[Tools for the diagnosis of attention-deficit/hyperactivity disorder in adults. Self-rating behaviour questionnaire and diagnostic checklist]. / Instrumente zur Diagnostik der Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung (ADHS) im ErwachsenenalterSelbstbeurteilungsskala (ADHS-SB) und Diagnosecheckliste (ADHS-DC).

We report on the development of a German self-rating behaviour questionnaire (ADHD-SR) and diagnostic checklist (ADHD-DC) for the diagnosis of attention-deficit/hyperactivity disorder in adults according to DSM IV and ICD 10 research criteria. When comparing self-rating with expert rating, we found good concordance measured by intraclass coefficients on the level of single symptoms and syndrome scores. High retest reliability of the ADHD-SR demonstrated the ability to assess time-stable behaviour traits. Evaluation of the psychometric properties revealed good internal consistency and adequate convergent and divergent validity measured by the "big five" derived from the NEO-FFI and the constructs impulsivity, venturesomeness, and empathy of Eysenck's impulsiveness questionnaire. We detected a remarkable correlation with the Wender Utah Rating Scale, which targets the detection of childhood ADHD symptoms. Diagnostic sensitivity for different cutoff points was calculated by ROC analysis at 65--88%. Specificity was 67% to 92%.

[Reliability and validity of the Wender-Utah-Rating-Scale short form. Retrospective assessment of symptoms for attention deficit/hyperactivity disorder]. / Reliabilität und Validität der Wender-Utah-Rating-Scale-Kurzform. Retrospektive Erfassung von Symptomen aus dem Spektrum der Aufmerksamkeitsdefizit/Hyperaktivitätsstörung.

The diagnosis of adult attention deficit/hyperactivity disorder (ADHD) requires the retrospective assessment of ADHD symptoms in childhood. The Wender Utah Rating Scale (WURS) is helpful in detecting ADHD-associated symptomatology in childhood. A German short version (WURS-k) of this instrument has been made available recently. In the present study, we investigated the validity of the WURS-k. In a population of 63 adult ADHD patients (according to ICD-10 and DSM-IV criteria) and 1,303 male controls, ROC analysis indicated a sensitivity of 85% and specificity of 76% at a cutoff of 30 points. In ADHD patients, seven individual factors explained 70.3% of the variance. The highest diagnostic precision was demonstrated using the WURS-k total score. The seven extracted factors of the WURS-k did not differ in diagnostic value. Significant correlations were found between impulsivity according to Eysenck's Impulsivity Questionnaire (EIQ) and excitability, aggression, emotional lability, and satisfaction on the Freiburg Personality Inventory (FPI-R) in ADHD patients. Concerning a 30-50% persistence of ADHD symptomatology in adults, these correlations underline the diagnostic validity of the WURS-k. The scale manifested excellent internal consistency (alpha=0.91) and a split-half correlation of r(12)=0.85.

[Wender Utah rating scale. The short-version for the assessment of the attention-deficit hyperactivity disorder in adults]. / Wender Utah Rating Scale (WURS-k) Die deutsche Kurzform zur retrospektiven Erfassung des hyperkinetischen Syndroms bei Erwachsenen.

This work presents a statistical analysis of the German version of the Wender Utah rating scale (WURS) for the retrospective diagnosis of attention-deficit/hyperactivity disorder (ADHD) in adults. Data were obtained from 703 subjects. Item selection according to item-total correlation scores, frequency, and plausibility led to a short version of the scale that includes 21 items with item-total correlations from 0.19 to 0.61. Retest reliability of the WURS-k was r=0.9.

[Symptoms from the spectrum of Attention-Deficit/Hyperactivity Disorder (ADHD) in sexual delinquents]. / Symptome aus dem Spektrum des hyperkinetischen Syndroms bei Sexualdelinquenten.

