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Biomedical subjects

R Finberg

Publications and source records attributed to R Finberg.

At least 19 recordsLinked to original sources
PubMed1992

Risk assessment in cancer patients with fever and neutropenia: a prospective, two-center validation of a prediction rule.

PURPOSE: The study was undertaken to validate a clinical model for predicting the medical risk of cancer patients with fever and neutropenia. PATIENTS AND METHODS: A consecutive sample of 444 cancer patients with fever and neutropenia (granulocyte count less than 500/microL) at two hospitals, a specialized cancer referral center and a university-affiliated general medical hospital, was studied to identify clinical characteristics in the first 24 hours that predict subsequent serious medical complications during the hospital stay. To control for bias, major risk factors and complications were subject to blinded review. RESULTS: Serious medical complications occurred in 34% of patients with risk factors identified in a prior study, including prior inpatient status (group I), outpatients with a serious independent comorbidity (group II), or uncontrolled cancer (group III), compared with 5% of the remaining patients (group IV) (P less than .000001). Two of the complications in group IV patients were transient asymptomatic hypotension, and the remaining three complications occurred after at least 1 week of progressive medical deterioration. These risk groups were independently significant in stepwise logistic regression analysis. Multiple complications (17%) and death (10%) were common among patients in groups I through III but did not occur in group IV patients. CONCLUSIONS: This risk assessment model accurately stratified the medical risk of these patients using only clinical information available on the first day of their course. Low-risk patients are an appropriate population in which to study less intensive treatment strategies.

Adolescent↗
PubMed1991

Prophylaxis of bacterial infections with ciprofloxacin in patients undergoing bone marrow transplantation.

Twenty-six oncology patients, 25 of whom received bone marrow transplants, were enrolled in a prospective, randomized, double-blinded, placebo-controlled trial assessing the efficacy of ciprofloxacin, 750 mg p.o. b.i.d., for preventing bacterial infections during prolonged neutropenia. Treatment was begun within 48 hr of initiation of chemotherapy and continued until the absolute granulocyte count recovered to greater than or equal to 500/microliters, or until the onset of fever (greater than or equal to 38.3 degrees C). Seven evaluable subjects received ciprofloxacin, and 11 received placebo. Risk factors for infection were comparable in both groups. Fever occurred in all study subjects, but onset was delayed in ciprofloxacin recipients (median = 6 days after the fall of the absolute granulocyte count to less than or equal to 500/microliters vs. 3 days for placebo recipients, P = 0.01). No clinically or microbiologically documented infections occurred in ciprofloxacin recipients vs. 10 infections in placebo recipients (5 bacteremias, 4 skin/soft tissue infections, 1 urinary tract infection, P = 0.0003). Ciprofloxacin recipients required fewer days of therapeutic antimicrobials (median: 28 antibiotic-days vs. 49, P0.02). The bioavailability of ciprofloxacin appeared comparable to that found in previously published studies of normal volunteers and patients not receiving chemotherapy. Adverse effects and colonization by ciprofloxacin-resistant microorganisms were monitored, but the sample sizes were too small to permit meaningful conclusions about these safety parameters. Ciprofloxacin appears to be effective for preventing bacterial infections in neutropenic patients. Additional trials are needed to establish the optimal dose of ciprofloxacin and to compare its safety and efficacy with those of currently used prophylactic regimens.

Adult↗
PubMed1990

Neurohormones regulate T cell function.

In this communication we show that T cell locomotion is affected by direct interaction with neurohormones. Opioid peptides, including beta-END, MET-ENK, LEU-ENK, and related enkephalin analogues enhanced migration of human peripheral blood T lymphocytes. Activity was dependent on the peptide NH2-terminal sequence, stimulated by enkephalin analogues with specificity for classical delta or mu types of opiate receptor, and inhibited by the opiate receptor antagonist naloxone. Our studies suggest that such neuropeptides stimulate T cell chemotaxis by interaction with sites analogues to classical opiate receptors. We propose that the endogenous opioids beta-END, MET-ENK, and LEU-ENK are potent immunomodulating signals that regulate the trafficking of immune response cells.

