Kraepelin-oriented research-diagnosable schizophrenia,mania, and depression in schneider-negative schizophrenics

Summary The rigorous neo-Kraepelinean research criteria of the St. Louis/ Iowa and Taylor groups were applied to case record data of 116 first admissions of Schneider-negative schizophrenics—that is, those without first-rank symptoms (FRSs)—hospitalized in a strongly Schneider-oriented German University Psychiatric Clinic from 1962 to 1971. This sample had a total of 45.7% (53 cases) of psychiatric illness diagnosable by research methods. Indeed, only 31% (36 cases) of Schneider-negative schizophrenics turned out to have research-positive Kraepelin-oriented schizophrenia; and of these, 21 fulfilled both sets of research criteria for schizophrenia. It is important that 14.6% (17 cases) of Schneider-negative schizophrenia consisted of research-diagnosable affective disorder, with mania making up 5.2% and depression 9.4% of this figure. The findings suggest that a sample of Schneider-oriented schizophrenia without FRSs as routinely diagnosed in Germany does not seem to represent a clear-cut homogeneous and uncontaminated group of schizophrenics.     

Sensitivity of normal and malignant cells to shock waves

We examined the cytotoxic effect of shock waves for primary (embryonic chick kidney and thigh muscle) and permanently growing normal and malignant cells (human, rat, and mouse) in suspension. To avoid the influence of different media, the cells were suspended in phosphate buffered saline and shock wave treated. In all cases the acute cytotoxic effect (measured by flow cytometry) was a function of the applied shock waves. The investigated cells differed in their LD 50 values which, however, do not reveal a general difference in sensitivity to shock waves for normal and malignant cells.     

Pharmacokinetics of a single oral dose of muzolimine in cardiac failure

Summary The pharmacokinetics of a new high ceiling diuretic, muzolimine (Bay g 2821), were investigated after a single oral dose of 40 mg in 7 patients with cardiac failure (Stages I–IV, New York Heart Association classification), and in 2 healthy subjects. Plasma concentrations peaked 1–3 h after administration and declined according to a two-compartment model. The -phase (distribution phase) lasted until 12–16 h after administration and the mean t_1/2 was 3.6 h (range 2.3–4.7) in patients, and 2.6 h (range 2.3–2.9) in healthy subjects. The mean t_1/2 was 13.5 h (range 7.4–22.4) in the patients and 14.0 h (range 12.4–14.6) in healthy subjects. T_1/2 was not correlated with the degree of heart failure or with the area beneath the plasma concentration curve, which varied three-fold. The renal clearance of muzolimine was in the range 2.7–15.3 ml · min^–1 in 5 subjects in whom it was investigated. The pharmacokinetics of muzolimine appear not to be significantly altered by cardiac failure. The prolonged half-lives of the drug are probably responsible for the longer duration of diuretic action reported for muzolimine than for furosemide and bumetamide.     

Desipramine and some other antidepressant drugs decrease the major norepinephrine metabolite 3,4-dihydroxyphenylglycol-sulphate in the rat brain

Summary The O-methylated and non-O-methylated end metabolites of norepinephrine (NE) in the rat brain were measured to investigate a presumed shift in metabolism of NE from intra- to extraneuronal metabolism by uptake inhibitory antidepressant drugs. Desipramine (DMI), protriptyline and maprotiline in doses from 2.5–20 mg/kg reduced the concentration of the major non-O-methylated NE metabolite 3,4-dihydroxyphenylglycolsulphate (DOPEG-SO₄) in the whole rat brain to about 60–70% of controls, while imipramine, amitriptyline, butriptyline and clorimipramine (20 mg/kg, 21/2 h) caused no significant decrease. The major O-methylated NE metabolite free plus conjugated 3-methoxy-4-hydroxyphenylglycol (total-MOPEG) was almost unaffected by all the drugs 21/2 h after administration. At longer time intervals, however, i.e. 5 h, a high dose of DMI (10 mg/kg, s.c.) decreased total-MOPEG to 75% of controls. DOPEG-SO₄ was decreased by DMI in all brain regions examined: cortex, hippocampus, cerebellum and brain rest. ³H-normetanephrine was increased 1/2h and 1 h after intraventricular injection of ³H-dopamine, and at the same time interval both total-³H-MOPEG and ³H-DOPEG-SO₄ were decreased. Amine storage in granules was not necessary for the action of DMI since DMI retained its metabolite-lowering effects in reserpinized rats. Inhibition of NE uptake in vivo did not induce the expected increase in the major extraneuronal NE metabolite MOPEG, but only the expected decreased in DOPEG-SO₄. The reduction of both the major NE metabolites by DMI suggests a decreased metabolism and turnover of NE.Abbreviations Used NE norepinephrine - DOPEG 3,4-dihydroxyphenylglycol - DOPEG-SO₄ DOPEG sulphate ester - MOPEG 3-methoxy-4-hydroxyphenylglycol - total-MOPEG free plus conjugated MOPEG - DOPAC 3,4-dihydroxyphenylacetic acid - HVA homovanillic acid - NM normetanephrine - DA dopamine - DMI desipramine - MAO monoamine oxidase     

