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Biomedical subjects

R S Bourke

Publications and source records attributed to R S Bourke.

At least 37 records · Page 2Linked to original sources
PubMed1978

Assessment of recovery from serious head injury.

A procedure for serial assessment of neuropsychological recovery after serious head injury was designed. The assessment procedure consists of four segments, each appropriate for different phases of the recovery process. Recovery can be traced from early in the period of post-traumatic amnesia until it reaches an asymptote. The course of recovery of several patients has been observed. The procedure is shown to be practical and appears to be valid. The recovery process is compared to ontogenesis, and is shown to be generally similar though differing in important particulars.

Brain Injuries↗
PubMed1978

Numerical grading of clinical neurological status after serious head injury.

A scheme to quantitate the clinical neurological status of the seriously head-injured patient has been devised. The neurological parameters used to quantify the degree of injury are based on neurological functions which have previously been accepted as indicators of the severity of the head injury. A numerical value is assigned to each parameter with emphasis on defining the level of consciousness. The accrued point total of each examination represents the neurological status of the patient at that time. Mean values and standard error from the means are determined from repeated examinations during a single 24 hour period, and are plotted against days after injury. From this graph a line which represents the rate of clinical recovery is determined by least squares analysis. General intensive care nurses were trained to score patients independently; their determinations were found to be in statistical agreement with scores derived from examinations by the attending physicians. The data presented highlight the effects of hypoxaemia in impeding the rate of neurological recovery from a serious head injury. This simple clinical analytical scheme for the quantitative assessment of patients with head injury permits evaluation of the efficacy of various modes of therapy in altering the rate of recovery.

Adult↗
PubMed1978

Camurati-Engelmann disease (progressive hereditary craniodiaphyseal dysplasia). Case report.

In a patient with Camurati-Engelmann disease, orbital and optic nerve decompression resulted in improvement of papilledema. Subsequent x-ray films of the optic canals, however, revealed reconstitution of osseous optic canals bilaterally, and papilledema has returned in one eye. Definitive treatment of this dysplastic metabolic bone disorder rests in the control of rapid abnormal bone formation.

Bone Diseases, Developmental↗
PubMed1978

Direct administration of methotrexate into the central nervous system of primates. Part 1: Distribution and degradation of methotrexate in nervous and systemic tissue after intraventricular injection.

Levels of methotrexate (MTX) measured by both 3H radioactivity and dihydrofolate reductase assays were determined in cerebrospinal fluid (CSF), plasma, urine, and both neural and non-neural tissues at varying times after a single intraventricular injection into Cynomolgus monkeys (Macaca fascicularis). Clearance of the MTX from CSF was rapid after injection. A relatively constant level of 3HMTX was reached in plasma 2 1/2 hours after injection, and about 30% of the 3HMTX dose was excreted in the urine within 4 hours after injection. Maximum levels in CNS tissues were obtained by 4 hours after injection, and average concentrations of 10(-6) M MTX (moles/kg wet weight) were maintained in CSF for up to 12 hours and in brain for up to 24 hours after injection. Conversion of MTX to non-MTX products was detected in CSF between 4 and 12 hours, and in brain tissue between 12 and 24 hours after injection, and the amount of these products increased with time. Regional distribution studies in the cerebrum showed a U-shaped distribution curve for 3HMTX up to 12 hours after injection, which closely followed the 14C inulin distribution. Thus, the levels in deep cerebral tissue were less than the average level for brain, and this suggests that treatment of CNS tumors by intraventricular injection may have variable results, partly due to complex tissue distribution patterns.

Animals↗
PubMed1978

Direct administration of methotrexate into the central nervous system of primates. Part 2: Distribution of 3H methotrexate after intrathecal lumbar injection.

