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Biomedical subjects

I Cunningham

Publications and source records attributed to I Cunningham.

At least 37 records · Page 2Linked to original sources
PubMed1992

Pulmonary infections after bone marrow transplant.

Pneumonia occurs in up to 50% of patients after bone marrow transplant and is the main cause of mortality. The patient may be predisposed to pulmonary complications by previous treatment and infections, by transplant conditioning and graft-versus-host disease prophylaxis regimens, and by prolonged severe immune-suppression. The period of greatest risk is within 3 months of transplant when focal or diffuse interstitial pneumonias may occur. The most common infectious etiologies are Aspergillus or other fungi and cytomegalovirus. Idiopathic, noninfectious, interstitial pneumonia occurring in this same period may represent treatment toxicity. Both fungal and cytomegalovirus infections have been associated with high mortality, but there has been significant success in treating cytomegalovirus with the combination of ganciclovir and immunoglobulin in recent years. Late bacterial pneumonia may occur more than 6 months after transplant because of prolonged immunedeficiency and functional asplenia. Prophylactic therapy to prevent the pneumonias anticipated after transplant should be an essential part of the care of the bone marrow transplant patient.

Bacterial Infections↗
PubMed1991

Treatment for acute myelocytic leukemia with allogeneic bone marrow transplantation following preparation with BuCy2.

One hundred twenty-seven patients with acute myelocytic leukemia (AML) were given busulfan 4 mg/kg on each of 4 days and cyclophosphamide 60 mg/kg on each of 2 days (BuCy2) followed by allogeneic bone marrow transplantation from an HLA-identical or one antigen disparate sibling. For 71 patients in first complete remission, 23 in second complete remission or initial relapse, and 33 patients with primary refractory disease, second or subsequent relapse, or a preceding hematologic disorder, the 3-year leukemia-free survival (LFS) is 63.1%, 32.6%, and 24.2% respectively. The actuarial probability of relapse for each group is 14.1%, 40.6%, and 61.0%. In multivariate analyses, relapse and decreased LFS were associated with advanced disease phase and with M4/M5 French-American-British classification. The LFS of first remission patients was adversely associated with a short time interval from diagnosis to transplantation. This study indicates that BuCy2 is an attractive preparative regimen for marrow transplantation in patients with AML and that prognostic factors for relapse and LFS are similar those described for regimens containing total body irradiation.

Adult↗
PubMed1991

Effect of polyclonal anti-procyclic antibodies on development of Trypanosoma brucei brucei in tsetse flies.

Results obtained in experiments testing the efficacy of anti-procyclic-form rabbit sera on the development of homologous and heterologous stocks of Trypanosoma brucei brucei in Glossina morsitans morsitans indicated that this development was affected little, or not at all, by such sera. The absence of effect of anti-procyclic stage antibodies can be explained by the failure to detect by either direct or indirect fluorescent antibody methods the presence of antibodies acquired in vivo by either the midgut procyclic forms or by uncoated salivary gland forms.

Animals↗
PubMed1991

Cyclosporine-associated seizures in bone marrow transplant recipients given busulfan and cyclophosphamide preparative therapy.

Five of 182 recipients of allogeneic bone marrow transplants performed between 2/84 and 6/90 developed seizures while receiving cyclosporine and methylprednisolone to prevent acute graft-versus-host disease. All received a radiation-free regimen of busulfan and cyclophosphamide as preparative therapy. Two patients received HLA-mismatched allografts; and three patients received marrow from HLA-identical sibling donors. Two patients had received extensive intrathecal therapy prior to transplantation. All patients were receiving standard prophylactic doses of CsA and MP at the time of onset (median 31 days posttransplantation) of seizures. Three patients had mild-to-moderate hypertension and varying degrees of morphologic evidence of microangiopathic hemolytic anemia. None had unusually low magnesium levels. Cyclosporine levels were not in the toxic range. Cranial magnetic resonance imaging and computed tomography (CT) showed bilateral abnormalities primarily in the posterior temporal, occipital, and parietal lobes. These abnormalities were shown to be transient on sequential MRI exams in two patients. Seizures as well as radiologic abnormalities resolved on stopping CsA and did not recur in 2 patients who subsequently received CsA in lower doses. These findings confirm and expand previous observations of CsA-associated seizures and demonstrate that they occur in allogeneic bone marrow transplant recipients following a radiation-free preparative regimen of busulfan and cyclophosphamide.

Adolescent↗
PubMed1991

Rapid, on-site diagnosis of chlamydial urethritis in men by detection of antigens in urethral swabs and urine.

