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Biomedical subjects

J G McComb

Publications and source records attributed to J G McComb.

At least 37 records · Page 2Linked to original sources

Does age or other factors influence the incidence of ventriculoperitoneal shunt infections?

Some studies indicate that infants, especially those less than 1 month of age have a higher incidence of ventriculoperitoneal shunt infections. To look at age as well as other variables that might relate to the rate of shunt infection, we reviewed the records of all patients undergoing a ventriculoperitoneal shunt insertion or revision at our institution from January 1, 1985, to December 31, 1994. There were a total of 2,325 ventriculoperitoneal shunting procedures performed on 1,193 patients with a male:female ratio of 678:515. The overall infection rate was 3.2% (74 infections). Analyzed by age, the infection rates were as follows: <1 month 9/223 (4.0%), 1-6 months 16/449 (3.6%), 6-12 months 13/297 (4.4%), 12-18 months 3/122 (2.5%), 18-24 months 7/116 (6.0%) and 24+ months 26/1, 118 (2.3%). There was no statistically significant difference between age groups (p > 0.05). Upon selectively examining premature neonates who developed hydrocephalus secondary to intraventricular hemorrhage from the figures given above, one finds that 2/44 (4.5%) of neonates became infected, which was also not significant. The infection rate was the same irrespective of whether the procedure was to insert or revise the shunt, or whether another operative procedure was done under the same anesthesia. The etiology of the hydrocephalus was not a factor, nor was the presence of an open neural tube defect. The presence of fluid accumulation along the shunt tract or at another neurological operative site was associated with a significant increase in incidence of infection 15/168 (8.9%) when compared to those with no fluid accumulation (p < 0.001). The type of infecting organism was divided roughly in thirds, with relatively equal representation from Staphylococcus epidermidis/coagulase negative and Staphylococcus aureus. The remaining third was comprised of a wide variety of organisms.

Adolescent↗

Histiocytosis X.

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Brain Diseases↗

Tissue plasminogen activator (tPA) deficiency exacerbates cerebrovascular fibrin deposition and brain injury in a murine stroke model: studies in tPA-deficient mice and wild-type mice on a matched genetic background.

Although the serine protease, tissue plasminogen activator (tPA), is approved by the US Food and Drug Administration for therapy to combat focal cerebral infarction, the basic concept of thrombolytic tPA therapy for stroke was challenged by recent studies that used genetically manipulated tPA-deficient (tPA-/-) mice, which suggested that tPA mediates ischemic neuronal damage. However, those studies were potentially flawed because the genotypes of tPA-/- and wild-type control mice were not entirely clear, and ischemic neuronal injury was evaluated in isolation of tPA effects on brain thrombosis. Using mice with appropriate genetic backgrounds and a middle cerebral artery occlusion stroke model with nonsiliconized thread, which does lead to microvascular thrombus formation, in the present study we determined the risk for cerebrovascular thrombosis and neuronal injury in tPA-/- and genetically matched tPA+/+ mice subjected to transient focal ischemia. Cerebrovascular fibrin deposition and the infarction volume were increased by 8.2- and 6. 7-fold in tPA-/- versus tPA+/+ mice, respectively, and these variables were correlated with reduced cerebral blood flow up to 58% (P<0.05) and impaired motor neurological score by 70% (P<0.05). Our findings indicate that tPA deficiency exacerbates ischemia-induced cerebrovascular thrombosis and that endogenous tPA protects the brain from an ischemic insult, presumably through its thrombolytic action. In addition, our study emphasizes the importance of appropriate genetic controls in murine stroke research.

Animals↗

Omental transfer to the brain: an experimental study in hydrocephalic rabbits.

Hydrocephalus is a common and potentially lethal condition in children that results from an imbalance between absorption and production of cerebral spinal fluid (CSF). Silastic shunts are inserted to drain excess CSF, but they are prone to a number of problems, and at times may be unreliable and ineffective. This study examines the physiological basis of a pedicled omental transfer to the brain as a functional conduit for CSF in an experimentally induced hydrocephalic rabbit model. The ability of the omentum to transport CSF from the subarachnoid space was tested using radioactive tracer substances: radio-iodinated serum albumin (125I-RISA), chromium 51-ethylenediaminetetraacetate (51Cr-EDTA), and technetium 99m (99mTc) glucoheptonate. Immediate ability of exteriorized omentum to transport artificial CSF, as well as transposed omental transport of subarachnoid CSF at 1 month, were examined. Nuclear scan measurements were correlated with clinical observation and a double-blind histological analysis with trichrome and hematoxylin-eosin stain. Exteriorized omentum rapidly absorbed 99mTc glucoheptonate-labeled artificial CSF, with a rapid appearance in the systemic circulatory and urinary systems. Transposed omentum to the brain in animals with artificially created hydrocephalus showed evidence of CSF-labeled 125I-RISA and 51Cr-EDTA absorption in those animals demonstrating histologically viable omentum.

