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Biomedical subjects

J G McComb

Publications and source records attributed to J G McComb.

At least 55 records · Page 3Linked to original sources
PubMed1997

Spinal extradural leiomyoma in a pediatric patient with acquired immunodeficiency syndrome: case report.

OBJECTIVE AND IMPORTANCE: We report a case of two separate cervicothoracic, extradural leiomyomas occurring in a male pediatric patient with acquired immunodeficiency syndrome (AIDS). To our knowledge, such a case has never been reported in the literature. CLINICAL PRESENTATION: A 9-year-old male patient with AIDS presented with progressive leg weakness. At examination, he was myelopathic with paraparesis and a T4 sensory level to pinprick. A magnetic resonance image revealed two separate cervicothoracic lesions causing cord compression. INTERVENTION: The patient underwent resection of both lesions. Postoperatively, he regained normal strength in his legs and was discharged home after 2 weeks. CONCLUSION: With the ever-growing number of pediatric patients with AIDS, the entity will likely be encountered with increasing frequency in the future. Because of the potential for neurological recovery and cure, the neurosurgeon should be cognizant of this entity.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Outcome for preterm infants with germinal matrix hemorrhage and progressive hydrocephalus.

OBJECTIVE: An analysis of 76 preterm infants with Grade III or IV intracranial hemorrhage and surgically treated progressive hydrocephalus was undertaken to determine mortality, intellectual impairment, and motor deficit. METHODS: The variables examined were degree of prematurity, birth weight, sex, Apgar scores, extent of intracranial hemorrhage, seizures, age at time of initial placement of a ventricular catheter reservoir to control hydrocephalus, need to convert the reservoir to a ventriculoperitoneal shunt, timing of the conversion of the reservoir to a ventriculoperitoneal shunt, and number of shunt revisions. Outcome was assessed for statistical significance using hierarchical linear regression and logistic regression analyses. RESULTS: Linear regression analysis determined that mortality was best predicted, in order of importance, by extent of intracranial hemorrhage, number of shunt revisions, and birth weight (P < 0.0001, R = 0.79). Grade of hemorrhage, weight at birth, and presence of seizure activity were the most important determinants of motor outcome (P < 0.001, R = -0.78). CONCLUSIONS: Logistic regression analysis of the 41 long-term survivors determined that grade of hemorrhage was the most important variable in determining cognitive outcome (P < 0.0001), motor function (P < 0.0001), and presence of seizure activity (P < 0.001). A logistic model of survival determined that grade of hemorrhage and multiple shunt revisions (more than five) were the most important determinants (P < 0.0001) of survival. In conclusion, the overwhelming factor in determining outcome in this patient group was the extent of intracranial hemorrhage.

Apgar Score↗
PubMed1997

Recurrence patterns and anaplastic change in a long-term study of pilocytic astrocytomas.

Thirty-six cases of pilocytic astrocytomas treated at the Childrens Hospital of Los Angeles from 1984 through 1995 were reviewed. The mean age at initial presentation was 8 years (range 15 months to 14 years). These patients were followed for an average of 5.5 years. No patient was given chemotherapy or radiation therapy after the initial surgery for pilocytic astrocytoma. Twenty-three patients (64%) had a gross total resection with no residual tumor on immediate postoperative imaging studies. Three of these children had tumor recurrences 2-5 years after their initial surgery, requiring re-excision of their tumors. All 3 patients are subsequently tumor-free, with follow-up ranging from 4 to 10 years. In 4 patients with residual tumor involving the brainstem, there has been neither imaging evidence of tumor enlargement nor progression of clinical findings at 2.5, 4, 6 and 6 years, respectively. Nine of the 13 patients with residual tumor underwent re-excision, either for progression of symptoms or documented tumor growth on imaging studies. The second operation was undertaken an average of 1 year (range 1 month to 6 years) after the first. In 4 of these children (11% of our whole series), the recurrent tumor was classified as anaplastic astrocytoma. Three of these 4 children received radiation and/or chemotherapy, with only 1 patient showing disease progression in the follow-up period. Repeat blinded histopathological examination of these tumors confirmed both diagnoses. However, it was noted that 3 of the 4 pilocytic astrocytomas which subsequently showed anaplastic change initially displayed increased perivascular cellularity, while only 2 of the remaining 32 tumors exhibited this feature. These results encourage continued vigilance in the follow-up of pilocytic astrocytomas, and describe a histological feature which might indicate a more aggressive disease course.

