2',5'-Oligoadenylate synthetase activity analysis and human papilloma virus typing as prognostic factors in patients with recurrent respiratory papillomatosis.

OBJECTIVE: Determination of early prognostic factors in patients with recurrent respiratory papillomatosis is extremely important, so the major goal of our prospective, multicentre study was to evaluate (1) the feasibility of various factors to determine prognosis of the clinical course, as well as (2) the response to interferon-alpha therapy in recurrent respiratory papillomatosis. METHODS: Forty-two patients with recurrent respiratory papillomatosis were treated with interferon-alpha (3 MU/m(2) three times per week; mean therapy duration was 2.7 +/- 1.8 years) in 1983-1994 and followed-up until 2003. Human papilloma virus (HPV) type, recurrent respiratory papillomatosis severity and 2',5'-oligoadenylate synthetase activity were determined by standard methods and analysed for correlation with the results of long-term clinical outcome. RESULTS AND CONCLUSION: Patients with HPV type 11, a severity score >4, a high number of surgical procedures prior to interferon-alpha therapy and a high basal 2',5'-oligoadenylate synthetase activity should be considered at high risk of an aggressive clinical course, often with spread to lower airway passages, malignant transformation and death. Human papilloma virus type, score for recurrent respiratory papillomatosis severity, number of surgical procedures and 2',5'-oligoadenylate synthetase activity showed significant association with response to interferon-alpha therapy and the long-term clinical course, so these factors have value in predicting prognosis in recurrent respiratory papillomatosis.

Cognitive-motor performance of methadone-maintained patients.

Fifty-four methadone-maintained patients and 54 healthy controls, matched for age, gender and educational attainment, completed a battery of six cognitive-psychomotor performance tests. Results of previous studies were replicated in four areas. An attention task was performed less well by patients [mean difference more than 0.7 standard deviations (SD)] as was a tachistoscopic perception task (0. 3 SD). On a simple-choice reaction test, patients showed higher speed in decision making and motor reaction as well as an increased number of decision errors (0.3 SD each). Performing a tracking test, patients showed less deviations (0.4 SD) combined with more time needed (0.8 SD). Our data go beyond previous (seemingly inconsistent) research findings by showing that patients did less well by more than 0.6 SD when on higher speed levels. Absolving a test on visual structuring, more patients than controls achieved a 100% accuracy level (52 vs. 30%), but at the same time patients were slower (0.6 SD) than controls. An inferior test performance of patients in methadone maintenance treatment has been confirmed in some areas, especially in attention. However, the fairly moderate size of these effects and the fact that in the majority of measures the observed variance was better explained by sociodemographic features than by group membership lead on the conclusion that belonging to the group of methadone patients alone is not necessarily sufficient to predict an impairment in cognitive-psychomotor skills. To conclude, assessment of fitness for certain tasks or occupations should be done individually for each patient and should take into account comorbidity, including the extent of alcohol and other drug use.

[Rehabilitation of psychiatric patients in the halfway house--a 10-year retrospective study]. / Rehabilitation psychisch Kranker im Ubergangswohnheim--Ein 10-Jahres-Rückblick.

In a period of ten years 159 residents were admitted to a transitional home. 90% of them were diagnosed as chronic schizophrenics with a marked psychic and social handicap. With an average age of 28.7 years and a mean duration of illness of 6.8 years most of the patients had been hospitalized several times; 95% had no job, lived on social assistance or were invalidity pensioners. There was poor success in vocational rehabilitation (22%). Better results were seen in solving the housing problems, showing a clear-cut tendency to move from the family of origin into protected group homes or independent living. Positive effects of social training with gains in life-coping abilities and social competence, i.e., in autonomy in everyday life could be observed as well.

Overexpression of chicken interferon regulatory factor-1 (Ch-IRF-1) induces constitutive expression of MHC class I antigens but does not confer virus resistance to a permanent chicken fibroblast cell line.

The chicken fibroblast cell line C32 has been transfected with the chicken homolog (Ch-IRF-1) of the mammalian transcription factor IRF-1. Stable transfectants were generated, constitutively overexpressing Ch-IRF-1 mRNA and protein. Cells overexpressing Ch-IRF-1 showed enhanced constitutive expression of MHC class I (B-F, beta-microglobulin) antigens. With increasing number of passages cells with normal B-F IV surface antigen expression accumulated. In the revertants, the amount of Ch-IRF-1 mRNA was reduced. Overexpression of Ch-IRF-1 had no effect on the constitutive expression and the induction by chicken interferon type-I and type-II (Ch-IFN) of guanylate-binding protein (GBP). Susceptibility to vesicular stomatitis virus, sindbis virus, Newcastle disease virus and vaccinia virus was not altered by overexpression of Ch-IRF-1. An antiviral state could be induced against all viruses tested by similar amounts of Ch-IFN type I in clone 20-18 expressing Ch-IRF-1 and cells transfected with empty vector.

