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Biomedical subjects

C M Kessler

Publications and source records attributed to C M Kessler.

At least 91 records · Page 5Linked to original sources
PubMed1988

Randomised controlled trial of recombinant tissue plasminogen activator versus urokinase in the treatment of acute pulmonary embolism.

The effect of intravenous recombinant human tissue-type plasminogen activator (rt-PA) was compared with that of urokinase in 45 patients with angiographically documented pulmonary embolism (PE) in a randomised controlled trial. The two principal end-points were clot lysis at 2 h, as assessed by angiography, and pulmonary reperfusion at 24 h, as assessed by perfusion lung scanning. All patients received the full dose of rt-PA but urokinase infusions were terminated prematurely (on average after 18 h) in 9 patients because of allergy in 1 and uncontrollable bleeding in 8. By 2 h, 82% of rt-PA-treated patients showed clot lysis, compared with 48% of urokinase-treated patients (p = 0.008; 95% CI for the difference = 10-58%). Improvement in lung scan reperfusion at 24 h was identical in the two treatment groups. The reduction in fibrinogen did not differ significantly between the rt-PA and urokinase groups (45% vs 39% at 2 h and 34% vs 40% at 24 h). The results indicate that in the dose regimens employed, rt-PA acts more rapidly and is safer than urokinase in the treatment of acute PE.

Acute Disease↗
PubMed1988

Tissue plasminogen activator and acute pulmonary embolism.

We assessed the efficacy and safety of peripheral intravenous recombinant human tissue-type plasminogen activator (rt-PA) in 47 patients with angiographically documented pulmonary embolism (PE). We administered 50 mg/2 h and, if necessary, an additional 40 mg/4 h. By 6 hours, 94% of the patients had angiographic evidence of clot lysis that was slight in 5, moderate in 12, and marked in 27 patients. Among the 34 patients with pulmonary hypertension prior to treatment, average pulmonary artery pressure decreased from 43/17 (27) to 31/13 (19) mm Hg (P less than 0.0001). The average lung scan perfusion defect decreased from 37% before therapy to 16% (P less than 0.01) after therapy among the 19 patients who had pre- and post-treatment lung scans. Of 7 patients with pre- and post-treatment imaging and Doppler echocardiograms, hypokinetic right ventricular wall movement (mild in 1, moderate in 2, and severe in 4) normalized in 5 and improved to mild hypokinesis in 2. Right ventricular diameter decreased from 3.9 +/- 1.0 to 2.0 +/- 0.5 cm (P less than 0.005). Fibrinogen decreased 33% from baseline at 2 h and 42% from baseline at 6 h. However, patients with the greatest degree of angiographic clot lysis at 2 h had a preponderance of fibrinogenolysis over fibrinolysis, demonstrated by a lower ratio of cross-linked fibrin degradation products to fibrin(ogen) degradation products (0.14 +/- 0.09 vs. 0.54 +/- 0.82) (P less than 0.04). Among selected patients, peripheral intravenous rt-PA is associated with rapid lysis of PE, improved pulmonary perfusion, and improved right ventricular function.

Biomarkers↗
PubMed1988

Acute pulmonary embolism treated with thrombolytic agents: current status of tPA and future implications for emergency medicine.

Pulmonary embolism is diagnosed 120,000 times yearly in the United States and contributes to 30,000 deaths. This probably represents an underestimate of incidence because massive acute pulmonary embolism may often result in rapid and therefore unexplained death in the absence of autopsy confirmation. The innovative and judicious use of thrombolytic agents by emergency department and paramedical ambulance personnel may lead to a decreased mortality for this disease. Clinical studies are necessary to determine if the cardiopulmonary compromise associated with massive pulmonary embolism can be rapidly reversed through thrombolysis and whether that reversal will lead to increased survival. The use of thrombolytic agents will gain favor only if their risk:benefit and cost:benefit ratios are acceptable. We discuss the results of using first- and second-generation thrombolytic agents in the treatment of pulmonary embolism and review the encouraging data that have emerged from our studies with recombinant tissue-type plasminogen activator (tPA). This agent has relative fibrin specificity and may provide therapeutic advantages over the conventional thrombolytic agents, urokinase and streptokinase, particularly when the latter are administered in the currently recommended dose schedules for treatment of pulmonary embolism.

Emergencies↗
PubMed1987

Thrombolytic therapy of acute pulmonary embolism: current status and future potential.

