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Biomedical subjects

John McCann

Publications and source records attributed to John McCann.

7 recordsLinked to original sources

Aggression after traumatic brain injury: analysing socially desirable responses and the nature of aggressive traits.

PRIMARY OBJECTIVE: To compare patients with traumatic brain injury (TBI) with controls on sub-types of aggression and explore the role of social desirability. DESIGN: Quasi-experimental, matched-participants design. METHODS AND PROCEDURES: Sixty-nine participants were included in the study. The sample comprised a TBI group (n = 24), a spinal cord injury (SCI) group (n = 21) and an uninjured (UI) group of matched healthy volunteers (n = 24). Participants were given self-report measures of aggression, social desirability and impulsivity. Sixty-one independent 'other-raters' were nominated, who rated participant pre-morbid and post-morbid aggression. MAIN OUTCOMES AND RESULTS: Using standardized norms, 25-39% of participants with TBI were classified as high average-very high on anger and 35-38% as high average-very high on verbal aggression. Other-raters rated participants with TBI as significantly higher on verbal aggression than SCI and UI participants. There were no differences between the groups on physical aggression. The TBI group also had higher levels of impulsivity than SCI and UI groups. Social desirability was a highly significant predictor of self-reported aggression for the entire sample. CONCLUSIONS: Impulsive verbal aggression and anger are the principal aggressive traits after brain injury. Physical aggression may present in extreme cases after TBI, but appears less prominent overall in this population. Social desirability, previously overlooked in research examining TBI aggression, emerged as an influential variable that should be considered in future TBI research.

Adolescent↗

Docetaxel and cyclooxygenase-2 inhibition with celecoxib for advanced non-small cell lung cancer progressing after platinum-based chemotherapy: a multicenter phase II trial.

PURPOSE: To assess the overall and progression-free survival, response rate, and toxicity of combined docetaxel and celecoxib in the treatment of patients with non-small cell lung cancer progressing after initial chemotherapy for advanced disease. PATIENTS AND METHODS: Patients with non-small cell lung cancer and either measurable or evaluable disease experiencing progression after one or more platinum-based chemotherapy regimens given for advanced or metastatic disease, ECOG performance status 0-2, and adequate hematologic and biochemistry parameters were eligible for study inclusion; exclusion criteria included symptomatic brain metastases and full dose anti-coagulation. Therapy consisted of docetaxel 75 mg/m(2) every 21 days for a maximum of six cycles and celecoxib 400 mg orally twice daily commencing 7 days prior to docetaxel and continuing until disease progression. RESULTS: A total of 41 patients were enrolled of whom 39 were deemed eligible and received at least one course of docetaxel. The mean age of enrolled patients was 60.5 years (range, 44-77); 67% were men and 79% white. All but one patient had an Eastern Clinical Oncology Group (ECOG) performance status of 0 or 1. Most (72%) had been treated with a prior taxane. Overall survival was 11.3 months (95% confidence interval [CI]: 7.9, 15.7) and progression-free survival 19.6 weeks (95% CI: 13.5, 25.0). A response rate of 10.2% (95% CI: 3%, 24%) for all eligible and treated patients was found. Grade 3 or 4 neutropenia occurred in 10/39 patients (25.6%); one death due to neutropenic sepsis occurred. No grade 3 or 4 renal or hepatic toxicities were documented. CONCLUSION: Treatment with combination celecoxib and docetaxel is a safe regimen with a toxicity profile similar to that of docetaxel alone. Survival data are encouraging compared to historical controls and may prolong time to disease progression compared with single-agent docetaxel.

Administration, Oral↗

Apoptotic neuronal death following deep hypothermic circulatory arrest in piglets.

BACKGROUND: Deep hypothermic circulatory arrest (DHCA), as used in infant heart surgery, carries a risk of brain injury. In a piglet DHCA model, neocortical neurons appear to undergo apoptotic death. Caspases, cytochrome c, tumor necrosis factor (TNF), and Fas play a role in apoptosis in many ischemic models. This study examined the expression of these factors in a DHCA piglet model. METHODS: Thirty-nine anesthetized piglets were studied. After cardiopulmonary bypass (CPB) cooling of the brain temperature to 19 degrees C, DHCA was induced for 90 min, followed by CPB rewarming. After separation from CPB, piglets were killed at 1, 4, 8, 24, and 72 h and 1 week. Caspase-8 and -3 activity, and concentrations of TNF-alpha, Fas, Fas-ligand, cytochrome c, and adenosine triphosphate (ATP) were measured in the neocortex by enzymatic assay and Western blot analysis. Caspase-8 and -3 activity and cell death were examined histologically. Significance was set at P < 0.05. RESULTS: In neocortex, damaged neurons were not observed in control (no CPB), rarely observed in CPB (no DHCA), and rarely observed in the DHCA 1-h, 4-h, and 1-week reperfusion groups. However, they were seen frequently in the DHCA 8-, 24-, and 72-h reperfusion groups. Although neuronal death was widespread 8-72 h after DHCA, cortical ATP concentrations remained unchanged from control. Both caspase-3 and -8 activities were significantly increased at 8 h after DHCA, and caspase-3 concentration remained elevated for as long as 72 h. Caspase-3 and -8 activity was also observed in damaged neocortical neurons. Cytosolic cytochrome c and Fas were significantly expressed at 1 h and 4 h after DHCA, respectively. Fas-ligand and TNF-alpha were not observed in any group. CONCLUSION: After DHCA, induction of apoptosis in the neocortex occurs within a few hours of reperfusion and continues for several days. Increased Fas, cytochrome c, and caspase concentrations, coupled with normal brain ATP concentrations and apoptotic histologic appearance, are consistent with the occurrence of apoptotic cell death.

