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Biomedical subjects

B Weir

Publications and source records attributed to B Weir.

At least 37 records · Page 2Linked to original sources
PubMed1996

Intraoperative angiography in cerebral aneurysm surgery: a prospective study of 100 craniotomies.

OBJECTIVE: To determine the frequency of unexpected major arterial occlusion and incomplete aneurysm clipping on intraoperative angiography after cerebral aneurysm clipping and to determine factors that predict these unexpected findings. METHODS: Data was collected prospectively on 100 consecutive craniotomies for the clipping of 107 aneurysms in 92 patients. Patient age and sex, aneurysm location and size, how the aneurysm presented, day of surgery after hemorrhage, intraoperative rupture, and postoperative course were recorded. After clipping, the surgeon recorded whether he thought the aneurysm was obliterated and whether he thought the clip occluded a major artery. Intraoperative angiography was then performed. The incidence of unexpectedly finding a major arterial occlusion or residual aneurysm was determined. Factors predicting these unexpected findings revealed by intraoperative angiography were identified by logistic regression. RESULTS: There were 11 giant (10%), 13 posterior circulation (12%), and 68 (64%) ruptured aneurysms. Unexpected angiographic findings necessitating at least one clip adjustment occurred in 12 cases (11%). Clip readjustments restored flow through six major arterial occlusions (6%) and completely obliterated 10 persistently filling aneurysms (10%). Logistic regression showed that factors predicting an unexpected arterial occlusion were giant aneurysm and basilar apex location (P < 0.05). Unexpected residual aneurysm was predicted by giant aneurysm and posterior communicating artery location (P < 0.05). CONCLUSION: Intraoperative angiography detects unexpected arterial occlusions and residual aneurysms in 12% of cases and can decrease complications of aneurysm surgery, although the yield in unselected patients is low. The subgroup of patients with giant, basilar apex, and posterior communicating artery aneurysms has a significantly higher incidence of untoward findings and may benefit from increased usage of intraoperative angiography.

Adolescent↗
PubMed1996

The University of Chicago Neurosurgical Program.

The current members of the faculty at the University of Chicago are acutely aware of the great historic tradition they have inherited. Like all academic medical centers, they are challenged by the current socioeconomic climate, but with the vast intellectual resources of the University of Chicago and its secure place in the community, both locally and nationally, we are confident of our ability to make a continuing contribution to the development of neurosurgery.

Chicago↗
PubMed1996

Changes in endothelial nitric oxide synthase mRNA during vasospasm after subarachnoid hemorrhage in monkeys.

OBJECTIVE: We attempt to determine whether changes in messenger ribonucleic acid (mRNA) for nitric oxide synthase (NOS) and soluble guanylate cyclase, enzymes that mediate endothelium-dependent vasodilation in cerebral arteries, occur after subarachnoid hemorrhage (SAH) in monkeys. METHODS: Baseline cerebral angiograms were obtained, and right-sided SAH was induced by microsurgically placing autologous blood clot against the right anterior circle of Willis in seven monkeys. Seven days later, angiographic studies were repeated and the animals were killed. Right (vasospastic) and left (control) middle cerebral arteries and underlying cortex were removed. The competitive reverse transcriptase polymerase chain reaction was used to quantify mRNA for soluble guanylate cyclase and two isoforms of constitutive NOS in these tissues. RESULTS: Comparison of angiograms at baseline and after 7 days showed a 41 +/- 7% (mean +/- standard error of the mean, P < 0.05, Wilcoxon test) decrease in diameter of the right middle cerebral artery. After the animals were killed, comparison of right and left middle cerebral arteries showed a 56 +/- 11% decrease (P < 0.005, paired t test) in endothelial NOS mRNA. There was a 142 +/- 39% (P < 0.05) increase in right cortex endothelial NOS mRNA compared to the left cortex. There were no significant differences between right and left sides in mRNAs for soluble guanylate cyclase or brain NOS. CONCLUSION: Decreased endothelial NOS mRNA in cerebral arteries 7 days after SAH may be caused by endothelial cell damage and could contribute to vasospasm after SAH. Increased endothelial NOS in brain tissue may reflect a compensatory vasodilator mechanism of the brain against the cerebral ischemia associated with vasospasm and SAH.

Animals↗
PubMed1996

Effect of P2-purinoceptor antagonists on hemolysate-induced and adenosine 5'-triphosphate-induced contractions of dog basilar artery in vitro.

