Biomedical subjects

R D Gingrich

Publications and source records attributed to R D Gingrich.

At least 19 recordsLinked to original sources

PubMed1991

Fungal pulmonary infections after bone marrow transplantation: evaluation with radiography and CT.

The authors reviewed 55 pairs of chest radiographs and computed tomographic (CT) studies obtained in 33 febrile bone marrow transplant (BMT) recipients. The images were read separately, without knowledge of the clinical diagnosis. Twenty-one episodes of fungal infection were documented. One chest radiograph showed a pneumonia-like opacity, and 17 showed nodular opacities, five with cavitation. In 20 of 21 episodes, CT showed nodules with cavitation (n = 7), halo (n = 4), hazy margin (n = 5), air bronchogram (n = 2), cluster of fluffy nodules (n = 1), or sharp margin (n = 1). In none of the nine bacteremic episodes, however, were there opacities on chest radiographs or CT studies. CT studies demonstrating complicated nodules in febrile BMT patients strongly suggest a fungal infection, whereas negative CT studies suggest bacteremia or non-filamentous fungal infection of nonpulmonary origin. CT appears to add useful information to radiographic analysis during the assessment of febrile episodes in BMT patients, especially when invasive diagnostic procedures pose a high risk.

Adult↗

PubMed1991

Nosocomial pneumonia in adult patients undergoing bone marrow transplantation: a 9-year study.

Two hundred seventy-five consecutive patients treated with bone marrow transplantation (BMT) during a 9-year interval were analyzed for the incidence and etiology of nosocomial pneumonia. Cases included adults who acquired pneumonia during the first hospitalization period within 100 days of the transplant. Fifty-five (20%) of the 275 patients developed nosocomial pneumonia, and the crude mortality during the hospitalization period was 74.5%. An etiology was established in 67.3% (37 of 55) of episodes. Thirty-six percent (20 of 55) of the cases were caused by Aspergillus species, either as the sole agent (15 patients) or in association with others. The crude mortality for patients with Aspergillus pneumonia was 95%. Elimination of 90% of Aspergillus cases in our unit would have the effect of reducing the overall attack rate of nosocomial pneumonia to 13.4% and the associated crude mortality to 43.4%.

Adult↗

PubMed1991

High-resolution ultrafast chest CT in the clinical management of febrile bone marrow transplant patients with normal or nonspecific chest roentgenograms.

Plain chest roentgenograms may be normal or show nonspecific abnormalities during the frequent febrile episodes that occur in patients after bone marrow transplantation. In this group, ultrafast 10-mm and 3-mm high-resolution CT scans were prospectively performed in 33 patients to determine if useful information was provided that either changed the patient's clinical management or added confidence to the clinical diagnosis. The 36 symptomatic episodes that occurred in 33 patients included fever in 20 episodes and fever combined with cough, dyspnea, chest pain, or rales in 16. Fourteen chest roentgenograms were interpreted as normal, and 22 were interpreted as demonstrating nonspecific changes; however, none of the roentgenograms was considered helpful in that they did not provide sufficient information for further management. In 2 of 14 episodes in patients with normal chest roentgenograms and in 9 of 22 episodes in patients with nonspecific chest roentgenograms, CT scanning resulted in a change in clinical management that included performing bronchoscopy, increasing or changing antibiotic coverage, starting white blood cell transfusions, requesting surgical biopsy, or a combination of these. In 1 of 14 episodes in patients with normal chest roentgenograms and in 8 of 22 episodes in patients with nonspecific roentgenograms, CT added confidence to the diagnosis. In the remaining 16 episodes, CT scans provided no additional information. We conclude that in many instances, noncontrast ultrafast chest CT scans can provide information that may either change a patient's clinical management or more clearly establish the extent of pulmonary disease.

Adult↗

PubMed1991

Two-year adjustment of bone marrow transplant survivors.

Very little systematic analysis exists on the psychological and emotional factors involved in bone marrow transplantation, either during or after treatment. However, recent published findings, contrary to earlier anecdotal and case study evidence, indicate that bone marrow transplant survivors appear to be functioning adequately on a variety of 'quality of life' variables. The purpose of the present study was to compare bone marrow transplant survivors to a matched sample of patients undergoing maintenance chemotherapy in four areas of function; physical health, including symptoms and physician visits; personal functioning, emphasizing ability to care for self; psychological functioning; and role functioning, including employment and sexual difficulties. Our data reveal that the bone marrow transplant patients were experiencing greater difficulties than the maintenance chemotherapy patients in several areas. For example, the bone marrow transplant patients had experienced greater disruption of vocational functioning and reported more sexual difficulties. However, in spite of more objective difficulties, bone marrow transplant patients, compared to maintenance chemotherapy patients, viewed themselves as equally healthy and reported similarly low levels of psychological distress. The findings are discussed in the context of necessary future research on bone marrow transplant survivors.

