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Biomedical subjects

T R Griggs

Publications and source records attributed to T R Griggs.

At least 37 records · Page 2Linked to original sources

Heart rates in fire fighters using light and heavy breathing equipment: similar near-maximal exertion in response to multiple work load conditions.

Intense exertion is an occupational hazard inherent to fire fighting. This study was designed to look at the exertion levels that fire fighters attain during a fire fighting exercise when using (1) no self-contained breathing apparatus (SCBA), (2) light SCBA, and (3) heavy SCBA. Exertion levels were measured as a function of the heart rate increase relative to the maximum predicted heart rate determined by a standard treadmill exercise test. Five fire fighters wore electrocardiographic monitors during a routine fire fighting exercise. Heart rates increased rapidly to 70% to 80% of maximum within the first minute and then plateaued at 90% to 100% until the attack on the fire was completed. There was no significant difference between exertion levels when using no SCBA, light SCBA, and heavy SCBA (split-plot analysis of variance, p greater than .25). These results suggest that fire fighters attain an intense level of physical activity quickly and maintain that level as long as they are actively engaged in fighting fire. These results also suggest that regardless of the weight of the SCBA, if employed, fire fighters exert themselves from 85% to 100% of their maximum and adjust their work output to maintain that near-maximal level.

Adult↗

Effect of carbon monoxide on atherogenesis in normal pigs and pigs with von Willebrand's disease.

The extent of coronary and aortic atherosclerosis was examined in pigs following balloon-catheter injury of coronary arteries and subsequent feeding of an atherogenic diet for 4 months. The pigs were either exposed intermittently to 100 ppm carbon monoxide or to ambient air alone. Three types of pigs were used: normals, homozygotes for von Willebrand's disease (bleeders), and heterozygotes (carriers). The 3 types of pigs developed coronary artery intimal lesions of similar thickness. Aortic lesions, quantified as percent of aortic surface involved with sudanophilia and raised fibrous plaques, were slightly less extensive in bleeder pigs than in normals. Carbon monoxide exposure did not increase the thickness of coronary artery intimal lesions, nor did it increase the percent of aortic surface involved with sudanophilia or raised fibrous lesions. These results suggest that exposure to low levels of carbon monoxide does not perceptibly enhance atherogenesis induced by hypercholesterolemia. None of 14 bleeder pigs showed evidence of myocardial infarction, despite significant coronary artery narrowing. Of the 24 normal and carrier pigs, 5 showed myocardial infarction. Four of these 5 pigs were exposed to carbon monoxide, while 1 was not exposed. These findings suggest that exposure to low levels of carbon monoxide may increase the incidence of myocardial infarction and that the absence of von Willebrand factor may be protective.

Animals↗

Platelet adhesion to damaged coronary arteries: Comparison in normal and von Willebrand disease swine.

The early response to coronary artery injury was investigated in normal swine and in swine with von Willebrand disease (vWD). Thirty minutes after coronary endothelial denudation, a monolayer of platelets was adherent to areas of simple injury in both bleeder and normal swine. The number of adherent platelets was not significantly different in the two phenotypes. Injury involving the media of the vessel produced platelet-fibrin thrombi. Platelet activation, as judged by pseudopod formation and platelet spreading over areas of simple injury, was significantly less in bleeder animals than in normal animals. These studies suggest that chemotaxis and initial contact adhesion of platelets to injured arterial wall is independent of the von Willebrand factor. On the other hand, the spreading and activation of platelets on the subendothelium appear to be dependent on the presence of plasma von Willebrand factor. Through this mechanism von Willebrand factor may contribute to arterial thrombosis and atherogenesis.

Animals↗

The role of noninvasive tests versus pulmonary angiography in the diagnosis of pulmonary embolism.

