Benign multiple sclerosis is characterized by a stable neuroimmunologic network

OBJECTIVES: Patients diagnosed with multiple sclerosis (MS) but without disability (Expanded Disability Status Scale score <2) form a specific group within those patients suffering from relapsing-remitting MS. Several neuroimmunologic effectors, including cytokines and melatonin, are known for their influence on the initiation of relapses and progression of the disease. METHODS: We evaluated 41 female patients with benign MS with respect to their clinical course, treatments and neuroimmunological parameters, including cytokines and melatonin. One subgroup was followed up for 7 years, and another group was evaluated during acute clinical relapse. RESULTS: The benign MS course in this homogeneous group of young patients was demonstrated by mild disease progression in 16% over 7 years. Initially, patients treated with azathioprine (AZA) revealed significantly reduced melatonin serum levels (p = 0.04) compared to untreated patients, but not at follow-up. During acute relapse, treatment with corticosteroids (CS) resulted in increased levels of type 2 cytokines as well as reduced type 1 cytokine levels. CONCLUSIONS: Our study supports the functional role of CS acting as an antiinflammatory protagonist during MS relapse, by inducing a shift towards predominance of type 2 cytokines. AZA showed a more subtle modulation of immune functions, reflected by reduced levels of the immune active hormone melatonin. During follow-up, it became apparent that stabilized levels of the interacting Th1/Th2-derived cytokines and melatonin are maintained in concordance with the benign course of MS. These findings are in accordance with the hypothesis that benign MS is characterized by a balanced cytokine and neuroendocrine network, which is supported by immune-modulating therapies.     

Single photon emission computed tomography (SPECT) of anxiety disorders before and after treatment with citalopram

Background  

Several studies have now examined the effects of selective serotonin reuptake inhibitor (SSRI) treatment on brain function in a variety of anxiety disorders including obsessive-compulsive disorder (OCD), posttraumatic stress disorder (PTSD), and social anxiety disorder (social phobia) (SAD). Regional changes in cerebral perfusion following SSRI treatment have been shown for all three disorders. The orbitofrontal cortex (OFC) (OCD), caudate (OCD), medial pre-frontal/cingulate (OCD, SAD, PTSD), temporal (OCD, SAD, PTSD) and, thalamic regions (OCD, SAD) are some of those implicated. Some data also suggests that higher perfusion pre-treatment in the anterior cingulate (PTSD), OFC, caudate (OCD) and antero-lateral temporal region (SAD) predicts subsequent treatment response. This paper further examines the notion of overlap in the neurocircuitry of treatment and indeed treatment response across anxiety disorders with SSRI treatment.     

Investigation of a genetic variation of a variable number tandem repeat polymorphism of interleukin-6 gene in patients with multiple sclerosis

Interleukin-6 (IL-6) plays an important role in the regulation of the inflammatory response in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Previous reports indicated that the C allele of a variable number tandem repeat (vntr) polymorphism located in the 3'flanking region of the IL-6 gene (IL-6) is associated with reduced activity of IL-6 in vivo. Since disease-modifying genes are likely to contribute to phenotypic differences in MS patients, we tested the hypothesis that the IL-6 C allele is associated with the clinical course of MS. The IL-6 C allele was equally distributed between 217 MS patients of German Caucasian origin and 111 age-mached healthy controls. Stratification of patients according to the course of disease revealed no significant difference of IL-6 C allele distribution between patients with primary progressive and those with either relapsing-remitting or secondary progressive MS although IL-6 C allele was more frequent in patients with RR-MS. Since IL-6 C allele has been associated with a benign course in Sardinian MS patients, we further analysed an independent sample of 125 Sardinian MS patients revealing that IL-6 C allele was much more frequent than in German MS patients. Taken together, a disease-modifying effect of IL-6 C allele could not be demonstrated in MS patients of German Caucasian descent. Received: 7 October 2002, Received in revised form: 16 December 2002, Accepted: 19 December 2002 Correspondence to S. Schmidt, MD     

High-dose rate brachytherapy for high-risk prostate cancer

To estimate disease-free survival it is necessary to allocate patients into tumor risk groups: locally advanced prostate carcinoma with extracapsular spread or localized prostate carcinoma of tumor stage T2c or one of the risk factors PSA >20 or Gleason > or =8 apply for the high-risk group. Intermediate-risk carcinomas are those belonging to tumor stage T2b or with PSA >10-20 or Gleason 7. Particularly for patients with intermediate and high-risk disease early PSA relapse is of major interest. This phenomenon could be a consequence of current inadequate imaging of lymph node or bone metastasis or as a consequence subclinical metastatic spread remains undetectable during radical treatment. However, tumor biology itself could lead to the progression of the disease in the high-risk group. As a consequence, risk-adapted therapy is very important in these cases. The applied radiation dose plays an important role in radiotherapy. Several publications have shown that the biochemical relapse correlates with the generally accepted risk factors and the radiation dose. Regarding this, high-quality treatment planning and HDR brachytherapy combined with EBRT (external beam radiation therapy) leads to good treatment results in selected groups. So far in our own experience, HDR brachytherapy in combination with EBRT is a successful form of treatment with few acute and late side effects in the first 42 patients examined. First results concerning to PSA relapse-free time, quality of life, miction, and erectile function are promising.     

