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Biomedical subjects

J J Corrigan

Publications and source records attributed to J J Corrigan.

At least 37 records · Page 2Linked to original sources
PubMed1988

Fibrin metabolism in patients with acute myocardial infarction during and after treatment with tissue-type plasminogen activator.

In order to define some of the determinants of successful thrombolysis and reocclusion during fibrinolytic therapy for acute myocardial infarction (AMI), specific molecular markers of fibrin metabolism were serially measured in 15 patients with AMI treated with tissue-type plasminogen activator (t-PA). Fibrin formation was assessed by measurement of fibrinopeptide A (FpA) and fibrinolysis by assay of B-beta peptides 1-42 and 15-42 and crosslinked fibrin degradation products (XDP). At baseline, FpA levels were high while markers of fibrinolysis were near normal. Following a 90-minute infusion of t-PA (0.5-1.1 mg kg-1 hr-1), all markers of fibrinolysis increased. Levels of FpA remained elevated despite heparin at the initiation of cardiac catheterization. None of these markers discriminated between patients with successful reperfusion from those without. At 4 hours, B-beta 15-42 peptide and XDP levels remained elevated suggesting persistence of fibrinolysis beyond the short circulatory half-life of t-PA. FpA levels at 4 hours were lower in patients who underwent acute coronary angioplasty compared to those who received additional low dose t-PA (12.3 +/- 4.5 vs. 30.4 +/- 5.5 ng/ml, p less than 0.05). By 48 hours, markers of fibrinolysis had returned toward normal except in 2 patients with persistently elevated B-beta 15-42 peptide levels who suffered reocclusion on days 5 and 6 (75 and 44 vs. 29 +/- 3 nM, p less than 0.005). In conclusion, molecular markers of fibrin metabolism during fibrinolytic therapy may provide clinically relevant data.

Angioplasty, Balloon↗
PubMed1988

Neonatal thrombosis and the thrombolytic system: pathophysiology and therapy.

In older children and adults the use of thrombolytic drugs appears to be a promising medical approach to thromboembolic disease. However, experience in newborns is limited, with both failure and success having been reported. In this article, the fibrinolytic mechanism is delineated. The similarities and differences in this mechanism between newborns and adults are indicated. It is clear that our understanding of the newborn's fibrinolytic system is limited. Thrombolytic therapy is reviewed. It is recommended that future clinical studies be designed to include three essential features: (a) a uniform clinical staging, (b) a dose-response relationship with a plasminogen activator based on in vivo and in vitro studies, and (c) detailed studies of the newborn's fibrinolytic mechanism before and during thrombolytic therapy.

Fibrinolysis↗
PubMed1987

Antiplatelet effects of oral diltiazem, propranolol, and their combination.

1. The antiplatelet effects of a single oral dose of the calcium entry blocker diltiazem (60 mg), the beta-adrenoceptor blocker propranolol (40 mg), and their combination were studied in five healthy subjects. 2. Platelet aggregation and ATP release induced by adrenaline and ADP and ADP induced platelet thromboxane A2 generation were significantly inhibited (P less than 0.05) by either diltiazem or propranolol, although propranolol tended to have greater inhibitory effects on platelet function than diltiazem that did not reach statistical significance. 3. Combination therapy resulted in additive antiplatelet effects that were significantly (P less than 0.05) greater than either drug alone. 4. These data indicate that combined administration of a calcium entry blocker and a beta-adrenoceptor blocker results in additive inhibitory effects on platelet function. These effects may mediate part of the therapeutic efficacy of combination therapy in patients with coronary artery disease.

Adenosine Diphosphate↗
PubMed1986

Effects of oral diltiazem on platelet function: alone and in combination with "low dose" aspirin.

