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Biomedical subjects

W P Webster

Publications and source records attributed to W P Webster.

At least 19 recordsLinked to original sources
PubMed1990

American Burkitt's lymphoma: a 10-year review and case study.

Burkitt's lymphoma is a malignancy of B-lymphocyte origin that was initially described in African children with jaw tumors. These tumors often spread to involve abdominal viscera and other sites, have rapid growth kinetics, and are principally responsive to chemotherapy. Prolonged survival is predicted by site and extent of tumor, with bone marrow and central nervous system involvement being indicators of a poor prognosis. The dental practitioner plays an important role in diagnosis of jaw lesions and treatment throughout the course of the disease. An examination of 17 cases of Burkitt's lymphoma diagnosed at The North Carolina Memorial Hospital, University of North Carolina at Chapel Hill, North Carolina, over a 10-year period is undertaken and an illustrative case study is presented to demonstrate the challenge of caring for the patient with Burkitt's lymphoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Prostaglandin inhibitor and radiotherapy in advanced head and neck cancers.

Radiotherapy is the usual mode of treatment for unresectable head and neck cancer. To improve cure rates, extend survival, and reduce morbidity, we use accelerated hyperfractionation radiotherapy and an adjuvant drug to inhibit prostaglandin synthesis. In this study, 19 patients received 300 rad/day of radiotherapy in two equally divided doses to a total dose averaging 6,200 rad. Either indomethacin, 25 mg, or placebo was given four times a day in a double-blind fashion during therapy. Radiation mucositis was graded as 0 to 4+; pain, nutritional status, and tumor status were monitored daily and recorded biweekly. Evaluation of the data showed delayed mucositis in the experimental group for grades 1 to 3, with a significant difference at grade 3 compared with controls. The significance of a long-term comparison of cure rates would be doubtful considering the heterogeneity of the primary sites and regional disease in this group coupled with the small size of our study.

Clinical Trials as Topic↗
PubMed1980

Haemostatic failure of prothrombin complex concentrates during elective dental procedure.

One haemophilia A patient with an inhibitor was exposed to a graded surgical procedure and treated with Prothrombin Complex Concentrates (PCC). Hemostasis was not obtained until the inhibitor was neutralized and the patient's factor VIII level was normal. This patient is presented to emphasize that PCC are not nearly as effective as once hoped in producing hemostasis in inhibitor patients. Consequently, major decisions should not be made presuming efficacy of these products in inhibitor patients.

Adult↗
PubMed1980

Medical complications of hemophilia.

The modern, comprehensive care of patients with hemophilia requires an awareness that complications other than those caused by acute hemorrhage can occur. The use of newer, more potent plasma concentrates has been accompanied by an increased incidence of liver disease in transfusion-requiring hemophiliacs. The progression to chronic active hepatitis and cirrhosis are particularly ominous developments in these patients. There is also a high incidence of urinary tract abnormalities in hemophiliacs, though the long-term consequences of these abnormalities are unknown. Furthermore, it must be remembered that urinary tract disorders unrelated to hemorrhage, such as nephrolithiasis, tumors, and nephritis, can occur in patients with hemophilia and may be mistaken for hemorrhage. Finally, hypertension occurs more frequently in patients with hemophilia than in the general population and may in part contribute to the occurrence of bleeding within the central nervous system. Methods for evaluating and treating these various disorders are discussed. Greater awareness of these potentially treatable medical complications will improve further the quality of care in hemophilia.

Acute Disease↗
PubMed1979

Thrombosis: a study of coagulation parameters and mechanisms during allograft rejection.

Thrombosis of the microvasculature has been recognized at the end product of organ rejection, but the exact biological pathway through which this occurs has not been clarified. Normal, factor VII deficient and heterozygous hemophilic (factor VIII) dogs were grouped to study the intrinsic and extrinsic clotting and platelet mechanisms during unmodified renal allograft rejection. The observed alterations of the hemostatic mechanisms are related to the changes observed in the microvasculature. Six groups of donor-recipient animals were studied: Group I -autografts (control); Group II - normal to normal allografts with bilateral nephrectomy; Group III - heterozygotes for factor VIII deficiency; Group IV - normal to normal allografts with unilateral nephrectomy; Group V - normal to factor VII deficiency without nephrectomy; and Group VI - normal to normal allografts with unilateral nephrectomy and dipyridamole. Each engrafted animal was followed pre- and posttransplantation for change in the blood clotting factors, fibrin split products, platelets, white blood cells, renal function and microvasculature. The animals with factor VII deficiency rejected in a similar fashion as the control animals. The group with impaired factor VIII synthesis and platelet function had longer survival times. These data suggest that the intrinsic clotting pathway and platelets are the primary mechanism through which thrombosis occurs secondary to immune injury.

Animals↗
PubMed1979

Glanzmann's thrombasthenia. Report of two oral surgical cases using a new microfibrillar collagen preparation and EACA for hemostasis.

Glanzmann's thromboasthenia is a rare congenital platelet disorder characterized by a prolonged bleeding time, a qualitative platelet defect, and severe hemorrhagic episodes. Patients with this disorder have been managed by administration of blood and blood components (most recently, platelet-rich plasma and platelet concentrates) to control hemorrhage resulting from trauma or surgical procedures. The two case reports presented here illustrate the use of a local hemostatic agent (microfibrillar bovine collagen, Avitene) and a systemic fibrinolytic inhibitor (epsilon aminocaproic acid, Amicar) to control postoperative hemorrhage secondary to elective extraction of teeth. The clinical results demonstrate excellent postoperative hemostasis and support recent in vitro observation of platelet adherence to the collagen preparation. This provides an alternate therapeutic modality in the management of patients with Glanzmann's disease and possibly other disorders of platelet function.