OBJECTIVE: To test the hypothesis that the vasoactive effects of hemolysate of dog erythrocytes on dog basilar artery in vitro are caused by adenosine 5'-triphosphate (ATP). METHODS: Dog erythrocyte hemolysate was assayed for ATP by high-pressure liquid chromatography. Dog basilar arteries were cut into rings and studied under isometric tension to determine the effects of the P2-purinoceptor antagonists suramin, pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid, and reactive blue 2 on contractions induced by hemolysate, prostaglandin F2 alpha (PGF2 alpha), KCl, uridine 5'-triphosphate, and ATP. RESULTS: Dog erythrocyte hemolysate contained 34 mumol/L of ATP. Hemolysate produced concentration-dependent contractions of dog basilar artery. Suramin (100 mumol/L) significantly inhibited contractions to hemolysate, ATP, and uridine 5'-triphosphate but not to PGF2 alpha and KCl (P < 0.05). Pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid (100 mumol/L) caused a small but significant reduction of the contractions to hemolysate and did not affect contractions to PGF2 alpha and KCl. Reactive blue 2 (30 mumol/L) produced significant inhibition of contractions to hemolysate and PGF2 alpha but did not affect contractions to KCl. CONCLUSION: These findings suggest that ATP mediates a smooth muscle contractile response of hemolysate on dog basilar artery. Because erythrocyte cytosol is known to be important in the pathogenesis of vasospasm, these results suggest that ATP may contribute to the vasoconstriction that occurs in vasospasm.

Adenosine Triphosphate↗
PubMed1996

Effect of BQ-123 and tissue plasminogen activator on vasospasm after subarachnoid hemorrhage in monkeys.

BACKGROUND AND PURPOSE: We aimed to determine the effect of intracisternal administration of an endothelin-A receptor antagonist (BQ-123) against vasospasm in a monkey model and to determine whether this drug would have adverse interactions with intracisternal tissue plasminogen activator (TPA). METHODS: Thirty-three monkeys were randomly allocated to undergo baseline cerebral angiography, creation of right subarachnoid hemorrhage (SAH), and intracisternal delivery of (1) placebo (n = 10); (2) low-dose BQ-123 (5 mg/kg per day, n = 7); (3) high-dose BQ-123 (10 mg/kg per day, n = 9); or (4) BQ-123 10 mg/kg per day plus TPA 1 mg every 12 hours for three doses (n = 7). Angiography was repeated after 7 days, and animals were killed. Vasospasm was assessed by comparisons of angiograms within groups across time by paired t test and by comparisons across groups at each time by ANOVA. RESULTS: Significant clot remained in the basal cisterns in all groups except those receiving TPA, in whom complete clot clearance was noted. Comparisons of angiograms at baseline and after 7 days showed significant vasospasm of the right middle cerebral artery in animals receiving placebo (mean +/- SEM reduction in diameter, 36 +/- 7%; P < .05) and low- and high-dose BQ-123 (16 +/- 4% and 18 +/- 7%, respectively). Animals that received TPA did not develop significant right cerebral artery vasospasm. Comparisons of arterial diameters at day 7 revealed significant variance in right middle cerebral artery diameter, with animals in the placebo group having significantly more and animals in the TPA group having significantly less vasospasm than the BQ-123 groups. Histopathological examination of the brains did not show inflammation or pathological change in animals that received BQ-123 or BQ-123 plus TPA. CONCLUSIONS: Intracisternal TPA was efficacious against vasospasm in monkeys. Combination therapy with TPA and BQ-123 was not associated with reduction in efficacy of either drug or with evidence of toxicity.

Animals↗
PubMed1996

Vertebrobasilar junction aneurysms associated with fenestration: treatment with Guglielmi detachable coils.

Three patients with vertebrobasilar junction aneurysms and associated fenestration were treated with Guglielmi detachable coils. The structure and hemodynamics of fenestrations may account for their frequent association with aneurysms. The complex hemodynamics of these aneurysms requires evaluation of both vertebral arteries. One treatment complication occurred but resulted in no deficit. All patients have returned to normal activity and remain healthy at 14 to 46 months.

Aged↗
PubMed1995

Protection of the brain after aneurysmal rupture.

The majority of patients survive the first dangerous hours after an aneurysmal rupture. However, many subsequently succumb as a result of a variety of lethal complications. The most important of these develop as sequelae of the initial ischemia, rebleeding and the delayed onset of vasospasm. Some of these deleterious cascades can be aborted. Since the delayed complications such as vasospastic infarction can be accurately predicted, this is one of rare "strokes" that can have pharmacological pre-treatment. The natural history of rebleeding and vasospasm are described as well as their effects on blood flow, oxygen delivery and metabolism. Strategies to ameliorate acute and delayed ischemia and hypoxia are discussed. Finally, potential pharmacotherapies are detailed.

Aneurysm, Ruptured↗
PubMed1995

Mechanisms of hemolysate-induced [Ca2+]i elevation in cerebral smooth muscle cells.

