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Biomedical subjects

A H Ilsley

Publications and source records attributed to A H Ilsley.

At least 19 recordsLinked to original sources

Influence of intestinal flora on the development of fibrosis and cirrhosis in a rat model.

BACKGROUND AND AIMS: The gut flora play a significant role in the disposition of many foreign substances, as well as producing nutrients and toxins that may be absorbed and reach the liver. This study examines the influence of antibiotic-induced alterations in gut flora on the development of hepatic fibrosis in a rat model. METHODS: Thirty-six male Porton rats were fed alcohol (3.9 g/kg per day) in the drinking water and exposed to carbon tetrachloride (CCl4) vapor (80 p.p.m.) for 6 h each night, five nights per week. Half were also given neomycin (330 mg/kg per day) and polymyxin B (105 mg/kg per day) in the drinking water. Fecal cultures were carried out at 0, 3, 8 and 13 weeks; rats were killed at 14 weeks. Coded liver section were assessed for fibrosis using a graded scale (0, no abnormal fibrosis to 4, early or established cirrhosis). RESULTS: Rats that received antibiotics had significantly higher fibrosis scores than those that did not (mean score 2.4 vs 1.4, P < 0.01, ordinal logistic regression). Three rats, all of which were in the antibiotic group, were cirrhotic. Rats that had received antibiotics fell into three groups. Four had overgrowth of Proteus mirabilis; in these the fibrosis scores (mean 1.5) were similar to those in the rats that did not receive antibiotic. In six, no organisms could be cultured; fibrosis scores of these (mean 2.3) were slightly elevated (P = 0.03), but this was mainly because of a single rat in this subgroup being cirrhotic. The remaining eight had overgrowth of Morganella morganii; these had significantly (P < 0.001) elevated fibrosis scores. Furthermore, in this subgroup, fibrosis scores were significantly correlated (Spearman's r = 0.82, P = 0.01) with the number of weeks of Morganella colonization. CONCLUSIONS: Antibiotic treatment exacerbated fibrosis in the alcohol/CCl4 rat model; this effect appeared to be related to the type of gut flora and may be endotoxin-mediated.

Animals↗

Dynamic calibration of mechanically, air- and electromagnetically braked cycle ergometers.

In this study we measured the accuracy of the following types of cycle ergometer against the criterion of a dynamic calibration rig (DCR): 35 friction-braked (Monark), 5 research-grade air-braked (Repco) and 5 electromagnetically braked (2 Siemens, 1 Elema-Schonander, 1 Ergoline, 1 Warren E. Collins). Monark ergometer power outputs over the range 58.9-353.2 W significantly (P < 0.001) underestimated those registered by the DCR with mean accuracies of 91.7-97.8%. The least accurate individual reading for each of the six up-scale (0-353.2 W) power outputs ranged from 81.6 to 91.6%; corresponding down-scale (353.2-0 W) accuracies were 85.1-92.5%. A hysteresis effect was furthermore evident for this ergometer in that up-scale measurements were significantly (P < 0.05) greater than down-scale ones. In addition, when the oldest [mean (SD): 11.3 (2.3) years old] and newest [1.4 (0.8) years old] eight ergometers were compared, the latter were significantly (P < 0.05) more accurate over the range 117.7-294.3 W. Apart from the two lowest power outputs of 47 W (62.2-96.0% accuracy) and 127 W (88.0-97.7% accuracy), the individual up-scale and down-scale accuracies of the Repco ergometers ranged from 98.0 to 104.2% for power outputs of 272.7-1137.8 W and the means were not significantly different from those of the DCR. There was also no evidence of hysteresis. Except for the initial power output of 50 W (40 rev/min: 83.8-99.2% accuracy; 60 rev/min: 93.2-122.6% accuracy), the individual accuracies of the electromagnetically braked ergometers ranged from 89.3 to 101.4% over the up-scale range of 100-400 W, and none of the means were significantly different from those of the DCR. The variability of individual errors for the preceding data emphasises that all cycle ergometers should be validated against the criterion of a DCR if accurate power outputs are required.

