Naturally occurring radioactivity in some Swedish concretes and their constituents - Assessment by using I-index and dose-model.

The reference level for effective dose due to gamma radiation from building materials and construction products used for dwellings is set to 1 mSv per year (EC, 1996, 1999), (CE, 2014). Given the specific conditions presented by the EC in report 112 (1999) considering building and construction materials, an I-index of 1 may generate an effective dose of 1 mSv per year. This paper presents a comparison of the activity concentrations of (4)(0)K, (226)Ra and (232)Th of aggregates and when these aggregates constitute a part of concrete. The activity concentration assessment tool for building and construction materials, the I-index, introduced by the EC in 1996, is used in the comparison. A comparison of the I-indices values are also made with a recently presented dose model by Hoffman (2014), where density variations of the construction material and thickness of the construction walls within the building are considered. There was a ∼16-19% lower activity index in concretes than in the corresponding aggregates. The model by Hoffman further implies that the differences between the I-indices of aggregates and the concretes' final effective doses are even larger. The difference is due, mainly to a dilution effect of the added cement with low levels of natural radioisotopes, but also to a different and slightly higher subtracted background value (terrestrial value) used in the modeled calculation of the revised I-index by Hoffman (2014). Only very minimal contributions to the annual dose could be related to the water and additives used, due to their very low content of radionuclides reported.

The juvenile face as a suitable age indicator in child pornography cases: a pilot study on the reliability of automated and visual estimation approaches.

OBJECTIVE: In cases of suspected child pornography, the age of the victim represents a crucial factor for legal prosecution. The conventional methods for age estimation provide unreliable age estimates, particularly if teenage victims are concerned. In this pilot study, the potential of age estimation for screening purposes is explored for juvenile faces. In addition to a visual approach, an automated procedure is introduced, which has the ability to rapidly scan through large numbers of suspicious image data in order to trace juvenile faces. METHODS: Age estimations were performed by experts, non-experts and the Demonstrator of a developed software on frontal facial images of 50 females aged 10-19 years from Germany, Italy, and Lithuania. To test the accuracy, the mean absolute error (MAE) between the estimates and the real ages was calculated for each examiner and the Demonstrator. RESULTS: The Demonstrator achieved the lowest MAE (1.47 years) for the 50 test images. Decreased image quality had no significant impact on the performance and classification results. The experts delivered slightly less accurate MAE (1.63 years). Throughout the tested age range, both the manual and the automated approach led to reliable age estimates within the limits of natural biological variability. CONCLUSIONS: The visual analysis of the face produces reasonably accurate age estimates up to the age of 18 years, which is the legally relevant age threshold for victims in cases of pedo-pornography. This approach can be applied in conjunction with the conventional methods for a preliminary age estimation of juveniles depicted on images.

The N-methyl-D-aspartate antagonist memantine retards progression of Huntington's disease.

According to the excitotoxicity hypothesis, neurotoxicity due to glutamate is regarded as potential factor in the progredient neurodegeneration of Huntington's disease (HD). Memantine, as a glutamate receptor antagonist, should counteract this mechanism. Its effectiveness (up to 30 mg/day) with regard to retardation of progression was thus examined in 27 HD patients in a two year, open and multicentre trial. The results suggest that memantine treatment of HD may be useful in terms of retardation of the progression of the disorder.

[Psychopharmacotherapy of bipolar affective diseases]. / Psychopharmakotherapie bipolarer affektiver Erkrankungen.

The broadening of the classification systems for manic-depressive illness towards a spectrum of bipolar disorders implicates a more differentiated use of pharmacotherapies. However, many questions still remain open. This implies that all consensus guidelines and recommendations have to be considered as preliminary. On the other hand, research in the last decade has developed many new treatment alternatives, both for mood stabilizers and antidepressants as well as antipsychotics. These recommendations, which have been developed in the process of two consensus meetings, try to consider the broadening of the concept of bipolar disorder by differentiating between subgroups according to acute symptomatology and characteristics of the long-term course, e.g., rapid cycling. In particular, the emerging role and new indications of mood stabilizing antiepileptic drugs, atypical antipsychotics, and new antidepressants will be discussed.

