Biomedical subjects
M Wood
Publications and source records attributed to M Wood.
Effects of anesthesia on norepinephrine kinetics. Comparison of propofol and halothane anesthesia in dogs.
Alteration of sympathetic function is a major determinant of the cardiovascular effects of anesthetic agents. Plasma norepinephrine (NE) concentrations are determined not only by the rate of NE release from sympathetic nerves but also by NE clearance rate. Therefore, NE concentration in plasma may be an inadequate index of sympathetic activity. We used an isotope dilution technique to investigate the effects of halothane and propofol anesthesia on NE kinetics. A relationship of NE kinetics to halothane dose was determined in six dogs. Halothane 1.0 MAC reduced plasma NE concentration by 35 +/- 9% versus awake (P less than 0.05). This was due to a reduction of 52 +/- 9% in NE spillover (P less than 0.05) accompanied by a reduction of 27 +/- 5% in NE clearance (P less than 0.005). The clearance changes were dose-dependent: reductions were 34 +/- 4% at 1.5 MAC (P less than 0.05 vs. 1.0 MAC) and 45 +/- 5% at 2.0 MAC (P less than 0.05 vs. 1.5 MAC). Six dogs were studied with a single halothane dose (1.0 MAC) and NE concentration, spillover, and clearance were found to be stable over a period of 5.5 h of anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)
Direct myocardial revascularization without extracorporeal circulation. Experience in 700 patients.
Between May 1978 and March 1990, 700 patients were operated on with direct coronary surgery without extracorporeal circulation (ECC): 529 (76 percent) were male and 171 (24 percent) were female. The average age was 64 years (range, 35 to 86 years), 454 (65 percent) had unstable angina, 163 (23 percent) had stable angina, 51 (7 percent) had postmyocardial infarction angina, and 32 (5 percent) had acute myocardial infarction at the moment of the operation. In this series of patients, all branches of the coronary arteries were bypassed; the mammary artery was used in 40 percent of the cases, the average bypass per patient was 2.2 (range, 1 to 5), and 26 percent had associated disease of high risk to undergo ECC. The morbidity was 4 percent and the mortality for this series of patients was 1 percent; the probability of survival at seven years was 90 percent. This experience shows us that this surgery is an alternative in the treatment of coronary disease, especially for aged patients with associated disease, in some cases of acute transmural infarction, and also for patients who need coronary angioplasty. Also, it can improve the relation cost/benefit in coronary surgery.
Pharmacokinetic drug interactions in anaesthetic practice.
Patients receive on average 10 different drugs while in hospital; when fewer than 6 are administered the probability of an adverse drug interaction is about 5%, but when more than 15 are given the probability increases to over 40%. Patients presenting for anaesthesia and surgery are likely to receive multiple preoperative drug therapy and also many perioperative medications as part of their anaesthetic regimen. Thus, there is a considerable potential for interactions to occur in anaesthetic practice. Pharmacokinetic interactions occur when the administration of 1 drug alters the disposition of another, and hence alters the concentration of drug at the receptor site, leading to altered drug response. These changes in drug concentration at the receptor site may be produced by alteration of (a) drug absorption and uptake into the body, (b) drug distribution, (c) drug metabolism and (d) drug elimination or excretion by nonmetabolic routes. Interactions affecting the absorption of orally administered medications are often due to the indirect effect of 1 drug on gastric motility and emptying, which leads to reduced, delayed or variable systemic drug availability. Gastric emptying time before elective surgery is normal, but premedication with morphine, pethidine (meperidine) and anticholinergics all delay gastric emptying and hence drug absorption. Inhalational anaesthesia of short duration does not appear to affect drug absorption, although halothane anaesthetic used for longer periods produces a slight delay in gastric emptying. Volatile anaesthetics have been shown to delay the intramuscular absorption of ketamine. Anaesthetic agents may affect drug distribution, and peak concentrations of propranolol, for example, are 4 times higher during halothane anaesthesia in dogs, accompanied by a marked decrease in volume of distribution. This effect has been noted for other drugs, including thiopental and verapamil. Volatile anaesthetics also affect plasma protein binding, leading to displacement interactions in some cases. Volatile anaesthetics affect the metabolism of concomitantly administered drug (a) by altering the rate of delivery to the organ of clearance (e.g. decreasing hepatic blood flow) and (b) by altering the activity of drug metabolising enzymes. It is now well recognised that all the volatile anaesthetics currently in use inhibit the metabolism of a large variety of drugs, e.g. propranolol, lidocaine (lignocaine), fentanyl and pethidine. Other examples of interactions of clinical importance to anaesthesiologists include those between cimetidine and the local anaesthetics and benzodiazepines; inhibition of plasma cholinesterase by drugs such as ecothiopate; interactions between monoamine oxidase inhibitors and sympathomimetics or pethidine and between monoamine oxidase inhibitors and sympathomimetics or pethidine and between isoniazid and enflurane.(ABSTRACT TRUNCATED AT 400 WORDS)
Plasma binding and limitation of drug access to site of action.
