[The ways of harmonization of clinical laboratory measurement techniques].

The results of implementation of different clinical laboratory techniques are to be equal in clinically significant limits to be optimally applied in diagnostics of diseases and treatment of patients. When the results of laboratory tests are not standardized and harmonized for the very same clinical assay the results can be expressed by unmatched numbers. Unfortunately, in some handbooks the values are presented based on the results of application of specific laboratory techniques without considering possibility or likelihood of differences between various techniques. When this is a case, accumulation of data of diferent clinical research studies and working out of clinical handbooks on this basis will be inconsistent. Inadequate understanding of issue that the results of laboratory tests are not standardized and harmonized can lead to incorrect clinical, financial, managerial or technical decisions. The standardization of clinical laboratory techniques was applied to many measurands related to primary referent techniques (standard specimen of pure substance) or/and developed referent measurement techniques. However, harmonization of clinical laboratory techniques for those measurands which are not related any developed measurement techniques is quite problematic due to inadequate determination of measurand, its inadequate analytical specificity, insufficient attention to commutability of referent materials and poor systematic approach to harmonization. To overcome these issues an infrastructure is to be developed to support systematic approach to identification and prioritization of measurands which are to be harmonized on the basis of clinical importance and technical applicability. The management of technical implementation harmonization process for specific measurands.

[Current issues in measurement and reporting of urinary albumin excretion]. / Données actuelles sur le dosage de l'excrétion urinaire de l'albumine.

Urinary excretion of albumin indicates kidney damage and is recognized as a risk factor for progression of kidney disease and cardiovascular disease. The role of urinary albumin measurements has focused attention on the clinical need for accurate and clearly reported results. The National Kidney Disease Education Program and the IFCC convened a conference to assess the current state of preanalytical, analytical, and postanalytical issues affecting urine albumin measurements and to identify areas needing improvement. The chemistry of albumin in urine is incompletely understood. Current guidelines recommend the use of the albumin/creatinine ratio (ACR) as a surrogate for the erro-prone collection of timed urine samples. Although ACR results are affected by patient preparation and time of day of sample collection, neither is standardized. Considerable intermethod differences has been reported for both albumin and creatinine measurement, but trueness is unknown because there are no reference measurement procedures for albumin and no referance materials for either analyte in urine. The recommanded reference intervals for the ACR do not take into account the large intergroup differences in creatinine excretion (e.g., related to differences in age, sex, and ethicity) nor the continuous increase in risk related to albumin excretion. Clinical needs have been identified for standardization of (a) urine collection methodes, (b) urine albumin and creatinine measurements based on a complete reference system, (c) reporting of test results, and (d) reference intervals for the ACR.

[Early development of childhood-onset schizophrenia]. / Frühentwicklung kindlicher Schizophrenien.

Childhood-onset schizophrenia (COS, age of onset between 7 and 14 years) is a rare and severe form of the disorder. The prevalence is about 1 / 50 of the rate of adult-onset schizophrenia. In COS-children emotional, cognitive and behavioural abnormalities are often seen years before illness onset. Premorbid symptoms including social withdrawal, isolation, introversion, peculiar behaviour, unmotivated temper tantrums, auto- and heteroaggressive acts, suicidal thoughts, anxiousness, paranoid ideas, represent early warning symptoms and are associated with an unfavourable outcome. About 60 % of 67 patients with COS examined by us (44 long-term-, 23 short-term-follow-up examinations) demonstrated premorbid abnormalities prior to the onset of their psychosis. We found a significant correlation between high M-PAS-scores, insidious onset, negative PANSS-Items, and early onset of age (< 12 years). High M-PAS-Scores were positively related to long duration of psychotic and residual states, and vice versa there was a negative correlation between M-PAS and a favourable outcome (long duration of recovery states). It is necessary to identify clinical states of elevated risk for psychosis as early as possible. This is difficult especially in young patients, in whom psychical peculiarities are ambiguous, and they may develop in different directions, most of them into normalization. Nevertheless, it is important to recognize risk-groups by time and to study their development carefully. Thus they could benefit from multiprofessional family-oriented early interventions.

Motivational effects on inhibitory control in children with ADHD.

