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Biomedical subjects

L R Smith

Publications and source records attributed to L R Smith.

At least 145 records · Page 8Linked to original sources

A Cytophaga species endotoxin as a putative agent of occupation-related lung disease.

A previous study suggested that a biologically active bacterial endotoxin was a putative agent of lung disease in a textile-producing facility. The endotoxin was isolated from the biomass growing in a chilled-water spray air humidification system. The bacterial flora of the air humidification system were isolated and taxonomically identified to the genus level. By using indirect immunofluorescence assays, a serologically reactive Cytophaga species was identified. A serologically reactive, biologically active (Limulus assay) endotoxin was purified from phenol extracts of the Cytophaga species. The endotoxin contained sugars, hexosamines, and lipids identical to those found in the humidifier biomass endotoxin. All subjects with biopsy-proven and suspected lung disease had antibodies directed toward the purified Cytophaga endotoxin. The data suggest that the Cytophaga endotoxin is the putative agent of lung disease in the textile facility.

Bacterial Infections↗

Clearance of 9-micron spheres and rubidium in the intestinal circulation.

Rubidium clearance and 9-micron-sphere entrapment were studied and compared in isolated intestinal preparations under various physiological conditions in 10 dogs anesthetized with intravenous pentobarbital sodium. The chosen intestinal segment was pumped with aortic blood at a constant rate and pressure of about 90-100 mmHg. The temperature of the isolated loop was maintained at 37-38 degrees C with an electrical pad. A mixture of 86Rb and 9-micron-spheres labeled with 141Ce was injected into the arterial cannula supplying the intestinal loop while mesenteric venous blood was collected for activity counting. Three to four intestinal segments were used from each dog. The following three experimental conditions were randomly used for each intestinal segment preparation: 1) a mesenteric venous pressure (MVP) equaling 0 cmH2O and warmed normal saline infused into the lumen of segment; 2) an MVP equaling 0 cmH2O and 5% glucose in saline infused into the intestinal lumen; and 3) the reservoir with venous blood elevated to provide an MVP equaling 17 cmH2O and warmed normal saline infused into the intestinal lumen. A very strong and significant correlation was found between rubidium and microsphere clearances (r = 0.99, P less than 0.0001). Rubidium extraction was inversely associated with blood flow through the intestinal segment (r = 0.49, P = 0.02), while microsphere entrapment (extraction) was independent from intestinal blood flow (r = 0.16). The data suggest that the shunting of 9-micron spheres through tissue reflects the arteriovenous shunting of blood and, therefore, can be used as a tool to study the nutritive and nonnutritive blood flows in tissues.

Animals↗

A randomized comparison of crystalloid and blood-containing cardioplegic solutions in 60 patients.

To determine whether adding blood to a cardioplegic solution affects myocardial preservation, a randomized prospective study was carried out in 60 patients undergoing coronary revascularization to compare the effects of crystalloid potassium cardioplegics (group C) and potassium cardioplegic solutions to which blood has been added (group B) on markers of myocardial metabolism (lactate, inorganic phosphate, base deficit release, glucose and lactate uptake, oxygen extraction), myocardial damage (creatine kinase [CK]-MB levels), and cardiac performance (cardiac index and left atrial pressure). The solution with added blood had a significantly (p less than .05) greater oxygen content, a lower pH, and higher concentrations of potassium, calcium, sodium, and glucose. In group B patients there was a suggestion (p less than .06) of greater uptake of oxygen during the beginning of the initial cardioplegic infusion. During reperfusion there was no evidence of differential release of the metabolites of anaerobiosis and myocardial oxygen extraction and glucose and lactate uptake were similarly depressed in both groups. Likewise, CK-MB release after bypass was the same in both groups. Prompt, adequate functional recovery of cardiac index and left atrial pressure was observed in both groups. It was concluded that although there may be more oxygen available from the blood-containing solution during early infusion, there is no evidence that under the conditions of this investigation adding blood to cardioplegic solution improves myocardial preservation.

Blood↗

Additive negative inotropic effect of a combination of diazepam and fentanyl.

