Enhancement of UDPgalactose: glycoprotein galactosyltransferase in cultured human skin fibroblasts by cationic polypeptides.

UDPgalactose : glycoprotein galactosyltransferase in normal human skin fibroblast homogenates has been assayed using ovalbumin as an acceptor. The activity in the homogenate fraction sedimenting between 51 300 X g and 105 000 X g was enhanced by the addition of a number of catonic polypeptides of L-configuration but not by those of D-configuration. In contrast to the enhancing effect of poly(L-lysine), poly(L-glutamic acid) inhibited the activity. Poly(D-glutamic acid) had no effect. Cationic or anionic amino acid derivatives, spermine or spermidine had no effect on activity. The enhancement of transferase activity by poly(L-arginine) is probably due to an increase in V for UDPgalactose and ovalbumin. The implication of these results for the regulation of glycoprotein synthesis in cultivated skin fibroblasts and for the pathogenesis of cystic fibrosis is discussed.

Cerebral vasospasm after subarachnoid hemorrhage.

Chronic cerebral vasospasm remains the most important cause of subsequent morbidity in patients who survive the first 48 to 72 hours after a subarachnoid hemorrhage. Prolonged arterial narrowing compromises cerebral hemodynamics and results in cerebral ischemia. Among patients in whom symptomatic chronic cerebral vasospasm develops, almost half die or have a serious residual neurologic deficit. Present evidence indicates that sustained vessel narrowing results from structural changes within the arterial wall rather than from active contraction of vascular smooth muscle. The mechanism (or mechanisms) responsible for these changes is unknown, but damage from prolonged active arterial contraction, depression of vessel wall respiration, and an inflammatory response have all been proposed as explanations. Despite more than 30 years of intensive study, an effective treatment program for chronic cerebral vasospasm remains elusive. Recent therapeutic trials, however, based on efforts to interrupt the mechanisms responsible for these structural changes hold some promise.

Encephalo-omental synangiosis in the management of moyamoya disease.

Moyamoya disease is a chronic occlusive cerebrovascular disorder characterized by stenosis of the intracranial internal carotid artery often accompanied by stenosis of the anterior and/or middle cerebral arteries. This results in cerebral ischemia, which manifests clinically as transient, repetitive episodes of hemiplegia, dysarthria, and involuntary movements. This case report documents a patient in whom an initial extracranial-intracranial bypass (superficial temporal-middle cerebral artery) failed to alleviate the ischemic symptoms. In a subsequent procedure, a pedicle graft of omentum was created and through a subcutaneous tunnel was placed on the right cerebral cortex. Over a 2 1/2-year period, this has resulted in a dramatic resolution of the patient's symptomatology. The report delineates the condition and reviews other therapeutic options.

Exposure rates to patients' blood for surgical personnel.

BACKGROUND: Surgical personnel are at risk of contracting blood-borne diseases through exposure to patients' blood. Exposure rates for each surgical subspecialty have not been previously reported. The purpose of this study was to determine the rates of exposure to patients' blood for operating room personnel. METHODS: The study was conducted at Yale-New Haven Hospital, a level I trauma center and tertiary care hospital. During a 3-month period, exposed personnel were interviewed by a study nurse immediately after a cutaneous exposure to blood or after a sharp injury. RESULTS: During 2292 surgical procedures, 70 sharp injuries and 168 cutaneous exposures to blood were reported. The combined exposure rate (skin contact and sharp injury) was 10.4 per 100 procedures (95% confidence interval, 9.1 to 11.6) and ranged from 21.2 for general surgery to 3.3 for pediatric surgery (goodness-of-fit chi-squared, p < 0.001). The combined exposure rates were also significantly different among types of surgery and ranged from 18 for laparotomies to 4.3 for craniotomies (chi-squared, p < 0.001). The overall sharp injury rate was 3.1 per 100 procedures (95% confidence interval, 2.3 to 3.8) and ranged from 4.3 for general surgery to 1.3 for vascular surgery. CONCLUSIONS: The rate of exposure to blood for operating room personnel, which differ from prior studies, was 10.4 per 100 procedures and was highest for general surgical procedures. The differences in rates among studies might be attributable to different surgical technique, dissimilar case-mix, or different research methods relating to definition or ascertainment of exposure.

Detachable balloon embolization: concomitant use of a second safety balloon.