OBJECTIVE: The problems children with attention-deficit/hyperactivity disorder (ADHD) encounter in tasks measuring inhibitory control are often theoretically related to deficits in cognitive processes. This study investigated the effects of different motivational incentives on the ability of children to inhibit intended or ongoing actions. METHOD: In a large German industrial town, 33 children with ADHD were compared with 33 members of a combined group of children with major depressive disorder, anxiety disorders, oppositional defiant disorder, or conduct disorder, and 33 children without any psychiatric disorder with respect to their performances in a stop-signal task. The children received continuous feedback under high- or low-incentive conditions. The children's performance was compared in terms of qualitative (inhibition rate) and quantitative (reaction time) measures. RESULTS: There were no indications of deficits in sustained attention in children with ADHD. Under conditions of low incentives, children with ADHD were less able to inhibit their reactions and had longer stop-signal reaction times. But when given high incentives, children with ADHD performed the task as well as both other groups. CONCLUSIONS: Supposed deficits in children with ADHD should be regarded from a perspective that differentiates performance from ability. Furthermore, the findings support a motivational explanation of the origins of lowered inhibitory control in children with ADHD.

[Characteristics of communication of schizophrenic, neurotic, and healthy adolescents]. / Gesprächsmanagement bei gesunden, neurotischen und schizophrenen Jugendlichen.

Research on communication skills in psychotic patients demonstrates that in dialogues schizophrenics neglect the needs of the listener. There are only few linguistic studies which investigate the speech of schizophrenic children and adolescents. The verbal and non-verbal communication of schizophrenic, neurotic, and healthy adolescents during a problem solving situation was transcribed and compared by a content analysis. The transcripts were screened for dialogue control and communication disturbance of verbal/non-verbal activities of the speaker and listener: Dialogue control was defined by the variables signals of the speaker or signals of hearer and eye or body contact of the test person to the experimenter. Communication disturbance was defined as the amount of incomprehensible articulation and selections. Neurotic test persons produce the highest signals of speaker rate. In dialogues with neurotic and schizophrenic test persons the experimenter uses more signals of hearer than in dialogues with healthy test persons. In dialogues with neurotic test persons the experimenter shows more signals of the speaker than in dialogues with healthy test persons. Schizophrenics neglect more often the statements of the experimenter than in other dialogues and vice versa. Although the experimenter was instructed to restricted verbal behavior the communication intensified in the neurotic group. The communication in the schizophrenic group was characterized by frequent communication disturbance.

Standardization of cardiac troponin I assays: round Robin of ten candidate reference materials.

BACKGROUND: Cardiac troponin I (cTnI) results vary 100-fold among assays. As a step toward standardization, we examined the performance of 10 candidate reference materials (cRMs) in dilution studies with 13 cTnI measurement systems. METHODS: Solutions of 10 cTnI cRMs, each characterized by NIST, were shipped to the manufacturers of 13 cTnI measurement systems. Manufacturers used their respective diluents to prepare each cRM in cTnI concentrations of 1, 10, 25, and 50 microg/L. For the purpose of ranking the cRMs, the deviation of each cTnI measurement from the expected response was assessed after normalization with the 10 microg/L cTnI solution. Normalized deviations were examined in five formats. Parameters from linear regression analysis of the measured cTnI vs expected values were also used to rank performance of the cRMs. RESULTS: The three cRMs demonstrating the best overall rankings were complexes of troponins C, I, and T. The matrices for these three cRMs values differed; one was reconstituted directly from the lyophilized form submitted by the supplier; one was submitted in liquid form, lyophilized at NIST, and subsequently reconstituted; and the third was evaluated in the liquid form received from the supplier. The cRM demonstrating the fourth best performance was a binary complex of troponins C and I supplied in lyophilized form and reconstituted before distribution. CONCLUSIONS: The cRMs demonstrating the best performance characteristics in 13 cTnI analytical systems will be included in subsequent activities of the cTnI Standardization Committee of the AACC.

Heterogeneity in human cardiac troponin I standards.

The LC-MS analysis of recombinant cardiac troponin I (cTnI) and cTnI extracted from human hearts showed a high degree of structural heterogeneity among all samples. The examined recombinant cTnI samples indicated posttranslational modifications, presumably due to their purification (i.e., 2-mercaptoethanol adducts and carbamylation) and related to their expression (i.e., an N-terminal expression tag). The extracted cTnI samples, while having a higher degree of structural heterogeneity, showed less structural variance between samples than the recombinant proteins. The LC-MS analysis of the extracted cTnI samples provided evidence of posttranslational modification by phosphorylation, acetylation, proteolytic cleavage, and intrachain disulfide bond formation.

Schizophrenia with onset before the age of eleven: clinical characteristics of onset and course.

