Serum interleukin-6 levels in metastatic renal cell cancer: correlation with survival but not an independent prognostic indicator.
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Carcinoma, Renal Cell↗
Biomedical subjects
J M Richards
Publications and source records attributed to J M Richards.
Effective chemotherapy for melanoma after treatment with interleukin-2.
Twenty patients with biopsy-proven metastatic malignant melanoma, previously treated with interleukin-2 (IL-2), received combination chemotherapy for progressive disease. Treatment included carmustine, cisplatin, dacarbazine, and tamoxifen (BCDT). Nausea was the most common toxicity (100%) and usually was mild. Persistent thrombocytopenia was the most frequent toxicity limiting further treatment. Eleven patients (55%) had an objective partial response, three patients (15%) had a minor response, and six patients (30%) had no change or progressive disease in response to this treatment. These results were comparable to the high response rates (21 of 40, 53%) achieved with BCDT in previously untreated patients with melanoma. It was concluded that prior therapy using IL-2 does not significantly alter the response rate of metastatic melanoma to BCDT, thus suggesting that immunomodulators (e.g., IL-2) and chemotherapeutic agents are not cross-resistant treatments.
Adult↗
Asthma severity: a factor analytic investigation.
PURPOSE: Reviewers of the asthma research literature have called for improved questionnaires and other measures, particularly for assessing the severity of asthma. To help meet this need, standard multivariate and psychometric techniques were used with data from asthma patients to develop and evaluate a series of scaled questions. Since there is no "gold standard" for assessing asthma severity, we hope this analysis will help improve our ability to more precisely define these important parameters. PATIENTS AND METHODS: Data were collected through interviews and review of clinic records for 199 adult patients with asthma from a university clinic population. For evaluating the severity of asthma, eight scales assessed asthma duration, the incidence of asthma symptoms, the extent to which asthma is an inconvenience to patients, the incidence of respiratory diseases, medication regimens, medication side effects, and health care utilization. Forced expiratory volume in 1 second as a percentage of predicted normal was included as an objective measure of pulmonary function. A physician rating scale assessed the severity of the underlying disease, not the severity of a particular episode, as either (1) mild (infrequent attacks with interim symptomatic treatment), (2) moderate (more frequent attacks with continuous daily treatment), and (3) severe (continuous symptom with continuous multiple drug regimen, including some systemic steroids). RESULTS: In the current analysis of data from adult asthma patients, the scales correlated positively with a physician judgment scale. Factor analysis with an oblique rotation yielded three factors that provided a concise summary of asthma severity. We have named the factors (A) Symptom Intensity, (B) Airflow Impairment, and (C) Management Intensity. CONCLUSION: Asthma severity appears to be multidimensional rather than unidimensional, including at least three components. The physician rating scale, in combination with measures of the three identified factors, could easily be included in other asthma research protocols to provide a standard, brief assessment of asthma severity and might thus promote greater comparability among studies.
Adult↗
Sequential chemoimmunotherapy in the treatment of metastatic melanoma.
PURPOSE: A phase II study that alternates the sequence of chemotherapy (carmustine [BCNU], cisplatin [CDDP], and dacarbazine [DTIC]) and biologic therapy (interleukin-2 [IL-2] and interferon alfa-2 alpha [alpha IFN]) was performed to establish a safe and efficacious way to sequence these forms of treatment for metastatic melanoma. PATIENTS AND METHODS: Patients who had measurable metastatic melanoma, a Karnofsky performance status of greater than or equal to 70, and no clinically significant cardiac or pulmonary dysfunction were eligible for entry onto this trial. Responses to treatment were assessed after a treatment cycle by two tumor evaluations at least 4 weeks apart. RESULTS: Forty-two consecutive patients with metastatic melanoma were treated with this sequential chemoimmunotherapy. Transient thrombocytopenia and neutropenia were observed frequently, but neither hemorrhage nor infection occurred in any of the patients. Of the 42 patients, 10 achieved a complete response (24%), 14 achieved a partial response (33%), two achieved a minor response (5%), eight had stable disease (19%), and eight (19%) had progressive disease. The median time to disease progression for all patients was 7 months. The median survival for all patients entered onto the trial was 11.5 months. A vitiligo-like depigmentation was induced in many patients by this treatment. CONCLUSIONS: Cytotoxic chemotherapy can be administered safely immediately before or immediately after IL-2 and alpha IFN. Sequential chemoimmunotherapy administered as previously described yields a response rate of more than 55%. The overall survival curve suggests that a proportion of patients may achieve a long-term benefit from this treatment. Also, cutaneous depigmentation induced by this treatment suggests that immune modulation may contribute to the antimelanoma effect of this treatment.