The implications of ADHD for sexual delinquent behavior were investigated in a sample of 127 male sexual delinquents for whom social, forensic and psychiatric data were collected. For the retrospective evaluation of ADHD-symptoms, we used the Wender Utah Rating Scale (WURS, 61-item version). We also used the Eysenck Impulsiveness Questionnaire for the assessment of impulsivity. The prevalence of ADHD within the group of sexual delinquents was 27.6 % with a persistence rate of 14.2 % at a cut-off point of 90 in the WURS. The prevalence of ADHD within the control group was 7.8 % with a persistence rate of 3.0 %. The prevalence within the group of sexual delinquents dropped to 15.7 % for childhood ADHD-symptoms and 11.0 % for partial ADHD persistence in adulthood using a cut-off score of 100. In the control group the rates were 4.8 % and 2.4 % respectively. Based on ICD-10 criteria, 35.4 % of the sexual delinquents had no psychiatric disorder. We found personality disorders of the antisocial type (22.1 % of the sample) and paraphilias in 25.2 %. Approximately, half of the delinquents with paraphilia met the criteria of pedophilia. We also found schizophrenia, organic psychiatric disorders and mental retardations in less than 5 %. The criminal careers of the sexual delinquent group with a history of childhood ADHD symptoms started 10 years earlier. We also found a significant correlation between previous convictions and the retrospective diagnosis of ADHD symptoms. This was more prominent when a previous sexual offence could be found in their criminal record. These results illustrate the hypothesis, that in addition to paraphilias the presence of ADHD-symptoms might be an important vulnerability factor for sexual delinquency, esp. when there is a persistence into adulthood. This demonstrates the need for an early therapeutical intervention, since 44.1 % of the sample had previously undergone psychiatric treatment.

[Assessment of the attention-deficit hyperactivity disorder in adults]. / Erfassung des hyperkinetischen Syndroms bei Erwachsenen.

The attention-deficit hyperactivity disorder (ADHD) is one of the most common disorders in childhood and adolescence with a prevalence of app. 5%. The importance of ADHD in childhood as a factor of vulnerability for psychiatric disorders in adults is becoming a focus of discussion. It was shown that there is a comorbidity in adults with substance abuse, delinquency and personality disorders. There is a growing evidence that ADHD will persist in a significant number of patients during adulthood. This is the first german study to evaluate this interdependence. We examined 164 adult inpatients and 48 healthy volunteers with the Wender Utah Rating Scale (WURS), a retrospective self-evaluation scale for the diagnosis of ADHD in childhood, and the Eysenck impulsiveness questionnaire I7. It could be shown that the WURS and the I7 are suitable instruments for the evaluation of the ADHD in adults especially concerning the aspects of attention deficits and impulsiveness.

Calorimetry of tetraether lipids from Thermoplasma acidophilum: incorporation of alamethicin, melittin, valinomycin, and nonactin.

The development and application of model membrane systems on the basis of tetraether lipids from Thermoplasma acidophilum has been proposed. In this respect incorporation of membrane proteins and ionophores is indispensable and is demonstrated in the case of alamethicin, melittin, nonactin, and valinomycin by calorimetry. Dipalmitoylphosphatidylcholine (DPPC) and dihexadecylmaltosylglycerol (DHMG) were chosen for comparison. Melittin and alamethicin prove to broaden the lipid phase transition and to reduce the melting temperature Tm and enthalpy change (delta H) of the main phospholipid from T. acidophilum (MPL) and DPPC. The decrease in Tm, however, is more pronounced in DPPC than in MPL. Valinomycin shows only a marginal effect on the temperature and width of the transition; delta H is reduced in MPL and remains constant in DPPC and DHMG. With nonactin the phase transition of DPPC is quenched, and delta H and the half-height width are increased. DHMG is affected to a lesser extent and MPL only marginally. The four ionophores exhibit different modulation of the phase transition behavior of the various lipids as expected from their varying molecular structures. Thus, the integral membrane protein alamethicin, the peripheral protein melittin, valinomycin, and nonactin interact primarily with lipid head groups and are readily incorporated into the tetraether lipid structures.

Fibroblasts from ataxia telangiectasia (AT) and AT heterozygotes show an enhanced level of residual DNA double-strand breaks after low dose-rate gamma-irradiation as assayed by pulsed field gel electrophoresis.

