Receptor binding of N-(methyl-11C) clozapine in the brain of rhesus monkey studied by positron emission tomography (PET)

By means of positron emission tomography the uptake and kinetics of N-(methyl-¹¹C)clozapine in different brain regions have been studied in Rhesus monkeys. ¹¹C-clozapine rapidly entered the brain and maximum radioactive uptake was seen 5–12 min after administration. Highest uptake was measured in the striatum. Other regions with an uptake higher than in the cerebellum were thalamus and mesencephalon. The radioactivity from different brain regions decreased with an elimination half-life of about 5 h and parallelled the plasma kinetics of unlabelled clozapine. The striatum/cerebellum ratio of ¹¹C-clozapine-derived radioactivity remained constant during the period studied and did not change after pretreatment with atropine. In contrast, the striatum/cerebellum ratio was somewhat lower after pretreatment with N-methylspiperone (NMSP), indicating competition for the same binding sites in the striatum. After pretreatment with increasing doses of clozapine, a dose-dependent protection of binding sites in the striatum for ¹¹C-NMSP was seen. It is concluded that clozapine is more loosely bound to dopamine receptors in the striatum than N-methylspiperone and that the kinetics of clozapine in the brain parallel that in the plasma. The binding properties of clozapine within the brain may explain some of the clinical properties of the drug.     

Wertigkeit des C-reaktiven Proteins (CRP) beim Amnioninfektionssyndrom

Ohne Zusammenfassung     

Isolation and interspecies-transfer of a plasmid from Pasteurella multocida encoding for streptomycin resistance

A plasmid encoding streptomycin-resistance could be detected in 13 of 32 Pasteurella multocida-cultures isolated from cattle and swine. The plasmid of these cultures proved to be similar upon Southern blot hybridization. It could be transformed into Escherichia coli 490A, where it also expressed streptomycin resistance.     

Ursachen und Diagnostik der Laterogenie

Zusammenfassung Zur Klärung möglicher Ursachenfaktoren, die zur Entstehung einer Laterogenie beitragen, wurden 22 Patienten nach klinisch funktionellen Kriterien ausgewählt und computertomographisch untersucht. Durch die bessere Vergleichbarkeit überlagerungsfrei abgebildeter morphologischer Strukturen im Computertomogramm konnte eine Einteilung in vier Ursachenbereiche erfolgen, innerhalb derer verschiedene asymmetrische Einzelabweichungen analysiert und diskutiert wurden. Es hat sich gezeigt, daß die computertomographisch strukturelle Analyse bei dieser Problemstellung anderen Untersuchungsmethoden überlegen ist und im Einzelfall neue Anhaltspunkte für eine prognostische Abschätzung weiterer Entwicklungstendenzen bietet.

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Summary To determine the possible reasons, contributing to the formation of laterogenia, 22 patients were investigated by computer tomography. The patients were selected according to clinical and functional criteria. As CT gives a more accurate comparison of structures without superimposition it was possible to subdivide the causative factors into four groups. Within each of them, different asymmetric deviations could be analysed and discussed. It was shown, that structural-CT analysis is superior to other methods of investigation, particularly for this kind of problem. Furthermore it provides new criteria for a prognostic evaluation of development.

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Résumé Pour rechercher les causes qui contribuent à la formation d'une latérogénie, on avait examiné 22 patients, sélectionnés par leur aspect clinique et fonctionnel, à l'aide d'un computer analysant des tomographies. Grâce à ce computer, la meilleure comparaison des structures, représentées sans superposition, donnait la possibilité d'en classifier les causes en quatre catégories, dans lesquelles on analysait et discutait les différentes déviations asymétriques. Il est évident, que dans ces problèmes l'analyse computertomographique-structurelle surpasse d'autres méthodes d'examen et qu'elle offre de nouveaux critères pour prévoir d'autres tendances du développement.

     

Hereditary spherocytosis. Recent experience and current concepts of pathophysiology.