Effectiveness of targeted intervention and maintenance pharmacotherapy in conjunction with family intervention in schizophrenia.

A sample of 85 patients with schizophrenia, of whom 34 later dropped out, received randomised treatment. There were no significant differences between treatment-takers and drop-outs in the variables assessed. Patients received either standard-dose maintenance neuroleptic treatment or targeted maintenance pharmacotherapy and all patients received behavioural family therapy. Measures of psychopathology, social adjustment, side-effects, family burden, and expressed emotion were assessed at baseline and then periodically over an 18-month period. The study was designed to compare the two alternative pharmacological maintenance approaches, each of them supported by psychosocial intervention. Any evaluation of the impact of behavioural family treatment on relapse rates and other outcome criteria is exclusively descriptive. A significantly higher rate of relapse was observed at 18 months in patients randomised to targeted treatment compared to those randomised to standard-dose treatment (35% vs 4%). Although patients assigned to the targeted maintenance group received significantly lower mean doses of neuroleptics, there were no significant differences between the two groups with regard to side-effects, global measures of social function, and overall psychopathology. Family burden was higher in the targeted-treatment group at six months, but did not differ at the one-year and eighteen-month time points. However, both groups improved significantly from baseline to 12 or 18 months in almost all variables assessed. Thus, the behavioural family approach did not compensate for the problems associated with the targeted medication strategy.

Recognition and management of acute neuroleptic-induced extrapyramidal motor and mental syndromes.

After nearly 50 years of therapeutic application of neuroleptics, diagnosis and classification of neuroleptic-induced extrapyramidal syndromes still concentrate on their "neurological" (motor) aspects. Psychiatric (mental) aspects are in general - if at all - regarded as "secondary" to motor symptoms. Psychiatric side effects of neuroleptics (including psychotic exacerbations during neuroleptic treatment) have, however, anecdotally been reported since 1954 but never developed into a systematic classification. Accordingly, psychiatric manifestations of extrapyramidal side effects frequently are overlooked, misdiagnosed as psychotic deteriorations and treated by increased dosing of neuroleptics instead anticholinergics, which in addition are falsely suspected of bearing a high addictive potential and the risk of development of tardive dyskinesia. It is suggested that neuroleptic-induced basal ganglia dysfunction results in motor as well as mental extrapyramidal side effects, whose recognition and management is essential to achieve better tolerability of and thereby compliance with neuroleptic treatment.

Abuse potential of anticholinergics.

Anticholinergics are widely used to treat extrapyramidal motor symptoms caused by neuroleptics or other drugs with antidopaminergic (dopamine D2) effects. In the medical literature, occasional reports are concerned with the abuse of centrally acting anticholinergic compounds. These drugs may be abused because of their stimulant effects, mostly by patients on neuroleptic treatment. Their supposed "euphoric" effect when too quickly parenterally administered (only after previous treatment with neuroleptics) seems to consist in the abolition of neuroleptic-induced anhedonia. In a few patients, excessive use of anticholinergics persists in the face of detrimental effects and is, therefore, properly termed "abuse". More commonly, however, patients with schizophrenia take more than the recommended dose of anticholinergics in an attempt to treat the adverse effects of neuroleptics. The abuse of anticholinergics in addicts who are not using neuroleptics is low.

A long-term, multicenter, open-label study of risperidone in elderly patients with psychosis. On behalf of the Risperidone Working Group.