Animals↗

Human blood-brain barrier receptors for Alzheimer's amyloid-beta 1- 40. Asymmetrical binding, endocytosis, and transcytosis at the apical side of brain microvascular endothelial cell monolayer.

A soluble monomeric form of Alzheimer's amyloid-beta (1-40) peptide (sAbeta1-40) is present in the circulation and could contribute to neurotoxicity if it crosses the brain capillary endothelium, which comprises the blood-brain barrier (BBB) in vivo. This study characterizes endothelial binding and transcytosis of a synthetic peptide homologous to human sAbeta1-40 using an in vitro model of human BBB. 125I-sAbeta1-40 binding to the brain microvascular endothelial cell monolayer was time dependent, polarized to the apical side, and saturable with high- and low-affinity dissociation constants of 7.8+/-1.2 and 52.8+/-6.2 nM, respectively. Binding of 125I-sAbeta1-40 was inhibited by anti-RAGE (receptor for advanced glycation end products) antibody (63%) and by acetylated low density lipoproteins (33%). Consistent with these data, transfected cultured cells overexpressing RAGE or macrophage scavenger receptor (SR), type A, displayed binding and internalization of 125I-sAbeta1-40. The internalized peptide remains intact > 94%. Transcytosis of 125I-sAbeta1-40 was time and temperature dependent, asymmetrical from the apical to basolateral side, saturable with a Michaelis constant of 45+/-9 nM, and partially sensitive to RAGE blockade (36%) but not to SR blockade. We conclude that RAGE and SR mediate binding of sAbeta1-40 at the apical side of human BBB, and that RAGE is also involved in sAbeta1-40 transcytosis.

Alzheimer Disease↗

Intravenous RMP-7 increases delivery of ganciclovir into rat brain tumors and enhances the effects of herpes simplex virus thymidine kinase gene therapy.

Herpes simplex virus thymidine kinase (HSV-tk) gene therapy for brain tumors depends on ganciclovir (GCV) and its transport across the blood-brain tumor barrier (BBTB). We examined whether RMP-7, the bradykinin analog and potent BBTB permeabilizer, could enhance the efficacy of GCV treatment of brain tumors by increasing the BBTB delivery of GCV. In vitro, a significant bystander cytocidal effect of GCV was shown in mixed HSV-tk-transduced (HSV-tk+) and control vector-transduced (HSV-tk-) C6 glioma cultures. A dose-dependent cytotoxic effect of GCV on untransformed C6 cells was also shown. In vivo, rats with 100% HSV-tk+ or 100% HSV-tk- intracerebral C6 gliomas were treated for 7 days with intravenous infusions of GCV alone or with GCV and RMP-7 (2.5 microg/kg/day). The growth of HSV-tk+ and HSV-tk- gliomas decreased with increasing doses of GCV. A high dosage (100 mg of GCV/kg/day) eradicated all HSV-tk- and HSV-tk+ tumors. An intermediate dosage (5 mg of GCV/kg/day) reduced the growth of HSV-tk- gliomas by 42% if given alone, and by 88% in combination with RMP-7. A low dosage (0.5 mg of GCV/kg/day) in combination with RMP-7 enhanced the regression of HSV-tk+ gliomas by 87% compared with GCV alone. Low-dose GCV was ineffective in HSV-tk- tumors. RMP-7 increased [3H] GCV tumoral uptake by 2.6- and 1.7-fold in the tumor center and periphery, respectively. We conclude that RMP-7 could be an important adjunctive treatment for suicide gene therapy of brain tumors, while an RMP-7/GCV combination may also have a significant antitumor effect in untransfected gliomas.

3T3 Cells↗

Stereoscopic head-mounted display incorporated into microsurgical procedures: technical note.