Adolescent↗
PubMed1997

Surgical management of sagittal synostosis: a comparative analysis of strip craniectomy and calvarial vault remodeling.

Although surgical treatment of sagittal synostosis has become normative, the procedure of choice is still debated. This retrospective analysis, during a 10-year period (1986-1995) at Children's Hospital Los Angeles, compares the more conservative strip craniectomy (SC) procedure with a more extensive occipital reduction-biparietal widening calvarial vault remodeling (CVR) technique for the management of sagittal synostosis. SC was performed in 72 patients (61%) and CVR in 46 (39%). Patients undergoing CVR were older (mean 5.3 vs. 3.0 months, p < 0.01), the procedure time longer (mean 126 min vs. 72 min, p < 0.01), intraoperative blood loss greater (mean 243 vs. 54 cm3, p < 0.01), and the frequency of intraoperative blood transfusion increased (100 vs. 38%, p < 0.01; mean volume 357 vs. 51 cm3, p < 0.01) compared to patients undergoing SC. No significant intraoperative complications occurred in either group. The total time of hospitalization was similar (mean 4.4 vs. 3.8 days, p = 0.02). No neurological, hematological, or transfusion-related complications or deaths were encountered in either group. Cosmetic outcomes were significantly better in the CVR group with 79% rated as excellent compared to 41% in the SC group (p < 0.01). Fifty-nine percent of the SC patients manifested bony defects at last follow-up visit. Two SC patients required reoperation for poor cosmetic outcomes; CVR was successfully employed in both cases. These findings demonstrate that CVR is superior to SC in providing immediate and lasting correction of calvarial deformities secondary to sagittal synostosis. The optimal age at time of surgery is <6 months; however, CVR can be utilized throughout infancy, while SC becomes progressively less effective after 6 months of age. No significant complications were observed in either group, despite the increased operative manipulation and greater incidence of blood transfusion in the CVR patients.

Craniotomy↗
PubMed1997

Surgical treatment of craniosynostosis: outcome analysis of 250 consecutive patients.

OBJECTIVE: Surgery for craniosynostosis has evolved rapidly over the past two decades, with increased emphasis on early, extensive operations. Older published series may not accurately reflect more recent experience. Our study was designed to analyze outcome in a large series of consecutive patients treated recently at a single center. METHODS: We reviewed 250 consecutive patients who underwent surgical treatment of craniosynostosis between January 1, 1987 and December 31, 1992. They were divided into nine groups by suture involvement: sagittal, unilateral coronal, bilateral coronal, unilateral lambdoid, bilateral lambdoid, metopic, multiple suture, the Klee-blattschädel deformity (cloverleaf skull), and acquired craniosynostosis. Outcome was analyzed in terms of residual deformities and irregularities, complications, mortality, as well as the need for additional surgery. RESULTS: There were 157 males (62. 8%) and 93 females (37.2%), with most of the male preponderance accounted for by the large sagittal synostosis group, which consisted of 82 males and 25 females. Median age at first operation was 147 days. A named syndrome was present in 23 patients (9.2%) and was more common than expected with bilateral and unilateral coronal synostosis, the Kleeblattschädel deformity, and multiple suture synostosis. There were two deaths (0.8%), both with Klee-blattschädel patients, and 17 other complications (6.8%). Morbidity and mortality were significantly associated with secondary vs primary operations and syndromic vs nonsyndromic patients. Outcome analysis revealed the best surgical results with metopic synostosis and significantly less good results with the Kleeblattschädel deformity, multiple suture synostosis, and bilateral coronal synostosis. CONCLUSIONS: Using modern surgical techniques, craniosynostosis can be corrected with good outcomes and relatively low morbidity and mortality, particularly for otherwise healthy, nonsyndromic infants.

