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Biomedical subjects

R W Anderson

Publications and source records attributed to R W Anderson.

At least 163 records · Page 9Linked to original sources
PubMed1982

Risk of handling injectable antineoplastic agents.

Uptake of mutagenic substances by persons handling injectable antineoplastic agents was studied, and various methods of preventing such exposure were evaluated. Six persons who prepared i.v. admixtures individually collected their urine in 24-hour batches during several eight-day study periods; each prepared from 12 to 90 admixtures per working day during each period. I.V. personnel prepared admixtures in both horizontal laminar-flow hoods and vertical-flow biological-safety cabinets, and using gloves and masks. Three pharmacy personnel who did not handle any drugs served as controls. Urine was concentrated (each 24-hour sample was concentrated to about 1 ml), and the Salmonella/mammalian microsome mutagenicity test (Ames test) was used to detect mutagenic activity in the urine concentrates. Mutagenicity was observed in the urine of all personnel during periods when they prepared antineoplastic admixtures in horizontal laminar-flow hoods, both when using no protection and while wearing gloves or masks. When admixtures were prepared in the vertical-flow biological safety cabinet by personnel wearing gloves, no urine mutagenicity was detected. The control group showed no urine mutagenicity. Protective intervention methods should be used by all persons handling antineoplastic agents. Guidelines for handling these drugs are presented.

Animals↗
PubMed1982

In vitro evaluation of hematopoiesis in mice treated with busulphan or nitrogen mustard.

Long term bone marrow cultures were established using combinations of untreated marrow and marrow treated with nitrogen mustard or busulphan in vivo. This study showed that 1) adherent cell layers, which morphologically resemble those derived from normal marrow, can be established from mice treated with busulphan or nitrogen mustard, 2) total cellularity in cultures containing a treated marrow is drastically reduced, 3) CFU-S content was slightly below control values in cultures of treated non-adherent cells on normal monolayers, and 4) CFU-S content was severely reduced when the monolayer was derived from drug-treated marrow. The usefulness of this long term culture system to study drug-induced modulation of hematopoiesis has been substantiated by this study.

Animals↗
PubMed1981

Effects of ischemia on left ventricular regional function in the conscious dog.

Three-dimensional regional geometry of the left ventricle was assessed in seven conscious trained dogs chronically implanted with pulse-transit ultrasonic-dimension transducers. Minor and major axis segment lengths and wall thickness were measured in the distribution of the left anterior descending coronary artery; transmural pressure (TMP) was measured with high-fidelity micromanometers. Data were recorded during the control state and following 30 s and 30 min of ischemia. Dimensions were normalized as a fractional extension from the length at zero TMP (Lo). Dynamic cube mass was calculated and remained constant throughout the cardiac cycle in both control and ischemic states, although the calculated mass decreased by an average of 5% during ischemia. The slope constants of the exponential diastolic pressure-dimension relationship increased following acute coronary occlusion indicating increases in regional myocardial stiffness with increasing periods of ischemia. Coronary occlusion also was associated with an increase in the Lo measurements in the major and minor axis dimensions and a decrease in the wall thickness Lo. These findings are consistent with an ischemia-induced plastic deformation of the regional myocardium defined as creep. Thus, acute ischemia results in a decline of regional systolic function, induces myocardial creep, and causes an immediate and sustained increase in regional myocardial stiffness.

Animals↗
PubMed1981

The deformational characteristics of the left ventricle in the conscious dog.

We studied left ventricular minor and major axis diameters and equatorial wall thickness in eleven conscious dogs with chronically implanted pulse-transit ultrasonic dimension transducers. Left ventricular transmural pressure was measured with micromanometers. Left ventricular volume was varied by inflation of implanted vena caval or aortic occluders. The geometry of the left ventricle was represented as a three-dimensioal ellipsoidal shell. Left ventricular eccentricity was found to be a linear function of ventricular volume during both diastole and ejection. However, the relationship was not the same for diastole and ejection, and during diastole the left ventricle was mre spherical at large volumes and more elliptical at small volumes than during ejection. The rearrangements in geometry observed during isovolumic contraction appeared to be transitional stages from the diastolic to the ejection-phase relationship. Thus, during isovolumic contraction, the left ventricle became more elliptical at large volumes and more spherical at small volumes. These relationships were not altered significantly by increased afterload or inotropic interventions. We also observed that the diastolic deformation of the ventricular chamber occurred in a set and predictable manner that seemed to be determined by the three-dimensional mechanical properties of the myocardium. The geometric inter-relationships of the ventricular wall determined the relationship between diastolic transmural pressure and mural stress. These findings probably reflect basic structural characteristics of the myocardium and provide a convenient method for quantitatively representing the dynamic geometry of the left ventricle.

