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Biomedical subjects

R K Narayan

Publications and source records attributed to R K Narayan.

At least 37 records · Page 2Linked to original sources

Jugular venous desaturation and outcome after head injury.

Early experience with continuous monitoring of jugular venous oxygen saturation (SjvO2) suggested that this technology might allow early identification of global cerebral ischaemia in patients with severe head injury. The purpose of the present study was to examine the relationship between episodes of jugular venous desaturation and neurological outcome. One hundred and sixteen severely head-injured patients had continuous monitoring of SjvO2 during days 1-5 after injury. Episodes of jugular venous desaturation (SjvO2 < 50% for more than 10 minutes) were prospectively identified, and the incidence of desaturation was correlated with neurological outcome: 77 episodes of desaturation occurred in 46 of the 116 patients; 27 had one episode and 19 had multiple episodes of desaturation. The causes of these episodes were systemic (n = 36), cerebral (n = 35), or both (n = 6). Most of the episodes were less than 1 hour in duration, and it is probable that many of them would not have been detected without continuous measurement of SjvO2. Episodes of desaturation were most common on day 1 after injury, and were twice as common in patients with a reduced cerebral blood flow as in patients with a normal or elevated cerebral blood flow. The occurrence of jugular venous desaturation was strongly associated with a poor neurological outcome. The percentage of patients with a poor neurological outcome was 90% with multiple episodes of desaturation and 74% in patients with one desaturation, compared to 55% in patients with no episodes of desaturation. When adjusted for all co-variates that were found to be significant, including age, Glasgow coma score, papillary reactivity, type of injury, lowest recorded cerebral perfusion pressure, and highest recorded temperature, the incidence of desaturation remained significantly associated with a poor outcome. Although a cause and effect relationship with outcome cannot be established in this study, the data suggest that monitoring SvO2 might allow early identification and therefore treatment of many types of secondary injury to the brain.

Adolescent↗

Evaluation of a microsensor intracranial pressure transducer.

This report describes the results of a laboratory evaluation of a new device for monitoring intracranial pressure (ICP), consisting of a miniature pressure transducer mounted on a pressure sensing diaphragm. In in vitro tests, 6 microsensor transducers were monitored for drift at pressures of 10 mmHg and 20 mmHg. The maximal drift of any of the transducers was 1 mmHg over 9 days. In in vivo tests, the ICP measurement obtained with the microsensor transducer correlated well with pressures recorded from a catheter in the cisternal magna with a Statham transducer over a wide range of ICP values (n = 511, r = 0.998, P < 0.001). If these laboratory findings can be duplicated in clinical studies, this microsensor transducer may be a useful alternative to the ventriculostomy catheter and other currently used devices for monitoring ICP.

Animals↗

The relationship between hormonal mediators and systemic hypermetabolism after severe head injury.

The relationships of hormonal mediators to the systemic hypermetabolism and catabolism of head injury were studied in 15 patients with severe head injuries. Resting energy expenditure (REE), urinary nitrogen balance, and plasma glucose concentration were measured daily for the first 2 weeks after injury as the major indicators of hypermetabolism. These dependent variables were correlated with daily measurements of urinary epinephrine, norepinephrine, metanephrine, normetanephrine, dopamine, and cortisol, and with plasma levels of insulin, glucagon, and C-reactive protein. Urinary catecholamine and cortisol excretion were markedly elevated in these patients throughout the 2 weeks of study. Catecholamine excretion peaked between days 7 and 10, whereas cortisol excretion tended to be highest on day 5 after injury. Urinary levels of norepinephrine, normetanephrine, and cortisol were highest in the two patients with Glasgow Coma Scale scores of 4. Plasma insulin and glucagon concentrations were elevated on day 1 after injury and tended to increase throughout the 2-week period of study. The variables significantly associated with REE were the severity of injury, reflected by the GCS score, the urinary excretion of norepinephrine during the first 2 days after injury, and the urinary excretion of epinephrine and norepinephrine during days 3 to 7 after injury. A negative nitrogen balance was associated with the urinary excretion of epinephrine and norepinephrine, with caloric balance, and with plasma C-reactive protein during days 1 and 2 after injury. During days 3 to 7, a negative nitrogen balance was associated with the urinary excretion of epinephrine and norepinephrine and with caloric balance, and during days 8 to 14, a negative nitrogen balance was associated primarily with urinary cortisol excretion.

Adult↗

Cerebral blood flow, arteriovenous oxygen difference, and outcome in head injured patients.