Craniosynostoses↗
PubMed1996

Glycoprotein 330/megalin: probable role in receptor-mediated transport of apolipoprotein J alone and in a complex with Alzheimer disease amyloid beta at the blood-brain and blood-cerebrospinal fluid barriers.

A soluble form of Alzheimer disease amyloid beta-protein (sA beta) is transported in the blood and cerebrospinal fluid mainly complexed with apolipoprotein J (apoJ). Using a well-characterized in situ perfused guinea pig brain model, we recently obtained preliminary evidence that apoJ facilitates transport of sA beta (1-40)-apoJ complexes across the blood-brain barrier and the blood-cerebrospinal fluid barrier, but the mechanisms remain poorly understood. In the present study, we examined the transport process in greater detail and investigated the possible role of glycoprotein 330 (gp330)/megalin, a receptor for multiple ligands, including apoJ. High-affinity transport systems with a Km of 0.2 and 0.5 nM were demonstrated for apoJ at the blood-brain barrier and the choroid epithelium in vivo, suggesting a specific receptor-mediated mechanism. The sA beta (1-40)-apoJ complex shared the same transport mechanism and exhibited 2.4- to 10.2-fold higher affinity than apoJ itself. Binding to microvessels, transport into brain parenchyma, and choroidal uptake of both apoJ and sA beta (1-40)-apoJ complexes were markedly inhibited (74-99%) in the presence of a monoclonal antibody to gp330/megalin and were virtually abolished by perfusion with the receptor-associated protein, which blocks binding of all known ligands to gp330. Western blot analysis of cerebral microvessels with the monoclonal antibody to gp330 revealed a protein with a mass identical to that in extracts of kidney membranes enriched with gp330/megalin, but in much lower concentration. The findings suggest that gp330/megalin mediates cellular uptake and transport of apoJ and sA beta (1-40)-apoJ complex at the cerebral vascular endothelium and choroid epithelium.

Amino Acid Sequence↗
PubMed1996

Blood-brain barrier uptake of the 40 and 42 amino acid sequences of circulating Alzheimer's amyloid beta in guinea pigs.

An intracarotid brain infusion/capillary depletion technique was used in guinea pigs to examine cerebral capillary sequestration and transport into brain parenchyma of sA beta 1-40 and sA beta 1-42, synthetic peptides identical to two forms of the amyloid beta peptide found in Alzheimer's disease lesions: the 40 residue form, found primarily in vascular deposits, and the 42 residue form, found primarily in senile plaques. The peptides crossed well into the brain parenchyma via a specific transport mechanism for which sA beta 1-40 had an approximately two-fold greater affinity than sA beta 1-42. There was significant capillary sequestration of sA beta 1-40, but retention by the microvasculature of sA beta 1-42 was negligible. These data suggest that the level of the 40 residue peptide in cerebral vasculature and of the 42 residue peptide in parenchyma could be regulated by blood-brain barrier sequestration and transport of their respective circulating precursors.

Alzheimer Disease↗
PubMed1996

Transport of circulating reduced glutathione at the basolateral side of the anterior lens epithelium: physiologic importance and manipulations.

Transport of circulating reduced glutathione (GSH) was studied at the basolateral side of the lens epithelium by using an in situ vascular eye perfusion technique in guinea-pigs with rapid sampling to ensure detecting initial uptakes. The unidirectional transport rates of [35S]-GSH (4 nM) from plasma and aqueous into the epithelial cytosol were 0.046 +/- 0.003 and 6.88 +/- 0.39 min-1, respectively. HPLC analysis indicated that over 94% of [35S]-GSH remained intact in the epithelium and cortex in the presence or absence of gamma-glutamyl transpeptidase inhibitor, serine borate. Simultaneous infusion of [35S-cysteine]-GSH and [3H-glycine]-GSH confirmed the non-involvement of gamma-glutamyl transpeptidase in GSH transport across the lenticular membranes by showing that 35S/3H ratio in the epithelium and cortex was the same as in the aqueous and plasma. GSH epithelial influx was reduced by 53% (P < 0.01) by 0.3 mM sulphobromophtalein-GSH, a GSH conjugate that does not inhibit the facilitative GSH transporter, RcGshT, recently found in the lens. At physiologic concentration of circulating GSH at 30 microM, GSH epithelial influx was 0.77 nmol min-1 g-1; a t1/2 of 85.4 hr was estimated if endogenous epithelial GSH had to be replaced exclusively by plasma-derived GSH. The level of GSH in the epithelium was increased by 38% (P < 0.05) by 1 hr arterial infusion of GSH at 20 mM. The aqueous concentration of GSH under these conditions was 1.2 mM so that accumulation in the epithelium occurred a greater than six-fold concentration gradient. It is concluded that: (a) transport of GSH at the basolateral side of the epithelium is mediated by a concentrative mechanism distinct from RcGshT: (b) circulating GSH may represent a major source for epithelial GSH under physiologic conditions; and (c) the level of GSH in the epithelium can be manipulated by exogenous GSH.

