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.

Evidence for molecular subtypes of HIV-associated lymphoma: division into peripheral monoclonal, polyclonal and central nervous system lymphoma.

The pathogenesis of the HIV-associated lymphomas is not well understood. In order to begin characterizing this class of lymphoma, we initiated a molecular genetic study of DNA extracted from 31 diagnostic biopsy specimens from patients diagnosed with AIDS-associated non-Hodgkin's lymphoma. Analysis of 25 peripheral lymphomas showed that 14 were monoclonal B-cell processes, while 11 appeared to be of polyclonal origin. Five of the 14 monoclonal lymphomas were found to have rearrangements of the c-myc gene. Epstein-Barr virus (EBV) genomes were found in seven out of 14 monoclonal samples, but only two out of nine polyclonal samples. The six primary central nervous system (CNS) lymphoma samples were more homogeneous than the peripheral samples and all were monoclonal, positive for EBV and lacked detectable c-myc gene rearrangements. This study allows us to subdivide the HIV-associated lymphomas into three major molecular subtypes: (1) monoclonal B-cell process frequently associated with c-myc rearrangement or detectable EBV genomes, (2) polyclonal B-cell process typically without evidence of EBV, and (3) monoclonal primary CNS process associated with EBV genomes and lacking detectable c-myc rearrangement.

Meningioma in four patients with human immunodeficiency virus infection.

We describe four patients infected with the human immunodeficiency virus (HIV) who had development of meningiomas. In contrast to those in the general population who have meningiomas, all our patients were young men; the mean age was 40 years (range, 32 to 50). Their risk behavior for HIV was homosexuality (three patients) and intravenous drug use (one patient). The CD4+ cell count in each of the three homosexual men was less than 50/microL and was 280/microL in the drug user. Imaging studies showed enhancing lesions in three of the patients. Although each of these meningiomas could have occurred in otherwise normal young to middle-aged men, we speculate that the meningiomas may have grown in these HIV-infected hosts because of either loss of immune function or dysregulation of cytokines.

Postoperative cerebrospinal fluid leaks of the lumbosacral spine: management with percutaneous fibrin glue.

PURPOSE: To assess CT-guided injection of fibrin glue for the management of lumbosacral cerebrospinal fluid (CSF) leaks. METHODS: Six consecutive patients with postoperative CSF leaks were treated after CSF aspiration under CT guidance. A solution of cryoprecipitate was simultaneously injected with a 10% calcium chloride solution containing 2000 units of thrombin per milliliter. In one patient, 0.5 mL of iopamidol was added to the calcium chloride/thrombin mixture before injection. Placement of the fibrin glue aggregate was confirmed by CT imaging. To determine outcomes we reviewed the patients' records, postprocedure imaging studies, and physical findings, and we interviewed the patients directly. RESULTS: In three patients with postoperative CSF leaks, symptoms resolved after treatment. Despite imaging evidence of successful plug deployment, two other patients still had severe symptoms, and they underwent surgery after 2 and 18 hours, respectively. One patient had a continued CSF leak and a headache after 12 hours; follow-up surgery repaired an unsuspected dural tear just distal to the site of original surgery underneath the lamina and not covered by the fibrin glue. After one of the successful procedures, the patient had a fever and a headache, probably because of aseptic meningitis, which resolved after 2 days. CONCLUSION: Percutaneous CT-guided placement of fibrin glue may provide nonsurgical treatment for postoperative CSF leaks, potentially avoiding a major and technically difficult surgical procedure.

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.

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.

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.

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.

Ultrasound evaluation of experimental hydrocephalus in dogs.

The use of real time ultrasound to evaluate experimental hydrocephalus in craniectomized dogs is described. Fifteen dogs were longitudinally evaluated by ultrasound after injection of silicone into the suprasellar cistern and injection of kaolin into the cisterna magna, and later killed. Ventricular size was classified as normal, moderately or severely hydrocephalic according to lateral ventricular width. In 93% (14/15) of the animals the classifications as determined by ultrasound and pathological examination agreed. Both lateral ventricular width and biventricular width as measured by ultrasound had a linear correlation with measurements on the pathologic specimens (p less than 0.001).

Simple methods to reduce patient exposure during scoliosis radiography.

Radiation exposure to the breasts of adolescent females can be reduced significantly through the use of one or all of the following methods: fast, rare-earth screen-film combinations; specially designed compensating filters; and breast shielding. The importance of exposure reduction during scoliosis radiography as well as further details on the above described methods are discussed. In addition, the early results of a Center for Devices and Radiological Health study, which recorded exposure and technique data for scoliosis radiography, is presented.

The effects of pH on the growth of Chlorella vulgaris and its interactions with cadmium toxicity.

