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Biomedical subjects

J P Gockerman

Publications and source records attributed to J P Gockerman.

At least 19 recordsLinked to original sources
PubMed1992

Parenteral anticoagulation with the heparinoid Lomoparan (Org 10172) in patients with heparin induced thrombocytopenia and thrombosis.

Progressive thrombocytopenia may develop in as many as 5% of patients receiving heparin anticoagulation. In these patients, the risk of thromboembolic complications as well as continued thrombocytopenia necessitates discontinuation of heparin and initiation of an alternative anticoagulant when indicated. The heparinoid Lomoparan (Org 10172) is a mixture of several non-heparin low molecular weight glycosaminoglycans with proven anticoagulant efficacy that is generally non-reactive with platelets in the presence of plasma from patients with heparin induced thrombocytopenia, whereas standard heparin will induce platelet aggregation. We evaluated the role of heparinoid as a potential alternative anticoagulant in patients with heparin induced thrombocytopenia. During a 6 month period, we identified six patients with heparin induced thrombocytopenia who required an alternative parenteral anticoagulant, four as primary treatment for specific medical problem, and two as anticoagulation during a necessary surgical procedure. Heparinoid was used successfully in both medical and surgical patients requiring parenteral anticoagulation. In no case was there an exacerbation of the thrombocytopenia nor thromboembolic complications while on heparinoid therapy. Three of our patients sustained hemorrhagic complications, predominantly in the post-surgical setting in association with elevated anti-factor Xa levels and additional anticoagulant agents. We feel that these results confirm the utility of heparinoid anticoagulation in a select subset of patients with heparin induced thrombocytopenia who require continued parenteral anticoagulation.

Anticoagulants↗
PubMed1991

The use of prophylactic eye drops during high-dose cytosine arabinoside therapy.

An ocular toxic reaction presenting as conjunctivitis or keratitis develops in a significant number of patients who are treated with high-dose cytosine arabinoside (ara-C). Although eye drops containing glucocorticoid reportedly decrease the incidence, they do not totally eliminate this side effect. In comparing this technique with artificial tears, both were found to be equally effective. The primary mechanism by which eye drops decrease ocular toxic reactions associated with high-dose ara-C is presumably due to dilution of intraocular concentrations of ara-C.

Adult↗
PubMed1990

Improved survival in advanced Hodgkin's disease with the use of combined modality therapy.

To compare the effectiveness of combined modality therapy and chemotherapy alone for the treatment of advanced Hodgkin's disease (Stages IIB-IV), records of 154 patients who achieved a complete or partial response to induction combination chemotherapy were analyzed. Sixty-seven patients received consolidation radiotherapy and 87 patients received no further treatment. Thirty of 154 patients participated in a prospective randomized trial of the Southeastern Cancer Study Group (SEG). Ten-year actuarial survival (Hodgkin's disease deaths only) was 93% for the combined modality therapy patients compared with 59% for the chemotherapy alone patients (p less than 0.0005). Combined modality therapy patients had an 87% 10-year actuarial freedom from relapse as opposed to 56% for the chemotherapy alone patients (p less than 0.0005). Relapse occurred in 33 of the chemotherapy alone patients, 28 (85%) being in sites involved at initial diagnosis. Seven combined modality therapy patients recurred with only two true in-field failures. Multi-variate analysis demonstrated treatment (combined modality) as the only variable affecting outcome. Patients prospectively treated with combined modality therapy in the Southeastern Cancer Study Group trial also showed a statistically significant improvement in both survival and freedom from relapse compared with patients receiving chemotherapy only. There was no apparent increase in toxicity from using combined modality therapy compared with chemotherapy. Three chemotherapy patients and one combined modality therapy patients developed acute leukemia.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Clinicopathologic and cytogenic features of CD34 (My 10)-positive acute nonlymphocytic leukemia.