Chronic treatment with desipramine caused a sustained decrease of 3,4-dihydroxyphenylglycol-sulphate and total 3-methoxy-4-hydroxyphenylglycol in the rat brain

Summary The 2 major metabolites of norepinephrine (NE), 3,4-dihydroxyphenylglycol-sulphate (DOPEG-SO₄) and free plus conjugated 3-methoxy-4-hydroxyphenylglycol (total-MOPEG), both their endogenous concentrations and their accumulation from the NE-precursors ³H-tyrosine or ³H-dopamine, were determined in the whole rat brain to assess the effect of chronic treatment with desipramine (DMI), imipramine and amitriptyline. DOPEG-SO₄ was decreased 2 h and 24 h after the last administration of DMI (10 mg/kg twice daily for 4, 10 or 20 days) or imipramine (10 mg/kg twice daily for 10 days). When measured within 24 h after the last dose of DMI or imipramine, several schedules resulted in reduced accumulation of total-³H-MOPEG and ³H-NE, while ³H-NE and MOPEG were unchanged in the remaining schedules. These results indicate that DMI retains its ability to decrease NE-turnover over a period of 20 days of treatment. Forty-eight hours or 72 h after the last administration of desipramine and imipramine an overshoot was observed in NE-metabolism, consisting of increased levels of total-³H-MOPEG and endogenous total-MOPEG; DOPEG-SO₄ was some-times concomitantly increased. The overshoot was more consistent after 20 or 10 days of treatment than after 4 days of treatment. This finding, together with a tendency to partial tolerance to the metabolite decreasing effects of DMI, indicate that adaptive changes occur in the NE system after treatment for 10–20 days with DMI or imipramine.Abbreviations Used NE norepinephrine - DOPEG 3,4-dihydroxyphenylglycol - DOPEG-SO₄ DOPEG sulphate ester - MOPEG 3-methoxy-4-hydroxyphenylglycol - total-MOPEG free plus conjugated MOPEG - DOPAC 3,4-dihydroxyphenylacetic acid - HVA homovanillic acid - NM normetanephrine - DA dopamine - DMI desipramine     

45. Die Schocklunge - ein neues Behandlungsprinzip

Zusammenfassung In einer retrospektiven Studie werden an 2 Kollektiven von je 38 und 60 Patienten mit Pneumonitis (Schocklunge) zwei Behandlungsmethoden verglichen. Die erste Gruppe erhielt Heparin in Kombination mit Aprotinin. Im zweiten Kollektiv gaben wir Heparin, Frischplasma, Nicotinsäure, Methylprednisolon und alpha-Receptor-Blocker. In dem ersten Kollektiv betrug die Gesamtletalität 50%. Von den beatmeten Patienten verstarben 64%. Im zweiten Kollektiv betrug die Gesamtletalität 26,5%. Von den beatmeten Patienten verstarben 33%. Auf Grund unserer Erfolge halten wir zum jetzigen Zeitpunkt eine Kombinationstherapie mit Aprotonin für nicht mehr indiziert.     

Validation of BIOMED-2 multiplex PCR tubes for detection of TCRB gene rearrangements in T-cell malignancies.

The BIOMED-2 Concerted Action BMH4-CT98-3936 on 'Polymerase chain reaction (PCR)-based clonality studies for early diagnosis of lymphoproliferative disorders' developed standardized PCR protocols for detection of immunoglobulin (Ig) and T-cell receptor (TCR) rearrangements, including TCR beta (TCRB). As no comparable TCRB PCR method pre-existed and only a limited number of samples was tested within the BIOMED-2 study, we initiated this study for further validation of the newly developed TCRB PCR approach by comparing PCR data with previously generated Southern blot (SB) data in a series of 66 immature (ALL) and 36 mature T-cell malignancies. In 91% of cases, concordant PCR and SB results were found. Discrepancies consisted of either failure to detect SB-detected TCRB rearrangements by PCR (6.5%) or detection of an additional non-SB defined rearrangement (2.5%). In 99% of cases (99/100), at least one clonal TCRB rearrangement was detected by PCR in the SB-positive cases. A predominance of complete Vbeta-Jbeta rearrangements was seen in TCRalphabeta(+) T-cell malignancies and CD3-negative T-ALL (100 and 90%, respectively), whereas in TCRgammadelta(+) T-ALL, more incomplete Dbeta-Jbeta TCRB rearrangements were detected (73%). Our results underline the reliability of this new TCRB PCR method and its strategic applicability in clonality diagnostics of lymphoproliferative disorders and MRD studies.