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Biomedical subjects

G Drummond

Publications and source records attributed to G Drummond.

At least 19 recordsLinked to original sources

Impact of silencing HO-2 on EC-SOD and the mitochondrial signaling pathway.

The contribution of heme oxygenase HO-2, the primary source of bilirubin and carbon monoxide (CO) under physiological conditions, to the regulation of vascular function has remained largely unexplored. Using siRNA HO-2, we examined the effect of suppressed levels of HO-2 on vascular antioxidant and survival proteins. In vivo HO-2 siRNA treatment decreased the basal levels of EC-SOD, pAKT proteins (serine-473 and threonine-308), without changing Akt protein expression. HO-2 siRNA treatment increased 3-nitrotyrosine (3-NT) and apoptotic signaling kinase-1 (ASK-1) (P < 0.01). HO activity was decreased by the use of siRNA HO-2. We extended these studies to the mitochondria, examining for the presence of HO-1 and its role in the regulation of pro- and anti-apoptotic proteins. HO activity was increased by the administration of CoPP resulting in the translocation of HO-1 into the mitochondria, mainly to the inner face of the mitochondrial inner membrane. These findings suggest that HO-2 is critical in the maintenance of heme homeostasis and also the regulation of apoptosis by controlling levels of EC-SOD, Akt, 3-NT, and ASK-1. In addition, localization of HO-1 in the mitochondrial compartment plays a critical role in mitochondria-mediated apoptosis.

Animals↗

Evaluation of propofol and remifentanil for intravenous sedation for reducing shoulder dislocations in the emergency department.

OBJECTIVES: To assess the combination of propofol and remifentanil for sedation to reduce shoulder dislocations in an ED. METHODS: Eleven patients with anterior glenohumeral dislocation were given propofol 0.5 mg/kg and remifentanil 0.5 microg/kg iv over 90 seconds and then further doses of 0.25 mg/kg and 0.25 microg/kg, respectively, if needed. Another practitioner attempted reduction using the Milch technique. RESULTS: Reduction was achieved in all patients within four minutes of giving sedation (range 0.3-4; mean 1.6). Seven required one attempt at shoulder reduction, three required two attempts, and one required three attempts. Mean time to recovery of alert status was three minutes (range 1-6). The mean pain score during the reduction was 1.7 out of 10 (range 0-5). Nine patients had full recall, one had partial recall, and one had no recall at all. Eight patients were "very satisfied" with the sedation and three were "satisfied". There were no respiratory or haemodynamic complications that required treatment. CONCLUSIONS: Propofol and remifentanil provide excellent sedation and analgesia for the reduction of anterior glenohumeral dislocation, enabling rapid recovery.

Adolescent↗

Assessment of pulse transit time to indicate cardiovascular changes during obstetric spinal anaesthesia.

BACKGROUND: Pulse transit time (PTT) measurement may provide rapidly available beat-to-beat cardiovascular information when conditions change quickly and routine invasive arterial pressure measurement is not justified, for example during obstetric spinal anaesthesia. Method. We obtained ethics approval for an observational study of PTT during the onset of spinal anaesthesia in patients having elective or urgent Caesarean section. PTT was measured as the difference in time between the peak of the ECG R wave and the upstroke of the toe plethysmograph. Arterial pressure was measured by non-invasive sphygmomanometry. RESULTS: We analysed data from 58 normotensive patients and 15 patients with pregnancy-induced hypertension (PIH). PTT increased with the onset of spinal anaesthesia as arterial pressure decreased. An increase of 20% in PTT was 74% sensitive and 70% specific in indicating a decrease in mean arterial pressure of more than 10%. Changes in PTT were related to changes in mean arterial pressure (r2=0.55, P<0.0001). Arterial pressure changes were greater and PTT increased significantly more quickly in the normotensive patients than in the patients with hypertension [median, quartiles: 32 (14, 56) ms min(-1) compared with 7 (6, 18) ms min(-1); P<0.01, Mann-Whitney U-test]. However, the relationship between PTT and arterial pressure was similar for the normotensive patients and the patients with PIH. CONCLUSION: PTT measurement gave a beat-to-beat indication of arterial pressure during spinal anaesthesia, and could be developed to allow prediction of the onset of hypotension.

Adult↗

Assessment of postsurgical recovery after discharge using a pen computer diary.

We assessed patients after their return home following gynaecological surgery, using a daily electronic diary. Thirty-two females aged 27-77 years took part. After a hospital stay of 1-6 days (mean 2.3), they were given a pen-based electronic diary and asked to record symptoms and other data over one month. They also completed a questionnaire at the end of the study. Substantial effects on quality and duration of sleep, pain during both the night and day, interference with daily activities, energy, and ability to concentrate were recorded, mostly during the first week of treatment. Symptoms reported in the final questionnaire correlated significantly with diary data. Most patients found the electronic diary easy to use, and none found it difficult. Daily electronic diaries are an acceptable method of obtaining better information on the extent and duration of symptoms and other difficulties after discharge following surgery.

Activities of Daily Living↗

Errors in performance testing: a comparison of ethanol and temazepam.

