%: 95% confidence interval, 17–48%). The median survival time was 43 weeks (range, 7–128 weeks). Grade 3 or 4 leukopenia occurred in only 7 patients (18%). Neurotoxicity was the most frequent adverse effect (grades 1 and 2.26 and 5%, respectively). Although all patients recovered rapidly with corticosteroid treatment, drug-induced pneumonitis was observed in 3 patients (8%). Conclusion: Low-dose weekly paclitaxel is a promising therapy with high effectiveness for advanced NSCLC in patients with NSCLC who have failed previous treatments.
Safety and Efficacy of S-1, a Novel Oral Fluorouracil Antitumor Drug, for a Chronic Renal Failure Patient Maintained on Hemodialysis
Authors: Tominaga Kazunari , Higuchi Kazuhide , Okazaki Hirotoshi , Suto Reiko , Hamaguchi Masaki , Tanigawa Tetsuya , Sasaki Eiji , Shiba Masatsugu , Watanabe Toshio , Fujiwara Yasuhiro , Oshitani Nobuhide , Matsumoto Takayuki , Arakawa Tetsuo
Published: August 2004

Objective: S-1 is a novel oral fluorouracil antitumor drug that combines three pharmacological agents: tegafur (FT), a prodrug of 5-fluorouracil (5-FU); 5-chloro-2,4-dihydroxypyridine (CDHP), an inhibitor of dihydropyrimidine dehydrogenase, and potassium oxonate (Oxo), a reducer of gastrointestinal toxicity. S-1 has safe and potent antitumor effects in patients with gastric cancer via these respective functions. However, the plasma 5-FU concentration is suspected to accumulate in patients with renal dysfunction, because 50% of the CDHP is excreted into the urine. There are no useful data on safety and efficacy of S-1 in chronic renal failure patients maintained on hemodialysis (HD). We examined the influence of HD on the pharmacokinetics (PK) of S-1 and its therapeutic efficacy in liver metastases from gastric cancer. Methods: For the HD patient, the dose of S-1 in a single-administration study was set at 50 mg/body/day (41.7% of the recommended dose of 80 mg/m2/day). S-1 was given to the patient 24 h after HD. Blood samples were obtained before administration and 2, 4, 6, 8, and 24 h thereafter and 1, 2, 4, and 72 h after the following HD session. The PK parameters (5-FU, CDHP, Oxo, and FT) were measured, and Cmax, Tmax, AUC0–24, and T1/2 were calculated. The dose of consecutive or maintained administrations was determined. Results: Both an increase in Cmax and an elongation of T1/2 for 5-FU, CDHP, and Oxo, but not for FT, occurred in this case as compared with controls. The AUC0–24 of 5-FU in this case was similar to that of controls at the standard dose. After HD, 87.8, 54.5, 77.4, and 66.2% of 5-FU, CDHP, Oxo, and FT, respectively, were eliminated. A slight accumulation of CDHP did not alter the 5-FU PK. Consecutive or maintained S-1 oral administration at the same dose showed similar effects on all PK parameters of a single-administration test. Liver metastases almost totally regressed with no adverse events 4 weeks after S-1 treatment (50 mg/body/day three times a week). Conclusion: Adjusted doses of S-1 according to the results of PK studies may provide therapeutic safety and high efficacy in liver metastases from gastric cancer, even in chronic renal failure patients maintained on HD.
Analysis of the Oligosaccharide Chain of Human Serum Immunoglobulin G in Patients with Localized or Metastatic Cancer
Authors: Kanoh Yuhsaku , Mashiko Takaomi , Danbara Mikio , Takayama Yoshinaga , Ohtani Shinichi , Imasaki Takao , Abe Tadashi , Akahoshi Tohru
Published: August 2004