The authors performed membrane antigen phenotyping on 75 patients with acute nonlymphocytic leukemia with a panel of myeloid-associated monoclonal antibodies. The 34 patients (45%) with CD34-positive leukemia were not significantly different from the 41 with CD34-negative leukemia with respect to age, hemoglobin, white blood cell count, or platelet count at presentation, but their blasts were more likely to lack the CD15 or CD33 antigens and to have FAB M1 or M2 morphologic characteristics. CD34-positive leukemia was more likely to arise after chemotherapy. Patients with CD34-positive leukemia were less likely to enter a complete remission even when analysis was limited to those patients receiving a high-dose induction-type chemotherapy regimen. Giemsa-banding karyotyping studies were obtained in 55 of the cases. In 30 of these cases (56%) clonal karyotypic abnormalities were demonstrated. Although the karyotypic abnormalities and phenotypes were varied, there was a high degree of association between the karyotypic abnormalities monosomy 7/del (7q) and the CD34-positive phenotype; this antigen was expressed on blasts from eight of the nine patients displaying this abnormality. Monoclonal antibody phenotyping of myeloid leukemia with reagents such as anti-CD34 may help to define biologically interesting subsets of ANLL with distinct clinicopathologic expression.

Antigens, Differentiation↗
PubMed1988

Evidence for a selective antileukemic effect of cytosine arabinoside in chronic granulocytic leukemia.

On the basis of in-vitro studies indicating that low concentrations of cytosine arabinoside exert preferential inhibition of granulocyte-macrophage colony-forming cells from patients with chronic granulocytic leukemia vs normal subjects, we treated two outpatients with low doses of this agent, administered by subcutaneous infusion for 12-31 days. Both patients continued their usual activities, including employment, during these infusions. They exhibited only Ph-positive metaphases at entry into the protocol but in both cases, Ph-positive cells were reduced to approx. 10% of marrow metaphases, after 2-3 successive infusions. Both patients exhibited significant increases in Ph-positive cells, to 46 and 72% of marrow metaphases, during subsequent chemotherapy with hydroxyurea, in dosage sufficient to maintain granulocytopenia and a normal serum B12 level. After additional cytosine arabinoside, both patients again showed decreases in Ph-positive cells, to 7% (p less than 0.01) and 19% (p less than 0.0001), respectively. This clinical experience is consistent with the conclusion that cytosine arabinoside (but not, hydroxyurea) exerts a selective antileukemic effect in some patients with CGL.

Adult↗
PubMed1988

High-dose combination alkylating agents with bone marrow support as initial treatment for metastatic breast cancer.

To evaluate the effect of high-dose chemotherapy in the treatment of metastatic breast cancer, we performed a phase II trial of a single treatment with high-dose cyclophosphamide (5,625 mg/m2), cisplatin (165 mg/m2), and carmustine (600 mg/m2), or melphalan (40 mg/m2) and bone marrow support as the initial chemotherapy for metastatic breast cancer. Twenty-two premenopausal patients with estrogen receptor negative, measurable metastatic disease were treated. Twelve of 22 patients (54%) obtained a complete response at a median 18 days. The overall response rate is 73% (complete and partial response). Median duration of response in the patients achieving complete response was 9.0 months with a median duration of survival for complete responders that is currently undefined. Relapse occurred predominantly at sites of pretreatment bulk disease or within areas of previous radiation therapy. Toxicity was frequent and five patients died of therapy-related complications. The results indicate that a single treatment with intensive combination alkylating agents with bone marrow support can produce more rapid and frequent complete responses than conventional chemotherapy when used as initial chemotherapy for metastatic breast cancer, although median disease-free and overall survival is not improved. Three patients (14%) remain in unmaintained remission beyond 16 months.

Adult↗
PubMed1986

Cytomegalovirus glomerulopathy: a controversial lesion.