Hearts were excised from 30 male Sprague-Dawley rats and perfused in a modified Langendorff system to examine the interactions of fentanyl and diazepam on myocardial contractility as measured by left ventricular dP/dtmax. Various concentrations of fentanyl and diazepam were added to the nonrecirculating 37 degrees C perfusate to determine ED25 and ED50 for depression of dP/dtmax. Combinations of fentanyl and diazepam at a fixed negative inotropic potency ratio of 1:1 were used to determine the ED25 and ED50 of this combination. Isobolographic analyses performed at ED25 and ED50 revealed that the negative inotropic interaction of fentanyl and diazepam is purely additive. It is unlikely that a supraadditive negative inotropic effect can explain the supraadditive hemodynamic depression reported in humans when diazepam and fentanyl are combined; perhaps systemic vascular effects of this drug combination account for the clinical drug interactions.

Animals↗

Regional blood flow during isoflurane and halothane anesthesia.

Cardiac output distribution and regional blood flow in 18 dogs during isoflurane and halothane anesthesia were studied in dose-related fashion. Surgical preparation consisted of left thoracotomy and placement of catheters in the left atrium and aorta through a femoral artery. Regional blood flow was studied one week after surgical preparation using a microsphere technique at the three stages: awake, 1 MAC, and 2 MAC of inhalation anesthesia. At each stage of the experiment, two sets of microspheres (15- and 9-micron diameter), labeled with different isotopes, were used simultaneously. Both anesthetics increased cerebral blood flow, decreased blood flow through preportal area, and preserved renal blood flow. Isoflurane increased hepatic artery blood flow at both levels of anesthesia, while halothane preserved the flow during 1 MAC and decreased it at 2 MAC. Apparently, isoflurane provided better oxygenation to the liver than halothane. Myocardial blood flow was increased during isoflurane (despite decrease in blood pressure and cardiac output) and decreased during halothane anesthesia. Isoflurane appears to be a coronary vasodilator with potential beneficial (improvement in myocardial blood supply) as well as hazardous ("steal effect") effects on the heart.

Animals↗

Scorpion sting producing severe muscular paralysis. A case report.

A case of scorpion (Parabuthus species) envenomation causing severe respiratory failure is presented. Systemic effects, which included muscular weakness, hypertonus and bulbar dysfunction, developed 8 hours after poisoning; this emphasizes the importance of close observation of victims of envenomation. Treatment included the administration of scorpion antivenom (SAIMR) and mechanical ventilation for 4 days.

Adolescent↗

Assessment of anaesthetic action of morphine and fentanyl in rats.

In 150 Sprague-Dawley rats, morphine and fentanyl dose-effect curves were determined for the following three end points--prevention of purposeful movement response to a noxious stimulus (PM), loss of righting reflex (RR), and prevention of heart rate increase to a noxious stimulus (HR). Accordingly, for each agent, three series of experiments were performed with intravenous administration of the following doses: morphine--3-10 mg X kg-1 for PM, 3-10 mg X kg-1 for HR, 35-55 mg X kg-1 for RR; fentanyl - 5-15 micrograms X kg-1 for PM, 18-30 micrograms X kg-1 for RR, 200-400 micrograms X kg-1 for HR. Dose-effect curves were calculated with the use of probit procedure and potency ratios were determined on the bases of ED50 values. It was found that potency ratios of morphine and fentanyl are different for the studied end points. The ratios of RR ED50 to PM ED50 were 7.8 for morphine vs 2.4 for fentanyl (p less than 0.001), the ratios of HR ED50 to PM ED50 were 1 and 33, respectively (p less than 0.001). These results suggest that blockade of movement response to noxious stimulation (which is usually regarded as an index for analgesic action of opioids) and blockade of heart rate increase to noxious stimulation (which is one of the goals of anaesthesia) is not necessarily induced by intravenous narcotic anaesthetics through the same mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Intravenous↗

Anesthetic potencies of isoflurane, halothane, and diethyl ether for various end points of anesthesia.

In experiments with rats, the authors compared potency ratios and slopes of dose-effect curves of isoflurane, halothane, and diethyl ether for three end points of anesthesia: loss of righting reflex (RR), abolition of purposeful movement (PM) response to painful stimuli, and abolition of heart rate (HR) response to painful stimuli. Determinations of potency were based on the direct measurement of brain concentrations of anesthetics with the use of gas chromatography. It was found that the ratio of the PM ED50 to RR ED50 was 2.41 for isoflurane, 1.74 for halothane, and 1.25 for diethyl ester. They were significantly different for all three agents. Differences between the slopes of the dose-effect curves for RR and PM were significant only with diethyl ether (7 vs. 28). The ratios of HR ED50 to PM ED50 were not significantly different for the studied agents and there were no differences found between the slopes of the dose-effect curves for PM and HR. The results suggest that heart rate response to a noxious stimuli in contrast to the righting reflex is depressed by inhalation anesthetics through a mechanism similar to that underlying the depression of purposeful movement response to a noxious stimuli. Heart rate response to a noxious stimuli might be used as an alternative index for the measurement of anesthetic potency.

