Primary central nervous system lymphomas: natural history and response to radiation therapy in 55 patients with acquired immunodeficiency syndrome.

The incidence of primary central nervous system (CNS) lymphoma has increased rapidly in patients with acquired immunodeficiency syndrome (AIDS) and is predicted to exceed 1800 cases annually by 1991. To characterize the natural history and response to radiation therapy (RT) of these lesions, the authors have reviewed the clinical histories of 55 AIDS patients with biopsy-proven primary CNS lymphomas. The tumors responded both clinically and radiologically to whole-brain RT consisting of 4000 rad in 267-rad fractions over 3 weeks or an equivalent neuroret dose. The mean duration of survival from the appearance of symptoms consistent with the mass lesion was significantly greater in patients who received RT than in those who did not (42 vs. 134 days, p less than 0.5; median 27 vs. 119 days). Autopsy findings showed that patients who did not receive RT died from tumor progression, whereas those who completed RT died of opportunistic infections. Patients with AIDS who are suspected of having primary CNS lymphoma should therefore immediately undergo biopsy and, if the diagnosis is confirmed, whole-brain RT. With early diagnosis and treatment, these tumors respond to, and patients benefit from, RT. Survival of such patients may in future be prolonged by more effective treatments for systemic opportunistic infections.

Examination of the utility of the rat as an animal model for human anticoagulation.

The feasibility of employing the rat as an experimental model for investigation of full-dose heparin anticoagulation was assessed. Striking similarities were found to exist between rats and humans regarding baseline-activated partial thromboplastin time (APTT) values, and dosage per kilogram of heparin required to produce an APTT value of 1 1/2-3 times normal, the clinical definition of full-dose heparinization. Based upon these similarities, it appears that the rat can effectively serve as an experimental model for investigating the effects of heparin in humans.

Evaluation of the risks of anticoagulation therapy following experimental craniotomy in the rat.

The risk of hemorrhagic complications with anticoagulation therapy in patients following intracranial surgery has prevented investigation of the potential use of heparin in the early postoperative period. The authors have evaluated the safety of anticoagulation therapy following experimental craniotomy in male Holtzman rats. The dose and schedule of heparin administration, which elevated and maintained the activated partial thromboplastin time (APTT) within the therapeutic range of 1 1/2 to 3 X control APTT, was alternating doses of 400 and 500 IU/kg injected subcutaneously every 6 hours. This schedule was initiated 2, 4, 7, 10, and 14 days after craniotomy and was continued for 72 hours thereafter. The results demonstrated that the incidence of intracerebral hemorrhage declined as the postoperative interval prior to initiation of anticoagulation increased. If anticoagulation therapy was initiated during the first 7 postoperative days, the risk of intracerebral hemorrhage was high (mean 14.7%): however, if an additional 3 to 7 days elapsed prior to initiation of anticoagulation, the incidence of intracerebral hemorrhage dropped significantly (mean 0%) (p less than 0.05). These results suggest that anticoagulation therapy can be safely initiated 10 to 14 days after craniotomy.

Ultrasound-guided periventricular stereotaxis.

Intraoperative ultrasound can aid the biopsy of deep intracranial lesions. It is, perhaps, less clear whether ultrasound could be useful in functional neurosurgery, where the target is not abnormal in echogenicity. As an example, we chose to investigate in a dog model the periventricular gray target, which is frequently the choice for the placement of electrodes to control intractable pain. Autopsies showed the placement of our electrodes with less than 1 mm of error in four of five brains and a 1.5-mm error in the fifth brain. The largest error was seen to occur on the video screen and was due to our failure to tighten the guide properly. The potential advantages of this technique over conventional stereotaxis include the avoidance of: ventricular catheterization, the injection of contrast agent into the ventricles, the necessity for a stereotactic frame, and multiple x-ray exposures. Also, with real time scanning the surgeon has instant visual confirmation of electrode placement and can observe quickly any significant hematoma formation.

Changes in food intake with electrical stimulation of the ventromedial hypothalamus in dogs.

