Efficacy and safety of intratumoral thermotherapy using magnetic iron-oxide nanoparticles combined with external beam radiotherapy on patients with recurrent glioblastoma multiforme.

Therapy options at the time of recurrence of glioblastoma multiforme are often limited. We investigated whether treatment with a new intratumoral thermotherapy procedure using magnetic nanoparticles improves survival outcome. In a single-arm study in two centers, 66 patients (59 with recurrent glioblastoma) received neuronavigationally controlled intratumoral instillation of an aqueous dispersion of iron-oxide (magnetite) nanoparticles and subsequent heating of the particles in an alternating magnetic field. Treatment was combined with fractionated stereotactic radiotherapy. A median dose of 30 Gy using a fractionation of 5 × 2 Gy/week was applied. The primary study endpoint was overall survival following diagnosis of first tumor recurrence (OS-2), while the secondary endpoint was overall survival after primary tumor diagnosis (OS-1). Survival times were calculated using the Kaplan-Meier method. Analyses were by intention to treat. The median overall survival from diagnosis of the first tumor recurrence among the 59 patients with recurrent glioblastoma was 13.4 months (95% CI: 10.6-16.2 months). Median OS-1 was 23.2 months while the median time interval between primary diagnosis and first tumor recurrence was 8.0 months. Only tumor volume at study entry was significantly correlated with ensuing survival (P < 0.01). No other variables predicting longer survival could be determined. The side effects of the new therapeutic approach were moderate, and no serious complications were observed. Thermotherapy using magnetic nanoparticles in conjunction with a reduced radiation dose is safe and effective and leads to longer OS-2 compared to conventional therapies in the treatment of recurrent glioblastoma.

High-frequency stimulation of the nucleus accumbens core and shell reduces quinpirole-induced compulsive checking in rats.

Electrical deep brain stimulation (DBS) is currently studied in the treatment of therapy-refractory obsessive compulsive disorders (OCDs). The variety of targeted brain areas and the inconsistency in demonstrating anti-compulsive effects, however, highlight the need for better mapping of brain regions in which stimulation may produce beneficial effects in OCD. Such a goal may be advanced by the assessment of DBS in appropriate animal models of OCD. Currently available data on DBS of the nucleus accumbens (NAc) on OCD-like behavior in rat models of OCD are contradictory and partly in contrast to clinical data and theoretical hypotheses about how the NAc might be pathophysiologically involved in the manifestation of OCD. Consequently, the present study investigates the effects of DBS of the NAc core and shell in a quinpirole rat model of OCD. The study demonstrates that electrical modulation of NAc core and shell activity via DBS reduces quinpirole-induced compulsive checking behavior in rats. We therefore conclude that both, the NAc core and shell constitute potential target structures in the treatment of OCD.

Factors predicting the time until atrial fibrillation recurrence after concomitant left atrial ablation.

OBJECTIVE: Treatment of atrial fibrillation, a risk factor for morbidity and mortality, by left atrial ablation is a less complex procedure which is increasingly performed in conjunction with surgery for various heart diseases. Although restoration of sinus rhythm is effective initially, atrial fibrillation may recur. We investigated factors predicting the time until its recurrence. METHODS: Between January 2003 and December 2005, 162 consecutive patients (52.5% male, age 69+/-8.7 years) with permanent atrial fibrillation underwent concomitant left atrial ablation and isolated or combined mitral valve surgery (42.6%), isolated or combined aortic valve surgery (32.1%), and isolated or combined coronary artery bypass grafting (24.1%). Ablation was performed by microwave (n=93, 57.4%) or radiofrequency (n=69, 42.6%) technology. Follow-up was after 3, 6, 12 months and yearly thereafter. Predictive values of variables for postoperative atrial fibrillation were examined using techniques of univariate and multivariate survival analysis (proportional hazards regression). RESULTS: Eight patients died perioperatively and 13 during follow-up (not ablation related). Two patients were lost to follow-up. At last follow-up (19+/-11.3 months), 86 patients (62%) were in stable sinus rhythm, 73 (52%) without antiarrhythmic drugs, and 43 (31%) were in atrial fibrillation. Predictors for the time until recurrence of atrial fibrillation in a multivariate model were preoperative atrial fibrillation duration (hazard ratio 1.005, 95% confidence interval 1.003-1.007, p<0.001) and left atrial diameter (hazard ratio 1.056, 95% confidence interval 1.020-1.093, p=0.002). Overall, sinus rhythm conversion rate was 75% when preoperative atrial fibrillation duration was less than 2 years, but 42% in longer lasting atrial fibrillation with left atrial dilatation (>50mm). Age, gender, primary heart disease, history of thromboembolism or cardioversion, presence of concomitant diseases, EuroScore, left ventricular size and function, aortic cross-clamp time, ablation technology, and treatment with antiarrhythmic drugs did not predict rhythm outcome. CONCLUSIONS: Preoperative atrial fibrillation duration and left atrial diameter predict the time until atrial fibrillation recurrence after concomitant left atrial ablation, whereas age, type of primary cardiac surgery, ablation technology and antiarrhythmic therapy do not.

