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Biomedical subjects

G B Young

Publications and source records attributed to G B Young.

At least 19 recordsLinked to original sources

Declaring pediatric brain death: current practice in a Canadian pediatric critical care unit.

OBJECTIVE: To document the criteria used to declare brain death in a pediatric critical care unit (PCCU). DESIGN: Retrospective chart review. SETTING: Regional PCCU in southwestern Ontario. PATIENTS: Sixty patients 16 years of age or less declared brain dead from January 1987 through December 1992. OUTCOME MEASURES: Presence or absence of documentation of irreversible deep coma, nonresponsive cranial nerves, absent brain-stem reflexes, persistent apnea after removal from ventilator, presence or absence of blood flow detected by radioisotope scanning, presence or absence of electroencephalographic evidence of electrocerebral activity. RESULTS: The 60 patients accounted for 1.5% of all PCCU admissions; 17 were under 1 year of age. In 39 cases brain death was diagnosed using clinical criteria ("certified brain death"), which could not be fully applied in the remaining 21 cases ("uncertifiable but suspected brain death"). Electroencephalography and cerebral blood-flow studies with technetium-99m hexamethyl-propyleneamine oxime were used as ancillary tests in 16 patients with certified brain death and in 17 with uncertifiable but suspected brain death who survived long enough to be tested. Electrocerebral silence was demonstrated in all nine patients who underwent electroencephalography. Cerebral blood flow was undetectable in 26 of the 30 patients tested, and an abnormal pattern of blood flow was seen in the remaining 4, all of whom received a diagnosis of certified brain death. CONCLUSIONS: Pediatricians in this large tertiary care referral centre are using clinical criteria based on the 1987 guidelines of the CMA to diagnose brain death in pediatric patients, including neonates. When clinical criteria cannot be fully applied, ancillary methods of investigation are consistently used. Although the soundness of this pattern of practice is established for adults and older children, its applicability to neonates and infants still needs to be validated.

Adolescent

Mesial temporal lobe seizures presenting as anxiety disorders.

Five patients had brief simple partial seizures that mimicked panic disorder. The following features assisted diagnosis: Seizures were briefer and more stereotyped than panic attacks; some progressed to typical complex partial seizures; and aphasia and dysmnesia occurred during seizures in some patients. Each patient had one mesial temporal structural lesion. Routine waking EEG was normal in 2 patients. Inadequate response to anti-epileptics necessitated partial temporal lobectomy in 4 patients, 3 of whom remain seizure free.

Adult

Neurologic complications of systemic critical illness.

Neurologic complications of systemic illnesses may affect any part of the nervous system in various conditions. In many systemic disorders, however, an acute confusional state is the first manifestation. It is urgent to make a definitive diagnosis and begin specific and supportive therapy to lessen mortality and morbidity. A case of severe septic illness with central and peripheral nervous system complications is reviewed. Septic encephalopathy and critical illness polyneuropathy are common conditions in the general ICU. The neuropathy often is the underlying cause for failure to wean from the ventilator.

Acute Disease

Alpha, theta and alpha-theta coma: a clinical outcome study utilizing serial recordings.

Alpha coma (AC), theta coma (TC) and alpha-theta coma (ATC) are transient clinical-electroencephalographic phenomena which do not differ from each other in etiology or outcome and are indicative of a severe disturbance in thalamo-cortical physiology. Although most patients do poorly, these patterns are not reliably predictive of outcome, regardless of etiology. We found that AC, TC or ATC usually change to a more definitive pattern by 5 days from coma onset. EEG reactivity in subsequent patterns is relatively favorable, while a burst-suppression pattern without reactivity is unfavorable in anoxic-ischemic encephalopathy.

Alpha Rhythm

Ataxia in institutionalized patients with epilepsy.