Skin fibroblasts from ataxia telangiectasia (AT) patients, obligate AT heterozygotes (ATH) and normal individuals were studied for colony-forming ability and repair of DNA double-strand breaks (dsb) after gamma-irradiation. AT cells were three to four times more radiosensitive than normal cells at high and low dose-rate exposures; ATH cells, however, showed a marginally increased radiosensitivity after high dose-rate gamma-irradiation and an intermediate response after low dose-rate exposure. The repair of DNA dsb was studied by pulsed field gel electrophoresis. After high dose-rate gamma-irradiation the repair time constant (t1/2) was around 1 h for normal, ATH and AT cells. After low dose-rate gamma-irradiation the fraction of residual dsb was 1.4% for normal, 2.1% for ATH and 5.2% for AT cells, demonstrating a deficiency in the repair of a small fraction of dsb in AT. Thus the fraction of residual dsb after low dose-rate exposure was not only four times higher in AT than in normal cells, but was also significantly increased in ATH compared to normal cells.

Thermotropic properties of dispersions of cholesterol with tetraether lipids from Thermoplasma acidophilum.

The main glycophospholipid from Thermoplasma acidophilum is composed of a diisopranol-2,3-glycerotetraether. The fraction of pentane cyclizations of its hydrocarbon chains increases with the growth temperature of the source organism (39-59 degrees C). Hydrated mixtures of these lipids together with cholesterol have been studied by calorimetry. With the reduction of the phase transition temperatures and enthalpy changes of the transitions, cholesterol is readily incorporated into lipid monolayers in the liquid-crystalline and the (metastable) solid-analogue phase. Lipid samples with a high number of acyclic hydrocarbon chains form a stable and a metastable solid-analogue phase. With the increasing concentration of cholesterol the metastable solid-analogue phase is stabilized and the time constant for the formation of the stable solid-analogue phase is prolonged.

Incorporation of synthetic peptide helices in membranes of tetraether lipids from Thermoplasma acidophilum. A calorimetric study.

Four analogues of the membrane-modifying, alpha-helical polypeptide antibiotic alamethicin were synthesized. the alpha-helical deca-, undeca-, heptadeca-, and icosapeptides were mixed with the main tetraether lipid of the Archaebacterium Thermoplasma acidophilum (MPL), dipalmitoylphosphatidylcholine (DPPC) and dihexadecylmaltosylglycerol (DHMG) in various ratios and the modification of the lipid phase transition was determined by differential thermal analysis (DTA). The polypeptides form mixed phases with MPL and DPPC, however, not with DHMG. Heptadeca- and icosapeptide exert a much stronger reduction of enthalpy (delta H) than deca- and undecapeptide and bind about 0.5 molecule of MPL (or one molecule of DPPC) per peptide molecule. delta H of the DPPC pretransition is reduced by the deca- and the undecapeptides and completely disappears with heptadeca- and icosapeptides (at 0.2 mole of peptide/mole of lipid). The modulation of the melting point Tm by the incorporation of peptides is more pronounced with MPL than with DPPC, the heptadecapeptide exhibiting the strongest reduction (with MPL) and the strongest broadening of the transition peak (with DPPC). Helix length, amphiphilicity and charge of the polypeptides can be correlated with the observed modifications of the lipid phase transitions.

DNA double strand breaks in fibroblast cell lines, from non-Hodgkin's lymphoma patients, showing increased sensitivity to chronic gamma irradiation.

Cultured skin fibroblast cell lines from two non-Hodgkin's lymphoma patients (NHL) and a normal subject were studied for cell killing, chromosomal aberrations (breaks, translocations, dicentrics and rings) and DNA double strand breaks (dsbs) following chronic gamma irradiation. Compared to the cell line from the normal donor, the NHL patients' fibroblasts showed enhanced radiosensitivity for both cell survival and chromosomal aberrations. While spontaneous breaks were observed in both normal and patients' cells, spontaneous translocations and radiation-induced dicentrics and rings were found only in the latter. Radiation-induced DNA double-strand breaks (dsb) were determined by CHEF electrophoresis. After chronic irradiation with gamma rays the fraction of residual dsb was significantly increased from 1.4% in controls to 1.9% in the NHL cell lines. These data, thus, suggest that the cellular and chromosomal sensitivity to chronic irradiation observed in NHL patients may be due to a deficiency in the repair of a small fraction of DNA double strand breaks.

