bluuebunny/crossref_metadata_2025 huggingface dataset:
In vitro Effects of Leptin on Human Adipocyte Metabolism
Authors: Elimam A. , Kamel A. , Marcus C.
Published: April 2003

Objective: Leptin receptors are expressed in adipocytes, suggesting potential autocrine/paracrine effects. Studies on the direct effects of leptin on adipose tissue metabolism in different species have yielded controversial data. To assess the in vitro effects of leptin on human adipocyte metabolism: lipolysis, the insulin-induced inhibition of lipolysis and lipogenesis were studied in adipocytes obtained from infants and adults. Methods: Lipolysis was studied by incubating adipocytes with increasing concentrations of leptin or isoprenaline. Glycerol in the incubation medium was measured as an indicator of lipolysis. For the lipogenesis and insulin-induced inhibition of lipolysis experiments, the cells were preincubated with 0, 25, or 250 ng/ml of leptin for 2 h. Results: Leptin did not stimulate lipolysis in human adipocytes, either in children or adults. Preincubation with leptin did not affect the insulin-induced inhibition of lipolysis, but decreased the insulin-induced lipogenesis (p < 0.05). Conclusions: This study shows that leptin has no direct lipolytic effect in human adipocytes. The lack of effect on the insulin-induced inhibition of lipolysis and the negative effect on lipogenesis indicates that the effect of leptin is not at the proximal insulin-signalling pathway but further downstream.
Estrogen Receptor-Alpha and Estrogen Receptor-Beta Are Present in the Human Growth Plate in Childhood and Adolescence, in Identical Distribution
Authors: Egerbacher M. , Helmreich M. , Rossmanith W. , Haeusler G.
Published: April 2003

Objective: To localize estrogen receptor-α (ER-α) and estrogen receptor-β (ER-β) within the growth plate and adjacent bony tissue of children in the prepubertal and pubertal age period. Methods: Tissue was taken during orthopedic surgery (epiphysiodesis) for correction of congenital or traumatic leg length difference in 2 prepubertal females and 2 adolescent males. Immunohistochemistry was performed on paraffin-embedded or cryostat sections by using commercially available rabbit polyclonal antibodies for ER-α and ER-β. Results: Both ER-α and ER-β were detected within the growth plate in all sections investigated. Immunostaining was restricted to hypertrophic chondrocytes. In the bony tissue adjacent to the growth plate, osteoblasts stained positive for both ER-α and ER-β, whereas osteocytes and osteoclasts were negative. Staining with ER-α was mainly nuclear but some cells also showed cytoplasmic signals, while ER-β staining was predominantly cytoplasmic, only few nuclei stained positive. There was no difference in the local distribution of both ERs between tissue from prepubertal and pubertal patients. Conclusion: Our findings indicate that the hypertrophic chondrocyte is the main target cell for estrogen action within the growth plate. The presence of ER in prepubertal children suggests that estrogens play a role in skeletal maturation under physiological conditions also in this age-group.
Plasma Soluble Intercellular Adhesion Molecule 1 Levels Are Increased in Type 2 Diabetic Patients with Nephropathy
Authors: Güler Serdar , Cakir Bekir , Demirbas Berrin , Yönem Arif , Odabasi Ersin , Önde Ufuk , Aykut Ömer , Gürsoy Gül
Published: April 2003

Background/Aim: Intercellular adhesion molecule 1 (ICAM-1) is a mediator in the recruitment of leukocytes in the glomerular cells. The role of ICAM-1 in diabetic complications is still a matter of debate. This study was performed to investigate the relation of plasma soluble ICAM-1 (sICAM-1) to nephropathy in patients with type 2 diabetes mellitus. Methods: Ninety-three patients (24 males and 69 females) with type 2 diabetes mellitus were included into the study. Fifty patients had nephropathy, and 43 were free from nephropathy. Fifty healthy subjects (14 males and 36 females) served as the control group (group 1). Twenty-five of the diabetic patients had microalbuminuria (group 2), 25 had macroalbuminuria (group 3), and 43 had neither micro- nor macroalbuminuria (group 4). The plasma sICAM-1 levels were measured in blood samples drawn after fasting. Results: The mean plasma sICAM-1 levels were not different in the 93 diabetic patients as compared with the healthy controls (392.7 ± 119.5 vs. 350.1 ± 90.2 ng/ml, p > 0.05). The mean sICAM-1 level was significantly higher in the diabetic patients with nephropathy than in those without nephropathy (430.3 ± 78.2 vs. 368.2 ± 122.5 ng/ml, p = 0.03) and in the controls (430.3 ± 78.2 vs. 350.1 ± 90.2 ng/ml, p = 0.016). The difference in sICAM-1 levels between groups 2 and 3 was not significant (p > 0.05). The plasma sICAM-1 levels were significantly higher in both groups 2 and 3 than in both groups 1 and 4 (434.5 ± 129.2 vs. 427.2 ± 113.7 ng/ml and 368.2 ± 122.5 vs. 350.1 ± 90.2 ng/ml, respectively). Conclusions: The plasma sICAM-1 levels in patients with type 2 diabetes mellitus are not significantly different from those in nondiabetic subjects. High levels of sICAM-1 suggest that sICAM-1 may play a role in the development of nephropathy in patients with type 2 diabetes mellitus.
Hormone Replacement Therapy Does Not Affect Plasma Homocysteine in Postmenopausal Women with Coronary Artery Disease
Authors: Os Ingrid , Os Audun , Sandset Per Morten , Bølling Silje , Seljeflot Ingebjorg , Djurovic Srdjan , Westheim Arne
Published: April 2003