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The use of statistical analysis to identify trends, issues and research questions on a nephrology unit.
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A delicate balance: scientific merit and clinical relevance.
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Usefulness of right ventricular pulse pressure as a potential sensor for hemodynamically unstable ventricular tachycardia.
The automatic implantable cardioverter defibrillator has had a major impact on the management of patients with ventricular tachyarrhythmias. Future devices will offer tiered therapy for ventricular arrhythmias, based on a sensor capable of discriminating hemodynamically stable from unstable ventricular tachycardia (VT). We studied 27 patients with sustained VT/ventricular fibrillation during 70 episodes of sustained ventricular arrhythmias (greater than 30 seconds or requiring cardioversion). In this study, phasic arterial pressure (mm Hg), VT cycle length (ms) and right ventricular (RV) pulse pressure (mm Hg) were measured before, during the first 30 beats and after each episode of VT. During the first 10 beats of 23 episodes of unstable VT, the mean (+/- standard error of the mean) decrease in RV pulse pressure from baseline was 22 +/- 1.8 mm Hg; it was 13.8 +/- 2.4 mm Hg during the first 10 beats of 47 episodes of stable VT, (p = 0.01, stable vs unstable). For the next 20 beats of VT, RV pulse pressure decreased from baseline by 22 +/- 2.5 mm Hg during unstable and by 12.0 +/- 2.5 mm Hg during stable VT (p = 0.0001, stable vs unstable). The percent decrease of RV pulse pressure correlated well with the percent decrease in mean arterial pressure and percent decrease in systolic arterial pressure (r = 0.70; r = 0.69, respectively; p less than 0.001) during VT, but poorly with the VT cycle length (r = 0.27, p less than 0.05). The percent decrease in RV pulse pressure is a useful hemodynamic sensor for discriminating between stable and unstable VT.
The incidence and correlates of erectile problems in patients with Alzheimer's disease.
Loss of erection was reported in 53% of 55 male Alzheimer's disease patients with a mean age of 70.25. Loss of erection is not related to degree of cognitive impairment, age, or depression. Modal time of onset of erectile problems is concurrent with onset of Alzheimer's symptoms. Patients with erectile problems were not taking more medications overall than those without problems and had no greater overall incidence of concurrent physical problems. Thus, the evidence suggests that there may be an elevated incidence of erectile failure in patients with Alzheimer's disease as a primary problem not attributable to other age-related factors.
Intraocular lens implantation in developing countries.
One of the chief aims of ophthalmic workers in developing countries is to operate on as many cataract patients as possible in the most cost-efficient manner. Therefore, our intraocular lens (IOL) implantation policy in Nakuru and Kikuyu, Kenya, is to reserve IOLs for monocular cataract patients of all ages, who otherwise would not have use of the aphakic eye. In this study, we review 105 of our first IOL implantations. In 60%, the uncorrected postoperative visual acuity was 20/60 or better.
Adrenergic response to nicardipine in the management of postoperative hypertension.