New approaches in the modulation of bladder smooth muscle cells on viable detrusor constructs

Identification of biochemical and mechanical stimuli in order to modulate the function of bladder smooth muscle cells (SMC) in viable detrusor constructs. Human bladder detrusor cells were seeded on bladder acellular matrix and cultured under different conditions. Cell viability and proliferation were assessed by fluorescent microscopic analyses. Histological, immunohistochemical and flow cytometric analyses were performed to compare growth characteristics and differentiation of SMC. The combination of medium conditioned with proliferative urothelium and mechanical stretch resulted in a more densely populated membrane. In this culture system, the expression of α-smooth muscle actin (α-SMA) and desmin were clearly induced after serum elimination. SMC-phenotype can be modulated in viable detrusor constructs by applying selected combinations of urothelial-conditioned media and mechanical stimulation under stepwise reduction and elimination of serum.     

Obesity, fitness and health in Taiwanese children and adolescents

OBJECTIVE: To examine the prevalence of childhood and adolescent obesity in Taiwan and investigate the association between excess weight and physical fitness and blood pressure. DESIGN: Cross-sectional study. SUBJECTS: A total of 13 935 children and adolescents aged 6-18 years (boys: 7031, girls: 6904) were involved in the 1999 survey and 24 586 (boys: 12 367, girls: 12 219) were available in the 2001 survey. MEASUREMENTS: Weight, height, systolic and diastolic blood pressures, and health-related fitness tests (bent-leg curl-ups, sit-and-reach test and step test) were measured. RESULTS: The overall prevalence of obesity (including overweight) in boys was 19.8% in 1999 and 26.8% in 2001. It was lower in girls with 15.2% in 1999 and 16.5% in 2001. The normal weight group performed better (P<0.05) than the overweight/obese group in all fitness tests except in the 2001 sit-and-reach test where there were no differences between the two groups. The risk of hypertension increased nearly two times for the overweight/obese-fit group and nearly three times for the overweight/obese-unfit group compared to the normal weight-fit group (adjusted odds ratio (AOR)=1.93, 95%CI=1.514-2.451 and AOR=2.93, 95%CI=2.493-3.454, respectively). CONCLUSION: Overall, the findings demonstrated that there is an increasing trend in overweight/obesity prevalence for Taiwanese youth even in a 2-year period. The overweight/obese youngsters tend to have poorer muscular strength and cardiovascular endurance than the normal weight group. The overweight/obese and unfit group had a greater risk of hypertension than other groups. However, this risk was significantly lower if obese/overweight children had a higher than average level of cardiovascular fitness.     

Radiation therapy for favorable histology Wilms tumor: prevention of flank recurrence did not improve survival on National Wilms Tumor Studies 3 and 4

PURPOSE: To determine whether radiation therapy (RT) of patients with Wilms tumor of favorable histology prevented flank recurrence and thereby improved the survival outcomes. METHODS AND MATERIALS: Recurrence and mortality risks were compared among groups of patients with Stage I-IV/favorable histology Wilms tumor enrolled in the third (n = 1,640) and fourth (n = 2,066) National Wilms Tumor Study Group studies. RESULTS: Proportions of patients with flank recurrence were 0 of 513 = 0.0% for 20 Gy, 12 of 805 = 1.5% for 10 Gy, and 44 of 2,388 = 1.8% for no flank RT (p trend = 0.001 adjusted for stage and doxorubicin); for intra-abdominal (including flank) recurrence they were 5 of 513 = 1.0%, 30 of 805 = 3.7%, and 58 of 2,388 = 2.4%, respectively (p trend = 0.02 adjusted). Survival percentages at 8 years after intra-abdominal recurrence were 0 of 5 = 0% for 20 Gy, 10 of 30 = 33% for 10 Gy, and 34 of 58 = 56% for no RT (p trend = 0.0001). NWTS-4 discontinued use of 20 Gy RT, and the 8-year flank recurrence risk increased to 2.1% from 1.0% on NWTS-3 (p = 0.013). However, event-free survival was unaltered (88% vs. 86%, p = 0.39), and overall survival was better (93.8% vs. 90.8%, p = 0.036) on NWTS-4. CONCLUSIONS: Partly because of lower postrecurrence mortality among nonirradiated patients, prevention of flank recurrence by RT did not improve survival. It is important to evaluate entire treatment policies with regard to long-term outcomes.     

Neurofibromatosis 2 leads to higher incidence of strabismological and neuro‐ophthalmological disorders

Purpose: Ophthalmic features of neurofibromatosis 2 (NF2) include juvenile cataract, retinal hamartomas and tumours of the cranial nerves. We hypothesize that these tumours lead to strabismological and neuro‐ophthalmological symptoms, including palsies of cranial nerves III, IV and VI, nystagmus and gaze palsies. Methods: We carried out a retrospective review of 73 patients with known genotype. They underwent ophthalmic, neuro‐ophthalmological and strabismological examination. Statistical analysis was performed by calculating odds ratios and their 95% confidence intervals. Results: Mean best corrected visual acuity was 0.85. Strabismus was found in 38 of 73 patients (52%). A deviation based on a cranial nerve palsy was found in 16 patients (22%) and three had supranuclear palsies. Eleven of 73 patients had a nystagmus, mostly caused by peripheral–vestibular disturbance. Binocular single vision was normal in 41 (58%), subnormal in six (8%) and not present in 24 (34%) patients. The average refractive error was ? 0.57 D. Myopia of ≥ 0.5 D was present in 47 (33%) eyes and hyperopia of ≥ 2.0 D was measured in 11 (8%) eyes. In the subgroup analysis of NF2 mutation types, the relative risk for cranial nerve palsies and negative stereopsis was statistically significantly increased for the nonsense mutation group. The mosaicism group had a statistically significant decreased relative risk for concomitant squint, as did patients with unfound mutations for strabismus and poor stereopsis. Conclusions: The present study is, to our knowledge, the first to examine a larger collection of NF2 patients for strabismological and neuro‐ophthalmological lesions. Compared with the normal population, our sample showed a higher amount of strabismus, refractive errors and an increased incidence of vestibular nystagmus.