Animals↗

Anogenital injuries in child pedestrians run over by low-speed motor vehicles: four cases with findings that mimic child sexual abuse.

OBJECTIVE: Differentiating between child sexual abuse and nonintentional causes of anogenital injury can be challenging, and a misdiagnosis can have a profound impact on the child and family. This case series documents an important nonintentional mechanism of anogenital injury that mimics the physical findings of child sexual abuse. METHODS: Four children were examined after being run over by a slow-moving motor vehicle. In each case, the wheel of the vehicle passed longitudinally over the child's torso. RESULTS: Two children had perianal lacerations, and 2 had hymenal lacerations. One child with hymen injuries was followed for 4 weeks and developed findings identical to those seen in healed sexual abuse. CONCLUSIONS: Children run over by motor vehicles should be evaluated for anogenital injury. If such injury is suspected, it should be fully delineated and documented with colposcopy and follow-up examination. Although the possibility of sexual abuse must be considered, awareness of the occurrence of anogenital injuries in children run over by motor vehicles may prevent the misdiagnosis of acute sexual abuse in children. Conversely, children presenting for evaluation of acute or past sexual abuse should be questioned as to whether they were ever run over by a motor vehicle.

Accidents, Traffic↗

Desflurane improves neurologic outcome after low-flow cardiopulmonary bypass in newborn pigs.

BACKGROUND: Despite improvements in neonatal heart surgery, neurologic complications continue to occur from low-flow cardiopulmonary bypass (LF-CPB) and deep hypothermic circulatory arrest (DHCA). Desflurane confers neuroprotection against ischemia at normothermia and for DHCA. This study compared neurologic outcome of a desflurane-based with a fentanyl-based anesthetic for LF-CPB. METHODS: Thirty piglets aged 1 week received either fentanyl-droperidol (F/D), desflurane 4.5% (Des4.5), or desflurane 9% (Des9) during surgical preparation and CPB. Arterial blood gases, glucose, heart rate, arterial pressure, brain temperature, and cerebral blood flow (laser Doppler flowmetry) were recorded. After CPB cooling (22 degrees C brain) using pH-stat strategy, LF-CPB was performed for 150 min followed by CPB rewarming, separation from CPB, and extubation. On postoperative day 2, functional and histologic outcomes were assessed. RESULTS: Cardiovascular variables were physiologically similar between groups before, during, and after LF-CPB. Cerebral blood flow during LF-CPB (13% of pre-CPB value) did not differ significantly between the groups. Functional disability was worse in F/D than in Des9 (P = 0.04) but not Des4.5 (P = 0.1). In neocortex, histopathologic damage was greater in F/D than in Des4.5 (P = 0.03) and Des9 (P = 0.009). In hippocampus, damage was worse in F/D than in Des9 (P = 0.01) but not Des4.5 (P = 0.08). The incidences of ventricular fibrillation during LF-CPB were 90, 60, and 10% for F/D, Des4.5 (P = 0.06), and Des9 (P = 0.0002), respectively. CONCLUSIONS: Desflurane improved neurologic outcome following LF-CPB compared with F/D in piglets, indicated by less functional disability and less histologic damage, especially with Des9. Desflurane may have produced cardiac protection, suggested by a lower incidence of ventricular fibrillation.

Anesthetics, Inhalation↗

Near-infrared spectroscopy cerebral oxygen saturation thresholds for hypoxia-ischemia in piglets.

Detection of cerebral hypoxia-ischemia remains problematic in neonates. Near-infrared spectroscopy, a noninvasive bedside technology has potential, although thresholds for cerebral hypoxia-ischemia have not been defined. This study determined hypoxic-ischemic thresholds for cerebral oxygen saturation (SCO2) in terms of EEG, brain ATP, and lactate concentrations, and compared these values with CBF and sagittal sinus oxygen saturation (SVO2). Sixty anesthetized piglets were equipped with near-infrared spectroscopy, EEG, laser-Doppler flowmetry, and a sagittal sinus catheter. After baseline, SCO2 levels of less than 20%, 20% to 29%, 30% to 39%, 40% to 49%, 50% to 59%, 60% to 79%, or 80% or greater were recorded for 30 minutes of normoxic normocapnia, hypercapnic hyperoxia, or bilateral carotid occlusion with or without arterial hypoxia. Brain ATP and lactate concentrations were measured biochemically. Logistic and linear regression determined the SCO2, CBF, and SVO2 thresholds for abnormal EEG, ATP, and lactate findings. Baseline SCO2 was 68 + 5%. The SCO2 thresholds for increased lactate, minor and major EEG change, and decreased ATP were 44 +/- 1%, 42 +/- 5%, 37 +/- 1%, and 33 +/- 1%. The SCO2 correlated linearly with SVO2 (r = 0.98) and CBF (r = 0.89), with corresponding SVO2 thresholds of 23%, 20%, 13%, and 8%, and CBF thresholds (% baseline) of 56%, 52%, 42%, and 36%. Thus, cerebral hypoxia-ischemia near-infrared spectroscopy thresholds for functional impairment are SCO2 33% to 44%, a range that is well below baseline SCO2 of 68%, suggesting a buffer between normal and dysfunction that also exists for CBF and SVO2.

Adenosine Triphosphate↗