Both ethanol and benzodiazepines impair psychomotor function. Previous work has suggested that ethanol may have a greater effect on errors while benzodiazepines may cause greater slowing, but this has not been tested in a direct comparison. We assessed the effects of ethanol, at blood concentrations of approximately 80-100 mg/100 ml, compared to two doses of temazepam (20 mg and 30 mg) on psychomotor speed and accuracy and on long-term memory. Sixteen healthy volunteers (eight male, aged 20-25 years) took part in a four-period, placebo-controlled cross-over study. Performance was evaluated using analysis of covariance (critical significance level, p = 0.05) comparing the areas under the response-time curves. Performance on a psychomotor maze showed an almost complete dissociation, with ethanol leading to a substantial and significant increase in errors with little effect on speed, while temazepam slowed performance with no significant change in accuracy. Other tasks showed a similar pattern, but the dissociation was less complete. Handwriting size was substantially increased by ethanol, but not by temazepam. Information processing capacity and long-term memory formation were reduced by a similar amount both for ethanol and 30 mg temazepam. The faster, more error-prone, behaviour on ethanol than with a similarly impairing dose of temazepam has clear implications for the relative potential of the two drugs to contribute to accidents. The results are also important in understanding the differential effects of drugs with different mechanisms of action on human performance.

Adult↗

Brainstem death and ventilator trigger settings.

A patient with cerebral infarction was certified clinically brainstem dead. However, 4 h after the diagnosis of death, while the patient was being ventilated using the biphasic positive airway pressure mode, the 'assist' indicator light on the Drager Evita 2 ventilator illuminated intermittently. There was no evidence of spontaneous breathing. 'Triggering' was probably caused by a decrease in airway pressure in time with cardiac contraction. The trigger flow rate is crucial as factors other than the patient's inspiratory effort can initiate flow from the ventilator with very sensitive settings.

Brain Death↗

Dual role of heme oxygenase in epithelial cell injury: contrasting effects of short-term and long-term exposure to oxidant stress.

This study examined the role of heme oxygenase (HO) in the acquisition of resistance to hydrogen peroxide (H2O2) and hemin toxicity by renal epithelial cells (BSC-1). BSC-1 cells adapted by long-term exposure to H2O2 exhibited a twofold increase in basal HO activity and expression of HO-1 mRNA as compared with their wild-type counterparts. Exposure of both adapted and wild-type BSC-1 cells to H2O2 induced HO-1 mRNA. When cells were exposed to H202 for 24 hours, cell viability was reduced; however, an inhibitor of HO activity, Zn 2,4-bis-glycol protoporphyrin IX, improved cell viability. In a similar manner, ZnDBG completely overcame the reduction in cell viability brought about by 1 hour of hemin treatment. In addition, cells preexposed to hemin for 24 hours maintained a high level of HO mRNA and acquired resistance to further challenge with H2O2. Hemin treatment per se was associated with a detectable reduction in BSC-1 cell viability; however, the effect of hemin was not additive to the cytotoxicity of hydrogen peroxide, suggesting a common pathway of cell injury. In conclusion, two interrelated stressors, H2O2 and hemin, produced a stimulation of HO-1, and this was associated with a reduction in the viability of BSC-1 cells. Long-term exposure (24 hours) to both stressors resulted in the acquisition of some resistance to a further acute challenge of oxidant stress in BSC-1 cells.

Adaptation, Physiological↗

Acoustic reflectometry for airway measurement. Principles, limitations and previous work.

Acoustic pulse reflectometry is a relatively recent technique which allows the non-invasive measurement of human airways. The technique consists of guiding an acoustic impulse through the subject's mouth and into the airway. Suitable analysis of the resulting reflection (the 'echo') allows a reconstruction of the area-distance function. The non-invasive nature of the technique offers significant advantages over the established methods of x-ray cephalometry and CT scanning, and makes it very attractive for the investigation of ENT problems and sleep apnoea, and in the anaesthetic management of patients. This paper describes the theory and limitations of acoustic reflectometry, discusses previous work, and suggests some modifications: it is currently being implemented clinically.

Acoustics↗

Temporary tarsorrhaphy induced with type A botulinum toxin.

We describe two children with corneal epithelial defects resistant to healing in whom protective temporary ptosis was induced with type A botulinum toxin injected to the levator palpebrae superioris. Epithelial healing was rapid, and no complications were noted. With further study this procedure may become useful in the treatment of corneal epithelial defects resistant to healing.

Blepharoptosis↗

Studies with the haeme oxygenase inhibitor Sn-protoporphyrin in patients with primary biliary cirrhosis and idiopathic haemochromatosis.

Sn(tin4+)-protoporphyrin, a potent competitive inhibitor of haeme oxygenase, the rate limiting enzyme in the degradation of haeme to bile pigments, was given intravenously to six patients with primary biliary cirrhosis and to four patients with idiopathic haemochromatosis. Serum bilirubin concentrations decreased in all patients after administration of 1-2 mumol/kg body weight of the metalloporphyrin, given in two doses eight to 24 hours apart. This reduction lasted approximately four to five days after injection of the compound. Excretion of endogenous haeme in bile increased (mean increase approximately two to threefold) in parallel with the decrease in serum bilirubin concentrations in both patient groups, and the highest biliary haeme concentrations were found during the first 48 hours after treatment. Sn-protoporphyrin was cleared rapidly from plasma with a half-life of 3.4 hours. Biliary bilirubin concentrations decreased (mean decrease, 49%) in the haemochromatosis patients after Sn-protoporphyrin administration. No decrease in biliary bilirubin concentrations could be detected in the primary biliary cirrhosis patients under the same conditions. Thus, Sn-protoporphyrin treatment resulted in a decrease in serum bilirubin concentrations and an increase in biliary haeme excretion in patients with haemochromatosis and primary biliary cirrhosis, as has previously been shown in normal subjects. The results indicate that the synthetic haeme analogue inhibits haeme oxidation activity in the two patient groups studied, as it does in normal people and in experimental animals. The lack of effect of Sn-protoporphyrin on biliary bilirubin excretion in primary biliary cirrhosis may be related to a differently affected hepatic clearance system or to a different distribution of tissue bilirubin pools in this condition.

Adult↗