A quantitative imbalance between matrix metalloproteinases produced by cancer cells and tissue inhibitors of metalloproteinases produced by fibroblasts and other types of cells has been demonstrated to be a causative factor in invasion and metastasis of cancer cells. On the other hand, it is reported that sugar chains of adhesion molecules such as integrins and CD44 also influence the metastasis of cancer cells. Here, alterations of serum IgG oligosaccharide chain structure were investigated during tumor progression using the new method of fluorophore-assisted carbohydrate electrophoresis (FACE). The structure of serum IgG oligosaccharide chains from 22 cancer patients (11 localized cancer, 11 metastatic cancer) and 10 healthy controls was evaluated by FACE. It was clearly demonstrated that serum IgG oligosaccharide chains without galactose (agalactosyl IgG oligosaccharide) significantly increased with tumor progression of lung and gastric cancers. It is concluded that a marked increase of agalactosyl IgG oligosaccharide in these cancer patients is associated with carcinogenesis and metastasis. Therefore, the analysis of serum IgG oligosaccharide chain structure by FACE may be useful for evaluating diagnosis and prognosis in patients with these carcinomas.
Mucin Phenotype and Background Mucosa of Intramucosal Differentiated-Type Adenocarcinoma of the Stomach
Authors: Sasaki Atsunori , Kitadai Yasuhiko , Ito Masanori , Tanaka Shinji , Yoshihara Masaharu , Haruma Ken , Chayama Kazuaki
Published: August 2004

Objectives: Gastric carcinomas have been divided into differentiated (intestinal) and undifferentiated (diffuse) types. Recently, classification studies based on mucin expression have revealed that some differentiated-type carcinomas are of a gastric phenotype. In this study, we investigated the clinicopathological features of differentiated-type adenocarcinomas and evaluated the background mucosa of the stomach based on mucin expression by the tumors. Methods: Seventy-six intramucosal differentiated-type adenocarcinomas of the stomach were evaluated macroscopically and histologically. The mucin expression of tumor cells was examined by immunohistochemical staining with monoclonal antibodies against human gastric mucin (45M1), class III mucin (HIK1083), small intestinal mucinous antigen (SIMA-4D3), and MUC2 (Ccp58). Tumors were classified by phenotype as gastric (G-type), intestinal (I-type), mixed (M-type), or null (N-type). Not only the clinicopathological features but also the background mucosa of the stomach of G-type and I-type carcinomas were compared histologically and serologically. Results: Seventeen tumors (22.4%) were classified as G-type, 31 (40.8%) as I-type, 22 (28.9%) as M-type, and 6 (7.9%) as N-type. The frequencies of elevated type tumors and papillary adenocarcinomas and the ratio of moderately/well-differentiated adenocarcinomas were higher in G-type than in I-type carcinomas. The scores for glandular atrophy and intestinal metaplasia were higher and the scores for chronic inflammation, polymorphonuclear neutrophil activity, and the density of Helicobacter pylori were lower in G-type than in I-type tumors. The serum level of pepsinogen I and the pepsinogen I/II ratio were significantly lower in G-type than in I-type tumors. Conclusions: G-type carcinoma is the predominant phenotype of papillary adenocarcinoma. The background mucosa of G-type carcinoma is associated with glandular atrophy and intestinal metaplasia, whereas that of I-type carcinoma is associated with active and chronic inflammation induced by H. pylori infection.
Serial Topoisomerase II Expression in Primary Breast Cancer and Response to Neoadjuvant Anthracycline-Based Chemotherapy
Authors: Martin-Richard M. , Muñoz M. , Albanell J. , Colomo L. , Bellet M. , Rey M.J. , Tabernero J. , Alonso C. , Cardesa A. , Gascón P. , Fernández P.L.
Published: August 2004

Objective: We analyzed the value of topoisomerase IIα (Topo II) in predicting the clinical response to anthracycline-based neoadjuvant chemotherapy in breast cancers and the potential changes in Topo II after chemotherapy. In parallel, HER2, which is commonly coexpressed with Topo II, and p53, a modulator of chemotherapy activity, were also analyzed. Methods: Forty-one patients with primary breast cancer and treated with neoadjuvant anthracycline-based chemotherapy (FAC or FEC) were included for the present study. Topo II, HER2 and p53 expression were measured by immunohistochemistry in pre and post chemotherapy (at the time of surgery), tumor specimens and the results were correlated with the clinical response. Results: Topo II was overexpressed in 16 of 41 (31%) tumors before treatment, and this overexpression was significantly associated with clinical response (p = 0.03). HER2 and p53 were unrelated to response. Notably, Topo II overexpression, but not HER2 or p53, was lost in specimens after chemotherapy (p = 0.01). Conclusion: The observed link between Topo II and the clinical response to neoadjuvant anthracycline-based chemotherapy, together with its loss after chemotherapy, implies that Topo II deserves further testing in a prospective setting as a predictive marker.
Molecular Mechanisms Associated with Chromosomal and Microsatellite Instability in Sporadic Glioblastoma multiforme
Authors: Martinez Ramon , Schackert Hans-K. , Plaschke Jens , Baretton Gustavo , Appelt Hella , Schackert Gabriele
Published: August 2004

