Search PubMed⌕ Search

Biomedical subjects

D Green

Publications and source records attributed to D Green.

At least 325 records · Page 18Linked to original sources

Thrombocytopenia in a prospective, randomized, double-blind trial of bovine and porcine heparin.

A prospective, randomized, double-blind clinical trial of bovine and porcine heparin was conducted. One hundred forty-one patients were randomized, of whom 89 received heparin treatment for six or more days (mean, ten days). Two developed severe thrombocytopenia (platelet count less than 20,000 per microliter); both were randomized to the bovine heparin group, but one inadvertently received two doses of porcine heparin. Laboratory investigation suggested that the thrombocytopenia in these two patients was immunologically mediated, and platelet reactivity to both bovine and porcine heparin was demonstrated. Twenty patients had a decline in platelet count of greater than 50,000 from baseline, although the total count remained above 150,000 per microliter. In seven of these subjects, the platelet count returned to its original level while heparin therapy was continued. Of the 13 patients with a persistent decrease in platelet count, ten had received bovine heparin and their counts decreased by an average of 88,000 per microliter; the reduction in the three porcine-treated patients was 68,000; this difference was not statistically significant. In the remaining patients, the post-treatment platelet counts in both groups were significantly higher than pretreatment values (p less than .005), perhaps indicating a cessation of the platelet consumption that accompanied the original thrombotic event.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effect of halothane on cardiac acceleration response to somatic nerve stimulation in dogs.

In six dogs, the authors investigated the effect of halothane on cardiac acceleration response to the electrical stimulation of a cutaneous nerve. It was found that increasing the concentration of halothane was associated with a proportional depression of the cardiac acceleration response to somatic nerve stimulation (y--99.8 - 44.3x; y--delta HR, x--halothane end-tidal concentration). Relationship of the response to end-tidal anesthetic concentration was characterized by a strong correlation (r= -0.93, P less than 0.0001). Complete abolition of the increase in heart rate in response to somatic nerve stimulation was observed at a halothane end-tidal concentration of 2.2 vol% (extrapolation). It is suggested that suppression of heart rate increase to noxious stimulation may be used as a graded index of the depth of anesthesia for halothane.

Animals↗

Mechanism and characteristics of platelet activation by haematin.

The mechanism as well as some characteristics of haematin-induced human platelet aggregation were investigated. Haematin-induced platelet aggregation required the presence of devalent cations; Mg2+, and to a lesser extent, Co2+, were just as effective as Ca2+ in supporting the aggregation. Mono- and trivalent cations were ineffective. Verapamil inhibited the aggregation. The aggregation was accompanied by thromboxane formation which could be abolished by aspirin. The release of adenine nucleotides was only slightly inhibited by aspirin. The rate of aggregation and the ultrastructure of the aggregated platelets were comparable between control and aspirin-treated samples. It is concluded therefore that haematin-induced aggregation is not dependent on platelet prosta-glandin synthesis. Haematin induced binding of fibrinogen to platelets, and failed to aggregate thrombasthenic platelets. These findings indicate that haematin may induce platelet aggregation by promoting influx of divalent cations in association with increased fibrinogen binding and release of adenine nucleotides.

Adenosine Triphosphate↗

A note on the temperature tolerance of Legionella.

A strain of Legionella pneumophila serogroup 1 isolated from the environment had a decimal reduction time in water at 50 degrees C (D50) of 111 min, a D54 of 27 min and a D58 of 6 min. There was little loss of viability at 46 degrees C. Other environmental organisms, a Pseudomonas sp., a Micrococcus sp. and a coliform survived less well at these temperatures. A species of Sarcina had a survival time greater than the L. pneumophila at all the temperatures tested. Other strains of legionellas were tested at 50 degrees C and decimal reduction times calculated. These ranged from 80 min for another strain of L. pneumophia serogroup 1 to 216 min for L. bozemannii . Legionella micdadei did not survive well at 50 degrees C.

Legionella↗

Effect of hematin on endothelial cells and endothelial cell-platelet interactions.