Recombinant human tissue-type plasminogen activator (rt-PA), a relatively clot-specific fibrinolytic agent, represents a novel and promising approach to thrombolytic therapy of pulmonary embolism. Therefore, the efficacy and safety of peripheral intravenous rt-PA therapy were assessed in 47 patients with angiographically documented pulmonary embolism. The drug regimen was 50 mg over 2 hours followed by repeat angiography and, if necessary, an additional 40 mg over 4 hours. By 6 hours, 44 of the 47 patients had angiographic evidence of clot lysis that was slight (n = 5), moderate (n = 12) or marked (n = 27). Among the 34 patients with pulmonary hypertension before treatment (mean pulmonary artery pressure exceeding 17 mm Hg), the pressure decreased from 43/17 (mean 27) to 31/13 (mean 19) mm Hg (p less than 0.0001). Fibrinogen decreased 33% from baseline at 2 hours and 42% from baseline at 6 hours. There were two major complications that required surgical control of bleeding: hemorrhage from a pelvic tumor and mediastinal tamponade in a patient 8 days after coronary artery bypass surgery. The initial results demonstrate that, among selected patients, peripheral intravenous rt-PA can rapidly and, for the most part, safely lyse pulmonary embolism within 6 hours.

Acute Disease↗
PubMed1987

In vitro correlation of platelet aggregation with occurrence of disseminated intravascular coagulation and subacute bacterial endocarditis.

Platelet-bacterial interactions were examined in vitro by incubating organisms isolated from patients with septicemia with normal platelet-rich plasma. The potency of various species of gram-positive and gram-negative bacteria to induce irreversible platelet aggregation was then determined in an aggregometer. The aggregation curves produced by the bacteria resembled the normal platelet response to collagen and were impeded by the presence of aspirin. Strains of Staphylococcus aureus and Pseudomonas aeruginosa isolated from 25 different patients produced maximum increases in light transmission and irreversible platelet aggregation with relatively rapid mean aggregation times; six of these patients had clinical and laboratory evidence of disseminated intravascular coagulation. In contrast, isolates of alpha streptococcus and Staphylococcus epidermidis induced irreversible platelet aggregation much less commonly and were associated with considerably longer mean aggregation times. None of the latter group of patients had evidence of disseminated intravascular coagulation. Isolates of bacteria from a small number of patients with subacute bacterial endocarditis uniformly induced irreversible platelet aggregation. Addition of paired bacterial isolates to normal platelet-rich plasma demonstrated a synergistic aggregation response. These data suggest that a relative hierarchy exists in bacterial strain potency to induce irreversible platelet aggregation. The rapidity and degree of aggregation in vitro correlated well with the clinical and laboratory evidence for subacute bacterial endocarditis and disseminated intravascular coagulation in vivo. These observations may provide useful adjunctive laboratory information to help establish the diagnosis of subacute bacterial endocarditis, especially in the clinical setting where the classical findings of endocarditis are not obvious during initial presentation.

Blood Platelets↗
PubMed1986

Acute pulmonary embolism treated with tissue plasminogen activator.

Recombinant human tissue-type plasminogen activator (rt-PA) was given via a peripheral vein to 36 patients with angiographically documented pulmonary embolism. The regimen was 50 mg/2 h followed by repeat angiography and, if necessary, an additional 40 mg/4 h. By 6 h, 34 of 36 patients had angiographic evidence of clot lysis, slight in 4, moderate in 6, and marked in 24. The quantitative score improved 21% by 2 h and 49% by 6 h. Fibrinogen decreased 30% from baseline at 2 h and 38% from baseline at 6 h. 2 patients had major complications: in one, bleeding from a pelvic tumour required surgery; in the other, who had had coronary artery bypass surgery eight days earlier, pericardial tamponade developed. These initial results in selected patients make a case for expanded investigational use of peripheral intravenous rt-PA in pulmonary embolism.

Acute Disease↗
PubMed1986

Treatment of silastic catheter-induced central vein septic thrombophlebitis.

Two patients with surgically implanted right atrial silastic catheters for home hyperalimentation developed central vein septic thrombophlebitis. Initial treatment including removal of the catheter and antibiotic therapy was unsuccessful and both patients had persistent fever and bacteremia. A clinical and microbiologic response occurred when anticoagulation therapy with heparin was added to the treatment regimen. Although a surgical approach has been emphasized in patients with peripheral vein suppurative thrombophlebitis, anticoagulation therapy may be a useful alternative in the treatment of patients with central vein infection.