This study reports on the long-term course of 11 patients (6 girls, 5 boys) with childhood onset schizophrenia (COS, age at onset < 10 years). Patients were examined twice (mean follow-up period 38 years after onset). The premorbid development is assessed in terms of the Modified Premorbid Adjustment Scale (M-PAS) and additionally described by distinct psychopathological categories. The psychopathology at the onset of psychosis and at the second follow-up examination was assessed by categorical application of the Positive and Negative Syndrome Scale (PANSS). The outcome was rated with the Disability Assessment Score (DAS). The course of psychotic episodes and intervals between them is presented according to DSM-IV subtype classifications. Ten of 11 patients presented premorbid developmental peculiarities that were not adequately covered by the M-PAS subscales. Whereas in the 4 patients with acute onset of psychosis the positive PANSS-type was predominant, in the 7 patients with an insidious onset the negative PANSS-type prevailed. The nature of the diagnostic subtypes varied markedly across the course of the illness. In case of a continuous predominant catatonic symptomatology the outcome was poor. Detailed case descriptions help to illuminate the heterogeneous psychopathology of COS. Various temporary premorbid behavioral peculiarities were precursors of COS. A differentiation between premorbid and prodromal signs proved to be arbitrary. Our results contradict the assumption that COS is characterized only by a negative symptomatology.

The ESSEN study of childhood-onset schizophrenia: selected results.

INTRODUCTION: We present the results of a 42 year long-term follow-up of 44 patients (19 males, 25 females) with childhood-onset schizophrenia (COS, age at onset: 7-14 years) who could be traced for a second follow-up examination 27 years after the first follow-up. METHOD: Data from interviews, clinical records, premorbid and social disability assessments were evaluated for statistical analyses. The symptomatology observed during the whole course of illness was rediagnosed by DSM-IV criteria. RESULTS: The paranoid, catatonic, and schizoaffectives subtypes appeared most frequently. There have been no gender differences in age of first psychiatric symptoms (AFS), AFPS, and age of first hospitalization. Kaplan-Meier's survival-analysis carried out for AFPS with sex as the grouping factor revealed that the cumulative prevalence appears to be earlier in females (between 7 and 15 years) than in males (between 10 and 18 years). Of the 44 patients 50 % had a continuing severe course. Patients with onset before 12 years of age were characterized by a chronic/insidious onset, marked premorbid abnormalities, and by a poorer remission. Premorbid features of social withdrawal and reluctance indicated a risk for social disability within the later course. CONCLUSION: COS, as a rare but severe variant of schizophrenia, frequently develops from premorbid social maladaptation to an insidious onset but is subsequently followed by a transition to a course and outcome not distinguishable from that of adult-onset schizophrenia.

Symptom dimensions in the course of childhood-onset schizophrenia.

The symptom dimensions of childhood-onset schizophrenia (COS) are described by focussing on the clinical features of 44 patients at onset of illness during the first episode and at follow-up investigation 42 years after onset. All subjects were re-diagnosed according to DSM IV. The symptomatology was evaluated with the Positive and Negative Symptom Scale (PANSS) at onset and at follow-up. Two principal component factor analyses with varimax-rotation were applied to the complete items set of the PANSS. The frequencies of positive, negative, and global symptoms were compared longitudinally in an ANOVA-repeated measures design. The factor analysis revealed 5 orthogonal symptom dimensions (factors) at onset of psychosis: Cognition, social withdrawal, antisocial behaviour, excitement, and reality distortion. At follow-up a five-factor solution was found, too, but different dimensions emerged: a positive, negative, excitement, cognitive, and anxiety/depression component which fits to the 5-factor model of White et al. (1997). The first psychotic episode of EOS is accompanied with more unspecific symptoms such as social withdrawal and antisocial behavior. In the later stages of (COS) the structure of symptom dimensions changes to that known from adult-onset schizophrenia (AOS). The results indicate that COS and AOS are comparable nosological entities and that more than 3 dimensions are required to describe the relevant clinical symptom structure. Positive and global symptoms decreased significantly during the course of illness. The frequencies of negative symptoms did not change which demonstrates their disabling impact.

[The 5 factor model of childhood schizophrenia]. / Fünf-Faktoren-Modell kindlicher Schizophrenien.

Forty-four first-admission patients with childhood-onset schizophrenia (age at onset < or = 14 years) were examined retrospectively for 30 clinical symptoms using the Positive and Negative Syndrome Scale (PANSS; 15). A principal component analysis with varimax rotation was applied to the full item set of this scale and revealed five orthogonal independent symptom groups: cognition affect, social withdrawal, anti-social behavior, excitement, and reality distortion. In order to validate these psychopathological dimensions we analyzed the relation between the five factor scores and outcome variables (Disability Assessment Schedule, DAS-M; 13) several years after onset: Social withdrawal was correlated with poor outcome; reality distortion was related to good outcome (P < 0.01). A multivariate ANOVA identified group differences in the anti-social behavior factor between acute and insidious onset of illness and between boys and girls; patients with an acute onset scored significantly higher on the excitement factor than those with an insidious onset (P < 0.05). According to our results more than two dimensions are necessary to describe the psychopathology of childhood-onset schizophrenia, similar to adolescent- and adult-onset schizophrenia.