Objective: The objective was to evaluate the effect of hormone replacement therapy (HRT) on plasma homocysteine levels in postmenopausal women with coronary artery disease (CAD) and to investigate associations of homocysteine to other cardiovascular risk factors. Methods: The women in this single-center, controlled, and randomized study were examined at baseline, and after 3 and 12 months, after they had been recruited consecutively from patients referred for investigational coronary angiography. All analyses were performed examiner blind. They were randomized to HRT consisting of transdermal application of continuous 17β-estradiol with cyclic medroxyprogesterone acetate (MPA) tablets for 14 days every 3rd month, or to a control group. Results: After 3 months of unopposed 17β-estradiol, no significant effect on homocysteine was observed compared to the control group. The absolute decrease of 5% in median plasma homocysteine levels after 12-month HRT did not reach statistical significance. Plasma homocysteine seemed slightly higher in women with three- or four-vessel disease, but the difference was not significant. With increasing homocysteine levels, free tissue factor pathway inhibitor (TFPI) antigen increased, whereas E-selectin decreased. In women with diabetes or elevated blood glucose >6.0 mmol/l, plasma homocysteine was correlated to body mass index, C-peptide and insulin as well as age. Conclusion: Transdermal application of 17β-estradiol and sequential MPA do not affect plasma homocysteine in women with established CAD. Plasma homocysteine is stable in women with CAD over time, and unless special intervention is undertaken, repetitive measurements are not necessary in this particular group of high-risk individuals. The circulating anticoagulant TEPI is related to plasma homocysteine.
Correlation between the Electrocardiogram and Regional Wall Motion Abnormalities as Detected by Echocardiography in First Inferior Acute Myocardial Infarction
Authors: Golovchiner Gregory , Matz Israel , Iakobishvili Zaza , Porter Avital , Strasberg Boris , Solodky Alejandro , Imbar Shula , Birnbaum Yochai
Published: April 2003

We assessed the correlation between ST deviation in each of the six precordial leads and the presence of regional wall motion abnormalities (RWMA) as assessed by transthoracic echocardiography in 109 patients with first inferior acute myocardial infarction. ST depression in lead V1 and V2 was associated with higher incidence of RWMA of the mid-posterior segment (p < 0.02 for both leads). The specificity of ST segment depression in leads V1 and V2 for RWMA in mid-posterior segment was 87 and 57%, and the sensitivity 36 and 70%, respectively. Patients with ST depression in leads V2 or V3 had worse global RWMA score than patients without ST depression in these leads (p = 0.009 and p = 0.025, respectively). Patients with an ST elevation in lead V1, but not in leads V2 or V3, had a higher prevalence of right ventricular involvement (p < 0.0001). ST elevation in lead V5 was associated with more frequent involvement of the apical portion of the inferior wall (p < 0.02), with specificity of 88% and sensitivity of 33%. Global RWMA score was significantly worse for patients with ST elevation than for patients with isoelectric ST in lead V5 (p = 0.024). ST elevation in lead V6 was associated with RWMA in the mid-posterior segment (p < 0.006), with specificity of 91% and sensitivity of 33%, and worse global RWMA score (p = 0.022).
Endocarditis due to Anaerobic Bacteria
Authors: Brook Itzhak
Published: April 2003

This review describes the microbiology, diagnosis and management of endocarditis due to anaerobic bacteria. Anaerobic bacteria are an uncommon but important cause of endocarditis. Most cases of anaerobic endocarditis are caused by anaerobic cocci, Propionibacterium acnes and Bacteroides fragilis group. Predisposing factors and signs and symptoms of endocarditis caused by anaerobic bacteria are similar to those seen in endocarditis with facultative anaerobic bacteria with the following exceptions: the gastrointestinal tract was the most common source for B. fragilis group endocarditis, the head and neck were the most common origin for Fusobacterium and Bacteroides spp., and the head and neck and genitourinary tract were the most common source for peptostreptococci. Complications with anaerobic endocarditis include valvular destruction, multiple mycotic aneurysms, aortic-ring abscess, aortitis, cardiogenic shock, dysrhythmias and septic shock. The mortality rate for patients with anaerobes endocarditis is 21–43%. Treatment of endocarditis involving anaerobic bacteria includes the use of antibiotic therapy effective against these organisms.
Exercise Test in Women and Men Aged 75–77 Years
Authors: Wetterqvist Hakon , Grimby Gunnar , Lernfelt Bodil , Svanborg Alvar
Published: April 2003

The purpose of this study was to investigate the physiological response to an exercise test in 75- to 77-year-old women and men. Out of a systematically chosen and representative sample of 1,245 persons from a population at the age of 70, 649 individuals remained available at the age of 75–77 years. An exercise test was performed in 335 participants (52%), 174 women and 161 men. 180 (28%) were excluded because of morbidity. 131 (20%) refused to perform an exercise test. Three persons had to be excluded because of missing data. The maximal heart rate was about 140 beats/min. Heart rates at different submaximal workloads were higher in females than in males. In males there was a significant nonlinear increase in heart rate at increasing work loads while in females this was not significant. The systolic blood pressure increased more in females than in males while working on the loads 30–50 W and 50–75 W. There was a significant nonlinear increase in systolic blood pressure in men without cardiovascular drugs during exercise on 30–75 W, but the corresponding increase was not significant in women. The highest average work load for the whole group measured during at least 4 min of near-maximal exercise on a bicycle was in women 48 W and in men 66 W. Forty-four percent of the women and 22% of the men had a physical working capacity presumably interfering with their ability to perform activities of daily living.
Effect of Superovulation on the Expression of Tissue Inhibitor of Metalloproteinase-3 in the Murine Endometrium
Authors: Ku Seung Yup , Choi Young Min , Suh Chang Suk , Kim Seok Hyun , Kim Jung Gu , Moon Shin Yong , Lee Jin Yong , Kim Yon Su
Published: April 2003

Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are important in the endometrial remodeling process during embryonic trophoblast invasion. Previous studies, using in situ hybridization, revealed that the predominant proteinase expressed by the implanting mouse embryo is matrix metalloproteinase-9 (MMP-9), and the major tissue inhibitor of metalloproteinases (TIMP) produced in the murine endometrium during this period is TIMP-3. Quantitative, competitive-reverse transcription-PCR was performed to evaluate the expression of TIMP-3 mRNA during the implantation period in the hyperstimulated murine endometrium from pregnant uteri of gestation day (g.d.) 6.0 and 7.0 after injection of 5 and 10 IU pregnant mare serum gonadotropin (PMSG). In PMSG groups, the expression of TIMP-3 mRNA, normalized by MMP-9 mRNA, showed a significant increase compared to the control group (natural coitus without PMSG injection) on g.d. 6.0 (p = 0.039) and an increasing tendency on g.d. 7.0. This study suggests that ovarian hyperstimulation by gonadotropin may have a detrimental effect on embryonic implantation possibly via an altered endometrial remodeling process by the increase in expression of TIMP-3 in the murine endometrium.
Insomnia in Ischemic Stroke Patients
Authors: Leppävuori A. , Pohjasvaara T. , Vataja R. , Kaste M. , Erkinjuntti T.
Published: April 2003

This is the first study that focuses on insomnia in stroke patients. A subgroup of 277 patients from a consecutive series of 486 stroke patients aged 55–85 years was subjected to a comprehensive psychiatric evaluation 3–4 months after ischemic stroke. Of 277 patients, 56.7% reported any insomnia complaint and 37.5% fulfilled the DSM-IV criteria of insomnia. In 38.6%, insomnia complaint/insomnia had already been present prior to the stroke and in 18.1%, it was a consequence of the stroke. Independent correlates of any insomnia complaint/insomnia were anxiety (Zung Anxiety Scale) and the use of psychotropic drug. Independent correlates of poststroke-onset insomnia complaint/insomnia were disability after stroke (Barthel Index), dementia, anxiety and use of psychotropic drug. Insomnia should be taken into consideration in treating and rehabilitating stroke patients.
Sexual Functioning in Chinese Stroke Patients with Mild or No Disability
Authors: Cheung Raymond T.F.
Published: April 2003

This study was conducted to assess the effects of stroke on sexual functioning of patients with mild or no disability and to explore the associations of clinical and psychosocial factors with post-stroke changes in sexual functions. Consecutive stable Chinese patients were invited to complete a self-administered questionnaire concerning their pre- and post-stroke sexual functions and habits. Results from this cohort of 63 men and 43 women revealed a post-stroke decrease in libido, coital frequency, sexual arousal, orgasm and sexual satisfaction in 54.3%, 43.8%, 25.0% (women) to 51.6% (men), 20.0% (women) to 45.9% (men) and 28.6% of patients, respectively. Logistic regression indicated unwillingness for sex and a belief in an adverse effect of stroke on sexuality as explanatory factors for decreased sexual satisfaction. Thus, sexual dysfunctions are common in Chinese stroke patients with mild or no disability.
Evaluation of the Incidence of Sensorineural Hearing Loss in Beta-Thalassemia major Patients under Regular Chelation Therapy with Desferrioxamine
Authors: Karimi Mehran , Asadi-Pooya Ali A. , Khademi Bijan , Asadi-Pooya Kamyar , Yarmohammadi Hooman
Published: April 2003

With the improved life expectancy of β-thalassemia major patients, new clinical problems, such as hearing loss, must be evaluated. To determine the incidence of sensorineural hearing loss and its relationship to desferrioxamine (DFO), 128 patients receiving subcutaneous DFO in doses from 21 to 39 mg/kg/day were studied. These patients had received their total weekly dose of DFO according to two different methods. The first group (QOD group of 52%) had received it on an every other day basis. The second group (QD group of 48%) had received it on 6 days a week. Otological examinations and pure tone audiometry were performed on the patients as they routinely visited Shiraz Cooley’s Center, to find a possible correlation between the dose and duration of therapy. 56 patients (44%) in both groups had no evidence of drug-induced auditory abnormalities. Of the patients in the QOD group 44.7% had hearing loss in the right ear and 41.8% in the left ear at a frequency of 8,000 Hz compared to the QD group, 27.8 and 23%, respectively (with p < 0.047 and p < 0.02, respectively). No correlation was found between the duration of DFO therapy and sensorineural deficit. A significant correlation was found between the dose of drug given at each episode of DFO therapy and hearing loss at the frequency of 8,000 Hz, when comparing the QOD group with the QD group. Hence, it may be concluded that DFO ototoxicity is determined not only by the total amount of the drug given, but also by its maximal plasma concentration. Thus we suggest periodical audiologic checkups and a low dosage of DFO (below 50 mg/kg/day) given on at least 5–6 days a week for the prevention and prompt diagnosis of audiologic complications.
Fundamental Mechanisms of Growth Failure in Inflammatory Bowel Disease
Authors: Ballinger Anne
Published: April 2003