Objective: Two chromosomal instability (CIN) pathways are described in glioblastoma multiforme (GBM), type 1 and type 2, which can be observed in up to 70% of the cases. Microsatellite instability (MSI) plays a pathogenic role in sporadic cancers such as colon, gastric and endometrial carcinomas with deficient mismatch repair (MMR). We aimed to perform a comprehensive analysis of the relationship between CIN and MSI mechanisms in sporadic glioblastomas. Methods: 129 GBMs were examined (109 newly diagnosed and 20 relapses) investigating MSI, immunohistochemical expression of MMR proteins as well as sequencing and promoter methylation of hMLH1. We characterized the molecular changes frequently correlated with CIN in MSI+ GBMs and compared them with 26 microsatellite-stable tumors. Results: Low-level MSI was observed in 11 of 129 (8.5%) cases and was higher in relapses than in primary GBMs (25 vs. 5.5%, p = 0.027). High-level MSI was not found in any case. A deficient expression of MLH1 and PMS2 without hMLH1 inactivation was observed only in one giant cell GBM. 55% of the MSI+ GBMs showed a profile which did not correspond to one of the known CIN pathways. An inverse association was observed between MSI and mutations of both p53 and PTEN. Conclusions: Our data suggest that CIN and MSI contribute to the genomic instability in GBMs via independent pathways. Since MSI was significantly more frequent in relapses, it might play a role in the malignant progression of GBM.
GLUT1 mRNA and Protein Expression in Ovarian Borderline Tumors and Cancer
Authors: Rudlowski Christian , Moser Markus , Becker Albert J. , Rath Werner , Buttner Reinhard , Schroder Willibald , Schurmann Annette
Published: August 2004

Objectives: Increased glucose uptake and utilization is a major feature of malignant tumors. Recent studies suggest that the key mechanism of enhanced glucose metabolism in carcinoma cells involves the overexpression of transmembrane glucose transporter proteins (GLUTs). The aim of the present study was to analyze the expression of different GLUT isoforms (GLUT1–4) and to investigate whether alterations in their expression pattern accompany the malignant transformation and progression of ovarian cancer. Methods: Tumor tissue of 94 patients suffering from primary ovarian cancer (n = 78) or borderline tumors (n = 16) and tissue from 16 patients with benign ovarian changes were examined in this study. Immunohistochemistry was performed using polyclonal GLUT1–4 antibodies. GLUT1 protein expression was quantified by Western blot analysis. GLUT1 mRNA expression was analyzed by mRNA in situ hybridization. Results: All of the invasive carcinomas were positive for GLUT1. In contrast, GLUT1 expression was moderate in borderline tumors and weak to negative in all benign ovarian neoplasms. High GLUT1 mRNA levels were observed only in ovarian cancer. The intensity of GLUT1 expression in malignant ovarian neoplasms was associated neither with tumor characteristics nor with patient survival. Only GLUT3 revealed weak but homogeneous expression in human ovarian cancer as well as in benign ovarian tumors. GLUT2 and GLUT4 showed no expression in ovarian tissue. Conclusions: GLUT1 mRNA and protein were found to be expressed specifically in primary ovarian cancer. The close relationship between GLUT1 mRNA and protein expression points towards the potential relevance of GLUT1 as a diagnostic tool and therapeutic target in ovarian cancer.
New Approaches to Medical Education: An International Perspective
Authors: Sefton Ann Jervie
Published: August 2004