RATIONALE: Studies have shown that risperidone is safe and efficacious in young and middle-aged adults with chronic schizophrenia, but considerably fewer data are available on the treatment of elderly patients with schizophrenia or other psychotic disorders, particularly long-term outcomes. OBJECTIVE: A 12-month, open-label study was conducted to assess the effects of risperidone in elderly, chronically ill, psychotic patients. METHODS: This study enrolled 180 elderly, chronically ill, psychotic patients (median age, 72 years [range 54-89]), 97 of whom completed the 12-month study. At endpoint, the mean dose of risperidone was 3.7 mg/day. RESULTS: Clinical improvement (> or =20% reduction in Positive and Negative Syndrome Score [PANSS] total score) was achieved by 54% of patients at endpoint. There were significant reductions in PANSS total, subscale (positive, negative, and general psychopathology), and cognition cluster scores at endpoint (p<0.001). Clinical Global Impressions severity of illness scores showed continued improvement through month 12 (p<0.001). In contrast, PANSS data from a historical comparable control group of patients receiving conventional antipsychotic agents showed no symptom improvement over a 12-month treatment period. The severity of preexisting extrapyramidal symptoms (EPS) in patients treated with risperidone decreased significantly from baseline to endpoint (p<0.001), and the use of antiparkinsonian medication decreased from 41.1% of patients before the trial to 25.6% during the trial. There were no spontaneous reports of tardive dyskinesia (TD) and the incidence of assessed TD was 4.3% in contrast to the expected 26% reported in middle-aged and elderly patients receiving conventional antipsychotic agents for 1 year. CONCLUSIONS: Long-term treatment with risperidone was associated with continued symptom improvement, a decrease in the severity of preexising EPS, and a low incidence of TD in elderly psychotic patients.

The benzamide tiapride: treatment of extrapyramidal motor and other clinical syndromes.

The benzamide derivative tiapride (Tiapridex, Synthelabo) has a highly selective antagonistic effect on striatal adenylate cyclase-independent dopamine-2 receptors. Its in vitro binding affinity is especially high for dopamine receptors which have been sensitized by pre-incubation with dopamine. The involvement of altered dopamine receptor sensitivity in several extrapyramidal dys- and hyperkinesia has been hypothesized. By its high affinity for these receptors, without any affinity for other neurotransmitter receptors of the brain, tiapride is especially well suited for the treatment of movement disorders related to functional dopamine hyperactivity. Even at higher doses, tiapride does not exceed a D2-receptor occupancy of 80%, which is in accordance with the finding that tiapride rarely causes acute extrapyramidal syndromes and has, up to now, never implicated in inducing tardive dyskinesias. On the contrary, clinical studies demonstrate its excellent efficacy in neuroleptic-induced tardive dyskinesia, L-Dopa-induced dyskinesias, psychomotor agitation in geriatric patients and choreatic movement disorders. Since tiapride is not available in the USA as yet, most of the studies concerning tiapride have been carried out in Europe. In a recent study, based on objective measurements, tiapride effectively controlled choreatic movements in patients suffering from Huntington's disease (HD). Tiapride is well tolerated in daily doses between 300 and 1200 mg. Adverse events are generally rare and mild.

Combined treatment of schizophrenic psychoses with haloperidol and valproate.

In accordance with a previous study of adjuvant effects of the anticonvulsant carbamazepine (CBZ) on the neuroleptic treatment of schizophrenic psychoses, the effects of valproate (VPA) were tested in a randomly assigned double-blind, placebo-controlled study. Apart from a (statistically nonsignificant) psychopathological deterioration following discontinuation of VPA while on continuous neuroleptic mediation after four weeks and a statistically significant effect on "hostile belligerence", no overall therapeutic effects of the combination of haloperidol (HPD) with VPA were observed under controlled conditions. Unlike the results with CBZ, concomitant use of VPA led to an even higher consumption of haloperidol and biperiden and to a higher rate of extrapyramidal symptoms compared with the corresponding placebo group, although these differences did not attain statistical significance. In regard to use of the sedative neuroleptic chlorprothixene, there was a trend toward lower doses in the VPA group than in the placebo group. From these results, adjuvant effects like those of carbamazepine in the neuroleptic treatment of schizophrenic psychoses could not be confirmed for valproate in the present study. However, the trend toward lower doses of sedative medication and observed effects on "hostile belligerence" may indicate sedative and/or antimanic properties of valproate which have recently been demonstrated in several controlled studies.