We studied 243 patients in whom 248 pulmonary angiograms were performed because of suspected pulmonary embolism. Ventilation and perfusion lung scanning in 140 of them revealed 38 to be in low and high probability groups. Of 19 patients with subsegmental and nonsegmental perfusion defects that were matched with ventilation defects, none had pulmonary embolism. Conversely, angiography was positive in 17 of 19 patients with multiple segmental or lobar perfusion defects in areas of normal ventilation. Doppler flow examinations of the veins of the legs showed normal flow in 61 of 79 (77 percent) patients with pulmonary emboli and, therefore, were insensitive indicators of embolism. There was no mortality from angiography, and serious complications occurred in 2 percent of the patients. Anticoagulation in 83 patients was associated with bleeding in 25, two of whom died. The data indicate that ventilation-perfusion lung scanning can be used to separate many of the patients suspected of having pulmonary embolism who need anticoagulant treatment from those who do not. However, there is a considerable number of patients with nonspecific abnormalities on lung scan. For this group of patients with nonspecific abnormalities, the risk of complications from empiric treatment with anticoagulant drugs is probably greater than the risk of complications from pulmonary angiography. Further, our data show that patients with negative angiography have a very low risk of subsequent pulmonary embolism. In this group of patients, therefore, pulmonary embolism should be demonstrated by angiography before long-term anticoagulant therapy is prescribed.

Anticoagulants↗

Susceptibility to atherosclerosis in aortas and coronary arteries of swine with von Willebrand's disease.

The development of coronary and aortic atherosclerosis was determined after balloon catheter injury of coronary arteries and administration of an atherogenic diet in normal pigs and pigs that were homozygous and heterozygous for von Willebrand's disease. Coronary atherosclerosis developed to a similar degree in all three phenotypic groups. The mean intimal thickness at the site of maximal thickness in ballooned vessels was .51 mm in the normal pigs, .67 mm in carrier pigs, and .55 mm in bleeder pigs. The intimal thickness of non-ballooned vessels was .28 mm in normal pigs, .28 mm in carrier pigs, and .35 mm in bleeder pigs. Fibrous lesions of atherosclerosis covered an average of 3.88% of the aorta in normal pigs, 2.83% in carrier pigs, and 2.37% in bleeder pigs. The difference between the aortic lesions of normal animals and bleeders was significant (P less than .05). Absence of von Willebrand factor was associated with limited resistance to atherosclerosis in the aortas of experimental pigs but did not affect the development of atherosclerosis in either ballooned or nonballooned coronary arteries. These findings suggest, first, that von Willebrand factor function is not essential to the development of the atherosclerotic lesion in this model and, second, that the role of the von Willebrand factor in the development of atherosclerosis is complicated and appears to involve interaction with variables not yet defined.

Animals↗

Impact of medical training on ambulance dispatching.

This study was designed to assess the ability of trained individuals to screen calls for emergency medical services to allow for safer or more appropriate responses. The degree of urgency of calls, as judged by dispatchers and a panel of physicians, was compared to estimates of the severity of the patient's illness or injury. Physicians were more likely to designate calls as emergencies than were dispatchers. Neither physicians nor dispatchers were able to discriminate between the severely ill or injured and those without severe problems. The emergency medical technicians were better able to assess severity and degree of urgency than were physicians or dispatchers. A tentative conclusion is that rapid response by an emergency medical services system will be based upon the caller's description of the situation rather than medical assessment of patient condition.

Allied Health Personnel↗

Macromolecular factor VIII complex: functional and structural heterogeneity observed in von Willebrand swine with transfusion.

The physiologic activities concerned with hemostasis and associated with the Factor VIII macromolecular complex were investigated in swine with von Willebrand's disease after infusion of cryoprecipitate, a lyophilized Factor VIII concentrate, or porcine serum. Immediately after each infusion the various activities antihemophilic factor, von Willebrand platelet aggregating factor, and Factor VIII-related antigen, were elevated in approximate proportion to dose and the bleeding time was shortened.There was a late secondary rise in antihemophilic factor. During the period after infusion, there was a differential fall-off of the various activities, with the bleeding time effect lost first, followed by the von Willebrand platelet aggregating factor and then by the Factor VIII-related antigen. The plasma from swine with von Willebrand's disease late after infusion contained high levels of antihemophilic factor without other detectable activities of the complex. Antihemophilic factor, free of the other components, obtained from plasma from swine with von Willebrand's disease either before or late after infusion eluted from agarose gel columns both as high and lower molecular weight material, unlike normal antihemophilic factor, which had a high molecular weight. In contrast, on ultracentrifugation the antihemophilic factor in these plasma sedimented slowly, even though chromatographically the plasmas contained both high and low molecular weight factor. All of the Factor VIII complex activities in normal porcine plasma sedimented rapidly. These studies demonstrate the heterogeneity of the Factor VIII complex and the apparent dependence of its chromatographic and sedimentation behavior on the functional activities associated with the complex.