Nicardipine, a new dihydropyridine calcium channel blocking agent, has been shown to be effective in the management of hypertension. The adrenergic response to intravenous nicardipine as measured by changes in plasma catecholamine concentrations in seven patients undergoing treatment of postoperative hypertension is reported. Postoperative hypertension was defined as a systolic blood pressure (SBP) greater than 140 mm Hg. Nicardipine or placebo was administered in doses of 10 mg/h, 12.5 mg/h, and 15.0 mg/h for 5 minutes, 5 minutes, and 15 minutes, respectively, to achieve a therapeutic response defined as a reduction of SBP of 15% or more. Once a therapeutic response occurred, patients entered a maintenance period when the study drug infusion rate was reduced to the equivalent of 3.0 mg/h, and the dose was adjusted by 1.0 to 2.5 mg/h every 15 minutes as needed to maintain blood pressure control. Patients who did not respond to the study drug had their treatment code broken and, if on placebo, received open-label nicardipine. Blood samples were taken for the measurement of plasma norepinephrine (NE) concentrations at baseline prior to nicardipine infusion, at the time of therapeutic response, during maintenance, and after discontinuation of nicardipine. There were no significant differences between the baseline heart rate prior to nicardipine infusion and at the time of therapeutic response, during maintenance, or after discontinuation of the infusion. Mean NE concentrations at baseline prior to nicardipine infusion were 589.3 +/- 140.1 pg/mL (normal range, 75 to 480 pg/mL). Thus, hypertensive patients in the recovery room have a high degree of background sympathetic stimulation. Nicardipine did not further increase plasma NE levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of enflurane and isoflurane in air-oxygen on changes in thermal balance during and after surgery.
The temperatures in the aural canal (core), skeletal muscle and skin surface were measured during anaesthesia and surgery in 32 healthy females undergoing total abdominal hysterectomy and for 4 h after operation. The patients were allocated randomly to one of four groups according to the end-tidal concentration of volatile anaesthetic: 1 MAC isoflurane, 1 MAC enflurane, 1.8 MAC isoflurane and 1.8 MAC enflurane. The lungs were ventilated with an air-oxygen mixture. Neuromuscular block was produced with pancuronium. Room temperature and i.v. fluid administration were standardized. Aural canal, muscle and mean skin temperatures decreased significantly in all groups during surgery (P less than 0.001). The decrease in core and muscle temperatures, and mean body heat was significantly greater in the 1.8 MAC groups than in the 1 MAC groups for both volatile agents (P less than 0.001). However, there was a significantly greater decrease in core temperature and mean body heat in the isoflurane compared with the enflurane group (P less than 0.026). Body temperature returned to preoperative values during the recovery period. There was a significantly greater rate of rewarming during the first 1 h of recovery in the 1.8 MAC groups compared with the 1 MAC equivalent (P less than 0.001), and this was independent of the volatile agent used. The present results are compared with those reported previously in which nitrous oxide was added to the volatile agents. The decrease in body temperature depends upon the concentration of vapour used. However, it appears that isoflurane, without nitrous oxide, caused greater loss of body heat than enflurane.
The effect of halothane on morphine disposition: relative contributions of the liver and kidney to morphine glucuronidation in the dog.
The present study determined the effect of halothane on the disposition of morphine by defining the effect of halothane anesthesia on the systemic, renal, and hepatic clearance of the parent compound, morphine, and on the generation of the primary metabolite, morphine-3-glucuronide (M3G) in the dog. Unlabeled morphine, 3H-morphine, and 14C-morphine were simultaneously administered into the portal vein, femoral vein, and renal artery, respectively, first during pentobarbital anesthesia and second during halothane (1.5 MAC) anesthesia; blood samples were taken for estimation of unlabeled plasma morphine and M3G concentrations by high performance liquid chromatography (HPLC). 3H- and 14C-morphine concentrations and corresponding M3G concentrations were determined by dual-channel liquid scintillation counting of the eluant corresponding to the appropriate peak on the HPLC. The portal clearance of morphine was not altered by halothane. However, intravenous (iv) morphine clearance (CLs) decreased (P less than 0.05) by 40% from 963 +/- 131 to 579 +/- 91 ml/min during halothane anesthesia, accompanied by an increase (P less than 0.05) in half-life from 78 +/- 8 to 106 +/- 8 min. The reduction in CLs of morphine occurred putatively on the basis of a halothane-induced decrease in hepatic blood flow, whereas morphine metabolism, reflected by morphine portal (intrinsic) clearance, was not significantly decreased by halothane. There was no significant effect of halothane on the partial metabolic clearance of morphine to M3G, and the ratio of area under the plasma concentration-time curve (AUC)-M3G to AUC unchanged morphine was not significantly altered by halothane, indicating that morphine glucuronidation is unaffected by halothane anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)
Nicardipine infusion for postoperative hypertension after surgery of the head and neck.