Adult↗
Features of asthma in older adults.
A study compared clinical and functional features of elderly patients with asthma to younger patients at a university medical center. Older patients had a larger than predicted reduction in pulmonary function parameters even though physician-assessed severity, duration of diagnosed asthma, and smoking status were no different between groups. A significant increase in the comorbid diagnosis of chronic obstructive pulmonary disease was noted in older patients with asthma. These two points support the hypothesis that long-standing asthma may lead to irreversible airflow obstruction. Older patients reported better medication compliance and decreases in some respiratory symptoms and demonstrated lower health care utilization.
Adolescent↗
Association of interleukin-2 therapy with staphylococcal bacteremia.
The authors prospectively monitored patients undergoing leukapheresis for peripheral stem cell harvesting (PSCH) or lymphokine activated killer (LAK) cell generation for 3 weeks after catheter placement for evidence of local or systemic infections. Over a 1-year period, 16 patients underwent leukapheresis for PSCH in preparation for autologous bone marrow transplantation (ABMT). The original catheters remained in place an average of 20 days without any documented infections. Seventeen patients underwent leukapheresis as part of a low-dose interleukin-2 (IL-2) treatment for LAK cell generation, and their catheters remained in place an average of 20.2 days with three documented episodes of bacteremia (18%). Eight patients treated with high-dose IL-2 also underwent leukapheresis for LAK cell generation and their catheters remained in place an average of 12 days with three documented episodes of bacteremia (38%). In all cases of bacteremia, Staphylococcus species were isolated from the blood. The IL-2 exposure level was associated with the risk of bacteremia (P = 0.01). Other potential risk factors (e.g., number of pheresis procedures, complement level, serum immunoglobulin levels, absolute neutrophil count) were not related to this risk.
Adult↗
Contraceptive female sterilization in Alabama: a replication of the WHO study.
The prevalence of female sterilization for contraceptive purposes has grown rapidly throughout the world, and is especially high in the United States. Yet the psychosocial impact of female sterilization is incompletely understood. Much of the previous research has been retrospective and has lacked comparison groups of women using other methods. Better designed, prospective studies have been needed, and the World Health Organization's Collaborative Prospective Study of Female Sterilization was conducted to address this need. No evidence was found in the WHO study of a significant impact of tubal ligation compared to other contraceptive methods on mental health, menstruation, or sexual satisfaction. The present study, a replication of the WHO study, compared 323 Alabama women undergoing elective contraceptive sterilization with 318 women using other techniques to control fertility. In general, the results supported the WHO study conclusions. Although sterilization produced a small increase in menstrual distress in Alabama, there were no significant differences between sterilization and comparison women in mental health or sexual satisfaction.
Adult↗
Effects of hypoxia and metabolic inhibitors on production of prostacyclin and endothelium-derived relaxing factor by pig aortic endothelial cells.
1. The content of adenosine triphosphate (ATP) and basal and bradykinin-stimulated production of prostacyclin and endothelium-derived relaxing factor (EDRF) was measured in primary cultures of porcine aortic endothelial cells under normoxic (14.4% O2) and hypoxic (2.8% O2) conditions, and following treatment with rotenone and 2-deoxy glucose, which inhibit oxidative and glycolytic metabolism, respectively. 2. ATP content and basal and bradykinin-stimulated production of prostacyclin were similar under normoxic and hypoxic conditions. EDRF production, assessed as endothelial guanosine 3':5'-cyclic monophosphate (cyclic GMP) content, was also similar under both conditions. 3. Treatment with rotenone (0.3 microM) had no effect on ATP content or basal or bradykinin-stimulated production of prostacyclin or of EDRF, measured as endothelial cyclic GMP content. Elevation of cyclic GMP content by atriopeptin II was also unaffected. 4. Treatment with 2-deoxy glucose (20 mM) in glucose-free Krebs solution lowered ATP content, reduced bradykinin-stimulated production of prostacyclin and abolished the bradykinin-stimulated elevation of cyclic GMP content. Resting production of prostacyclin was unaffected but basal content of cyclic GMP was lowered in some experiments. Elevation of cyclic GMP content by atriopeptin II was abolished. 5. Combined treatment with rotenone (0.3 microM) and 2-deoxy glucose (20 mM) lowered ATP content more than with 2-deoxy glucose alone. Basal production of prostacyclin rose slightly and bradykinin-stimulated production was powerfully inhibited. Basal content of cyclic GMP was unaffected, but bradykinin-stimulated production was abolished. Elevation of cyclic GMP by atriopeptin II was also abolished. 6. Cascade bioassay experiments using endothelium-denuded rings of rabbit aorta as a detector system confirmed that bradykinin-stimulated production of EDRF was blocked by 2-deoxy glucose, but not by rotenone. 7. These data indicate that porcine aortic endothelial cells in culture operate under mainly glycolytic metabolism and this probably explains why production of prostacyclin and EDRF is unaffected under hypoxic conditions. They also indicate that glycolytic metabolism is required for agonist-stimulated production of prostacyclin and EDRF by these cells.