Hereditary spherocytosis is a clinically heterogeneous, genetically determined red blood cell membrane disorder resulting in hemolytic anemia. A deficiency of spectrin, the largest and most abundant structural protein of the erythrocyte membrane skeleton, results in the formation of spherocytes which lack the strength, durability, and flexibility to withstand the stresses of the circulation. Clinical manifestations of the disease are primarily dependent on the severity of hemolysis, which additionally results in an increased incidence of pigment gallstones. The likelihood of cholelithiasis is directly related to patient age and is uncommon before 10 years of age. Splenectomy is indicated in virtually every patient. When the disease is diagnosed in early childhood, the risk of overwhelming postsplenectomy sepsis makes it advisable to delay splenectomy until after 6 years of age if possible. At the time of splenectomy, it is important to identify and remove any accessory spleens. If gallstones are present, cholecystectomy should be performed. Although spherocytosis persists following splenectomy, hemolysis is alleviated and clinical cure of the anemia is achieved for most patients. Patients with recessively inherited spherocytosis are exceptions. Although they are significantly benefited by splenectomy, their anemia is not completely corrected. Splenectomy reduces hemolysis in all patients and thereby decreases the risk for development of pigment gallstones. Excision of an enlarged spleen removes the danger of traumatic rupture.     

Pressure stability of nasal CPAP and bilevel devices

Summary Question of the study   Nasal continuous positive airway pressure (CPAP) prevents collapse of the upper airway during sleep in patients with obstructive sleep apnea provided that a positive transmural pressure can be maintained during inspiration. We examined pressure-flow characteristics in seven CPAP and bilevel devices during spontaneous breathing.
Methods   The CPAP devices were set to a pressure level of 9.8  hPa (10  cm H₂O) and adapted to a pneumotachograph using a standard CPAP hose and an outlet valve. We continuously measured flow, volume and pressure during resting ventilation and increasing voluntary hyperventilation and analysed the dependence of the variables on a breath-to-breath basis.
Results   Mean CPAP pressures differed between the devices (9.9 – 10.6  hPa) despite the same settings. In all machines pressure fell during inspiration to 8.4 – 9.8  hPa and increased during expiration to 11.1 – 11.7  hPa. This effect increased with higher flow rates. Maximum expiratory pressures rose to 12 – 19  hPa at peak flow rates of 2 l/s, mean expiratory pressures to 9.5 – 16  hPa. Inspiratory pressures dropped to 8.5 – 4.5  hPa (minimum) and 10.5 – 6.0 (mean). Bilevel devices showed a higher stability than CPAP devices. Pressure swings during the respiratory cycle increased the additional work of breathing.
Conclusions   Due to differences in mean and effective CPAP levels CPAP devices are not simply exchangeable but should be individually adapted. Patients with higher minute ventilation might benefit from more stable CPAP machines. The impact on patients' compliance remains to be evaluated.     

Fibrosarcoma of the breast: mammographic findings in five cases.

The mammographic features of fibrosarcoma of the breast, a rare malignant tumor, have not been described. Accordingly, we reviewed the mammograms, pathology reports, and medical records of five women with this tumor. All cases had surgical biopsies and a diagnosis made by histologic evaluation. The age of the patients ranged from 48 to 79 years. Histologically, three of the five fibrosarcomas were thought to have arisen from phyllodes tumor, and four were palpable. On mammograms, the tumors were dense masses with largely indistinct margins, ranging from 1.5 to 7.0 cm in diameter. One contained calcified osseous elements suggesting osseous trabeculae. Although the osseous trabeculae in that tumor strongly suggested sarcoma, most of the tumors had a nonspecific appearance on mammograms. Fibrosarcomas of the breast have a nonspecific mammographic appearance. Surgical biopsy and histologic evaluation are necessary for definitive diagnosis.     

HLA-DR7 predicts the response to alkylating agents in steroid-sensitive nephrotic syndrome

There is a lack of reliable predictors of the response to alkylating agents in children with idiopathic nephrotic syndrome (NS). HLA-DR7 is strongly associated with the frequency of relapses in steroid-sensitive NS before cytostatic therapy. We therefore examined retrospectively the time to the first relapse and the incidence of subsequent relapses in 54 HLA-typed children with frequently relapsing NS, after treatment with cyclophosphamide (n = 49) or chlorambucil (n = 5) for 8 or 12 weeks; 38 patients were HLA-DR7 positive and 16 negative with 80% in both groups being steroid dependent. HLA typing was performed using serological or DNA typing methods. Renal biopsy showed minimal glomerular changes. A lower proportion of HLA-DR7 positive than negative patients remained in remission after 3 years (36% vs. 81%, P<0.02) and 5 years (36% vs. 72%, P<0.03). In the first 3 years after cytostatic therapy the mean number of prednisone-treated relapses was 1.3/patient per year in HLA-DR7-positive patients compared with 0.4 in negative patients (P<0.025). There was no statistically significant difference in the proportion of relapse-free patients with and without steroid dependency. The HLA status predicts the response of NS patients to alkylating agents better than the rate of previous relapses. Received September 19, 1995; received in revised form and accepted April 16, 1996