Atmosphere↗

Influence of premedication with diazepam or morphine on the induction dose of eltanolone.

BACKGROUND: This study examined the influence of premedication with morphine or diazepam on the dose of eltanolone, a steroidal intravenous anaesthetic agent, required to induce anaesthesia. METHODS: Two hundred and sixteen patients, aged 18 to 65 years, were randomly assigned to receive premedication with diazepam 10 mg orally, morphine 10 mg intramuscularly, or placebo. The double-dummy technique was used to maintain blinding. Eltanolone 0.16-0.75 mg x kg(-1) was given intravenously over 20 s. At the commencement of injection patients were instructed to begin counting; if the patient ceased counting within 120 s and failed to respond to commands to continue, anaesthesia was considered to have been induced. The dose required to anaesthetise 50% of patients (ED50) was determined by logistic regression. RESULTS: The ED50 (95% confidence interval) of eltanolone in patients who received placebo premedication was 0.31 (0.27-0.34) mg x kg(-1). It was reduced slightly and nonsignificantly by premedication with diazepam, to 0.27 (0.24-0.30) mg x kg(-1), or morphine, to 0.26 (0.23-0.29) mg x kg(-1). Involuntary movement occurred in 65% of placebo premedicated patients. Its incidence was not significantly reduced by diazepam (57%), but was significantly (P<0.001) reduced by morphine (37%). Morphine premedication was, however, associated with a significant (P<0.01) increase in the incidence of apnoea (21%) compared to placebo premedicated patients (4%). CONCLUSION: Premedication with diazepam or morphine had little influence on the dose of eltanolone required to induce anaesthesia.

Adjuvants, Anesthesia↗

Identification of movement artefact by the Nellcor N-200 and N-3000 pulse oximeters.

OBJECTIVES: The Nellcor N-3000 pulse oximeter is designed to be able to identify signal artefact related to movement of the body part to which the probe is attached. It may therefore provide a reliable means of monitoring arterial oxyhemoglobin saturation (SpO2) in awake, moving patients. This study compared the Nellcor N-3000 and N-200 pulse oximeters in terms of their ability to identify readings associated with movement, in a group of volunteers making standardized movements. METHODS: Thirty-six volunteers were studied. Volunteers breathed room air throughout the study. SpO2 of each volunteer was monitored by both a Nellcor N-200 and a Nellcor N-3000 simultaneously on both hands. Volunteers made a series of five standardized movements, each lasting one minute, with each hand during the monitoring session, while SpO2 and oximeter status were recorded from all four oximeters. The mean SpO2 reading was calculated during each movement. SpO2 readings which the oximeter identified as being associated with movement, pulse search not locked, sensor not attached, or break in communications were excluded from analysis. RESULTS: The N-3000 rejected from 17 to 78% of readings taken during movement, compared to 0 to 2% with the N-200. Although the remaining readings of both types of oximeters were subject to some movement artefact, which led to spuriously low SpO2, this was significantly less with the N-3000. CONCLUSIONS: The Nellcor N-3000 pulse oximeter is able, to some extent, to identify movement artefact. It should offer an advantage over the N-200 when monitoring moving patients.

Adolescent↗

A technique for obtaining repeated liver biopsies from rats.

Many morphological, pharmacological and toxicological studies of hepatotoxicity require frequent sampling of liver over time. In the past this has been achieved by including large numbers of animals in the study and killing subgroups at different times. In this paper we describe a technique for repeated liver biopsy that procures sufficient liver tissue for histopathological assessment and for additional studies, for example measurement of hepatic iron concentration or vitamin A measurement. The advantages and disadvantages of this technique are discussed.

Animals↗

Use of artificial sweeteners to promote alcohol consumption by rats.