Adult↗

PubMed1990

Identification and characterization of a new surface membrane antigen found predominantly on malignant B lymphocytes.

A monoclonal antibody, 1D10, was derived that identifies a new antigenic epitope on the surface of malignant B lymphocytes. Normal resting and stimulated lymphocytes do not express the antigen. The majority of individuals with acute Epstein-Barr virus infection express the antigen on their lymphocytes, and in these patients, the T lymphocyte may also be antigen positive. The antigen was found on B-lymphoid neoplasia from the early pre-B cell stage through terminally differentiated plasma cells, a characteristic not reported for other B cell-associated antigens. Studies on homozygous typing cells and cells from individuals with known HLA phenotypes indicate that the antigen does not segregate in a pattern characteristic for major histocompatibility antigens. The molecule is a heterodimeric polypeptide with the molecular weight and isoelectric points of the alpha and beta chains being 32,000 d/4 and 28,000 d/6, respectively. Evidence is presented that the 1D10 molecule is not HLA-DR, -DP, or -DQ. By extrapolation, we suggest that this novel molecule may represent HLA D-region gene expression of a gene(s) not normally expressed. Potential candidates are D-region pseudogenes. We conclude that the antigenic epitope identified by the 1D10 monoclonal antibody is unique among previously described B-lymphocyte antigens. Further studies of the factors controlling the expression of this molecule, as well as studies designed to look at the possible cellular function, may provide insights for understanding crucial events in the malignant transformation of lymphocytes.

Antibodies, Monoclonal↗

PubMed1990

BVAC ablative chemotherapy followed by autologous bone marrow transplantation for patients with advanced lymphoma.

Forty-one consecutive patients with lymphoma resistant to conventional combination chemotherapy have been entered into a study in which chemo-ablative therapy and autologous marrow rescue were used with curative intent. The actuarial proportion of 20 patients with Hodgkin's lymphoma remaining alive and free of recurrent disease is 49%, while that for 21 patients with non-Hodgkin's lymphoma is 41%. Our clinical approach to these patients involved a strategy whereby lymphomatous nodes greater than 2 cm in diameter that persisted despite salvage chemotherapy were given boost radiation therapy immediately before chemo-ablation. However, patients with this variable had a significantly lower survival due to septic complications rather than recurrent disease. We conclude that the treatment strategy used in this study with some modification may improve further on the already high probability of long-term disease-free survival experienced by this group of patients.

Adolescent↗

PubMed1989

Adult acute lymphoblastic leukemia: results of the Iowa HOP-L protocol.

Fifty-nine consecutive previously untreated adult patients with acute lymphoblastic leukemia (ALL) were entered onto a prospective single-arm trial of doxorubicin, vincristine, prednisone, and asparaginase (HOP-L) induction therapy followed by CNS prophylaxis and 3 years of maintenance therapy. Consolidation therapy was not administered. The study population included a large number of older (greater than 50 years) patients. Seventy-five percent of patients achieved complete remission. With a median follow-up of 6 years, the median duration of complete remission is greater than 4 years, with 53% of patients expected to remain in remission at both 3 and 5 years. Overall, median survival duration is 27.9 months, with 45% and 35% of all patients expected to survive 3 and 5 years, respectively. Multivariate analysis identified patients with T-cell disease and mediastinal masses (P less than .001) and those with low values of lactic dehydrogenase (LDH) (P = .057) as being at greatest risk of relapse. Therapy was well tolerated by patients under age 35, but older patients suffered appreciable mortality. We conclude that this treatment program is effective therapy for adult ALL, yielding a large proportion of durable remissions despite the exclusion of consolidation therapy.

Adolescent↗

PubMed1989

Disseminated Fusarium infections in patients following bone marrow transplantation.

Intensive immunosuppressive therapy and broad spectrum antibiotics predispose cancer patients to opportunistic fungal infections. Fusarium has rarely been reported as a pathogen in immunocompromised patients, but is almost uniformly fatal. Only six cases of disseminated Fusarium infection have been described in patients following bone marrow transplantation (BMT). We report here two additional cases. Fusarium infection initially presented with pyomyositis in one patient and with embolic skin lesions in another following T cell-depleted BMT. Both patients died with active Fusarium infection despite an extensive course of amphotericin B, rifampicin and granulocyte transfusions. From this experience and from a review of the literature, Fusarium infections appear to be increasing in prevalence as significant pathogens in immunocompromised hosts and are resistant to many conventional forms of therapy.

Adult↗

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↗

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↗