Seven autopsies performed on immunosuppressed bone marrow transplant recipients who died with documented herpes virus infection were reviewed. The kidneys were studied by light and electron microscopy and revealed no pathological findings, specifically no glomerulopathy or tubular interstitial nephritis. Seven renal biopsies performed on kidney transplant recipients in whom a diagnosis of cytomegalovirus glomerulopathy was entertained were also studied. These patients exhibited clinical parameters suggestive of cytomegalovirus infection. Three patients had subsequent nephrectomies and two showed severe acute vascular rejection. The one kidney without demonstrable acute vascular rejection was negative for cytomegalovirus on culture. Three additional patients improved or stabilized their renal function under therapy for rejection. Light, electron microscopic and immunofluorescent studies, although confirmatory of endothelial cell damage, did not substantiate active cytomegalovirus renal infection in these patients. An additional group of fifteen children with disseminated cytomegalovirus infection revealed no evidence of glomerulopathy. Finally, two kidney transplant recipients with proven cytomegalovirus infection (one with associated tubular interstitial nephritis) also showed no glomerular alterations. It is the author's opinion that the entity that has been considered as cytomegalovirus glomerulopathy probably represents rejection, either a peculiar anti-endothelial type of rejection or a protracted, early, or partially resolved acute vascular rejection without residual or identifiable acute vascular rejection changes in the tissue sampled.

Adolescent↗
PubMed1978

The lipids of the erythrocyte in paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is a disorder characterized by the production of abnormal erythrocytes (PNH-E). The PNH-E undergoes early intravascular destruction which appears to be related to an intrinsic membrane defect that results in extreme sensitivity to lysis by complement. The lipids of the PNH-E have been evaluated because of the variable results reported in the past. This study shows a normal content of cholesterol and lipid phosphorus with a normal distribution of the phospholipids except for a slight increase in lysophosphatidyl choline (LPC) when measured using the complete lipid extract of the PNH-E. Fractionation of the lipid extract over a silicic acid column produced an alteration in the distribution of the phospholipids, with LPC and sphingomyelin increasing, and the other phospholipids decreasing. These alterations were seen only when the phospholipids were fractioned over a silicic acid column and were clearly an in vitro phenomenon. The levels of plasmalogen and malonaldehyde were normal, unlike those seen with oxidant stress. Fatty acid analysis of the phospholipids showed small but consistent changes: increased 16:0 and decreased 18:2. The total glycosphingolipids were slightly decreased in the patients with severe PNH. The results support and extend previous lipid data indicating abnormalities in the phospholipids of the PNH-E. The alterations of the phospholipids with fractionation correlate with previous whole cell data that suggest lipid instability in the PNH-E.

Animals↗
PubMed1977

Heparin-induced decrease in circulating antithrombin-III.

Plasma-antithrombin-III (AT-III) concentrations were measured throughout therapy in 24 patients receiving continuous intravenous heparin infusion and in 2 patients treated with repeated intravenous heparin injections. In all patients, including 1 with congenital AT-III deficiency, heparin therapy was associated with a considerable progressive reduction in AT-III-binding capacity and antigenic protein. The net individual decrease in plasma-AT-III was 0-31 +/- 0-05 units/ml (normal plasma-AT-III was 1-00 units/ml) or 9-5 +/- 2-0 mg/dl and the decrease was independent of initial concentration. Plasma-AT-III returned to normal two to three days after heparin was stopped. There was no decrease in plasma-AT-III after a single dose of intravenous heparin. When present in blood for long periods heparin significantly reduced AT-III, the proteinase inhibitor that is responsible for the anticoagulant effect of this drug. The finding is very relevant to the interpretation of clinical data in patients treated with heparin and suggests that AT-III depletion may underly the thromboembolic complications sometimes encountered during heparin therapy.

Antigens↗
PubMed1977

RBC transfusions in paroxysmal nocturnal hemoglobinuria.

Frozen-thawed, deglycerolized RBCs can be substituted for saline-washed RBCs for transfusion of patients with paroxysmal nocturnal hemoglobinuria (PNH). The effect of transfusion is to decrease bone marrow production of RBCS, which results in a decreased percentage of complement-sensitive erythrocytes. In the presence of small numbers of complement-sensitive erythrocytes, major vascular surgery can be performed without hemolytic problems. This study suggests that the percentage of complement-sensitive RBCs, as well as the complement sensitivity of these cells, influence the severity of hemolysis in persons with PNH.