Aged↗
PubMed1986

Circulating coagulation inhibitors in the acquired immunodeficiency syndrome.

Abnormal coagulation profiles were identified in ten patients with the acquired immunodeficiency syndrome (AIDS) associated with opportunistic infections and malignancies. Activated partial thromboplastin times were elevated in all patients; three of seven had elevated prothrombin times. All patients had lupus-type anticoagulants characterized by rapid prolongations of the partial thromboplastin time in mixing studies, prolonged dilute thromboplastin inhibition assays, and increased Russell viper venom clotting times. Ivy bleeding times were prolonged in three patients with defective platelet aggregation. The lupus anticoagulant was isolated from the sera of healthy heterosexual men and from patients with AIDS with and without the lupus anticoagulant, and in the presence and absence of opportunistic infections. Both polyclonal IgM and IgG lambda from plasma with lupus anticoagulant interfered with clotting studies and platelet aggregation. The inhibitors usually accompanied active opportunistic infections and tended to disappear with successful resolution of infection.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Phase I/II trial of thymosin fraction 5 and thymosin alpha one in HTLV-III seropositive subjects.

Forty-two male homosexuals and/or hemophiliacs with depressed helper/suppressor T-cell ratios were treated with one of three different doses of thymosin fraction 5 (TF5, 30, 60, and 120 mg), or a single dose of thymosin Alpha One (TA1, 600 micrograms), by daily subcutaneous (SQ) administration for 10 weeks, followed twice weekly for 4 weeks. No major toxicity was noted for any of the preparations tested, although three subjects treated with TF5 had to discontinue therapy because of severe local skin reactions. Of the doses and preparations tested, only 60 mg TF5 was capable of significantly improving (p less than 0.02) mean T-cell lymphoproliferative responses to alloantigens (MLR) for six HTLV-III seropositive subjects who were abnormal prior to therapy. Peripheral blood lymphocytes from subjects treated with 60 mg TF5 also exhibited a transient restoration of mean mitogen-induced interleukin-2 (IL-2) production to normal. No effects were observed with any of the four treatment regimens on absolute helper T-cell numbers, NK activity, antibody titers to HTLV-III, or in the expression of a variety of surrogate markers for acquired immunodeficiency syndrome (AIDS). Four of the six seropositive subjects treated with 60 mg TF5 exhibited a return to depressed baseline MLR, after switching to twice weekly injections. With a median follow-up time of 20 months, six cases of AIDS developed. However, none of the five subjects whose MLR improved following treatment progressed to AIDS. We recommend daily subcutaneous (SQ) administration of 60 mg (40 mg/m2) TF5 for use in combined modality trials, along with drugs capable of suppressing replication of HTLV-III.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Phenotypic and ultrastructural characterization of a medullary thymocyte acute lymphoblastic leukemia with cellular procoagulant activity.

The phenotypic and ultrastructural characterization of the blast cells from a T-cell acute lymphoblastic leukemia (T-ALL) that was associated with disseminated intravascular coagulation (DIC) is described. The bone marrow blasts were considered to represent neoplastic medullary thymocytes and were acid phosphatase (+), terminal deoxynucleotidyl transferase (-), acid alpha-naphthyl acetate esterase (-), E-rosette (+) at 4 degrees C and 37 degrees C, Fc- and C3-receptor (-), and cALLA-, Ia-, 9.6+, OKT3+, OKT4+, OKT6+/-, OKT8+, OKT10+. On transmission electron microscopic study, the predominant cell was 6 micron in diameter and possessed an irregular nucleus, moderate-sized nucleolus, marginated heterochromatin, abundant Golgi elements and granules, and prominent intermediate filaments. The cells were analyzed with normal and factor-deficient human plasmas and contained significant amounts of tissue factor-like procoagulant activity. This is the first report of a well-characterized medullary thymocyte T-ALL in which DIC was an accompanying feature, and the first demonstration of tissue factor-like procoagulant activity in acute lymphoblastic leukemia. In view of thrombohemorrhagic phenomena observed in association with other medullary thymocyte leukemias, these findings suggest that tissue factor-like procoagulant activity may be a characteristic of medullary thymocyte-derived lymphoid leukemias.

Acute Disease↗
PubMed1985

Microwave technology for the rapid thawing of frozen blood components.

