PubMed HealthSearch

Biomedical subjects

C E Gross

Publications and source records attributed to C E Gross.

At least 19 recordsLinked to original sources

In vitro evidence supporting two mechanisms of action for the anion transport inhibitor L-644,711 in cerebral ischaemia.

L-644,711 is a novel anion channel inhibitor which has previously been shown to decrease brain injury in two related rabbit models of cerebral ischaemia. We hypothesize two mechanisms of action of L-644,711 for its salutary effects on cerebral ischaemia: inhibition of neutrophil function and prevention of excitotoxin release from astrocytes. We present in vitro evidence supporting these two mechanisms of action. L-644,711 demonstrated a dose dependent inhibition of fMLP-induced neutrophil aggregation and superoxide anion release. In addition, L-644,711 demonstrated a dose dependent inhibition of glutamate release from swollen astrocytes in primary culture. We conclude that L-644,711 may prevent brain injury in cerebral ischaemia by inhibiting neutrophil function and preventing release of glutamate from swollen astrocytes.

Animals

A non-linear haemodynamic model for the arterial pulsatile component of the intracranial pulse wave.

An indication that pressure pulses in cerebral arteries may play a role in the configuration of intracranial pressure pulsations is given by the observation that vasospasm of cerebral arteries narrows the amplitude of the intracranial pressure wave. The present work develops a mathematical model for the transmission of arterial pressure pulses across the compliant arterial wall to the surrounding intracranial space. Compliance of both the arterial segment and the intracranial space are considered. So as to retain accuracy at higher values of the mean intracranial pressure, a physiological range in which pulse transmission is enhanced due to lower pressure gradients but intracranial compliance is not necessarily decreased, a logistic fit is used to model the intracranial pressure-volume relationship. A sequence of approximations (with error bounds) is obtained for the induced intracranial pressure pulse amplitude as a function of arterial pulse amplitude, mean transmural pressure, and mean intracranial pressure. It is found that at higher mean intracranial pressures, where the usual exponential assumption for the intracranial pressure-volume curve loses validity, the amplitude of the transmitted arterial pressure pulse depends non-linearly on the mean intracranial pressure.

Animals

Orbital paraganglioma: case report and review of the literature.

Paragangliomas of the orbit are extremely rare. A case of an orbital paraganglioma, including the first magnetic resonance imaging description of this tumour is described here. The patient underwent surgery with gross total removal of the tumour and relief of his initial chief complaint of visual blurring. The differential diagnosis and therapeutic options for the management of this tumour are discussed.

Humans

Reduction in ischemic brain injury in rabbits by the anion transport inhibitor L-644,711.

BACKGROUND AND PURPOSE: We studied the anion transport inhibitor L-644,711, which is known to reduce astrocyte swelling and excitotoxin release in primary astrocyte culture, in two models of thromboembolic stroke to assess its capacity to influence ischemic brain injury. METHODS: New Zealand White rabbits were used in this study. The two models include autologous clot embolized to the brain via the carotid artery, with one model using a transient period of systemic hypotension. Cerebral blood flow was determined by the hydrogen clearance method, intracranial pressure was measured with a fiberoptic transducer, and infarct size was assessed with triphenyltetrazolium chloride staining of the coronally sectioned brain. Both models received a 2-hour infusion of L-644,711 (total dose, 12 mg/kg) beginning 20 minutes before embolization. RESULTS: In both the normotensive (p less than 0.01) and the hypotensive (p less than 0.05) model, treatment with L-644,711 resulted in a significant reduction in infarct size and a significant improvement in regional cerebral blood flow (p less than 0.03, normotensive model, and p less than 0.05, hypotensive model). Raised intracranial pressure, unique to the hypotensive model, was abolished by the administration of L-644,711 (p less than 0.05). A hyperglycemic response associated with embolization, also unique to the hypotensive model, was significantly reduced by the administration of L-644,711 (p less than 0.05). CONCLUSIONS: The ability of L-644,711 to limit brain injury in two related models of thromboembolic stroke suggests a potential therapeutic role for anion channel blockers in cerebral ischemia.