The effects of hemolysate on free cytosolic [Ca2+] ([Ca2+]i) homeostasis were studied in freshly isolated rat basilar artery smooth muscle cells using fura 2 and dual excitation wavelength microfluorimetry. Hemolysate reversibly produced a transient [Ca2+]i peak followed by a slowly decaying plateau which was absent in Ca(2+)-free solution. This effect of hemolysate was attenuated by 1) the sarcoplasmic reticulum Ca2+ pump inhibitors thapsigargin and cyclopiazonic acid, 2) the Ca2+ release-blocking agents ryanodine and dantrolene, 3) the cytochrome P-450 inhibitor econazole, and 4) the inorganic Ca2+ channel blocker lanthanum but was not significantly attenuated by 1) the receptor-regulated Ca2+ channel blocker SKF-96365 or 2) the voltage-dependent Ca2+ channel blocker nimodipine. Fractionation of hemolysate using membranes with specific pore sizes (0.5, 1, and 12-14 kDa) indicated that a component(s) > 0.5 but < 1 kDa could produce a similar [Ca2+]i peak and plateau while fractions > 1 and > 12-14 kDa produced a small and slow [Ca2+]i rise without a significant peak. ATP, which was found in hemolysate, produced a [Ca2+]i response similar to that of hemolysate. P2-purinoceptor antagonists significantly attenuated the effect of ATP, hemolysate, and the fractions < 1 and < 12-14 kDa. We conclude that hemolysate elevates [Ca2+]i by both releasing Ca2+ from internal stores and triggering Ca2+ entry, possibly from a voltage-independent Ca2+ influx pathway, an effect apparently identical to that of ATP.

2,3-Diphosphoglycerate↗
PubMed1995

Activation of protein kinase C inhibits potassium currents in cultured endothelial cells.

The effect of protein kinase C on potassium channels in cultured endothelial cells was investigated by using whole-cell patch-clamp techniques. Activation of protein kinase C by phorbol 12-myristate 13-acetate (PMA) and phorbol 12,13-dibutyrate (PDBu), but not phorbol 12-monomyristate (PMM), an inactive analogue of phorbol esters, depressed an outward calcium-dependent potassium current. The inhibitory actions of PMA and PDBu could be reversed by the kinase inhibitor H-7. Cyclopiazonic acid, an inhibitor of the sarcoplasmic reticulum calcium pump, and LP-805, a novel vasodilator which also releases endothelium-derived relaxing factors, activated the outward calcium-dependent potassium conductance. PMA and PDBu, but not PMM, reduced the outward conductance induced by cyclopiazonic acid and LP-805. These effects of PMA and PDBu on potassium currents may be mediated either by phosphorylation of ion channels, or by decreasing intracellular calcium concentration.

Animals↗
PubMed1994

Cyclopiazonic acid stimulates Ca2+ influx through non-specific cation channels in endothelial cells.

A non-specific cation channel in cultured human umbilical vein endothelial cells was obtained by cell-attached patch-clamp study. This channel showed a conductance of 28 pS when both pipette and bath contained 140 mM potassium chloride. when pipette solution was changed into 140 sodium chloride with 5 mM calcium chloride, the conductance was 26 pS. when 120 mM calcium chloride was used as the only cation in the pipette, a conductance of 6 pS was obtained. Bath application of cyclopiazonic acid, an inhibitor of the sarcoplasmic reticulum Ca2+ pump in smooth muscle and other tissues, dose dependently activates this non-specific cation channel. It is assumed that cyclopiazonic acid by blockade of the refilling of Ca2+ stores depletes the rapidly exchanging intracellular Ca2+ stores and this action stimulates Ca2+ influx through the non-specific cation channels in human umbilical vein endothelial cells.

Calcium↗
PubMed1994

Endothelin-1 inhibits inward rectifier potassium channels and activates nonspecific cation channels in cultured endothelial cells.

A predominant inward rectifier and a small outward potassium current were obtained in whole-cell patch-clamp recordings from cultured bovine pulmonary arterial endothelial cells. Application of endothelial-1 (ET-1; 10-100 nmol/l) inhibited the inward rectifier. Washout with bath solution did not recover the current decreased by ET-1. In cell-attached studies, ET-1 (1 nmol/l) inhibited single-channel activity of the inward rectifier and in some patches enhanced activity of the outward potassium current without change of conductance. A non-specific cation current which is permeable to calcium was identified in cell-attached patches in cultured human umbilical vein endothelial cells. ET-1 (1 nmol/l) increased activity of the nonspecific cation channel. ET-1 may increase calcium influx into endothelial cells and promote synthase and release of endothelium-derived factors.