Internationally, medical education has increasingly been the subject of scrutiny and debate. This article represents a review of the burgeoning literature on medical education. The focus is on encouraging teachers to improve the quality of students’ learning. The educational rationale for some of the major current developments is considered. Change imposes significant challenges for teachers and students, although there are helpful examples from the literature. The curriculum must be internally consistent, based on well-defined educational principles and effectively managed. Goals or outcomes – broadly defined – must be debated and determined so that they are clear to staff, students and the community. Several interrelated issues must be considered and resolved – student selection, specification of content, identification of core clinical skills and broader academic and professional behaviours. The most effective educational processes must be determined in order to support active learning. Problem-based learning is now well established and its underlying principles are discussed. Assessment of students must encourage learning and ensure that well-defined academic and professional skills are achieved. Programmes must be subject to evaluation so that the quality of the experiences of students, staff and patients is progressively improved. In order to develop effective skills in teaching and in the management of programmes, teachers need to be supported by good staff development.
Psychiatric Morbidity among Housemaids in Kuwait
Authors: Zahid M.A. , Fido A.A. , Razik M.A. , Mohsen M.A.M. , El-Sayed A.A.
Published: August 2004

Objectives: To determine the first hospital admission rates and the nature of psychiatric disorders among housemaids and compare them with the Kuwaiti female patients. Subjects and Methods: Based on the International Classification of Diseases (10th revision; ICD-10) symptom checklist, a semi-structured interview was administered to all the housemaids and the Kuwaiti female patients hospitalized during the 2-year study period. Results: The hospital admission rates were 1.86 times higher in housemaids than in the Kuwaiti female patients and the nature of psychiatric disorders was also different in the two groups. The stress-related disorders were more common among housemaids while schizophrenia was the commonest disorder among Kuwaiti patients. Duration of hospital stay was significantly shorter for housemaids, and four fifths of them were repatriated on mental health grounds. Conclusions: The psychiatric morbidity is higher among housemaids than Kuwaiti females and a substantial number of them are prematurely repatriated on health grounds. Further studies are needed to explore the possible pre-immigration risk, and post-immigration precipitating factors, to prevent this ‘expatriate failure’.
Confirmation of Brain Death Using Brain Radionuclide Perfusion Imaging Technique
Authors: Al-Shammri S. , Al-Feeli M.
Published: August 2004

Objective: To determine the reliability of radionuclide cerebral blood perfusion imaging in confirming brain death irrespective of continued heartbeat. Subjects and Methods: Twenty-eight patients (19 male and 9 female, aged 17–63 years) with severe brain injury and fully supported until the final cardiac asystole were included in the study. Two sets of clinical tests aimed at ascertaining brain death in each subject were performed separately for each case within an interval of 24 h. Dynamic, planar and single photon emission computed tomographic (SPECT) brain scintigraphy were also performed after intravenous administration of 550 MBq (15 mCi) technetium-99m hexamethyl propyleneamine oxime. Results: Following the clinical diagnosis of brain death, none of the patients was withdrawn from cardiopulmonary support or had any organ harvested. Dynamic, planar and SPECT imaging performed thereafter did not reveal any intracranial cerebral perfusion in any of the subjects, except in 1 patient where the initial scan showed posterior fossa activity that ceased, in a subsequent scan obtained after 24 h. All of the patients were declared dead only after the emergence of cardiac asystole. Conclusion: The findings indicate that radionuclide brain perfusion imaging is reliable, reproducible, noninvasive and simple to perform for the confirmation of brain death and as such we recommend it as an alternative to exhaustive neurophysiological tests and invasive catheter angiography.
Tumor Necrosis Factor Alpha and Interleukin 6 Productions in Response to Platelet-Activating Factor in Chronic Hepatitis B Virus Infection
Authors: Buke A. Cagri , Buke Munir , Erdem Altuglu Imre , Ciceklioglu Meltem , Kamcioglu Saniye , Karakartal Guney , Huseyinov Afig
Published: August 2004

