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T Griggs

Publications and source records attributed to T Griggs.

5 recordsLinked to original sources
PubMed1996

An experimental model for testing von Willebrand factor function: successful SLA-matched crossed bone marrow transplantations between normal and von Willebrand pigs.

To assess the relative in vivo roles of von Willebrand factor (vWF) of different origins, we performed crossed bone marrow transplantations (BMTs) among normal pigs and pigs with the von Willebrand disease(vWF). The two groups were fully compatible immunologically according to typing by swine leukocyte antigen (SLA). After total-body irradiation (8-10 Gy), all pigs received 0.5X10(9) to 10(10)/kg mononuclear bone marrow cells without any immunosuppression. The nadir of aplasia occurred between days 5 and 7 after irradiation (white blood cell [WBC] count 0.6X10(9)/L, platelet [Plt] count 76X10(9)/L. Three weeks after the graft, WBC and Plt counts had returned to normal levels. Animals were followed for at lease 50 days, during which no bone marrow rejection occurred; no evidence of graft-vs-host disease (GVHD) was observed. Each BMT was confirmed by karyotype analysis. In the six homozygous pigs with vWD grafted with normal marrow, platelet vWF antigen (vWFAg) and platelet vWF activity rose from <3 to 450 U/dl with a normal multimeric pattern; plasma vF increases slightly. No correction of bleeding time was observed. In the five normal pigs grafted with bone marrow form pigs with vWD, platelet vWFAg and platelet vWF activity decreased from >100 U/dl to undetectable levels; bleeding time and plasma vWFAg remained unchanged. A derivative of normal porcine plasma, a concentrate containing factor VIII and vWF, was infused into a homozygous vWD pig before and after BMT from a normal pig. Co correction of bleeding time was obtained, even though plasma nd platelet vWFAg levels were normal. W concluded that crossed BMT among SLA-identical pigs is a feasible model of studying the synthesis and the roles of vWF in hemostasis and thrombosis.

Animals↗
PubMed1985

Purified human factor VIII procoagulant protein: comparative hemostatic response after infusions into hemophilic and von Willebrand disease dogs.

The procoagulant protein F.VIII:C is noncovalently bound to von Willebrand factor (vWF) to give the factor VIII macromolecular complex. New highly purified preparations of isolated human F.VIII:C, devoid of vWF and about 500,000-fold purified, were administered to hemophilia A and von Willebrand disease (vWD) dogs to determine their hemostatic effectiveness and survival in the circulation. Two preparations of F.VIII:C were used: peak 1, with active components of Mr 185,000-280,000, and peak 2, with a single component of Mr 170,000. In hemophilic dogs, with no plasma F.VIII:C but normal vWF, both preparations immediately elevated plasma F.VIII:C to expected levels, promptly stopped induced and spontaneous hemorrhages, and gave sustained plasma levels of F.VIII:C. The isolated F.VIII:C immediately complexed with endogenous vWF in hemophilic plasma and was eliminated exponentially, with a half-life (t1/2) of about 9 hr. Survival of peak 2 F.VIII:C was longer than that of peak 1 material. In contrast, F.VIII:C complexed to vWF in a therapeutic concentrate administered to hemophilic dogs was eliminated biexponentially with first-phase t1/2 of 3.2 hr and second-phase t1/2 of 9 hr. In vWD dogs with no vWF and reduced F.VIII:C levels, the isolated F.VIII:C produced supernormal levels of F.VIII:C without effect on induced bleeding. It was rapidly eliminated from plasma with a t1/2 of about 1 hr, as was the complexed F.VIII:C in the concentrate. These data indicate that isolated F.VIII:C promptly complexes with vWF and in this form is highly effective in controlling hemophilic hemorrhages with good survival in plasma. Without endogenous vWF with which to complex, the F.VIII:C is promptly eliminated.

Animals↗
PubMed1985

Beta-blocker therapy after myocardial infarction: secondary prevention in all patients?

The ability of beta-adrenergic blocking drugs to prevent death in patients after myocardial infarction has been demonstrated by several large trials. However, the need to treat patients at low risk has been challenged. Retrospective analysis of the data from one of these studies plus results from many additional studies have shown that electrical, mechanical and ischemic complications after myocardial infarction imply a high risk of subsequent death or recurrent infarction. On the other hand, absence of complications with a negative exercise tolerance test, good exercise tolerance, absence of arrhythmias and normal increase of ejection fraction with exercise documents a very low risk. These considerations lead to the following practical implications: The physician should watch for any evidence of left ventricular dysfunction or arrhythmia. Any such complication justifies treatment or more intensive study. Patients without complications can be further characterized with exercise testing, exercise radionuclide blood pool ventriculography, and Holter monitoring. If these tests expose risk indicators, treatment or more study should again be recommended. Because the beta-blockers are probably life-saving in a considerable portion of the patients with moderate and high risk, the decision to treat or not to treat should be made with due, affirmative consideration. In those patients with a carefully documented uncomplicated course and who have a normal exercise test and appropriate increase in ventricular ejection fraction with stress, beta-blockade is probably of no benefit. Under these conditions, a physician and patient might logically decide not to use the drug.

Adrenergic beta-Antagonists↗