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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
PubMed2001

Cervical flexion myelopathy after valproic acid overdose.

STUDY DESIGN: Case report and literature review of cervical flexion myelopathies. OBJECTIVE: To increase awareness that prolonged extreme neck flexion, in association with profound muscular relaxation, can produce a severe cervical myelopathy. SUMMARY OF BACKGROUND DATA: Similar case reports of cervical myelopathies have been documented in the neurosurgical literature after intraoperative prolonged neck flexion, and after forcible prolonged neck flexion during a robbery. To the authors' best knowledge, this is the first report of a cervical flexion myelopathy after a medication overdose, and the only clinical-pathologic correlation. METHODS: Retrospective case report with clinical, radiographic, and postmortem data available for analysis. RESULTS: A transverse myelopathy at the sixth cervical level developed in a 25-year-old woman after an overdose of valproic acid in a suicide attempt. She was found in the sitting position, with her neck in extreme flexion, where she had been for an estimated 18 hours. Magnetic resonance imaging showed that her cervical cord was enlarged, maximally at C6, with prominent paraspinal soft tissue swelling. The patient died of pulmonary embolism and pneumonia. Pathologic findings included transverse spinal cord necrosis at C6; central gray matter necrosis extended to several segments below this. CONCLUSION: Prolonged extreme neck flexion, in association with profound muscular relaxation, can produce a severe myelopathy that is at least partly related to compromise of the spinal cord's microcirculation.

Adult↗
PubMed2001

Improved outcomes in stroke thrombolysis with pre-specified imaging criteria.

BACKGROUND: A 1995 National Institute of Neurological Disorders (NINDS) study found benefit for intravenous tissue plasminogen activator (tPA) in acute ischemic stroke (AIS). The symptomatic intracranial hemorrhage (SICH) rate in the NINDS study was 6.4%, which may be deterring some physicians from using this medication. METHODS: Starting December 1, 1998, patients with AIS in London, Ontario were treated according to NINDS criteria with one major exception; those with approximately greater than one-third involvement of the idealized middle cerebral artery (MCA) territory on neuroimaging were excluded from treatment. The method used to estimate involvement of one-third MCA territory involvement bears the acronym ICE and had a median kappa value of 0.80 among five physicians. Outcomes were compared to the NINDS study. RESULTS: Between December 1, 1998 and February 1, 2000, 30 patients were treated. Compared to the NINDS study, more London patients were treated after 90 minutes (p<0.00001) and tended to be older. No SICH was observed. Compared to the treated arm of the NINDS trial, fewer London patients were dead or severely disabled at three months (p=0.04). Compared to the placebo arm of the trial, more patients made a partial recovery at 24 hours (p=0.02), more had normal outcomes (p=0.03) and fewer were dead or severely disabled at three months (p=0.004). CONCLUSIONS: The results of the NINDS study were closely replicated and, in some instances, improved upon in this small series of Canadian patients, despite older are and later treatment. These findings suggest that imaging exclusion criteria may optimize the benefits of tPA.

Acute Disease↗
PubMed2001

Continuous EEG monitoring in a patient with massive carbamazepine overdose.

The authors report a woman who took a massive overdose (OD) of carbamazepine (CBZ). On admission she was unconscious with absent brainstem reflexes and multifocal stimulus-sensitive myoclonus. Continuous EEG recordings showed a burst-suppression pattern with bursts containing only generalized spikes accompanying myoclonic activity. Myoclonus and EEG bursts were both spontaneous and stimulus induced. With treatment, the serum CBZ concentration declined, and the EEG became more continuous and rhythmic without epileptiform discharges. Unfortunately, the patient died from adult respiratory distress syndrome. Autopsy revealed that cortical and subcortical structures were normal without neuronal necrosis or eosinophilia. Massive CBZ OD may produce a reversible encephalopathy that includes cortical hyperexcitability, a profound burst-suppression EEG pattern, and cranial nerve areflexia. Continuous EEG monitoring is helpful in managing seizures that occur as a complication of CBZ OD, after the course of recovery or worsening, and in providing assistance with prognosis.

Adult↗
PubMed2001

Solvent-induced collapse of alpha-synuclein and acid-denatured cytochrome c.

