Analysis of surgical management of calvarial tumours and first results of a newly designed robotic trepanation system.

This study was performed to evaluate the surgical strategy in patients with calvarial tumours, in order to design and modify a robot-assisted trepanation system. A total of 75 patients underwent craniectomy for the treatment of calvarial tumours during the 10-year period from 1993 to 2002. The patients' complaints, the size, location and histology of the tumour, and the various cranioplasty techniques used were analysed retrospectively. In a second procedure several craniectomies at typical locations according to the study's results were performed in a laboratory setting using a hexapod robotic tool, constructed at the Helmholtz-Institute, RWTH Aachen University, and plastic model heads. The workflow was documented and the reproducibility and the accuracy of the procedure were registered. A total of 83 surgical procedures were performed on 75 patients. The majority (87 %) of lesions treated surgically were located in the frontal, temporal and anterior parts of the parietal region. Histological examination revealed benign lesions in 66 % of the patients and dural involvement in 46 %. According to these results craniectomies were performed using the robotic system. Mean positioning accuracy of the robotic system while milling was 0.24 mm, with a standard deviation of 0.04 mm, and maximum error under 1 mm. Craniectomies leaving a 1-mm layer of the tabula interna intact to ensure a healthy dura were performed in several regions successfully. The majority of calvarial tumours, requiring surgical treatment in our patients, were located in cosmetically relevant areas in which drilling can be carried out with the robotic trepanation system. Consequently, the surgical approach had to be planned carefully in order to achieve a good cosmetic outcome.     

Phase I evaluation of diaziquone in childhood cancer

Summary We conducted a phase I clinical study of aziridinylbenzoquinone (Diaziquone, AZQ) given as a 4 hour infusion weekly × 4. Forty-five children with recurrent acute leukemia and 33 children with various advanced solid tumors participated. Severe myelosuppression was the dose limiting toxic effect, occurring in all patients at the upper dose levels. Gastrointestinal and hepatic toxicities were infrequent and not severe. No allergic reactions occurred. Objective tumor regression was noted in 3 of 25 patients with a CNS tumor and in 6 of 45 patients with acute leukemia. For phase II trials the recommended dosage of Diaziquone given by this schedule is 18 mg/M²×4 for patients with a solid tumor, and is 30 mg/M²/week × 4 for children with acute leukemia.     

Flumazenil exerts intrinsic activity on sleep EEG and nocturnal hormone secretion in normal controls

The physiological function of benzodiazepine (BDZ) receptors includes regulation of sleep and neuroendocrine activity. Most of the pharmacological effects of BDZ are blocked by flumazenil. However, recent neurological and behavioral studies suggest that flumazenil has its own central intrinsic activity. This issue was addressed in a study of the sleep EEG and the nocturnal secretion of growth hormone and cortisol in ten normal male controls, who were given flumazenil either alone or in combination with the BDZ agonist midazolam, placebo and midazolam alone. Flumazenil prompted an increase in sleep onset latency, a decrease in slow wave sleep and an increase in wakefulness. Plasma cortisol concentrations after flumazenil administration were lower than after midazolam. Both flumazenil and midazolam decreased nocturnal growth hormone secretion. After simultaneous application of both BDZ receptor ligands the growth hormone blunting was amplified. Our study demonstrates that at the level of the sleep EEG and neuroendocrine activity flumazenil is capable of exerting both agonistic and inverse agonistic or antagonistic effects.Parts of this study were presented at the 69th Meeting of the Deutsche Physiologische Gesellschaft, Freiburg, 6–8 March, 1991     

Nocturnal sleep in huntington's disease

Summary Nocturnal sleep was studied in 16 inpatients with Huntington's disease. In comparison with healthy controls, patients exhibited a disturbed sleep pattern with increased sleep onset latency, reduced sleep efficiency, frequent nocturnal awakenings, more time spent awake and less slow wave sleep. These abnormalities correlated in part with duration of illness, severity of clinical symptoms, and degree of atrophy of the caudate nucleus. Patients showed an increased density of sleep spindles.     

