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Biomedical subjects

R K Narayan

Publications and source records attributed to R K Narayan.

70 records · Page 4Linked to original sources

Lysis of intracranial hematomas with urokinase in a rabbit model.

Urokinase (UK), a potent thrombolytic agent, was tested in a rabbit model for safety and efficacy in lysing intracranial hematomas. Intracerebral-intraventricular (IC-IV) hematomas were created by stereotaxically injecting 0.2 ml of clotted human blood into the frontal lobe and lateral ventricle of a total of 57 anesthetized adult New Zealand White rabbits (weighing 1.6 to 2.5 kg). Control animals received 0.2 ml of normal saline injected into the clot, and the experimental group received an equal volume of UK solution (50,000 units/ml) immediately after the clot injection. Some animals were sacrificed at 3 hours and others at 24 hours postinjection. At 3 hours, clot lysis had been achieved in nine (90%) of 10 UK-treated animals as compared to one (14%) of seven controls. By 24 hours, clots had been lysed in 10 (83%) of 12 UK-treated animals and in two (33%) of six controls. Overall, clot lysis was demonstrated in 19 (86%) of the 22 UK-treated animals and in only three (23%) of the 13 controls (p less than 0.001). There was no significant difference in results between these animals and a further set of 22 rabbits that were treated with UK or saline 24 hours after clot injection. There was no histological evidence of damage or inflammation noted on careful light microscopic examination of three to five sections from each brain, although findings consistent with encephalitozoonosis, an incidental protozoan infestation, were encountered in four animals. These studies suggest that UK may be safely and effectively employed for the lysis of intracranial hematomas in this animal model, and that a delay in therapy of up to 24 hours does not significantly compromise its efficacy.

Animals↗

Ventriculostomy-related infections. A prospective epidemiologic study.

We concluded a prospective epidemiologic study of ventriculostomy-related infections (ventriculitis or meningitis) in 172 consecutive neurosurgical patients over a two-year period to determine the incidence, risk factors, and clinical characteristics of the infections. Ventriculitis or meningitis developed in 19 of 172 patients (11 per cent) undergoing a total of 213 ventriculostomies. When data from all these cases plus five cases of nonventriculostomy-related infection were combined, cerebrospinal-fluid pleocytosis was more significantly associated with the diagnosis of ventriculitis or meningitis (P less than 0.0001) than were fever and leukocytosis (P = 0.07). Risk factors for ventriculostomy-related infections included intracerebral hemorrhage with intraventricular hemorrhage (P = 0.027), neurosurgical operations (P = 0.016), intracranial pressure of 20 mm Hg or more (P = 0.019), ventricular catheterization for more than five days (P = 0.017), and irrigation of the system (P = 0.021). Previous ventriculostomy did not increase the risk of infection with subsequent procedures. We conclude that ventriculostomy-related infections may be prevented by maintenance of a closed drainage system and by early removal of the ventricular catheter. If monitoring is required for more than five days, the catheter should be removed and inserted at a different site.

Bacteria↗

Proteins in normal, irradiated, and postmortem human brain quantitatively compared by using two-dimensional gel electrophoresis.

Using a combination of two-dimensional gel electrophoresis (2DE), silver staining, and computerized densitometry, we studied protein patterns in human cerebral cortex: normal fresh-frozen, fresh-frozen but previously irradiated, and post-mortem. The relative molecular mass of the resolved proteins ranged from 14 400 to 100 000, the isoelectric points from 4.75 to 7.0. The pattern of proteins (six of them identified) was essentially the same for all three groups. However, computerized densitometry demonstrated significant alterations in the density of several spots in the irradiated and postmortem groups as compared with the normal controls. Irradiated cortex showed statistically significant changes in only six spots (three increased and three decreased in density); postmortem material showed 20 altered spots (16 diminished and four increased). Evidently normal human cerebral cortex has a consistent protein pattern on 2DE, which is quantitatively (but not qualitatively) altered in irradiated and postmortem material. These findings provide a point of reference against which proteins from abnormal brain material can be compared, both qualitatively and quantitatively.

Cerebral Cortex↗

GC/MS analysis of prostaglandins in ventricular cerebrospinal fluid from head injured humans.

The purpose of this study was to determine the levels of prostaglandins in ventricular cerebrospinal fluid (CSF) from severely head injured humans on successive days following injury. Sixteen samples from three patients were purified using XAD-2 and high pressure liquid chromatography and PGE2, PGF2alpha, and 6-keto-PGF1alpha were quantitated utilizing deuterated internal standards and gas chromatography-mass spectrometry. Generally, the levels of PGs in ventricular CSF were found to be higher than has previously been reported for PGs in CSF from spinal taps. PG levels ranged from reported for PGs in CSF from spinal taps. PG levels ranged from nondetectable to 11.8, 3.3 and 27.3 ng per ml for PGE2, PGF2alpha, and 6-keto-PGF2alpha, respectively. However, in one sample, PG levels were much higher than this range and approached the levels found in human cortical tissue. Analysis of red and white blood cell numbers in the CSF showed no relationship between cell numbers and prostaglandin levels. This study confirms a previous report that 6-keto-PGF2alpha is the major prostaglandin in CSF and demonstrates that PG levels in ventricular CSF from head traumatized humans can be greatly elevated.

