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.     

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     

Late onset unilateral asterixis secondary to posterior cerebral artery infarction

Unilateral asterixis developed in a 56 year old man, 5 months after an infarct in the posterior cerebral artery territory, involving the posterolateral nuclear complex of the thalamus, documented by CT-scan and MRI. Unilateral asterixis in rarely reported in association with thalamic lesions and usually develops as an immediate postictal phenomenon. We discuss possible physiopathological mechanisms explaining the occurrence and the delayed onset of these involuntary movements.

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Sommario Un uomo di 56 anni ha sviluppato un'asterixis unilaterale, 5 mesi dopo aver presentato un infarto nel territorio dell'arteria cerebrale posteriore, che coinvolgeva i nuclei postero-laterali del talamo, come evidenziato dalla TC e dalla MRI. Asterixis unilaterali si sviluppano raramente in seguito a lesioni vascolari a livello del talamo e generalmente rappresentano un evento immediatamente successivo all'ictus. Nel caso descritto invece, i movimenti involontari si sono manifestati a notevole distanza di tempo. Gli autori discutono i possibili meccanismi fisiopatologici alla base di questi movimenti involontari e della loro insorgenza a distanza di tempo dall'ictus.

     

Urination Frequency and Cystic Pressure Resistance After Fractionated whole or Partial Irradiation of the Rabbit Urinary Bladder

Urination frequency and cystic pressure resistance have been used as end-points to assess x-ray-induced changes of bladder function. Whole or half bladders of adult male rabbits were irradiated, caudally or cranially. The absorbed dose was 33 Gy, 36 Gy or 39 Gy, given in 5 daily fractions. Animals which received a whole bladder dose of 39 Gy or 36 Gy showed increased urination frequency and enhanced bladder pressure resistance during the whole follow-up time of 100 weeks, compared with the sham-irradiated controls. At half bladder irradiation, only the highest doses (39 Gy to the cranial part of the bladder and 39 Gy or 36 Gy to the caudal part) gave rise to a slight increase in frequency at about 20 weeks after exposure.     

Cisplatinum Dose Dependent Response in Germ Cell Cancer Evaluated by Tumour Marker Modelling

This study presents an analysis on longitudinal tumour marker series in twenty-two patients with non-seminomatous germ cell cancers treated with cisplatinum (DDP) based combination chemotherapy. Series of alphafoetoprotein (AFP), human chorionic gonadotropin (HCG) and lactate dehydrogenase (LDH) were analyzed applying a dynamic mathematical marker model. The model analysis provided quantitated values for growth rate and treatment response in the marker producing cells. The analysis showed that LDH had to be above 2 000 U/l to be a trustworthy tumour marker. HCG producing cells tended to grow faster than AFP producing cells, and were 3-5-fold more sensitive to the chemotherapy given than AFP producing cells. Treatment response versus DDP dose appeared to be bi-phasic, but with no significant change in treatment efficiency within the given range of DDP doses.     

Prevalence and localization of nodal metastases in squamous cell carcinoma of the oral cavity: role and extension of neck dissection

Lymph node (LN) metastases represent the most important negative prognostic factor in squamous cell carcinoma (SCC) of the oral cavity, even though controversies still exist regarding their management. The aim of this study was to retrospectively analyze our experience in surgical management of SCC of the oral cavity with particular focus on the prevalence and localization of lymph nodal metastases and recurrences. The clinical records of 89 consecutive patients treated from 1983 to 2002 by concomitant surgery on both the T and N sites, excluding those undergoing salvage surgery, were reviewed. A total of 119 neck dissections (ND) were performed. Survival outcomes were calculated by the Kaplan–Meier method, while univariate comparisons by the log-rank and non-parametric tests were performed between different groups of patients. Five-year overall and determinate survivals were 50 and 57%, respectively. LN metastases were observed in 52% (56% of these showing extracapsular spread) and their presence strongly correlated with determinate survival (p < 0.0001). The prevalence of clinical and occult nodal disease was not related to the pT status. Neck levels II (59%) and I (56%) were most frequently involved. Metastases to level IV accounted for 15% of positive LN, even though 28% of them turned out to be skip metastases. Five neck recurrences were observed, only one of which was salvaged by surgery. The high prevalence of clinical and occult LN metastases in this setting suggests that ND should be performed on a nearly routine basis, even for lesions with a low-T category and a cN0 neck. Moreover, ND should always encompass level IV due to the possibility of skip metastases, particularly in tumors involving the oral tongue. In patients with a cN+ neck, levels from I to V should be addressed, particularly in the presence of metastases at levels III and IV.     

Radiological detection of bone and bone marrow metastases

Bone scintigraphy is the primary method for the diagnosis of skeletal métastases. This investigation is sensitive, but the interpretation must be performed in the knowledge that it is also nonspecific. Despite this, a correct diagnosis can usually be achieved. The first-hand supplementary investigation, after a doubtful scintigraphic finding, is radiography. In most cases this is sufficient for a diagnosis. When a scintigraphic abnormality cannot be adequately explained, usually because of a negative radiographic examination, a more sensitive modality must be used. Computerized tomography offers increased sensitivity and specificity, and is primarily used for this purpose. In this way contrast resolution is increased and problems caused by obscuring tissue and complicated anatomy are reduced. Since bone metastases migrate via the active bone marrow an alternative supplementary investigation is bone marrow scintigraphy. Its usefulness is restricted by disturbing activity, from the liver and the spleen, which obscures a significant part of the active marrow, and by the fact that a lesion must be of a certain size to become apparent. Magnetic resonance imaging yields excellent images of the extension of a tumor in soft tissue. Owing to high costs and restricted availability it is still mainly used for preoperative location of metastases.     

Case report: fusion of positron emission tomography (PET) and computed tomography (CT) images for image-guided endoscopic navigation in maxillofacial surgery: clinical application of a new technique.

INTRODUCTION: Surgery based on computed tomography (CT) data is becoming increasingly important in the head and neck region. The technique for hardware fusion between positron emission tomography (PET) and computed tomography (CT) has only been established commercially in the last 4 years. The advantages over CT alone are obvious. The surgeon is simultaneously provided with a map of anatomical as well as of functional (metabolic) details. The fused images offer improved localization of malignant lesions and improved targeting of biopsy, especially for small lesions. PURPOSE: A new technique for image-guided tumour localization for maxillofacial surgery based on PET/CT-image fusion is described. PATIENT AND METHOD: A 78-year-old woman was admitted to this department with a tumour of the skull base. Three dimensional fusion of computed CT with positron PET images on a commercially available navigation system is described. After patient-to-image registration, a high-resolution endoscope was calibrated intraoperatively. Image-guided biopsy specimens were taken under direct visual control. CONCLUSION: PET/CT-image fusion proved extremely helpful to navigate the endoscope to the target lesion and to identify the tumour.