Amino Acid Sequence↗
PubMed1990

Human immunodeficiency virus infection is efficiently mediated by a glycolipid-anchored form of CD4.

Two broad roles have been revealed for the CD4 molecule. It serves as a receptor for both class II major histocompatibility complex molecules and human immunodeficiency virus (HIV). Upon binding class II major histocompatibility molecules, CD4 functions to enhance T-cell activation. By binding to CD4, HIV gains entry into the cell. We have used a chimeric molecule of CD4 and lymphocyte function-associated antigen 3 (LFA-3), CD4PI, which lacks a membrane-spanning domain and is instead anchored in the membrane by linkage to glycosyl-phosphatidylinositol. To further define the structural attributes of viral receptors, and specifically those of CD4 required for HIV infection, we have expressed CD4PI and CD4 in a human T-cell line, HSB-2. We find that CD4PI is able to mediate infection of these cells by HIV with similar, if not greater efficiency, compared with wild-type CD4. Thus the membrane-spanning region of CD4 is not required for HIV infection, and a lipid-anchored protein can serve as a viral receptor.

Amino Acid Sequence↗
PubMed1990

Use of IFN-gamma in patients with AIDS.

The tolerance and toxicity of interferon-gamma (IFN-gamma) was assessed in a phase I/II study of 21 patients with acquired immune deficiency syndrome (AIDS). A highly purified preparation of human recombinant E. coli-produced IFN-gamma was given i.v. twice weekly for an 8 week period. Patients were enrolled in the study in groups of four or five; the initial group received an IFN-gamma dose of 0.03 mg/m2 and subsequent groups received higher IFN-gamma doses of 0.3, 1, or 3 mg/m2. Toxicity resulting from IFN-gamma was minimal and the therapy was well tolerated even at the maximum dose (3 mg/m2). No patients developed antibodies that neutralized IFN-gamma. Clinical responses were observed in 3 of 17 patients with Kaposi's sarcoma (KS). A complete clinical response was achieved in one individual and a partial, temporary regression of KS lesions was observed in two other patients. HIV p24 antigen was decreased in plasma samples obtained from six of nine patients with initially detectable HIV protein. These data suggest that IFN-gamma should be considered as a therapeutic agent, possibly with other antivirals, in the treatment of patients with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Recombinant human gamma interferon enhances in vitro activation of lymphocytes isolated from patients with acquired immunodeficiency syndrome.

Decreased responses to antigens and lectins are a characteristic feature of peripheral blood lymphocytes isolated from patients with the acquired immunodeficiency syndrome (AIDS). The in vitro addition of recombinant gamma interferon (IFN-gamma) to cultures of peripheral blood lymphocytes obtained from patients with AIDS resulted in an augmented proliferative response [( 3H]thymidine uptake) to phytohemagglutinin (PHA) and an enrichment in CD4+ and CD8+ T lymphocytes. In AIDS cultures stimulated with PHA, IFN-gamma increased the release of T-cell growth factors and enhanced the expression of interleukin-2 receptors on activated lymphocytes. Responsiveness to PHA was augmented, albeit to a lesser extent, by IFN-gamma in cultures derived from normal donors. Proliferation to microbial antigens including herpes simplex virus, cytomegalo virus, and Candida albicans was increased by IFN-gamma in cultures established from a group of AIDS patients with Kaposi's sarcoma who had no history of opportunistic infection.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Trojan horse lymphocytes: a vesicular stomatitis virus-specific T-cell clone lyses target cells by carrying virus.

