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Biomedical subjects

D Longo

Publications and source records attributed to D Longo.

At least 37 records · Page 2Linked to original sources
PubMed1989

Myelostimulatory activity of recombinant human interleukin-2 in mice.

In a series of studies designed to extend our understanding of interleukin-2 (IL-2) and to study the effect of biologic response modifiers on bone marrow, we observed that administering recombinant human (rH) IL-2 to normal mice resulted in an increase in the frequency of colony-forming units-culture (CFU-C) in bone marrow. In addition, rH IL-2 was able to accelerate host recovery from cyclophosphamide (CTX)- or radiation-induced bone marrow depression and peripheral blood leukopenia. Not only can rH IL-2 accelerate, in a dose-dependent manner, the return of bone marrow, peripheral blood cellularity, and CFU-C frequency to normal levels following cytoreduction by CTX or irradiation, but it also significantly increases CFU-C frequency to greater than normal levels. Furthermore, rH IL-2 can significantly prolong survival of animals receiving a lethal dose of irradiation or CTX. Thus, multiple mechanisms are responsible for the synergistic therapeutic activity associated with rH IL-2 and CTX. rH IL-2 does not act only as an immunomodulatory agent in the presence or absence of suppressor T cells, but also accelerates host recovery from cytoreductive agents, resulting in decreased leukopenia and perhaps resistances to secondary infection. Thus, rH IL-2 plus chemotherapy may increase therapeutic activity against neoplastic disease, not only by adding immune stimulation to the direct antitumor effect of the drug but also by allowing delivery of higher, more effective doses of chemotherapy.

Animals↗
PubMed1989

Variant translocation of the bcl-2 gene to immunoglobulin lambda light chain gene in chronic lymphocytic leukemia.

The bcl-2 gene has been identified as a gene directly involved in the consistent chromosome translocation t(14;18), which is found in approximately 90% of human follicular lymphoma cases, and is a prime candidate for the oncogene playing a crucial role in follicular lymphomagenesis. In this paper, we describe a case of chronic lymphocytic leukemia showing the juxtaposition of the bcl-2 gene on chromosome 18 to immunoglobulin lambda light chain (Ig lambda) gene on chromosome 22 in a head-to-head configuration. Sequencing analysis of the joining site of the bcl-2 gene and Ig lambda gene has shown that the breakpoint is within the 5' flanking region of the bcl-2 gene and about 2.2 kilobases 5' to the joining segment of Ig lambda locus in a germ-line configuration. The extranucleotide, commonly appearing at the joining site of the t(14;18) translocation involving the IgH locus, is absent from the joining site of bcl-2 and Ig lambda. The lack of extranucleotide suggests that the juxtaposition of the bcl-2 and Ig lambda genes occurred during physiological rearrangement of the Ig lambda gene since it has been shown that the rearrangement of the Ig lambda locus is not accompanied by extranucleotides.

Base Sequence↗
PubMed1988

IL-2-dependent expansion of CD3+ large granular lymphocytes expressing T cell receptor-gamma delta. Evidence for a functional receptor by anti-CD3 activation of cytolysis.

The nature and function of the TCR on PBL of a patient with a chronic CD3+ large granular (LGL) proliferation was studied. Fresh peripheral blood from this individual was comprised of 80% lymphocytes, 65 to 75% of which were CD3+, CD8+, Leu-7+ LGL. Of these LGL, 72% initially expressed the TCR-alpha beta heterodimer, whereas 21% did not. Cytotoxicity directed against MHC-unrestricted targets was minimal. After several days of exposure to rIL-2, cytotoxic activity was greatly enhanced, correlating with a disappearance of CD3+ cells expressing the alpha beta heterodimer. Twelve days after rIL-2 exposure, the LGL expressed only TCR-gamma delta heterodimer in association with CD3 and alpha beta heterodimer expression could no longer be detected. The TCR/CD3 complex on these cells was demonstrated to be functional as anti-CD3 elicited an increase in cytoplasmic free calcium concentration, stimulated cytolytic activity, and stimulated granule enzyme secretion from the LGL.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1988

Orocoecal transit time in healthy and constipated children.