Animals

The effect of the 21-aminosteroid U74006F in a rabbit model of thromboembolic stroke.

U74006F, a novel 21-aminosteroid, is an inhibitor of iron-dependent lipid peroxidation that is devoid of glucocorticoid and mineralocorticoid side effects. The efficacy of U74006F in reducing cerebral infarct size was investigated in a rabbit model of thromboembolic stroke. Each animal received either U74006F (3.0 mg/kg immediately before and 2 hr after embolization, n = 8) or vehicle control (n = 10). Hematocrit, mean arterial pressure, PCO2, PO2, and pH were measured and controlled both before and after the administration of an autologous clot into one internal carotid artery. Regional cerebral blood flow (in ml/100 g/min, mean +/- SEM) measured by hydrogen clearance was similar in both groups, being reduced from 68.2 +/- 9.6 to 5.2 +/- 1.9 in the control group immediately after clot embolization and from 73.3 +/- 14.9 to 7.0 +/- 1.7 in the U74006F group. Four hours after embolization the brain was harvested and cerebral infarct size was determined using the triphenyl-tetrazolium chloride technique (% hemisphere, mean +/- SEM). In the U74006F-treated group, the infarct size was significantly reduced (P < 0.05) to 14.8 +/- 6.4 from a control value of 36.0 +/- 6.4. Additionally, cerebral blood flow values after embolization were consistently higher in the U74006F group, although the differences were not statistically significant. This data suggests that the 21-aminosteroid U74006F may have a protective effect in cerebral ischemia.

Animals

The role of neutrophils and platelets in a rabbit model of thromboembolic stroke.

Cerebral ischemia is accompanied by many of the cardinal features of acute inflammation such as neutrophil and platelet activation and accumulation. We sought to determine whether circulating neutrophils or platelets contribute to brain injury in a rabbit model of thromboembolic stroke that includes a fixed duration of superimposed systemic hypotension. We randomized 18 rabbits to receive either antineutrophil antiserum (n = 6), antiplatelet antiserum (n = 5), or nonimmune serum (n = 7). We assessed brain ischemia by measuring cerebral blood flow, intracranial pressure, and infarct size. Following the intracarotid administration of an autologous clot, cerebral blood flow in all groups fell to less than 5 ml/100 g/min during induced hypotension. After restoration of baseline blood pressure, mean cerebral blood flow in neutropenic animals recovered to 20-30 ml/100 g/min while that in control and thrombocytopenic rabbits remained at less than 10 ml/100 g/min. Intracranial pressure in control animals rose steadily to a final value of 241% of baseline, while a much smaller increase (148% of baseline) was noted in the thrombocytopenic group; no change from baseline was evident in the neutropenic group. Infarct size was significantly (p less than 0.05) reduced in the neutropenic group but not in the thrombocytopenic group. These results suggest that neutrophils may be important contributors to ischemia-induced brain injury whereas the role of platelets is more subtle.

Animals

Increased cerebral blood flow in idiopathic pseudotumour cerebri.

Cerebral blood flow was studied in nine patients with idiopathic pseudotumour and one patient with cortical vein thrombosis in Denver, Colorado using the 133Xe inhalation method. Globally elevated blood flows were found in all of the idiopathic pseudotumour patients averaging 149% of control values generated in the same setting. The patient with the cortical vein thrombosis demonstrated normal global flows. Possible pathophysiological mechanisms for these findings are discussed.

Adult

Tissue plasminogen activator reduces brain injury in a rabbit model of thromboembolic stroke.