Cerebral blood flow (CBF) and other physiological variables were measured repeatedly for up to 10 days after severe head injury in 102 patients, and CBF levels were related to outcome. Twenty five of the patients had a reduced CBF [mean (SD) 0.29 (0.05) ml/g/min]; 47 had a normal CBF, (0.41 (0.10) ml/g/min); and 30 had a raised CBF (0.62 (0.14) ml/g/min). Cerebral arteriovenous oxygen differences were inversely related to CBF and averaged 2.1 (0.7) mumol/ml in the group with reduced CBF, 1.9 (0.5) mumol/ml in the group with normal CBF, and 1.6 (0.4) mumol/ml in the group with raised CBF. Patients with a reduced CBF had a poorer outcome than patients with a normal or raised CBF. Mortality was highest in patients with a reduced CBF, and was 32% at three months after injury, whereas only 21% of the patients with a normal CBF and 20% of the patients with a raised CBF died. There were no differences in the type of injury, initial score on the Glasgow Coma Scale, mean intracranial pressure (ICP), highest ICP, or the amount of medical treatment required to keep the ICP less than 20 mm Hg in each group. Systemic factors did not significantly contribute to the differences in CBF among the three groups. A logistic regression model of the effect of CBF on neurological outcome was developed. When adjusted for variables which were found to be significant confounders, including age, initial Glasgow Coma Score, haemoglobin concentration, cerebral perfusion pressure and cerebral metabolic rate of oxygen, a reduced CBF remained significantly associated with an unfavourable neurological outcome.

Adult↗

Intraoperative endomyelography during syrinx drainage: technical note.

There is no currently available noninvasive technique to ascertain with certainty the continuity of the cavity of a septated syrinx. A technique is described that allows the confirmation of the continuity before the surgical drainage of a syrinx. This technique may prevent the failure of the drainage because of septations and double cavities. Intraoperative endomyelography is simple to perform and requires no special equipment. Pressure measurements made before the injection of the contrast agent may provide insights into the pathogenesis of the syrinx and may be of prognostic and therapeutic significance.

Adult↗

Effect of head elevation on intracranial pressure, cerebral perfusion pressure, and cerebral blood flow in head-injured patients.

The traditional practice of elevating the head in order to lower intracranial pressure (ICP) in head-injured patients has been challenged in recent years. Some investigators argue that patients with intracranial hypertension should be placed in a horizontal position, the rationale being that this will increase the cerebral perfusion pressure (CPP) and thereby improve cerebral blood flow (CBF). However, ICP is generally significantly higher when the patient is in the horizontal position. This study was undertaken to clarify the issue of optimal head position in the care of head-injured patients. The effect of 0 degree and 30 degrees head elevation on ICP, CPP, CBF, mean carotid pressure, and other cerebral and systemic physiological parameters was studied in 22 head-injured patients. The mean carotid pressure was significantly lower when the patient's head was elevated at 30 degrees than at 0 degrees (84.3 +/- 14.5 mm Hg vs. 89.5 +/- 14.6 mm Hg), as was the mean ICP (14.1 +/- 6.7 mm Hg vs. 19.7 +/- 8.3 mm Hg). There was no statistically significant change in CPP, CBF, cerebral metabolic rate of oxygen, arteriovenous difference of lactate, or cerebrovascular resistance associated with the change in head position. The data indicate that head elevation to 30 degrees significantly reduced ICP in the majority of the 22 patients without reducing CPP or CBF.

Adult↗

Continuous monitoring of jugular venous oxygen saturation in head-injured patients.

The continuous measurement of jugular venous oxygen saturation (SjvO2) with a fiberoptic catheter is evaluated as a method of detecting cerebral ischemia after head injury. Forty-five patients admitted to the hospital in coma after severe head injury had continuous and simultaneous monitoring of SjvO2, intracranial pressure, arterial oxygen saturation, and end-tidal CO2. Cerebral blood flow, cerebral metabolic rates of oxygen and lactate, arterial and jugular venous blood gas levels, and hemoglobin concentration were measured every 8 hours for 1 to 11 days. Whenever SjvO2 dropped to less than 50%, a standardized protocol was followed to confirm the validity of the desaturation and to establish its cause. Correlation of SjvO2 values obtained by catheter and with direct measurement of O2 saturation by a co-oximeter on venous blood withdrawn through the catheter was excellent after in vivo calibration when there was adequate light intensity at the catheter tip (176 measurements: r = 0.87, p less than 0.01). A total of 60 episodes of jugular venous oxygen desaturation occurred in 45 patients. In 20 patients the desaturation value was confirmed by the co-oximeter. There were 33 episodes of desaturation in these 20 patients, due to the following causes: intracranial hypertension in 12 episodes, hypocarbia in 10, arterial hypoxia in six, combinations of the above in three, systemic hypotension in one, and cerebral vasospasm in one. The incidence of jugular venous oxygen desaturations found in this study suggests that continuous monitoring of SjvO2 may be of clinical value in patients with head injury.