Orocoecal transit time (OCTT), assessed by means of H2 breath test after lactulose and/or after a semisolid standard meal, was studied in normal and constipated children. Both control subjects and patients with constipation showed a significantly longer OCTT after a standard meal than after lactulose ingestion (p less than 0.01). Whereas the OCTT after lactulose did not differ in the two groups, the constipated patients had a significantly longer transit time after a standard meal when compared to controls (p less than 0.05). No correlation was observed within each group between the OCTT after a standard meal or after lactulose ingestion (r = -0.077; p greater than 0.01). These findings suggest that 1) measurement of the transit of a standard meal instead of a lactulose solution may offer more direct insight into the role of small intestinal transit of food, both in physiological and pathological conditions, 2) gastrointestinal segments other than colon may play a role in chronic non organic constipation of childhood.

Breath Tests↗
PubMed1987

Combination chemotherapy of disseminated Kaposi's sarcoma in patients with the acquired immune deficiency syndrome.

Two clinical trials were conducted to assess the efficacy and safety of a combination chemotherapy regimen for the treatment of Kaposi's sarcoma in patients with the acquired immune deficiency syndrome (AIDS). Eighteen consecutive patients with disseminated Kaposi's sarcoma were treated with a six-drug regimen of doxorubicin (Adriamycin), vinblastine, bleomycin/actinomycin D, vincristine, dacarbazine (ABV/ADV). A brief partial or complete response was achieved in 13 patients. Most patients died of opportunistic infections. Eighteen consecutive patients with disseminated Kaposi's sarcoma were then randomly assigned to therapy with either recombinant alpha interferon or ABV/ADV. The treatment responses in these two groups were comparable to results of earlier trials, and the incidence of opportunistic infections during therapy did not differ between the two treatment arms. It is concluded that chemotherapy is effective and safe for use in palliative management of Kaposi's sarcoma in patients with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1986

A randomized trial comparing ceftazidime alone with combination antibiotic therapy in cancer patients with fever and neutropenia.

To assess the efficacy of single-agent therapy relative to standard combination antibiotic therapy for the initial management of fever and neutropenia in cancer patients, we conducted a randomized trial comparing ceftazidime alone with a combination of cephalothin, gentamicin, and carbenicillin. Of 550 evaluable episodes of fever and neutropenia, 282 were treated with ceftazidime alone and 268 with the combination. All episodes were evaluated for responses at 72 hours after the start of treatment and at resolution of the neutropenia. Of the patients with unexplained fever who were given ceftazidime alone, 99 percent were alive at 72 hours and 98 percent were alive when the neutropenia resolved, as compared with 100 percent and 98 percent, respectively, of those given combination therapy. Of the patients with documented infection who were given ceftazidime alone, 98 percent were alive at 72 hours and 89 percent when the neutropenia resolved, as compared with 98 percent and 91 percent, respectively, of those given combination therapy. The majority of episodes of documented infection in both treatment groups necessitated additional antimicrobial treatment or other modifications of the initial regimen, as compared with only 22 percent of the episodes of unexplained fever. We conclude that initial single-agent therapy with certain beta-lactam antibiotics is a safe alternative to standard combination antibiotic therapy, although patients with documented infection or protracted neutropenia are likely to require additional or modified treatment.

Adolescent↗
PubMed1985

New beta-lactam antibiotics in granulocytopenic patients. New options and new questions.

Infectious complications are a frequent cause of morbidity and, at many centers, the major cause of death in patients with cancer. The increased risk and severity of infectious sequelae result from profound alterations in normal host defenses that occur secondary to the underlying malignancy and the treatment thereof. During the last decade, early empiric antibiotic therapy has become standard practice in the initial management of febrile granulocytopenic patients and has contributed significantly to the improved outcome among patients undergoing cancer therapy. Although early death due to unsuspected or inadequately treated bacterial infection has been largely overcome, new problems--also with life-threatening implications--have emerged. As the use of cancer chemotherapy continues to increase, new populations of patients are being placed at increased risk of infection. Defining the host and environmental factors that contribute to this risk assumes central importance for delineating those patients who require the most intense surveillance. Changing medical practices (e.g., increased use of indwelling catheters) have contributed to the emergence of new pathogens. Recent drug developments (e.g., the third-generation cephalosporins and extended-spectrum penicillins) offer new treatment options, as well as generate controversy and confusion. For example, authorities disagree on the optimal duration and modifications in treatment that are required by cancer patients who remain granulocytopenic and who thus are at continued risk of multiple infectious episodes or superinfections. A question of current interest is whether combination therapy with synergistic agents is important in light of the development of the third-generation cephalosporins and extended-spectrum penicillins. Several of these new antibiotics have an exceedingly broad spectrum of activity that includes Pseudomonas aeruginosa, as well as Enterobacteriaceae, Serratia, Citrobacter, indole-positive Proteus, and anaerobes (including Bacteroides fragilis). However, the third-generation cephalosporins are not as active against staphylococci and streptococci as are the first-generation cephalosporins, and none is effective against enterococci. Nonetheless, these agents achieve serum levels that can be 10 to 100 times greater than the minimal inhibitory and bactericidal concentrations of gram-negative bacteria, raising the possibility that these drugs might be effective as single agents. The advantages of the third-generation cephalosporins are their minimal toxicity and long serum half-lives.(ABSTRACT TRUNCATED AT 400 WORDS)

