[Severe treatment-resistant tardive dystonia: is deep brain stimulation a treatment option]. / Ernstige, therapieresistente tardieve dyskinesie: is diepe hersenstimulatie een behandeloptie?

BACKGROUND: Severe tardive dyskinesia or dystonia (TD) are side-effects of dopamine-blocking agents, most of which are antipsychotics. A small subgroup of patients develop a severe debilitating treatment-resistant form of TD. AIM: To assess the effects and side-effects of deep brain stimulation (DBS) in this subgroup of TD patients. METHOD: We searched PubMed and Embase using the search terms 'tardive' and 'deep brain stimulation'. We found 19 articles containing data referring to 52 patients. Using the Burke Fahn Marsden Dystonia Rating Scale (BFMDRS), the Abnormal Involuntary Movement Scale (AIMS) and the Extrapyramidal Symptoms Rating Scale (ESRS) we calculated the average improvement in the patients' condition. RESULTS: On all the scales the improvement was statistically significant (p < 0.00001), the average improvement being 67% to 78%. In only 4% of the patients was there a deterioration in the psychiatric disorder. CONCLUSION: DBS seems to be an effective treatment for treatment-resistant TD and the side-effects seem to be limited. However, the evidence is limited because our conclusion is based on case-reports and on small-scale trials without randomisation or blinding.

Rabies control in rural Africa: evaluating strategies for effective domestic dog vaccination.

Effective vaccination campaigns need to reach a sufficient percentage of the population to eliminate disease and prevent future outbreaks, which for rabies is predicted to be 70%, at a cost that is economically and logistically sustainable. Domestic dog rabies has been increasing across most of sub-Saharan Africa indicating that dog vaccination programmes to date have been inadequate. We compare the effectiveness of a variety of dog vaccination strategies in terms of their cost and coverage in different community settings in rural Tanzania. Central-point (CP) vaccination was extremely effective in agro-pastoralist communities achieving a high coverage (>80%) at a low cost (US$5/dog) and inadequate (<20% coverage); combined approaches using CP and either house-to-house vaccination or trained community-based animal health workers were most effective with coverage exceeding 70%, although costs were still high (>US$6 and >US$4/dog, respectively). No single vaccination strategy is likely to be effective in all populations and therefore alternative approaches must be deployed under different settings. CP vaccination is cost-effective and efficient for the majority of dog populations in rural Tanzania and potentially elsewhere in sub-Saharan Africa, whereas a combination strategy is necessary in remote pastoralist communities. These results suggest that rabies control is logistically feasible across most of the developing world and that the annual costs of effective vaccination campaigns in Tanzania are likely to be affordable.

Trends in the postmortem epidemiology of invasive fungal infections at a university hospital.

BACKGROUND: Due to the lack of reliable diagnostic tools, clinical data on the significance of most invasive fungal infections are difficult to assess and information on frequency, disease pattern and prognostic impact still largely relies on autopsy data. METHODS AND RESULTS: To determine temporal trends in invasive fungal infections, we analyzed data from 8124 autopsies performed between 1978 and 1992 on patients who died at the University Hospital of Frankfurt/Main. During that period, a total of 278 invasive fungal infections were found. The prevalence rose from 2.2% (1978-82) and 3.2% (1983-87) to 5.1% in the most recent years (P < 0.001). Besides the emergence of mixed and unclassified infections, this was mainly due to a significant increase in Aspergillus infections (P < 0.001), whereas the prevalence of Candida infections was stable and even showed a declining trend within the last years. The highest infection rates were found in aplastic syndromes (68%), followed by AML (25%) and AIDS (19%). In the majority of cases (76%), invasive fungal infection was related to the immediate cause of death. However, the proportion of patients with endstage underlying conditions increased significantly over time from 53% to 80% (P < 0.001). Accordingly, the number of patients who were not considered terminally ill but had died from fungal infection dropped from 35% to 17% within the last years (P < 0.01). CONCLUSIONS: These observations document significant changes in frequency, aetiology and underlying disease processes in invasive fungal infections at autopsy and underscore the continuing need for more effective prevention, diagnosis, and treatment.

Studies on the binding of antibody against mouse lactate dehydrogenase (isoenzyme X) by preimplantation mouse embryos.

The binding of antibodies against LDH-X by preimplantation mouse embryos was studied to detect LDH-X from spermatozoa in embryos after fertilization. Incubation of preimplantation mouse embryos with rabbit anti-mouse-LDH-X-IgG and then with peroxidase-labelled goat anti-rabbit IgG revealed a strong peroxidase staining of the zona pellucida of normal fertilized and unfertilized 1-cell ova. However, the reaction was significantly weaker with both fertilized and unfertilized 1-cell ova from females induced to superovulate and normal and superovulated blastocysts. Pure antibody against mouse LDH-X was obtained by affinity chromatography of the rabbit anti-mouse LDH-X-IgG on pure mouse LDH-X covalently bound to sepharose. The pure antibody against mouse LDH-X reacted immunochemically identically to anti-mouse LDH-X-IgG, but it was not bound by any stage of preimplantation mouse embryos. The IgG fractions which had passed through the affinity column during the purification procedure and which did not contain any anti-LDH-X activity were bound by the zonae of preimplantation mouse embryos in the same manner as was unpurified anti-mouse LDH-X-IgG. Histochemical studies indicated LDH activity only in the embryo proper, but not on the zona pellucida. It is concluded that LDH-X is not present in preimplantation mouse embryos.

Rapid purification of lactate dehydrogenase X from mouse testes by two steps of affinity chromatography on oxamate-sepharose.

At concentrations of 200 muM NADH and 0.5 M NaCl LDH-X is separated from the other LDH isozymes of mouse testes on oxamate-sepharose. In a second step LDH-X is bound to the same matrix at lower NADH and NaCl concentrations and the pure enzyme can subsequently be eluted.

PIP: Results of a method of rapid purification of lactate dehydrogenase X (LDH-X) from mouse testes by 2 stepts of affinity chromatography on oxamate-sepharose at different sodium chloride (NaCl) and NADH concentrations are discussed. At concentrations of 200 mcM NADH and .5 M NaCl, LDH-X is separated from other LDH isoenzymes. The binding of LDH-X to the column is then carried out on the unbound fractions containing LDH-X and contaminating proteins after a 1:5 dilution. The resulting NADH and NaCl concentrations allow the binding of LDH-X. The specific activity of purified mouse LDH-X from testes was 120 IU/mg. The main advantage of this technique is the rapidity and ease of purification.