Comparison of clinical efficacy and toxicity of conventional and optimum biological response modifying doses of interferon alpha-2C in the treatment of hairy cell leukemia: a retrospective analysis of 39 patients

Hairy cell leukemia (HCL) has been shown to be extraordinarily sensitive to treatment with alpha-interferon (IFN). In order to define clinically effective IFN doses associated with minimal toxicity, the therapeutic efficacy and side effects of recombinant IFN-alpha-2C treatment of HCL were compared for two different dose regimens: 18 patients (group A) received conventional doses of recombinant IFN-alpha-2C (2 x 10(6)U/m2) for a median time of 35 weeks (range 26-52 weeks), and 21 patients (group B) received optimum biological response-modifying doses of IFN-alpha-2C (0.2-0.6 x 10(6)U/m2) for a median time of 31 weeks (range 12-52 weeks). Interferon was administered daily subcutaneously for 3 months and then every second or third day. Induction of neopterin excretion was chosen as the marker for definition of biological response. The smallest IFN dose causing maximum in vivo induction of biosynthesis of the GTP-degradation product neopterin was deemed "biologically optimal." Both dose regimens were effective, but the low-dose regimen was almost free of toxicity. Thus, in HCL patients alpha-IFN related toxicity can be separated from its antineoplastic activity. Low doses of alpha-IFN should be considered for treatment of HCL patients who develop toxic side effects and for primary treatment of HCL patients with severe cytopenia.     

Increase of regulatory T cells in the peripheral blood of cancer patients.

PURPOSE: T cells constitutively expressing both CD4 and CD25are essential for maintenance of self-tolerance and therefore have been referred to as regulatory T cells (Treg). Experimental tumor models in mice revealed that Tregs are potent inhibitors of an antitumor immune response. The current study was designed to determine whether cancer patients exhibit an expanded Treg pool. EXPERIMENTAL DESIGN: The frequency of Tregs in the peripheral blood of 42 patients suffering from epithelial malignancies and from 34 healthy controls was determined by flow cytometry. The immunoregulatory properties of CD4(+)CD25(+) and CD4(+)CD25(-) T cells were characterized by proliferation and suppression assays. Cocultures with natural killer (NK) cells were performed to determine the impact of Tregs on NK-mediated cytotoxicity. RESULTS: Patients with epithelial malignancies show an increase of CD4(+)CD25(+) T cells in the peripheral blood with characteristics of Tregs, i.e., they are CD45RA(-), CTLA-4(+), and transforming growth factor beta(+). Notably, CD4(+) T cells from cancer patients are characterized by an impaired proliferative capacity, which is restored to the extend of CD25-depleted CD4(+) T cells from control persons by prior removal of CD25(+) T cells. In contrast to CD4(+)CD25(-) T cells, isolated CD4(+)CD25(+) T cells from cancer patients were anergic towards T cell receptor stimulation. In addition, CD4(+)CD25(+) T cells suppressed the proliferation of CD4(+)CD25(-) T cells. When cultured together with CD56(+) NK-cells, CD4(+)CD25(+) T cells from cancer patients effectively inhibited NK-cell-mediated cytotoxicity. CONCLUSIONS: Thus, we provide evidence of an increased pool of CD4(+)CD25(+) regulatory T cells in the peripheral blood of cancer patients with potent immunosuppressive features. These findings should be considered for the design of immunomodulatory therapies such as dendritic cell vaccination.     

Impulsiveness in borderline personality disorder predicts the long-term outcome of a psychodynamic treatment programme

Despite the preponderance of treatment outcome predictors in patients with borderline personality disorder (BPD), the predictive value of measures of impulsiveness is inconclusive. This naturalistic study consecutively included hospitalized patients with BPD (N = 99) who underwent a standardized and structured 12-week inpatient treatment programme, which integrated cognitive-behavioural and psychodynamic elements. The Brief Symptom Checklist (BSCL) was applied as outcome measure over four time points: pretreatment, posttreatment, first follow-up at 6 to 8 weeks and second follow-up at 1 year after discharge. Impulsiveness was measured using the Barratt Impulsiveness Scale (BIS) at the pretreatment time point. The BSCL significantly decreased between pretreatment and posttreatment, followed by an increase after posttreatment without reaching pretreatment extent. The temporal course of the BSCL significantly varied with pretreatment BIS in that patients with higher impulsiveness revealed a stronger re-increase of symptom severity from posttreatment to end of follow-up than those with lower impulsiveness. The least impulsive patients thereby showed no rebound effect. The robustness of the results was examined by cross-validation. The results indicate that irrespective of the level of impulsiveness, patients with BPD profit from a structured inpatient treatment. However, long-term treatment success was impaired in patients with high level of impulsiveness at pretreatment. Thus, self-ratings of impulsiveness in BPD patients can be utilized for treatment planning. After discontinuation of interventions, relapse prevention should be implemented early in high impulsive patients as symptoms recrudesce in the course after discharge.     