The therapy of postoperative hypertension (POH) after head and neck surgery was evaluated in a prospective, randomized, double-blind trial. Nicardipine hydrochloride, a Ca channel-blocker for iv use, was compared with placebo. Patients were initially randomized to receive nicardipine infusion or placebo. Those not responding to placebo were given nicardipine infusion on an open basis. Hypertension was significantly better controlled in patients treated with nicardipine infusion compared with placebo (83% vs. 22%, p less than .002). Subsequently, six (86%) of seven of the placebo failures were successfully treated with nicardipine. There were no significant complications in either group. We conclude that the titratable infusion of nicardipine is an effective and safe method for the control of POH after surgery of the head and neck. Further studies are now warranted comparing nicardipine with other drugs currently used to treat this condition.
Complementary use of Doppler sonography and delayed right lateral scintigraphy for the diagnosis of choledochal cysts.
Both sonography and hepatobiliary scintigraphy can help to demonstrate a choledochal cyst. Our case further demonstrates that Doppler sonography and right lateral or oblique scintigraphic views can be used to differentiate more completely this entity from other infantile cholestatic syndromes. These additional maneuvers may be particularly advantageous in the affected infant under a year old in whom a confusing clinical picture may obscure the correct diagnosis.
A prospective study of right ventricular pulse pressure and dP/dt to discriminant-induced ventricular tachycardia from supraventricular and sinus tachycardia in man.
In the future, automatic implantable cardioverter defibrillators (AICD) may incorporate sensors to differentiate hemodynamically stable from unstable ventricular tachycardias (VT). These sensors should also discriminate between ventricular and supraventricular tachycardias to avoid inappropriate responses from the device. Right ventricular pulse pressure (RVPP) and maximal systolic right ventricular dP/dt (dP/dt) were measured before, during and after 91 episodes of hemodynamically stable VT (VTs), hemodynamically unstable VT (VTus), supraventricular tachycardia (SVT) and sinus tachycardia (ST) induced in 49 male patients. The mean percent changes (mean +/- S.E.M.) in RVPP from baseline (% delta RVPP) during VTs and VTus were -35 +/- 3% and -72 +/- 3%, respectively (both P less than 0.001). The % delta RVPP during ST was +56 +/- 11% (P less than 0.01) and % delta RVPP was unchanged from baseline during SVT (+2 +/- 9%; P greater than 0.01). Mean % change in RV dP/dt from baseline was -20 +/- 3% during VTs (P less than 0.001), -36 +/- 5% during VTus (P less than 0.001), +15 +/- 13% during SVT (P less than 0.01), and +85 +/- 23% during ST (P greater than 0.01). The mean percent changes in RVPP were significantly different between each arrhythmia group (P less than 0.01). The mean % changes in RV dP/dt were significantly different only between ST and VTs or VTus and between SVT and VTus. The range of values for % delta RVPP during VTs overlapped considerably with the ranges of % delta RVPP during VTus and SVT. The ranges of % delta RVPP overlapped minimally between VTus and SVT. Percent change RVPP separated each episode of VTs and VTus from those of ST. The range of common values for % delta dP/dt between all four groups was extensive. It is concluded that % delta RVPP from baseline is significantly different between groups of patients during VTs, VTus, SVT, and ST, but that a large degree of overlap in the range of values for % delta RVPP and RV dP/dt between different arrhythmias groups may limit the specificity of these hemodynamic variables in separating different arrhythmias.
DNA, a Possible Site of Action of Aluminum in Rhizobium spp.
Al was found to penetrate the cell envelopes of both sensitive and tolerant Rhizobium strains and bind to DNA in vivo. Despite causing a reduction in viability, Al stimulated DNA synthesis in the sensitive strain, which suggested that an excision repair mechanism was operating. The Al-stimulated DNA synthesis was reduced by the simultaneous addition of chloramphenicol. In contrast to the sensitive strain, DNA synthesis was unaffected by Al binding to DNA in the tolerant strain. It is proposed that Al enters the cell and binds to the DNA helix, increasing stabilization and preventing successful replication. Different repair mechanisms appear to operate in response to Al in tolerant and sensitive strains.