Animals↗
PubMed1996

Transport of dopamine at the blood-brain barrier of the guinea pig: inhibition by psychotropic drugs and nicotine.

PURPOSE: Transport of dopamine (DA) across the blood-brain barrier (BBB) was examined in guinea pigs. METHODS: In situ brain perfusion (1-10 min), capillary depletion, and high pressure liquid chromatography (HPLC) were used. RESULTS: There was a saturable DA influx into the brain with a KM of 389 +/- 55 nM, and a VMAX of 1.95 +/- 0.25 pmol/min/g of brain. The diffusion constant, KD, was not significantly different from zero. About 0.5% of DA remained tightly bound to cerebral microvessels isolated from the perfused brain. DA influx into the brain was not altered by the monoamine oxidase-B (MAO-B) inhibitor pargyline (50 microM). HPLC analysis of perfused brain confirmed transport of intact DA, and no detectable increases in DA metabolites were observed. At perfusate concentrations of 500 nM, several dopaminergic receptor antagonists inhibited [3H]-DA (21 nM) influx; the percent inhibitions for the mixed D1 and D2 antagonists haloperidol and chlorpromazine, the D1 antagonist SCH-23390, and the D2 antagonist spiperone were 90%, 68%, 77%, and 50%, respectively. Brain perfusion with nicotine (500 nM) inhibited DA uptake by 86%. This nicotine effect was not altered by mecamylamine, but was partially prevented by the nicotinic receptor antagonist hexamethonium. CONCLUSIONS: (a) A significant cerebrovascular permeability to intact DA is mediated by a MAO-B independent specific transport system at the BBB, (b) this system could be inhibited by D1 and D2 DA receptor antagonists, and (c) DA blood-to-brain transport was inhibited by nicotine.

Animals↗
PubMed1996

C1-C2 fusion in children with atlantoaxial instability and spinal cord compression: technical note.

Children with atlantoaxial instability and subluxation that will not reduce with extension of the cervical spine often present with clinical and/or radiographic evidence of spinal cord compression at the C1-C2 level. If the patient requires a laminectomy at the C1 level, occipital fusion is necessitated with associated reduction in mobility and high incidence of nonunion, as compared with a C1-C2 fusion. Also, passing wires under the intact lamina at C1 can further compromise an already compressed cervical cord. To address the problems associated with either of the above options, we used a C1-C2 fusion with removal of the mid 2 cm of the lamina of C1. Another option is the application of a transarticular screw fixation of C1-C2, which does not require the posterior element of C1. The current study was performed before the introduction of this type of fixation. Over a 10-year period, we have used the described technique to treat 13 patients. After decompression and fusion at the C1 and C2 levels as described, all patients had resolution of their preoperative neurological symptoms and all have achieved a stable fusion. Partial removal of the lamina at C1 and then C1-C2 fusion are safe and effective procedures to treat children with atlantoaxial instability and spinal cord compression.

Adolescent↗
PubMed1996

Cellular uptake and transport of methylprednisolone at the blood-brain barrier.