Probing the interactions of putidaredoxin with redox partners in camphor P450 5-monooxygenase by mutagenesis of surface residues.

The role of surface amino acid residues in the interaction of putidaredoxin (Pdx) with its redox partners in the cytochrome P450cam (CYP101) system was investigated by site-directed mutagenesis. The mutated Pdx genes were expressed in Escherichia coli, and the proteins were purified and studied in vitro. Activity of the complete reconstituted P450cam system was measured, and kinetic parameters were determined. Partial assays were also conducted to determine the effect of the mutations on interactions with each redox partner. Some mutations altered interactions of Pdx with one redox partner but not the other. Other mutations affected interactions with both redox partners, suggesting some overlap in the binding sites on Pdx for putidaredoxin reductase and CYP101. Cysteine 73 of Pdx was identified as important in the interaction of Pdx with putidaredoxin reductase, whereas aspartate 38 serves a critical role in the subunit binding and electron transfer to CYP101.

Characterization of the glycation of albumin in freeze-dried and frozen human serum.

Human serum albumin (HSA) in fresh frozen and freeze-dried serum reference materials was examined by mass spectrometry and a variety of affinity chromatography techniques. The relative molecular mass distribution of HSA in fresh frozen serum was found to be identical to that of an HSA standard. However, the HSA in the freeze-dried reference serum exhibited a relative molecular mass distribution that was shifted to higher mass, broader, and substantially more heterogeneous than that of HSA in fresh frozen serum. A proteolytic cyanogen bromide digestion of the HSA from freeze-dried serum contained adducts approximately 162 u higher in mass than digest fragments 124-298 and 447-548, suggesting glycation. The presence of glycation on fragments 124-298 and 447-548 correlates with the known sites of HSA glycation. Glycation was further confirmed by the mass spectral analysis of the retained and unretained fractions from glycoaffinity chromatography of HSA from freeze-dried serum. The relative molecular weight of the HSA in the retained fraction indicated the presence of a doubly glycated species. The chemical heterogeneity of Cys-34, the site of the only free thiol in HSA, was examined and found not to be a substantial source of molecular mass heterogeneity for HSA from either fresh frozen of freeze-dried serum.

The long-term course of childhood-onset schizophrenia: a 42-year followup.

This article presents results of a 42-year long-term followup of 44 patients (19 males, 25 females) with childhood-onset schizophrenia. Age at onset ranged from 6 to 14 years (mean =11.8 years). The patients and their first-degree relatives were interviewed in 1994, 27 years after the first followup, by the same investigator with the Present-State Examination (PSE) and the Disability Assessment Schedule. The clinical records were analyzed with the Instrument for the Retrospective Assessment of Onset of Schizophrenia and with sections of the PSE. The cases were rediagnosed according to DSM-III-R, based on longitudinal data obtained between onset and the first hospital admission. Although cumulative prevalence is earlier in females than in males, no gender differences exist in average age at onset. An acute onset was significantly more frequent after 12 years of age. An early age at onset was correlated with high social disability scores. Of the patients, 25 percent were completely, 25 percent partially, and 50 percent were poorly remitted at the second followup. None of the patients with chronic onset remitted completely. The results are discussed with respect to epidemiology, gender differences, and etiological hypotheses of childhood schizophrenia.

Tissue resistance and the contractile state of lung parenchyma.