We describe a relatively unusual case of carotid cavernous fistula in association with a persistent trigeminal artery, presumably related to aneurysm rupture near the carotid origin of the vessel. We emphasize the use of a second, nondetachable balloon solely for the purpose of stabilizing placement of the first device at the time of detachment.

Nuances of middle cerebral artery aneurysm microsurgery.

Middle cerebral artery aneurysms, a common source of subarachnoid hemorrhage, occur predominantly at the main bifurcation of the middle cerebral artery. Microsurgical clipping is the most effective treatment of these aneurysms because of their peripheral location, wide necks, and straightforward surgical anatomy. Despite the moderate technical requirements of this type of surgery, patients with ruptured aneurysms often have poor outcomes because of the high incidence of intracerebral hematomas. Although several different surgical approaches can be used, we favor a lateral-to-medial transsylvian approach for most aneurysms. This description of our surgical technique stresses minimizing retraction to avoid injury to the brain and preparing broad-based middle cerebral artery aneurysms for clipping. Management of outcomes when using these techniques also is presented.

Patterns of failure of aspirin treatment in symptomatic atherosclerotic carotid artery disease.

Over a 24-month period, 291 patients were consecutively admitted to the West Haven Veterans Administration Medical Center with new ischemic neurological symptoms. Of these, 90 patients (31%) developed ischemic neurological symptoms while taking aspirin (aspirin treatment failure). Of those in whom aspirin treatment failed, 66 patients had ischemic symptoms in the distribution of the carotid artery. Aspirin treatment failed in 21 patients with severe carotid stenosis (greater than 75% stenosis). Eleven of these 21 patients had cerebral infarctions while taking aspirin, and 7 of these 11 infarcts occurred without the prior warning of transient ischemic attacks. Aspirin treatment failed in 45 patients with lesser degrees of carotid stenosis. Transient ischemic attack without permanent ischemia was the most common manifestation of failure in these patients. Infarction occurred in only 12 of these 45 patients and in only 4 patients did infarction occur without warning. We conclude that patients with symptomatic high-grade carotid stenosis (greater than 75%) in whom aspirin treatment failed are likely to suffer an infarct without warning as the first sign of treatment failure (P less than 0.033). We suggest that this subgroup of patients should be considered for alternative forms of therapy.

Morphometric analysis of reticular and elastin fibers in the cerebral arteries of patients with intracranial aneurysms.

Elastin and reticular fibers were identified using standard histological strains in middle cerebral arteries taken from patients who had died from aneurysmal subarachnoid hemorrhage and control patients who did not have cerebral aneurysms. Examination of cerebral arteries from normal individuals revealed a dense network of fine reticular fibers in the arterial media that were uniformly distributed. Computerized morphometric analysis indicated that reticular fibers in the arterial media of cerebral arteries were significantly decreased in patients with aneurysms. In addition, these fibers were irregularly distributed and shortened when compared to those seen in control arteries. In both patients with aneurysms and control patients, elastin fibers were limited almost exclusively to the internal elastin lamina. No differences were observed in the appearance or content of elastin fibers in control patients and patients with aneurysm. Although other explanations cannot be excluded, these observations are consistent with the hypothesis that "intrinsic" abnormalities in the walls of cerebral arteries lead to conditions that favor the formation and rupture of cerebral aneurysms.

Solitary eosinophilic granuloma of the frontal lobe.

Solitary intracranial eosinophilic granulomas are rare and most frequently involve the hypothalamus. We report an unusual case of solitary eosinophilic granuloma of the frontal lobe in a patient without evidence of systemic disease. Previously reported cases of solitary intracranial nonhypothalamic lesions are reviewed, and the clinical, radiographic, and histological features of this case are discussed.

Preliminary report: effects of high dose methylprednisolone on delayed cerebral ischemia in patients at high risk for vasospasm after aneurysmal subarachnoid hemorrhage.

Mounting evidence suggests that chronic cerebral vasospasm may be linked to the inflammatory response that follows subarachnoid hemorrhage. Twenty-one patients judged to be at high risk for vasospasm because of either poor admitting grade or a large amount of subarachnoid blood shown by computed tomography were treated with a course of high dose methylprednisolone, and management results were compared to those of a cohort of contemporary control patients matched for grade, number of hemorrhages, time from hemorrhage to admission, time from hemorrhage to operation, aneurysm location, age, and sex. Patients treated with high dose methylprednisolone were twice as likely to have an excellent result and half as likely to die as those who were not treated. The incidence and severity of delayed cerebral ischemia were reduced in treated patients when compared to control patients. None of the treated patients developed a serious side effect that could be attributed to steroid treatment. These findings are consistent with the conclusion that chronic vasospasm is an inflammatory vasculopathy and suggest that early treatment with high dose methylprednisolone may benefit this high risk group of patients.