6-Ketoprostaglandin F1 alpha↗

Primary dural melanoma: a clinical and morphological study.

This study reviews the literature pertaining to primary meningeal melanoma and reports the clinical and ultrastructural findings in a case where the tumor appeared to be of pachymeningeal (dural) origin. This is clearly a departure from all previously described cases, in which a leptomeningeal (pial-arachnoidal) origin was either defined or assumed. Clinically, this case was remarkable in its rarity, its presentation as a cerebellopontine angle syndrome, and its occurrence in a Negro, a race in which melanomas are uncommon. Ultrastructurally, the tumor did demonstrate the presence of basement membrane abnormalities and numerous endothelial fenestrations. However, it was found to be made up of a homogenous cell population, consisting only of electron-lucent, melanin-laden cells. The mixed cell population noted previously in a primary leptomeningeal melanoma was not found in this tumor. In view of the fact that this patient continues to do well 1 1/2 years after operation, with no evidence of tumor recurrence, it is suggested that a homogenous cell population noted on electron microscopy could indicate a better prognosis. In addition, it may also indicate a pachymeningeal rather than a leptomeningeal origin for the tumor. A plea is made for greater specificity in terminology when describing primary meningeal melanomas and for a concerted effort to distinguish between those of dural and those of leptomeningeal origin.

Adult↗

Significance of CT in head injury: correlation with intracranial pressure.

The authors correlated the computed tomographic (CT) findings and intracranial pressure (ICP) in 150 consecutive comatose head injury patients to determine if noninvasive CT can help identify the patients not requiring ICP monitoring. The study reveals that a majority of patients (55%) with hemorrhagic lesions shown by CT suffer from intracranial hypertension and require ICP monitoring for proper management. Of the patients with normal initial CT, 98% had normal ICP during the first 24 hr. Of the patients with normal CT, 15% developed intracranial hypertension later, irrespective of the initial Glasgow coma scale score or age. More than half of the patients who developed intracranial hypertension subsequently had normal ICP through the first 48 hr. The study indicates that ICP monitoring need not routinely be performed on admission on severe head injury patients with a normal CT. However, repeat CT at 24--48 hr before ICP monitoring in patients with initially normal CT may be valuable, particularly if their clinical status deteriorates.

Adolescent↗

Improved confidence of outcome prediction in severe head injury. A comparative analysis of the clinical examination, multimodality evoked potentials, CT scanning, and intracranial pressure.

An analysis of clinical signs, singly or in combination, multimodality evoked potentials (MEP's), computerized tomography scans, and intracranial pressure (ICP) data was undertaken prospectively in 133 severely head-injured patients to ascertain the accuracy, reliability, and relative value of these indicants individually, or in various combinations, in predicting one of two categories of outcome. Erroneous predictions, either falsely optimistic (FO) or falsely pessimistic (FP), were analyzed to gain pathophysiological insights into the disease process. Falsely optimistic predictions occurred because of unpredictable complications, whereas FP predictions were due to intrinsic weakness of the indicants as prognosticators. A combination of clinical data, including age, Glasgow Coma Scale (GCS) score, pupillary response, presence of surgical mass lesions, extraocular motility, and motor posturing predicted outcome with 82% accuracy, 43% with over 90% confidence. Nine percent of predictions were FO and 9% FP. The GCS score alone was accurate in 80% of predictions, but at a lower level of confidence (25% at the over-90% level), with 7% FO and 13% FP. Computerized tomography and ICP data in isolation proved to be poor prognostic indicants. When combined individually with clinical data, however, they increased the number of predictions made with over 90% confidence to 52% and 55%, respectively. Data from MEP's represented the most accurate single prognostic indicant, with 91% correct predictions, 25% at the over-90% confidence level. There were no FP errors associated with this indicant. Supplementation of the clinical examination with MEP data yielded optimal prognostic power, an 89% accuracy rate, with 64% over the 90% confidence level and only 4% FP errors. The clinical examination remains the strongest basis for prognosticating outcome in severe head injury, but additional studies enhance the reliability of such predictions.

Adult↗

Prognostic implications of early multimodality evoked potentials in severely head-injured patients. A prospective study.