Objective: The aim of this study was to determine tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) release in response to platelet-activating factor (PAF) induction in peripheral blood mononuclear cells (PBMCs) from chronic hepatitis B virus (HBV) carriers. Methods: Subjects were grouped into three subgroups. The mean age was 37 ± 10 years. Group A (n = 15), group B (n = 10) and group C (n = 9) subjects were HBV serology-negative, had natural immunity after recovery from an acute HBV infection, and were chronic HBV carriers, respectively. Results: Compared with group A, PBMCs from naturally immune subjects and chronic HBV carriers produced significantly higher amounts of TNF-α and IL-6 in response to PAF. In chronic HBV carriers, TNF-α (1,633.3 ± 793.7) and IL-6 (2,533.3 ± 466.3) production was statistically lower than TNF-α (2,630.0 ± 727.3) and IL-6 (3,870.0 ± 728.4) obtained from naturally immune subjects to HBV. Conclusion: Differences of TNF-α levels between chronic HBV carriers and naturally immune subjects suggest that TNF-α may be a critical mediator of HBV clearance.
Physician-Related Barriers to Hypertension Management
Authors: Wang Lexin
Published: August 2004

Objective: To investigate the levels of understanding and implementation of current hypertension guidelines among specialist physicians. Subjects andMethods: A survey of the understanding and practice in the management of hypertension was conducted among 56 physicians who individually had managed more than 150 new hypertensive patients annually. Results: All respondents were familiar with the current hypertension guidelines and 51.8% always or usually followed these guidelines in treating their patients. Most believed that the lowest blood pressure where pharmacological therapy should be initiated was 155/95 mm Hg. Forty-five (80.4%) physicians considered a blood pressure of less than 140/ 90 mm Hg should be achieved in hypertensive patients. Only 12 (21.4%) respondents provided routine advice on lifestyle modification to their patients. Fifty-four (96.4%) respondents ranked poor adherence to antihypertensive drugs as the major patient barrier to blood pressure control. Conclusions: Most physicians are familiar with the current hypertension guidelines but the implementation of these guidelines in clinical practice is inadequate. Systematic educational programs are needed to enhance physicians’ awareness of the optimal goals of blood pressure control.
An Unusual Angiosarcoma
Authors: Al-Meshan M.K. , Katchy K.C.
Published: August 2004

Objective: To document a retroperitoneal angiosarcoma with a 12-year disease-free period. Clinical Presentation and Intervention: A 50-year-old farmer was referred to the Urology Clinic, Al-Sabah Hospital, Kuwait, with a 1-year history of recurrent left renal colic. Radiological investigations revealed 2 renal cysts at the lower pole and an extrarenal soft tissue mass, presumably of adrenal origin, at the upper pole. Laparotomy confirmed both the renal cysts and a circumscribed soft tissue mass. The latter was separate from the adrenal gland but had a vascular connection with an adrenal vessel. Pathological examination showed an encapsulated angiosarcoma. The patient did not have any adjuvant therapy after surgery but was followed up with annual radiological investigations for 12 years. No evidence of recurrence or metastasis was seen. Conclusion: The 12-year disease-free period in this case is exceptional for angiosarcomas, which is a high-grade sarcoma.
Gustav Schimmelpenning and the Syndrome Bearing His Name
Authors: Happle Rudolf
Published: August 2004

Gustav Schimmelpenning was born in 1928 in Oldenburg (Germany). From 1971 until 1994 he was head of the Department of Psychiatry at the University of Kiel. In 1957, while training in neurology and psychiatry, he comprehensively described a case of sebaceous nevus involving the head, with ipsilateral ocular lesions including coloboma of the upper lid, increased density of cranial bones, epileptic seizures and mental retardation. He concluded that this combination of anomalies represented a new ‘phacomatosis’. Subsequently this phenotype was reported by other authors under many different names, such as ‘Schimmelpenning syndrome’, ‘Feuerstein-Mims syndrome’, ‘Schimmelpenning-Feuerstein-Mims syndrome’, ‘epidermal nevus syndrome’, ‘Solomon syndrome’, ‘linear sebaceous nevus syndrome’, ‘organoid nevus phacomatosis’, or ‘Jadassohn nevus phacomatosis’. As a consequence of this confusing terminology, Schimmelpenning syndrome even has two different OMIM entries (no. 163200 and no. 165630). The term ‘Schimmelpenning syndrome’ is both historically justified and practically sufficient to distinguish this phenotype from other epidermal nevus syndromes.