Inflammation and intracranial aneurysms.

OBJECTIVE: An intracranial aneurysm is an important acquired cerebrovascular disease that can cause a catastrophic subarachnoid hemorrhage. Despite modern therapy, most patients die or are left disabled as a direct result of a severe initial hemorrhage. The development of more effective treatment strategies depends on understanding the fundamental biology of cerebral aneurysms. The purpose of the present study is to determine whether inflammation or immunological reaction occurs in cerebral aneurysms. METHODS: Aneurysm tissue was collected at the time of microsurgical repair from 23 unruptured and 2 ruptured aneurysms (25 patients) and compared with 11 control basilar arteries harvested at autopsy. Immunohistochemistry was used to localize complement (C3c, C9), immunoglobulins (IgG, IgM), vascular cell adhesion molecule-1, macrophages and monocytes (CD68), T lymphocytes (CD3), and B lymphocytes (CD20). RESULTS: Complement (C3c, P < 0.0001; C9, P = 0.0017), immunoglobulin (IgG, P = 0.0013; IgM, P = 0.031), vascular cell adhesion molecule-1 (P = 0.0022), macrophages (CD68, P = 0.004), and T lymphocytes (CD3, P = 0.0004) were all frequently present in the wall of aneurysm tissue but were rarely identified in control basilar arteries. A few B lymphocytes (CD20, P = 0.41) were found in aneurysm tissue, but none were found in the basilar arteries. CONCLUSION: Extensive inflammatory and immunological reactions are common in unruptured intracranial aneurysms and may be related to aneurysm formation and rupture.

Prevention of chronic cerebral vasospasm in dogs with milrinone.

OBJECTIVE: Delayed cerebral ischemia resulting from vasospasm is a major cause of morbidity and death in patients with aneurysmal subarachnoid hemorrhage. Milrinone, because it inhibits Type IV cyclic adenosine monophosphate-specific phosphodiesterase enzyme in both cardiac and vascular smooth muscle, is a powerful inotrope and vasodilator, but it has little effect on heart rate or blood pressure. Because of these properties, milrinone is an attractive potential therapy after subarachnoid hemorrhage. The purpose of the present study was to investigate the effect of milrinone on chronic experimental cerebral vasospasm. METHODS: A double-hemorrhage canine model of vasospasm was used to study the efficacy of milrinone. Angiographic vasospasm and systemic hemodynamics were compared in a treatment group of animals that received a loading dose of milrinone (0.05 mg/kg, intravenously) and then slow-release (0.05 microgram/kg/min) milrinone pellets (n = 10) and a control group that received placebo pellets (n = 9), over an 8-day period after the initial subarachnoid hemorrhage. The hemorrhage was created by injection of 4 ml of autologous, nonheparinized, arterial blood into the cisterna magna on Days 1 and 3. Hemodynamic measurements, including cardiac output determinations, were made on Days 0, 1, 3, 6, and 8 with a pulmonary artery catheter, and angiographic vasospasm was assessed on Day 8 by comparison with baseline angiograms. RESULTS: Treatment with milrinone caused no significant changes in systemic hemodynamics. Angiographic vasospasm, however, was significantly reduced in the Day 8 angiograms for the treated group, compared with the control group (98.28 +/- 14.06 and 67.89 +/- 13.06% of original vessel cross-sectional area, respectively; P < 0.001). CONCLUSION: Milrinone is effective in preventing chronic cerebral vasospasm in a canine model of experimental chronic cerebral vasospasm. This effect is independent of changes in systemic hemodynamics. Milrinone and related drugs warrant further investigation for the treatment of cerebral vasospasm.

Vascular malformations of the brain stem.