The effects of solution conditions on protein collapse were studied by measuring the hydrodynamic radii of two unfolded proteins, alpha-synuclein and acid-denatured ferricytochrome c, in dilute solution and in 1 M glucose. The radius of alpha-synuclein in dilute solution is less than that predicted for a highly denatured state, and adding 1 M glucose causes further collapse. Circular dichroic data show that alpha-synuclein lacks organized structure in both dilute solution and 1 M glucose. On the other hand, the radius of acid-denatured cytochrome c in dilute solution is consistent with that of a highly denatured state, and 1 M glucose induces collapse to the size and structure of native cytochrome c. Taken together, these data show that alpha-synuclein, a natively unfolded protein, is collapsed even in dilute solution, but lacks structure.

Circular Dichroism↗
PubMed2000

Effects of morphine on the electroencephalograms of neonates: a prospective, observational study.

OBJECTIVES: Although opiates have been reported to profoundly alter the EEG and cause seizures in full-term and premature newborn babies, no prospective study has systematically studied the effects of morphine on the EEG of normal neonates. METHODS: A prospective observational study was conducted on 20 neurologically and metabolically normal newborn babies of > or =26 weeks post-conceptional age, with EEG recordings performed while on and off morphine infusions. RESULTS: The recordings performed while the babies were on morphine were all abnormal; the principal abnormalities consisted of prolonged periods of electrical quiescence (PPEQs) and excessive interictal epileptiform activity. After the morphine was discontinued, the PPEQs resolved and the EEG background rhythms were normal for age, but 5 continued to have excessive sharp transients. All babies did well clinically and did not require anti-epileptic drug therapy. CONCLUSIONS: Morphine produces a profound, largely reversible alteration of all neonatal EEGs at various post-conceptional ages. The study has implications for caution in formulating conclusions regarding the clinical significance of EEGs of critically ill neonates on morphine infusions.

Brain↗
PubMed2000

Ethics in the intensive care unit with emphasis on medical futility in comatose survivors of cardiac arrest.

Medical futility refers to situations or cases in which treatment offers no meaningful benefit to the patient. Brain death does not pose a management problem because patients are considered to be dead. Management of other cases requires sequential considerations. First, the prognosis must be established with certainty. Then, if it is determined that there is no possibility of the patient regaining conscious awareness, a level of care should be decided through discussions involving the physician and significant others. Usually there is a consensus that high-level intensive care is not justified to maintain such a low quality of life. When the patient's advance directives or the substitute decision maker's request differs from the physician's recommendations, there are methods of resolving the issues that respect ethical and legal principles.

Attitude to Health↗
PubMed2000

The EEG in coma.

The EEG allows insight into thalamocortical function in comatose patients when this is inaccessible clinically. A single EEG can help with broad diagnostic categorization whereas continuous or serial EEG provides monitoring for unstable and potentially treatable conditions and for monitoring the effects of therapy. The EEG plays a supplemental role in establishing the prognosis in disease states that are capable of causing neuronal death. The most prevalent and problematic of these conditions involves survivors of cardiac arrest who are initially in coma with intact brainstem reflexes. In such patients single EEGs are of 100% specificity for no possibility of recovery of consciousness only for essentially complete generalized suppression (<10 microV) after the first day of the arrest. Several other generalized patterns, including less marked suppression, burst-suppression, epileptiform activity, periodic complexes, and alpha-theta coma patterns, usually but not invariably indicate a poor outcome. Serial EEGs, continuous raw and automated "trending," testing of reactivity, and the inclusion of multiple variables hold promise for an improved role in the prognostic determination in these patients.

Brain Diseases, Metabolic↗
PubMed2000

Sleep in critically ill patients requiring mechanical ventilation.