Results of multimodality evoked potential (MEP) studies recorded from 100 comatose patients soon after severe head injury were analyzed prospectively, using a previously established grading system, to assess the prognostic value of MEP's with respect to patient outcome, to evaluate the effect of clinically relevant sequelae of head injury on the prediction of outcome by MEP's and to describe time to clinical recovery as a function of initial MEP grade. Graded MEP's when recorded in the first few days after head injury, could predict patient outcome at 1 year with approximately 80% accuracy. Exclusion from the analysis of patients who died from causes unrelated to the brain and those with severe systemic complications that occurred after the evoked potentials were recorded improved the accuracy of outcome prediction to nearly 100%. The presence of a mass lesion requiring surgery reduces the probability if good to moderate outcome for a given MEP grade by approximately 25% to 40% from the seen in patients without mass lesions. The clinical outcome predicted shortly after head injury by MEP grades may not be realized for many months. Patients with mild MEP abnormality (Grade I or II) generally reach their outcome by 3 to 6 months, whereas those with more severe deficits (Grade III) may not show improvement for at least 1 year.

Adolescent↗

Constraints upon the composition of supplementary DNA.

Speciation in eukaryotes is often accompanied by massive changes in nuclear DNA amount resulting from the accumulation or deletion of DNA base sequences within chromosomes. Our evidence shows that, among related species, the DNA lost or gained during divergence is of a remarkably consistent and restricted composition in respect of the ratio of repetitive to non-repetitive base sequences. It is argued that the restriction may in part at least be imposed by natural selection, in the sense that the only changes tolerable are confined to DNA fractions of particular composition and organisation.

Amphibians↗

A technique for C-banding chromosomes with pinacyanol chloride.

A technique is presented for rapid C-banding of eukaryotic chromosomes with pinacyanol chloride. This technique has given excellent definition and clarity to chromosome bands in plant and animal chromosomes. In permanent mounts the chromosomes did not fade after storage for up to two years.

Carbocyanines↗

The immunosuppressive effect of concanavalin A in monkeys.

These studies were performed to evaluate the immunosuppressive effect of concanavalin A (ConA) in monkeys. Bonnet monkeys (Macaca radiata) weighing between 2.5-3.5 kg were used. Following the exchange of full thickness skin allografts in randomly selected animals, gross and histopathological studies of the rejection reaction were performed. Gross observations showed the allograft reaction in control animals to be a well defined phenomenon occurring at 9.0 +/- 0.7 days. In contrast the rejection process in animals that received i.v. ConA was a poorly defined prolonged process occurring at 14.8 +/- 3.9 days (single 75-mg dose of ConA), and 19.0 +/- 2.2 days (75 mg 1 day before and 25 mg 3 days after grafting). In monkeys that received the double dose schedule of ConA, histopathological studies showed distinct retardation of the rejection reaction with reduced lymphocytic infiltration of the graft-host junction. Control grafts showed almost complete rejection in 7-9 days while allografts on ConA-treated animals showed corresponding degrees of destruction only by the 15th day. These studies indicate that ConA does have an immunosuppressive effect in vivo in monkeys. The local and systemic toxic effects of ConA encountered in these animals have been reported and its haematological effects in vivo briefly described.

Animals↗

Symptomatic choroid plexus xanthogranuloma of the lateral ventricle. Case report and brief critical review of xanthogranulomatous lesions of the brain.

Xanthogranulomas of the choroid plexus are found relatively frequently at autopsy; however only 8 cases of symptomatic choroid plexus xanthogranuloma of the lateral ventricle have been reported. We describe an additional case in a 63-year-old man who presented with headache. A well circumscribed mass located in the trigone of the right lateral ventricle and extending into the periventricular white matter was detected on imaging studies. The clinical impression was metastasis. The resected material had the typical histological appearance of a xanthogranuloma of the choroid plexus. The clinical and histopathologic features of these lesions are reviewed and other xanthogranulomatous processes involving the brain are briefly discussed.

Calcinosis↗

Human glioma associated intermediate filament proteins: over-expression, co-localization and cross-reactivity.

The identification of human brain tumor-associated markers could facilitate the development of new diagnostic and therapeutic strategies for these malignancies. The type III intermediate filament proteins (IFPs): vimentin, desmin and glial fibrillary acidic protein (GFAP) were studied in human glioma tissue extracts, in sera from glioma patients and in low passage glioma cell lines prepared from primary cultures of freshly dissected tumors. Radioimmunoassay (RIA) studies, using anti-GFAP, anti-desmin and anti-vimentin mAbs, showed high levels of these proteins in glioma extracts. Binding studies with authentic IFPs indicated the absence of circulating antibodies against these proteins in the sera of glioma patients. On the other hand, these sera showed high levels of vimentin. Binding studies with these antibodies using RIAs and western immunoblotting, showed that while anti-GFAF mAbs were specific to GFAP, anti-desmin mAb cross-reacted completely with GFAP, anti-vimentin mAb cross-reacted substantially with desmin and GFAP. Immunofluorescence staining of frozen sections revealed high levels of neurofilaments in gliomas and strikingly low levels in normal brain tissue. Double immunofluorescence staining showed co-occurrence of all three IFPs in the same filaments. This suggests either co-expression or cross-reactivity of these proteins due to their high degree of homology. Thus, caution should be exercised in the use and interpretation of immunohistochemical data using antibodies to IFs.

Antibodies, Monoclonal↗