Agranulocytosis↗
PubMed1985

Human lymphoblastoid interferon treatment of Kaposi's sarcoma in the acquired immune deficiency syndrome. Clinical response and prognostic parameters.

Thirty consecutive patients with the acquired immune deficiency syndrome were treated with intramuscular human lymphoblastoid interferon for Kaposi's sarcoma. Patients were divided into three groups receiving 7.5 million units/m2 per day, 15 million units/m2 per day, or 25 million units/m2 per day for 28 days. Because of dose-limiting toxicity in the highest dose group, all patients received between 6 and 15 million units/m2 per day. There were three partial responses and four minor responses. The responses were not dependent on drug dose, but did correlate with higher total lymphocyte and OKT4-positive lymphocyte numbers and absence of prior opportunistic infection. Patients who had endogenous acid-labile alpha-interferon prior to therapy were more likely to have progressive disease during interferon administration.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Prospective randomized study of open lung biopsy versus empirical antibiotic therapy for acute pneumonitis in nonneutropenic cancer patients.

Diffuse pulmonary infiltrates and acute respiratory compromise frequently occur in patients with cancer who are undergoing chemotherapy, and treatment remains controversial. We initiated a prospective randomized trial in 22 nonneutropenic patients to compare the efficacy of immediate open lung biopsy with that of empirical trimethoprim-sulfamethoxazole and erythromycin therapy with delayed open lung biopsy if no clinical improvement occurred after 4 days of therapy. Diagnoses included non-Hodgkin's lymphoma (15 patients), T-cell lymphoma (2), acute lymphoblastic leukemia (3), Hodgkin's disease (1), and breast cancer (1). The median age was 40 years, and fever (18) and tachypnea (13) were the most frequent signs. Median room air arterial oxygen tension in 18 hypoxic patients was 53 mm Hg; 19 patients had diffuse pulmonary infiltrates. Eight of the 10 patients randomized to empirical antibiotic therapy showed improvement after 4 days. The 2 patients whose condition did not improve and who underwent delayed open lung biopsy had Pneumocystis carinii pneumonia. One of them did show improvement, and the other died of respiratory failure. Time to clinical resolution in the 9 surviving patients was 14 days; 4 required prolonged ventilation (longer than 24 hours). Findings for the 12 patients randomized to immediate open lung biopsy were P. carinii pneumonia in 7 and nonspecific pneumonitis in 5; there were 3 deaths related to open lung biopsy. Time to resolution in the surviving patients was 13 days for those with P. carinii pneumonia and 5 days for those with nonspecific pneumonitis; 7 required prolonged ventilation.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1985

Interferon-induced 2'-5' oligoadenylate synthetase during interferon-alpha therapy in homosexual men with Kaposi's sarcoma: marked deficiency in biochemical response to interferon in patients with acquired immunodeficiency syndrome.

Titers of circulating interferon (IFN) and the activity of 2'-5' oligoadenylate (2-5A) synthetase, an enzyme specifically induced by IFN, were measured in 28 homosexual men with acquired immunodeficiency syndrome (AIDS) who received one- to six-month courses of antineoplastic therapy with IFN-alpha and in homosexual and heterosexual controls. Fifteen of the patients and two of seven healthy homosexual men had high endogenous levels of 2-5A synthetase. IFN therapy induced further increases in this enzyme in only 10 of the 28 patients with AIDS. Furthermore, peripheral blood cells from all but one of the patients with AIDS and homosexual controls tested were markedly deficient in their ability to respond to IFN in vitro, as measured by increased levels of 2-5A synthetase. We did not find a statistical correlation between cytomegalovirus viremia and pretherapy endogenous circulating IFN, nor any apparent correlation between disseminated infection with cytomegalovirus and either basal levels of 2-5A synthetase or changes in enzyme level during therapy. Pretherapy circulating IFN was significantly correlated with progressive Kaposi's sarcoma during therapy, but rises in levels of 2-5A synthetase were not sufficient to predict a good clinical response.