Animals↗

The role of exertion as a determinant of carboxyhemoglobin accumulation in firefighters.

The firefighter's exposure to carbon monoxide represents a relatively contant occupational hazard. Unfortunately, attempts to predict the level of this exposure in work situations have failed to be of practical benefit. This study was designed to examine the several determinants of carbon monoxide uptake by firefighters in a controlled situation. Twenty firefighters were monitored for heart rate and carboxyhemoglobin (COHb) levels during a search-and rescue drill in a smokefilled building. Carbon monoxide levels were maintained at 200 to 1000 ppm. Heart rates increased to 90% of maximum for age within minutes, and COHb levels increased at more than 1% per minute. The use of breathing apparatus provided full protection from uptake of COHb but was associated with significantly increased heart rates. The results show that exertional levels and, therefore, ventilatory rates may be so great during firefighting that even in moderate or low levels of atmospheric carbon monoxide the COHb can rise to dangerous levels within minutes. These findings suggest that no firefighter should be allowed to work in a burning or smoke-filled structure without the protection of breathing apparatus.

Adult↗

Factor VIII synthesis: hepatic and renal allografts in swine with von Willebrand's disease.

Transplantation experiments were utilized to study the possible sites of synthesis of von Willebrand factor (vWF) and factor VIII (F VIII) activities. Three normal kidney and two normal liver allografts were implanted into five swine with von Willebrand's disease (vWD) that survived for 1,6, and 7, and 4 and 9 days, respectively. The correction of the multiple hemostatic defects of vWD by organ transplantation was evaluated using the F VIII procoagulant activity, bleeding time, and platelet aggregating factor (PAF) levels; i.e., vWF levels. Normal kidney allografts produced no changes in the bleeding times or increases in F VIII or PAF. Transfusions for surgical hemostasis produced transient increases in F VIII and PAF. In animals receiving normal liver allografts, the levels of F VIII exceeded 100%, PAF was increased, and sustained correction of the bleeding time and maintenance of hemostasis was observed. These data suggest that the kidney is incapable of synthesizing either the vWF or the F VIII and that cells contained in the liver, possibly the endothelial cells, are one of the sites of synthesis of these factors.

Animals↗

Von Willebrand factor: gene dosage relationships and transfusion response in bleeder swine--a new bioassay.

Aggregation of human platelets by bovine plasma was recently recognized as a marker for the study of the antihemophilic and von Willebrand factors. A similar marker in porcine plasma is shown to be specific for the platelet-active von Willebrand factor of plasma, but not for the antihemophilic factor (factor VIII). A new quantitative assay for the von Willebrand factor is based on the dose-response relationship observed between the concentration of von Willebrand factor and platelet aggregation times determined macroscopically. Bleeder swine, homozygous for von Willebrand disease, had no detectable platelet aggregating activity, while heterozygotes, carriers of the disease, had reduced levels of approximately 50% of normal. Exact detection of non-obligate carriers, hitherto impossible, becomes readily feasible because of the gene dosage relationship to the von Willebrand factor plasma levels. Transfusion of bleeder swine with normal plasma results in an immediate post-transfusion rise of the von Willebrand factor, followed by a rapid falloff. At 24 hr post-transfusion, no von Willebrand factor is detectable at a time when the factor VIII response is at its maximum. The discordance in plasma levels of this platelet-active von Willebrand factor and factor VIII in carrier animals and in the bleeder animals after transfusion suggests a different molecular and genetic basis for these two biological activities.