Hematin, a therapeutic agent for acute porphyrias, induces a coagulopathy characterized by thrombocytopenia and prolonged clotting times. In vitro, it activates platelets and inhibits thrombin and plasmin. Hematin has also been shown to participate in the activation of microsomal cyclooxygenase. The apparent diversity of hematin's effects on multiple hemostatic components as well as its role in prostaglandin synthesis led the authors to investigate the effects of hematin on endothelial cells and endothelial cell-platelet interactions. Marked morphologic alterations of cultured bovine aortic endothelial cells ( BAECs ) were noted after exposure to as little as 2 micrograms/ml hematin in HEPES buffer or to 40 micrograms/ml of hematin in plasma (a level achieved during hematin therapy). These changes included cell retraction and surface vesiculation. Despite the apparent severity of the changes, there was no associated cell lysis or detachment. Furthermore, the cells resumed their cobblestone appearance after hematin had been removed. Platelet adhesion to hematin-treated monolayers was significantly increased, especially when low concentrations of hematin were included in the platelet suspensions. Prostacyclin production was not increased by BAECs exposed to hematin, presumably because of the inaccessibility of hematin to cyclooxygenase in intact cells. The endothelial changes observed in tissue culture are consistent with the clinical observations of phlebitis at the injection site and provide an additional explanation for the thrombocytopenia in patients receiving hematin therapy.

Animals↗

Factor VIII-related antigen in occluded human arteries and grafts.

Direct immunofluorescence was used to determine the disposition of factor VIII-related antigen (VIIIR:Ag) in occluded arteries and grafts from patients undergoing reconstructive operation. The presence of VIIIR:Ag on the luminal surface of these vessels was equated with their endothelialization according to the work of others. In 12 of the 20 arteries examined, stain for VIIIR:Ag was absent or markedly reduced from the luminal surfaces, and in six more it was only present focally. The adventitial capillaries were brightly stained in most of these specimens. Both of two saphenous vein grafts and all of six Dacron grafts stained for VIIIR:Ag along their luminal surfaces and in the adventitial capillaries as brightly as normal arteries. However, all of eight Gore-tex grafts had little or no stain for VIIIR:Ag along their luminal surfaces, and the capillaries of the adventitia were not as plentiful as those in the normal arteries and Dacron grafts. With one exception, the Gore-tex grafts had become occluded less than 1 year after implantation, while the Dacron grafts had remained patent for 2 to 8 years. Thus many of the diseased arteries and the short-lived Gore-tex grafts were characterized by relative absence of VIIIR:Ag from their luminal surfaces, presumably reflecting the loss or absence of endothelialization.

Adult↗

The management of factor VIII inhibitors in non-hemophilic patients.

The experience of 118 coagulation specialists in the treatment of 215 non-hemophilic patients with inhibitors to factor VIII:C was recently reviewed. In approximately half these patients there were no illnesses which may have predisposed to inhibitor formation, while "auto-immune" disorders such as rheumatoid arthritis and systemic lupus erythematosus were present in 18%. Major bleeding was reported in 87% of the patients, and 22% died as a consequence of having the inhibitor. While inhibitors in a few patients, particularly those that developed in association with pregnancy, disappeared without treatment, most patients were given prednisone in doses of up to 2 mg/kg per day. This therapy was most effective in patients without associated disorders, but disappearance of the inhibitor in patients with rheumatoid arthritis usually occurred only when cyclophosphamide or azathioprine was added to the therapeutic regimen. Subjects with inhibitor titers in excess of 10 Bethesda Units were usually refractory to all therapeutic modalities. The management of acute bleeding episodes in the patient with an inhibitor has been the subject of a number of recent reports. Successful stratagems have included intensive plasmapheresis combined with massive infusion of antihemophilic factor concentrates, the use of porcine factor VIII concentrates, and the administration of clotting factor concentrates which bypass the locus of factor VIII participation in clotting. All of these methods expose the patient to potential serious side-effects, and the ultimate solution to the problem of the development of factor VIII inhibitors will require insights into the reasons for the production of these antibodies and measures to regulate aberrant immune processes.