2',5'-Oligoadenylate Synthetase↗
PubMed1985

ProMACE-MOPP combination chemotherapy for diffuse lymphomas.

Until the mid 1960s the advanced stage, high grade non-Hodgkin's lymphomas were rapidly progressive, fatal diseases with few patients remaining alive at 5 years. Studies conducted at the NCI demonstrated that 47% of all patients with advanced stages of diffuse mixed, large cell, and undifferentiated non-Burkitt's lymphoma could achieve a complete remission documented by reevaluation of all initially involved sites following treatment with either the C-MOPP or BACOP combination chemotherapy regimens. Furthermore, 70% to 80% of these complete responders had long-term disease-free survival tan-tamount to cure. The third generation of NCI studies, termed the ProMACE-MOPP flexible induction program, significantly improved these results. Complete remissions were achieved in 74% of all patients and 73% of these remain disease free in excess of 3 years. Myelosuppression was dose limiting with a 10% septic death rate. Studies are currently underway in an attempt to minimize the toxicity of the new regimen, while preserving the increased complete response rates and long-term survival.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1984

Approaching the controversies in antibacterial management of cancer patients.

The principles for management of infectious complications in cancer patients are continuing to evolve. The critical element includes the prompt institution of broad-spectrum antibiotic(s) empirically when granulocytopenic patients become febrile and continuation and modification of the regimen in patients with persistent fever and granulocytopenia. The view is presented that antibiotics provide systemic prophylaxis as well as therapy in persistently granulocytopenic patients and that they should be continued until all signs of infection have cleared or the granulocyte count has recovered. Such aggressive therapy, supplemented by continued evaluation and monitoring of the patient, can significantly reduce infection-relation morbidity and mortality.

Agranulocytosis↗
PubMed1984

Ophthalmic involvement in acquired immunodeficiency syndrome.

Forty patients with acquired immunodeficiency syndrome (AIDS) were examined for ocular abnormalities. Twenty of these patients died and the eyes were obtained for culture and histopathologic examination. These patients have multiple opportunistic infections and neoplasms as the result of a severe depression of cellular immunity. Fifty percent of all patients with AIDS and 75% of the autopsy group have ocular signs attributable to AIDS. Ocular findings were confined to four major categories: cytomegalovirus retinitis (10 patients), retinal cotton wool spots (11 patients), conjunctival Kaposi's sarcoma (2 patients) and neuro-ophthalmic motility abnormalities (3 patients). Cytomegalovirus retinitis was a significant cause of visual loss. Seven of 40 autopsy eyes had hand motion or worse visual acuity prior to the patients' death because of CMV retinitis. This necrotic retinitis showed minimal inflammation and progressed to involve the entire retina in three to six months, resulting in a gliotic retinal membrane. Therapy with antiviral agents was not effective. Recognizing the ocular signs of AIDS may facilitate the diagnosis. The ophthalmologist also has a major role in the observation of progression or regression of these ocular manifestations, and can assist in the evaluation of therapy in patients with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Persistence of Pneumocystis carinii in lung tissue of acquired immunodeficiency syndrome patients treated for pneumocystis pneumonia.

Eleven patients with acquired immunodeficiency syndrome (AIDS) and Pneumocystis carinii pneumonia (PCP) were studied by repeat bronchoscopy during PCP treatment to assess histologic evidence of resolution of the pneumonia. Nine of 10 patients studied after 8 to 21 days of therapy demonstrated evidence of persistent PCP. Four of 6 patients studied after 22 to 35 days of therapy continued to demonstrate Pneumocystis carinii cysts on repeat examination, while only 1 of 4 patients studied after 35 days of therapy showed evidence of PCP pneumonia. The rate of resolution of PCP in patients with AIDS may be different from the rate of resolution of PCP in patients without AIDS. There was no apparent correlation between rate of clinical response and likelihood of histologic resolution on follow-up biopsy. The PCP in patients with AIDS may require more prolonged therapy for complete resolution of this pneumonic process.

Acquired Immunodeficiency Syndrome↗