Anesthetics↗

Comparison of isoflurane and halothane safety margins in rats.

In rat experiments, the dose-effect curves for three different end points of anesthesia [loss of righting reflex (RR), prevention of movement (PM), and heart rate response (HR) to noxious stimuli] and for the lethal effect (LE) due to cardiovascular depression were determined with isoflurane and halothane. The obtained data were used to calculate LD50/ED50 ratios and standard safety margins (SSM) for assessment of each agent's safety. It was found that isoflurane provides an equal degree of separation between dose-effect curves for different end points of anesthesia as halothane does. However, isoflurane provides greater margins of safety. The margin between the highest of anesthetic doses--the loss of HR response--and the lethal dose for isoflurane was twice that for halothane (LD50/HR ED50 4.3 vs. 2.2, P less than 0.01). The standard safety margin for the loss of HR response was also greater with isoflurane (142 vs. 43, P less than 0.05). These results agreed that isoflurane may provide greater cardiovascular safety for anesthesia than halothane does.

Anesthesia, Inhalation↗

The pharmacokinetics of midazolam in chronic renal failure patients.

Fifteen patients with chronic renal failure (CRF) were given midazolam 0.2 mg/kg iv over 15 s. All but one lost consciousness in a time ranging from 22-100 s (mean +/- SD was 55 +/- 26 s) after drug administration. Patients regained consciousness from 6-105 min (mean 53 +/- 32) after drug administration. The calculated mean plasma level of midazolam at arousal was 81 +/- 47 ng/ml. Pharmacokinetics parameters were determined from midazolam plasma levels measured in 16 consecutive venous blood samples. The pharmacokinetic parameters in CRF patients were compared with those of healthy volunteers matched for age, sex, and body size with the CRF patients. Protein binding was determined by equilibrium dialysis. CRF patients had a significantly higher (P less than 0.005) plasma-free drug fraction (6.5% +/- 0.7) compared with the control patients (3.9% +/- 0.1). Total (bound plus unbound) kinetics differed in the two groups: volume of distribution 3.8 +/- .3 1/kg in CRF patients versus 2.2 +/- .2 1/kg in controls (P less than 0.001), and clearance 11.4 +/- 1.6 ml X min-1 X kg-1 in CRF patients versus 6.7 +/- 0.9 ml X min-1 X kg-1 in controls (P less than 0.02). When kinetic parameters were corrected for protein binding, CRF patients unbound volume of distribution (63.5 +/- 6.8 1/kg) and free drug clearance (189 +/- 29 ml X min-1 X kg-1) were not different from the control group's volume of distribution (55.6 +/- 5.7 1/kg) and free drug clearance (176 +/- 24 ml X min-1 X kg-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effects of volatile anesthetics on myocardial oxidation-reduction status assessed by NADH fluorometry.

In experiments on isolated rat heart perfused by the Langendorff method, the effect of halothane, isoflurane, enflurane, and diethyl ether on myocardial oxidation-reduction status was evaluated with reduced nicotinamide adenine dinucleotide (NADH) fluorometry. All inhaled anesthetics studied caused a dose-dependent increase in NADH fluorescence. Concentrations of anesthetics necessary to produce 10% of the maximal increase in NADH fluorescence caused by anoxia were 1.1% for halothane, 1.6% for isoflurane, 2.6% for enflurane, and 6.8% for diethyl ether (all concentrations are different from each other at P less than 0.05 level, n = 24). These findings indicate that the order of potency with regard to the effect of the agent on NADH paralleled their potencies as general anesthetics. The deterioration in myocardial oxidation-reduction status probably is related to the ability of the anesthetic agents to inhibit the electron transport chain in mitochondria.

Anesthetics↗

Human excretion patterns following occupational uptake of 3H-, 14C- and 35S-labeled compounds.