Bispectral index versus COMFORT score to determine the level of sedation in paediatric intensive care unit patients: a prospective study.

INTRODUCTION: Most clinicians give sedatives and analgesics according to their professional experience and the patient's estimated need for sedation. However, this approach is prone to error. Inadequate monitoring of sedation and analgesia may contribute to adverse outcomes and complications. With this in mind, data obtained continuously using nonstimulating methods such as bispectral index (BIS) may have benefits in comparison with clinical monitoring of sedation. The aim of this prospective observational trial was to evaluate the use of electroencephalographic (EEG) BIS for monitoring sedation in paediatric intensive care unit (PICU) patients. METHODS: Forty paediatric patients (<18 years) were sedated for mechanical ventilation in a cardiac surgical and general PICU. In each paediatric patient BIS and COMFORT score were obtained. The study protocol did not influence ongoing PICU therapy. BIS and corresponding COMFORT score were collected three times for each patient. Measurements with the best starting EEG impedances were analyzed further. Deep sedation was defined as a COMFORT score between 8 and 16, and light sedation as a score between 17 and 26. Biometric and physiological data, and Pediatric Risk of Mortality III scores were also recorded. RESULTS: There was a good correlation (Spearman's rho 0.651; P = 0.001) between BIS and COMFORT score in the presence of deep sedation and low starting impedance. Receiver operating characteristic (ROC) analysis revealed best discrimination between deep and light sedation at a BIS level of 83. CONCLUSION: In the presence of deep sedation, BIS correlated satisfactorily with COMFORT score results if low EEG impedances were guaranteed.

Prevalence, severity, and severity risk factors of acne in high school pupils: a community-based study.

A cross-sectional, community-based study was performed to determine the prevalence and severity of acne vulgaris in adolescents and of factors influencing the acne severity risk. The presence of acne was clinically determined and the secondary outcome measures of family acne history and the relation of acne to nutrition habits, emotional stress, menstruation, and smoking were recorded in a questionnaire. A representative sample of 1,002 pupils aged 16+/-0.9 years was enrolled. The overall acne prevalence was 93.3, 94.4% for boys and 92.0% for girls. Moderate to severe acne was observed in 14%. The prevalence of moderate to severe acne was 19.9% in pupils with and 9.8% in those without a family history of acne (P<0.0005; OR: 2.3). Acne severity risk increased with the number of family members with acne history. A mother with acne history influenced the severity of acne the most. Increasing pubertal age, seborrhea, the premenstrual phase, mental stress, and sweet and oily foods were recognized as risk factors for moderate to severe acne. In contrast, gender, spicy foods, and smoking were not associated with acne severity. In conclusion, acne is a common disorder in Iranian adolescents, with a low rate of moderate to severe acne. A genetic background is suggested, with mother's acne history being the most important prognostic factor. Skin quality and certain nutrition habits may affect acne severity.

Comparison between logopedic and MRI findings in evaluating tongue function.