Abscess↗
PubMed1978

Dental management of mild hemophilia with polycythemia vera.

Classic hemophilia (hemophilia A. Factor VIII deficiency, antihemophilic factor deficiency) and polycythemia vera were diagnosed in a patient who presented for management of his dental disease. This case report summarizes the history, laboratory findings, and clinical course and discusses the various diagnostic considerations in the management of two rare disorders. A review of current concepts of hemophilia and polycythemia vera is presented.

Adult↗
PubMed1977

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↗
PubMed1977

Liver biopsy in hemophilia A.

Hepatitis is a significant complication of the treatment of hemophilia A with factor VIII concentrates. Chronic liver disease in these patients is infrequently documented in the literature. The results of percutaneous liver biopsy, under the coverage of glycine-precipitated factor VIII, in six patients with hemophilia A who had the persistence of abnormal liver-function tests for at least 6 months, are described. Three patients had chronic active hepatitis, and three had chronic persistent hepatitis. No complications were encountered as a result of the biopsy procedure. These results suggest that percutaneous liver biopsy should be considered in patients with hemophilia A with continuously abnormal liver-function tests to establish a histologic diagnosis and to guide further therapy.

Acute Disease↗
PubMed1976

Infusion of human and canine factor VIII in dogs with von Willebrand's disease: studies of the von Willebrand and factor VIII synthesis stimulating factors.

Dogs with von Willebrand's disease (VWD) were infused with a highly purified human and canine factor VIII preparation. Control infusions were performed using isotonic saline solution. Following all of the concentrate infusions, the bleeding times were shortened to within the normal range for up to 4 h. Factor VIII activity rose immediately after infusion, rapidly returned to preinfusion levels, and then increased again at 18 h. The levels of factor VIII-related antigen (F VIII-RA) as measured with anticanine factor VIII also increased after infusion and then gradually declined. There was no further increase in F VIII-RA at 18 h, when the factor VIII activity showed the secondary increase characteristic of VWD. With antihuman factor VIII, two identifiable antigens were present in the plasma of the dogs given human factor VIII. The reduced platelet retention of these animals was not significantly altered following infusion, whereas ristocetin-induced platelet aggregation was corrected in one of the dogs given human factor VIII. These studies indicate that factor VIII procoagulalant and von Willebrand factor activities reside on a single molecule or form part of a molecular complex. In addition, the factor VIII preparations appeared to contain the factor VIII synthesis-stimulating factor and/or a precursor of factor VIII procoagulant activity.

Animals↗
PubMed1976

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↗
PubMed1975

Antibody nature of circulating inhibitor of plasma von Willebrand factor.

A circulating plasma inhibitor of the "von Willebrand factor" was observed in a multiply tranfused subject with severe von Willebrand's disease. The platelet-active von Willebrand factor is associated with a plasma protein macromolecular complex that is deficient in the disease. The inhibitor appears to be an IgG antibody, kappa type, based on neutralization tests with goat antisera to specific human immunoglobulins. The IgG and inhibitor separated out together in plasma fractions obtained by "salting-out" and chromatographic procedures. Two separate inhibitor neutralization tests for the platelet-active factor, one with human plasma and ristocetin, the other with bovine plasma, gave similar results, based on the macroscopic aggregation time test of fixed human platelets. With cryoprecipitate transfusions the inhibitor was transiently neutralized with the temporary appearance of von Willebrand factor, factor VIII, and factor VIII-like antigen in the plasma. The plasma inhibitor level increased after transfusion, suggesting an anamnestic response. Lower titer inhibitor plasmas neutralized only the platelet activity. Highest titer plasma also neutralized human factor VIII, but only in part; it did not neutralize either bovine factor VIII or the human small active factor VIII fragment. The anti-factor VIII activity of the von Willebrand factor inhibitor may be due to steric hindrance, dependent on the spatial relationship of factor VIII sites on the macromolecular complex.

Animals↗
PubMed1975

Dominant inheritance of hemophilia A in three generations of women.

A bleeding diathesis is described which is phenotypically indistinguishable from hemophilia A and which has been transmitted as a dominant trait in three generations of women in a North Carolina kindred. The abnormal phenotype is characterized by clinical mildness and slightly abnormal clotting time, prothrombin consumption, and partial thromboplastin time. Bleeding time, platelet count, clot retraction, tourniquet test, and prothrombin time are normal. Concentration of factors I, II, V, VII, IX, X, and XII are normal, while factor VIII activity is reduced to 2%-5% of control values. De novo synthesis of factor VIII does not occur after transfusion; factor VIII-related antigen is normal; patients' plasmas aggregate platelets normally in the presence of ristocetin, and a typical protein pattern is seen when a chymotryptic digest of cryoprecipitate of the proband is examined by SDS-polyacrylamide gel electrophoresis. Six possible genetic explanations are entertained. Balanced X-autosomal translocation of hemophilia A heterozygotes has been excluded by cytogenetic analysis of metaphase chromosomes. Classes von Willebrand's disease (vWd) is probably excluded on the basis of the laboratory data, and extreme lyonization of hemophilia A heterozygotes on probabilistic grounds. The genetic possibilities which cannot be excluded include a previously unrecognized variant mutation at the vWd locus, a dominant mutation at the hemophilia A locus on the X chromosome, and dominant mutation at a hypothetical fourth locus involved in factor VIII synthesis and control.

Animals↗