Growth failure is common in children with inflammatory bowel disease (IBD) and has been attributed chiefly to undernutrition. Liquid enteral feeding can reverse the calorie deficit and increase growth velocity. The inflammatory process per se may also directly inhibit linear growth. After institution of enteral nutrition, significant changes in serum growth factors and inflammatory indices have been observed before any changes in nutritional parameters [Bannerjee et al., Gastroenterology 2000;118:A526]. In rats with trinitrobenzenesulphonic acid (TNBS)-induced colitis, about 60% of the final growth impairment can be attributed to undernutrition, inflammation accounting for the remaining growth deficit. Young patients with Crohn’s disease and growth failure have normal stimulated and spontaneous growth hormone (GH) secretion and reduced plasma concentrations of insulin-like growth factor-1 (IGF-I), suggesting a degree of GH resistance. Rats with TNBS colitis also have normal plasma GH and reduced IGF-I concentrations, mediated by a combination of undernutrition and active inflammation. Immunoneutralization of interleukin-6 (IL-6) increases hepatic IGF-I mRNA expression, plasma concentrations of IGF-I and linear growth. In contrast, administration of anti-tumour necrosis factor-α antibodies (TNF-ab) had no effect on IGF-I in this model. TNFab did, however, increase linear growth, suggesting inhibitory effects of TNF-α on the growth axis by mechanisms other than reduction in IGF-I. Preliminary data suggests that TNF-α inhibits maturation of growth plate chondrocytes. We have identified IL-6 receptors on growth plate chondrocytes but to date have not identified the effect, if any, of IL-6 directly at the growth plate.
Growth and Body Composition in Type 1 Diabetes mellitus
Authors: Dunger David , Ahmed Lynn , Ong Ken
Published: April 2003

Over the last 50 years the prognosis for growth and pubertal development in children with type 1 diabetes mellitus (T1DM) has improved considerably. The early reports of Mauriac’s syndrome were related not only to relative deficiency of insulin but also reduced caloric intake. Improved insulin delivery and liberalisation of caloric intake has resulted in improved growth, but subtle abnormalities persist. The frequently reported increased height at diagnosis may relate to prior hyperinsulinaemia and genetic background with respect to lDDM2 the insulin gene VNTR. Subsequent growth faltering is thought to be related to impairment of the GH/IGF-1 axis but children with T1DM are also more at risk of hypothyroidism and coeliac disease. At puberty, persisting abnormalities of the GH/IGF-1 axis and our inability to reverse these totally, even with intensified insulin therapy, contribute to the blunted pubertal growth in the girls but abnormal sex steroid concentrations may also be important. Intensification of insulin therapy may result in leptin resistance and excessive gains in fat mass, particularly in girls. Although it is likely that most children with T1DM will have normal final heights, this excessive weight gain in girls may lead to problems with compliance. Furthermore, hyperinsulinaemia in these subjects may also lead to ovarian hyperandrogenism, increased early risk of microvascular complications and long-term risk of cardiovascular disease.
Growth in Disorders of Adrenal Hyperfunction
Authors: Savage M.O. , Scommegna S. , Carroll P.V. , Ho J.T.F. , Monson J.P. , Besser G.M. , Grossman A.B.
Published: April 2003

Growth is disturbed by adrenal hypersecretion of androgens or cortisol. Androgen excess in virilizing adrenal tumours causes advanced growth and bone age. In 9 girls with virilizing tumours, mean heights at diagnosis and final heights were 1.23 ± 0.42 and 1.3 ± 0.37 SDS respectively. In poorly controlled CAH, excess androgens cause early epiphyseal fusion and adult short stature. Increased growth occurs only after 18 months of age, even in untreated CAH, i.e. hydrocortisone >10 mg/m2/day is not generally required and may suppress infantile growth, affecting childhood and adult height. Growth was studied in 19 patients, aged 6.4–17.8 years, with Cushing’s disease (CD). At diagnosis, mean height SDS was –1.81 (1.2 to –4.17), 53% < –1.8 SDS, height velocity in 6 was 0.9–3.8 cm/year and mean BMI SDS 2.29 (0.7–5.06). From 1983 to 2001, CD was cured in 18 patients (61%) by transsphenoidal surgery (TSS) alone and 39% by TSS plus pituitary irradiation (RT). In 13 patients, growth hormone (GH) was assessed by ITT/glucagons at 1–108 months after cure. Four had severe GH deficiency (<9 mU/l), 7 subnormal (10–29 mU/l) and 2 normal (>30 mU/l) GH status. Subnormal GH was present in 7 subjects >2 years after TSS or RT cure. In 10 subjects, aged 12.9 ± 3.4 years, growth after cure was studied for 9.1 ± 5.0 years. Nine had no catch-up growth in the interval of 0.3–1.1 years after cure (mean HV 5.3 ± 2.4 cm/year). All these had GH deficiency peak GH 0.5–20.9 mU/l, and received hGH 2.7 mg/m2/week, 3 with GnRHa. All 10 showed long-term catch-up growth with mean delta SDS at diagnosis (Ht SDS–target Ht SDS) –1.72 ± 1.26 improving to –0.83 ± 1.08 (p = 0.0005) at latest of final Ht. At diagnosis, virilization was present in 82% of 17 patients with CD. Mean SDS values of serum androstenedione, DHEA-S and testosterone were normal, i.e. 0.72 (–2.9 to 3.0), –0.8 (6.0 to 2.2), 0.7 (–7.9 to 9.5) respectively, whereas SHBG was reduced at –2.1 (–5.3 to 1.2), increasing free androgen levels. Bone age (BA) was delayed (mean 1.46 years) in 14/16 patients, suggesting cortisol excess contributed more then androgen effect to skeletal maturation. In conclusion, most paediatric patients with CD had subnormal linear growth with delayed BA. After cure by TSS or pituitary irradiation, GH deficiency was frequent and persisted for many years. Treatment with hGH induced significant long-term catch-up growth leading to reasonable final height.
Atypical Antipsychotic Drug Use and Diabetes
Authors: Ananth Jambur , Venkatesh Ravi , Burgoyne Karl , Gunatilake Sarath
Published: April 2003