Fifty-four per cent of 41 chronically institutionalized adult patients with epilepsy had ataxia of gait (wide mean stride width). None of the following correlated with stride width: serum phenytoin, previous phenytoin toxicity, seizure frequency, or status epilepticus. Seventeen of the 41 patients had computed tomographic head scans. Patients with radiological evidence of cerebellar atrophy had a wider mean stride width, later age of onset of seizures, greater peak serum concentrations of phenytoin than did those without cerebellar atrophy. Ataxia of gait was inconsistently associated with cerebellar atrophy. Elevated serum/plasma concentrations of phenytoin may be a risk factor for cerebellar atrophy, but seizure frequency or status epilepticus are not independently related to this complication.

Adult

Initial enlargement of the opposite pupil as a false localising sign in intraparenchymal frontal haemorrhage.

Ipsilateral third nerve palsy with early pupillary enlargement is an important sign of transtentorial herniation from a supratentorial mass lesion. A case of frontal, intraparenchymal haemorrhage is reported in which the first ocular manifestation of transtentorial herniation was enlargement of the contralateral pupil. The ipsilateral pupil dilated only after complete oculomotor palsy of the contralateral eye. After partial frontal lobectomy and removal of blood clot, the ipsilateral third nerve recovered before the contralateral third nerve. Clinical findings localised the contralateral third nerve lesion to an extra-axial site. The possible mechanisms of contralateral third nerve compression are discussed. This seems to be the first example of pupillary enlargement as a false localising sign from a contralateral, supratentorial, intraparenchymal mass lesion.

Adult

Lack of water transport by amino acid side chains or peptides entering a nonpolar environment.

Water has been reported to enter cyclohexane in association with 3-methylindole, a model compound representing the side chain of tryptophan. Entrainment of water would cloud the interpretation of measured partition coefficients as a simple index of hydrophobicity. NMR and isotope-exchange experiments indicate that the reported entrainment of water resulted from unrecognized exchange of 3H from water into the -NH- group of the indole ring. A more detailed analysis shows that no significant amounts of excess water (less than 0.1 molecule/molecule of solute) enter cyclohexane with molecules representing the side chains of tryptophan, phenylalanine, threonine, lysine, or the peptide bond itself.

Amino Acids

The neurological complications of sepsis.

Encephalopathy and polyneuropathy occur in 70% of septic patients. The encephalopathy is diffuse, appears early, is often severe, but reverses quickly with successful treatment of the sepsis. The electroencephalogram is a sensitive indicator of the incidence and severity of the encephalopathy, but computed tomograms of the brain and cerebrospinal fluid findings are unremarkable. Critical-illness polyneuropathy develops later and in association with multiple-organ failure. Recovery is more gradual. Difficulty in weaning from the ventilator is an important early manifestation. Electromyography should be routinely performed to establish the diagnosis. The polyneuropathy is a primary axonal degeneration, predominantly of distal motor fibers. A persistent deficit may eventuate in severe cases. Whether muscle is affected as consistently as brain and peripheral nerve, and by the same process, has not been determined. Medications used in critical care units, notably sedatives and neuromuscular blocking agents, often confuse the clinical picture. The neurological pathophysiology is unknown but current evidence suggests that nervous system dysfunction arises through the same mechanisms as for systemic organs in the septic syndrome.

Brain Diseases

Amide proton exchange rates of oxidized and reduced Saccharomyces cerevisiae iso-1-cytochrome c.

Proton NMR spectroscopy was used to determine the rate constant, kobs, for exchange of labile protons in both oxidized (Fe(III)) and reduced (Fe(II)) iso-1-cytochrome c. We find that slowly exchanging backbone amide protons tend to lack solvent-accessible surface area, possess backbone hydrogen bonds, and are present in regions of regular secondary structure as well as in omega-loops. Furthermore, there is no correlation between kobs and the distance from a backbone amide nitrogen to the nearest solvent-accessible atom. These observations are consistent with the local unfolding model. Comparisons of the free energy change for denaturation, delta Gd, at 298 K to the free energy change for local unfolding, delta Gop, at 298 K for the oxidized protein suggest that certain conformations possessing higher free energy than the denatured state are detected at equilibrium. Reduction of the protein results in a general increase in delta Gop. Comparisons of delta Gd to delta Gop for the reduced protein show that the most open states of the reduced protein possess more structure than its chemically denatured form. This persistent structure in high-energy conformations of the reduced form appears to involve the axially coordinated heme.

