Spätdiagnose einer Phenylketonurie bei einem 21/2 Jahre alten Mädchen

Zusammenfassung Neugeborenen-screening-Untersuchungen auf angeborene Stoffwechseldefekte werden seit 1962 in der Bundesrepublik durchgeführt. Wir berichten über eine Patientin, bei der die Diagnose einer Phenylketonurie trotz zun?chst korrekt durchgeführtem Neugeborenen-screening mit pathologischem Ergebnis von 1067 μmol/l bzw. 17,6 mg% Phenylalanin erst im Alter von 2¹/₂ Jahren gestellt wurde, was eine bleibende k?rperliche und geistige Behinderung der Patientin zur Folge hat. Diskussion: Anhand des beschriebenen Falls wird erneut auf die Notwendigkeit der korrekten Verfolgung pathologischer Screening-Befunde durch Screening- und Behandlungszentren hingewiesen.      

Neurophysiological findings in long-term survivors of acute lymphoblastic leukaemia in childhood treated with the BFM protocol 81 SR-A/B

Monitoring of therapy-related late effects after acute lymphoblastic leukaemia (ALL) therapy in childhood has become an increasingly important field in posttherapeutic patient surveillance. The usefulness of neurophysiological investigations (e.g. EEG, evoked potentials (EP)) as part of these attempts is controversial. The present report focuses on this problem and the question whether and to what extent routinely performed EEG recordings and visual evoked potentials (VEP) were correlated with further measures of CNS integrity. EEGs and VEPs were recorded in 163 asymptomatic long-term survivors of ALL in childhood during a large retrospective multicentre study evaluating CNS late sequelae following antileukaemic therapy. Fifty-two ALL long-term survivors (4.5–10.6 years after end of therapy, median: 8.8 years), who had been treated according to BFM-81 SR-A (n=30) or SR-B (n=22) were selected for this analysis focusing on therapy-related CNS late effects. Therapy protocols differed with regard to the mode for CNS prophylaxis: SR-A, cranial irradiation with intrathecal methotrexate; SR-B, intrathecal and iv methotrexate. Neurophysiological findings were correlated with illness- and treatment-related parameters, as well as with data on the morphological, neurological and psychological status of the CNS. At the time of follow-up neurophysiological measures were abnormal in 28/52 cases (53.8%). Neither illness- nor therapy-specific differences in CNS prophylaxis showed any relationship to EEG/VEP outcome any relationship to EEG/VEP outcome in this reduced group of the whole study population. Children with EEG/VEP abnormalities showed a significantly higher incidence of structural CNS disturbances compared to those with inconspicuous neurophysiological recordings (60.9% vs 31.8%). However, in this special subject group there was no specific neurophysiological finding for a specific morphological substrate, neurological or psychological deficiency and vice versa. Conclusion Routinely performed EEG/VEP investi gations are not very helpful measures to predict the presence or degree of behavioural deficiencies, neuro‐logical disturbances, or morphological CNS abnor‐malities. Patients who received cranial irradiation or systemic methotrexate applications showed the same incidence of neurophysiological disturbances without evidence for specific neurotoxic correlates. Received: 29 March 1996 / Accepted: 9 December 1996     

Unexpected severe myelotoxicity of gemcitabine in pretreated breast cancer patients

Gemcitabine is a chemotherapeutic agent with proven antitumor effects in pancreatic and non-small cell lung cancer; however, studies establishing the definite significance in other solid tumors are still in progress. We herein present three female patients with advanced breast cancer who received gemcitabine as salvage chemotherapy. Gemcitabine at a dose of 1250 mg/m2 was scheduled for days 1, 8 and 15 with a subsequent rest for 1 week. However, within 1 week after the very first administration of gemcitabine myelotoxicity WHO grade IV occurred in all patients, leading to discontinuation of therapy. In two patients this gemcitabine-induced hematotoxicity could be overcome by means of vigorous supportive care, but one patient died after cerebral bleeding due to severe thrombocytopenia. We conclude that gemcitabine in heavily pretreated breast cancer patients should only be used with extreme caution with special focus on platelet counts until solid data from clinical studies for doses and schedules are available.     

Home self-assessment and self-treatment of obsessive-compulsive disorder using a manual and a computer-conducted telephone interview: replication of a UK-US study.