OBJECTIVE: We have previously evaluated video technologies that have allowed for the use of electronic imaging during microneurosurgical and endoscopic procedures. This stereoscopic camera set and monitor/recording system allows for the use of stereoscopic images during surgery by the primary surgical assistant and ancillary personnel. It also allows for stereoscopic recording and playback using a wide video home system format. We describe a novel prototype of a head-mounted display (HMD) that allows the surgical team to simultaneously visualize the surgical field stereoscopically and includes picture-in-picture, voice control, and stereoscopic recording capabilities. INSTRUMENTATION: A stereoscopic HMD with 640 x 480 (video graphics array) pixel resolution and the ability to display 24-bit images has been designed. This device weighs 900 g. It is interfaceable with common video display formats. RESULTS: This stereoscopic HMD is being evaluated in a prospective multicenter trial of open microsurgical and endoscopic minimally invasive procedures. In our experience to date, there have been no equipment failures or complications attributable to the use of the display system. The equipment was well accepted by users who reported significant benefits in visualization. CONCLUSION: The use of a stereoscopic HMD may result in improved efficiency and safety in both endoscopic and open microsurgical procedures. We have verified that the HMD is comfortable during the course of a surgical procedure, is reliable, and allows for accessibility to the operative field with an excellent field of view and three-dimensional perception. Positioning and dexterity within the operative field are also enhanced. Additional uses relate to surgical training, multimodal information display, and operative rehearsals.

Depth Perception↗

The internet as a pediatric neurosurgery information resource.

The Internet is evolving as a powerful source of medical information for patients, family members, and health care providers; however, critical analyses of this information are generally lacking. This investigation was carried out to ascertain the sources, nature, and accuracy of information acquired via searches on the Internet for ten common pediatric neurosurgical topics. Thirteen source types and nine categories of information were characterized and examined. With few notable exceptions, the educational information was highly accurate. It is concluded that the Internet represents an important new pediatric neurosurgery educational resource for the layman and health care providers. Guidelines are offered to assist in the use of this new medium.

Computer Communication Networks↗

Familial occurrence of an arteriovenous fistula with a giant perimedullary pseudoaneurysm of the thoracic spinal cord in 2 young siblings.

Two siblings, a sister at age 3 years and a brother (15 years later) at 4 years of age, both presented with similar clinical pictures consisting of back pain, progressive gait difficulty, lower extremity weakness and hyperreflexia. Imaging studies in both cases showed the presence of a perimedullary mass with expansion of the bony spinal canal at T10-T12. Angiography demonstrated almost identical vascular lesions that in each case was being fed by a single left-sided T8 fistulous vessel that expanded into a giant perimedullary venous pseudoaneurysm. Each malformation was successfully obliterated using endovascular techniques, balloon occlusion of the feeding vessel in the first case and coil embolization of the pseudoaneurysm in the second. Following treatment the neurologic deficits resolved in both patients. These young siblings represent the first known case of familial occurrence of very similar giant perimedullary venous pseudoaneurysms of the thoracic spinal cord.

Adolescent↗

A method of cranioplasty using coralline hydroxyapatite.

INTRODUCTION: Current cranioplasty materials include autologous or homologous bone grafts, wire mesh and methyl methacrylate, either alone or in combination. However, each material has its own unique disadvantages. Although hydroxyapatite has been used extensively in other specialties as a bone substitute, the coralline form has rarely been used to repair cranial bone defects. Coralline hydroxyapatite, similar to that found in bone, provides a matrix on which living tissue can form and grow. Because it is an ideal bioimplant, a method of cranioplasty using coralline hydroxyapatite was employed. METHODS: The hydroxyapatite granules are mixed with Avitene and autologous blood to form a paste which can be contoured as needed. RESULTS: Over the past few years, we have used hydroxyapatite either alone or in combination with tantalum mesh in 19 pediatric patients for a variety of conditions. The cosmetic results were good to excellent. Furthermore, postoperative CT scans have documented bony substitution of the hydroxyapatite granules. Follow-up ranged from 1 to 43 months with a mean of 26 months. CONCLUSION: In neurosurgical procedures when a bone substitute is needed, hydroxyapatite is an effective alternative to other currently available materials.

Bone Substitutes↗

Neonatal neurosurgical trauma.

Birth injury has been defined as any condition that adversely affects the fetus during labor or delivery. This article discusses neonatal injury that results in a condition that requires neurosurgical management. The majority of these conditions result from a primary mechanical injury to the central or peripheral nervous system.

Birth Injuries↗

Optimization of the operative corridor for the resection of craniopharyngiomas in children: the combined frontoorbitozygomatic temporopolar approach. Technical note.

Complete extirpation of tumor remains the primary goal of neurosurgeons in treating intracranial craniopharyngiomas. The intimate relationship of these lesions with the structures of the skull base and the difficulties of obtaining adequate operative visualization often make total removal an elusive goal. The authors describe the use of a combined fronto-orbitozygomatic temporopolar craniotomy to maximize the operative corridor and thereby increase the probability of maximum tumor resection without morbidity and mortality. They applied this approach in four children with craniopharyngiomas that involved the sellar and parasellar, third ventricle, cavernous sinus, and interpeduncular fossa regions. The surgical results are summarized with a presentation of pre- and postoperative imaging from two illustrative cases. A detailed description of the operative procedure is provided with a comparison to other previously described surgical approaches.

