PubMed Health⌕ Search

Biomedical subjects

K Alonso

Publications and source records attributed to K Alonso.

At least 19 recordsLinked to original sources
PubMed1995

Is metastatic breast cancer, refractory to usual therapy, curable?

Breast cancer with metastatic disease is presently incurable. Significantly shorter survival rates are seen in premenopausal women despite usual therapies when compared to survival rates in older women. Median survival rates of 24-30 months are documented in large-scale prospective clinical trials of previously untreated women with metastatic breast cancer regardless of the protocol employed (chemotherapy, hormone therapy). High dose chemotherapy followed by autologous stem cell rescue (bone marrow or peripheral blood) is associated with significant response and possibly improved survival in chemosensitive patients with metastatic disease without visceral metastases though with significant toxicities and cost (median survival rate of 20 months). Patients with refractory disease have dismal results regardless of therapy (median survival rates of 8-9 months in a number of prospective trials with or without stem cell rescue). The use of alpha-interferon in such patients has not improved response. Whole body hyperthermia is of benefit in the presence of liver metastases although median survival rate is in the range of 12 months. New treatment approaches with curative intent are clearly required. We report fifty-nine patients with metastatic breast cancer refractory to common therapies who were treated with whole body hyperthermia (40 degrees C) with low dose chemotherapy and immunomodulation: five presented with brain metastases; 13 with multiple bone metastases; 8 with liver metastases; 10 with lung metastases; and 23 with multiple soft tissue metastases. Fifteen were premenopausal; 44 postmenopausal. Twenty-three achieved complete remission. Fourteen have been sustained with patients remaining alive from 17-80 months (median, 40 months). Nine failed after 20-40 months of being disease-free (mean, 32 months).(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗
PubMed1995

Whole body hyperthermia associated with beta-carotene supplementation in patients with AIDS.

The objective of this work was to check possible additive beneficial effects of whole body hyperthermia (WBH) associated with beta-carotene (BC) supplementation in patients with AIDS. In a pilot study, 10 HIV positive patients, (8 with AIDS and 2 with AIDS related complex, ARC), after AZT or DDI discontinuation, were first treated with one single session of WBH applied with a non-invasive procedure at 42 degrees C core temperature for one hour, and subsequently supplemented with BC 120 mg daily continuously. All patients well tolerated the non-invasive WBH as well as the high dose BC supplementation. Apart from one patient who died after 4 months, all the others underwent an HIV burden diminution, clinical improvement and amelioration of laboratory data, along with an subjective improvement of their life quality. With reference to control groups, namely (a) only WBH applied with extracorporeal procedure to 31 AIDS patients, and (b) only BC supplementation at high dosage applied to 64 ARC patients, the combined physical and BC supplemental treatments clearly showed a better and longer lasting response.

AIDS-Related Complex↗
PubMed1995

Immunomodulation in the treatment of multiple sclerosis and amyotrophic lateral sclerosis: a model for autoimmune disorders.

Seventeen multiple sclerosis (MS) patients progressing under conventional therapy (average treatment duration: 3 years) with performance status 3-4 (mean Disability Status Scale [DSS]: 82) who demonstrated circulating lymphokine inhibitor factors were selected for a monthly immunomodulatory protocol using plasmapheresis, followed by 3 days of human intravenous immunoglobulin, and low-dose methylprednisolone, cyclophosphamide, interferon-a, and interferon-g, as well as octreide. Twelve of the 17 patients presented with visual problems, 12 had lower extremity weakness or paraperesis/paralysis, and 6 had bladder/bowel dysfunction. Following 4 months of therapy, 4 recovered completely, 7 showed loss of paralysis/paraparesis, and 5 had improvement in lower extremity weakness. One patient progressed (mean DSS: 51). Lymphokine inhibitor factors declined in 14 patients with concomitant normalization of circulating immune complexes. Eight patients experienced rises in CD4 levels with stabilization of CD8 levels. Hypotension and hypocalcemia were observed during plasmapheresis. Twelve patients with amyotrophic lateral sclerosis with poor performance status also were studied. Four of the 12 improved with the regimen, whereas six stabilized disease. Similar alterations in laboratory parameters were described. The rationale for this approach is discussed.

