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Biomedical subjects

J P Crowley

Publications and source records attributed to J P Crowley.

At least 19 recordsLinked to original sources

Immune responses to major histocompatibility complex homozygous lymphoid cells in murine F1 hybrid recipients: implications for transfusion-associated graft-versus-host disease.

Graft-versus-host disease (GVHD) is currently encountered after bone marrow transplantation and transfusion. GVHD associated with transfusion (TA-GVHD) in apparently immunocompetent recipients has been recently reported with increasing frequency. A consistent finding in many of these cases is that the recipient received blood from a donor homozygous for one of the recipient's HLA haplotypes. However, the observed frequency of TA-GVHD is much lower than the estimated probability of this donor/recipient combination. The potential role of recipient immune responses in controlling TA-GVHD was investigated using an analogous murine model in which GVHD is induced by the injection of parental lymphoid cells into unirradiated F1 hybrid recipients. The effect of various immune manipulations of the recipient of GVHD induction was assessed by determining the number of donor lymphoid cells required to induce GVHD responses. Whereas depletion of recipient CD4+ cells increased the number of donor cells needed to induce GVHD, depletion of recipient CD8+ and natural killer cells resulted in fewer donor cells being needed to induce a GVHD response. These studies suggest a central role for functioning recipient CD8 and natural killer cells in the down-regulation of TA-GVHD development in recipients.

Animals

Thrombotic thrombocytopenic purpura and HIV infection.

We report on a man who was HIV-seropositive and who was initially admitted following multiple episodes of syncope. He gradually developed fulminant thrombotic thrombocytopenic purpura (TTP). Twenty-one patients with TTP who were HIV-positive have been reported previously. Of these 22 patients, all treated with plasmapheresis, 7 died from TTP and 3 suffered relapse but eventually recovered. Delay in initiating plasmapheresis may be fatal. We have correlated the laboratory data of these patients at time of admission with subsequent clinical outcome; only the platelet count correlated with outcome. Patients with lower platelet counts were less likely to relapse or die with therapy. Physicians caring for patients infected with HIV should always consider the possibility of TTP in those patients with thrombocytopenia of unknown etiology. Review of the peripheral blood smear, allowing the detection of microangiopathic hemolytic anemia, is an important clue, enabling one to consider the correct diagnosis.

Adult

Therapeutic support of the patient with thrombocytopenia.

This article provides an update on the methods of collection, preservation, storage, and administration of platelet concentrates. The current indications for platelet transfusions are reviewed, and current knowledge concerning alloimmunization and its prevention is summarized. In addition, the ongoing controversies related to prophylactic administration of platelets versus therapeutic administration are reviewed.

Blood Platelets

Easy bruisability, aspirin intolerance, and response to DDAVP.

Easy bruisability raises the issue of bleeding during otolaryngological surgery. Ten female patients with easy bruisability were evaluated by aspirin challenge; clinical history and screening coagulation studies in these patients had revealed no evidence of a bleeding disorder. The baseline Ivy bleeding time (BT) test (4.5 to 9.5 minutes) was found to be normal in 6 patients and prolonged in 4 patients. Following treatment with aspirin, the bleeding time prolonged significantly in the three groups evaluated: normal controls (6.0 +/- 1.5 minutes vs. 8.4 +/- 2.0 minutes), patients with easy bruisability and a normal baseline (7.8 +/- 1.3 minutes vs. 12.0 +/- 1.6 minutes), and patients with easy bruisability and an abnormal baseline (11.0 +/- 0.7 minutes vs. 14.5 +/- 0.9 minutes). Administration of DDAVP (desmopressin acetate) 0.3 microgram/kg normalized the prolonged bleeding times in all groups after 7 days of daily aspirin therapy. Performing bleeding times before aspirin challenge, after aspirin challenge, and after DDAVP therapy following aspirin challenge is both a useful way of confirming aspirin sensitivity in patients with easy bruisability as well as a useful way of documenting improved hemostasis after DDAVP administration.

Adult

Infusion of stroma-free cross-linked hemoglobin during acute gram-negative bacteremia.

Twelve dogs were divided into two groups of six each, and were infused with bis-3,5-dibromosalicyl fumarate stroma-free hemoglobin (DBBF-Hb) or albumin. Their responses to an intravenous bolus of Escherichia coli were followed for 4 hr. Bacterial clearance from the blood stream was studied using standard colony counting methodology as well as blood counts, blood chemistries, and clotting factor analysis. There was a significant difference in mean arterial pressure (MAP) over time between DBBF-Hb-treated dogs and those treated with albumin (P < 0.02). While the DBBF-treated dogs had a higher MAP during the 10 min of bacteremia, after 1 hr, there were no longer any appreciable differences between septic dogs treated with DBBF-Hb vs. albumin. Consumption of clotting and natural anticoagulant factors was observed to be similar in both groups, as were endotoxin levels. Blood urea nitrogen (BUN) increased slightly in both groups, while white blood cell counts and clotting factor levels fell in both groups in a similar fashion. There was a more pronounced fall (P < 0.04) in platelet counts in the animals treated with DBBF-Hb. In the dogs treated with DBBF-Hb, there was also a late rise in pCO2 (P < 0.01), a more pronounced fall in pO2, and greater acidosis, which suggested that ventilation perfusion abnormalities may have been exacerbated by DBBF-Hb treatment. Since the exacerbation of respiratory abnormalities was not related to diminished bacterial or endotoxin clearance, the possibility is raised that DBBF-Hb interferes with compensatory respiratory changes during sepsis.