Correlates of the DSM-III-R global assessment of functioning scale in patients attending a child and adolescent psychiatric service

Sex, socioeconomic status, intelligence, a clinical symptom score, and an index of abnormal psychosocial situations as proposed by a recent WHO draft were studied as correlates of the Global Assessment of Functioning Scale (GAFS), which comprises Axis V of theDSM-III-R. Whereas all parameters correlated significantly with the GAFS score, only total symptom domain score displayed a meaningful association. It was concluded that the GAFS contributes significantly to clinical information as an independent source.

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Zusammenfassung Es wurden ein klinischer Symptomwert, ein Index für abnorme psychosoziale Situationen gemäß einem unlängst erschienenen WHO-Dokument, Geschlecht, sozioökonomischer Status und Intelligenz als Korrelate der Global Assessment of Functioning Scale (GAFS) untersucht, welche die Achse V des DSM-III-R bildet. Während alle Parameter

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Résumé Le sexe, le statut socio-économique, l'intelligence, le score des symptômes cliniques, et un index de situations psychosociales anormales proposés par un récent projet del'OMS furent étudiés en corrélation avec l'évaluation globale de l'échelle de fonctionnement (Global Assessment of Functioning Scale G.A.F.S.) qui correspond à l'axe V du DSM III R. Tandis que tous les paramètres sont corrélés significativement avec un score GAFS, seul le score symptomatique total n'offre pas d'association significative. Les auteurs ont conclu que le GAFS contribue significativement à l'information clinique en tant que source indépendante.

     

Partial replication of a DRD4 association in ADHD individuals using a statistically derived quantitative trait for ADHD in a family-based association test.

BACKGROUND: Previous research found an association between single nucleotide polymorphisms (SNPs) in the promoter region of DRD4 and statistically derived phenotypes generated from attention-deficit/hyperactivity disorder (ADHD) symptoms. We sought to replicate this finding by using the same methodology in an independent sample of ADHD individuals. METHODS: Four SNPs were genotyped in and around DRD4 in 2631 individuals in 642 families. We developed a quantitative phenotype at each SNP by weighting nine inattentive and nine hyperactive-impulsive symptoms. The weights were selected to maximize the heritability at each SNP. Once a quantitative phenotype was generated at each SNP, the screening procedure implemented in PBAT was used to select and test the five SNPs/genetic model combinations with the greatest power to detect an association for DRD4. RESULTS: One of the four SNPs was associated with the quantitative phenotypes generated from the ADHD symptoms (corrected p-values = .02). A rank ordering of the correlation between each of the ADHD symptoms and the quantitative phenotype suggested that hyperactive-impulsive symptoms were more strongly correlated with the phenotype; however, including inattentive symptoms was necessary to achieve a significant result. CONCLUSIONS: This study partially replicated a previous finding by identifying an association between rs7124601 and a quantitative trait generated from ADHD symptoms. The rs7124601 is in linkage disequilibrium (LD) with the SNPs identified previously. In contrast to the previous study, this finding suggests that both hyperactive-impulsive and inattentive symptoms are important in the association.     

Sodium fluxes during hemodialysis

Three sets of experiments were performed to determine the effect of the dialysate sodium concentration on the sodium balance of patients undergoing maintenance hemodialysis. First, patients were treated with three different dialysate bath sodium concentrations: 125-132 mEq/l (n = 7), 135-140 mEq/l (n = 11) and 145-150 mEq/l (n = 6). We demonstrated that the pretreatment plasma sodium concentration was independent of the sodium concentration of the dialysate used. Second, the plasma sodium concentration available for diffusion during the treatment was calculated from the plasma sodium concentration and the plasma proteins. The accuracy of this calculation was demonstrated by comparing the predicted value with the concentration of sodium measured in an ultrafiltrate obtained at minimal filtration fraction. Third, the sodium fluxes using a hypernatremic or hyponatremic dialysate were calculated for 100 ml of plasma going through the dialyzer. At steady state, no significant differences in net sodium fluxes were demonstrated between hyper- and hyponatremic dialysis.