Cirrhosis may be reliably produced in rats by exposing them intermittently to low levels of carbon tetrachloride vapour while feeding alcohol in the Lieber-DeCarli liquid diet. Providing the alcohol in drinking water that has been sweetened with sucrose is a cheaper and more convenient method but it does not yield reliable results. This study aimed to determine whether alcohol in drinking water sweetened with artificial sweeteners would give adequate alcohol intake to achieve the desired hepatic effects. Rats were fed alcohol (8% v/v) in drinking water sweetened with sucrose (5% w/v) (n = 12), or with one of the artificial sweeteners aspartame (0.025%), saccharin (0.025%) or cyclamate (0.05%) (n = 8 per agent). During the alcohol treatment the animals were exposed to carbon tetrachloride vapour, 40 ppm, six hours per night for five nights per week, over a period of 14 weeks. All groups achieved good alcohol intakes of 5-6 g/kg/day. Only one rat, in the aspartame group, became cirrhotic; all the others had varying degrees of fibrosis which did not differ significantly among the treatments. Although it was not effective in reliably achieving cirrhosis, sweetening the alcohol solution with artificial sweeteners led to reasonable alcohol intakes with resultant hepatic fibrosis, and without the high carbohydrate intake which occurs when sucrose is used.

Alcohol Drinking↗

Morphine patient-controlled analgesia is superior to meperidine patient-controlled analgesia for postoperative pain.

The choice between morphine and meperidine for postoperative pain is usually based on the preference of the prescriber, as few objective comparative data are available. This blind, randomized study compared the efficacy and side effects of morphine and meperidine administered by patient-controlled analgesia (PCA) for postoperative pain. One hundred two consenting patients scheduled for major abdominal surgery were randomly assigned to receive PCA with morphine (0.75, 1.0, or 1.5 mg bolus dose size) or meperidine (9, 12, or 18 mg) for pain control. Postoperative assessments included pain at rest and on sitting, nausea, unusual dreams, the Multiple Affect Adjective Check List (a measure of mood), and the trailmaking tests A and B (measures of ability to concentrate). Pain on sitting (P = 0.037) but not pain at rest (P = 0.8) was significantly less in patients receiving morphine. Meperidine use was associated with poorer performance in the trailmaking tests and a greater incidence of dryness of the mouth. Severity of nausea, mood, and incidence of unusual dreams did not differ significantly between drugs. We conclude that meperidine should be reserved for those patients in whom morphine is judged inappropriate.

Abdomen↗

Dose-related effects of dietary iron supplementation in producing hepatic iron overload in rats.

The influence of varying the level of supplemental dietary iron on the development of hepatic iron overload was examined in rats. Two days after giving birth, Porton rats were fed a diet supplemented with 0, 0.5, 1 or 2% carbonyl iron, to institute dietary iron supplementation to the young via breast milk. After weaning, the offspring continued to receive the assigned diet until 32 weeks of age. Liver biopsies were taken from some rats at 8, 16 and 24 weeks of age and from all rats at 32 weeks of age, for assessment of iron overload. For both male and female rats, hepatic iron content was increased in a dose-related manner by feeding supplemented diet. Hepatic iron content of male rats tended to reach a plateau after 8, 16 weeks of supplementation, while that of female rats continued to rise throughout the experimental period, such that the hepatic iron content of female rats was 2.8-fold that of similarly treated males at 32 weeks of age. Iron supplementation was associated with only moderate retardation of growth. By choosing an appropriate level of iron supplementation, good (grade III-IV) hepatic iron loading can be achieved with minimal adverse effects on the animals' overall health.

Animals↗

Sustained-release ibuprofen as an adjunct to morphine patient-controlled analgesia.