First-void urine (FVU) sediments of 240 men were tested for Chlamydia trachomatis antigens by two enzyme immunoassays, TestPack Chlamydia (15 min) and Chlamydiazyme (3.5 h), and the results were compared with urethral swab culture results. The sensitivity and specificity on FVU sediment for TestPack Chlamydia were 76.2% (32 of 42 specimens) and 95.5% (189 of 198 specimens) versus 81.0% (34 of 42 specimens) and 96.5% (191 of 198 specimens) for Chlamydiazyme, respectively. Rapid, on-site detection of chlamydial antigen in male FVU would shorten the infectious period by hastening diagnosis and treatment.

Adult↗
PubMed1990

Anti-leukemia potential of interleukin-2 activated natural killer cells after bone marrow transplantation for chronic myelogenous leukemia.

The anti-leukemia potential of natural killer (NK) cells has been evaluated in 40 patients transplanted for chronic myelogenous leukemia (CML) to determine whether differences in NK cell function were correlated with subsequent leukemic relapse. Cells from patients and their donors were tested in 51Cr release assays against fully allogeneic CML targets and against cultured K562 targets; cells from 26 patients were tested against host-derived CML targets that were cryopreserved before transplantation. Cultured CML targets (K562) were highly susceptible to lysis by freshly isolated peripheral blood lymphocytes (PBL) and to a greater degree by PBL cultured in medium containing interleukin-2 (IL-2) in all assays performed. In contrast, noncultured CML targets were lysed only by IL-2-activated cells from a subset of patients. When present, lytic activity to CML targets was detectable as early as 3 weeks after bone marrow transplantation, and remained positive throughout the posttransplant period. Optimal lytic activity developed within the first week of culture and required greater than or equal to 250 U/mL of IL-2 in the culture medium. Lytic activity to fully allogeneic and host-derived CML targets appeared to be mediated by CD16+ and CD56+ cells but not by CD3+ cells. Lysis of allogeneic CML targets was variable, but patients could be divided into two groups: those with and those without lytic activity to the majority of targets tested. The basis for the differences in lytic activity could not be ascribed to target susceptibility to lysis, the proportion of NK cells in the cultures, or to the phenotype of the NK cell subsets in the cultures. When tested in parallel, the lytic activity of donor and recipient cultures against host-derived CML targets was highly correlated, suggesting that there may be inherent differences in the ability of NK cells to recognize CML targets. The risk of relapse for patients who failed to generate lytic activity against host-derived CML targets was significantly increased over that for patients with lytic activity against host leukemia. These data indicate that posttransplant immunotherapy with IL-2 designed to activate NK cells will likely augment the graft-versus-leukemia potential of the graft.

Adolescent↗
PubMed1990

Cytogenetic analysis of chimerism and leukemia relapse in chronic myelogenous leukemia patients after T cell-depleted bone marrow transplantation.

Serial cytogenetic studies were performed on 64 patients with chronic myelogenous leukemia (CML) after T cell-depleted allogeneic bone marrow transplantation (BMT). Forty patients with CML in chronic phase (CP) received cytoreduction followed by BMT with HLA-matched T cell-depleted allogeneic marrow. The remaining 24 patients were transplanted in second chronic, accelerated, or blastic phase, or received T cell-depleted grafts with a dose of T cells added back. The Y chromosome and autosomal heteromorphisms were used to distinguish between donor and host cells. Mixed hematopoietic chimerism (presence of donor and host cells) was identified in 90% of patients in first CP. The Philadelphia (Ph) chromosome reappeared in 16 of the 40 first CP CML patients. As expected, patients who had detectable Ph chromosome positive cells at any time during the posttransplant period had a high likelihood of subsequent clinical relapse. Transient disappearance of the Ph positive clone was rarely observed, and was followed by reappearance of the Ph chromosome or clinical relapse. A subset of engrafted patients with greater than 25% host cells within 3 months post-BMT had a significantly shorter survival time free of cytogenetic or clinical relapse compared with other patients. In patients who had received donor T cells added to the T cell-depleted graft, there was a higher proportion of complete chimerism. Clonal progression of Ph positive as well as negative cells was observed and may be the result of radiation induced breakage. Serial cytogenetic studies of patients post-BMT can provide useful information regarding the biologic and clinical behavior of CML.

Adult↗
PubMed1990

Importance of long-term follow-up in evaluating treatment regimens for adults with acute lymphoblastic leukemia.