Tissue plasminogen activator is an endogenous fibrin-specific serine protease with potent thrombolytic activity. We investigated the efficacy of tissue plasminogen activator in reducing cerebral infarct size after thromboembolic stroke in a rabbit model. Seventeen rabbits were randomized to receive either tissue plasminogen activator (2.5 mg/kg, n = 6) or vehicle control (n = 11). We controlled mean arterial pressure, hematocrit, and arterial blood gases before and after the intracarotid embolization of an autologous clot. Cerebral blood flow (cm3/100 g/min) (mean +/- SEM) was immediately reduced from 55.2 +/- 7.7 to 8.5 +/- 2.5 in the control group and from 61.8 +/- 14.8 to 10.0 +/- 3.5 in the treated group after embolization. Cerebral blood flow recovered significantly within 60 minutes of thrombolytic therapy and attained a value of 59.6 +/- 10.0 cm3/100 g/min 4 hours after embolization, whereas cerebral blood flow in control animals demonstrated only a minimal recovery to 15.3 +/- 8.9 cm3/100 g/min. Cerebral infarct size (percent of hemisphere) was reduced from 34.4 +/- 5.6% in control animals to 8.8 +/- 5.6% in treated animals (mean +/- SEM, p less than 0.01). These results suggest that tissue plasminogen activator may be efficacious in restoring cerebral blood flow and thus limiting infarct size in acute thromboembolic stroke.

Animals

Colloidal volume expansion during acute cerebral ischaemia: assessed by local cerebral blood flow and computerized power ratio index.

Colloidal volume expansion during acute cerebral ischaemia was assessed by local cerebral blood flow (CBF) and the power ratio index (PRI) in 8 anaesthetized Macaque monkeys. Focal cerebral ischaemia was produced by right middle cerebral artery occlusion. The animals were then volume expanded (to maximum cardiac output) with 6% hetastarch and then exsanguinated to baseline cardiac output. During volume expansion, local CBF in the ischaemic hemisphere increased from 25 +/- 12 to 39 +/- 23 cc/100 g/min (p less than 0.01) and during exsanguination decreased to 32 +/- 18 cc/100 g/min. Local CBF did not change significantly in the nonischaemic hemisphere. EEG power data, as assessed by PRI [(delta + theta power/alpha + beta power) x 100] changed significantly during blood volume manipulation. The mean PRI value in the right hemisphere deteriorated by increasing from 65 +/- 22 to 94 +/- 25 (p less than 0.01) following vessel occlusion but improved by decreasing to 81 +/- 23 (p less than 0.05) following volume expansion. Following exsanguination, the PRI value increased to 87 +/- 21. These data demonstrate the benefits of volume expansion during acute cerebral ischaemia. Changes in local CBF were consistently associated with changes in the PRI maps and values.

Animals

Acute middle cerebral artery occlusion: experience with volume expansion therapy.

Five consecutive patients with acute neurological deficits after middle cerebral artery (MCA) occlusion were given emergency treatment with colloidal volume expansion. In each case, the diagnosis was confirmed promptly by computed tomography and cerebral angiography. Aggressive volume expansion therapy was started 2 to 18 hours (mean, 11 hr) after the onset of the neurological deficit. The mean colloidal volume used was 920 ml/day for an average of 4 days. During volume expansion, the mean cardiac output increased 57% from 4.6 +/- 0.6 to 7.2 +/- 1.9 litres/min (P less than 0.05). The mean hematocrit decreased 19% from 46 +/- 3% to 37 +/- 4% (P less than 0.01). The mean arterial blood pressure remained stable, and the pulmonary artery wedge pressure was maintained at less than 15 mm Hg. Three patients improved dramatically with volume expansion therapy and have returned to their previous life-styles. Two patients made partial recoveries and manage at home with nursing care. The three patients who improved dramatically were young (aged less than 34) and, when compared to the older patients, they had greater increases in cardiac output (67% vs. 19%). No major complications or deaths were attributed to the volume expansion therapy. We propose that intravascular volume expansion and its concomitant augmentation of the cardiovascular dynamics may be effective in the treatment of acute neurological deficits after acute MCA occlusion.

Acute Disease

Pulsatile versus nonpulsatile blood flow in the treatment of acute cerebral ischemia.

