Considerations for the Use of Cytokine-Secreting Tumor Cell Preparations for Cancer Treatment

Limited efficacy of chemotherapy in most solid tumors has revived interest in immunotherapeutic approaches for cancer. One novel form of immunotherapy is the use of cancer vaccines consisting of tumor cells genetically engineered to secrete cytokines. The rationale for this immunization strategy is based on the existence of tumor-specific antigens, on the importance of the cellular arm of the immune system in mediating an effective antitumor response, and on the role of cytokines in regulating the cellular immune response. Such tumor vaccines showed considerable promise in various animal models and induced potent antitumor immunity in the host, which led to regression of established tumors and, moreover, produced immunological memory protecting animals from a subsequent tumor challenge at a distant site. Translated to the human patient, this implies that genetically modified tumor vaccines may be able to eradicate or reduce existing tumor deposits to subclinical levels as well as provide long-term protection from regrowth of tumor cells. This report will review and discuss the concept and rationale for the use of cytokine-secreting tumor vaccines for the treatment of human malignancies.     

Movement disorders after intervertebral disc surgery: Coincidence or causal relationship?

It is well known that brain injury or central traumatic lesions may result in the subsequent appearance of movement disorders such as dystonia or tremor. The concept that peripheral lesions to neural structures may be involved in the pathogenesis of movement disorders has been discussed controversely but has gained more widespread acceptance only recently. Here, we report on 6 patients who developed movement disorders after spinal disc surgery. The movement disorders became manifest with a delay of 1 day to 12 months after surgery. Of the six patients, 4 underwent cervical disc surgery, and 2 patients were operated on for lumbar disc herniation; 2 patients presented with paroxysmal kinesigenic segmental dystonia, 1 patient with focal dystonia, 2 with unilateral tremor, and 1 with bilateral tremor. The appearance of the movement disorder was associated with persistent dermatomal or segmental pain. In all patients, the anatomic distribution of the movement disorder was related to the nerve root or spinal segment of the corresponding disc level and the manifestation was in close temporal relation to the surgery. We conclude that spinal disc surgery may be another, thus far neglected, cause for movement disorders. The postoperative pain syndrome in all patients should be considered as an important factor of pathogenesis. Overall, movement disorders associated with disc surgery appear to be rare, yet they may cause significant discomfort to the affected individual.     

One-year follow-up of patients with first-episode schizophrenia (comparison between remitters and non-remitters)

Patients admitted to hospital after being diagnosed with first-episode schizophrenia were comprehensively assessed prior to acute treatment (on admission), at the end of the acute treatment (at discharge), and at follow-up after 1 year. The psychopathology was evaluated using the Positive and Negative Syndrome Scale (PANSS). 93 patients were reassessed after 1 year. 73/93 (78%) of the patients fulfilled the criteria for remission. No statistically significant differences in the total PANSS or subscales scores were found between remitters and non-remitters before or after the first episode treatment. However, non-remitters had a significantly higher total PANSS score after 1 year than remitters. There was no significant difference in mean psychopathology on admission or at discharge, with the exception of items conceptual disorganization, difficulty in abstract thinking, and lack of judgment and insight between remitters and non-remitters. However, significantly higher mean values were found for all items after 1 year in non-remitters than remitters. On admission the occurrence of positive, negative and general symptoms was balanced; at discharge and after 1 year negative and general symptoms were the most frequently observed. At the 1-year follow-up the impairment of insight and judgment is one of the most frequent symptoms in both remitters (10%) and non-remitters (70%).     

Cerebral sodium sensors in the sodium-deplete sheep

The sodium intake of sodium deplete sheep was studied during local, push-pull perfusion of different solutions within the third cerebral ventricle. Sheep were made sodium deplete by continuous loss of parotid saliva, and were allowed access to 0.6 M NaHCO₃ solution for 2 h daily. Local perfusion within the third cerebral ventricle was performed before and during the access to sodium solution. Four perfusion sites were used: anterior dorsal and ventral, and posterior dorsal and ventral. Perfusion of 200 mM Na-csf caused a decrease in sodium intake at each perfusion site. Perfusion of ouabain, 10⁻⁶M, caused a reduction in sodium intake only during perfusions within the anterior portion of the third ventricle. The results may indicate that specific neuronal elements sensitive to changes in intracellular sodium concentrations are located around the anterior portion of the third cerebral ventricle. These neurones, however, are not exclusive sites from where sodium intake of sodium deplete sheep can be influenced.     

Twenty-four-hour ambulatory blood pressure profiles in pediatric patients after renal transplantation

Ambulatory blood pressure monitoring was applied in 27 pediatric patients aged 6.3 – 24.3 (median 15.0) years who had been transplanted 1.5 – 8.4 years previously. Daytime values were compared with the mean of 10 concomitant casual blood pressure recordings. At the time of the study, antihypertensive drugs were given to 17 patients. Inulin clearance ranged from 18 to 116 (median 66) ml/min per 1.73 m². Ambulatory blood pressure monitoring confirmed hypertension or normotension determined by casual blood pressure measurements in 63% of patients. The physiological nocturnal dip in blood pressure was attenuated or reversed in 8 of 27 patients. It was reduced in all 3 patients with renal artery stenosis of the graft, in 3 of 4 patients with chronic rejection, in the only patient with recurrent focal segmental glomerulosclerosis, and in 1 of 6 patients with past acute rejection. The dipping was not related to inulin clearance. In conclusion, casual blood pressure measurements do not accurately reflect blood pressure in pediatric patients transplanted more than 1.5 years previously. A reduced nocturnal dip in blood pressure may indicate an underlying renovascular or renoparenchymal pathology. Ambulatory blood pressure monitoring should regularly be applied in patients with renal transplants. Received May 23, 1995; received in revised form June 18, 1996; accepted June 20, 1996