A conserved tryptophan at the ferredoxin-binding site of ferredoxin:nitrite oxidoreductase.

Treatment of spinach leaf ferredoxin-dependent nitrite reductase with N-bromosuccinimide (NBS), under conditions where slightly less than 1 mol of tryptophan is modified per mole of nitrite reductase, inhibits the catalytic activity of the enzyme by ca. 80% without any effect on substrate binding or other enzyme properties. Complex formation between nitrite reductase and ferredoxin completely protects the enzyme against this inhibition. Transient kinetic measurements show that the second-order rate constant for reduction of NBS-modified nitrite reductase by reduced ferredoxin is approximately four-fold larger than that observed for the native, unmodified enzyme. Also, reduction of NBS-modified nitrite reductase by the 5-deazariboflavin radical shows a different kinetic pattern than that observed with the native enzyme, suggesting that tryptophan modification increases access of the radical to the low-potential [4Fe-4S] cluster of the enzyme, decreases the accessibility to the siroheme group of the enzyme, or both. The tryptophan that is modified has been identified as the absolutely conserved W92. A methionine, M73, that is also modified by NBS, has been identified. The ferredoxin-binding site on spinach nitrite reductase thus appears to include W92 and perhaps M73, in addition to the previously identified R375, R556, and K436.

The ferredoxin-binding site of ferredoxin: Nitrite oxidoreductase. Differential chemical modification of the free enzyme and its complex with ferredoxin.

Spinach (Spinacea oleracea) leaf ferredoxin (Fd)-dependent nitrite reductase was treated with either the arginine-modifying reagent phenyl-glyoxal or the lysine-modifying reagent pyridoxal-5'-phosphate under conditions where only the Fd-binding affinity of the enzyme was affected and where complex formation between Fd and the enzyme prevented the inhibition by either reagent. Modification with [14C]phenylglyoxal allowed the identification of two nitrite reductase arginines, R375 and R556, that are protected by Fd against labeling. Modification of nitrite reductase with pyridoxal-5'-phosphate, followed by reduction with NaBH4, allowed the identification of a lysine, K436, that is protected by Fd against labeling. Positive charges are present at these positions in all of the Fd-dependent nitrite reductase for which sequences are available, suggesting that these amino acids are directly involved in electrostatic binding of Fd to the enzyme.

[Informed consent requirement in treatment with clozapine according to section 1904 of the patient rights law?]. / Genehmigungspflicht einer Behandlung mit Clozapin nach section 1904 des Betreuungsrechtes?

Clozapine-treatment of schizophrenic psychoses under observation of the producer's directions regarding indication, warnings, information of the patient and control-examinations is no measure which entails (according to section 1904 of German Civil Code-"Betreuungsrecht") the existing risk that the person concerned will die or suffer a serious or lasting health-injury. Therefore, in case of patient's inability to consent, the curator's approval after proper information is regarded to be sufficient in most cases of an intended treatment with clozapine. An approval by the Guardianship Court according to section 1904 should be applied for when--because of medical reasons after evaluating risks and benefits--clozapine-treatment is taken into consideration despite risks and contraindications according to the producer's informations.

[Detection of early warning signs in schizophrenic patients. Possible applications in prevention of recurrence]. / Zur Erfassung von Frühwarnzeichen bei schizophrenen Patienten. Einsatzmöglichkeiten in der Rückfallprophylaxe.