6-Ketoprostaglandin F1 alpha↗
Aspergillus fumigatus contamination of lymphokine-activated killer cells infused into cancer patients.
Lymphokine-activated killer (LAK) cells, prepared by incubating autologous lymphocytes in cell culture medium with interleukin-2, selectively lyse tumor cells and are effective immunotherapy of some cancers. During a 3-month period, two patients at our center were infused with LAK cells subsequently found to have been contaminated by Aspergillus fumigatus. Each case was investigated by obtaining environmental cultures and assessing aseptic practices during LAK cell preparation. Investigation of the first case demonstrated a malfunction of the laminar air flow hood, under which interleukin-2 and the patient's lymphocytes had been added to cell culture medium, and showed heavy A. fumigatus contamination of the hood, adjacent countertop, and cell culture incubator. Despite repair of the laminar air flow hood and cleaning of the laboratory, a second case occurred, and cultures at that time implicated the humidified cell culture incubators as the source of A. fumigatus. Following incubator sterilization and removal of the humidification apparatus from the incubators, weekly environmental cultures in the LAK cell laboratory were negative, and none of the LAK cell cultures from the 20 patients treated during the ensuing 15 months grew A. fumigatus. Our findings show that growth of fungi in humidified incubators, which previously has caused contamination problems in tissue culture and clinical microbiology laboratories, can result in patient infections when humidified incubators are used to prepare cells for reinfusion.
Adult↗
Medication adherence patterns in chronic obstructive pulmonary disease.
While medical treatment of COPD has advanced, the failure to adhere to regimens for medication poses a significant barrier to effective management. Furthermore, no data are available regarding adherence for patients within the United States. Data from this investigation indicate that 78 outpatients from a medical center in the southeastern region of the United States were prescribed an average of 6.26 medications with both various dosing schedules and different modes of administration. Adherence was poor, with 42 patients (54 percent) underutilizing medications, 39 patients (50 percent) overutilizing medications during periods of respiratory distress, and 24 patients (31 percent) employing ineffective inhaler dosing techniques. Prescription patterns and adherence were not associated with demographic variables; however, adherence was related to classes of medication and situational variables.
Administration, Inhalation↗
Sequential chemoimmunotherapy for metastatic melanoma.
Since February, 1990 we have evaluated a sequential form of chemoimmunotherapy as an investigative method for the treatment of metastatic melanoma. A cycle of therapy consisted of: carmustine (150 mg/m2) on day 1, dacarbazine (220 mg/m2) and cisplatin (25 mg/m2) on days 1 through 3 and 22 through 24, interleukin-2 (1.5 x 10(6) IU/m2 every 8 hours) and alpha-interferon (IFN alpha) (6.0 x 10(6) IU/m2 subcutaneously once daily) on days 4 through 8 and 17 through 21, and tamoxifen 10 mg orally twice daily for 6 weeks. Patients were evaluated for response 2 to 3 weeks after completing each cycle of therapy. Thirty-nine patients had been entered into this trial as of December 1, 1990, and 25 had completed at least one cycle of therapy and have been evaluated for response. The responses are as follows: complete response, six of 25 (24%); partial response, nine of 25 (36%); minor response, one of 25 (4%); stable disease, eight of 25 (32%); and progressive disease, one of 25 (4%). Median response duration has not been reached but is at least 5 months. Immunologic alterations associated with response and associated toxicity data will be presented.
Adult↗
Serum soluble interleukin-2 receptor is associated with clinical and pathologic disease status in hairy cell leukemia.
