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Biomedical subjects

R L Nelson

Publications and source records attributed to R L Nelson.

At least 163 records · Page 9Linked to original sources

Rectilinear thyroid scanning as a predictor of malignancy.

Rectilinear scan findings were correlated with the surgically documented size, location, and histology of thyroid carcinoma in 67 patients. At the site of the carcinoma, 36 (54%) had hypofunction, associated with a palpable abnormality in all but one patient; 16 (24%) had an abnormality on palpation but not on scanning; 11 (16%) had both a normal clinical examination and a normal scan, associated with a benign abnormality in another part of the thyroid; and four (6%) had a patchy uptake. A literature review established that use of the gamma camera with pinhole collimator does not increase the specificity of carcinoma predictability, despite the enhanced sensitivity. The scan may still be used in evaluating the clinically solitary nodule that is not obviously malignant. However, unless that module is hyperfunctioning, clinical criteria rather than appearance of the scan should contribute most to the decision of whether to treat surgically.

Diagnostic Errors↗

Quantitation of blood flow after anterior maxillary osteotomy: investigation of three surgical approaches.

The radioactive microsphere method was used to quantitate preoperative and postoperative blood flows in macaque monkeys when three different surgical approaches for anterior maxillary osteotomy were performed. Despite distinct variations in flap designs among the experimental groups, preoperative and postoperative determinations of blood flow were essentially unchanged. Results of the study suggest that a palatal, labial, or combined mucoperiosteal pedicle should be adequate to preserve the flow of blood to tissues in the osteotomized segment.

Animals↗

Optimizing myocardial supply/demand balance with alpha-adrenergic drugs during cardiopulmonary resuscitation.

In 14 dogs the determinants of myocardial blood supply and metabolic demands were assessed during cardiopulmonary resuscitation (CPR) and under steady-state conditions in fibrillating hearts on cardiopulmonary bypass. During open chest cardiac massage (nine dogs), coronary diastolic blood pressure and blood flow were low. Vasopressor infusion (methoxamine or epinephrine) raised diastolic pressure from 33 +/- 3 to 55 +/- 3 mm. Hg and increased coronary blood flow (CBF) 124 percent (from 38 +/- 3 to 85 +/- 11 c.c. per 100 Gm. per minute. Comparison of these drugs in fibrillating hearts on cardiopulmonary bypass showed that epinephrine increased the "vigor of fibrillation" (intraventricular balloon pressure rose 24 percent and oxygen uptake increased 42%) but impeded subendocardial flow 53% (endocardial/epicardial flow ratio fell from 0.79 to 0.48). In contrast, methoxamine did not significantly change intraventricular balloon pressure, oxygen uptake, coronary flow, or its distribution. We conclude that augmentation of diastolic pressure with alpha adrenergic drugs during CPR improves coronary perfusion and that inotropic drugs may worsen myocardial ischemia during CPR by raising oxygen demands while simultaneously impeding subendocardial blood supply.

Animals↗

Isolation of osteoclasts by velocity sedimentation at unit gravity.

A method is presented for separating osteoclasts from the heterogeneous population of bone and marrow cells. Cell suspensions were prepared from femora of young rabbits by mechanical dispersion. The starting cell suspension typically contained only 1.0% +/- 0.5 osteoclasts. Following an initial 45 min of unit gravity sedimentation in a lucite chamber osteoclasts were primarily distributed in fractions 2-5. A second 45-min sedimentation of these pooled fractions yielded cell suspensions containing greater than 30% osteoclasts (as much as a 50-fold increase over starting percentages). Linear scan analysis, however, revealed that osteoclasts accounted for 73.14% +/- 0.58 of the cell colume. Subsequent in vitro experiments demonstrated linear incorporation of 3H-leucine into TCA precipitable protein for cells comprising the osteoclast fraction. Concomitant radioautographs revealed radioactive label in isolated osteoclasts.

Animals↗

Detection after electrophoresis of enzymes involved in ammonia metabolism using L-glutamate dehydrogenase as a linking enzyme.

The use of L-glutamate dehydrogenase (GLUD) as a reagent in staining mixtures to detect the isozymes of enzymes which catalyze the production of ammonia has been investigated. Methods have been devised for the electrophoresis and detection, using GLUD, of seven enzymes: cytidine deaminase, adenosine deaminase, adenosine monophosphate deaminase, arginase, argininosuccinase, D-amino acid oxidase, and D-aspartate oxidase. GLUD-linked staining methods appear to be sensitive, specific, and of general application.

