Computerized cortical surface electroencephalography after temporary middle cerebral artery occlusion in rabbits

The sensitivity and regional specificity of intraoperative electroencephalographic (EEG) monitoring in cerebral ischemia was evaluated in a new experimental model of temporary focal cerebral ischemia in rabbits. EEG potentials were recorded directly from the cortical surface using a bipolar disc electrode grid and were analyzed by computer. Groups of 5 animals each underwent temporary occlusion of the left middle cerebral arterial trunk for 5, 10, 20, 30, 45, or 60 minutes. EEG data were recorded from the cortex proximal (temporal site) and distal (parasagittal site) to the middle cerebral arterial trunk during occlusion and 2 hours of reperfusion. EEG suppression was detected immediately after occlusion at the temporal site by analysis of power spectra in 29 of 30 rabbits (mean power, 32% of base line), by compressed spectral array (CSA) edge analysis in 23, and by analysis of the conventional EEG wave form in 24. Within 5 minutes after the start of occlusion, all 30 rabbits showed EEG power suppression and 26 showed decrease in the CSA edge frequency or in the routine EEG wave form. By the end of the occlusion period, EEG power at the temporal site had decreased to 20.5% of base line. At the parasagittal site, a lesser degree of EEG suppression was detected; 20 rabbits had an initial loss of EEG power (mean, 85.7% of base line), 13 had decrease in the CSA edge, and 7 had suppression of the EEG wave form. By the end of the occlusion period, spectral power at the parasagittal site had decreased in 25 of 30 rabbits to a mean of 86.9% of base line.(ABSTRACT TRUNCATED AT 250 WORDS)     

Construction and validation of a Parkinson's disease mutation genotyping array for the Parkin gene.

Parkin mutations account for the majority of familial and sporadic early onset Parkinson's disease (EOPD) cases with a known genetic association. More than 100 mutations have been described in the Parkin gene that includes homozygous, compound heterozygous, and single heterozygous mutations. We have designed a Parkin mutation genotyping array (gene chip) that includes published Parkin sequence variants and allows their simultaneous detection. The chip was validated by screening 85 PD cases and 47 controls previously tested for Parkin mutations. Similar genotyping microarrays have been developed for other genetically heterogeneous diseases including age-related macular degeneration. Here, we show the utility of a genotyping array for Parkinson's disease by analysis of 60 subjects from the Genetic Epidemiology of Parkinson Disease (GEPD) study that includes 15 early-onset PD case probands and 45 relatives.     

Jugular venous desaturation following cardiac surgery

Twenty-two patients undergoing coronary artery bypass surgery underwent postoperative measurement and recording of jugular venous oxyhaemoglobin saturation (SjO2) with desaturation defined as a value of less than 50% for 5 min or longer. Fifteen of the 22 patients monitored experienced desaturations. An average of four episodes were experienced by those 15 patients (range 1-14). The mean duration of a single episode was 46 (range 5-212) min whilst mean total duration of desaturation was 175 (range 5-570) min. The mean duration of desaturation in the 15 patients, expressed as a percentage of monitored time, was 21.1% (range 0.58%-61.96%). SjO2 desaturation, possibly indicating cerebral hypoperfusion, occurs in the early post-operative period following cardiac surgery.      

Longitudinal patterns of enrollment and expenditures for a Medicaid cohort.

This article is based on 4 years of data for a cohort of Medicaid enrollees in California and Georgia to determine patterns of enrollment and expenditures. The analyses were developed from the statistical system known as Tape-to-Tape, which is based on Medicaid enrollment and claims files from these and other States. The composition of the cohort changed over times as a result of the differential rates of turnover for subgroups of the Medicaid population. Longitudinal expenditure patterns also varied by health service and eligibility group. These Medicaid expenditure patterns differed from those observed previously in Medicare studies, undoubtedly reflecting differences in service coverage under Medicare and Medicaid.     

Effects of diaspirin cross-linked haemoglobin on post-traumatic cerebral perfusion pressure and blood flow in a rodent model of diffuse brain injury

Diaspirin cross-linked haemoglobin (DCLHb) is a new oxygen carrying blood substitute with vasoactive properties. Vasoactive properties may be mediated via high affinity binding of nitric oxide by the haem moiety. Using a rodent model of head injury combined with ischaemia, we studied the effects of DCLHb on cerebral blood flow (CBF) and intracranial pressure (ICP). Twenty anaesthetized rats were allocated randomly to receive treatment with DCLHb 400 mg kg-1 i.v. or placebo (oncotically matched plasma protein substitute 4.5% i.v.). To produce diffusely increased ICP, after a severe weight drop injury, all animals underwent a 30-min period of bilateral carotid ligation combined with a period of induced hypotension. After reperfusion, DCLHb or placebo was infused and the animals instrumented for measurement of intraventricular ICP and CBF in the region of the sensorimotor cortex using the hydrogen clearance technique. Mean arterial pressure (MAP), ICP, cerebral perfusion pressure (CPP) (CPP = MAP - ICP) and CBF were measured 4 h after injury in all animals. DCLHb significantly reduced ICP from mean 13 (SEM 2) to 3 (1) mm Hg (P < 0.001), increased CPP from 52 (8) to 95 (6) mm Hg (P < 0.001) and increased CBF from 21 (2) to 29 (2) ml 100 g-1 min-1 (P = 0.032). We conclude that DCLHb improved CPP without a reduction in CBF in a rodent model of post-traumatic brain swelling.      