Electrophoretic separation of multiprotein complexes from blood platelets and cell lines: technique for the analysis of diseases with defects in oxidative phosphorylation.

A two-dimensional electrophoretic technique combining blue native polyacrylamide gel electrophoresis (BN-PAGE) with Tricine sodium dodecyl sulfate (SDS)-PAGE was previously used for the localization of oxidative phosphorylation (OXPHOS) defects in human diseases starting from biopsy or autopsy tissues (Schägger, H., Electrophoresis 1995, 16, 763-770). In the present work the technique was extended for the resolution of OXPHOS enzymes from platelets and tissue-cultured cells. Silver staining is required to detect the protein subunits of OXPHOS complexes in two-dimensional gels. However, the use of cultured cells has major implications for patients with mitochondrial encephalomyopathies since it will reduce the number of invasive muscle biopsies. The ease of isolating the platelet membrane glycoprotein complex from a few milliliters of blood makes it possible to analyze this complex and its protein subunits in bleeding disorders like Glanzmann's thrombasthenia.

PINV--topography and primary negative symptoms in chronic schizophrenia.

PINV was recorded during a warned reaction time paradigm in 16 chronic schizophrenics in remission. Clinical symptoms were assessed by BPRS, SANS, and the anhedonia scale of the Chapman Questionnaire. Ten healthy controls were studied in the same manner. Over the frontocentral area we found a significantly elevated PINV amplitude with an altered topographical distribution in the patient group. The difference values "PINVCz-PINVFz" were correlated negatively with primary negative symptoms of schizophrenia.

[Demands and reality in the rehabilitation of psychiatric patients. Results of a follow-up study in established need for rehabilitation with reference to the housing and/or vocational sphere]. / Anspruch und Wirklichkeit der Rehabilitation psychiatrischer Patienten. Ergebnisse einer Verlaufsuntersuchung bei festgestelltem Rehabilitationsbedarf auf der Wohn- und/oder Arbeitsachse.

At an index day all 166 patients of the Department of General Psychiatry were asked whether changes of working or housing condition were considered necessary and which definite steps had to be done. In 85 (51.2%) of 166 patients changes were considered necessary. What measures had been initiated or carried out? Concerning the housing situation age and disease (psychiatric diagnosis) proved to be important factors; concerning the working situation age, sex, socioeconomic status and length of unemployment were important.

Altered fronto-central PINV topography and the primary negative syndrome in schizophrenia.

Postimperative negative variation (PINV) was recorded during a warned reaction time paradigm in 16 chronic DSM-IIIR schizophrenics in remission. Clinical symptoms were assessed by BPRS, SANS and the anhedonia scale of the Chapman Questionnaire. Ten healthy controls were studied in the same manner. Over the fronto-central area we found a significantly elevated PINV amplitude with an altered topographical distribution in the patient group. The difference values 'PINV Cz-PINV Fz' were correlated negatively with primary negative symptoms of schizophrenia.

Postimperative negative variation and skin conductance response in chronic DSM-III-R schizophrenia.

The hypothesis was tested that there are relationships between schizophrenic negative or deficit symptoms, the skin conductance nonresponding and an elevated amplitude of the postimperative negative variation (PINV). These variables were recorded in 16 chronic schizophrenics and 10 healthy controls. Clinical symptoms were assessed by the Brief Psychiatric Rating Scale, Scale for the Assessment of Negative Symptoms, Frankfurt Complaint Questionnaire 3 and Chapman Questionnaire. In the patient group we found a significantly elevated PINV at Fz. Surprisingly, only one patient was a skin conductance nonresponder. PINV amplitude at Fz and the number of skin conductance responses to habituation were not correlated with negative or deficit symptoms inclding anhedonia. The hypothesis thus had to be rejected.

[Event-related potentials in schizophrenic patients in the acute phase and in remission]. / Ereigniskorrelierte Potentiale bei schizophrenen Patienten im akuten Krankheitsschub und in Remission.