INTRODUCTION AND AIM: The logopedic examination according to Kittel (1998) is a method frequently used to diagnose tongue dysfunction. There has been a lack of reliable parameters to confirm this analysis. MR images visualize resting position and tongue movement as well as surrounding structures relevant to oral function. The aim of this study was to compare logopedic and MRI findings in evaluating tongue function and to assess whether MRI findings can replace logopedic examination for diagnostic purposes. MATERIAL AND METHODS: 56 subjects were examined by the following methods: - Logopedic examination according to Kittel (1998) - MR images of the tongue resting position (T1-weighted) and deglutition process (2D-FIESTA technique) - MRI analysis according to Fujiki et al. (2000) RESULTS: We observed marked differences between the logopedic and MRI findings, yet there were no significant correlations between the logopedic outcome and distances measured via MRI in tongue resting position and swallowing patterns. CONCLUSION: We noted little concordance between logopedic findings according to Kittel and MRI analysis according to Fujiki et al. Which of these findings correctly reflects the actual clinical situation remains unclear.

Validity and reliability of logopedic assessments of tongue function.

OBJECTIVE: This study investigated the validity and reliability of logopedic assessments of tongue function. MATERIALS AND METHODS: At two practices for myofunctional therapy, diagnosis of tongue dysfunction according to Kittel (1984, 1996, 2008) was carried out in 52 subjects (aged 5 to 63 years) by three speech pathologists at each practice. RESULTS: The agreement of the logopedic assessments was mostly satisfactory at one of the two practices but was unsatisfactory in most cases at the other practice. CONCLUSION: The inconsistent agreement between the logopedic assessments does not permit a definitive statement about the actual clinical situation.

Yttrium-90 ibritumomab tiuxetan radioimmunotherapy in primary cutaneous B-cell lymphomas: first results of a prospective, monocentre study.

Radioimmunotherapy with Yttrium-90 ((90)Y) ibritumomab tiuxetan (IT) has been shown to be effective in systemic B-cell lymphomas. We conducted a pilot study to evaluate the outcome and assess complications of (90)Y IT therapy in patients with primary cutaneous B-cell lymphomas (PCBCL). Ten patients, all but one, with relapsed PCBCL were included and treated with rituximab (250 mg m(-2)/body surface) on days 1 and 8 followed by a single dose of (90)Y IT (11-15 MBq kg(-1)). The overall response rate was 100%. The complete response rate was 100%. The median time to relapse was 12 months. Ongoing remissions were achieved in four patients (median follow-up 19 months). Transient and reversible myelosuppression (grade 3-4) was the most frequent adverse event. Radioimmunotherapy with (90)Y IT is an effective treatment in relapsed primary cutaneous follicle centre lymphomas and diffuse large B-cell lymphoma leg-type. Further investigations in controlled randomised clinical trials evaluating the role of (90)Y IT versus rituximab in PCBCL are needed.

Nicotine and biochanin A, but not cigarette smoke, induce anti-inflammatory effects on keratinocytes and endothelial cells in patients with Behçet's disease.

During periods of smoking, patients with Behçet's disease have less oral aphthae than in abstinence. To elucidate this observation, human keratinocytes and dermal microvascular endothelial cells (HMEC-1) were incubated with serum of 20 patients with Behçet's disease and 20 healthy controls for 4 hours. Maximum non-toxic concentrations were determined and the cells were further treated with 6 microM nicotine, 3.3% cigarette smoke extract (CES), 100 microM biochanin A, and 6.25/12.5 microM pyrrolidine dithiocarbamate alone and in combinations for 24 hours. Serum IL-8 levels of patients were significantly lower than those of controls. However, after 4 hours incubation with patients' sera, IL-8 release by both cell types was markedly increased when compared with the corresponding serum levels. The levels of IL-6 and vascular endothelial growth factor (VEGF) release were after 4 hours similar with the corresponding levels in serum. IL-1 was not detected. Nicotine significantly decreased IL-8 and -6 release by HMEC-1 maintained in both patients' and controls' sera, but only IL-6 release by keratinocytes maintained in patients' sera. VEGF release by both cells was markedly increased after nicotine treatment in either serum. CES significantly decreased IL-8 release and increased production of VEGF in keratinocytes maintained in patients' serum. The phytoestrogen biochanin A alone and in combination with nicotine further decreased the secretion of IL-8, -6, and VEGF in all experimental settings. Our data support a specific anti-inflammatory effect of nicotine on keratinocytes and endothelial cells maintained in the serum of patients with Behçet's disease. Moreover, biochanin A is likely to exhibit similar and even more profound results than nicotine.