Animals↗
PubMed1981

The diagnosis of postprandial hypoglycemia.

Our observation that hypoglycemia, often self-diagnosed by our patients, was seldom confirmed led the authors to establish norms for the glucose tolerance test. We first obtained values for 650 patients who were entirely free from symptoms before and during testing. The median nadir in this group was 64 mg/dl. Ten percent of the patients had plasma glucose nadirs of 47 mg/dl or below and 2.5% had values of 39 mg/dl or less. Utilizing these values in combination with clinical criteria, we confirmed hypoglycemia after glucose load in 16 (median nadir 39.5 mg/dl) of 118 patients presenting with this diagnosis, and only 5 of the 16 were hypoglycemic after their usual meals. The other 102 patients, whose many complaints were unrelated to measured plasma glucose levels, had nadirs similar to those of the control group. Placebo tests performed on 14 nonhypoglycemic patients provoked symptoms (recorded by the patients themselves) and they considered indicative of hypoglycemia. Some accepted other diagnoses after we demonstrated that their symptoms occurred when they were normoglycemic. Since nadirs of hypoglycemics and control subjects overlap, we conclude that accurate diagnosis of hypoglycemia requires that symptoms develop concurrently with low blood sugar and that they are absent at other times. Low plasma glucose must be considered only one of the criteria in diagnosing functional hypoglycemia along with a relationship between food intake, timing of symptoms, correlation of symptoms and low glucose levels, and reproducibility of test results.

Adolescent↗
PubMed1981

Postoperative hemodynamics in children with polytetrafluoroethylene shunts.

Twenty-two consecutive infants and children underwent aortopulmonary shunt operations with polytetrafluoroethylene grafts. Thirteen infants younger than 6 months of age (group I) received 14 grafts (4--5 mm in diameter, 0.5--2.5 cm long). Two shunts became obstructed, including kinking in the single 2.5-cm graft. Eight of the nine long-term survivors had pulmonary artery pressures measured a mean of 14 months postoperatively. In all infants, pulmonary resistance was normal and mean pulmonary artery pressure was less than or equal to 20 mm Hg, except in the infant with a 5-mm graft. In nine children 7 months to 15 years of age (group 2), the rate of graft occlusion was higher (five of nine). There was no evidence of pulmonary artery distortion secondary to shunt placement in either group. On late follow-up, blood hemoglobins were less than 20 g% as late as 30 months of age; acceptable palliation may be expected until at least 2 years of age and 12 kg in weight are reached. We conclude that short, 4-mm-diameter polytetrafluoroethylene grafts provide good palliation in infants with cyanotic congenital heart disease, with minimal risks from pulmonary hypertension or pulmonary artery distortion. Such grafts are less successful in older children, and should only be considered when other forms of surgical relief are not feasible.

Adolescent↗
PubMed1981

Evaluation of monolayer, liquid, gelfoam sponge and artificial capillary culture systems for the study of hematopoiesis.

This study evaluated the usefulness of a matrix culture system, the artificial capillary culture system, for the growth of hematopoietic cells, the maintenance of CFUS and the collection of GM-CSF. The system was compared to monolayer, gelfoam sponge and Dexter liquid cultures. Monolayer cultures of adherent lymphohematopoietic stromal cells were prepared from bone fragments, whole bone marrow (Dexter system), spleen, fetal liver and thymus preparations. Morphologically, all the adherent cell populations were similar and tended to accumulate macrophages. Despite these morphological similarities, the ability of bone marrow adherent cell monolayers to maintain CFUS early in the culture period was significantly greater than adherent cells from other sources. Low but significant levels of GM-CSF were detected by bioassay in the supernatants of all but bone marrow adherent cell cultures. However, adherent cells selected from whole marrow cultures by differential trypsinization contained bioassayable levels of CSF suggesting that Dexter cultures contain a supernatant inhibitor/inactivator of GM-CSF. The greatest capability of the artificial capillary culture system was to increase about 500-fold over monolayers the GM-CSF collected from bone fragment derived stromal cells. Unfortunately, CFUS maintenance was poor, the system was more expensive than monolayer cultures and in our hands, suffered many mechanical failures usually resulting in loss of sterility. Histological evaluation suggested there was inadequate matrix for optimal attachment and growth of lymphohematopoietic stromal cells. Even so this system has a much greater potential for development than gelfoam sponges. Overall, Dexter cultures appear to be the most useful system currently available for the study of hematopoiesis and hematopoietic regulatory interactions.

Animals↗
PubMed1981

Stability and compatibility of antitumor agents in glass and plastic containers.