The kinetics of distribution of 3H methotrexate (3HMTX) in the central nervous system, plasma, and urine after intraventricular, lumbar percutaneous puncture, and spinal catheter injections were compared. Levels of 3HMTX in whole brain after lumbar percutaneous injection were 40 times less than after intraventricular injection. Injection of 3HMTX via a spinal catheter increased the level of 3HMTX in whole brain but this was still tenfold less than after direct intraventricular instillation. Also, it was found that a disproportionately high amount of 3HMTX was in the brain-stem-cerebellum region which would further reduce the concentration of methotrexate in the cerebral hemispheres. Both intraventricular and lumbar spinal catheter administration of 3HMTX produced 3HMTX levels greater than 10(-6)M (moles/kg wet weight) in spinal cord tissue as measured by 3H specific activity between 2 to 8 hours after injection. Administration by lumbar percutaneous puncture, however, rarely resulted in this suggested therapeutic level of 10(-6)M. Initial 3HMTX levels in plasma after lumbar percutaneous instillation was 24 times greater than after intraventricular or lumbar spinal catheter injections. This indicated significant and unavoidable extradural leakage after lumbar percutaneous puncture, which may account for the substantially lower levels of 3HMTX in the brain and spinal cord tissue. It is concluded that intraventricular instillation of methotrexate is the best route of administering the drug to achieve therapeutic levels of methotrexate in both whole brain and throughout the spinal cord.

Animals↗
PubMed1978

Evaluation of experimental spinal cord injury by measuring spontaneous spinal cord potentials.

The relationship between the spontaneous spinal electrogram and the degree of spinal cord injury was studied in anesthetic-free, surgically decerebrate cats that received experimental blunt trauma by the graded weight-drop method. It was found that the characteristic spontaneous slow negative potential of the spinal electrogram showed a frequency dependency that correlated positively with the intensity of the injury (impulse expressed in gm-sec). Graphs of the frequency of occurrence of the slow negative potentials as a function of time following initial injury indicated that both the slope and shape of the curve were dependent on the severity of the injury measured in gm-sec at the time of the injury and confirmed histologically. These results indicate that the spontaneous spinal electrogram may serve as a sensitive indicator of the degree of spinal cord injury and may be useful in the assessment of various treatment modalities.

Animals↗
PubMed1978

Delayed impairment of arterial blood oxygenation in patients with severe head injury: preliminary report.

A drop in the arterial PO2 occurring 24 hours after head injury was identified in eight patients. Traditional modes of therapy include administration of supplemental oxygen and provision of an unobstructed airway. The latter proved to be inadequate to continually maintain the PaO2 at a level consistent with the O2 content of the inspired air. Initially, determination of the PaO2, after institution of supplemental oxygen, may demonstrate adequate oxygenation, but blood gas monitoring should be continued since a delayed fall in arterial oxygen tension may occur 24 hours after head injury. This period of potentially deficient blood oxygenation, if severe enough, may further aggravate preexisting brain damage and profoundly affect the ultimate outcome of the patient. The delayed fall in PaO2 is the result of intrapulmonary shunting principally due to a ventilation/perfusion mismatch. The precise mechanism of the ventilation/perfusion inequality in the brain-injured patient awaits further elucidation, but may differ from the alteration in pulmonary function seen in the Respiratory Distress Syndrome.

Brain Edema↗
PubMed1977

Distribution and degradation of [3H]methotrexate after intravenous and cerebral intraventricular injection in primates.

Four hr after either a single injection or continuous infusion of methotrexate (MTX) plus purified [3',5',9(n)-3H]MTX in cynomolgus or rhesus monkeys, 80 to 98% of the 3H radioactivity present in the plasma was found not to represent intact MTX. The percentage of 3H-containing MTX products in the urine after 4 hr was considerably less, although more variable. This variability seemed to be related to variability in the amount of the total dose excreted. Non-MTX products were also found in selected tissues and the percentage of intact MTX found 4 hr after i.v. injection varied from 2 to 26%. The percentage of intact MTX was routinely measured by comparing the values obtained using the dihydrofolate reductase assay with values based on the specific activity of [3',5',9(n)-3H]MTX. Results obtained by diethylaminoethyl column chromatography on a few samples, however, showed good agreement with results from the reductase assay. [3',5',9(n)-3H]MTX products appeared in peaks eluting from the diethylaminoethyl column both earlier and later than the MTX peak, with the earlier peaks being present in only small amounts in the urine. After continuous i.v. infusion, only 2% or less of the radioactivity found in the cerebrospinal fluid after 4 hr represented intact MTX, with the remaining radioactivity eluting much earlier than MTX. In contrast, after direct injection into the left lateral ventricel, all the 3H radioactivity in both cerebrospinal fluid and brain tissue represented intact MTX for up to 4 hr after injection. The appearance of MTX products in the plasma and selected tissues of these primates a short time after i.v. injection is compared to other work in experimental animals and man and suggests a greater metabolism of MTX than was previously suspected.