The effects of 3 days of oral diltiazem, "low dose" aspirin (40 mg/day), and their combination on platelet function was studied in 5 normal subjects. Both drugs inhibited platelet aggregation and ATP release induced by collagen, epinephrine and threshold concentrations of ADP. Aspirin and diltiazem decreased thromboxane A2 generation during ADP induced aggregation by 94 percent and 53 percent respectively, however both agents inhibited aggregation similarly, which suggests that diltiazem's anti-platelet effect was due to mechanisms other than inhibition of thromboxane metabolism alone. Combination therapy resulted in a partially additive inhibitory effect on ADP induced aggregation and thromboxane A2 generation. Two subjects had bleeding times over 15 minutes after receiving combination therapy.

Adenosine Diphosphate↗
PubMed1986

PROPLEX vs. PROPLEX SX: a controlled double blind study of the effectiveness in treating acute hemarthroses in hemophilia A patients with inhibitors to factor VIII.

A blinded randomized multicenter trial of two non-activated prothrombin complex concentrates was carried out to determine the clinical effectivity in the treatment of acute hemarthrosis in hemophiliac patients with inhibitors. The one product was prepared via DEAE Sephadex chromatography, while the second was fractionated via various precipitation procedures including polyethylene glycol. Equivalence of the two products was established with less than 15% difference in efficacy rates.

Blood Coagulation Factors↗
PubMed1985

Danazol-induced factor VIII and IX bypassing activity in hemophiliacs.

Danazol, a synthetic androgen reported to increase factor VIII and IX activity levels, was given to 6 hemophiliacs. With danazol therapy (600 mg/da) the APTTs shortened by 30-45% of pre-treatment times. However, the activity levels of the deficient factors did not increase significantly nor consistently with the APTT change. The prothrombin times and activity levels of factors XI and XII also did not change during the study period. Addition of plasma from danazol-treated patients to plasma with a known factor VIII inhibitor and to plasma from an untreated severe hemophilia A patient caused a similar shortening of the respective APTTs. Absorption of the danazol plasma with precipitating antibody against factor VIII and IX did not remove the APTT correcting principal. The data suggest that danazol may cause the de novo appearance of an intrinsic coagulation pathway activator having factor VIII and IX bypassing activity.

Calcium↗
PubMed1985

Effect of danazol on coagulation parameters and bleeding in hemophilia.

Danazol was given orally at a dose of 600 mg/day to six hemophiliacs for eight to 14 weeks. All patients showed a significant decrease in activated partial thromboplastin time (APTT) beginning with the first measurement (two weeks) and persisting until use of the drug was discontinued. However, a corresponding increase in the deficient factor activity could not be consistently demonstrated. Despite the shortened APTT, bleeding episodes continued in the severe hemophiliacs and the patient with Christmas disease. In four patients, bleeding appeared to increase in severity or change in pattern, and in two cases the bleeding manifestations did not respond to usual factor infusions but responded to discontinuation of the drug therapy and further factor replacement. Euglobulin lysis times were measured in five patients (one hemophiliac and four with nonhemophilic conditions) who were receiving danazol. The lysis times were markedly shortened. Increased fibrinolytic activity may be responsible for the increased bleeding manifestations in danazol-treated hemophiliacs.

Adult↗
PubMed1985

Treatment of hemophilic arthritis with D-penicillamine: a preliminary report.

Current medical management programs for established joint diseases in hemophiliacs are unsatisfactory and do not modify the eventual outcome. D-penicillamine, a drug effective in the proliferative synovitis of rheumatoid arthritis, was evaluated in a rabbit model of hemarthroses-induced arthritis and in four hemophiliacs with chronic synovitis. The animals had intra-articular injections of citrate (left knees) and autologous citrated whole blood (right knees). Eight weeks later, the rabbits were divided into two groups: no treatment and D-penicillamine (50 mg/kg/day, IM) until sacrificed at 6 months. The saline-injected joints showed no inflammation and no iron deposition. The blood-injected knees showed iron deposition in both groups, the D-penicillamine animals had marked suppression of chronic inflammation. Of the four patients treated, three had clinical responses (reduction in synovial thickness, reduction in number of bleeds in the affected joint). One patient, who did not respond, developed mild-moderate proteinuria. Those patients who responded received between 5.3 and 7.1 mg/kg/day of the drug. Mild abnormalities in platelet aggregation were seen in the responders. This preliminary study suggests that D-penicillamine is beneficial in the chronic synovitis/arthritis induced by hemarthroses. Further trials are recommended.