Six adult dogs were implanted stereotaxically with chronic indwelling Medtronic platinum-tipped electrodes in the left ventromedial hypothalamic area (VMH); two dogs with electrodes placed in the subcortical white matter served as controls. Following 24 hours of food deprivation, VMH-stimulated dogs delayed their next meal for a period ranging from 1 to 18 hours. When not stimulated, however, each dog ate immediately upon receiving its food and consumed greater than average daily intake (p less than 0.005). The two control dogs ate immediately upon receiving food regardless of whether they were stimulated or not. Dogs that received 1 hour of VMH stimulation every 12 hours for 3 consecutive days maintained an average daily food intake of 35% of normal baseline levels (range 13% to 51%), and water consumption averaged 50% of baseline intake (range 29% to 67%). Both of these results were statistically significant (p less than 0.01). After cessation of stimulation, food and water intake returned to normal within 6 to 9 days, with no observable "rebound hyperphagia." The two animals that received subcortical electrodes showed no change in food or water intake with stimulation. Blood pressure, pulse, respiration, temperature, and gross behavior were not altered during or after stimulation. These results suggest that the use of electrical stimulation of the VMH may be a useful modality for regulating food intake, and deserves further examination as a potential alternative therapy for human morbid obesity.

Elevated beta-endorphin in cerebrospinal fluid after electrical brain stimulation: artifact of contrast infusion?

Beta-Endorphin-like immunoreactivity in cerebrospinal fluid was assayed in 11 patients receiving electrical stimulation of the brain for chronic pain. Immunoreactivity increased dramatically after contrast ventriculography prior to stimulation. No further elevations were observed after stimulation. The magnitude and time course of elevations were identical after placement of electrodes either in the thalamus or in the periventricular gray matter. These results suggest that previous findings of stimulation-induced elevation of beta-endorphin-like immunoreactivity in cerebrospinal fluid are attributable to an artifact of contrast ventriculography.

beta-Endorphin-like immunoreactivity increases in human lumbar cerebrospinal fluid following routine metrizamide myelography.

Much interest has recently been focused on the possible role of the endogenous opiates in the perception of pain in humans. Several investigators have examined the levels of these substances in human cerebrospinal fluid (CSF) in attempts to identify the mechanisms by which electrical stimulation of the brain might induce analgesia. Most of these CSF samples were collected at the time of ventriculography or myelography. In the present study, the levels of beta-endorphin in the CSF of 22 patients undergoing myelography were examined before and after the injection of a contrast agent. beta-Endorphin increased an average of 356% (p less than 0.0005) 15 to 20 minutes following the injection of contrast material into the lumbar subarachnoid space. Thus, routine myelography may have a profound effect on the levels of beta-endorphin measured by radioimmunoassay in human CSF, and great care must be taken in interpreting the significance of changes seen in beta-endorphin levels in CSF collected from patients at the time of myelography or ventriculography. The effect of the injection of contrast material on beta-endorphin immunoreactivity must be distinguished from the postulated effects of any analgesia-inducing therapy.

Effect of contrast media on radioimmunoassay of beta-endorphin in cerebrospinal fluid.

An effect of metrizamide, a contrast medium, on results of beta-endorphin radioimmunoassay was examined. We found that 1, 5, and 10 microL of the medium added to 100 microL of standard containing 0 to 500 pg of beta-endorphin shifted the standard curve to the left in proportion to the metrizamide concentration. Three other contrast media showed a similar effect at low concentrations of beta-endorphin. This effect of contrast media artificially increased results in radioimmunoassay of beta-endorphin in cerebrospinal fluid, the mean overestimate being 121.9% (range, 0 to 435%). For plasma samples, this effect of contrast media resulted in an average 11.7% overestimate of beta-endorphin (range, -16% to 41%). These observations bring into question the validity of a previous suggestion that an increase in beta-endorphin in cerebrospinal fluid after intracerebral electrical stimulation is the mechanism for stimulation-produced analgesia.