Vascular malformations of the brain stem are unusual lesions that may pose a diagnostic and therapeutic challenge. Seven patients with vascular malformations involving the brain stem were evaluated; six were treated surgically, with complete obliteration of the lesion in five patients. In five patients symptoms developed only after a hemorrhage had occurred, and three of these suffered a rebleed before appropriate treatment was given. Angiography failed to demonstrate lesions in three cases, which did not appear to protect from repeat hemorrhage since two of the three rebled. There were no operative deaths, and no patients were made permanently worse after surgery. Useful recovery occurred commonly after appropriate treatment and appeared to be possible even in patients who had suffered a catastrophic neurological deficit at the time of presentation. These data indicate that surgical removal of the lesion may be warranted in some patients with symptomatic brain-stem vascular malformation.

In situ photocoagulation of spinal dural arteriovenous malformations using the Nd:YAG laser.

Spinal dural arteriovenous malformations (AVM's) are the most common type of AVM involving the spinal cord in adults. Direct obliteration of the fistula nidus located in the dura is the preferred method of treatment. Five cases of spinal dural AVM were treated by open surgical exposure, microsurgical disconnection of the dural nidus from the coronal venous plexus, and in situ obliteration of the nidus using the Nd:YAG laser. Use of the Nd:YAG laser reduced nidus obliteration to a simple 10-minute technical exercise. All patients improved neurologically following surgery, and complete obliteration of all lesions was verified by delayed angiography. There were no permanent complications related to either the surgical exposure or the use of the Nd:YAG laser. Open surgical treatment of spinal dural AVM's using the Nd:YAG laser appears to be a safe, effective, and durable method of treating these lesions. Photocoagulation is discussed in the context of the other treatment modalities available.

Functional outcome after repair of unruptured intracranial aneurysms.

OBJECT: Repair of unruptured aneurysms is a reasonable course of action if their expected natural history is worse than the predicted risks of treatment. The purpose of this study was to examine the presenting symptoms of unruptured aneurysms and to test the hypothesis that unruptured intracranial aneurysms can be repaired without significant functional worsening. A second hypothesis was also examined--that is, that the experience of the surgeon, the aneurysm size, and the patient age can be used to predict functional outcome. METHODS: Consecutive patients who underwent repair of an unruptured intracranial aneurysm at a single institution between 1980 and 1998 were studied. Clinical and radiographic data were collected in all patients. Their modified Rankin Scale (mRS) score was determined before treatment (baseline), at 6 weeks, and at 6 months. The primary endpoint for analysis was the mRS score. Four hundred forty-nine aneurysms were repaired in 366 patients by 10 surgeons. The mean size of the primary lesion repaired was 14.6 + 10.4 mm and 27% were judged to be symptomatic. Aneurysm treatment involved either microsurgical clipping (78%), wrapping (4%), trapping with or without bypass (5%), hunterian ligation with or without bypass (9%), or other methods (4%). The mRS scores at 6 weeks were worse than at baseline (p < 0.0001), but there was no significant difference between the baseline and 6-month mRS score. At 6 months, 94% of patients showed no significant functional worsening as a result of treatment. The number of aneurysms treated by a specific surgeon was a strong predictor of better functional outcome (r = 0.99, p = 0.05). Increasing patient age (r = 0.16, p = 0.003) and increasing aneurysm size (r = 0.15, p = 0.004) were predictors of worsened functional outcome. CONCLUSIONS: Many unruptured aneurysms produce symptoms. Unruptured intracranial aneurysms can be treated without significant permanent functional worsening. The surgeon's experience, aneurysm size, and patient age are predictors of functional outcome.

Response of chronic experimental cerebral vasospasm to methylprednisolone and dexamethasone.

The authors have previously demonstrated that high-dose methylprednisolone (30 mg/kg intravenously every 8 hours) prevents severe chronic vasospasm in dogs. In the present study, lesser doses of methylprednisolone (15 mg/kg intravenously every 8 hours) and dexamethasone (0.1 mg/kg intravenously every 8 hours), although better than no treatment at all, were significantly less effective than the higher dose of methylprednisolone. These data suggest that methylprednisolone can prevent chronic experimental vasospasm from occurring only when given in high doses (30 mg/kg).

Profound hypothermia and circulatory arrest for aneurysm surgery. Case report.

Direct surgical repair of technically difficult or otherwise inoperable vascular lesions of the brain may become possible or safer using profound hypothermia and circulatory arrest. Most surgeons who use this technique establish extracorporeal circulation by cannulating the femoral vessels. To avoid difficulties associated with this closed chest method, a method was devised to establish extracorporeal circulation, profound hypothermia, and circulatory arrest by direct cannulation of the right atrium and aorta through the chest. This technique is described in a patient whose otherwise inoperable vertebral artery aneurysm was successfully treated. This approach is simple and offers several advantages over the closed chest method.