The stability of methotrexate, fluorouracil, cytarabine, dactinomycin, doxorubicin, bleomycin sulfate, mitomycin, mithramycin, vincristine sulfate, vinblastine sulfate, cyclophosphamide, dacarbazine, carmustine, and leucovorin calcium in underfilled plastic and glass administration containers was determined. Drugs were reconstituted according to manufacturers' instructions and added to 5% dextrose injection 50 ml in both polyvinyl chloride bags and glass partial-fill bottles. In addition, mitomycin was added to 0.9% sodium chloride injection 50 ml in both polyvinyl chloride bags and glass partial-fill bottles. All admixtures were stored at room temperature, not protected from light. Stability was determined over 24 hours (48 hours for doxorubicin and fluorouracil) by high-pressure liquid chromatography, except for cyclophosphamide (analyzed by mass spectrometry) and carmustine (analyzed by spectrophotometry). Methotrexate, leucovorin calcium, cytarabine, dactinomycin, mithramycin, vinblastine sulfate, cyclophosphamide, and dacarbazine were equally stable (10% or less change in concentration over 24 hours) in glass and plastic containers. Doxorubicin and fluorouracil were more stable in plastic containers than glass containers. The T90 value for doxorubicin in glass was 40 hours; there was no apparent decrease in plastic even after 48 hours. The T90 value for fluorouracil in glass was seven hours and in plastic, 43 hours. Vincristine sulfate, bleomycin sulfate, and carmustine were more stable in glass than plastic. The T90 value for vincristine sulfate in plastic was 10 hours. The T90 value for bleomycin sulfate in plastic was 0.7 hour. The T90 value for carmustine in plastic was 0.6 hour. Mitomycin dissolved in 0.9% sodium chloride injection was more stable in plastic. Mitomycin dissolved in 5% dextrose injection was not stable. Carmustine and bleomycin sulfate should be administered only in glass containers. Continuous infusions of doxorubicin and fluorouracil are more completely delivered from plastic containers. Mitomycin should not be dissolved in 5% dextrose injection.

Antineoplastic Agents↗
PubMed1981

Left ventricular dynamic geometry and diastolic mechanics in a model of chronic cyanosis and right ventricular pressure overload.

Left ventricular (LV) mechanics and dynamic geometry were studied in eight dogs 1 to 151 days after creation of a model of cyanosis and increased right ventricular (RV) pressure. In each dog, an 8 mm conduit was interposed between the main pulmonary artery and left atrium; the pulmonary artery was then banded distal to this shunt. Ultrasonic dimension transducers were subsequently implanted for the measurement of LV equatorial minor axis and wall thickness. Catheter-tipped micromanometers were used to measure LV and pleural pressures; RV pressure was measured with a fluid-filled catheter and an external transducer. Eight control animals were similarly instrumented. At the time of study, the cyanotic dogs had significantly decreased arterial oxygen saturations (66% +/- 7% versus controls: 96% +/- 5%), significantly elevated peak RV pressures, (55 +/- 7 mm Hg versus controls: 30 +/- 5 mm Hg) and significantly elevated ratios of RV to LV mass (0.52 +/- 0.05 versus controls: 0.36 +/- 0.05). Diastolic pressure-dimension curves were generated and time constant for LV relaxation were calculated for each animal. The diastolic curves obtained from the cyanotic dogs were not significantly different from those of the control animals, and LV relaxation was not prolonged in the cyanotic dogs. In the three dogs that were cyanotic for 4 months or longer, there was a profound abnormality in the geometric pattern of LV contraction, manifested by asynchronous shortening of the anteroposterior equatorial minor axis. In two of these three dogs, inotropic reserves were assessed by means of postextrasystolic potentiation and were found to be normal. The results of this study indicate that short-term mild cyanosis and RV pressure overload do not alter diastolic compliance nor prolong relaxation of the LV. LV dynamic geometry may become abnormal after 4 months, with preservation of global LV inotropic reserves.

Animals↗
PubMed1980

Characterization of monolayer and organ cultures of cloned and enriched lymphohematopoietic stroma cell populations.

The role of hematopoietic microenvironments in the regulation of maturation and differentiation of hematopoietic cells, although heavily debated, remains uncertain. Several investigators have suggested that the adherent "stromal" cell populations, which grow as colonies in cultures of lymphomyeloid tissues, include the cells involved in such regulatory processes. Grossly, the colonies described by several investigators appear similar morphologically, and the cells giving rise to them have been variously termed 1) fibroblast colony forming cells (FCFC), 2) plaque forming units-culture (PFU-C), 3) macrophage colonies, and 4) marrow stromal cells. FCFC have been reported to re-establish their parent microenvironment when transplanted in an allogeneic system. In this study, cloned and enriched cell populations obtained from such colonies in cultures of murine lymphomyeloid tissues have been characterized by their growth in culture and using morphological, histochemical, and electron microscopic techniques. The results demonstrated that, although the initial stromal colonies appeared to be identical, the constituent cell types varied considerably. Some colonies were comprised primarily of macrophages, while others appeared to contain predominantly fibroblasts; two additional cell types that established colonies have not yet been satisfactorily identified. These results demonstrate the heterogeneity of lymphomyeloid stromal colonies. There is a need for caution in the analysis of experiments in which uncharacterized stromal cell colonies are transplanted or employed as supporting monolayers in culture systems in experiments designed to evaluate the origins and functions of lymphohematopoietic stroma.