Graphs of excretion patterns following occupational uptake of 3H, 14C and 35S labeled compounds in humans are presented. A brief description of New England Nuclear's bioassay program and analytical methods is given. One or two exponential regression curves are found to fit most sets of data. Exceptions where exponentials do not closely fit the data are discussed. Characteristic rate constants are estimated and used to establish retention equations. When groups of workers were exposed to the same source excretion parameters were not found to strongly correlate with weight or sex. Variations in individual excretion patterns following low level group exposure did not significantly effect individual dose commitment estimates. Excretion rates following uptake of 14C and 3H labeled compounds were found to span three orders of magnitude. This indicates that health physicists may tend to dissipate resources in unnecessary investigations if conservative ICRP recommendations are assumed.

Body Weight↗

Intake and subsequent fate of a ceramic particle containing 2.85 microCi 241Am: a case study.

Intake of 241Am was reported in a young female technologist. External monitoring, whole body counting, urinalysis and fecal analysis were performed to determine the subsequent fate of the contaminant. Five days later, more than 99.5% of the radioactivity was voided in a fecal sample. A single particle, containing 2.85 microCi of 241AmO2 incorporated in a ceramic matrix, was isolated from the fecal sample. Brief descriptions of the radioanalytical results and dosimetry implications are presented. A shadow shield whole body counter was conveniently used to make an early estimate of the intake. This initial estimate enabled staff to decide that it was not necessary to artifically remove the contaminant. It was estimated that the lower large intestine was the organ which received the highest dose due to the passage of the ceramic particle. Systemic uptake of 241Am was indicated by urinalysis. The fractional transfer of 241Am from the GI tract to the blood was estimated to be less than 6 X 10(-5). This maximum estimate is limited by the MDA of the analytical procedures used. The fractional transfer of the 241Am from the GI tract to blood in this case is about an order of magnitude less than recent ICRP recommendations for "all compounds of americium".

Accidents, Occupational↗

Hemodynamic responses to nifedipine in dogs anesthetized with halothane.

The interaction of nifedipine and halothane was examined in 19 dogs. Nifedipine (10 micrograms/kg) was infused over 2 min in animals anesthetized with either 1% or 2% halothane. The predominant hemodynamic effect of nifedipine was a short-lived reduction (less than 15 min) in mean blood pressure accompanied by a decrease in systemic vascular resistance. During 2% halothane anesthesia hypotension mean blood pressure was greater (P less than 0.05) 15 and 30 min after nifedipine than during 1% halothane. Nifedipine hypotension was initially (2 min) associated with a 23% increase in heart rate and a 22% increase in cardiac output in animals anesthetized with 1% halothane, but during 2% halothane there was no change in heart rate. Changes in dP/dt and contractile force were minimal after nifedipine in both groups. The clinical implications of this study are that nifedipine given during halothane anesthesia may be associated with significant hypotension and that higher concentrations of halothane attenuate the reflex compensatory increase in heart rate. Doses of halothane and nifedipine must be chosen cautiously when the drugs are used together.

Anesthesia, Inhalation↗

Regional blood flow during cross-clamping of the thoracic aorta and infusion of sodium nitroprusside.

Labeled microspheres, 15 microns in diameter, were used to determine cardiac output and regional blood flow response to cross-clamping of the midthoracic aorta and subsequent sodium nitroprusside (SNP) infusion in 11 dogs. During aortic cross-clamping, mean arterial pressure above the occlusion (MAPa) increased 30% to 35%, mean arterial pressure below the occlusion (MAPb) decreased 87%, cardiac index decreased 12% to 14%, left atrial pressure (LAP) doubled, and renal and spinal cord (lower part) blood flows decreased substantially (85% to 94%). SNP infusion returned MAPa to baseline values, decreased MAPb by half, and substantially and further decreased renal blood flow (to 3% to 5% of baseline values). Myocardial and cerebral blood flows increased substantially (up to 250% to 400%). An increase in preload (fluid load) was accompanied by an increase in LAP, cardiac index, and myocardial blood flow only but not in renal or spinal cord flow. There was a strong association between cortical renal blood flow and MAPb (r2 = 0.92; p less than 0.0001), which suggests that blood flow through organs and tissues below the occlusion is pressure dependent. The data show that SNP infusion during thoracic aortic cross-clamping improves systemic and regional circulation above the occlusion but decreases MAPb and therefore blood flow below the occlusion. SNP infusion should be used with caution during aortic cross-clamping, since arterial hypotension of any degree may be deleterious to organs below the cross-clamp.

Animals↗