Adult↗

Cerebral blood flow, AVDO2, and neurologic outcome in head-injured patients.

A reduced cerebral blood flow (CBF) and a widened arteriovenous oxygen difference (AVDO2) almost always have been associated with a poor neurologic outcome. The literature on this relationship is reviewed. A logistic regression analysis model of the effect of CBF on neurologic outcome was developed, which was adjusted for various confounding factors. CBF remained significantly associated with neurologic outcome-despite these adjustments.

Adult↗

Evaluation of the Leeds prognostic score for severe head injury.

According to the Leeds scale for identifying severely head injured patients, death can be predicted with certainty within 12 hours of admission if a patient has a score higher than 13. The withdrawal of treatment from such patients has considerable moral and legal implications. Therefore, to test the reliability of the Leeds scale, it was applied to two patient populations with severe head injuries (479 retrospectively, 131 prospectively). In both groups the scale failed to predict mortality with 100% accuracy: in the first group, 16 of 23 (69.6%) of the patients with a score of more than 13 (and therefore predicted to die) died, and 380 (83.3%) of 456 patients with scores of 13 or less survived; the data for the second group are 6/10 (60%) and 98/121 (81%), respectively. The findings suggest that the Leeds prediction model is not infallible and should be applied cautiously when making decisions about the early termination of care in severely head injured patients.

Adolescent↗

Paucity of humoral response in patients to glioma-associated antigen(s): antigen localization by immunofluorescence.

Xenogeneic immunization of freshly-prepared human glioma extracts into goats has yielded a polyclonal antiserum, which after multiple absorptions specifically identifies antigenic entities only in glioma extracts, and not in appropriate controls, both by radioimmunoassays (RIAs) and Western immunoblots. The results from the absorbed polyclonal antiserum have been confirmed by the successful generation of six stable murine monoclonal antibodies (MAbs) which recognize a subset of the same antigens with high specificity on immunoblots and with no apparent cross-reactivities by RIA to normal brain, serum, liver, muscle, kidney, spleen, or melanoma tissues. Moreover, the tested murine MAbs (B12C4) reveal a striking and abundant glial filament protein, possibly related to glial fibrillary acidic protein (GFAP) or other intermediate filament proteins, by frozen-section immunofluorescence. This is seen only in gliomas and is absent, or dramatically reduced, in normal human cortex. Use of potent immortalizing strain (FF41) of Epstein-Barr virus (EBV) to establish antibody-secreting human lymphoblastoid lines, and the generation of mouse-human chimeric fusions, have yielded lines possessing variable supernatant human antibody secretion. Radioimmunoassays using culture supernatants, and sera from glioma patients and an normal individual, have demonstrated surprisingly similar reactivity profiles, even after a sensitive sandwich RIA employing the B6C6 murine MAb. These results suggest that, although human glioma-associated antigens, including possibly the up-regulation of GFAP expression, clearly exist, there seems to be a muted humoral response as evidenced by a paucity of tumor-specific B-cells. This may be due to antigenic shielding by the blood-brain barrier, or due to a form of immunological compromise in patients harboring these malignancies.

Antibodies, Neoplasm↗

Preparation and characterization of antisera and of murine monoclonal antibodies to human glioma-associated antigen(s).

Human glioma-associated markers can be exploited for the development of new diagnostic strategies and treatment modalities for these malignancies. A goat antiserum was first raised against human anaplastic astrocytoma (AC or AA) and glioblastoma multiforme (GB or GBM) extracts. Extensive sequential absorptions with normal brain tissue, normal serum, and human serum albumin (HSA) gave an antibody fraction specific for glioma. Balb/c mice were subsequently immunized with these glioma extracts. B-cell hybridomas from these mice were then cloned and subcloned by limiting dilution, yielding six monoclonal antibodies (MAbs) that were entirely specific for tumor tissues, and did not react with normal human serum or with normal human brain, liver, kidney, spleen, or muscle. Moreover, the murine MAbs did not cross-react with certain other human tumors, including melanoma. The fully absorbed antiserum and the murine MAbs both identify a polypeptide pattern possibly related to human glial fibrillary acidic protein (GFAP) or other intermediate filament proteins on immunoblots. These immunological reagents could serve as powerful tools for the diagnosis and possibly therapy of these uniformly fatal tumors.