In the treatment of schizophrenia, two new strategies have been developed with the aim of adequate relapse prevention accompanied by lowest possible risk of side-effects. One strategy is to have the patient continue to take medication at a highly reduced dosage (10-20% of the standard dose). The other is to gradually stop neuroleptic medication after remission and to reinstitute medication only in the case of prodromal symptoms (termed targeted or intermittent treatment). According to Herz and Melville [13] many schizophrenic patients show signs of relapse well before recurrence of overt psychotic features. Monitoring to detect prodromal symptoms is especially important in targeted treatment because, otherwise, neuroleptic medication often cannot be initiated in time. In the present study of 51 schizophrenic patients we were able to replicate the results of Herz & Melville in the German-speaking countries. Prior to acute exacerbation of psychosis, most patients experience alterations of feelings and behaviour. These alterations may also be recognized by family members. Such early warning signs of relapse mainly consist of non-specific, non-psychotic symptoms: tenseness and nervousness, eating less, trouble concentrating and sleeping, depressive mood and seeing friends less. Furthermore, the regular monitoring and use of early warning signs specific to each patient in the aftercare of schizophrenic patients seems to be practicable, especially in psychoeducative family therapy.

Transdermal clonidine for ameliorating post-orchiectomy hot flashes.

To determine the efficacy of transdermal clonidine for alleviating post-orchiectomy hot flashes, a randomized, double-blind, crossover clinical trial was designed including 70 men with a history of prostate cancer who had undergone a medical or surgical orchiectomy and were suffering from hot flashes. The results of this study demonstrated that clonidine did not significantly decrease hot flash frequency or severity. Future research is necessary to find effective means of alleviating hot flashes in post-orchiectomy patients.

Deliverability of psychoeducational family management.

As part of an open clinical trial currently underway at the Max Planck Institute of Psychiatry in Munich, the feasibility of behavioral family management (Falloon et al. 1984) for schizophrenia in combination with two different neuroleptic medication strategies was investigated. The treatment approaches were psychoeducational family management with a standard dose or with targeted medication. In this article the following questions were addressed: (1) What proportion of the total schizophrenia population admitted as inpatients might be eligible for psychoeducational family treatment (assessment based on n = 411 over a 33-month period)? (2) How representative of this population are the patients who were randomized to the experimental groups? (3) How many patients dropped out of treatment after entering the trial? The results show that about 60 percent (247) of the patients were eligible for a psychoeducational treatment approach. Of these, 34 percent (85) participated in the trial and were randomized to the treatments. Only 4 percent of the relatives but 20 percent of the patients refused to take part in the study. The 85 trial patients did not differ from the total eligible on the numerous socioeconomic and symptom variables assessed. The treatment dropout rate was 11 percent. Those patients who accepted treatment did not differ from those patients who dropped out on socioeconomic or illness variables. The results indicate that early identification of dropouts is not possible at least with the methods used in this study.

Characterization of two low-potential cytochromes from bean sprouts.

Two cytochromes have been isolated from chlorophyll-free bean sprouts, purified and characterized. The more abundant cytochrome was purified to apparent homogeneity and exhibits visible region absorbance maxima at 416, 520 and 550 nm in the reduced form and at 410 and 530 nm in the oxidized form. Although Resonance Raman spectra of this cytochrome closely resemble those of c-type cytochromes, pyridine hemochromogen analysis suggests that this cytochrome may contain a variant of heme c as its prosthetic group. The cytochrome has an apparent molecular mass of 12.5 kDa, an isoelectric point > 9.0 and a midpoint oxidation-reduction potential (Em) of -130 mV at pH 8.0. The less abundant of the two cytochromes, which was not completely purified, exhibits absorbance maxima at 438 and 560 nm in the reduced form and at 411 nm in the oxidized form and was shown to contain heme c as a prosthetic group. This cytochrome, which may also contain FAD, has an apparent molecular mass of approx. 38 kDa, an isoelectric point > 9.0 and Em = -300 mV. Preliminary results indicate that both cytochromes can form electrostatically-stabilized complexes with ferredoxin, suggesting the possibility that one or both of the cytochromes may participate in low-potential, non-photosynthetic electron transfer pathways involving ferredoxin.