In 15 schizophrenic patients event-related potentials were recorded during an auditory two-tone-discrimination task in the acute phase and after remission. The control group consisted of ten healthy subjects of the same age. The schizophrenic patients showed reduced amplitudes of N1, P2 and P3 and prolonged latencies of N2 and P3 independent of neuroleptic medication and clinical state. We found no differences in the topographical distribution of P3 between schizophrenic patients and controls. The changes of the event-related potentials in the schizophrenic patients may be interpreted as electrophysiological correlates of basic disturbances in information processing in schizophrenia.

Trimipramine--an atypical neuroleptic?

Trimipramine and clozapine show some similarities in their receptor binding profiles. Since both have the same affinity for the D2 receptor and since the affinity for this receptor correlates closely with the antipsychotic potency of a drug, an antipsychotic efficacy of trimipramine in acute schizophrenia could be expected. Therefore 28 schizophrenic patients in an acute phase were treated with trimipramine up to 400 mg/d in an open clinical trial. For the whole group of patients the BPRS total score changed from 58 +/- 5 before treatment to 46 +/- 18 at the last rating (p less than 0.05). According to our clinical judgement the patients were divided into three subgroups. Thirteen patients showed a good remission under trimipramine so that they could be discharged on a trimipramine maintenance treatment. They improved on the BPRS from 58 +/- 6 before treatment to 32 +/- 8 at endpoint. Six patients deteriorated during the first week of treatment and had to be withdrawn from the study. Nine patients showed insufficient improvement or became worse after an initial improvement. The observed side-effects (dry mouth, sedation, sweating, increased appetite, constipation, tremor, vertigo) are well known under trimipramine and were therefore expected. Beyond these, one patient developed a cardiac insufficiency. No clinical relevant extrapyramidal side-effects occurred. Since the improvement of florid psychotic symptoms seems to be markedly higher under trimipramine than the one reported under placebo, our results indicate that trimipramine may have an antipsychotic potency.

[Serum interferon level and (2'-5')-oligo(A) synthetase activity in malignant melanoma]. / Serum-Interferonspiegel und (2'-5')-Oligo(A)-Synthetaseaktivität bei malignem Melanom.

Both the serum levels of interferon and the activity of lymphocytic (2'-5')-oligoadenylate synthetase (OAS) of 37 patients suffering from malignant melanoma-15 with low (I,I-II,II) and 22 with higher (III,IV,V) Clark levels-were compared with those of a group of healthy controls in order to detect a possible involvement of the interferon system in the pathological process. Previous results obtained in studies on relatively small groups of patients had suggested that melanoma patients with low Clark levels (i.e. biologically early melanoma) show elevated activities of OAS, while those with higher levels show normal values. In our present investigation on a larger sample of patients, we did not find any differences between these two melanoma groups and healthy persons with regard to the OAS activity. Thus we were not able to confirm the provisional results set up by previous studies.

[Serum interferon level and (2'-5')-oligo(A) synthetase activity in pityriasis rosea, basalioma, melanoma and molluscum contagiosum]. / Serum-Interferonspiegel und (2'-5')-Oligo(A)-Synthetaseaktivität bei Pityriasis rosea, Basaliom, Melanom und Molluscum contagiosum.

In various skin diseases with a possible viral and/or autoimmune etiology, the peripheral lymphocytes were studied with regard to serum interferon levels and the interferon-induced activity of (2'-5')-oligoadenylate synthetase (OAS). This enzyme is a sensitive marker of interferon and can be detected even some days after the clearance of interferon from the blood. In patients with pityriasis rosea (n = 13), basal cell carcinoma (n = 12), malignant melanoma (n = 11), and molluscum contagiosum (n = 13), the serum interferon levels were not increased. In comparison to healthy persons, 5 patients with melanoma (Clark's levels I, I-II and II) showed a significantly elevated activity of OAS. In 6 other patients with melanoma (Clark's level III, III-IV and IV), the OAS activity was not increased. Although the elevated activity of OAS found in patients with melanoma of lower Clark's levels indicates a participation of the interferon system in the course of the disease, our results do not allow a clear statement regarding a viral and/or an autoimmune etiology of the skin disease.

Influence of anticoagulants on the determination of interferon.

The presence of anticoagulants in plasma samples can spuriously increase the titers obtained in interferon bioassays by influencing interactions between the cell and the challenge virus. These artifacts can be eliminated by washing the test cell cultures before the virus challenge is added.

[Optical hallucinations in the aged with diseases of the eye]. / Optische Halluzinationen bei älteren Menschen mit Erkrankungen des Auges.