Methylprednisolone (MP) is one of the most widely used neuroprotective drugs in neurosurgery. Our knowledge of its pharmacokinetics in the brain and, in particular, whether it can penetrate the blood-brain barrier (BBB) and act in the brain parenchyma is still limited. In this study, we used a vascular brain perfusion technique in guinea pigs, combined with a capillary depletion method, to determine brain uptake and transport of MP at the BBB. 3H-Labeled MP was delivered to the brain by carotid arterial infusions lasting from 1 to 10 minutes; the effects of plasma protein binding, different concentrations of MP, and the glucocorticoid receptor inhibitor, RU486, were examined. The existence of a transport system was inferred from the observation that the volume of distribution of MP in the brain after perfusion exceeded by 2.6 to 6.3 times the plasma volume of the cerebrovascular space marker, sucrose. The rates of undirectional [3H]MP blood-to-brain transport of 0.5 to 0.7 microliters per minute per gram indicated significant but slow transfer. MP available for BBB transport was not restricted to its free plasma fraction but, instead, included the albumin- and globulin-bound fractions. A portion of steroid remained concentrated (sequestered) by the capillary endothelium, and from there, the label was distributed into brain parenchyma. Both MP binding and transport at the BBB exhibited saturable kinetics. RU486 produced an inhibition of MP BBB transport and binding with an affinity that seemed to be 30 to 60% higher than that of the steroid itself. We concluded that MP first binds to the brain capillaries and then crosses the BBB at a low rate, most likely by using a saturable mechanism that may involve a cytoplasmic endothelial glucocorticoid receptor.

Animals↗
PubMed1996

Surgical treatment of 95 children with 102 intracranial arachnoid cysts.

Our review of 95 children with 102 intracranial arachnoid cysts treated surgically from 1976 to 1996 is presented. These patients are divided into two groups, those initially treated from 1976 to 1986 and those treated from 1987 to May 1996, to see whether any improvement in outcome had occurred. There were 31 patients (20 males/11 females) with 34 cysts treated from 1976 to 1986 and 64 patients (45 males/19 females) with 68 cysts treated from 1987 to 1996. The mean age at presentation for all cases was 4.9 years (range from 3 days to (7.8 years). The most common cyst location was the middle fossa. Treatment options for the management of intracranial arachnoid cysts include fenestration or shunting. We consider the avoidance of a shunt as a primary goal in the management of these patients. Accordingly, 82 (80%) of the cysts in our series were treated initially by fenestration. Fifty percent of those initially fenestrated from 1976 to 1986 required no further treatment as compared with 60% fenestrated from 1987 to 1996. The success rate of fenestration among those patients without associated hydrocephalus was significantly higher than in those with hydrocephalus; 73% without hydrocephalus required no additional treatment versus 32% with hydrocephalus. Seventeen percent of the patients treated from 1976 to 1986 required a subsequent ventriculoperitoneal shunt as compared with 22% treated from 1987 to 1996. Twenty-nine percent of those patients initially fenestrated from 1976 to 1986 required a subsequent cystoperitoneal shunt as compared with only 12% treated from 1987 to 1996. Although not statistically significant, the second group of patients had a lower rate of reoperation, fewer complications, and a better clinical outcome than the first group. We recommend that in patients without evidence of hydrocephalus, cyst fenestration be considered as the primary procedure, as 73% of the patients in the two series remain shunt free. In those patients with hydrocephalus, we still recommend cyst fenestration, but with a ventriculoperitoneal shunt inserted before fenestration if the hydrocephalus is marked or after fenestration if the hydrocephalus is progressive.

Adolescent↗
PubMed1996

Experience with use of extended length peritoneal shunt catheters.

The placement of a ventriculoperitoneal (VP) shunt is the current treatment of choice for diversion of cerebrospinal fluid associated with hydrocephalus. Although there are a host of reported potential abdominal complications related to the procedure, they are notably uncommon. The authors report their experience with the primary insertion of an extended length open-ended peritoneal tubing (120 cm) undertaken expressly to avoid the need for a lengthening procedure because of growth of the patient. In a review of new insertions of VP shunts using the extended length tubing over a 14-year period at Childrens Hospital of Los Angeles, a total 998 shunts were placed in 952 patients, with a mean follow-up period of 6.7 years. The patients experienced a total of 52 distal shunt revisions for a variety of malfunction etiologies. In patients ranging in age from premature neonate to 20 years, there was no increase in the distal complication rate, and specifically no complications were experienced that were directly related to the use of the extended length tubing. The authors conclude that the use of an extended length peritoneal shunt catheter is not associated with an increase in complications and eliminates the need to lengthen the peritoneal catheter for growth of the patient.