We have isolated a vesicular stomatitis virus (VSV)-specific CD4+ CD8- murine T-cell clone. This clone proliferates only in response to VSV and lyses infected tumor cells bearing class II major histocompatibility antigens in short-term chromium release assays. In addition, the cell has VSV antigens on its surface and is capable of killing uninfected tumor cells without major histocompatibility antigen restriction in a 2-day assay. This latter cytolytic activity is eliminated by anti-VSV antibody, indicating that its lytic activity is provided by the virus. [35S]methionine labeling and immunoprecipitation experiments demonstrated that viral protein translation is initiated after incubation of the clone with a tumor target cell, defining this as the mechanism of its cytolytic activity.

Animals↗
PubMed1988

Cyclophosphamide and thiotepa with autologous bone marrow transplantation in patients with solid tumors.

Autologous bone marrow transplantation to avoid dose-limiting myelosuppression may allow significant drug dose escalations and exploitation of the linear-log correlation between chemotherapy and tumor cytotoxicity. In a phase I trial of cyclophosphamide and thiotepa (with subsequent addition of melphalan), 23 patients were entered; there were two deaths due to toxic effects. The maximum tolerated dose was 6 g of cyclophosphamide/m2 and 720 mg of thiotepa/m2. No significant dose of melphalan could be added. Stomatitis was dose limiting. Eleven of 20 patients who were able to be evaluated responded. Plasma thiotepa concentrations correlated more closely with toxicity and response than with drug dose level. Continuous infusion cyclophosphamide and thiotepa is an active core regimen for the further design of high-dose combination chemotherapy regimens.

Adult↗
PubMed1988

The medical course of cancer patients with fever and neutropenia. Clinical identification of a low-risk subgroup at presentation.

To determine whether cancer patients with fever and neutropenia differ in their medical stability, 261 medical records of 184 cancer patients who were hospitalized with fever and neutropenia and treated with conventional antibiotic therapy were studied to determine whether their presenting clinical characteristics influenced the likelihood of subsequent clinical events thought to require urgent medical attention. Overall, serious medical complications, including those without an obvious relationship to infection, occurred in 56 patient courses (21%). We distinguished three clinically determined subgroups of our study population at significantly higher risk than the remaining patient group, which seemed to be at low risk. Major complications occurred in 34 (34%) of 101 inpatients, 12 (55%) of 22 outpatients with concurrent comorbidity requiring inpatient care, and eight (31%) of 26 outpatients without concurrent comorbidity requiring inpatient care but with uncontrolled cancer. However, the remaining patients, who presented as outpatients without significant comorbidity or uncontrolled cancer, had major complications in only 2% of 112 hospitalizations. These results suggest that it may be possible to assess the medical stability of patients with fever and neutropenia based on presenting clinical features. If confirmed prospectively, these results may enable clinicians to identify groups of medically stable patients for whom conventional supportive care, including appropriately administered antibiotics, may be given safely under medical supervision of less intensity or of shorter duration than conventional treatment in the acute-care hospital setting.

Adult↗
PubMed1987

Ribavirin treatment of the acquired immunodeficiency syndrome (AIDS) and the acquired-immunodeficiency-syndrome-related complex (ARC). A phase 1 study shows transient clinical improvement associated with suppression of the human immunodeficiency virus and enhanced lymphocyte proliferation.