Animals↗
PubMed1980

Effect of heart rate on myocardial blood flow in dogs with left ventricular hypertrophy.

Because of the previous suggestion that subendocardial perfusion may be inadequate in the hypertrophied heart, this study was carried out to examine the response of transmural myocardial blood flow to pacing induced tachycardia in dogs with chronic left ventricular hypertrophy. Myocardial hypertrophy, produced by banding the ascending aorta of puppies at 5-6 wk of age, resulted in an 87% average increase in relative left ventricular mass compared with the control dogs. Myocardial blood flow was examined during ventricular pacing at heart rates of 100, 200, and 250 beats/min using radionuclide-labeled microspheres. Mean blood flow per unit myocardial mass was similar in the two groups of dogs at a heart rate of 100 beats/min and increased regularly during pacing in both groups of animals. Increasing heart rates did not change the transmural pattern of myocardial blood flow in the normal dogs, but in the animals with left ventricular hypertrophy pacing at 250 beats/min resulted in a significant redistribution of perfusion away from the subendocardium, with the ratio of subendocardial/subepicardial blood flow falling from 1.03 +/- 0.08 at 100 beats/min to 0.83 +/0 0.06 at 250 beats/min (P < 0.01). This redistribution of blood flow away from the subendocardium was especially marked in the regions encompassing the papillary muscles and the intervening left ventricular lateral wall.

Animals↗
PubMed1980

An analysis of the pulsatile hemodynamic responses of the pulmonary circulation to acute and chronic pulmonary venous hypertension in the awake dog.

In this study we measured high fidelity pulsatile pressure and flow waveforms at the inlet to the pulmonary vascular bed to assess the differences in adaptation to acute and chronic pulmonary venous hypertension in awake dogs. Acute elevations in left atrial pressure (P1a) were effected by inflation of left atrial balloons, while chronic elevations were accomplished by placement of aorta to left atrial shunts. Pulmonary artery hydraulic impedance was calculated and analysis of these data revealed marked differences between the responses to acute and chronic elevations of left atrial pressure. The acutely stressed dogs (n = 12) had significantly decreased pulmonary vascular resistance (when P1a = 16.9 +/- 1.0 mm Hg, PVR = 212 +/- 57 dynes sec/cm5; when P1a = 28.6 +/- 1.4 mm Hg PVR = 18 +/- 115 dynes sec/cm5; control P1a = 6.1 +/- 1.5 mm Hg, and PVR = 355 +/- 69 dynes sec/cm5) and normal characteristic impedances (ZO) (210 +/- 36, 227 +/- 39, 178 +/- 14 dynes sec/cm5, respectively), indicating recruitment of arteriolar-capillary perfusion density and no change in proximal pulmonary arterial physical properties. The chronic pulmonary venous hypertension group (n = 11) retained normal PVR (496 +/- 30 dynes sec/cm5) but demonstrated a markedly higher characteristic impedance, ZO = 361 +/- 11 dynes sec/cm5 (P < 0.001). This indicated a measurably different and extremely potent effect of chronic venous hypertension on the physical properties of the pulmonary vessels with an apparently increased arterial stiffness correlating with a 4-fold increase in Young's elastic modulus. These changes were not reversed by alpha-adrenergic blockade or acute lowering of left atrial pressures.

Acute Disease↗
PubMed1980

The diastolic mechanical properties of the intact left ventricle.

Recent studies have improved our understanding of the diastolic mechnical properties of intact myocardium. In order to obtain meaningful data, pressures external to the heart should be measured, forces and dimensions should be properly normalized, and measurements should be obtained over a wide range of ventricular volumes. Diastolic filling appears to be a passive phenomenon and is not affected significantly by systolic relaxation or mural inertia. Thus, the relationship between diastolic myocardial force and length is determined primarily by the elastic properties of the muscle and by viscous properties during dynamic filling. In the absence of ischemia, the diastolic mechanics of intact myocardium are not altered significantly by acute physiological interventions. Chronic changes in diastolic properties do occur, however, and are fundamentally important to the regulation of cardiac function. Myocardial creep induced by chronically elevated diastolic presssure produces ventricular dilatation, thereby altering chamber geometry, systolic loading, and overall global function. Thus, a detailed analysis of diastolic mechanical properties is essential to the assessment of the performance characteristics of the intact heart.

Animals↗