Structured reporting in petrous bone MRI examinations: impact on report completeness and quality

Purpose

To investigate whether structured reports (SRs) provide benefits regarding the completeness and the clarity of reports, as well as regarding the satisfaction of the referring physicians compared to narrative freetext reports (NRs) of MRI examinations of the petrous bone.

Methods

After sample size calculation, 32 patients with clinically indicated MRI examinations of the petrous bone were included in this retrospective study. The already existing NRs were taken from the radiologic information system. The corresponding SRs were retrospectively generated by two radiologists using an online-based application. All 64 reports (one NR and one SR per patient) were evaluated by two head and neck physicians using a questionnaire.

Results

While 41% of the SRs showed no missing report key feature, all NRs exhibited at least one missing key feature (p?<?0.001). SRs achieved significantly higher satisfaction rates regarding the linguistic quality and overall report quality compared to NRs: Using a 6-point Likert scale (1?=?insufficient to 6?=?excellent), SRs were rated with a median value of 6 [interquartile range (IQR): 1] for linguistic as well as overall quality, and NRs were rated with a median of 5 (IQR: 0) for linguistic as well as overall quality (p?<?0.001).

Conclusions

Structured reporting of petrous bone MRI examinations may positively influence the completeness and quality of radiologic reports. Due to the easier readability and facilitation of information extraction, SRs improve the satisfaction level of the referring physicians.

     

Rapid and Reliable Identification of Staphylococcus aureus Capsular Serotypes by Means of Artificial Neural Network-Assisted Fourier Transform Infrared Spectroscopy

Staphylococcus aureus capsular polysaccharides (CP) are important virulence factors and represent putative targets for vaccine development. Therefore, the purpose of this study was to develop a high-throughput method to identify and discriminate the clinically important S. aureus capsular serotypes 5, 8, and NT (nontypeable). A comprehensive set of clinical isolates derived from different origins and control strains, representative for each serotype, were used to establish a CP typing system based on Fourier transform infrared (FTIR) spectroscopy and chemometric techniques. By combining FTIR spectroscopy with artificial neuronal network (ANN) analysis, a system was successfully established, allowing a rapid identification and discrimination of all three serotypes. The overall accuracy of the ANN-assisted FTIR spectroscopy CP typing system was 96.7% for the internal validation and 98.2% for the external validation. One isolate in the internal validation and one isolate in the external validation failed in the classification procedure, but none of the isolates was incorrectly classified. The present study demonstrates that ANN-assisted FTIR spectroscopy allows a rapid and reliable discrimination of S. aureus capsular serotypes. It is suitable for diagnostic as well as large-scale epidemiologic surveillance of S. aureus capsule expression and provides useful information with respect to chronicity of infection.     

Negative parenting behaviour as a mediator of the effects of telephone-assisted self-help for parents of pharmacologically treated children with attention-deficit/hyperactivity disorder

A previous randomised controlled trial demonstrated the effects of a telephone-assisted self-help (TASH) intervention for parents of pharmacologically treated children with attention-deficit/hyperactivity disorder (ADHD) on ADHD symptoms, oppositional symptoms, functional impairment, and negative parenting behaviour (per-protocol analyses). In the current study, we examined whether changes in positive and negative parenting behaviour mediated the effects on symptoms and impairment. Parents in an enhancement group (n = 51) participated in a 12-month TASH intervention (eight booklets plus up to 14 telephone consultations) as an adjunct to routine clinical care, whereas parents in a waitlist control group (n = 52) received routine clinical care only. Parents completed measures of child symptoms, child functional impairment, and parenting behaviour at baseline, at 6 months, and at 12 months. The mediating effects of parenting behaviour were examined using regression analyses. Per-protocol analyses (n = 74) revealed a significant indirect intervention effect on functional impairment through negative parenting behaviour at 6 months as well as indirect intervention effects on oppositional symptoms and functional impairment through negative parenting behaviour at 12 months. The indirect effect on ADHD symptoms through negative parenting behaviour at 12 months just failed to reach significance. The analyses yielded no indirect intervention effects through positive parenting behaviour. The study provides some, albeit limited, support for the importance of changes in negative parenting behaviour to achieve changes in symptoms and functional impairment during parent training. In consideration of the inconsistent results of previous studies concerning the mediating role of positive and negative parenting behaviour, further research is required to better understand the mechanisms of change during parent training, also including other possible mediators like parenting stress and parental self-efficacy.