Size distribution of DNA molecules recovered from non-denaturing filter elution.

DNA fragments removed from the filter during non-denaturing filter elution were collected and loaded on top of neutral sucrose gradients. Their size distribution was determined by low-speed centrifugation in neutral sucrose gradients. The average size of eluted DNA was found to be approximately 110 S, yet the average size of DNA collected after short elution times was found to be slightly larger than that after long elution times. It is concluded that the size of eluted DNA fragments is not correlated with their elution rate, and it is proposed that shear forces generated at the pores of the filter cause degradation of the DNA. A comparison of the sedimentation profiles of carefully prepared cellular DNA before and after elution revealed that the generated shear forces during elution break down the DNA to an extent equivalent to around 20,000 DNA double-strand breaks (dsb) per G1 cell. The size of DNA fragments decreased with increasing radiation dose; however, five times more dsb were found than expected after exposure to radiation alone. It is proposed that this excess of dsb may derive from the transformation of other radiation-induced lesions to dsb under the action of the shear forces generated during elution.

Comparison of DNA double-strand break rejoining as measured by pulsed field gel electrophoresis, neutral sucrose gradient centrifugation and non-unwinding filter elution in irradiated plateau-phase CHO cells.

The initial (up to 30 min) rate of DNA double-strand break (dsb) rejoining was measured in irradiated plateau-phase CHO cells, in a set of parallel experiments using the same cell suspension, by means of non-unwinding filter elution, neutral sucrose gradient centrifugation, and two pulsed-field gel electrophoresis assays: asymmetric field inversion gel electrophoresis (AFIGE) and clamped homogeneous electric field (CHEF) gel electrophoresis. The rate of DNA dsb rejoining was compared to the rate of rejoining of chromatin breaks measured, also in the same cell population, using the technique of premature chromosome condensation (PCC). Two radiation exposures, 25 Gy and/or 50 Gy, were used and applied to the individual parts of the experiments according to the sensitivity of the assay under investigation. Similar values for the initial rate of DNA dsb rejoining were obtained with all assays used, with t 1/2 ranging between 10 and 12 min after exposure to 25 Gy and between 15 and 20 min after exposure to 50 Gy. The initial rate of rejoining of chromatin breaks was slower than that of DNA dsb and occurred with t 1/2 of 87 min. The results suggest that all major techniques currently used for assaying rejoining of DNA dsb give similar results despite their widely different biophysical basis, and indicate that more information is required before a direct correlation between rejoining of DNA dsb and rejoining of chromatin breaks can be established.

Dose response in neutral filter elution.

In neutral filter elution a nonlinear relationship between fraction of eluted DNA and dose is usually observed, which is often interpreted as a nonlinear induction of DNA double-strand breaks (DSBs) with dose. The conclusiveness of this hypothesis is questioned here on the basis of theoretical considerations regarding the size distribution of DNA fragments. A simple hydrodynamic model is proposed which generates the typical features of the dose response of neutral filter elution: (1) the shoulder at low doses, (2) a quasilinear correlation in an intermediate dose range, (3) a saturation at high doses, and (4) a linearization of the curve in the intermediate and higher dose range in a semilogarithmic plot. These features were derived even with the assumption of a linear induction of DSBs with dose. Thus it is demonstrated that the fraction of eluted DNA could conceivably be a nonlinear function of dose even if the induction of DSBs is directly proportional to the radiation dose.

DNA double-strand break analysis by CHEF (clamped homogeneous electrical field) electrophoresis.

Pulsed-field gel electrophoresis (PFGE) has become a powerful tool for the study of high-molecular-weight DNA. In this technical note the application of clamped homogeneous electrical field (CHEF) electrophoresis for the determination of DNA double-strand breaks is described, and a number of parameters that influence the sensitivity of the assay are discussed. They include the concentration of the cell sample, agarose concentration in the plug and the electrophoresis gel, lysis conditions, pulse time, electric field gradient and the temperature of electrophoresis.