During the past 20 years, we have treated 250 previously untreated adults (greater than age 15 years) with acute lymphoblastic leukemia (ALL) with five successive multidrug protocols: L2, L10, L10M, L17/17M, and L20. The L10 and L10M protocols had the highest percentage of long-term (greater than 5 years) remissions (52% and 40% respectively) compared with the L2 and more recent protocols (24%-32%); this is partly attributable to a greater prevalence of adverse risk factors among the latter protocols. The overall long-term survival of the first 199 patients with minimum 3 years follow-up is now 31%, with 35% of the 163 patients achieving complete remission (CR) remaining free of relapse for greater than 5 years. The disease-free survival of the 163 patients reaches a plateau of 33% after 6 years. The percentages of patients subsequently relapsing after remaining in continuous CR for 1.5, 3, and 5 years are 42%, 28%, and 6%, respectively; no relapses have yet occurred after 6 years in this series. Postrelapse survival improved progressively with longer duration of first remission. The results of treatment in second or later remission with either chemotherapy or bone marrow transplantation (BMT) were unsatisfactory and there were only a few long-term survivors. Recently we have attempted to select patients at highest risk of early relapse for BMT in first remission, but the number of eligible patients actually having BMTs has been low for a variety of reasons, including early death, failure to reach CR, early relapse, patient refusal, or medical contraindications.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Total body irradiation for bone marrow transplantation: the Memorial Sloan-Kettering Cancer Center experience.

In May 1979, Memorial Sloan-Kettering embarked on a programme of hyperfractionated TBI (HFTBI), 1320 cGy in 11 fractions over 4 days with partial lung shielding (1 HVL), followed by cyclophosphamide (60 mg/kg/d x 2d) for cytoreduction prior to allogeneic bone marrow transplantation (BMT). Anterior and posterior chest wall electron "boosts" were given to the areas blocked (600 cGy in 2 fractions) on the last two days of treatment. Since then, we have treated over 600 patients with HFTBI, the majority for allogeneic BMT. Several modifications have occurred over the years. We have added a "boost" electron dose of 400 cGy to the testes in all male leukemic patients; this reduced testicular relapses from a rate of 14% (4/28) to 0%. In an attempt to increase engraftment of T-depleted BMTs, we added one additional fraction; since our present dose/fraction was also increased to 125 cGy, we now deliver a total dose of 1500 cGy in 12 fractions over 4 days for allogeneic transplants. Tolerance to HFTBI has been excellent relative to the single dose (SD) regimen utilised prior to May, 1979. The incidence of fatal interstitial pneumonitis (IP) decreased from 50% in the SD regimen to 18% after the introduction of HFTBI. In children, the incidence of IP was only 4% with HFTBI. With the introduction of T-depleted marrows, fatal IP in adults has decreased also, e.g. to less than 10% in CML patients. With conventional BMT after HFTBI, relapse at 5 years has been exceedingly low (e.g. in children, 13% for ALL, 2nd remission and 0% for AML, 1st remission) and engraftment has been 100%. With matched T-depleted BMT, rejections have occurred in 15% overall; the incidence of graft failure has not been reduced by the higher dose of HFTBI. Relapses in this setting are equivalent to relapses with conventional BMT for AML, but appear to be increased for ALL. Radiobiological findings related to HFTBI will also be discussed.

Bone Marrow Transplantation↗
PubMed1990

Detection of Chlamydia trachomatis antigens in urine as an alternative to swabs and cultures.

By using commercially available spectrophotometric and immunofluorescent immunoassays, Chlamydia trachomatis antigens were detected in first-void urine (FVU) sediments from 224 men attending a sexually transmitted disease clinic at a frequency of 81.6%-86.8% compared with 86.8% (33/38) positive by urethral swab culture (P less than .05). Endocervical cultures from 228 women attending a gynecology clinic yielded 92.3% (12/13) positive compared with 61.5%-76.9% for urine samples in three antigen-detection assays. Culturing urine from either gender yielded low positivity rates (23.7% for men, 15.4% for women). Defining truly infected patients as positive by culture or by any two of the three antigen tests, all assays were 100% specific. Immunodiagnostic testing of male FVU sediment appears to be a reliable, rapid, nontraumatic method for diagnosing chlamydia infection.

Adult↗
PubMed1990

Autoreactive platelet antibody in post transfusion purpura.

Post transfusion purpura in a DR3, DRw52 positive, PlA1 negative woman rapidly responded to high-dose intravenous gammaglobulin therapy. Using the platelet immunofluorescence test (PIFT) high titre IgG and IgM alloantibodies were detected in the patient's acute serum. These alloantibodies had PlA1 specificity and the patient's serum produced a broad, 100 kDa band on Western Blot with PlA1 positive platelets. Acute phase serum also contained an IgG antibody which reacted in the PIFT with the patient's own platelets, and PlA1 negative platelets. When tested by Western Blot with PlA1 negative and Glanzmann's Thrombasthenia platelets, the acute serum produced bands at 180 and 200 kDa. The autoreactive antibody was not detected once the platelet count returned to normal. These findings provide evidence for the hypothesis that the mechanism of autologous platelet destruction in PTP is autoimmune.

Autoantibodies↗
PubMed1990

Bone marrow transplantation for chronic myelogenous leukemia.