STUDY OBJECTIVES: To objectively measure sleep in critically ill patients requiring mechanical ventilation and to define selection criteria for future studies of sleep continuity in this population. DESIGN: Prospective cohort analysis. SETTING: University teaching hospital medical-surgical ICU. PATIENTS: Twenty critically ill (APACHE II [acute physiology and chronic health evaluation II] acute physiology score [APS], 10 +/- 5), mechanically ventilated adults (male 12, female 8, age 62 +/- 15 years) with mild to moderate acute lung injury (lung injury score, 1.8 +/- 0.9) 10 +/- 7 days after admission to the ICU. MEASUREMENTS AND RESULTS: Patients were divided into three groups based on 24-h polysomnography (PSG) findings. No patient demonstrated normal sleep. In the "disrupted sleep" group (n = 8), electrophysiologic sleep was identified and was distributed throughout the day (6:00 AM to 10:00 PM; 4.0 +/- 2.9 h) and night (10:00 PM to 6:00 AM; 3.0 +/- 1.9 h) with equivalent proportions of non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. Nocturnal sleep efficiency was severely reduced (38 +/- 24%) with an increased proportion of stage 1 NREM sleep (40 +/- 28% total sleep time [TST]) and a reduced proportion of REM sleep (10 +/- 14% TST). Severe sleep fragmentation was reflected by a high frequency of arousals (20 +/- 17/h) and awakenings (22 +/- 25/h). Electrophysiologic sleep was not identifiable in the PSG recordings of the remaining patients. These were classified either as "atypical sleep" (n = 5), characterized by transitions from stage 1 NREM to slow wave sleep with a virtual absence of stage 2 NREM and reduced stage REM sleep, or "coma" (n = 7), characterized by > 50% delta or theta EEG activity with (n = 5) and without (n = 2) evidence of EEG activation either spontaneously or in response to deep painful stimuli. The combined atypical sleep and coma groups had a higher APS (13 +/- 4 vs 6 +/- 4) and higher doses of sedative medications than the disrupted sleep group. CONCLUSION: Sleep, as it is conventionally measured, was identified only in a subgroup of critically ill patients requiring mechanical ventilation and was severely disrupted. We have proposed specific criteria to select patients for future studies to evaluate potential causes of sleep disruption in this population.

Adult↗
PubMed1999

Phylogenetic characterization of novel transport protein families revealed by genome analyses.

As a result of recent genome sequencing projects as well as detailed biochemical, molecular genetic and physiological experimentation on representative transport proteins, we have come to realize that all organisms possess an extensive but limited array of transport protein types that allow the uptake of nutrients and excretion of toxic substances. These proteins fall into phylogenetic families that presumably reflect their evolutionary histories. Some of these families are restricted to a single phylogenetic group of organisms and may have arisen recently in evolutionary time while others are found ubiquitously and may be ancient. In this study we conduct systematic phylogenetic analyses of 26 families of transport systems that either had not been characterized previously or were in need of updating. Among the families analyzed are some that are bacterial-specific, others that are eukaryotic-specific, and others that are ubiquitous. They can function by either a channel-type or a carrier-type mechanism, and in the latter case, they are frequently energized by coupling solute transport to the flux of an ion down its electrochemical gradient. We tabulate the currently sequenced members of the 26 families analyzed, describe the properties of these families, and present partial multiple alignments, signature sequences and phylogenetic trees for them all.

Amino Acid Sequence↗
PubMed1999

The amino acid/auxin:proton symport permease family.

Amino acids and their derivatives are transported into and out of cells by a variety of permease types which comprise several distinct protein families. We here present a systematic analysis of a group of homologous transport proteins which together comprise the eukaryotic-specific amino acid/auxin permease (AAAP) family (TC #2. 18). In characterizing this family, we have (1) identified all sequenced members of the family, (2) aligned their sequences, (3) identified regions of striking conservation, (4) derived a family-specific signature sequence, and (5) proposed a topological model that appears to be applicable to all members of the family. We have also constructed AAAP family phylogenetic trees and dendrograms using six different programs that allow us to trace the evolutionary history of the family, estimate the relatedness of proteins from dissimilar organismal phyla, and evaluate the reliability of the different programs available for phylogenetic studies. The TREE and neighbor-joining programs gave fully consistent results while CLUSTAL W gave similar but non-identical results. Other programs gave less consistent results. The phylogenetic analyses reveal (1) that many plant AAAP family proteins arose recently by multiple gene duplication events that occurred within a single organism, (2) that some plant members of the family with strikingly different specificities diverged early in evolutionary history, and (3) that AAAP family proteins from fungi and animals diverged from the plant proteins long ago, possibly when animals, plants and fungi diverged from each other. The Neurospora protein nevertheless exhibits overlapping specificity with those found in plants. Preliminary evidence is presented suggesting that proteins of the AAAP family are distantly related to proteins of the large ubiquitous amino acid/polyamine/choline family (TC #2.3) as well as to those of two small bacterial amino acid transporter families, the ArAAP family (TC #2.42) and the STP family (TC #2.43).