Recently, there has been increased concern about the occurrence of diabetes associated with the use of atypical antipsychotic (AAP) drugs. The relationship between diabetes, schizophrenia, and antipsychotic drugs is complex and intriguing, as untreated patients with schizophrenia are known to suffer from diabetes more often than the general population. Thirty individual case reports of clozapine-, 26 cases of olanzapine- and a few others of seroquel- and risperidone-associated diabetes mellitus, hyperglycemia and diabetic ketoacidosis were found by a Medline search. The case reports do not provide the incidence of diabetes in patients treated with AAP drugs, but they suggest that AAP drugs may cause hyperglycemia. Further research is needed to identify the cause of the susceptibility of the schizophrenic population, and to elucidate the mechanisms by which the antipsychotic drugs either cause diabetes or precipitate its onset. Which antipsychotic drugs have a higher and which have a lower potential to induce diabetes is not conclusively answered at present. However, the findings that 50% of the patients completely improve upon drug discontinuation, and that hyperglycemia promptly recurs upon reinstitution of the incriminated drug indicate that this side effect is reversible and is drug related. African Americans are particularly susceptible to AAP drug-induced diabetes. Until the new research data become available, AAP drug treatment of schizophrenic patients aims at prevention, institution of vigilant screening procedures, and management of hyperglycemia.
Treatment-Resistant Depression and Axis II Comorbidity
Authors: Petersen Timothy , Hughes Megan , Papakostas George I. , Kant Alexis , Fava Maurizio , Rosenbaum Jerrold F. , Nierenberg Andrew A.
Published: April 2003

Background: Researchers of unipolar depression have speculated that personality disturbance is a contributing factor in the development of treatment resistance. The purpose of this study was to compare the prevalence of Axis II disorders between a sample of rigorously defined, treatment-resistant depressed outpatients and a sample of depressed outpatients not having experienced treatment resistance. Methods: 53 patients with treatment-resistant depression (TRD) and 105 patients with non-treatment-resistant depression (non-TRD) were recruited through respective outpatient clinical trials at the Massachusetts General Hospital’s Depression Clinical and Research Program. Diagnosis of Major Depressive Disorder was made using the Structured Clinical Interview for the DSM-III-R, personality disorders were assessed using the Structured Clinical Interview for DSM-III-R Personality Disorders, and antidepressant treatment resistance was defined using the McLean Hospital Antidepressant Treatment Record. Participants from both studies were matched for baseline HAM-D-17 total score and gender. Multiple chi-square analysis was used to compare frequencies of Axis II disorders between TRD and non-TRD patients as well as to compare categorical baseline demographic variables. Unpaired t tests were used to compare baseline demographic and clinical variables measured in a continuous manner. Results: Non-TRD patients had a higher rate of obsessive-compulsive personality disorder than TRD patients, but this difference was not statistically significant after adjusting for multiple comparisons. No other differences were found to be statistically significant. Range of Axis II comorbidity was 0.0–30.2% for TRD patients and 2.9–37.1% for non-TRD patients. Conclusions: In this sample, treatment resistance in a current major depressive episode was not associated with an increased rate of Axis II disorders. Strengths of this study include the use of structured interview instruments to assess Axis I and II conditions, and having the two study groups matched for gender and baseline severity of depression. Limitations of this study include a modest sample size and reliance on DSM personality constructs.
Subjective Quality of Life: Its Relationship with Clinician-Rated and Patient-Rated Psychopathology
Authors: Lasalvia Antonio , Ruggeri Mirella , Santolini Nazario
Published: April 2003

Background: The study compared clinician-rated and patient-rated psychopathology and analysed their relationship with subjective quality of life (QoL) in a sample of patients with a wide range of psychiatric conditions attending a community-based mental health service. Methods: In the context of the South-Verona Outcome Project (SVOP), 139 patients were assessed for both clinician-rated and self-rated psychopathology (by using respectively the Brief Psychiatric Rating Scale and the revised version of the Symptom Checklist 90), and asked to report on their subjective quality of life (by using the Lancashire Quality of Life Profile). In order to explore the associations between psychopathology and subjective QoL bivariate and multivariate analyses were performed. Results: BPRS and SCL-90-R were poorly correlated, both in their total scores and in their various dimension scores. BPRS showed only a modest negative correlation with LQL, which, in contrast, was highly negatively correlated with SCL-90-R. Regression analyses showed that patient-rated psychopathology was the strongest predictor of subjective quality of life, with self-rated depressive symptoms and self-reported paranoid ideation having the highest predictive power. Conclusions: Self-reported psychological distress is more important than clinician-rated symptom severity in predicting subjective QoL. In order to improve QoL, psychiatric treatment should focus not only on simple reduction of symptoms but also on patients’ subjective psychological distress.
The Relevance of Psychiatric and Somatic Comorbidity in Depressed Chronic Benzodiazepine Users
Authors: Couvée Jaap E. , Bakker Abraham , Zitman Frans G.
Published: April 2003