Journal Article↗

Differentiation between cortical atrophy and hydrocephalus using 1H MRS.

Quantitative 1H MRS to determine cerebral metabolite patterns and MRI to determine CSF flow were applied to 12 patients with ventricular dilation-Group A, cortical atrophy (N = 5); or Group B, hydrocephalus (N = 7)- and in 9 normal controls. While mean brain water (Group A = 80% +/- 6; Group B = 86% +/- 5; normal = 85% +/- 4) did not differ between the two groups of patients and controls, 1H MRS distinguished those patients with cortical atrophy (Group A) (N-acetylaspartate/ creatine (NAA/Cr) = 0.69 +/- 0.17, versus normal = 1.06 +/- 0.16; P < 0.002; [NAA] = 5.9 +/- 1.3 mmoles/kg, versus normal 8.0 +/- 1.4; P < 0.02) from those with hydrocephalus (Group B) (NAA/Cr = 1.16 +/- 0.11; [NAA] = 9.2 +/- 1.2; P > 0.13 and P > 0.07). Lactate levels were elevated in 3/5 patients with cortical atrophy, but in 0/7 of those with hydrocephalus. Mean absolute concentrations (mmoles/kg) of the five major cerebral osmolytes were 41 +/- 4 (Group A), 43 +/- 6 (Group B), and 42 +/- 4 (normal), so that despite massive brain deformation, constant osmolality was maintained. 1H MRS may directly benefit surgical planning in hydrocephalus infants by clearly identifying those with cortical atrophy who do not require CSF diversion. Thinning of the cortical mantle in hydrocephalus may result from osmotically driven reduction in individual cell volumes, (shrinkage), rather than brain-compression.

Adult↗

Spinal and cranial neural tube defects.

Developmental lesions of the central nervous system with failure of normal midline fusion are often referred to as being dysraphic and vary from inapparent and insignificant to a massive deformity incompatible with survival. Several different schemata are used to classify this wide variety and often complex set of malformations; however, the nomenclature is confusing and even contradictory. As most of these congenital lesions of clinical significance involve an aberration in the formation of the neural tube, it is suggested that the term neural tube defects (NTD) be used to characterize this entire group of anomalies. From a practical clinical standpoint, NTD can be subdivided into three main groupings: open spinal NTD, closed spinal NTD, and cranial NTD. This article briefly covers the epidemiology, embryology, classification, clinical presentation, and management of this group of congenital lesions.

Case Management↗

Isoform-specific effects of apolipoproteins E2, E3, and E4 on cerebral capillary sequestration and blood-brain barrier transport of circulating Alzheimer's amyloid beta.

Cerebral capillary sequestration and blood-brain barrier (BBB) permeability to apolipoproteins E2 (apoE2), E3 (apoE3), and E4 (apoE4) and to their complexes with sA beta(1-40), a peptide homologous to the major form of soluble Alzheimer's amyloid beta, were studied in perfused guinea pig brain. Cerebrovascular uptake of three apoE isoforms was low, their blood-to-brain transport undetectable, but uptake by the choroid plexus significant. Binding of all three isoforms to sA beta(1-40) in vitro was similar with a K(D) between 11.8 and 12.9 nM. Transport into brain parenchyma and sequestration by BBB and choroid plexus were negligible for sA beta(1-40)-apoE2 and sA beta(1-40)-apoE3, but significant for sA beta(1-40)-apoE4. After 10 min, 85% of sA beta(1-40)-apoE4 taken up at the BBB remained as intact complex, whereas free sA beta(1-40) was 51% degraded. Circulating apoE isoforms have contrasting effects on cerebral capillary uptake of and BBB permeability of sA beta. ApoE2 and apoE3 completely prevent cerebral capillary sequestration and blood-to-brain transport of sA beta(1-40). Conversely, apoE4, by entering brain microvessels and parenchyma as a stable complex with sA beta, reduces peptide degradation and may predispose to cerebrovascular and possibly enhance parenchymal amyloid formation under pathological conditions.

Amino Acid Sequence↗

Pediatric intracranial hemangioendotheliomas: case report.