Bone marrow transplantation is the only therapy currently available with the potential to cure chronic myelogenous leukemia. The best results and most experience have been in HLA-matched transplants for patients with CML in the chronic phase. Various protocols have resulted in lengthy disease-free survival in 49-69% of patients. The limitation to greater success is significant mortality associated with graft-versus-host disease. Attempts to improve results have focused on decreasing GVHD by drug regimens or removing donor T-cells. Studies using T-cell depletion by different techniques have improved survival in groups with higher median patient age. These methods have had varying effects on incidence of GVHD, graft failure, and relapse. Transplant for patients in the advanced phases of CML have produced lower disease-free survival rates, due mainly to resistant disease. Early experience with busulfan and cyclophosphamide conditioning have shown improved survival in these patients.

Bone Marrow Transplantation↗
PubMed1989

Graft failure after T-cell-depleted human leukocyte antigen identical marrow transplants for leukemia: I. Analysis of risk factors and results of secondary transplants.

Risk factors for graft failure were analyzed in 122 recipients of an allogeneic T-cell-depleted human leukocyte antigen (HLA)-identical sibling marrow transplant as treatment for leukemia. In each case pretransplant immunosuppression included 1,375 to 1,500 cGy hyperfractionated total body irradiation and cyclophosphamide (60 mg/kg/d x 2). No patient received immunosuppression prosttransplant for graft-versus-host disease (GVHD) prophylaxis. Nineteen patients in this group experienced graft failure. The major factors associated with graft failure were transplants from male donors and the age of the patient (or donor). Among male recipients of male donor-derived grafts a low dose per kilogram of nucleated cells, progenitor cells (colony forming unit-GM) and T cells was also associated with graft failure. Additional irradiation to 1,500 cGy, high dose corticosteroids posttransplant, and additional peripheral blood donor T cells did not decrease the incidence of graft failure. In addition, type of leukemia, time from diagnosis to transplant, an intact spleen, or the presence of antidonor leukocyte antibodies did not correlate with graft failure. To ensure engraftment of secondary transplants, further immunosuppression was necessary but was poorly tolerated. However, engraftment and survival could be achieved with an immunosuppressive regimen in which antithymocyte globulin and high dose methylprednisolone were administered both before and after infusions of secondary partially T-cell-depleted marrow grafts.

Age Factors↗
PubMed1989

Detection of posttransplant minimal disease chronic myelogenous leukemia by bcr rearrangement analysis.

Until recently, cytogenetic detection of the Philadelphia chromosome (Ph) was the only reliable test to diagnose chronic myelogenous leukemia (CML) and detect minimal disease or early relapse following treatment. However, the recently developed ability to detect the Ph chromosome as a rearrangement in the bcr gene of chromosome 22 permits identification of the leukemic clone comprising as little as 5% of the cell population. We present results of simultaneous cytogenetic and DNA rearrangement studies in 28 CML patients considered for or treated with bone marrow transplantation. Our results show that the molecular method is significantly more sensitive than the cytogenetic method in the detection of minimal disease Ph-positive clones.

Bone Marrow Transplantation↗
PubMed1989

The public controversies of AIDS in Puerto Rico.

All articles using the word 'AIDS' that have appeared in the five major daily newspapers in Puerto Rico since 1982 were studied to analyze the way in which AIDS has been presented in the daily press. Virtually all of the articles regarding AIDS, at least those pertaining to Puerto Rico, presented controversies. These were of two kinds. Articles regarding prevalence, incidence, and sources of funding were presented as controversies between the two main political parties of the island. They can be considered extensions of other political arguments between the parties. Those regarding risk factors, prevention, and treatment were presented as controversies between representatives of the people, such as union leaders, and government officials. The victims of AIDS, the homosexuals, drug addicts and hemophiliacs, were generally left out of the controversies as participants. The controversies are generally nonmedical and nonscientific, suggesting that the public perceives insufficient interest on the part of medical and political leaders and is expropriating the problem. That the proposed solutions are directed more toward the victims than the causative organims is also characteristics of past epidemics.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Platelet anti-Bakb antibody associated with neonatal alloimmune thrombocytopenia.

A platelet alloantibody of IgG class but unknown specificity was detected in the serum from the mother of an infant with neonatal alloimmune thrombocytopenia. The antibody reacted by indirect immunofluorescence with 33/65 random donors, 10/11 Baka-negative donors and 23/54 Baka-positive donors. The mother's platelet phenotype was PLA1, Koa, Kob, Baka and the father's was PLA1, Koa, Kob, Baka. Immunoblotting and immunoprecipitation of maternal serum with paternal platelets produced a band at molecular weight 140 kilodaltons identical to the band obtained with Baka antiserum. Family studies confirmed the allelic distribution of Baka and the unknown antigen. The platelet-specific antibody in this patient meets the criteria for an antibody to the new platelet antigen, Bakb.

Adult↗