When challenged with a contractile agonist in increasing graded concentrations, lung parenchymal tissue assumes a sequence of mechanical states. That sequence is mapped here. Isolated lung parenchymal strips from male Hartley guinea pigs were mounted in a bath containing Krebs solution at 37 degrees C, aerated with 95% O2-5% CO2. One end was attached to a force transducer and the other to a servo-controlled lever arm. After stress adaptation, sinusoidal length oscillations (1% strain at 0.31 Hz) yielded force-length loops from which we computed induced changes in active tension (F), tissue stiffness (E), and hysteresivity (eta) (J. J. Fredberg and D. Stamenovic. J. Appl. Physiol. 67:2408-2419, 1989). Changes of tissue resistance (R) were, by definition, governed by those of eta and E. Histamine (10(-6) -10(-3) M), prostaglandin D2 (10(-5) -10(-4) M), and prostaglandin F2 alpha (10(-5) -10(-4) M) caused dose-related increases of F, eta, and E. Plotting induced changes of E vs. those of F revealed a unique relationship that was identical for these as well as a wider panel of contractile agonists; changes of E and F were closely associated. However, plotting induced changes of E vs. those of eta revealed relationships that differed distinctly between agonists; changes of eta were dissociated from those of F and E. This latter observation demonstrated the existence of distinct mechanical states that differed according to the specific agonist by which the tissue was stimulated. In producing agonist-induced changes in R, changes of E were of equal or greater importance compared with those of eta. We conclude that guinea pig lung parenchyma, viewed as an integrated physiological tissue system, exhibits different kinds as well as varying intensities of mechanical response according to the specific agonist present in the cellular microenvironment. These differences in contractile state reveal themselves principally in the hysteretic nature of the tissue.

[The significance of psychodynamic relationship factors for psychopathogenesis in childhood Nazi persecution]. / Die Bedeutung beziehungsdynamischer Faktoren für die Psychopathogenese von im Kindesalter Naziverfolgten.

UNLABELLED: This study focuses on psychiatric disorders following extreme traumatisation experienced by children born during the Holocaust in World War II. According to numerous epidemiological investigations and case studies on survivors who lived through the Holocaust as children or in adulthood, these traumatic experiences are associated with a higher risk for various psychiatric disturbances during the entire life span. Besides the extreme psychological and physical distress during persecution and following traumatisation (parent-child-separation, discrimination while living in other countries) the coping with the trauma and the development of autonomy and ego-strength is additionally impaired by the specific psychodynamics of families with psychologically altered and disturbed parents. OBJECTIVE: What sort of psychodynamic parent-child relationships developed during traumatisation and after the war in subjects currently suffering from chronic impairment of mental health? METHOD: Retrospective analysis of 22 cases with applications for pensions of invalids evaluated by diagnostic categories. RESULTS: The implicit pressure on the children to be sensitive to the needs of their deprived parents places a sense of guilt on their attempts to develop autonomy. The parents were experienced as restrictive or overprotective on the one hand or liable to be rejected or to be intolerant on the other. The suffering and trauma continues to be perceived in family communication to the extent that coping with loss of relatives and the development of independence are impaired. CONCLUSION: The results are discussed critically in terms of current procedures for expertise on pension applications.

Fragmentation of proteins in the 13- to 29-kDa mass range observed by 252Cf-plasma desorption mass spectrometry.

Results are presented on the observation of sequence-specific fragmentation of proteins in the 13- to 29-kDa mass range (ribonuclease A, papain, and proteinase K) by 252Cf-plasma desorption mass spectrometry. For these proteins, extensive N-terminal an, cn + 2, and dn fragment ions are observed with mass accuracies approaching 200 ppm for the most prominent fragment ions. The fragmentation pattern of these proteins shows the same fundamental behavior (arginine-directed, charge-remote fragmentation) that is observed in the fragmentation of small peptides, indicating that similar processes are occurring when large proteins and small peptides fragment in plasma desorption mass spectrometry.

Influence of bifurcations on forced oscillations in an airway model.

Forced oscillations is a technique to determine respiratory input impedance from small amplitude sinusoidal pressure excursions introduced at the airway opening. Models used to predict respiratory input impedance typically ignore the direct effect of bifurcations on the flow, and treat airway branches as individual straight tubes placed appropriately in parallel and series. The flow within the individual tubes is assumed equivalent to that which would occur in infinitely long tubes. In this study we examined the influence of bifurcations on impedance for conditions of the forced oscillatory technique. We measured input impedance using forced oscillations in straight tubes and in an anatomically-relevant, four generation physical model of a human airway network. The input impedance measured experimentally compared well to that obtained theoretically using model predictions. The predictive scheme was based on appropriate parallel and series combinations of theoretically computed individual tube impedances, which were computed from solutions to oscillatory flow of a compressible gas in an infinitely long rigid tube. The agreement between experimental measurements and predictions indicates that bifurcations play a relatively minor direct role on the flow impedance for conditions of the forced oscillations technique. These results are explained in terms of the small tidal volumes used, whereby the axial distance traveled by a fluid particle during an oscillation cycle is appreciably smaller than branch segment lengths. Accordingly, only a small fraction of fluid particles travel through the bifurcation region, and the remainder experience an environment approaching flow in an infinite straight tube. The relevance of the study to the prediction of impedances in the human lung during forced oscillations is discussed.