Previous studies have demonstrated reduced postoperative morphine requirements and/or improved pain relief when nonsteroidal antiinflammatory drugs are administered in conjunction with patient-controlled analgesia (PCA). This double-blind study aimed to determine whether these effects could be obtained with a sustained-release ibuprofen formulation (Brufen Retard) given preoperatively, obviating the need for oral administration during the early postoperative period. We aimed also to determine whether the anticipated reduction in morphine requirements was associated with reduced opioid side effects. One hundred fifteen patients scheduled for lower abdominal gynecological surgery were randomly assigned to receive either sustained-release ibuprofen, 2 x 800 mg (n = 57), or placebo (n = 58) preoperatively and again 24 h after the first dose. Arterial oxyhemoglobin saturation (Spo2) was monitored preoperatively and for 24 h postoperatively. Patients were assessed every 4 h up to 24 h postoperatively. Those receiving ibuprofen reported significantly less pain at rest (P = 0.023) and less pain on movement, although the latter was not statistically significant (P = 0.051). Patients' opinions of the efficacy of their pain-relieving medication (P < 0.001) and quality of sleep (P = 0.036) favored ibuprofen. Morphine consumption was slightly but not significantly lower in the ibuprofen group (32 vs 38 mg/24 h, P = 0.096). Spo2 (P = 0.54), level of consciousness (P = 0.65), and number of antiemetic administrations (P = 0.15) did not differ significantly between groups. These results demonstrate improved efficacy with no increase in side effects when sustained-release ibuprofen is used as an adjunct to morphine PCA.

Adolescent↗

A comparison of variable-dose patient-controlled analgesia with fixed-dose patient-controlled analgesia.

We examined the effect on the quality of analgesia and side effects of increasing the patient control component of morphine patient-controlled analgesia (PCA) by offering the patient a choice of bolus dose sizes. Using a three-button hand piece, patients could choose between 0.5-, 1.0-, and 1.5-mg boluses of morphine (variable-dose PCA, VDPCA). Successful demands were delivered by a modified Graseby 3400 Anaesthesia Pump controlled by a Toshiba T1900 computer. This system was compared with conventional fixed-dose PCA (FDPCA) (1.0 mg of morphine) delivered by a Graseby 3300 PCA Pump. Both treatment groups had a 5-min lockout interval. Sixty patients were randomly assigned to receive either VDPCA or FDPCA after major abdominal gynecological surgery or hip or knee arthroplasty. Treatment groups did not differ in their duration of PCA therapy, total morphine consumption, or time spent with mild or severe oxyhemoglobin desaturation. There were no differences in their ease of controlling pain, satisfaction with pain control, experience of pain on movement, quality of sleep, severity of nausea, or incidence of vomiting. Although the more complex VDPCA technique provides adequate postoperative analgesia, it does not offer any advantage over conventional FDPCA.

Adult↗

Evaluation of the influence of movement on saturation readings from pulse oximeters.

This study aimed to develop a protocol for assessing the influence of movement on oxyhaemoglobin saturation readings from pulse oximeters. Thirty-six volunteers took part in the study. In each volunteer, each hand was monitored by both a Nellcor N200 oximeter using a disposable probe and by a Datex Satlite DS103 oximeter using a clip-on finger probe. Volunteers made five standardised movements during which output was recorded from all four oximeters. All movements were associated with apparent decreases in oxyhaemoglobin saturation which were statistically significant for two movements with the Nellcor equipment and for four movements with the Datex equipment. Movement was associated with increases in the magnitude of pulse amplitude, but this was not quantitatively associated with magnitude of artefactual changes in saturation. Use of this standardised movement protocol allows quantification of movement artefact from pulse oximeters and should facilitate the development of equipment less affected by movement.

Adolescent↗

A double-blind randomized controlled trial of ginger for the prevention of postoperative nausea and vomiting.

