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Biomedical subjects

R D Gingrich

Publications and source records attributed to R D Gingrich.

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

Allogeneic marrow grafting with partially mismatched, unrelated marrow donors.

Forty patients with advanced hematologic malignancies or severe aplastic anemia received marrow grafts from partially mismatched, unrelated marrow donors. All patients were administered conventional prophylaxis for acute graft-v-host disease (GVHD) consisting of methotrexate and low-dose glucocorticoids. All but two patients who survived at least 30 days showed durable engraftment. Six patients survive 17+ to 36+ months following transplantation. Severe acute GVHD was seen in 47% of the patients; however, no direct correlation between GVHD and the degree of mismatching could be determined. Fatal infections were seen in 29 patients, and in the majority the infection occurred after the granulocyte count had risen to greater than 500 cells/microL. We conclude that the problems encountered in this pilot study can potentially be solved, and that further studies with this type of marrow grafting are warranted.

Adolescent↗
PubMed1987

Successful treatment of hepatic venocclusive disease in a bone marrow transplant patient with side-to-side portacaval shunt.

Hepatic venocclusive disease developed in a 14-yr-old white girl after allogenic bone marrow transplantation from an HLA-identical sibling donor. Clinical diagnosis of venocclusive disease was based on the development of ascites, hepatomegaly, and jaundice 3 wk after transplantation. Current treatment of hepatic venocclusive disease is ineffective. The pathophysiology of the hepatic lesion suggests that construction of a side-to-side portacaval shunt should be beneficial in relieving the ascites and preventing further hepatic damage. Because the ascites was refractory to medical therapy and she was clinically deteriorating, a side-to-side portacaval shunt was performed. Histologic examination of a liver biopsy specimen obtained at surgery documented the presence of venocclusive disease. Postoperatively, the patient diuresed and returned to her baseline weight. One year after surgery the patient was doing well, her weight was stable, and she was being maintained on salt restriction alone. While the resolution of ascites and improvement of hepatic function in our patient after side-to-side portacaval shunt does not guarantee that such an approach will be uniformly successful, it should serve to encourage others to consider such therapy for this frequently devastating complication of chemoradiation therapy.

Adolescent↗
PubMed1986

Cytogenetic analysis of adult acute lymphoblastic leukemia including a Ph+ case surviving more than 5 years.

We have performed cytogenetic analysis on 25 consecutive adult patients with previously untreated acute lymphoblastic leukemia (ALL) who were subsequently treated with the same protocol at this institution. Ten of the 25 patients studied (40%) demonstrated karyotypic abnormalities. The most frequent abnormalities were hyperdiploidy (six patients) and presence of the Philadelphia (Ph) chromosome (three patients). Univariate analysis of 12 features identified only immunophenotype as differing between patients with abnormal and normal karyotype. The cells of patients with an abnormal karyotype were more often non-B, non-T and less often T cell in phenotype. One patient initially with Ph remains cytogenetically normal in complete remission 272 weeks post diagnosis. We confirm that cytogenetic abnormalities are frequent in adult ALL. The attainment of disease free survival in Ph-positive ALL of more than 5 years with persistently normal cytogenetics demonstrates that aggressive multimodal therapy can induce long-term remissions and possible cure of this usually unfavorable situation.

Adolescent↗
PubMed1986

Trial of high-dose cytarabine, cyclophosphamide, total-body irradiation, and autologous marrow transplantation for refractory lymphoma.

Twenty-one patients with advanced non-Hodgkin's lymphoma or Hodgkin's disease who had failed to be cured with standard therapy were the subjects of this clinical trial. The patients received cytarabine (3 g/m2 at 12-hour intervals for six or eight doses), cyclophosphamide (90 mg/kg once), and total-body irradiation (one 900-cGy fraction or five 250-cGy fractions). Bone marrow was aspirated and cryopreserved before treatment and reinfused after the completion of radiotherapy. Eighteen patients (86%) had objective response and 12 (57%) achieved complete response. Three patients remain in continuous complete remission for 566+, 604+, and 1035+ days after marrow infusion. Six complete responders had tumor recurrence. One of these patients developed a localized lymphoma of another histology that was successfully treated with local radiotherapy and the patient is currently well 1004+ days after marrow infusion. Another relapsing patient responded to a brief course of salvage chemotherapy and is in remission at 1271+ days. Three of the complete responders died from infectious complications. This regimen was associated with significant toxicity. Six patients died from sepsis during the period of aplasia and three others died from interstitial pneumonia 42-105 days after marrow infusion. Although this regimen demonstrated a high level of antitumor activity, the value of adding high-dose cytarabine to the combination of cyclophosphamide and total-body irradiation remains unclear and would require a randomized clinical trial to demonstrate.