AMP Deaminase↗

Effects of conventional hypothermic ischemic arrest and pharmacological arrest on myocardial supply/demand balance during aortic cross-clamping.

Aortic cross-clamping may produce ischemic damage due to a discrepancy between supply and demand. Supply is determined by noncoronary collateral flow and substrate stores, and demand by electromechanical activity, wall tension, and temperature. The effects of 60 minutes of conventional hypothermic ischemic arrest were compared to those of pharmacological arrest. Noncoronary collateral blood supply was comparable in both groups during cross-clamping. With ischemic arest, mechanical activity and endocardial electrical activity persisted and wall tension fell progressively. With pharmacological arrest, electromechanical activity stopped in less than 1 minute but returned (with increased wall tension) nearly 1 hour. Thirty minutes following reperfusion, coronary flow was redistributed away from subendocardium after ischemic arrest and toward endocardium after pharmacological arrest. Myocardial performance was depressed severely after conventional arrest and only mildy after pharmacological arrest. We conclude that aortic cross-clamping is safer with pharmacological arrest than with ischemic arrest. The cardioplegic solution modifies the supply/demand balance favorably, but it is washed out by noncoronary collateral blood supply.

Animals↗

Painless thyroiditis and transient hyperthyroidism without goiter.

Eight women had painless thyroiditis, transient thyrotoxicosis, and low radioactive iodine uptakes but were without goiter; they constituted 15% of all thyrotoxicosis cases that we saw during the past year. Standard antithyroid antibody tests by tanned erythrocyte hemagglutination, complement fixation, and colloid and microsomal fluorescence, if present initally, were only weakly psotivie and became negative by 9 months. However, human antithyroglobulin antibody levels by a sensitive radioimmunoassay were elevated initially in all patients. In general, these radioimmunoassayable antibody levels fell, but they had not returned to normal by 9 months. Serial thyroid function tests and standard antithyroid antibody tests were most compatible with subactue thyroidtis. However, the persistence of radioimmunoassayable antithyroblobulin antibodies and recent reports of histologic evidence of lymphocyte thyroiditis in similar patients with goiter leaves open the possibility that this is a previously unrecognized presentation of chronic lymphocytic thyroiditis. Neither the cause nor the ultimate course of this syndrome is known.

Adult↗

Quantitation of blood flow after Le Fort I osteotomy.

Le Fort I maxillary osteotomies were performed on ten macaque monkeys. The particle distribution method (nondiffusible radioactive microspheres) was used to quantitate local blood flow before and after surgery. Significant reduction in blood flow to the osteotomized maxillary segment was noted in those animals (group S) where the descending palatine vessels were transected. Those animals in which the vascular pedicle was intact (group I) showed decreased blood flow to the attached gingiva and alveolar bone, but palatal tissue blood flow was unchanged or increased. The results reinforce the precept of the importance of maintaining an adequate nutrient pedicle when performing orthognathic surgical procedures.

Alveolar Process↗

Blood flow changes after sagittal split of the mandibular ramus.

Blood flows to various cephalic tissues were determined by the microsphere method before and after unilateral sagittal split of the mandible in macaque monkeys. Significant blood flow decreases were found in certain bony regions of the osteotomized mandible while blood flow to the masseter and medial pterygoid muscles on theosteotomized side was significantly increased. Judicious stripping of the mucoperiosteum and pterygomassteric sling may be an important consideration when planning the sagittal split approach to correct certain mandibular anomalies.

Animals↗

Studies of the effects of hypothermia on regional myocardial blood flow and metabolism during cardiopulmonary bypass. I. The adequately perfused beating, fibrillating, and arrested heart.

The effects of hypothermia (32 degrees, 28 degrees, and 22 degrees C.) on left ventricular flow distribution (microspheres) and oxygen uptake in adequately perfused, beating, empty, fibrillating, and arrested hearts were studied. Minute left ventricular oxygen uptake fell progressively as myocardial temperature was reduced under all conditions. In beating hearts, however, left ventricular oxygen uptake per beat increased significantly due to the inotropic effect of hypothermia and diastolic compliance fell. Cold fibrillating hearts consumed slightly less oxygen per minute than beating hearts at comparable temperatures as fibrillation became less forceful with hypothermia. Myocardial wall tension, however, was always higher in fibrillating than beating hearts at each level of hypothermia. The lowest myocardial oxygen requirements were always found in arrested hearts (70 to 80 per cent less than either beating empty or fibrillating hearts) at any myocardial temperature. Left ventricular coronary flow remained distributed evenly across the beating heart at all myocardial temperatures and in fibrillating hearts at 28 degrees, and 22 degrees C. Left ventricular flow became redistributed toward the subendocardium in fibrillating hearts at 37 degreegs and 32 degrees C. and in arrested hearts at all myocardial temperatures.