Early versus late intracranial aneurysm surgery in subarachnoid hemorrhage.

The management results in 244 patients admitted to one institution within 3 days of aneurysmal subarachnoid hemorrhage (SAH) from January, 1979, to December, 1985, were analyzed with respect to the timing of surgical intervention. Twenty-six patients died prior to surgery. Patients surviving to surgery were divided into three groups according to the interval between preadmission SAH and surgery: 0 to 3 days (85 cases), 4 to 9 days (83 cases), and 10 or more days (50 cases). Of the patients who were categorized neurologically into Botterell Grades 1 and 2 (Hunt and Hess Grades I to III) on admission, 87% had an excellent or good result on follow-up evaluation. Patients undergoing surgery 0 to 3 days after SAH had a statistically significant increase in the incidence of postoperative ischemic symptoms (p less than 0.005), which was balanced by similar complications preoperatively in the 10-day post-SAH surgical group. Most rebleeds occurred before admission but delaying surgery did increase the risk of rebleeding in the hospital (p less than 0.0005). Management morbidity and mortality occurred primarily as a direct result of a severe initial hemorrhage; thus, the measured benefits of early surgery were less than might have been predicted.

Vascular extracellular matrix remodeling in cerebral aneurysms.

OBJECT: The occurrence of cerebral aneurysms has been linked to alterations in the extracellular matrix and to matrix-degrading proteases. The purpose of the present study was to determine whether active extracellular matrix remodeling occurs within cerebral aneurysms. METHODS: Aneurysm tissue was collected from 23 patients (two of whom had a ruptured aneurysm and 21 of whom had an unruptured aneurysm) and compared with 11 control basilar arteries harvested at autopsy. Active proteinases capable of gelatin lysis were identified by performing in situ zymography in the presence and absence of a metalloproteinase inhibitor (ethylenediamine tetraacetic acid) and a serine proteinase inhibitor (phenylmethylsulfonyl fluoride). Immunohistochemical analysis was used to localize plasmin, tissue-type (t)-plasminogen activator (PA), urokinase-type (u)-PA, membranetype (MT1)-matrix metalloproteinase (MMP), MMP-2, MMP-9, and tenascin. Focal areas of gelatin lysis occurred in most cerebral aneurysm tissue samples (17 of 21), but rarely in control arteries (two of 11) (p = 0.002). Both serine proteinases and MMPs contributed to gelatin lysis; however, the MMPs were the predominant enzyme family. Plasmin (p = 0.04) and MT1-MMP (p = 0.04) were expressed in the aneurysm tissue but were unusual in control tissue. The MMP-2 was also expressed more commonly in aneurysm than in control tissue (p = 0.07). The MMP-9 and t-PA were expressed in both groups; however, different staining patterns were observed between aneurysm and control tissue. Tenascin staining was commonly present in both groups, whereas u-PA staining was rarely present. CONCLUSIONS: Aneurysm tissue demonstrates increased proteolytic activity capable of lysing gelatin and increased expression of plasmin, MT1-MMP, and MMP-2 when compared with normal cerebral arteries. This activity may contribute to focal degradation of the vascular extracellular matrix and may be related to aneurysm formation and growth.

Prevention of chronic experimental cerebral vasospasm with ibuprofen and high-dose methylprednisolone.

Severe chronic cerebral vasospasm was reliably induced in dogs by two injections, 2 days apart, of autologous blood into the cisterna magna. Treatment with ibuprofen or high-dose methylprednisolone after the first injection prevented or reduced vasospasm. Both drugs reduced meningismus and accelerated the rate of neurological recovery. Compared with specimens from normal dogs, rings of basilar arteries obtained from untreated dogs contracted weakly in response to 5-hydroxytryptamine, prostaglandin F2 alpha, potassium chloride, and barium chloride. Rings of arteries from dogs who received ibuprofen or methylprednisolone contracted more strongly. Electron micrographs of basilar arteries from untreated dogs showed degeneration of smooth muscle, whereas those from treated dogs did not. Thus, what is termed "chronic cerebral vasospasm" probably represents a structural derangement of the blood vessel wall leading to its narrowing, rather than a sustained contraction of the vascular smooth muscle. Administration of high-dose methylprednisolone and ibuprofen can prevent its occurrence.