Background: Comorbid conditions may add to the burden of depressed patients and hamper their treatment. We therefore investigated the impact of anxiety disorders and somatic comorbidity in a group of depressed chronic benzodiazepine users on disease status, treatment, benzodiazepine history and discontinuation outcome. Methods: At screening for a discontinuation programme, full psychiatric status was determined using the MINI-interview and psychopathology was assessed using several rating scales. Relevant medical history, including surgeries, was recorded as well. Results: Patients with comorbid anxiety disorders were 8 years younger (p < 0.001), more anxious (p = 0.004) and reported more benzodiazepine withdrawal symptoms (p = 0.011) than depressed patients without comorbid anxiety disorders. They also had been using more long-acting benzodiazepines (p = 0.003), in higher dosages (p = 0.019). However, this did not result in more difficulty in tapering off benzodiazepines, either at post-test, or at follow-up 2.3 years later. Somatic comorbidity was not associated with the level of psychopathology and not related to the outcome of the discontinuation programme. Conclusions: Comorbid anxiety disorders are associated with a more severe disease status in depressed chronic benzodiazepine users, but have no influence on the benzodiazepine discontinuation. Somatic comorbidity has no impact on the severity of the psychopathology, or on benzodiazepine discontinuation.
Antagonist/Agonist Balance of the Nonsteroidal Antiandrogen Bicalutamide (Casodex) in a New Prostate Cancer Model
Authors: Hobisch Alfred , Hoffmann Jens , Lambrinidis Leonidas , Eder Iris E. , Bartsch Georg , Klocker Helmut , Culig Zoran
Published: April 2003

Androgen ablation is standard therapy for advanced prostate carcinoma. It can be administered either as a monotherapy or as a combined androgen blockade. In the present study we have investigated molecular mechanisms which are responsible for the development of resistance to therapy in advanced prostate cancer. For this purpose, we have cultured LNCaP cells in steroid-depleted medium for 1 year. The newly generated subline LNCaP-abl was characterized. In early passages (<75) LNCaP-abl cells showed a biphasic hypersensitive response to androgenic stimulation. Passages later than 75 are inhibited by androgen. Proliferation of LNCaP-abl cells was stimulated by the pure nonsteroidal antiandrogen bicalutamide (Casodex). To improve our understanding of changes which occur during intermittent androgen ablation, we have generated the sublines LNCaP-R (reversal; cultured with fetal calf serum) and LNCaP-RA (reversal and androgen; cultured with fetal calf serum and androgen) from LNCaP-abl cells. In both cell lines an increase of the basal proliferation rate was observed. Androgen receptor expression in LNCaP-abl cells was 4-fold higher than that in parental LNCaP cells (4.7 vs. 1.2 fmol/µg protein). Androgen receptor content in LNCaP-R cells was 1.8 fmol/µg protein and in LNCaP-RA cells 1.0 fmol/µg protein. The basal androgen receptor activity was 30-fold higher in LNCaP-abl cells compared to that in parental LNCaP cells. This basal activity was reduced in LNCaP-RA cells. Both androgen and the nonsteroidal androgen receptor antagonist hydroxyflutamide induced a 2- to 4-fold higher activation of androgen receptor in LNCaP-abl than in LNCaP cells. There was a switch from an antagonist to an agonist of the nonsteroidal antiandrogen bicalutamide (Casodex) in LNCaP-abl cells. Antagonistic properties of this androgen receptor blocker were again observed in both sublines (LNCaP-R and LNCaP-RA) derived from LNCaP-abl cells. In concordance with proliferation data in vitro, growth of LNCaP-abl cells in nude mice was stimulated by bicalutamide. In contrast, supplementation of androgen led to inhibition of proliferation of these cells. The present study provides new information that is useful for a better understanding of therapy-refractory prostate cancer. It is also important for the development of new therapy strategies for advanced carcinoma of the prostate.
Qualitative Determination of Urinary Human Complement Factor H-Related Protein (hcfHrp) in Patients with Bladder Cancer, Healthy Controls, and Patients with Benign Urologic Disease
Authors: Heicappell Rüdiger , Müller Markus , Fimmers Rolf , Miller Kurt
Published: April 2003

Objectives: To assess the diagnostic quality of human complement factor H-related protein (hcfHrp, BTA STATTM) as a qualitative urinary marker for bladder cancer. Methods: Urine samples of 354 individuals (76 healthy volunteers, 111 patients with benign urologic disorders, 167 patients with histologically proven bladder cancer) were examined prior to therapy for the presence of hcfHrp. Results: Overall test sensitivity was 62.9%. Sensitivity of low-grade/low-stage tumors was <50% and was thus comparable to published sensitivities of urinary cytology. In high-stage, high-grade tumors sensitivity was 100 and 77.3%, respectively. Superficial tumors with high risk of progression (pT1G3) were detected significantly better (88.9% sensitivity) than low-risk superficial tumors (pTa G1–3/pT1G1–2; 48.2%; p < 0.001). The overall specificity (healthy individuals and patients with benign urologic disease) was 93.0%. Conclusion: Since test sensitivity is comparable to urinary cytology and specificity is excellent, hcfHrp should be further evaluated in prospective studies focussing on the follow-up of patients with bladder cancer.
Acupuncture on Clinical Symptoms and Urodynamic Measurements in Spinal-Cord- Injured Patients with Detrusor Hyperreflexia
Authors: Honjo Hisashi , Naya Yoshio , Ukimura Osamu , Kojima Munekado , Miki Tsuneharu
Published: April 2003