Adolescent↗
PubMed1996

Surveillance imaging in children with primitive neuroectodermal tumors.

Controversy surrounds the benefits of routine surveillance magnetic resonance or computed tomographic imaging for monitoring children after resection of primitive neuroectodermal tumors. A recent study suggested that serial imaging studies detect only a small minority of tumor recurrences in patients with symptoms. The authors concluded that even in patients with recurrence documented by imaging, no patient with a recurrence survived long (average, 5 mo) and that surveillance scanning is of little clinical value in children with primitive neuroectodermal tumors. We reviewed our experience with 25 patients (28% of our total series) who presented to the Children's Hospital Los Angeles, Los Angeles, CA, from 1985 to 1993 with recurrent tumors after surgery and adjuvant therapy. Recurrent tumors were detected on routine imaging in 19 asymptomatic patients (76%) and in 6 symptomatic patients (24%). Recurrences were documented 15 months (mean) after the initial diagnosis in asymptomatic children and 5 months (mean) after the initial diagnosis in children with symptoms of recurrent tumor (P < or = 0.01). Asymptomatic patients with recurrence documented on serial imaging had prolonged survival when compared with those who were symptomatic (P < or = 0.05). The surviving patients with recurrence remained alive for more than 24 months after documentation of recurrence. Early detection of local tumor recurrence by surveillance scanning may provide a critical therapeutic window for successful treatment with aggressive or novel therapies.

Adolescent↗
PubMed1995

Pediatric traumatic intracranial aneurysms.

During the past 17 years, 7 children have been treated at Children's Hospital Los Angeles (CHLA) for traumatic intracranial aneurysms. These patients presented with subarachnoid or intraparenchymal hemorrhage (5 cases), growing fracture (1 case), and behavioral change (1 case). All patients were managed with surgery, and no patient died or was made neurologically worse as a result of such management. The existence of a traumatic aneurysm should be considered when new neurological symptoms develop in a patient with a history of head injury.

Adolescent↗
PubMed1995

Enlarging subependymal cyst: case report.

A 1-month-old infant with a Dandy-Walker malformation underwent the placement of a ventriculoperitoneal shunt to treat progressive hydrocephalus. On the initial computed tomographic scan, a subependymal cystic lesion larger than 1 cm in diameter was noted in the head of the right caudate nucleus, which enlarged to 3 cm in diameter on follow-up imaging studies over the course of a year. Biopsies taken at the time of fenestration failed to show the presence of neoplasia. This appears to be the first reported case of a cyst of this nature to show progressive enlargement.

Biopsy↗
PubMed1994

Brain uptake of circulating apolipoproteins J and E complexed to Alzheimer's amyloid beta.

Amyloid beta (A beta) is a fibrillar component in Alzheimers' disease amyloid deposits and a soluble peptide (sA beta) normally present in body fluids. We have recently reported that the blood-brain barrier (BBB) has a capability to control cerebrovascular sequestration and transport of circulating sA beta. In this study, we examined whether two circulating amyloid-associated proteins shown to bind sA beta, apolipoproteins J (apo J) and E (apo E), can cross the BBB alone and/or complexed to a synthetic peptide homologous to a major form of sA beta, sA beta 1-40. Brain perfusion experiments in guinea pigs showed significant uptake of both apo J and sA beta 1-40-apo J complexes. In contrast, blood-brain transport of sA beta 1-40-apo E was negligible, while apo E had a limited access across the BBB, indicating that the apo E found within the brain is produced locally. It is concluded that sA beta 1-40 binding to apo J and apo E results in significant (> 100-fold) difference in brain uptake of their respective complexes. We hypothesize that in normal brain apo J facilitates sA beta transport.

Amyloid beta-Peptides↗