Surgical resections in parous patients with distal ileal and colonic Crohn's disease.

The surgical resection rates among parous women with distal ileal and colonic Crohn's disease have been compared with resection rates among distal ileal (n = 197) and colonic (n = 332) Crohn's disease patients. Thirty of 44 parous women with distal ileal Crohn's disease and 28 of 44 with colonic Crohn's disease had achieved their first pregnancy on average 8 years and 6.2 years respectively before the diagnosis of Crohn's disease was established. Resections for each patient were negatively correlated with parity in both groups. (Distal ileal disease (p = 0.034, rs = 0.3207), colonic disease (p = 0.051, rs = -0.2960)). Patients with distal ileal Crohn's disease and a history of pregnancy at diagnosis (n = 30, mean follow up = 15 years) had fewer resections/patient when compared with the published resection group: mean (SD); 1.17 (0.65) v 1.57 (1.05), p = 0.006. Patients with colonic Crohn's disease and a history of pregnancy at diagnosis (n = 28, mean follow up = 16.5 years) had fewer resections/patient when compared with the published resection group: mean (SD); 0.68 (0.77) v 1.05 (0.77), p = 0.019. In summary, patients with distal ileal and colonic Crohn's disease, who had been pregnant in the past subsequently need fewer surgical resections. Pregnancy could influence the natural history of Crohn's disease either by decreasing immune responsiveness or by retarding fibrous stricture formation, which is the commonest indication for surgical intervention.     

Transcranial cytokine gradients in patients requiring intensive care after acute brain injury

After acute brain injury there may be increased intracranial production of cytokines, with activation of inflammatory cascades. We have sought to determine if a transcranial cytokine gradient was demonstrable in paired sera of 32 patients requiring intensive care after acute brain injury. The difference between concentrations of IL-1 beta, IL-6, IL-8 and TNF alpha in jugular venous and arterial serum was measured on admission, and at 24, 48 and 96 h after the primary injury. There were no differences in IL-1 beta, IL-8 or TNF alpha, but median gradients of 6.7 and 11.5 pg ml-1 for IL-6 were demonstrated in the traumatic brain injury (n = 22) and subarachnoid haemorrhage (n = 10) groups, respectively (normal values in serum < 4.7 pg ml-1; P < 0.001 both groups). This suggests that there is significant production of IL-6 by intracranial cells after acute brain injury. Therapy directed towards combatting the negative effects of IL-6 may potentially benefit patients who have sustained an acute brain injury.      

The ligand for c-kit, stem cell factor, stimulates the circulation of cells that engraft lethally irradiated baboons.

Recombinant human stem cell factor (SCF), the ligand for c-kit, has been shown to stimulate increased numbers of hematopoietic progenitor cells of multiple types to circulate in the blood of baboons, but it was not known if the cells stimulated to circulate by SCF contained cells capable of engrafting and rescuing lethally irradiated baboons. Peripheral blood mononuclear cells (PBMNC) were collected by leukapheresis from four untreated control baboons and from three baboons on the 10th or 11th day of treatment with SCF (200 micrograms/kg/d). All animals were transplanted with 1.00 to 1.04 x 10(8)/kg of cryopreserved autologous PBMNC after treatment with a single dose of 1,020 cGy total body irradiation (TBI). Three animals were transplanted with PBMNC that had been collected during SCF treatment, 24 to 38 days after the last dose of SCF. Rapid trilineage engraftment was documented by bone marrow biopsy in all three. The mean time to a total white blood cell count (WBC) > or = 500/microL, WBC > or = 1,000/microL, and an absolute neutrophil count (ANC) > or = 500/microL was 15 +/- 3 (mean +/- SD), 19 +/- 1, and 19 +/- 2 days, respectively. Two animals remain alive with stable engraftment more than 180 and 245 days posttransplant. The third died of sepsis 32 days posttransplant with a hypercellular marrow showing trilineage engraftment. The surviving animals were transfusion independent by 10 and 59 days posttransplant. Four control animals were transplanted with PBMNC collected in the absence of SCF stimulation. One was treated for 11 days with SCF (200 micrograms/kg/d) after PBMNC were collected. This animal was transplanted 25 days after the last dose of SCF. None of the four control animals engrafted and they died 13, 16, 28, and 38 days posttransplant with marrow aplasia. Treatment with SCF stimulates the circulation of cells that engraft and rescue lethally irradiated baboons. The characteristics of the transplantable cells present in the circulation are now amenable to direct study.