STUDY OBJECTIVE: To assess safety, tolerance, and the clinical and laboratory effects of oral ribavirin in patients with the acquired immunodeficiency syndrome (AIDS) and the AIDS-related complex. DESIGN: Three uncontrolled phase I trials of increasing duration: 14 days, 8 weeks, and 12 months. SETTING: Outpatient clinic of a university-referral hospital. PATIENTS: All patients were antibody-positive for the human immunodeficiency virus (HIV) by radioimmunoprecipitation assay, all had recovered from Pneumocystis carinii pneumonia, and none had Kaposi sarcoma at entry. Nine of ten patients with AIDS had less than 100 CD4+ lymphocytes/mm3 at entry and all patients with the AIDS-related complex had fewer than 200 CD4+ lymphocytes/mm3. Five patients with AIDS and five with the AIDS-related complex entered the 14-day trial. All but two patients with AIDS went on to the 8-week trial, along with seven additional patients with AIDS. Five surviving patients with AIDS and 3 patients with the AIDS-related complex went on to the 1-year study. INTERVENTIONS: Oral ribavirin, 1200 mg twice daily for 3 days was given, followed by 300 mg twice daily for 11 days. During an 8-week trial, a loading dose of oral ribavirin was administered for 3 days, followed by a dose of 300 mg twice daily for 8 weeks. Prolonged regimen of a 3-day loading dose was given, followed by a dose of 300 mg twice daily for 1 year. MEASUREMENTS AND MAIN RESULTS: Ribavirin treatment was well tolerated, with anemia requiring transfusion in one of the ten patients with AIDS receiving the drug for 8 weeks; no other significant toxicity occurred. Six of nine patients initially positive for HIV-1 in blood became negative during ribavirin treatment. Six of nine patients with AIDS had a twofold improvement in lymphoproliferative response to at least one lectin with ribavirin treatment. Mean survival from first episode of P. carinii pneumonia was 17.3 months in patients with AIDS receiving 8 weeks of ribavirin and 21.2 months in patients with AIDS receiving prolonged treatment. CONCLUSIONS: Oral ribavirin, 600 mg daily, was well tolerated and safe in the patients with severe AIDS and the AIDS-related complex. Ribavirin therapy merits extensive evaluation in a multicenter controlled trial to assess its efficacy.

AIDS-Related Complex↗
PubMed1987

High-dose combination alkylating agent preparative regimen with autologous bone marrow support: the Dana-Farber Cancer Institute/Beth Israel Hospital experience.

Fifty-nine patients received 61 courses of cyclophosphamide, cisplatin, and carmustine combined. The phase I study consisted of seven dose escalations. Dose levels 5 and 6 also included the attempted addition of melphalan at 40 and 80 mg/m2. The maximum tolerated dose for the three-drug combination was 5620 mg/m2 of cyclophosphamide, 165 mg/m2 of cisplatin, and 600 mg/m2 of carmustine. The dose-limiting toxic effect was fatal veno-occlusive disease of the liver in two of five patients treated at the highest dose level. Veno-occlusive disease of the liver was fatal in two of 40 patients treated at Dose level 4, the maximum tolerated dose. The median time to recovery of polymorphonuclear leukocyte counts to greater than 500/microliters and platelet counts to transfusion independence greater than 20,000/microliters was 19 and 22 days, respectively, after marrow reinfusion. Other toxic effects observed included postdischarge pulmonary toxicity, which appeared to respond to prednisone therapy. Thus, this combination of alkylating agents can be combined at close to the transplant dose of each individual agent. The response rate was high despite considerable prior treatment in most patients. Of 16 evaluable patients with breast cancer, 15 responded (six complete responses). Of six evaluable patients with sarcoma, six responded (one complete response). While patients with melanoma had had no prior treatment, 11 of 17 patients responded (65%). There are currently three patients who are disease-free. Two patients with melanoma were rendered disease-free by excisional biopsy of the only remaining nodule after good partial response, and a patient with metastatic breast cancer remains disease-free after a complete response at 36+ months.

Adult↗
PubMed1986

High-dose combination alkylating agents with autologous bone marrow support: a Phase 1 trial.

Twenty-nine patients were treated with 31 courses of high-dose combination cyclophosphamide, cisplatin, and carmustine (BCNU) with and without melphalan with autologous bone marrow support. Toxicity was dose related. The maximum tolerated dose for cyclophosphamide, cisplatin, and BCNU in this combination in mg/m2 was 5,625, 165, and 600, respectively. Further dose escalation was precluded by the development of multiple organ toxicity, including venoocclusive disease, refractory thrombocytopenia, and hypertension. Melphalan added to the three-drug combination produced excessive renal and gastrointestinal toxicity. Objective tumor regression occurred in 21 of 25 evaluable cases. The results suggest that selected alkylating agents can be combined in full or nearly full doses before nonmyelosuppressive dose-limiting toxicity precludes further escalation.