Animals↗
PubMed1976

The effects of temperature and inhibitors on HCO3-stimulated swelling and ion uptake of monkey cerebral cortex.

In the presence of high concentrations of K+, additions of HCO3- as low as 0.35 mM caused a 23% increase in swelling, and concomitant increases in the chloride content of incubating monkey cerebrocortical slices. The uptake of chloride was accompanied by increased uptake of sodium and was highly temperature dependent, showing a marked activation at approximately 30 degrees C. A similar temperature activation was also found for a Mg2+-dependent, HCO3-stimulated ATPase activity in monkey cerebral cortex, consistent with a possible role for this enzyme in the K+ and HCO3-dependent swelling process and its associated ion movements. K+-dependent, HCO3-stimulated cerebrocortical tissue swelling with uptake of Na+ and Cl- was inhibited by acetazolamide indicating that carbonic anhydrase was also involved. The addition of ouabain also inhibited swelling and K+ and Cl- uptake at low concentrations, but led to increased swelling at higher concentrations ( greater than 10 mum). A similar biphasic effect on swelling was also seen following addition of ethacrynic acid.

Acetazolamide↗
PubMed1976

The effect of entrapment in liposomes on the in vivo distribution of [3H]methotrexate in a primate.

Entrapment of methotrexate (MTX) plus [3',5', 9(n)-3H]methotrexate into positively charged liposomes greatly alters the subsequent distribution of [3H]MTX in a cynomologous monkey (Macaca irus) after a single i.v. injection ([3H]MTX; refers to total radioactivity derived from purified [3H]MTX). When [3H]MTX is incorporated into small, sonically disrupted liposomes, the level of the entrapped [3H]MTX in the total plasma volume was still 50% of the total injected dose after 4 hr, which is 100 times greater than the level found when the same amount of free MTX (1 to 4 mg) plus [3H]MTX was injected. When entrapped in larger mechanicanically disperesed liposomes, however, the plasma levels of liposome-entrapped [3H]MTX at 4 hr was only 6-fold greater than free [3H]MT. The liposome-entrapped MTX (refers to MTX measured by dihydrofolate reductase assay) did not show detectable breakdown in the plasma whereas free MTX showed up to 97% breakdown. Increased clearance of [3H]MTX entrapped in mechanically dispersed liposomes was complemented by its much greater uptake into tissues, especially spleen, compared with sonically disrupted liposomes. There was over a 160-fold increased uptake by the spleen of liposome-entrapped [3H] MTX relative to free [3H]MTX, whereas for sonically disrupted liposomes the comparable ratio was 20. Although this liposome-entrapped MTX showed significant breakdown, it was less than that found after injection of free MTX. In certain tissues, especially the small intestine, a reduced uptake of liposome-entrapped [3H]MTX WAS FOUND. Uptake of liposome-entrapped [3H]MTX into liposomes led to a much lower renal clearance of [3H]MTX, especially in the case of sonically disrupted liposomes. Possible reasons for these effects and the relationship of our findings to those of others are discussed.

Animals↗
PubMed1975

Inhibition of renal tubular transport of methotrexate by probenecid.

The mechanism of excretion of methotrexate (MTX) has been investigated in the monkey. Under steady-state conditions of varied plasma levels of MTX, it was determined that MTX was excreted by renal tubular transport as well as by glomerular filtration. The maximum rate of renal tubular transport of MTX (81 mug/min) was attained at plasma levels of MTX from 6 to 8 mug/ml. Correspondingly, the rate of clearance of MTX from plasma was shown to diminish from a value that was 3-fold greater than the glomerular filtration rate at plasma levels of MTX from 6 to 32 mug/ml. Pretreatment of animals with probenecid (700 mg/sq m) totally inhibited renal tubular transport of MTX when MTX was administered in doses from 1.8 to 621 mg/sq m. Following inhibition of renal tubular transport of MTX by probenecid, steady-state plasma levels of MTX in animals pretreated with probenecid (700 mg/sq m) was reduced by a factor of 2.6 from values determined in non-probenecid-pretreated control animals receiving similar varied doses of MTX (1.8 P to greater than 600 mg/sq m). The mode of i.v. injection of MTX was seen to effect the concentration of MTX in plasma. Initial loading followed by continuous sustaining infusion of MTX provided stable and higher levels of MTX in plasma than was determined in controls or in experimental animals pretreated with probenecid and receiving identical doses of MTX by single bolus injection.

Aminohippuric Acids↗