Adolescent↗
PubMed1986

Effect of high-dose cyclophosphamide and total-body irradiation on left ventricular function in adult patients with leukemia undergoing allogeneic bone marrow transplantation.

Protocols used to prepare patients with leukemia for bone marrow transplantation have the potential for cardiac toxicity due to high-dose cyclophosphamide and total-body irradiation. We have reported one regimen, combining cytarabine (5 mg/kg), cyclophosphamide (90 mg/kg), and total-body irradiation (900 cGy), which is relatively effective in the treatment of leukemia. To assess cardiac effects of this treatment regimen, we performed serial echocardiography and radionuclide ventriculography in 28 patients with leukemia (age range, 18-48 years; mean, 31; 21 males) undergoing allogeneic bone marrow transplantation. No significant change in left ventricular fractional minor axis shortening or increase in left ventricular diastolic dimension was seen with weekly echocardiography. At an average of 77 days (range, 28-358) after transplant, repeat radionuclide ventriculography in 17 patients revealed no significant change in resting left ventricular ejection fraction compared to that on admission to the hospital (58% +/- 6.8% vs 56% +/- 8.0% SD; P = not significant). In seven of these 17 patients (41%), resting ejection fraction fell between baseline and discharge (from mean of 60% to 50%). Resting ejection fraction in four of these patients (23% of the entire group) fell into the abnormal range (from mean of 56% to 44%; lowest, 41%). Ten patients also had exercise radionuclide ventriculography and all had normal responses (greater than 5% increase with exercise) pre- and post-transplant. We conclude that this effective bone marrow transplantation regimen has little apparent short-term cardiac toxicity in the majority of patients; since a few patients do exhibit a deterioration in left ventricular function, continued cardiac surveillance is probably indicated in posttransplant patients.

Adolescent↗
PubMed1985

The use of partially matched, unrelated donors in clinical bone marrow transplantation.

It is estimated that 60-70% of patients who might benefit from a bone marrow transplant will not have a suitably matched, related donor. We have, therefore, designed a clinical experiment to test the safety and feasibility of using marrow from partially matched, unrelated donors. This paper details our transplant experience in the first eight patients with leukemia. The first four patients had advanced leukemia at the time of transplantation. Each showed hematopoietic recovery, but all died from septic complications largely related to extended neutropenia encompassing both the pre-marrow-grafting and the post-marrow-grafting period. The next four patients were in remission at the time of transplantation. Each showed prompt and sustained hematopoiesis with variable graft-versus-host disease (GVHD). No acute or chronic GVHD was seen in two patients, grade II (skin only) was seen in one patient, and grade IV (skin, liver, and gut) was seen in one patient. One patient has died from sepsis five-and-one-half months following transplantation, and three are alive and well six-and-one-half to nine-and-one-half months postengraftment. This preliminary experience, together with several case reports in the literature, leads us to conclude that bone marrow transplantation with partially matched, unrelated marrow is a safe and feasible approach. If these results are confirmed by longer follow-up in a larger group of patients, the development of marrow donor pools would appear to be justified.

Adolescent↗
PubMed1985

Identification and characterization of an endothelial, cell-specific antigen with a monoclonal antibody.