Objectives: We investigated the possible use of acupuncture for the treatment of urinary incontinence caused by detrusor hyperreflexia in patients with chronic spinal cord injuries. Methods: A total of 13 patients (11 males, 2 females) suffering from urinary incontinence due to spinal cord injuries were treated by acupuncture, which was carried out with disposable stainless steel needles inserted into the bilateral BL-33 (Zhongliao) points on the skin of the third posterior sacral foramina. Urodynamic studies were also performed before acupuncture, immediately after the 1st acupuncture and 1 week after the 4th acupuncture. In 6 patients, these urodynamic studies were performed again 1 month after the 4th acupuncture. Results: No side effects were recognized throughout the treatment period. Of the 13 patients, incontinence disappeared in 2 (15%) and decreased to 50% or less compared to baseline in a further 6 (46%). Maximum cystometric bladder capacity increased significantly from 76.2 ± 62.3 to 148.1 ± 81.5 ml 1 week after the 4th acupuncture (p < 0.01). In the 6 patients in whom cystometry was repeated 1 month after the 4th acupuncture, bladder capacity decreased from 187.5 ± 90.4 ml 1 week after the 4th acupuncture to 128.3 ± 93.4 ml. Conclusion: In spinal cord injury patients acupuncture could represent another valuable therapeutic alternative to the treatment of urinary incontinence caused by detrusor hyperreflexia.
The Shrinking Seminoma – Fact or Fiction?
Authors: Naseem S. , Azzopardi A. , Shrotri N. , Mufti G.R.
Published: April 2003

We report 2 cases of testicular seminoma with unusual but dissimilar clinical presentations, which may represent different stages of spontaneous regression of a primary testicular seminoma, the so-called ‘shrinking seminoma’. The aetiology of this phenomenon is discussed. These cases also illustrate that, like enlargement, reduction in the size of a testicle warrants investigation for malignancy.
Comparative in vitro Activity of Levofloxacin and Ciprofloxacin against Bacterial Isolates from Neutropenic Patients
Authors: Di Bonaventura G. , D’Antonio D. , Catamo G. , D’Ercole S. , Piccolomini R.
Published: April 2003

Background: Novel fluoroquinolones have been recently introduced in the management of neutropenic patients because of their increased activity against gram-positive and gram-negative micro-organisms. Methods: The activities of levofloxacin and ciprofloxacin were determined by the E test against 223 bacterial isolates from patients with haematological malignancies. Results: In general, the activity of levofloxacin was comparable to that of ciprofloxacin. Levofloxacin was somewhat more active against methicillin-resistant Staphylococcus aureus isolates. All methicillin-susceptible S. aureus isolates were inhibited by ciprofloxacin and levofloxacin at a concentration of ≤0.5 and ≤0.25 µg/ml, respectively. Among gram-negative isolates tested, levofloxacin was significantly (p < 0.001) more active than ciprofloxacin against Stenotrophomonas maltophilia, inhibiting 68 and 53% of these isolates, respectively. Conclusions: Levofloxacin was not superior to ciprofloxacin in its overall antibacterial activity, although small differences between these agents were seen depending on the species tested. In particular, our data suggested that levofloxacin may potentially be used for the management of S. maltophilia infections in neutropenic patients.
Antiviral Activity of Petiveria alliacea against the Bovine Viral Diarrhea Virus
Authors: Ruffa M.J. , Perusina M. , Alfonso V. , Wagner M.L. , Suriano M. , Vicente C. , Campos R. , Cavallaro L.
Published: April 2003

Background: Natural products are a relevant source of antiviral drugs. Five medicinal plants used in Argentina have been assayed to detect inhibition of viral growth. Methods: Antiviral activity of the infusions and methanolic extracts of Aristolochia macroura, Celtis spinosa, Plantago major, Schinus areira, Petiveria alliacea and four extracts obtained from the leaves and stems of the last plant were evaluated by the plaque assay. Results:P. alliacea, unlike A. macroura, C. spinosa, P. major and S. areira, inhibited bovine viral diarrhea virus (BVDV) replication. Neither P. alliacea nor the assays of the other plants were active against herpes simplex virus type 1, poliovirus type 1, adenovirus serotype 7 and vesicular stomatitis virus type 1. Four extracts of P. alliacea were assayed to detect anti-BVDV activity. Ethyl acetate (EC50 of 25 µg/ml) and dichloromethane (EC50 of 43 µg/ml) extracts were active; moreover, promising SI (IC50/EC50) values were obtained. Conclusion: BVDV is highly prevalent in the cattle population, there are no antiviral compounds available; additionally, it is a viral model of the hepatitis C virus. For these reasons and in view of the results obtained, the isolation and characterization of the antiviral components present in the P. alliacea extracts is worth carrying out in the future.
Progressive Aphasia with Lewy Bodies
Authors: Caselli Richard J. , Beach Thomas G. , Sue Lucia I. , Connor Donald J. , Sabbagh Marwan N.
Published: April 2003

Dementia with Lewy bodies (DLB) may include both Alzheimer and Lewy body pathology, but has never been reported to cause primary progressive aphasia. We report a 69-year-old woman who died 11 years after presenting with the syndrome of progressive aphasia. Six years after aphasia onset she developed visual hallucinations, and subsequently parkinsonism. Autopsy examination revealed Alzheimer’s disease (AD), cortical Lewy bodies, and depigmentation and Lewy bodies in the substantia nigra and locus ceruleus. The aphasia most likely reflected the initial onset of AD, and the psychosis and parkinsonism most likely reflected the subsequent onset of Lewy body pathology. This first reported case of progressive aphasia occurring within the context of AD and Lewy body pathology uniquely illustrates the clinical and pathological nosological relationships between these two disease processes, and demonstrates a limitation of the general term, ‘DLB’.
Depression in Alzheimer’s Disease Might Be Associated with Apolipoprotein E ε4 Allele Frequency in Women but Not in Men
Authors: Müller-Thomsen Tomas , Arlt Sönke , Ganzer Stefanie , Mann Ulrike , Mass Reinhard , Naber Dieter , Beisiegel Ulrike
Published: April 2003