The effects of pH alone, and in combination with exposure to 0.89 microM cadmium, on the growth response of the green alga Chlorella vulgaris were evaluated. Acidic (3.0-6.2) and alkaline (8.3-9.0) pH values retarded the growth of this alga. Optimal growth occurred when the pH of the medium was adjusted to values of 7.5 and 8.0. When the cells were exposed to pH adjusted medium plus the presence of 0.89 microM Cd, a value known to reduce population growth by 50% at the control pH of 6.9, the affects were additive at the acidic (3.0-5.0) pH ranges. At alkaline pH values of 8.3-9.0 all toxicity responses could be explained by pH adjustment alone, indicating that additional cadmium toxicity was absent. At pH values of 7.5 and 8.0, cadmium toxicity was mitigated against, and resultant growth at pH 8.0 was at the same enhanced rate as this pH without cadmium.

Ultrastructural changes in Dunaliella minuta following acute and chronic exposure to copper and cadmium.

The ultrastructural changes taking place after short-term acute exposure to copper, cadmium and a combination of the two metals were examined. Additionally, the effects of long-term (8 months) exposure to ambient concentrations of these metals were investigated. Exposure to 0.34 microM cadmium affected the photosynthetic potential of this alga, by reducing the relative volume of the chloroplast by 23.27%. It also led to 74.6% increase in the relative volume of starch granules. Cells challenged with 0.34 microM cadmium and 7.57 microM copper had 33.49% larger volumes than controls, and their relative lipid volumes increased by 170%. In contrast, the relative volume of their pyrenoids decreased by 41.46%. Similar results were obtained after chronic exposure to 4.9 x 10(-4) microM copper with the relative volume of the pyrenoid being 28% smaller than the controls.

The toxic action and interactions of copper and cadmium to the marine alga Dunaliella minuta, in both acute and chronic exposure.

The effective concentrations of copper and cadmium which reduced the population growth of Dunaliella minuta by 50% after 96 h of static exposure, were determined to be 7.57 microM Cu and 0.34 microM Cd. Short-term static exposure to both metals indicated that their combined action is antagonistic with respect to growth of this chlorophyte. Additionally, long-term exposure to low levels of Cu or Cd led to the acquisition of tolerance towards Cu and Cd, respectively, and co-tolerance towards Cu.

Acute and chronic exposure of Dunaliella salina and Chlamydomonas bullosa to copper and cadmium: effects on growth.

Effective copper and cadmium concentrations which limited the growth of two chlorophytes by 50%, EC(50)s, after 96 h of static exposure were determined. EC(50)s were 5.94 microM copper and 4.55 microM cadmium for Dunaliella salina, and 0.78 microM copper and 0.025 microM cadmium for Chlamydomonas bullosa. The relationship of the two cations was synergistic towards the growth of both species. Chronic exposure to 4.5 x 10(-6) microM cadmium or 4.9 x 10(-4) microM copper increased the sensitivity of C. bullosa by 26% and 29% towards cadmium and copper, respectively. Changes in co-tolerance were not observed. Cd-treated D. salina was 50% more tolerant towards this cation, whereas Cu-treated cultures showed extreme sensitivity towards copper and "co-sensitivity" towards cadmium. Furthermore, the phylogenetic hypothesis, predictive of toxic response, failed to hold at the familial level.

Acute and chronic exposure of Dunaliella salina and Chlamydomonas bullosa to copper and cadmium: effects of ultrastructure.

The ultrastructural changes of Dunaliella salina and Chlamydomonas bullosa taking place after short term exposure to established copper and/or cadmium EC(50) or exposure to low levels of these cations for 8 months were examined. Cadmium had a greater impact on the ultrastructure of these species than copper. Metal stress affected a variety of cellular parameters including total cell volume, pyrenoid, nucleus, starch granules, polyphosphate bodies, lipids, vacuoles, cell wall, and periplasmalemmal space. The measurements of these cellular parameters used the technique of electron microscopic stereoscopic morphometry. Differences resulting from acute vs. chronic exposure to the cations are documented.

The growth response of the green alga Chlorella vulgaris to combined divalent cation exposure.

Using the growth response of the green alga Chlorella vulgaris as a model system, the effects of combinations of the environmentally active cations Cd, Co, and Cu were evaluated. The 96-h static EC50 for these cations to C. vulgaris were, respectively, 0.89 microM, 9.0 microM, and 2.8 microM, yielding a toxicity series such that Cd > Cu > Co. The cation combinations of Cd + Cu, and Cu + Co acted synergistically, while Cd + Co, and the tri-metallic combination Cd + Cu + Co resulted in antagonistic interactions. Examination of these toxic combinations at 24, 48, 72, and 96 h indicate that the cellular response is not a uniform one. Failure of energy dispersive X-ray spectrophotometric analysis to demonstrate any intracellular incorporation of these cations (except for a weak cytoplasmic Cu peak at the 8.0 KEV position) suggests that the toxic actions of these cations at EC50 concentrations are exerted at the level of the plasma membrane.