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Ohne Zusammenfassung     

Beyond tremor and rigidity: non-motor features of Parkinson’s disease

Parkinson’s disease (PD) is the second most common neurodegenerative disease and primarily considered as a movement disorder defined by the presence of motor symptoms, such as bradykinesia, tremor and rigidity. However, it is nowadays widely accepted that PD is associated with a wide variety of non-motor features, which affect the vast majority of patients during the course of the disease and may even precede the onset of motor symptoms. The spectrum of these non-motor disturbances is very broad and comprises neuropsychiatric conditions, such as depression, dementia and hallucinations, as well as autonomic, sensory and sleep disorders. Physicians need to be aware of these non-motor features, since they have substantial impact on the health-related quality of life of PD patients, even ahead of motor symptoms. This article aims to provide an overview of frequently observed non-motor features in PD and discusses prospects and limitations of currently available options for symptomatic treatment of these disturbances.     

Levodopa-induced striatal activation in Parkinson's disease: A functional MRI study

ObjectiveTo assess the effect of a single levodopa dose (200 mg levodopa, 50 mg carbidopa = sdLD) on cortical and subcortical motor-circuit activation during bimanual grip force in patients with Parkinson's disease (PD).Patients and methodsWe studied 12 right-handed patients with PD (Hoehn–Yahr stages I–II) after a period of at least 12 h without medication (OFF state) and a second time 1 h after oral administration of sdLD (ON state) using functional magnetic resonance imaging (fMRI). Blood-oxygenation-level-dependency (BOLD) fMRI was measured while participants underwent two unilateral and two bimanual grip force movements with a defined movement amplitude and force (10 N) in a block design. 12 age matched healthy subjects were studied as controls (without administration of sdLD).ResultsBimanual grip force tasks activated a specific pattern of cortical and subcortical structures in all patients during the OFF state and after levodopa administration with statistically significant differences in putamen and thalamus comparing the OFF and ON condition. In contrast, no such significant changes were observed in cortical structures. Between-group analysis revealed higher putaminal activity in controls compared to OFF state in bimanual tasks, while these differences disappeared after administration of levodopa.ConclusionsOur results indicate that the putamen and thalamus are the regions within the cortico-subcortical motor-circuit with most prominent response to levodopa. In our study, cortical motor areas did not respond to levodopa as one could have expected from previous studies. These findings contribute to the increasing evidence that an extended model of the underlying pathophysiology of motor dysfunctions in PD is warranted.     

Almost a tragedy: severe methotrexate toxicity in a hemodialysis patient treated for ectopic pregnancy

Background

Methotrexate (MTX), an antimetabolite of folic acid, is the drug of choice for the nonsurgical management of ectopic pregnancy. MTX-related toxicity may include leukopenia, thrombocytopenia, pancytopenia, nausea, vomiting, stomatitis, mucositis, and liver and lung toxicity, depending primarily on the dosage of the drug and patients' renal function. Currently, the use of MTX in hemodialysis patients, even at a low dosage, is controversial, and no clear-cut guidelines are available.

Case report

We report here a rare case of a life-threatening complication characterized by severe pancytopenia and skin and mucosal injury, which developed in a young patient on hemodialysis after oral treatment with MTX for ectopic pregnancy.

Conclusion

We conclude that even low-dose MTX administration is not to be used in patients with renal insufficiency, and when no other therapeutic options are available we suggest taking several clinical measures to prevent or treat myelosuppression.     

The relevance of analogue studies for understanding obsessions and compulsions

Analogue samples are often used to study obsessive–compulsive (OC) symptoms and related phenomena. This approach is based on the hypothesis that results derived from such samples are relevant to understanding OC symptoms in individuals with a diagnosis of obsessive–compulsive disorder (OCD). Two decades ago, Gibbs (1996) reviewed the available literature and found initial support for this hypothesis. Since then there have been many important advances addressing this issue. The purpose of the present review was to synthesize various lines of research examining the assumptions of using analogue samples to draw inferences about people with OCD. We reviewed research on the prevalence of OC symptoms in non-clinical populations, the dimensional (vs. categorical) nature of these symptoms, phenomenology, etiology, and studies on developmental and maintenance factors in clinical and analogue samples. We also considered the relevance of analogue samples in OCD treatment research. The available evidence suggests research with analogue samples is highly relevant for understanding OC symptoms. Guidelines for the appropriate use of analogue designs and samples are suggested.     

Effectiveness of Cognitive Behavioral Therapy for Individuals with Autism Spectrum Disorders and Comorbid Obsessive-Compulsive Disorder: A Review of the Research

Autism spectrum disorders (ASD) and obsessive-compulsive disorder (OCD) are highly comorbid, precipitating an urgent need to identify evidence-based practices that might be used to address this comorbidity exclusively. The aim of this study was to conduct a review of intervention research and clinical reports to examine the use of cognitive behavioral therapy (CBT) with individuals who have comorbid ASD and OCD. Based on the pre-determined review inclusion criteria, 11 studies were included in the review: three randomized control trials (RCT), one case controlled study, two single subject experimental designs, and five case studies. These studies offer promising data on the use of CBT interventions for individuals with ASD and comorbid OCD as well as for individuals with OCD and comorbid ASD when standard CBT protocol is enhanced with modifications such as parental involvement, increased use of visuals, personalized treatment metaphors, self-monitoring, positive reinforcement, and use of clear language and instructions. Limitations and implications for future research and practice are discussed.     