The association between depression and apolipoprotein E (apoE) was investigated in 137 out-patients with Alzheimer’s disease. An ICD-10 diagnosis of depression was found in 21.1% of all patients. There was a good correlation between clinicians’ diagnoses and blinded rating by the Montgomery-Åsberg Depression Rating Scale (r = 0.70). In male patients, apoE 3/3 was detected in 34.1%, 3/4 in 38.6%, 4/4 in 13.6%, 2/4 in 6.8% and 2/3 in 6.8% of cases. In female patients, apoE 3/3 was detected in 35.5%, 3/4 in 45.2%, 4/4 in 12.8%, 2/4 in 3.2% and 2/3 in 3.2% of cases. When analyzing the variance of gene dosage effect, the frequency of the apoE Ε4 allele was significantly increased in depressed women but not in men. This effect remained stable in stepwise regression analysis when depression as the dependent variable was tested against the independent variables age, age of onset, duration of disease, cognitive status and years of school education.
A Comprehensive Review of Proton Magnetic Resonance Spectroscopy Studies in Dementia and Parkinson’s Disease
Authors: Firbank M.J. , Harrison R.M. , O’Brien J.T.
Published: April 2003

We reviewed the literature of proton magnetic resonance spectroscopy (MRS) in dementia and Parkinson’s disease (PD) and quantitatively compared the reported values of the markers N-acetyl aspartate (NAA), choline, and myo-Inositol between control and disease groups. We analysed a total of 27 reports in dementia. Combining the quantitative data from these showed a relative decrease of 15% in NAA level in the temporal lobe tissue in patients with Alzheimer’s disease (AD) compared with controls. The rest of the brain showed a seemingly uniform 10% decrease in NAA levels in AD compared with controls. myo-Inositol was raised by about 15%, again uniformly throughout the brain, but there was no evidence for changed levels of choline. We found 15 reports of MRS in PD, which show a small decrease (5%) in the NAA level in the lentiform nucleus compared with controls. In progressive supranuclear palsy (PSP), there is a greater decrease in NAA levels in the frontal region and the lentiform nucleus. This may aid in the diagnosis of PSP. Further research is needed to determine spectroscopic changes in other dementias, to monitor how markers change with disease progression and to establish clinical utility.
Suicide amongst Alzheimer’s Disease Patients: A 10-Year Survey
Authors: Barak Yoram , Aizenberg Dov
Published: April 2003

Suicide is a major public health problem with advancing age being one of the factors associated with increased risk. It has been suggested that most DSM axis-I disorders contribute to increased suicidal risk while dementia is one of the few exceptions. We conducted a 10-year retrospective analysis of all elderly patients suffering from dementia admitted to a large urban mental health center. Between 1991 and 2000 there were 1,551 admissions to our center who were 65 years or older. Of these, 341 were diagnosed (DSM-IV criteria) as suffering from dementia and 215/341 as suffering from Alzheimer’s disease (AD). Sixteen AD patients (7.4% of all AD patients) were admitted immediately following a suicide attempt. The control group consisted of the next admission of an elderly AD patient matched for age and gender. The index group (suicidal patients) differed from controls in Clinical Dementia Rating scores (p = 0.017) and higher frequency of previous suicide attempts (p = 0.022). Lifetime psychopathology was not associated with higher rates of suicide attempts (p = 0.068). Physicians should be aware that suicide attempts are not rare in elderly AD patients. Higher level of daily functioning and previous suicide attempts are associated with increased suicidal risk.
Adding Culture to Studies of Development: Toward Changes in Procedure and Theory
Authors: Goodnow Jacqueline J.
Published: April 2003

This paper asks how an interest in culture and in development can be combined to the benefit of both and at the level of theory and procedures. Three steps are considered, noting for each some existing moves and some recommended extensions. The first step has to do with the sampling of people. Here the main existing move has been toward greater social diversity in sampling. The extensions have to do with giving closer attention to the bases for choice, the ‘subjects’ view of events, within-group diversity or consensus, and one’s own culture. The second step has to do with sampling tasks and situations. Here the existing moves have been toward the greater use of everyday tasks, life-course problems, and tasks that involve two or more people: all shifts based on changes in concepts of ability and its bases. The extensions have to do with considering larger groups (going beyond dyads), the impact of audiences, the expectations people hold about appropriate contributions to shared tasks, and the conceptual bases for choice. The third step consists of alertness to unexpected or missing pieces in data or theory. It is illustrated by progressions within research by Peggy Miller and by the author and her colleagues (e.g., progressions in the latter case from Piagetian tasks to parents’ concepts of development and household divisions of labour).
Culture Structures the Environment for Development
Authors: Super Charles M. , Harkness Sara
Published: April 2003

Culture is usefully conceived for developmentalists as the organization of the developmental environment. This definition makes available to scientific scrutiny the processes by which culture affects the course of development, that is, how it generates the relationships and meanings of variables that are more familiar, individually, to traditional developmental scientists. One framework for parsing the environment is the ''developmental niche'', which identifies three operational subsystems – the physical and social settings, the historically constituted customs and practices of child care and child rearing, and the psychology of the caretakers, particularly parental ethnotheories which play a directive role and are, by definition, shared with the community. Three organizational aspects of the niche create particularly important developmental outcomes: contemporary redundancy, which is the mutually reinforcing repetition of similar influences from several parts of the environment during the same period of development; thematic elaboration, which is the repetition and cultivation over time of core symbols and systems of meaning; and chaining, in which no single element of the environment is sufficient in kind to produce a particular outcome, but the linking of disparate elements creates a qualitatively new phenomenon. In addition, there is a more complex set of second-order effects; sex and temperament, for example, are characteristics whose meaning and consequence are organized by features of the environment. Finally, it is argued that theoretical recognition of variable relationships between development and the environment represents our discipline''s growth toward abstract thinking.