Amides

Probing weakly polar interactions in cytochrome c.

Theoretical, statistical, and model studies suggest that proteins are stabilized by weakly polar attractions between sulfur atoms and properly oriented aromatic rings. The two sulfur-containing amino acids, methionine and cysteine, occur frequently among functional alleles in random mutant libraries of Saccharomyces cerevisiae iso-1-cytochrome c genes at positions that form a weakly polar aromatic-aromatic interaction, the wild-type protein. To determine if a weakly polar sulfur-aromatic interaction replaced the aromatic-aromatic interaction, the structure and stability of two variants were examined. Phenylalanine 10, which interacts with tyrosine 97, was replaced by methionine and cysteine. The cysteine was modified to form the methionine and cysteine analog, S-methyl cysteine (CysSMe). Proton NMR studies indicate that changing Phe 10 to Met or CysSMe affects only local structure and that the structures of sulfur-containing variants are nearly identical. Analysis of chemical shifts and nuclear Overhauser effect data indicates that both sulfur-containing side chains are in position to form a weakly polar interaction with Tyr 97. The F10M and F10CSMe variants are 2-3 kcal mol-1 less stable than iso-1-cytochrome c at 300 K. Comparison of the stabilities of the F10M and F10CSMe variants allows evaluation of the potential weakly polar interaction between the additional sulfur atom of F10CSMe and the aromatic moiety of Tyr 97. The F10CSMe;C102T variant is 0.7 +/- 0.3 kcal mol-1 more stable than the F10M;C102T protein. The increased stability is explained by the difference in hydrophobicity of the sulfur-containing side chains. We conclude that any weakly polar interaction between the additional sulfur and the aromatic ring is too weak to detect or is masked by destabilizing contributions to the free energy of denaturation.

Cysteine

Seizures involving secondary sensory and related areas.

Five patients with seizures involving the secondary sensory and/or related areas (SSRA) are presented. Four of five experienced ictal numbness and/or tingling bilaterally and/or axially; this involved fingertips (three patients), lips (two), tongue (two), and was diffuse in one. The fifth patient experienced bilateral ictal pain. Associated ictal symptoms implicating adjacent regions appeared in all five patients, including contralateral clonic movements (two patients), hypersalivation (two), taste (one), vocalization (two), dysphagia (one), and contralateral sensory march (one). Two patients had ictal symptoms suggestive of adjacent temporal lobe involvement. By history, the SSRA was involved at seizure onset in four and by spread in one. All five patients had electroencephalogram (EEG) or subdural EEG supportive evidence of SSRA involvement: ictal (three) and interictal (three). Three patients had lesions in this area shown by magnetic resonance imaging or computerized tomography and all three had histologically proven glial tumours. Relevant experimental physiological and anatomical data are reviewed.

Adult

The electroencephalogram in sepsis-associated encephalopathy.

To define the EEG and associated clinical features of septic encephalopathy, we studied 62 patients with positive blood cultures. Patients were divided into three clinical groups: nonencephalopathic (NE), mildly encephalopathic (ME), and severely encephalopathic (SE); the latter two groups had diffuse cerebral dysfunction. EEGs were classified into five groups: normal, excessive theta, predominant delta, triphasic waves, and suppression or burst suppression, in ascending order of severity. The EEG (1) was more sensitive than our clinical criteria for encephalopathy, (2) showed features that were, when considered with clinical and laboratory characteristics, compatible with a potentially reversible encephalopathy, and (3) had well-defined categories that correlated with percent mortality, even within a single clinical group. We conclude that the EEG is a sensitive index of brain function in septic encephalopathy and that it is especially useful in the intensive care monitoring of patients with sepsis.

Adult