Based on a continuing need to provide a more rapid response to requests for thawed fresh frozen plasma, the authors evaluated plasma thawing with the use of a microwave oven and compared it with conventional 37 degrees C waterbath thawing methods. Their results indicate that microwave-thawed plasma contains precipitated denatured protein (mainly albumin and fibrinogen) and that there is a significant reduction of coagulation Factors IX, X, XI, and fibrinogen compared with fresh plasma. They also measured levels of di-ethyl hexyl phthalate after microwave thawing and found its rate of accumulation similar to that of the 37 degrees C waterbath. More importantly, fundamental principles of microwave heating preclude uniform temperatures being maintained throughout the thawing of plasma; hence, the denaturation of plasma proteins is expected to occur under even low heating conditions.

Blood Preservation↗
PubMed1985

Ultrastructural markers in circulating lymphocytes of subjects at risk for AIDS.

One hundred random lymphocytes in each of 168 buffy coat preparations from 59 subjects at risk for AIDS (50 homosexuals, 7 hemophiliacs, and 2 combined, all with T4:T8 ratios of less than or equal to 1.2) were screened for the presence of ultrastructural markers, "tubuloreticular structures" (TRS), and "test tube and ring-shaped forms" (TRF). Twenty-six (44%) of the subjects were TRS positive (71 specimens) and 12 (20%) were TRS/TRF positive (34 specimens). TRF were only observed in TRS-positive specimens. There was an inverse relationship between the incidence and abundance of markers and the T4:T8 ratios, i.e., mean T4:T8 +/- SE for TRS-negative, TRS-positive, and TRS/TRF-positive subjects were 0.59 +/- 0.05, 0.42 +/- 0.05, and 0.19 +/- 0.06, respectively. Markers were present for as long as 16 months before AIDS was diagnosed in four subjects and before the appearance of features suggestive of AIDS in two others. The assessment of TEM markers in peripheral blood lymphocytes is a simple method for screening at-risk subjects in whom AIDS is likely to develop.

Acquired Immunodeficiency Syndrome↗
PubMed1985

IgA inhibitor to factor VIII/von Willebrand factor.

A 60-year-old Black female presented with a haemorrhagic diathesis and an acquired factor VIII/von Willebrand factor (VIII/vWf) inhibitor. This inhibitor was classified as an IgA immunoglobulin and was active not only against factor VIII coagulant (VIII:C) activity but also against plasma von Willebrand factor (vWf). The purified IgA also interacted with normal platelets to inhibit ristocetin-induced platelet aggregation (RIPA). In contrast, studies with haemophilia A plasma and platelets revealed that the inhibitor did not react significantly with these plasmas or platelets. The significant differences in the inhibition of vWf assay both of the plasma and the platelets of the haemophilia A patients suggests that part of the haemorrhagic diathesis may be related not only to the inhibition of VIII:C but also to interference with platelet function. In addition, these studies suggest that there may be significant differences in the factor VIII-related antigen (VIII R:Ag) on platelets in haemophilia A patients compared to normal.

Blood Coagulation Factors↗
PubMed1984

Inverse correlation between age related abnormalities of T-cell immunity and circulating thymosin alpha 1 levels in haemophilia A.

T-cell immunity and serum levels of thymosin alpha 1, beta 2-microglobulin, circulating immune complexes, serum immunoglobulin levels, antibodies to hepatitis surface or core antigen, and to cytomegalovirus, and Epstein-Barr virus were investigated in 51 patients with haemophilia A ranging in age from 2 to 52 years. All patients had received commercial U.S. lyophilized concentrates of antihaemophilic factor (AHF). The mean helper/cytotoxic-suppressor (OKT4/OKT8) ratio of 11 pre-adolescents (1.6 +/- 0.4 SE) was not significantly different from that of age matched normal controls. In contrast, the mean OKT4/OKT8 ratios of 13 adolescent (1.2 +/- 0.2 SE) and 23 adult (0.8 +/- 0.1 SE) haemophiliacs were significantly reduced. Abnormalities of lymphocyte mitogenic responses were found only in adult haemophiliacs. Nine individuals treated with commercial U.S. prothrombin complex concentrates for antibodies directed against AHF or for haemophilia B had normal mean OKT4/OKT8 values. The mean serum thymosin alpha 1 levels for each age category was similar to that of age matched controls; however, regression analysis revealed a significant relationship between elevated thymosin alpha 1 levels and decreased OKT4/OKT8 ratios in adult haemophiliacs (P = 0.012). Although the mean serum level of beta 2-microglobulin was significantly increased in the adult haemophiliac group, there was no correlation between OKT4/OKT8 ratios and any of the other serologic parameters studied.

Adolescent↗