Proliferation of human malignant hematopoietic cells in immunodeficient mice: suppression by antibody to pluripotent K-562 leukemia cells involves direct cytolysis and effector cells

Six human hematopoetic cell lines were successfully heterotransplanted into athymic (nude) and asplenic-athymic (lasat) neonatal mice. The tumors arising from leukemia and lymphoma cells could then be serially transplanted into adult nude mice. Seven days after the fourth serial mouse passage, each mouse was treated with goat immune gamma globulin against K-562 cells. One control group was treated similarly, but with nonimmune (normal) gamma globulin, while another control group was not treated. The goat gamma globulin was not toxic for nude and lasat mice, and the immune, but not the normal, gamma globulin suppressed local subcutaneous growth of myelosarcomas, lymphosarcomas, and Burkitt lymphoma cells. On the other hand, the growth of lung, breast, and prostatic carcinomas and a melanoma of human origin were not altered by the immune gamma globulin. Since suppression of cell growth occurred equally well in decomplemented mice, a complement-mediated cytotoxicity apparently cannot be considered as responsible for the abrogation. The Fab fragment of the immunoglobulin did not suppress the growth of the myelosarcomas. We conclude that antibody suppression of the in vivo proliferation was specific for malignant hematopoietic cells and that the Fc portion of IgG is necessary for in vivo cytolysis of leukemia cells. The most probable mechanisms are direct antibody cytolysis and antibody-dependent macrophage-mediated cytotoxicity.     

Loss to follow-up among youth accessing outpatient HIV care and treatment services in Kisumu,Kenya

Youth are particularly vulnerable to acquiring HIV, yet reaching them with HIV prevention interventions and engaging and retaining those infected in care and treatment remains a challenge. We sought to determine the incidence rate of loss to follow-up (LTFU) and explore socio-demographic and clinical characteristics associated with LTFU among HIV-positive youth aged 15–21 years accessing outpatient care and treatment clinics in Kisumu, Kenya. Between July 2007 and September 2010, youth were enrolled into two different HIV care and treatment clinics, one youth specific and the other family oriented. An individual was defined as LTFU when absent from the HIV treatment clinic for ≥?4 months regardless of their antiretroviral treatment status. The incidence rate of LTFU was calculated and Cox regression analysis used to identify factors associated with LTFU. A total of 924 youth (79% female) were enrolled, with a median age of 20 years (IQR 18–21). Over half, (529 (57%)), were documented as LTFU, of whom 139 (26%) were LTFU immediately after enrolment. The overall incidence rate of LTFU was 52.9 per 100 person-years (p-y). Factors associated with LTFU were pregnancy during the study period (crude HR 0.68, 95% CI 0.53–0.89); CD4 cell count >350 (adjusted hazard ratios (AHR) 0.59, 95% CI 0.39–0.90); not being on antiretroviral therapy (AHR 4.0, 95% CI 2.70–5.88); and non-disclosure of HIV infection status (AHR 1.43, 95% CI 1.10–1.89). The clinic of enrolment, age, marital status, employment status, WHO clinical disease stage and education level were not associated with LTFU. Interventions to identify and enrol youth into care earlier, support disclosure, and initiate ART earlier may improve retention of youth and need further investigation. Further research is also needed to explore the reasons for LTFU from care among HIV-infected youth and the true outcomes of these patients.     

Expression of pertussis toxin adenosine diphosphate-ribosyltransferase in a T-cell hybridoma reduces metastatic capacity

T-cell hybridomas are highly metastatic, and their in vitro invasiveness correlates with metastatic capacity. Invasion is blocked by pertussis toxin (PT), which adenosine diphosphate (ADP)-ribosylates G1-proteins, and we have provided evidence that the PT-sensitive signal stimulates leukocyte function-associated antigen-1 (LFA-1)-mediated adhesion required for invasion. PT pretreatment of TAM2D2 T-cell hybridoma cells reduced metastasis, but only to a limited extent. In the present study, we have transfected the cDNA of the PT ADP- ribosyltransferase S1 subunit into TAM2D2 cells to abrogate G1-protein function permanently. We report here a substantial reduction in the metastatic capacity of two transfectants, S05 and S09, in which 88% and 95% of the G1-proteins was ADP-ribosylated. Two-thirds of the mice injected with S09 cells were tumor-free. Metastasis to the liver was almost completely prevented and less metastases were formed in the spleen and kidneys. Metastasis formation by S05 cells in liver and spleen was much reduced, but in lymph nodes and peritoneal tissues, metastases occurred with a frequency similar to that of controls. We conclude that G1-proteins play an important role in T-cell hybridoma metastasis. We propose that the reduction in metastasis is due to diminished entry of tumor cells from the blood into tissues.