Hairy cell leukemia is a chronic lymphoproliferative disorder of B-cell lineage, whose malignant cells express the interleukin-2 (IL-2) receptor. A soluble form of the IL-2 receptor is released by these cells in culture, and the sera of patients with hairy cell leukemia contain elevated levels of this soluble receptor. Four hundred twenty-seven serum samples from 101 patients were analyzed for soluble IL-2 receptor (sIL-2R). The clinical status of patients appeared to be associated with the serum level of sIL-2R. The hairy cell index (a measure of tumor cell burden) was correlated with the square root of the serum sIL-2R level (r = .77). Improved clinical status was associated with decreasing serum sIL-2R levels, whereas disease relapse was associated with increasing levels. Notably, every patient who responded to therapy had a decline in serum sIL-2R level, and every patient with disease progression had an increase in serum sIL-2R level. This phenomenon was observed for several different treatments, including standard-dose interferon, low-dose interferon, and deoxycoformycin. The predictive reliability of this test is currently being prospectively evaluated.
Dose-Response Relationship, Drug↗
Neurotoxicity after treatment with muromonab-CD3.
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Antibodies, Monoclonal↗
Characteristics and correlates of asthma in a university clinic population.
To contribute more comprehensive information about the characteristics of asthma, this article analyzed patients served by the University of Alabama at Birmingham Comprehensive Asthma Program. Their physicians rated one fifth of these patients as having "severe" asthma with the remainder about equally divided between "moderate" and "mild". One in two first received a diagnosis of asthma ten or more years previously. Common comorbidities were hypertension, obesity, rhinitis, bronchitis, sinusitis, and arthritis. One half had visited an emergency room or been hospitalized for asthma in the past year. Inhaled bronchodilators and continuous theophylline were the most commonly prescribed medications. Side effects, especially tachycardia and insomnia, were common and almost exclusively associated with theophylline or corticosteroid therapy. Spirometric assessment showed chronic airflow obstruction in those with more severe asthma. Prevalence of respiratory symptoms, intensity of medication regimen, incidence of side effects, and health care utilization increased as asthma severity increased.
Adult↗
Evaluation of the efficacy and cost effectiveness of health education methods to increase medication adherence among adults with asthma.
We randomized 135 adult asthma patients to a control group, and 132 patients to an experimental group which received a special health education intervention. Four adherence measures were documented at baseline and 12-month follow-up: correct inhaler use, inhaler adherence, medication adherence, and total adherence rating. Costs to routinely deliver the intervention were $32.03/patient. Experimental group patients exhibited a significantly higher level of improvement in adherence (44 percent) than control group patients (2 percent).
Adolescent↗
Biologic response modifiers in non-Hodgkin's lymphomas.
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Antibodies, Monoclonal↗
Peripheral blood-derived stem cell collections for use in autologous transplantation after high dose chemotherapy: an alternative approach.
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Adult↗
Peripheral blood-derived stem cell collections for use in autologous transplantation after high dose chemotherapy: an alternative approach.
Peripheral blood-derived hematopoietic stem cells (PBHSC) can be utilized to reconstitute hematopoiesis in patients after high dose myeloablative chemotherapy. We have performed PBHSC reinfusion in 18 patients who have or had a history of tumor involving the bone marrow or a hypocellular bone marrow. The PBHSC were collected by continuous flow leukapheresis and subsequently cryopreserved. A median of 31.9 X 10(9) (range 18 X 10(9)-67.2 X 10(9)) mononuclear cells or a median of 4.85 X 10(8) mononuclear cells/kg (range 2.7 X 10(8)-11.0 X 10(8)) were collected. Fifteen patients had in vitro assays of granulocyte-monocyte colony-forming cells (CFU-GM) performed with a median of 2.7 X 10(4) (range 0-11.5 X 10(4)) CFU-GM/kg. To date, of the 18 patients collected, all have undergone high dose chemotherapy and PBHSC reinfusion. For the evaluable patients, granulocyte recovery (greater than 500 X 10(6)/ml) has occurred in a median of 15 days and platelet recovery (greater than 50 X 10(9)/ml without transfusion support) has occurred in a median of 43 days. Four patients have had prolonged thrombocytopenia and still require platelet transfusion at 80+, 97+, 124+, and 270+ days. PBHSC collection is safe and effective for hematopoietic reconstitution after high dose chemotherapy in the majority of patients; however incomplete hematopoietic reconstitution has been observed in 4/18 evaluable patients. This procedure requires further investigation.
Adult↗