High frequency of multidrug-resistant Mycobacterium tuberculosis isolates in Georgetown, Guyana.

Emergence of multidrug-resistant (MDR) Mycobacterium tuberculosis isolates constitutes a threat to public health worldwide. This study aimed at acquiring first epidemiological data for Guyana. Thirty-six M. tuberculosis isolates from patients of the Georgetown Chest Clinic were subjected to susceptibility testing on solid agar and in broth media. Resistance to at least one first-line drug was observed in 8 (22.2%, 95% confidence interval 8.3-36.1%) and simultaneous resistance to rifampicin and isoniazid (MDR) in 4 (11.1%, 95% confidence interval 0.6-21.6%) of the 36 isolates. The risk of infection with resistant isolates was significantly related to earlier antituberculosis therapy (P=0.040). These data indicate a high proportion of resistant M. tuberculosis isolates in Guyana and call for the implementation of control strategies based on an improved laboratory diagnosis of TB.

Early TCR-beta and TCR-gamma PCR detection of T-cell clonality indicates minimal tumor disease in lymph nodes of cutaneous T-cell lymphoma: diagnostic and prognostic implications.

The lymph nodes are generally the first extracutaneous manifestation in patients with cutaneous T-cell lymphoma (CTCL); however, their early involvement is difficult to assess. The aim of our study was to define the diagnostic and prognostic value of T-cell clonality analysis for a more precise assessment of lymph node involvement in CTCL. T-cell clonality was determined by 2 independent polymerase chain reaction (PCR) assays, namely a recently developed T-cell receptor-beta (TCR-beta) PCR technique as well as an established TCR-gamma PCR. T-cell clonality was found in 22 of 22 lymph nodes with histologically detectable CTCL involvement as well as in 7 of 14 histologically noninvolved dermatopathic lymph nodes. The clonal T-cell populations in the lymph nodes were in all cases identical to those detected in the corresponding skin lesions, identifying them as the tumor cell population. T-cell clonality was not found in any of the 12 dermatopathic lymph nodes from 12 patients with inflammatory skin diseases. Clonal T-cell detection in 7 of 14 dermatopathic lymph nodes of patients with CTCL was associated with limited survival (74 months; confidence interval [CI], 66-82 months) as in patients with histologically confirmed lymph node involvement (41 months; CI, 35-47 months), whereas all patients without T-cell clonality in the lymph nodes (7 patients) were alive at the last follow-up. Thus, T-cell clonality analysis is an important adjunct in differentiating benign dermatopathic lymphadenitis from early CTCL involvement.

High frequency of multidrug-resistant Mycobacterium tuberculosis isolates in Georgetown, Guyana

Emergence of multi-drug resistance (MDR) Mycobacterium tuberculosis isolates constitutes a threat to public health worldwide. This study aimed at acquiring first epidemiological data for Guyana. Thirty-six M. tuberculosis isolates from patients of the Georgetown Chest Clinic were subjected to susceptibility testing on solid agar and in broth media. Resistance to at least one first-line drug was observed in 8 (22.2 percent, 95 percent confidence interval 8.3 -36.1 percent) and simultaneous resistance to rifampicin and isoniazid (MDR) in 4 (11.1 percent, 95 percent confidence interval 0.6-21.6 percent) of the 36 isolates. The risk of infection with resistant isolates was significantly related to earlier antituberculosis therapy (P=0.040). These data indicate a high proportion of resistant M.tuberculosis isolates in Guyana and call for the implementation of control strategies based on an improved laboratory diagnosis of TB(AU)