Animals↗
PubMed1985

Effects of preeclampsia on maternal and cord blood clotting activity.

This study was undertaken to evaluate the effect of preeclampsia on maternal and cord blood clotting parameters. Pregnant controls and preeclamptics plus their offspring had plasma analyzed for prothrombin time, partial thromboplastin time, fibrinogen, and clotting activity for factors II, V, VII, VIII, IX, X, XII, plus factor II antigen. Maternal data was consistent with that previously reported by numerous authors. The cord blood data showed that neonates of the preeclamptic mother had elevated fibrinogen and decreased II, V and VII activity, plus decreased II antigen. The data indicates that abnormal clotting parameters seen in the neonates from preeclampic mothers may result from impaired liver function and not as previously thought, from a deficiency in neonatal vitamin K.

Apgar Score↗
PubMed1985

Iron and the exclusively breast-fed infant from birth to six months.

This study was designed to determine whether normal, full-term, exclusively breast-fed infants develop iron deficiency anemia, as defined by hemoglobin or red blood cell indices more than two standard deviations below the age-specific mean, or depletion of iron stores, as defined by an abnormally low serum ferritin level. Thirty-three breast-fed infants were followed from birth to 6 months. Maternal blood and cord blood at delivery, and venous blood from the infants at 2, 4, and 6 months were analyzed for anemia as defined above. At 6 months of age, the mean hemoglobin concentration of these infants was slightly higher than the normal mean; four of 33 infants (12%) had a mean corpuscular volume greater than 2 SD below the reported normal mean; and two of 33 infants (6%) had a serum ferritin level less than 12 ng protein/ml. These data suggest that the infant who is exclusively breast-fed for the first 6 months of life is not at high risk for the development of iron deficiency anemia or the depletion of iron stores during that time.

Anemia, Hypochromic↗
PubMed1984

Vitamin K-dependent coagulation factors in gram-negative septicemia.

Coagulation studies were performed on 16 children with gram-negative septicemia without the complications of septic shock, liver disease, malnutrition, or laboratory evidence of classic disseminated intravascular coagulation (DIC). Ten (63%) of the 16 cases were found to have abnormal partial thromboplastin and/or prothrombin times. The coagulopathy was caused by a reduction in the vitamin K-dependent coagulation factors. The mechanism that produced this coagulopathy was not known, but evidence was found that suggested that endotoxin may interfere with the vitamin K-carboxylation reaction. The data indicated that abnormal coagulation screening test results in children with gram-negative septicemia were not specific for DIC and that a significant number of patients had a coagulopathy not related to DIC.

Blood Coagulation Disorders↗
PubMed1984

In vivo effect of polymyxin B on pertussis vaccine.

Pertussis vaccine contains lipopolysaccharide (endotoxin). Polymyxin B sulfate neutralizes endotoxin activity in vivo and in vitro from Enterobacteriaceae and Salmonella-derived endotoxin. In vitro, polymyxin B eliminates the endotoxin reaction of pertussis vaccine in the Limulus lysate test. In this study, platelet and WBC counts and antibody response were compared in rabbits given either pertussis vaccine alone or pertussis vaccine and polymyxin B intravenously. Pertussis vaccine-induced leukopenia and thrombocytopenia were eliminated in the polymyxin B group. The antibody titers in the animals receiving pertussis vaccine and polymyxin B were somewhat lower and rose more slowly. Since the toxicity of pertussis vaccine is related in part to endotoxin, we suggest that a clinical study using a combination of the vaccine with an endotoxin-neutralizing agent be done to assess both amelioration of side effects caused by the vaccine and any effect on immunogenesis.

Animals↗