Amino Acid Sequence↗
PubMed1999

EEG in epilepsy: current perspectives.

The electroencephalogram (EEG) plays an important diagnostic role in epilepsy and provides supporting evidence of a seizure disorder as well as assisting with classification of seizures and epilepsy syndromes. Emerging evidence suggests that the EEG may also provide useful prognostic information regarding seizure recurrence after a single unprovoked attack and following antiepileptic drug withdrawal. Continuous EEG video telemetry monitoring has an established role in the diagnosis of non-epileptic pseudo-seizures and in localizing the seizure focus for epilepsy surgery. Newer tools such as EEG mapping and magneto-encephalogram, although still investigational, appear potentially useful for defining the seizure focus in epilepsy. This review examines the traditional concepts of clinical EEG in the light of newly available data.

Electroencephalography↗
PubMed1999

Seizure and electroencephalographic changes in the newborn period induced by opiates and corrected by naloxone infusion.

OBJECTIVE: To describe the association between opioid administration in the newborn period and neurologic abnormalities. STUDY DESIGN: Case reports of two infants who presented with seizure activity and abnormal electroencephalograms associated with opiate administration, and reversed by naloxone. RESULTS: The first was a preterm infant who developed a burst-suppression pattern on the electroencephalogram while receiving a continuous infusion of morphine and muscle paralysis. Naloxone injection during the electroencephalogram recording reversed the burst-suppression pattern. The second was a term infant receiving fentanyl infusion for pain control following surgery, who presented with motor seizure that was only partially controlled with barbiturates. An abnormal electroencephalogram recording during the opiate infusion improved with naloxone administration. CONCLUSION: Our observations indicate a potential for neurologic abnormalities, including induction of seizure activity and electroencephalogram abnormalities, suggesting caution when opiates are used for sedation and/or pain control in the newborn period.

Brain↗
PubMed1999

EEG monitoring in the intensive care unit: pitfalls and caveats.

Electroencephalogram monitoring is a valuable means of monitoring thalamocortical function in the comatose, sedated, or paralyzed patient in the intensive care unit. The following problems arise especially with long-term recordings that are beyond those experienced in the standard EEG laboratory: 1) faulty electrodes, either single- or multiple-scalp electrodes or ground or reference electrodes; 2) connections of electronic equipment; 3) induced artifacts from electronic devices and nonelectronic equipment; 4) electrode placement issues; and 5) biologic, including movement-related, artifacts. Continuous quality improvement strategies should be implemented to minimize problems. Prompt troubleshooting and regular review sessions are two important components.

Artifacts↗
PubMed1999

EEG and clinical associations with mortality in comatose patients in a general intensive care unit.

The authors examined EEG findings and clinical factors for their association with outcome in comatose patients in their general intensive care unit. The following individual and combinations of factors were strongly related to mortality, with positive predictive values of >0.80 and odds ratios >2.0: age over 65 years, anoxic/ischemic encephalopathy, EEG suppression, lack of EEG reactivity; anoxia-ischemia with partial or complete cranial nerve areflexia, anoxia-ischemia with EEG suppression; anoxia-ischemia and generalized epileptiform activity; anoxia-ischemia with partial cranial nerve areflexia and EEG suppression. Conversely, the following factors favored survival rather than death: systemic infection/sepsis, metabolic derangement (excluding anoxic-ischemic insult), trauma; dysrhythmia, focal epileptiform activity, and regional delta and reactivity on EEGs. The findings of this study support the integration of these data into intensive care unit prognostic scoring systems, such as later versions of the Acute Physiology and Chronic Health Evaluation (APACHE).

Coma↗