Animals↗

Plasma aggregating factor (bovine) for human platelets: a marker for study of antihemophilic and von Willebrand Factors.

The human-platelet aggregating factor in preparations of bovine plasma and bovine antihemophilic factor has been reported to be an activity of bovine antihemophilic factor. However, we show that activities of aggregating factor and antihemophilic factor are present in varying proportion in different preparations of antihemophilic factor. Aggregating factor activity is more stable on storage than is antihemophilic factor activity and can be selectively adsorbed by human platelets. Further, antihemophilic factor activity free of aggregating activity was eluted from DEAE-Sephadex. The factors were also separated during agarose chromatography in 0.25 M CaCl(2), which yields a small-molecular-weight moiety with antihemophilic factor activity; aggregating factor activity continued to elute in the void volume. Thus, aggregating factor activity is clearly separable from antihemophilic factor activity. The usual physiologic platelet-aggregating reactions require fresh platelets. Fresh, aged, and sonicated platelets, but not platelets that have been frozen and thawed, react with aggregating factor, indicating that the platelet "receptor sites" for the aggregating factor are unusually stable.

Animals↗

Factor VIII recombination after dissociation by CaCl12.

Factor VIII is a large protein molecule of molecular weight 2,000,000 or larger that elutes in the void volume on agarose gel chromatography. It has been shown previously that high concentrations of alkali halides and, more specifically, 0.25 M Ca(2+) dissociate the molecule into a large carrier protein and a small fragment that retains the factor VIII activity. Factor VIII was prepared from normal canine plasma collected in sodium oxalate and heparin and adsorbed with BaSO(4). Results with Ca(2+) dissociation were the same as those obtained with fraction prepared from canine plasma collected in sodium citrate. The addition of 0.1 M epsilon-aminocaproic acid in the dissociation step had no effect. Fractionation of canine hemophilic plasma produced preparations without activity, and no activity was found when these inert preparations were dissociated with Ca(2+). These results indicate that the Ca(2+) dissociation is a true dissociation and not caused by enzymatic degradation by plasmin, thrombin, or activated factors VII, IX, or X. The apparent molecular weight of the small active fragment of factor VIII determined by gel chromatography was about 100,000. Finally, when the large carrier protein and the small active fragment of factor VIII were separated by gel chromatography, mixed, and dialyzed free of Ca(2+), they recombined to form a large active molecule that appeared in the void volume on agarose gel chromatography.

Aminocaproates↗

von Willebrand factor and occlusive arterial thrombosis. A study in normal and von Willebrand's disease pigs with diet-induced hypercholesterolemia and atherosclerosis.

The thrombotic response of atherosclerotic arteries to stenosis and injury was studied in 14 pigs, eight normal and six with von Willebrand's disease (vWD). Atherosclerosis was produced by feeding a 1% to 2% cholesterol diet for 24 weeks. Both groups of pigs developed severe hypercholesterolemia, greater than five times baseline values. Coronary atherosclerosis was detected in all vWD pigs and in all but one normal pig and was not significantly different between groups. At sacrifice under general anesthesia, a Goldblatt clamp (GC) was positioned around the left anterior descending coronary (LAD) and carotid arteries to produce a stenotic segment, which was pinch-injured with needle holders. A 20 MHz Doppler velocity crystal was placed distal to the GC to detect cyclic flow reductions or permanent cessation of flow velocity indicative of occlusive thrombosis. In the phenotypically normal pigs with diet-induced atherosclerosis, occlusive thrombosis was detected in seven of seven LAD and seven of seven carotid arteries. In atherosclerotic vWD pigs, occlusive thrombosis failed to form in six LAD and 10 carotid arteries (p less than 0.003, Wilcoxon rank sum test). Scanning electron micrographs demonstrated platelet-fibrin microthrombi in both groups of pigs; only phenotypically normal pigs had occlusive thrombi. Von Willebrand factor is essential for the development of occlusive thrombosis and appears to support the progression of a mixed microthrombus to an occlusive thrombus.

Animals↗