Animals↗

Sequential changes in coagulation and platelet function following femorotibial bypass.

Twenty-four patients who received no antiplatelet medications and underwent femorotibial bypass grafting (nine vein, 12 polytetrafluoroethylene [PTFE], and three composite PTFE-vein) had serial measurements taken of their platelet function and coagulation. The concentration of collagen required to produce half-maximal platelet aggregation (Kd), the platelet aggregation ratio, antithrombin III, factor VIII-related antigen, and fibrinolytic activity (platelet-rich plasma) was measured preoperatively and 3 and 7 days after surgery. Before surgery eight patients exhibited an increase of platelet reactivity to collagen. Following femorotibial bypass grafting, the mean preoperative Kd of 0.52 +/- 0.37 microgram/ml fell to 0.34 +/- 0.35 microgram/ml on the third postoperative day (P less than 0.001) and returned to 0.41 +/- 0.72 microgram/ml on day 7. Factor VIII-related antigen increased from a mean preoperative value of 248 +/- 29% of normal activity to a mean of 360 +/- 96% on postoperative day 3 (p less than 0.01) and further increased to 428 +/- 78% on day 7 (p less than 0.01). Fourteen patients had antithrombin III measurements taken, and their levels also fell on the third postoperative day (110 +/- 5.7% to 71 +/- 6.5%; p less than 0.001). No significant changes in fibrinolytic activity were noted. Persistent platelet reactivity was found in seven patients beyond the seventh postoperative day. After administration of 325 mg of aspirin, the abnormal platelet reactivity ceased. Increased platelet reactivity to collagen, factor VIII-related antigen, and a decrease in the antithrombin III level are indicative of a hypercoagulable state in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens↗

Antithrombin III deficiency as a reflection of dynamic protein metabolism in patients undergoing vascular reconstruction.

Antithrombin III (AT-III) deficiency has been associated with increased risk of venous and arterial thromboses and arterial graft failure. Deficiency of this circulating glycoprotein may be congenital; however, acquired deficiencies may develop in protein-losing or protein-wasting states. In the present study, AT-III levels of 108 patients undergoing vascular surgical procedures were determined preoperatively and at intervals (third, fifth, and seventh days) postoperatively. The mean AT-III level was then compared to the patient's protein status. The effect of reduced AT-III activity on early graft failure was also noted. A low preoperative AT-III level (less than 80%) was found in 16.3% of the patients studied. Among 83 patients with serum albumin levels greater than 3.0 gm/dl or transferrin levels greater than 180 mg/dl, reduced AT-III activity was present in only 10 (12%). In contrast, when serum albumin levels were less than 3.0 gm/dl, AT-III deficiency was found in 12 of 25 patients (48%) (p less than 0.01). Early thrombosis of a femorodistal graft occurred in 5 of 15 patients (33%) with reduced AT-III levels. When AT-III levels were normal, early bypass failure occurred in only 9 of 67 grafts (13.4%). However, this difference was not statistically significant. An additional 15 patients had sequential pre- and postoperative measurements (up to 3 weeks) of serum protein and AT-III levels to illustrate the relationship between the dynamics of protein metabolism and AT-III levels. There was a clear temporal relationship between albumin, transferrin, and AT-III levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Increased pulmonary edema with crystalloid compared to colloid resuscitation of shock associated with increased vascular permeability.