The efficacy of ginger for the prevention of postoperative nausea and vomiting was studied in a double-blind, randomized, controlled trial in 108 ASA 1 or 2 patients undergoing gynaecological laparoscopic surgery under general anaesthesia. Patients received oral placebo, ginger BP 0.5g or ginger BP 1.0g, all with oral diazepam premedication, one hour prior to surgery. Patients were assessed at three hours postoperatively. The incidence of nausea and vomiting increased slightly but nonsignificantly with increasing dose of ginger. The incidence of moderate or severe nausea was 22, 33 and 36%, while the incidence of vomiting was 17, 14 and 31% in groups receiving 0, 0.5 and 1.0g ginger, respectively (odds ratio per 0.5g ginger 1.39 for nausea and 1.55 for vomiting). These results were essentially unchanged when adjustment was made for concomitant risk factors. We conclude that ginger BP in doses of 0.5 or 1.0 gram is ineffective in reducing the incidence of postoperative nausea and vomiting.

Adjuvants, Anesthesia↗

The dynamic calibration of cycle ergometers.

The components of our rig, which is used for the dynamic calibration of cycle ergometers, were purchased for $4,080 (USA); interfacing the instrument with a computer and printer increased the cost by an additional $2,550 (USA). The rig is essentially a torque balance and was therefore validated against the primary measurements of: angular velocity (rev.min-1), distance (m) and mass (kg). Summing the inaccuracies associated with these 3 measurements yields a worst case error of only 0.3%. The coefficients of variation for a dynamic calibration rig and mechanically braked Monark cycle ergometer assembly ranged from 0.6 to 3.2% for 6 trials at each of the following power outputs: 117.7, 176.6, 235.4, 294.3 and 353.2 W. The instrument therefore has a high degree of precision.

Calibration↗

Epinephrine infusion in sheep: systemic and renal hemodynamic effects.

OBJECTIVE: To evaluate the dose-response effects of graded epinephrine infusions on systemic and renal hemodynamics. DESIGN: Prospective, dose-response study. SETTING: Laboratory at a university hospital. SUBJECTS: Thirteen conscious, chronically catheterized, adult merino sheep. INTERVENTIONS: Ten sheep received five infusions of epinephrine (5, 10, 20, and 40 micrograms/min; the 40-micrograms/min dose was repeated) and a placebo (saline) on separate days (at least 1 day apart). Each drug infusion was administered for 4 hrs on separate days after a 90-min baseline was established. Plasma catecholamine values and renin activity were measured in an additional three sheep infused with 40 micrograms/min epinephrine. MEASUREMENTS AND MAIN RESULTS: Renal blood flow was measured, using an electromagnetic flow transducer; these data, along with aortic and pulmonary arterial pressure, were continuously recorded after analog-to-digital conversion. Cardiac output was intermittently measured by thermodilution. Epinephrine resulted in a dose-dependent increase in mean arterial pressure (p < .001), and in cardiac output at 30, 60, and 120 mins after the start of the infusion. Concurrently, systemic vascular resistance was initially depressed below baseline, but then gradually increased during the 4-hr infusion period. Although a dose-dependent increase in renal vascular resistance was found, 5- and 10-micrograms/min of epinephrine failed to alter renal vascular resistance. However, 20- and 40-micrograms/min of epinephrine increased renal vascular resistance by 77% and 94% respectively, at 10 mins, but these values decreased to 17% and 16% of baseline by 120 mins. Consequently, an early dose-dependent decrease in renal blood flow was also time dependent, with renal blood flow increasing back to or above baseline at all studied infusion rates of epinephrine. CONCLUSIONS: Using a clinically relevant dose regimen, epinephrine increased mean arterial pressure and cardiac output. Renal blood flow decreased transiently, but returned to baseline within 30 to 60 mins.

Analysis of Variance↗

Dose-response relationships in hepatic injury produced by alcohol and carbon tetrachloride.