Animals↗
PubMed1993

Attempted experimental modification of the postlaminectomy membrane by local instillation of recombinant tissue-plasminogen activator gel.

A prospective, randomized, blinded trial involving 25 adult mongrel dogs was performed to evaluate whether placement of a fat graft or local instillation of recombinant tissue-plasminogen activator gel (rt-PA) could modify the development of a postlaminectomy membrane. One component of the study involved the performance of a lumbar laminectomy and placement of gel rt-PA, free fat, or no tissue placement over the exposed dura mater. Three months later the animals were killed and sections of spine were removed en bloc, decalcified, and examined histologically. No significant differences were found in the degree of cellular fibrosis or heavy collagen production. A similar laminectomy at another lumbar level was also followed by gel rt-PA, free fat, or no tissue placement. Three months after surgery, surgery was performed again at this level immediately before death. There were no differences in the adhesiveness of the laminectomy membrane to dura mater or roots. It was concluded that the local instillation of gel rt-PA after laminectomy did not inhibit scar formation or scar adherence to the dura mater.

Adipose Tissue↗
PubMed1993

Procollagen types I and III and transforming growth factor-beta gene expression in the arterial wall after exposure to periarterial blood.

The stiffening and thickening of the arterial wall after subarachnoid hemorrhage may reflect increased connective tissue. The purpose of this study was to examine the nature of collagen synthesis in response to periarterial blood. Rat femoral arteries were exposed to periarterial blood for varying lengths of time (control, 1, 3, 7, and 14 d). Dot-blot analysis of total ribonucleic acid extracted from the arteries (n = 10 to 15 animals each) demonstrated that the expression of procollagen Types I and III messenger ribonucleic acid increased at 7 (threefold) and 14 days. The expression of transforming growth factor-beta (TGF-beta), an important regulator of collagen synthesis, was markedly increased by 3 days (threefold), followed by a gradual decline. There were marked differences in procollagen Types I and III and TGF-beta gene expression between arteries exposed to blood and sham-operated arteries for a period of 7 days (n = 25 animals). Northern blot analysis of total ribonucleic acid extracted from cultured vascular smooth muscle cells showed that the treatment with a higher concentration of serum for 48 hours increased the expression of procollagen Types I and III and TGF-beta, whereas exposure to oxyhemoglobin did not. After exposure to periarterial blood, arterial walls show increased synthesis of procollagen Types I and III, perhaps a response to the increased secretion of TGF-beta, which in turn could be the result of exposure to serum factors.

Animals↗
PubMed1993

Antibiotic prophylaxis in cesarean section: use of cost per case comparison to influence prescribing practices.

Results of a previously conducted DUE revealed that 91% of obstetric patients received antibiotic prophylaxis with cefoxitin despite the existence of obstetric department guidelines recommending the use of cefazolin. In the present DUE, antibiotic selection in C-section prophylaxis was reviewed and individual prescribers, both compliant and noncompliant with guidelines, were identified. Over a 2-month period, physicians who prescribed other than cefazolin for C-section prophylaxis were issued "Dear Doctor" letters, reminding them of existing guidelines. A significant change in prescribing patterns following this intervention was not demonstrated. A multidisciplinary approach was then undertaken. Prescribers were stratified by number of procedures, antibiotic requested, and antibiotic cost per case (average and median). Results were reviewed with Co-chiefs of Ob/Gyn. Letters to both compliant and noncompliant prescribers were issued. A grand rounds presentation describing the results of the DUE was also given. A follow-up review showed that the conversion to cefazolin prophylaxis reached 80%, with accompanied extrapolated yearly cost avoidance of nearly $5,500.

Adult↗
PubMed1993

Cerebral vasospasm.

If patients are treated within the first 3 days after rupture, early definitive clipping associated with mechanical clot removal to the extent practical and instillation of fibrinolytic agents seems likely to become standard therapy. Patients should also receive calcium antagonists and be maintained in normal fluid and electrolyte balance. At the first sign of delayed ischemic deficits, therapy with hypervolemia and hypertension should be instituted. If clinical deterioration is progressive despite this, consideration should be given to intra-arterial vasodilators or balloon angioplasty. If patients are referred more than 3 days after hemorrhage, we still advocate the same course of action unless the patient presents with established severe diffuse vasospasm and is unconscious. Operation in such a setting is likely to be associated with prohibitive mortality and morbidity. In such cases, it might be worth the risk of using intra-arterial vasodilators or balloon angioplasty despite the presence of an unclipped aneurysm. The last decade has witnessed substantial advances in our knowledge of the pathogenesis of vasospasm and we now have a reasonable chance at effective prophylaxis and treatment.

Aneurysm, Ruptured↗