OBJECTIVE AND IMPORTANCE: Intracranial hemangioendotheliomas are rare lesions, especially in the pediatric age group. Recognizing hemangioendotheliomas as a differential in intracranial tumors of vascular origin is important; complete excision results in a cure, and medical therapy for those lesions that are not resectable produces long-term survival. CLINICAL PRESENTATION: We report two patients, a 7-year-old female patient with a lesion in the right gasserian ganglion and a 3-month-old male patient with a cervicomedullary junction tumor. INTERVENTION: The 7-year-old underwent a gross total removal with no recurrence. The 3-month-old underwent a partial resection followed by treatment with interferon alpha-2a, with a decrease in the size of the residual tumor. Both patients have been followed for more than 4 years without a recurrence or progression of the tumor. CONCLUSION: Hemangioendotheliomas are fairly indolent tumors and may be treated with complete surgical resection, resulting in a cure. In cases in which complete tumor removal is not possible, adjunctive therapy with interferon alpha-2a may control residual tumor growth.

Brain Neoplasms↗

Heads-up intraoperative endoscopic imaging: a prospective evaluation of techniques and limitations.

OBJECTIVE: Endoscopes have been used adjunctively for spinal and cranial microsurgical procedures and directly for ventricular exploration, fenestration, and catheterization. Technological advances now allow for multi-imaging technologies, including a so-called "heads-up display," allowing the surgeon to view the operative field and the endoscopic image simultaneously. INSTRUMENTATION: A high-resolution, active matrix liquid crystal display is built into the frame of the eyewear, with a display density of 182,000 pixels (280 x 650 pixels) and a resolution of 200 lines. The display occupies approximately 20% of the visual field. The headgear weighs 4 oz, with dimensions of 9 x 18 x 17 cm. The modular interface weighs 7 oz. Two different visualization systems can be used. The first uses a single integrated interface (IM 300), whereas the second (remote 900) is a 900-MHz frequency modulation wireless system that provides for a line-of-sight link between the NTSC source and the modular interface (range = 100 ft). RESULTS: Heads-up adjunctive endoscopy was used in 60 patients during 18 months. The procedures included 16 craniotomies, 1 intradural lumbar biopsy, and 42 ventriculoperitoneal shunt placements. Follow-up was obtained at a minimum of 1 year. Patient age ranged from 1 month to 58 years. The only complication was a transient loss of auditory evoked potentials after contact of the eighth nerve by the endoscope. CONCLUSION: We describe a portable, light-weight heads-up display imaging system, which we have used in 60 operative procedures. Benefits of the heads-up system include portability and a high-resolution digital monocular image, which reduces eye strain and vertigo. The ideal headgear will likely be an extremely high-resolution liquid crystal display-based or cathode ray tube-based semi-immersive system, with all of the benefits currently described for two-dimensional heads-up systems (i.e., light weight, portability, image quality, and the avoidance of complications associated with immersive systems).

Adolescent↗

Outcome, cost analysis, and long-term follow-up in preterm infants with massive grade IV germinal matrix hemorrhage and progressive hydrocephalus.

OBJECTIVE: The benefit of aggressive management and surgical intervention in preterm infants with massive Grade IV intracranial hemorrhage has been questioned based on the poor outcome of this group of patients despite such therapy. To further delineate this problem, we reviewed the records of premature neonates in this category as to outcome and initial hospital cost. METHODS: We performed a retrospective review of the medical records at our institution from 1977 to 1987 to identify premature neonates who had sustained massive hemorrhagic infarction of one hemisphere in addition to having blood in both ventricles and progressive hydrocephalus. RESULTS: During the study, a total of 52 such patients were identified, only 19 (6 female and 13 male patients) of whom survived. Intellectual function was observed to be greater than 2 standard deviations below the mean in 15 of the 19 patients, between 1 and 2 standard deviations below the mean in 1 of 19, and 1 standard deviation below the mean in 3 of 19. Motor function was as follows: 12 of 19 had marked spastic quadriparesis, 2 of 19 had moderate spastic quadriparesis, 3 of 19 had spastic hemiplegia, 1 of 19 had spastic diplegia, and 1 of 19 had mild spastic hemiparesis. Eleven of 19 had chronic seizure disorders. The first hospitalization cost for the group of patients exceeded, on the average, $150,000 per patient for the 19 long-term survivors. CONCLUSION: As we have previously reported, logistic regression analysis determined that grade of hemorrhage was the only significant predictor of cognitive and motor outcomes. Most premature neonates with massive intracranial hemorrhages do not survive. The outcomes in those who do is very poor and the cost so high that we suggest that until therapeutic intervention exhibits efficacy, the consideration of withdrawal of life support should be presented as an option to the parents of these unfortunate children.

Brain Damage, Chronic↗