Animals↗

Epidemiological characteristics of subarachnoid hemorrhage in an urban population.

Several risk factors for unfavorable outcome from subarachnoid hemorrhage (SAH) have been identified. The prevalence of such risk factors varies among ethnic groups and among men and women. The influence of ethnic background and gender as factors in the outcome after SAH has not been adequately studied and is the focus of the present investigation. Outcome in 145 consecutive patients was dichotomized as good and moderately disabled vs severely disabled, vegetative, and dead. A multiple logistic regression model was used to examine the factors of gender, ethnic group (white and non-white), age, admission neurological grade, pre-existing hypertension, and intravenous drug abuse. Our data reveal that hypertensive, white males, with a history of intravenous drug abuse, have a high risk of unfavorable outcome following SAH. These observations are important for the design and interpretation of future studies relating to SAH.

Adolescent↗

Continuous infusion of intrathecal baclofen: long-term effects on spasticity in spinal cord injury.

The effects of intrathecal baclofen infusion were studied in 9 spinal cord injury patients whose spasticity had been refractory to oral medications. In a two stage, placebo controlled trial, baclofen was administered into the lumbar intrathecal space and subsequent clinical and neurophysiologic changes were assessed. In stage 1, 9 patients underwent a 5 day percutaneous infusion of baclofen and placebo via an external pump. Ashworth and reflex scores were assessed at time of enrollment, after infusion of that amount of baclofen which provided optimal spasticity control and after intrathecal infusion of placebo. The mean Ashworth grade decreased from 3.78 +/- 1.34 to 1.16 +/- 0.48 (p less than 0.001) while mean reflex score decreased from 3.57 +/- 1.05 to 0.64 +/- 0.87 (p less than 0.001). These values differed significantly from those associated with placebo therapy (Ashworth grade--2.54 +/- 1.04, p less than 0.001; reflex score--2.56 +/- 1.04, p less than 0.01). Objective improvements in functional abilities and independence were noted in 8 patients, while somatosensory and brainstem auditory evoked potentials were unchanged in all patients. Urodynamic evaluation revealed increased bladder capacity in 3 patients, while in 4 no change was observed. In Stage 2, permanent programmable infusion pumps were implanted in 7 patients who demonstrated a good response during Stage 1. In this group, mean Ashworth score decreased from 3.79 +/- 0.69 to 2 +/- 0.96 (p less than 0.001) and mean reflex score decreased from 3.85 +/- 0.62 to 2.18 +/- 0.43 (p less than 0.001). Baclofen dosage increased from 182 +/- 135 to 528 +/- 266 mcg/day over the 3-22 month follow-up period. Most of the dosage increase occurred within the initial 12 months following infusion pump implantation and tended to plateau thereafter. Minor complications such as catheter dislodgement/kinking and nausea occurred infrequently while no device related infections were observed. There was no clinical evidence of any significant baclofen neurotoxicity either in Stage 1 or 2. The only ambulatory patient developed marked lower extremity weakness during Stage 1 intrathecal baclofen infusion and was temporarily unable to walk. We conclude that continuous administration of intrathecal baclofen is an effective and safe modality for spasticity control in patients who are refractory to oral medications.

Administration, Cutaneous↗

Shielding of the spinal cord by cervical and facial structures in penetrating trauma.

Penetrating trauma to the cervical spine can result in major neurological deficits due to spinal cord damage. Discussed are four civilian cases of dramatic penetrating cervical injuries without spinal cord involvement. These injuries occurred in the anteroposterior direction, and the facial structures and/or vertebral bodies appeared to have provided some protection to the spinal cord. It is proposed that the cervical spinal cord may be less vulnerable to penetrating injuries in the anteroposterior plane due to incrementally collapsible compartments of facial soft tissue and bony sinus structures which can absorb kinetic energy and dissipate momentum.

Adult↗

Intrathecal baclofen for intractable axial dystonia.

Following spinal instrumentation for scoliosis, a patient developed intractable axial dystonia refractory to conservative medical management. We describe the successful treatment of this dystonia with a continuous infusion of intrathecal baclofen and the subsequent long-term management.

Adolescent↗