Intracranial germ-cell tumours — treatment results and residuals

There is only sparse information about the development of children after successful treatment for intracranial germ-cell tumours. Between January 1981 and June 1992, 26 children with intracranial germ-cell tumours were treated in the University Hospital Hamburg-Eppendorf. We report on treatment results, long standing residuals and the quality of life of these patients. The long-term event-free survival was 88% for the germinomas and 43% for the malignant teratomas. Of the patients 58% had no relevant functional neurological deficits and 37% had mild impairment. Only 1 patient with metastatic disease was severely handicapped. Six patients showed neuro-endocrine dysfunction. All of them had suprasellar/hypothalamic lesions and all received successful substitution therapy. As to neuropsychological functions, 53% of the patients had no or only mild disturbances. The most affected function was speed of information processing. Of the children 69% were able to proceed with their education at the same level as before therapy. The overall self-assessment revealed good results in 75% of the patients.Conclusion After surgical removal and radiation therapy long-term survival of intracranial germinomas amounts to 88%. Despite craniospinal axis radiation severe residuals are rare and a good quality of life is common. In malignant teratomas treatment regimens including chemotherapy are much less successful.     

Antimetastatic action of the prostacyclin analogue cicaprost in experimental mammary tumors

Summary In breast cancer, the survival rate strongly depends on the number of lymph nodes involved. A drug with a specific inhibitory activity on lymph node and organ metastases would therefore be a candidate for adjuvant therapy after surgery. Prostacyclin and its stable analogues have been shown to interfere with certain steps of the metastatic cascade and to inhibit the number of lung colonies after i.v.-inoculation of various tumor cell lines. Our data reveal that cicaprost, a metabolically stable and orally active analogue of prostacyclin, has pronounced antimetastatic effects in a series of spontaneously metastasizing rodent tumors. In the SMT 2a and 13762 MTLn3 mammary carcinomas of the rat, cicaprost given daily from the day of tumor implantation strongly inhibits the number of lung metastases as well as lymph node weights without exerting an effect on the primary tumor. Even starting treatment when palpable primary tumors are present gives a pronounced antimetastatic activity. To demonstrate that cicaprost has an effect on metastases already settled in the respective organ, treatment was started after surgical removal of the primary tumor. In the SMT 2a tumor, a strong inhibition of the number of metastases was shown. Interestingly, a perioperative treatment schedule was also effective in both models used. As primary tumor growth in vivo or proliferation in vitro remained unchanged by cicaprost, its mode of action seems to be related to one or more mechanisms of the metastatic process. In tumor cell lines expressing a functional prostacyclin receptor, stimulated tumor cell migration is inhibited and changes of differentiation status are obvious. In conclusion, cicaprost strongly inhibits lymph node and organ metastases of spontaneously metastasizing rodent mammary tumors with a mode of action different from cytostatic or antihormonal drugs.Presented at the symposium "New Approaches in the Therapy of Breast Cancer", Georgetown University Medical Center, Washington DC, October 1994, generously supported by an education grant from Bristol-Myers Squibb.     

Healing more than the body

Louisville has become the Mecca for new and classical theater, growing far beyond mere regionalism, with continual support from Humana.     

Citrate and recurrent idiopathic calcium urolithiasis

Summary In idiopathic recurrent calcium urolithiasis (RCU) in men (n=37) the metabolic effects of oral tripotassium citrate (PC) were investigated in a longitudinal field study. The patients were either normo- (n=22) or hypocitraturic (n=15). Laboratory examinations were performed before, and after 3, 6, and more than 12 months of medication. Acceptance of PC was poor, mainly because of the salty taste of the tablet preparation chosen, and a number of participants dropped out of the study. In the remaining participants, compliance was acceptable when evaluated on the basis of urinary potassium and undesired side effects did not occur. In the short term (up to 3 months), PC evoked compensated metabolic alkalosis (pH and citrate in urine increased; blood gases remained normal), a drop in urinary calcium, together with increasing oxaluria, hydroxyapatite supersaturation, and calcium phosphate crystalluria. In the long term (>12 months) PC urinary pH and citrate dissociated, in that pH returned to pretreatment baseline values, whereas citrate stayed at high levels. In normocitraturics but not in hypocitraturics, urinary urea and sodium in creased with PC. Hypocitraturics appeared to be less sensitive to the effects of PC, as reflected by the relatively small rise in urinary pH and citrate, and they maintained higher mean levels of indicators of bone metabolism (osteocalcin, alkaline phosphatase, hydroxyproline) despite continuous administration of PC. It was concluded that although the PC tablet preparation was effective it may not be an ideal anti-stone drug treatment in the long term and that, especially in hypocitraturiecs, the intrinsic metabolic defect of RCU may not be sufficiently well controlled.     

Frontal dysfunction in schizophrenia – a new electrophysiological classifier for research and clinical applications

We determined whether schizophrenic patients can be reliably classified with electrophysiological tools. We developed a fully computerized classifier based on 5 minutes of EEG recording during an acoustical choice reaction time task (AMDP-module IV). We included factorized variables from the frequency domain and evoked potentials (N100/P200-complex) from central and frontal electrodes, which were preprocessed in a sample of 150 normal subjects prior to classification. We applied discriminant analyses to the electrophysiological data from depressive, schizophrenic and schizotypal subjects, most of them being unmedicated or drug-naive. The classifier was developed on a training set (33 schizophrenics, 49 normals) and tested on an independent sample (32 schizophrenics, 49 normals). A simple three-variable classifier was found to classify schizophrenics and normals in 77% of those tested correctly. Diagnostic specificity of the classifier proved to be low as the inclusion of depressive patients (n= 60) significantly decreased classification power. It was demonstrated that atypical but not typical neuroleptic drugs may influence the classification results. Correctly classified schizophrenics showed significantly more negative symptoms and slower reaction times than those schizophrenics who were misclassified as normals. In contrast, these misclassified schizophrenics showed a non-significant trend for more positive symptoms and shorter reaction times. As the correctly classified schizophrenics showed increased frontally pronounced delta-activity and decreased signal power of the N100/P200 amplitude, it was concluded that these schizophrenics show dysfunction of the frontal lobe. It is proposed that this new classifier can be useful for clinical and research applications when subtyping of schizophrenics with detection of frontal dysfunction as the aim.