Dose-response relationships were examined for the production of hepatic fibrosis and cirrhosis by combined exposure of male Porton rats to alcohol and carbon tetrachloride. Alcohol was administered orally in Lieber-DeCarli liquid diet at levels of 75, 150, or 300 kcal/liter, giving mean daily intakes of 2.29, 4.61, and 8.16 g/kg/day, respectively. Carbon tetrachloride was administered by inhalation at concentrations of 10, 20, or 40 ppm, 6 hr/night, 5 nights/week. Liver biopsies were taken at intervals up to a maximum treatment period of 20 weeks. All four rats that received the high dose of both agents, and 1 of 4 that received the medium alcohol and high carbon tetrachloride treatments, were cirrhotic by 10 weeks. Two of the 4 rats that received the low alcohol and high carbon tetrachloride dose were cirrhotic at 20 weeks. Cirrhosis was not observed in rats that received the low or medium carbon tetrachloride dose, but some degree of hepatic fibrosis was observed in all treatment groups. Severity of fibrosis was significantly associated with both dose of alcohol and dose of carbon tetrachloride received. It is concluded that, in the alcohol-carbon tetrachloride rat model for chronic liver injury, both alcohol and carbon tetrachloride contribute to the response in a dose-related manner. Hepatic injury was observed even when relatively low doses of these agents are administered together.

Alcohol Drinking↗

In-circuit analysers.

Explore the source record for details and available documents.

Anesthesia, Closed-Circuit↗

Changes in oxygen saturation in the 72 hours after hip surgery: the effect of oxygen therapy.

The aim of this study was to investigate changes in oxygen saturation (SpO2) occurring during the three days following hip surgery in patients in this hospital and to determine to what extent SpO2 might be improved by oxygen therapy for 24 or 72 hours. Eighty-three patients (aged 43-96 years) scheduled for elective total hip replacement or emergency surgery for hip fractures were studied. Forty-four patients had 24 hour postoperative oxygen prescribed by their anaesthetist or surgeon; we randomized these to either continue oxygen for a total of three days (Group 1) or to discontinue oxygen after Day 1 (Group 2). Patients not prescribed oxygen by the surgeon or anaesthetist (n = 39) were randomly assigned either to receive oxygen for three days (Group 3) or not to receive oxygen (Group 4). Oxygen was administered through nasal cannulae at a flow of 2 l.min-1. SpO2 was measured every 10 seconds for three days and stored on computer disc. Percentage of time spent with SpO2 below 90% was used as an index of desaturation. Patients receiving oxygen had significantly improved SpO2. In patients not receiving oxygen, desaturation was most severe on Days 1 and 2, improving somewhat on Day 3. On Day 2 desaturation was similar in Groups 2 and 4. When oxygen was not being administered males were significantly more desaturated than females. Our investigations indicate that following hip surgery poor saturation continues for at least two days and can be improved by oxygen therapy.

Adult↗

Evaluation of five small turbine-type respirometers used in adult anesthesia.

OBJECTIVE: The purpose of this study was to determine the accuracy of five rotating vane or turbine-type respirometers--fdE Magtrak Respiratory Monitor, fdE Haloscale Standard Wright Respirometer, Micro-Medical Pocket Monitor II, and Ohmeda 5400 and 5410 Volume Monitors--which are marketed as suitable for measuring expired gas volume in anesthetized adult patients. METHODS: The devices were tested for accuracy at simulated minute ventilations ranging from 2.4 to 15 L/min with three gas mixtures: air, air saturated with water vapor, and N2O/O2 (70:30). RESULTS: In the usual range for adult minute ventilation during general anesthesia with intermittent positive-pressure ventilation (5-12 L/min), all devices were on average accurate to within 12%. At the lowest minute volume readings (2.4 L/min) all devices except the Pocket Monitor tended to have low readings. No significant differences in readings were introduced by either saturation with water vapor or introduction of 70% N2O, except with ventilation below 4 L/min with both Ohmeda respirometers. CONCLUSIONS: All monitors showed reasonable clinical accuracy in the usual adult minute ventilation range during general anesthesia with intermittent positive-pressure ventilation (> 5 L/min) when used to measure air, water vapor-saturated air, or N2O/O2 mixtures.

Adult↗