BACKGROUND: This open study replicates and extends previous pilot work with BT STEPS, a self-therapy system to assess and treat obsessive-compulsive disorder (OCD) through exposure and ritual prevention. METHOD: 21 OCD patients entered this open trial, using a self-guiding manual and any Touch-Tone telephone to access computer-driven interviews via an Interactive Voice Response system. The patients also used the system to rate progress on rating scales. RESULTS: The results support those of the previous open study. Of the 21 patients, 16 (76%) completed self-assessment over a mean of 21 days. Of these, 10 patients (48%) went on to do 2 or more exposure and ritual prevention sessions over a mean of 64 days; they improved significantly on OCD symptoms, as much as is usual with serotonin reuptake inhibitor medication, and in mood and work/social adjustment. Improvement was predicted by baseline motivation and by rapid completion of self-assessment with BT STEPS, even though self-assessment alone was not therapeutic. CONCLUSION: The significant improvement in the intent-to-treat analysis was due to the subgroup of patients (48% of those who began BT STEPS) who went beyond self-assessment to do exposure and ritual prevention self-therapy at home guided by BT STEPS. A controlled trial is now needed.     

In vitro and in vivo assessment of the Ventrak 1550/Capnogard 1265 for single breath carbon dioxide analysis in neonates

The Ventrak 1550/Capnogard 1265 (V&C) enables deadspace (VD) measurements to be made in neonates. The aim of our studies was to validate the V&C device for VD measurement in vitro (lung model) and in vivo (adult rabbits). Methods of measurement of VD using the V&C (automatic computation, interactive carbon dioxide-volume plot analysis, Bohr equation) were tested by comparing known added deadspace volumes (VDadd) with calculated VDadd. After producing a change in alveolar (VDalv) and physiological (VDphys) deadspace by in vivo broncho-alveolar lavage, VDalv and VDphys computed automatically were compared with values calculated by the Bohr-Enghoff equations. VDadd was slightly underestimated (absolute error in mean: automatically - 0.61 ml; interactively -0.55 ml; Bohr -0.54 ml). The higher the VDadd, the lower the absolute errors and coefficients of variation (cv). The highest cv occurred for automatic analysis (approximately 11%) compared with < 6% for interactive analysis or the Bohr equation. Average differences between results calculated automatically and by the Bohr- Enghoff equation were -0.79 ml for VDalv (95% confidence interval -2.02 to 0.44 ml) and -0.23 ml for VDphys (-0.6 to 0.14 ml). We conclude that the V&C can be used in newborn infants undergoing mechanical ventilation, if changes in VD are < 5 ml, interactive analysis or the Bohr equation should be used.      

Electronmicroscopical and morphometrical study of rat hippocampal synapses]

The neuronal structure and synaptology of the hippocampus of the rat are studied using neurohistological, electron microscopical and morphometrical methods. After Golgi-impregnations the neurons of the hippocampus were classified by reason of special morphological features (pericaryon, dendritic, ramification, course and termination of the axons). The neurons of the hippocampus show from the region CA4 towards the region CA1 an increasing "pyramidalization" which is explained respecting the neuronal structure and synaptic architectonics as the result of a specific presynaptic representation of afferents at the neurons. The high degree of differentiation of the CA1-pyramids speaks for the progressive developmental tendency in the phylogenesis of these pyramids compared to the neocortical neurons. The ultrastructural investigations of the hippocampus show that each individual layer of the regions CA1, CA3 and CA4 has a characteristic synaptic architectonics. In all hippocampal layers the axo-spino-dendritic contacts are the most frequent type of synapses with the structural characteristics of the excitatory synapses; the synaptic contact appears as "Bouton en passage" respectively as "Bouton terminal". The axosomatic synapses of the stratum pyramidale (CA1 to CA3) predominantly are developed as symmetrical contacts with inhibitory function. As the terminals of the basket cells they represent the morphological correlate for the recurrent inhibitation of the pyramids by the inhibitory effecting basket cells. In the supra- and infrapyramidal layers of the regions CA3 and CA4 special contacts are developed for the connection withe the mossy fiber terminals--at the pericarya and the main dendrites as so-called somatic and dendritic protrusions and as micro-dendrites. As has been established for the neocortex, the dendritic spines are the decisive receptive postsynaptic structural characteristic of the hippocampus as well. Pre- and postsynaptic elements show a broad scope of variation in forming their structures. This also applies to the intrahippocampal systems with their highly complex structure which is the morphological expression of an extremely high degree of differentiation. The morphometrical investigations of the ultrastructure of synapses enclose the calculation of the number of synapses per mm3 of the volume of layers, the average individual volume of synapses, the presynaptic portion of volume of the relative volume of cortex of the hippocampal layers as well as the average number and size of the synaptic vesicles. The average number of synapses per mm3 brain tissue runs in CA1 to 5,9 X 10(9), in CA3 to 7,9 X 10(9) andin CA4 to 8,7 X 10(9) synapses per mm3. The average individual volume of synapses amounts to 0,2-0,3 mm3 whereas the average portion of volume of the presynaptic structures per relative cortical volume comes to 14% in CA1, 16-19% in CA3 and 15% in CA4.