The purpose of these studies was to use monoclonal antibodies to identify and characterize plasma membrane components unique to the vascular endothelium. Our assumption is that such components may perform some of the specialized functions of the endothelium and, by their identification with antibody probes, we may be able to study further their function and structure. Thus, primary cultures of human umbilical vein endothelium were used to immunize mice whose spleen cells were fused with the mouse myeloma cell NS-1. HEC-1 is a monoclonal antibody derived from such a fusion that appears to react with an antigen located only on endothelial cells. The antigen has been characterized by immunoprecipitation and polyacrylamide gel electrophoresis as a glycoprotein with a mol wt of 180,000 daltons under nonreducing conditions and 90,000 daltons under reducing conditions. Despite a close resemblance to a membrane component shown by others to be a receptor for transferrin, several lines of evidence reported in this paper indicate that this is not the function of the HEC-1 antigen. These data show that monoclonal antibodies can be used to identify and characterize membrane components of the vascular endothelium. Moreover, these probes can be used to inquire about the structure and function of the antigen with which they react.

Antibodies, Monoclonal↗
PubMed1985

Long-term relapse-free survival in adult acute lymphoblastic leukemia.

An intensive treatment program with curative intent was designed for adults with acute lymphoblastic leukemia (ALL). Forty-eight consecutive patients were treated with this protocol and 39 (81%) obtained a complete remission. Although the complete remission rate was high for patients with both null- and T-cell disease, those with null-cell leukemia had a significantly greater median duration of remission (greater than 306 weeks) than patients with T-cell disease (62 weeks). The median survival by life-table analysis for the 48 patients is projected to be greater than 310 weeks, and five patients have finished the 3-year treatment program and have been off therapy for 1-3 years without recurrence of disease. Classification of adult ALL by immune marker status is an important and easily done pretherapy maneuver that identifies subsets of patients with a significantly different prognosis when treated with the protocol described in this study. Those patients for whom leukemic cells had T-cell characteristics had a short median duration of remission. Most importantly, this treatment protocol identifies by therapeutic response a subset of adult patients with ALL whose leukemic blasts are characterized by the absence of immunological markers and who appear, in substantial proportion, to be potentially curable.

Actuarial Analysis↗
PubMed1984

A comparison of bone marrow transplantation with maintenance chemotherapy for patients with acute nonlymphoblastic leukemia in first complete remission.

Twenty patients treated with maintenance chemotherapy for acute nonlymphoblastic leukemia after achieving complete remission were compared with 13 patients who underwent bone marrow transplantation from an HLA-identical sibling. The median age was 27 years for both maintenance chemotherapy patients (range 17-42 years) and for patients undergoing bone marrow transplantation (range 16-42 years). The 1-year survival for maintenance chemotherapy was 80% vs. 54% with bone marrow transplantation (p = NS). Complete remission durability was 70% at 1 year for maintenance chemotherapy (34% projected for 5 years) compared with no relapses in the first year with bone marrow transplantation (p = 0.01). Patients on maintenance chemotherapy were hospitalized for an average of 22 days (range 0-171 days) during the first 12 months of treatment. Patients undergoing bone marrow transplantation were hospitalized for an average of 82 days (range 41-113 days) in the same time period. Severe hematologic toxicity was seen in 13/13 bone marrow transplantation patients and 6/20 maintenance chemotherapy patients. Chronic graft-vs.-host disease occurred in 3/7 surviving bone marrow transplantation patients. Maintenance chemotherapy had an average first year cost of +3,076.00 for patients who did not relapse and +48,827.00 for patients that relapsed. The first year costs for bone marrow transplantation averaged +84,102.00. Thus, maintenance chemotherapy was associated with a better early survival, less toxicity, and lower cost than bone marrow transplantation in the first year after initiating therapy. However, fewer relapses with bone marrow transplantation suggest that it will yield a higher long-term survival rate.

Acute Disease↗
PubMed1984

Marrow transplantation for stable-phase chronic granulocytic leukemia.