Acute Disease

Comparing the transfusion medicine content of the NBME's examinations in 1984-1985 and 1989-1990.

Recognition of the seriousness of transfusion-transmitted diseases has been demonstrated by U.S. medical schools through the integration of transfusion medicine (TM) content into their curricula. To evaluate the degree to which these changes in curricula have been reflected in the National Board of Medical Examiners' (NBME) examinations, a study conducted in 1991 evaluated the proportions of TM-related items on Parts I and II of the NBME examinations for 1984-1985 versus 1989-1990. Both Part I (basic sciences) and Part II (clinical sciences) demonstrated significant gains in TM items between the comparison periods (p less than .001), with Part II having the higher gain. An analysis of students' knowledge revealed that students in 1989-1990 tended to perform better on TM items than on examination items generally. The increases in TM content and student performance on TM items on the 1989-1990 examinations suggest that the national effort to expand and improve teaching of TM in U.S. medical schools has been effective.

Blood Transfusion

The effect of viable and nonviable autologous red blood cell transfusions on experimental bacteremia.

Nonviable red blood cells are rapidly cleared from the peripheral blood by the reticuloendothelial system. Since bacteria present in the blood stream are also cleared by the reticuloendothelial system, the possibility that nonviable red blood cells would interfere with the clearance of bacteria has been raised. Groups of dogs were studied in whom an experimental bacteremia was produced by the injection of E. coli (1 x 10(10)/kg). Bacterial clearance, endotoxin clearance, changes in mean arterial pressure, changes in oncotic pressure, and coagulation responses were monitored before and following autologous transfusion of approximately 10 cc/kg of packed red blood cells (PRBC) preserved with acid citrate dextrose or heparinized PRBC stored without preservative. In the latter blood product the majority of the red blood cells were nonviable. Clearance of E. coli over a 4-hr period was similar in the two transfused groups and in a control group without blood transfusion. Mean arterial pressure and blood pH fell significantly in all groups, but was again not significantly different among the groups studied. Endotoxin clearance, changes in oncotic pressure, blood oncotic proteins, and parameters of the blood coagulation system were also similar in all three groups. The results of this study indicate that in normal dogs made acutely bacteremic with E. coli, there were no significant differences over a 4-hr period in their hemodynamic or hematologic responses following transfusion of viable or nonviable autologous red blood cells.

Animals

Blood histamine levels following graded cold challenge in atypical acquired cold urticaria.

Acquired cold urticaria with a negative cold stimulation test has been described in seven patients in whom the standard ice cube test did not induce localized urticaria. Subsequent total body cold exposure induced a generalized urticaria. A patient with this syndrome is presented where blood histamine levels rose from 9 to 60 micrograms/dL after a negative local cold stimulation test and from 60 to 90 micrograms/dL after total body cold exposure. Urticaria occurred only after generalized cold exposure. Blood histamine levels following the ice cube test may represent a sensitive method to diagnose this form of atypical acquired cold urticaria, without subjecting the patient to the risk of anaphylaxis reported following total body cold exposure.

Adult

Human immunodeficiency virus-associated Hodgkin's disease. Clinicopathologic studies of 24 cases and preponderance of mixed cellularity type characterized by the occurrence of fibrohistiocytoid stromal cells.

Hodgkin's disease (HD) was diagnosed in 24 patients who were either seropositive for human immunodeficiency virus (HIV) (21) or members of a high-risk group (three), but had not developed acquired immune deficiency syndrome (AIDS). Clinical presentation of the disease was characterized by constitutional symptoms in all, especially fever (23/24) and disseminated disease (22/24) at diagnosis. Mediastinal adenopathy was rare. Bone marrow involvement was particularly frequent (12/24), and a positive bone marrow biopsy preceded lymph node biopsy in 5 of the 12. Histopathologic features of these tumors included an increased number of nonlymphoid stromal cells, i.e., histiocytic and/or fibroblastoid. In some tumors these fibrohistiocytoid stromal cells were arranged in bundles, but distinct nodule with birefringent collagen band formation was not observed. Twenty-two patients were treated, most with combination chemotherapy; one was untreated; one, unknown. Sixteen, including the one untreated, died with disease at 3 to 25 months; one died of an unrelated cause; four were alive at 3 to 24 months; three were lost to follow-up. Frequent bone marrow involvement at presentation suggests the usefulness of the bone marrow biopsy for diagnosis in subjects at risk, especially when they present with spiking fever of unknown origin. Contrary to most previous series, virtually all of our cases were of mixed cellularity type, characterized by increased fibrohistiocytoid stromal cells in place of depleting lymphocytes. The classic nodular sclerosing feature with birefringent collagen band formation was not observed. In conclusion, HIV-associated HD was characterized by advanced stage with fever at presentation, preponderance of mixed cellularity histologic type with increased fibrohistiocytoid stromal cells, and poor outcome. Hodgkin's disease in AIDS patients presents an intriguing biological model to study the role of stromal histiocytes in immunodeficient patients.