Animals↗

Studies of the effects of hypothermia on regional myocardial blood flow and metabolism during cardiopulmonary bypass. V. Profound topical hypothermia during ischemia in arrested hearts.

This study compares the effects of 60 minutes of ischemic arrest with profound topical hypothermia (10 dogs) on myocardial (1) blood flow and distribution (microspheres), (2) metabolism (oxygen and lactate), (3) water content (wet to dry weights), (4) compliance (intraventricular balloon), and (5) performance (isovolumetric function curves) with 180 minutes of cardiopulmonary bypass with the heart in the beating empty state (seven dogs). Studies performed before and 30 minutes after 1 hour of ischemic arrest with profound topical hypothermia showed: (1) total left ventricular blood flow increased 50 per cent but became redistributed away from the subendocardium (endocardial/epicardial flow ratio fell from 1.13 to 0.77,(2) left ventricular oxygen consumption fell 30 per cent while left ventricular oxygen extraction fell from 51 to 29 per cent; (3) lactate extraction fell from 15 to 4 per cent (two dogs produced lactate); (4) left ventricular endocardial (papillary muscle) water content rose 2.4 per cent; (5) left ventricular compliance decreased from 1.68 to 1.01 ml. H2O/mm. Hg (at 25 ml.); (6) left ventricular performance was depressed 49 per cent below control values. In contrast, 3 hours of cardiopulmonary bypass in the beating empty heart produced only minimal changes in these variables.

Animals↗

Pharmacokinetics of divided-dose ifosfamide.

The pharmacokinetics of a divided-dose schedule of ifosfamide was investigated in 3 patients given 1, 600 to 2,400 mg/sq m/day for 3 days, with a second course of treatment 21 days later. In contrast to the biexponential decay seen with single-dose ifosfamide (5,000 mg/sq m), data for divided low-dose plasma ifosfamide are best fitted by a monoexponential decay function compatible with a one-compartment open model. Plasma half-life for ifosfamide given in the divided-dose schedule was 6.9 hr, less than half that previously reported for high single-dose ifosfamide. Renal excretion rates and clearances for unchanged drug were similar in both schedules. The proportion of drug metabolized was larger and amount of unchanged drug excreted in the urine was smaller than after single large doses. The elimination constant for unchanged ifosfamide increased from day 1 to day 2 of treatment and remained relatively stable from day 2 to day 3 in the multidose regimen, with all parameters reverting to the pretreatment values 21days later.

Alkylating Agents↗

The utility of pharmacokinetics to the pharmaceutical industry.

Pharmacokinetic studies done early in the course of drug development can favorably influence the course of research by suggesting optimum dosage regimens, drug delivery methods, and fixed-ratio combinations and by alerting the clinical pharmacologist to potential problems. Pharmacokinetic data can be useful in the design of rational clinical drug research and thereby expedite clinical trials and save research costs. Thus, in addition to their value in the area of comparative bio-availability, pharmacokinetic studies carried out by the pharmaceutical industry are useful economically as well as scientifically.

Animals↗

Relation of mosquito density to bird: mammal feeding ratios of Culex tarsalis in stable traps.

Stable traps, each baited with a jackrabbit and either a chicken or a pheasant, collected more than 21,000 mosquitoes in the Sacramento Valley, California, in 1972 and 1973. The focus of interest was the feeding behavior of Culex tarsalis, a primary vector of encephalitis viruses. Generally, feeding success was less and feeding rates on the jackrabbit were greater when larger numbers of mosquitoes were collected, or when a bird was exposed that was less receptive to mosquito feeding. Greater feeding rates on the jackrabbit apparently resulted from decreased feeding on the avian host and from diversion of mosquitoes to the jackrabbit. Figures are given that show how changes in feeding rates on birds affect the probabilities that a mosquito that feeds twice would feel both times on a bird, or on a bird and then on a mammal. Relatively small collections of nine mosquito species other than C. tarsalis revealed distinct species differences in feeding behavior. Aedes malanimon showed a preference for jackrabbit, which is relevant to its role as a vector of western equine encephalitis and California encephalitis viruses.

Aedes↗