Ten patients with chronic granulocytic leukemia in the stable phase underwent marrow transplantation from HLA-identical siblings (nine cases) or an identical twin (one case) following preparation with cytarabine, cyclophosphamide, and total body irradiation. Marrow cytogenetics on all patients prior to transplantation revealed the Philadelphia chromosome without other evidence of aneuploidy. The immediate posttransplant course was in most cases relatively uncomplicated with only two serious infections and one death. All patients recovered with cytogentically normal marrow and leukemia has recurred only in the syngeneic transplant recipient. At present, nine patients are surviving from 358 to 961 days (median 597 days) after bone marrow transplantation. Bone marrow transplantation is capable of eliminating the abnormal clone of myeloid cells in patients with stable-phase chronic granulocytic leukemia and can be performed relatively safely in this "healthy" group of patients.

Adolescent↗
PubMed1983

Nosocomial Legionnaires' disease. Occurrence in recipients of bone marrow transplants.

Nosocomial pneumonia caused by Legionella pneumophila serogroup 1 occurred in five patients after bone marrow transplantation for hematologic malignancies. Two patients died as a result of the infection despite treatment with erythromycin. Serologic screening revealed no other cases of Legionnaires' disease in 40 consecutive recipients of bone marrow transplants, giving a frequency of infection of 13 percent. These five cases represent 23 percent of the pneumonia occurring in this group of patients. Patients undergoing bone marrow transplantation are highly susceptible to infectious complications. Legionnaires' disease must now be added to the list of pathogens infecting this group of patients. Erythromycin is not generally a part of standard empiric antibiotic regimens in febrile neutropenic patients, but appears to be a reasonable addition when pneumonia does not respond to conventional, empiric treatment. Even with appropriate therapy, Legionnaires' disease remains a highly lethal infection in immunocompromised hosts.

Adolescent↗
PubMed1983

Second lymphoid malignant neoplasms occurring in patients treated for Hodgkin's disease.

Patients who have been treated for Hodgkin's disease are at increased risk for second malignant neoplasms, particularly acute nonlymphoblastic leukemia and non-Hodgkin's lymphoid malignant neoplasms (NHLMs). We diagnosed five cases of NHLM in 242 patients initially treated for Hodgkin's disease between 1973 and 1980, giving a minimum incidence for this occurrence of 2.1%. The initial therapy for Hodgkin's disease, irradiation in three patients and chemotherapy in two patients, resulted in a complete remission in each case. The NHLM appeared 12, 13, 26, 30, and 54 months after the diagnosis of Hodgkin's disease. The cell type of NHLM and immunologic phenotype were as follows: large cell, immunoblastic T; large cell, immunoblastic null; large cell, cleaved and noncleaved B; large cell, cleaved and noncleaved (not studied); and lymphoblastic T. A review of 24 other cases of NHLMs, occurring in patients treated for Hodgkin's disease, reported in the literature, confirm the morphologic and immunologic heterogeneity. The poor response to therapy in our patients and those previously described demonstrate the seriousness of this phenomenon.

Adolescent↗
PubMed1981

Immunological delineation in normal and malignant cells of a membrane protein involved in glucose transport. II. Function of the antigen.

A review of the literature suggested that the antigen detected by the M/27 antibody described in the preceding paper might be involved in the transport of glucose across the cell membrane. This idea was tested by measuring the amount of M/27 antibody bound to cells under a range of conditions known to influence the rate of glucose uptake. Glucose starvation and the administration of insulin under appropriate conditions are known to increase the Vmax for glucose uptake in certain cells, and high cell density in vitro is known to decrease the Vmax. Glucose starvation was found to increase the amount of M/27 antigen present on the surface of 2 malignant cell lines, but produced no detectable change in 5 different non-malignant cell types. Insulin increased the amount of M/27 antigen on the surface of both malignant and non-malignant cells. At high cell density, the amount of M/27 antigen present on the cell surface decreased. The changes in the Vmax for glucose uptake produced by these manipulations have been shown not to require the synthesis of protein. This was also found to be true for the changes in M/27 antigen concentration. By disrupting cells in detergent, it could be shown that there was an intracellular pool of M/27 antigen. The total amount of M/27 antigen in the cell was found to be about 4 times as large as the amount of the antigen on the cell surface. This figure agrees with the value given in the literature for the size of the intracellular pool of the glucose transport system. The amount of M/27 antigen on the cell surface was found to vary during the cell cycle. A dramatic increase occurred early in S phase.