Physicochemical characterization of tetraether lipids from Thermoplasma acidophilum. V. Evidence for the existence of a metastable state in lipids with acyclic hydrocarbon chains.

The main glycophospholipid of Thermoplasma acidophilum, grown at 39 degrees C, is composed of a di-isopranol-2,3-glycerotetraether. It has been characterized in hydrated systems by calorimetry. Unlike its equivalent grown at 59 degrees C, it shows complex phase properties, which include at least three different phases, (1) a liquid-analogue state (C), which is stable above 20 degrees C, (2) a metastable solid-analogue state (A) formed by supercooling of the liquid-analogue state (C) and (3) a stable solid-analogue state (B), which is slowly formed and may include a close chain packing of lipids and a network of hydrogen bonds between the headgroups. A high fraction of acyclic isopranol chains seems to be a prerequisite for the formation of state (B). A phase diagram, displaying the observed states and the transitions between them is proposed.

In CHEF electrophoresis a linear induction of dsb corresponds to a nonlinear fraction of extracted DNA with dose.

A theory for DNA double-strand break (dsb) analysis by pulsed field electrophoresis is presented, based on the size distribution of DNA fragments, which converts an induction of dsb linear with dose into a nonlinear fraction of extractable DNA, in agreement with experimental observations.

Responses of two mammalian cell lines to low gamma-ray doses.

We have observed that low gamma-ray doses regularly improve the survival (plating efficiency) above that of unirradiated control cultures, which we postulate could arise through inducible DNA repair, and would have profound effects on the interpretation of cell culture experiments.

CHEF electrophoresis, a sensitive technique for the determination of DNA double-strand breaks.

It has been demonstrated that clamped homogeneous electrical field (CHEF) electrophoresis is a suitable method for the determination of DNA double-strand breaks in Chinese hamster ovary (CHO) cells. It allows the separation of DNA molecules up to 10 Mbp. The fraction of DNA fragments of this size is correlated with the number of radiation induced double-strand breaks. The resolution limit of the technique is equivalent to the effect of about 1 Gy (gamma-rays). Double-strand break repair was monitored after irradiation with Co-60 gamma rays and the repair time constant determined to t1/2 = 30-35 min. In combination with the detection of DNA by fluorescence, CHEF electrophoresis provides an easy and sensitive method for the determination of double-strand break repair which does not require the radioactive labelling of cells.

DNA double-strand break repair determines the RBE of alpha-particles.

Radiation-induced DNA double-strand breaks (dsb) were studied in Ehrlich ascites tumour cells (EATC) by sedimentation in neutral sucrose gradients at low centrifuge speed. Dsb induction was found to be linear with dose with a frequency of: ndsbmr-1D-1 = (11.7 +/- 2) x 10(-12)Gy-1 for 140 kV X-rays and ndsbmr-1D-1 = (19.1 +/- 4) x 10(-12)Gy-1 for 3.4 MeV 241Am-alpha-particles. Postirradiation incubation of cells under non-growth conditions leads to repair of dsb, reaching a maximum after trep = 24 h. More than 97 per cent of dsb were repaired after an X-ray dose of 25 Gy. The number of residual dsb was found to be a linear-quadratic function of dose: nresmr-1 = (0.0161 +/- 0.0008) x 10(-12)Gy-2D2 for X-rays and nresmr-1 = (1.2 +/- 0.7) x 10(-12)Gy-1D + (0.105 +/- 0.017) x 10(-12)Gy-2D2 for alpha-particles. Thus, after cellular repair the RBE value of alpha-particles was increased from RBE = 1.6 +/- 0.4 (induction of dsb) to a dose-dependent value of RBE = 2.7 +/- 0.4 (at 100 Gy alpha-particles) to 3.8 +/- 1.2 (at 10 Gy alpha-particles) for residual dsb. From the data presented it is concluded that residual dsb are a major cause for loss of the reproductive capacity of EATC after irradiation with X-rays as well as alpha-particles.