The effects of pulsatile and nonpulsatile perfusion on local cerebral blood flow (CBF) and on computerized mapping (CME) of electroencephalograms (EEG) in nonischemic and ischemic brain were studied using a canine stroke model. Nine anesthetized mongrel dogs were placed on normothermic right atrial-femoral artery cardiopulmonary bypass at a flow of 100 ml/kg/minute. Local CBF measurements and CME data were collected during nonpulsatile perfusion and maximal pulsatile perfusion. The stroke model was then produced, and local CBF measurements and CME data were again collected during nonpulsatile and pulsatile perfusion. In the nonischemic brain, local CBF increased 19%, from 32 +/- 10 to 38 +/- 11 ml/100 g/minute (P less than 0.01), when perfusion was changed from nonpulsatile flow (pulse pressure less than 4mm Hg) to pulsatile flow (pulse pressure 39 +/- 11 mm Hg). In the ischemic brain, local CBF increased 55%, from 11 +/- 5 to 17 +/- 7 ml/100 g/minute (P less than 0.01), when perfusion was changed from nonpulsatile (pulse pressure less than 3 mm Hg) to pulsatile (pulse pressure 36 +/- 7) flow. EEG power data, expressed as a power ratio index (PRI = low frequency power/high frequency power), improved significantly, from 110 +/- 33 to 101 +/- 41 (P less than 0.01) with pulsatile perfusion. These data demonstrate the importance of pulsatile blood flow in ischemic brain.

Acute Disease

Contraction and relaxation of rabbit basilar artery by thiopental.

Tension measurements were made on rabbit basilar artery segments to test the direct effect of thiopental on serotonin (5HT)- and norepinephrine (NE)-induced contraction. At concentrations of 3 X 10(-5) M or greater, thiopental caused relaxation of NE-induced tension. Thiopental doses greater than 3 X 10(-4) M had a similar relaxing effect on 5HT-induced contraction. However, thiopental doses below 3 X 10(-4) M demonstrated an unexpected dose-dependent potentiation of the 5HT-induced contraction.

Animals

Topographic electroencephalographic study with power ratio index mapping in patients with malignant brain tumors.

A variant of electroencephalogram (EEG) power spectral mapping called power ratio index (PRI) mapping was used to monitor 15 patients with malignant brain tumors. This index is generated by dividing the low frequency (delta, theta) power by the high frequency (alpha, beta) power. Because the nonparoxysmal effect of a brain tumor on the EEG is reflected as a relative loss of high frequency power and a gain in low frequency power, utilization of the PRI has the effect of placing the epicenter of the "power dysfunction" coincident with the epicenter of the tumor.

Adult

Cerebral revascularization.

Cerebral vascular insufficiency due to occlusive lesions regarded as inaccessible is a common problem. The degree of cerebral dysfunction associated with such lesions is dependent in part on the amount of collateral circulation present. By anastomosing the superficial temporal artery to a branch of the middle cerebral artery an increase in collateral circulation is provided to the affected hemisphere. This report describes the results of twenty such procedures. Postoperative angiography demonstrates a 90% patency rate. There is frequent neurological improvement following surgery, and the rate of new TIA's or strokes seems less than would be expected. The most damaging complication of the procedure ist intracerebral haemorrhage. The indications for, and the complications of, such procedures are discussed.

Adult

Contrast agents for myelography: clinical and radiological evaluation of Amipaque and Pantopaque.

The diagnostic quality and side effects of Amipaque and Pantopaque as myelographic contrast agents were compared prospectively using the identical protocol in 167 cases (117 Amipaque, 50 Pantopaque). Good ratings were attained in 74% of Amipaque and 76% of Pantopaque examinations. Demonstration of nerve rootlets in the cauda equina and filling of lumbar root sleeves were superior with Amipaque. Amipaque more easily demonstrated the high posterior cervical subarachnoid space and the anterior and posterior margins of the cervical spinal cord. The incidence of postmyelographic headache was 38% with Amipaque and 32% with Pantopaque. Nausea and vomiting were more common with Amipaque. Two patients experienced grand mal seizures after examination sith Amipaque.

Adolescent