Antigen-Antibody Reactions↗
PubMed1976

Procoagulant and platelet aggregating properties of antilymphocyte sera.

Ten anti-human lymphocyte sera in clinical use at six transplant centers and five anti-nonhuman lymphocyte sera were studied for their procoagulant and platelet-aggregating properties. This investigation was initiated following the observation of a clinical episode of renal artery thrombosis, associated with the use of one of the sera in a patient who had received a cadaveric renal transplant. The procoagulant from this serum shortened the clotting times of individual samples deficient, respectively, in factors XII, XI IX, X VIII, and VII. Esterolytic activity, demonstrated on the substrate benzoylarginine ethyl ester, was completely inhibited by phenylmethylsulfonyl fluoride, but coagulant activity was variably affected. The platelet-aggregating activity (PAA) has been identified as a complement-fixing gamma G antibody that was absorbed from the antilymphocyte serum (ALS) with human spleen lymphocytes. Five of the ten anti-human lymphocyte sera showed varying procoagulant activity (PCA), and six sera demonstrated PAA. Three sera contained both activities. The presence of both PCA and PAA in the same preparation may predispose patients to thrombotic events, particularly if administered intravenously. Sera should be screened for PCA and PAA prior to clinical use, and sera with these properties should be used with caution.

Animals↗
PubMed1975

Vitamin A in liposomes. Inhibition of complement binding and alteration of membrane structure.

Incorporation of vitamin A aldehyde (retinal) into liposomes had an inhibitory effect on the amount of human complement protein bound in the presence of specific antiserum. The total membrane-bound protein was directly measured on liposomes which were washed after incubation in antiserum and fresh human serum (complement). At every concentration of complement, decreased protein binding was found with liposomes which contained retinal. Binding of the third component of complement (C3) was also measured directly on washed liposomes and was found to be decreased in the presence of retinal. The diminution in protein binding due to retinal was not caused by differences in the amount of antibody bound and this was shown by two experiments. First, specific antibody protein binding to liposomes was directly measured and was essentially unaffected by retinal. Second, liposomes were prepared from lipid extracts of sheep erythrocytes. These liposomes were used as as immunoadsorbants to remove antisheep erythrocyte antibodies. The immunoadsorbant capacity was the same in both the presence and the absence of retinal. A further conclusion from these experiments was that retinal did not change the number of liposomal glycolipid antigen molecules available for antibody binding and thus presumably did not change the total number of lipid molecules present on the outer surface of the liposomes. Retinal did have an effect on the geometric structure of the liposomes. Size distribution measurements were performed in the diameter range of 1-6.35 mum by using an electronic particle size analyzer (Coulter Counter). Liposomes containing retinal were shifted toward smaller sizes and had less total surface area and volume. It was suggested that retinal-containing liposomes may have had a tighter packing of the molecules in the phospholipid bilayer. This effect of retinal on liposomal structure may have been responsible for the observed decreased binding of C3 and total complement protein.

Animals↗
PubMed1975

The abnormal surface characteristics of the red blood cell membrane in congenital dyserythropoietic anaemia type II (HEMPAS).

The red blood cell membranes of patients with congenital dyserythropoietic anaemia Type II (CDA-II) were found to be abnormal. They had altered antigenic characteristics, decreased electrophoretic mobility, decreased sialic acid content, and abnormal filtration through polycarbonate filters. Proteins extracted from the CDA-II erythrocytes showed a different banding pattern on polyacrylamide gels compared to normal erythrocytes. Erythrocytes from clinically unaffected siblings and parents showed similar but less striking abnormalities of antigenic surface characteristics and banding patterns on polyacrylamide gels with nearly normal surface charge, sialic acid content, and filtration properties. These studies suggest a correlation between the degree of membrane abnormality and the clinical state of the CDA-II family member, demonstrate the erythrocyte in the heterozygote state is not normal, and support the concept of CDA-II as an autosomal recessive disease.

Agglutination Tests↗