Two cases of Charles Bonnet Syndrome (CBS) showing an unusual history are reported. In a 67-year-old man visual hallucinations developed 38 years after bilateral optic nerve damage due to methyl alcohol poisoning. A 78-year-old woman suffering from bilateral advanced cataract experienced visual hallucinations which ceased after improvement of vision resulting from cataract extraction. Sensory deprivation and--possibly--central neurophysiological disturbance are to be regarded as important pathogenetic factors. Signs of cerebral dysfunction which could be relevant to the pathogenesis of CBS were revealed by the EEG.

[Results of long-term leukocyte interferon (alpha IFN) therapy using an individually determined dose schedule in recurrent laryngeal papillomatosis]. / Ergebnisse einer Langzeit-Leukozyten-Interferon (alpha-IFN)-Therapie nach einem individuell ermittelten Dosierungsschema bei rezidivierender Larynxpapillomatose.

Out of 24 patients with laryngeal papillomatosis 6 (5 female, 1 male) suffered from repeated relapses and underwent long-term treatment with alpha-IFN-therapy. Age at onset of the disease: 1 5/12-16 2/12 years. Duration of illness: 1-7 years, with several relapses were treated surgically and with laser-coagulation. Three out of 6 patients had a tracheal cannula and were cauterized by podophylline at 2-4 week intervals. IFN was given in dosages of 5-20 X 10(4) U/kg 2 or 3 times a week. IFN-dosage for each patient was determined using the induction kinetics of (2'-5')-oligo(A)synthetase (OAS) in the mononuclear cells of the circulating blood of patients with laryngeal papillomatosis. A continuous effect could be achieved by the dose of IFN determined in the described way always before OAS activity decreased to its initial level. All 6 patients responded favorably to the alpha-IFN-therapy. Two patients treated only with IFN showed remission without relapses. In 2 cases IFN was successfully used to prevent relapses after surgical treatment and laser-coagulation. In 2 patients with papillomatosis extending into the main bronchi the disease could only be brought to a standstill, i.e. it was not necessary to remove the papillomas. Two out of 3 patients with laryngeal papillomatosis could be decannulated. Long-term therapy following the above described principles is efficient and without significant side-effects. Three patients are in treatment for more than 3 10/12 years.

Evoked potential assessment of mental function during recovery from severe head injury.

Event-related potential recording and neuropsychologic testing were carried out on 18 severely head-injured patients and on a control group. At early stages of injury the patients had prolonged P3 latencies and reduced psychometric scores. In the assessment of individual patients the P3 latency proved to be a measure that diagnosed cognitive impairment with clinically acceptable levels of accurate classification. On retesting 4.6 +/- 1.6 months after trauma, normal values were found for the neuropsychologic measures and a residual latency prolongation for P3, indicating the P3 latency to be a sensitive index of subtle residual brain dysfunction due to head injury.

[Event-related brain potentials and intellectual impairment--a study in patients with brain tumor and craniocerebral trauma]. / Ereigniskorrelierte Hirnpotentiale und intellektuelle Beeinträchtigung--Eine Untersuchung bei Patienten mit Hirntumor und Schädelhirntrauma.

Event-related potential recording (component N1, P2, N2, and P3) and neuropsychological assessment of cognitive impairment were carried out on 15 patients with brain tumour, 15 patients with severe head injury and 24 controls. The tumour and trauma patients had significantly lower psychological test scores, smaller N1 amplitudes and longer N2 and P3 latencies than normals. For the tumour and trauma patients significant correlations were found between N2 and P3 latency and the Mini-Mental State test and memory tests. For individual patients abnormally increased N2 and P3 latency was found to occur in association with abnormally reduced neuropsychological test scores. N2 and P3 latency proved the only electrophysiological variables examined which provided a measure of cerebral functioning correlating with the psychometric variables. N2 and P3 latency may be regarded as a useful diagnostic test for cognitive impairment especially in patients with motor handicaps, to whom neuropsychological tests cannot be administered.

[Alpha interferon in the therapy of cutaneous T cell lymphomas]. / alpha-Interferon in der Therapie kutaner T-Zell-Lymphome.

5 patients suffering from T-cell lymphomas at different stages were treated with human alpha-interferone. One of the patients showed mild partial remission, two patients had but a poor and short-lasting improvement of their condition, in one case there was no change at all, and in another case, worsening of the clinical picture was observed. Controls of the relevant laboratory parameters (including NK-cells, T-cell subpopulations, antibodies and complement, oligo-(A)-synthetase, and interferone serum levels) did not always reveal the changes that had been expected to be induced by the therapy.