Adult↗
PubMed1985

Seroepidemiology of human T-lymphotropic virus type III among homosexual men with the acquired immunodeficiency syndrome or generalized lymphadenopathy and among asymptomatic controls in Boston.

We studied a cohort of 45 homosexual men with the acquired immunodeficiency syndrome, 78 with persistent unexplained generalized lymphadenopathy, and 160 asymptomatic homosexual controls for serologic evidence of infection with human T-lymphotropic virus type III (HTLV-III). Study participants were recruited from a community-based health center and a university hospital practice. Ninety-eight percent of men with the syndrome and greater than 90% of men with generalized lymphadenopathy had antibody to HTLV-III, while 21% of the controls were positive (p less than 0.001). Six patients with generalized lymphadenopathy developed the acquired immunodeficiency syndrome over 2 years; all were seropositive for HTLV-III. Thirty-six asymptomatic controls had had sexual contact with a man with the syndrome; receptive anal intercourse in this group was associated with seropositivity for HTLV-III. These data suggest that persistent generalized lymphadenopathy and the acquired immunodeficiency syndrome are part of a clinical spectrum of HTLV-III infection and that most high-risk homosexual men in some regions of the United States have not yet been infected with this virus.

Acquired Immunodeficiency Syndrome↗
PubMed1979

Generation of cytolytic T lymphocytes after reovirus infection: role of S1 gene.

Cytotoxic T lymphocytes (CTLs) can be generated if spleen cells from reovirus-infected mice are stimulated in vitro with syngeneic reovirus-infected cells. These cytolytic effector cells demonstrate: (i) serotype specificity (i.e., maximal cytolytic activity is observed on target cells infected with the serotype used to induce the CTLs) and (ii) H-2 restriction. The SI gene was shown to be the predominant viral gene determining the specificity of the cytotoxic T cells. This genome segment has previously been demonstrated to encode the viral hemagglutinin and determines reovirus cell tropism in the nervous system.

Animals↗
PubMed1979

The cytolytic T lymphocyte response to trinitrophenyl-modified syngeneic cells. I. Evidence for antigen-specific helper T cells.

Mice were primed subcutaneously with trinitrophenyl (TNP)-modified syngeneic spleen cells. Seven days later, spleen cells from these in vivo primed mice, or spleen cells from naive mice, were co-cultured with TNP-modified syngeneic cells. Spleen cells from the in vivo primed mice demonstrated augmented cytolytic T lymphocyte (CTL) activity. The spleens of these in vivo primed mice contained a population of radioresistant, antigen-specific, helper T cells. Specifically, spleen cells from these mice, after x-irradiation, were able to augment the in vitro CTL response of normal spleen cells to TNP-modified syngeneic cells.

Animals↗
PubMed1979

The cytolytic T lymphocyte response to trinitrophenyl-modified syngeneic cells. II. Evidence for antigen-specific suppressor T cells.

The subcutaneous administration of trinitrophenyl (TNP)-coupled syngeneic cells 7 days before co-culture with TNP-coupled syngeneic stimulator cells results in increased cytolytic activity. This augmented cytotoxic response has been shown to be dependent, at least partially, on radioresistant "helper" T cells. In this paper we have demonstrated that TNBS-generated suppressor T cells that are capable of suppressing contact sensitivity can specifically suppress the augmented response seen after subcutaneous priming. The i.v. administration of TNP-coupled cells results in priming of the recipient; however, if cells from these animals are transferred to a second recipient, there is evidence of suppressor activity. Thus, the cytotoxic T lymphocyte response is controlled by the same type of complex interactions previously demonstrated for humoral and delayed-type hypersensitivity responses.

Animals↗