Physiologic effects of colloidal (5% albumin, 6% hydroxyethylstarch, 6% dextran-70) and crystalloidal (Ringer's lactate) fluids were examined in rats (six in each fluid group) after infusion of an LD99 of rattlesnake venom, previously shown to produce shock secondary to increased vascular permeability. Venom infusion (iv, 2.0 mg/kg, 30 min) was followed by fluid infusion (iv, 30 min) in quantities sufficient to reverse venom-induced hemoconcentration. Venom infusion decreased mean arterial pressure, increased blood lactate, and increased hematocrit in all animals (p less than .01). Fluid infusion reversed these changes, although six times the volume of crystalloid was required to produce hemodilution comparable to the colloidal fluids (120 ml/kg Ringer's lactate, 20 ml/kg colloids). Although no significant changes in the respiratory parameters were noted after administration of the three colloids, Ringer's lactate produced decreases in PaC2 (107 +/- 6 torr, mean +/- SEM to 72 +/- 7, p less than .05), increases in PaCO2 (30 +/- 4 torr to 55 +/- 5, P less than .001), decreases in plasma colloid osmotic pressure (14.2 +/- 0.8 torr to 6.6 +/- 0.9, p less than .001) at the end of fluid infusion. These changes were associated with significantly increased wet-dry lung ratios (p less than .001) in identically prepared animals, sacrificed after fluid infusion. In spite of the development of pulmonary edema in the crystalloid-treated animals, survival was similar for each group (6/6 for albumin and dextran, 5/6 for hydroxyethylstarch and Ringer's lactate). We thus conclude that both colloidal and crystalloidal fluid resuscitation leads to survival in permeability shock. Resuscitation with crystalloidal fluid, however, requires significantly greater volumes and is associated with the development of pulmonary edema.

Animals↗

Biphasic changes in hemoglobin A1c concentrations during normal human pregnancy.

Analyses of hemoglobin A1c concentrations were performed throughout gestation in 377 nondiabetic women. We observed significant biphasic changes in hemoglobin A1c concentrations, with an initial gradual decline to a nadir level at 24 weeks, followed by a subsequent slow reascension to peak near term. All these changes fell within the usual range of normal values for hemoglobin A1c. Values for plasma glucose estimated 1 hour after a 50 gm oral glucose load in 1,756 normal gravid women showed similar biphasic excursions, with the nadir occurring 4 weeks earlier, i.e., at 20 weeks' gestation. We conclude that the small but significant changes in hemoglobin A1c during the course of normal gestation reflect, with an appropriate displacement in time, the biphasic alterations in mean blood sugar that characterize the sequential changes in glucoregulation during normal pregnancy.

Blood Glucose↗

Warfarin-induced factor VII deficiency and the bleeding time.

The effect of warfarin-induced factor VII deficiency on the skin bleeding time was investigated in 10 consecutive patients with mean prothrombin times of 33 sec and factor VII levels of 7%. Bleeding times in all but one subject were entirely within the normal range. We conclude that warfarin administration, even to the point of prolonging the prothrombin time beyond the therapeutic range, is not associated with an abnormal bleeding time. Furthermore, from the above evidence and a review of the literature, it is considered doubtful that factor VII plays a major role in primary hemostasis.

Bleeding Time↗

Acquired immunodeficiency syndrome in a patient with multiple risk factors.

To our knowledge, we report the first case of a homosexually active man with severe hemophilia A in whom acquired immunodeficiency syndrome (AIDS) developed. Alterations in cell-mediated immunoregulation and development of AIDS have been described in both healthy homosexually active men and heterosexual men with hemophilia A. Patients with multiple risks may be more likely to have AIDS develop. Physicians should be aware of the risk factors associated with AIDS; persons with multiple predisposing factors require intensive examination and close follow-up.

Acquired Immunodeficiency Syndrome↗

Structure and evolution of human Y chromosome DNA.

Two repeated sequences account for 70% of the DNA of the human Y chromosome. They are located in the heterochromatin of the long arm. These sequences are related to others found on human chimpanzee and gorilla autosomes, and on the human X chromosome but have diverged in a characteristic way from the non Y copies. They have no detectable phenotypic effect when translocated to autosomes. We have cloned DNA from the human Y chromosome using fluorescence activated cell sorting. At least one single copy sequence is present on both the X and Y chromosomes.

Animals↗

Numerical judgments with Kanji and Kana.

Native Japanese speakers were timed to judge the numerically larger of two numbers, written either in Kanji (an ideographic script) or in Kana (a syllabic script). For Kanji, irrelevant variations in the physical size of the numbers speeded reaction time in one condition and slowed it in another. Such variations only slowed processing for Kana, except when subjects had previously performed with Kanji. For both scripts, reaction time varied with the numerical difference between the two numbers but not in an identical manner. The implications of the findings are considered.

Adolescent↗