Animals↗
PubMed1981

Immunological delineation in normal and malignant cells of a membrane protein involved in glucose transport. I. Preparation and properties of the antibody.

Partially purified preparations of the 200000 Mr membrane glycoprotein described by Bramwell & Harris were used as antigens to generate monoclonal antibodies. Whether the protein was prepared from human or mouse tumours, the mice immunized with it yielded monoclonal antibodies of broadly similar specificities. All the antibodies obtained were of the immunoglobulin M class, despite a prolonged immunization schedule, and recognized an antigen that was present on the surface of mouse, rat and human cells. One such antibody, M/27, was studied in detail. With the exception of 2 rat kidney cell lines, the antigen detected by M/27 was found on the surface of all cells grown in culture, whether malignant or not. However, in the mouse, the species in which the antibody was generated, M/27 discriminated sharply between malignant tumours and normal tissues excised directly from the animal. In normal adult or embryonic mouse tissues, whether they were composed of multiplying cells or not, the antigen detected by M/27 was present on the cell surface only at the lower limit of detection, if at all. Malignant mouse tumours grown in the animal produced large amounts of the antigen. Explantation of embryonic mouse fibroblasts induced the expression of the antigen, which was not detected on these same cells in their normal habitat in the growing embryo. Conversely, non-malignant cells that express the antigen in vitro cease to do so when they are re-introduced into the animal. The antigenic determinant appeared to be polypeptide in nature rather than polysaccharide.

Animals↗
PubMed1979

Disseminated coagulopathy in chronic myelomonocytic leukemia.

The clinical and laboratory features of nine patients with chronic myelomonocytic leukemia are described. Hepatic or splenic enlargement accompanied by an absolute monocytosis in an older patient with an elevated serum or urine lysozyme and serum vitamin B12 levels were characteristic of the majority of patients in this series. No single clinical or laboratory finding was diagnostic for the disease. Most importantly, seven of nine patients had abnormal coagulation values; in two cases the abnormalities were consistent with disseminated intravascular coagulation and correlated with a hemorrhagic diathesis. It is concluded that patients with chronic myelomonocytic leukemia who have thrombocytopenia or a bleeding tendency should be evaluated for evidence of disseminated intravascular coagulation.

Aged↗
PubMed1979

Acquired agranulocytosis with granulocyte specific cytotoxic autoantibody.

Multiple infections and severe neutropenia were found in a previously healthy 29 year old man with no history of similar syndromes in the family, drug ingestion or exposure to environmental toxins. There was no evidence at the time of presentation of diseases previously associated with agranulocytosis (e.g., neoplasia, thyrotoxicosis, chronic infection, collagen-vascular disease or leukoagglutinating antibody). His serum contained a nonagglutinating, complement-dependent, cytotoxic antibody, however, reactive with peripheral blood granulocytes from 35 per cent of normal donors. The neutropenia was not affected by steroids but resolved promptly after splenectomy. Microscopic examination of the spleen revealed ingestion of polymorphonuclear leukocytes by splenic macrophages. Family studies indicated that the target antigen was non-HLA and that the antibody was not absorbed by lymphocytes or platelets. We conclude that the agranulocytosis was autoimmune in origin and suggest that similar myeloid-specific immune responses could influence granulocyte tranfusion and bone marrow transplantation by alloimmune "rejection" that would not be avoided by matching only for HLA specificities.

Adult↗
PubMed1979

Platelet-endothelial cell interactions.

We are in an era in which there has been a rapid accumulation of new information about the endothelium and the interactions of platelets with the vessel wall. The decade of the 70s could aptly be designated as the "prostaglandin and endothelium period." One can only speculate that the future will be equally interesting and challenging. It is quite possible that discoveries of congenital and acquired defects of the endothelium will parallel those already described for the platelet and coagulation factors. What is currently looked upon today as a baffling and frustrating case of resistant thrombosis by the clinician may be unraveled tomorrow by the talented and creative investigator who can develop better approaches to the study of the endothelium and platelet interactions with the vessel wall.

Animals↗