Adult

Increased levels of tissue plasminogen activator with a low plasminogen activator inhibitor-1 in a patient with postoperative bleeding.

Recurrent postoperative bleeding in a previously healthy man with a moderate prolongation of PT and PTT which did not correct with vigorous fresh-frozen plasma infusion was identified as a unique abnormality of the fibrinolytic system: a combination of an excess of tissue plasminogen activator (t-PA) at 300% of normal activity accompanied by a concurrent deficiency of plasminogen activator inhibitor-1 activity (PAI-1) of 10-20% of normal activity. This observation underscores the potentially important regulatory role of PAI-1 in the degree to which clinical manifestations of bleeding tendencies may occur in patients in whom an excess amount of t-PA is expressed.

Aged

The estimation of whole blood viscosity by a porous bed method.

A significant impediment in determining the relative contribution of whole blood viscosity to the pathogenesis of cardiovascular and cerebrovascular disease has been the lack of an uncomplicated method to measure whole blood viscosity. To address this problem, a simplified porous bed viscometer has been developed to measure whole blood viscosity. Whole blood is passed through a porous bed of branching channels with a mean pore diameter of 69.6 +/- 20.2 microns and an estimated mean shear rate of 19.6 seconds-1. The effects of sample collection, sample storage, and temperature are described. The mean whole blood viscosity of 242 healthy persons was 22.7 +/- 5.3 seconds, which, when corrected to centipoise using Darcy's equation, corresponds to an apparent viscosity of 5.7 +/- 1.3 cp. There was a significant difference in the whole blood viscosity of normal men and women related to their different packed cell volumes. Platelets and granulocytes influenced whole blood viscosity in proportion to their contribution to the total packed cell volume. Fibrinogen levels did not significantly influence measured whole blood viscosity, which is consistent with the disaggregating conditions and the mean shear rate of the instrument. The porous bed viscometer is a convenient means to measure whole blood viscosity and it should be useful as a screening test for clinical and epidemiologic studies.

Anticoagulants

Splenic artery ligation for splenic salvage: clinical experience and immune function.

Documentation of overwhelming post-splenectomy sepsis, characterized by infection from encapsulated organisms, has led to development of surgical techniques for preservation of the injured spleen to maintain splenic clearance of encapsulated, opsonized organisms from the circulation. In this study splenic artery ligation (SAL) was performed as an adjunct to successful splenorrhaphy in 20 adults suffering blunt splenic injury. There were no deaths and no reoperations. Twenty units of blood were transfused in ten patients. Splenic removal of blood-borne opsonized particles was measured as the clearance of anti-Rh-antibody-coated 51Cr-radiolabeled autologous red blood cells from the circulation in five SAL patients and nine normal volunteers. The clearance of opsonized red cells 120 minutes after injection was not different (40 +/- 7% of injected dose in controls, 40 +/- 4% in SAL patients). These results demonstrate that SAL can safely be applied as an adjunct to splenorrhaphy and that SAL does not diminish splenic clearance of opsonized particles from the circulation.

Adolescent

Lymphocyte subpopulations in long-term dialysis patients: a case-controlled study of the effects of blood transfusion.

Lymphocyte subsets in a group of intensely transfused (greater than 10 units/year) patients on long-term hemodialysis were compared with those in a carefully controlled population of lightly transfused (1-10 units/year, no units during study period) long-term dialysis patients. The data confirm previous reports of lymphopenia and a symmetrical reduction of both T- and B-cell subpopulations in patients on long-term dialysis. Eleven (36.7%) of 30 intensely transfused dialysis (ITD) patients had a low T8 population when expressed as a percentage value, while 0 of 25 lightly transfused dialysis (LTD) control patients exhibited a low percentage of T8 cells. There were no significant absolute differences between the lymphocyte subsets in the ITD and LTD patients. These data contrast with previous reports of other groups of ITD patients in whom there was an observed increase in T8 cytotoxic suppressor cells. Our findings suggest that the immunologic effects of renal failure and long-term dialysis largely override the increase in T8 lymphocyte subsets observed in other groups of transfused patients. There is little difference between ITD and LTD patients, but both groups are significantly different from nontransfused controls. Further longitudinal studies are needed in completely untransfused patients to resolve the contribution of minimal transfusion therapy to the immunologic deficits observed in long-term dialysis patients.

Adolescent