Adjuvants, Immunologic↗
PubMed1995

Fetal weights and measurements as determined by postmortem examination and their correlation with ultrasound examination.

Two hundred fifty fetuses from healthy singleton pregnancies terminated other than on health grounds at 21 to 26 weeks gestation were examined by ultrasound in utero and by autopsy. No significant maturational difference between male and female fetuses was noted, although larger biparietal distances (0.2 cm) and smaller femur lengths (0.2 cm) were seen in female fetuses at 23 weeks gestation, and heavier body weights were also noted (80 g). No maturational difference was noted between white and nonwhite populations. Maternal age was not a significant variable. Organ weights and fetal anthropometric measurements are provided. Biparietal diameter as determined by ultrasound examination of the fetus in utero is an excellent predictor of gestational age and correlated well with actual caliper measurements on the fetus (coefficient of variation [CV] < 5%). Femur length determined by ultrasound examination of the fetus in utero is significantly low compared with actual length (CV = 23%) and is not a reliable indicator of fetal development. A large CV (17%) was also seen for calculated fetal weight.

Autopsy↗
PubMed1994

Plasmapheresis combined with interferon: an effective therapy for multiple sclerosis.

The rationale for the use of interferon (IFN) in the treatment of multiple sclerosis (MS) is based on its recognized antiviral and immunomodulating actions. The pathogenesis of MS is believed to be due to an immunologic response in a genetically predisposed individual, localized within the central nervous system white matter, and triggered by exposure to an environmental agent such as a virus. Based on our personal experience we find that the efficacy of IFN therapy is hampered in MS patients by the presence of an interferon inhibitor factor (IIF) in the patients' sera which we have isolated and characterized. When plasmapheresis (PP) was done on 24 MS patients with intermittent 3-day administration of IFN-alpha and human leukocyte IFN, marked increase of IFN in 18 patients and modest increase in three patients correlated with clinical improvement. Three clinical nonresponders showed no increase in IFN levels following therapy. The ability to remove IIF and lymphokine inhibitor factor (LIF) by PP may explain the successful treatment of our patients. We describe the evaluation of helper T cells, suppressor T cells, HLADR antigen, natural killer cells, and monocyte/macrophage cell populations by flow cytometry before and after PP. A significant increase in these immune-competent cells correlated with marked improvement in Kurtzke disability status scale in 13 patients, while eight stabilized. Patients showing progression of the disease either showed decrease or no change in these parameters after therapy. Encouraging results from this pilot study suggest that PP combined with immunomodulatory regimens of IFN may be an effective therapy for MS.

Adult↗
PubMed1994

Immunomodulation in the treatment of malignant disorders.

In this study, 91 patients with metastatic solid tumor were treated with an immunomodulatory regimen of interferons -a and -g as well as octreide in pulse administration, followed in selected patients by low dose perilymphatic administration of interleukin-2. Pharmacosensitivity studies of patient tumor directed concomitant chemotherapy. High levels of circulating interferon-a (> 50 IU/ml) and the presence of lymphokine inhibitor factor were identified prior to treatment. None of the patients was able to produce autologous interferon. All patients had been previously treated with surgery and/or radiation therapy and/or chemotherapy. Patients had also received second line chemotherapy and/or radiotherapy per current protocols. At 30 days following immunomodulatory therapy, 6/91 patients were in complete remission; 12/91 were in partial remission; six patients progressed. At 180 days, with concomitant stem cell assay directed chemotherapy, 24/91 patients were in complete remission; 36/91 demonstrated a partial remission. Six patients progressed. Responders demonstrated a fall in circulating interferon levels as well as lymphokine inhibitor factor concomitantly with reduction in tumor burden. NK cell activity increased. Marrow studies demonstrated rises in granulocyte and thrombocyte stem cell activity. Macrophage activity also increased. The rationale for the approach is discussed.

Drug Administration Schedule↗
PubMed1994

Systemic hyperthermia in the treatment of HIV-related disseminated Kaposi's sarcoma. Long-term follow-up of patients treated with low-flow extracorporeal perfusion hyperthermia.

Treatment of HIV and related malignancies with pharmacologic and biologic agents has not appreciably modified the course of disease. Immunologic impairment remains the critical factor in response. We report the long-term results of a single session of low-flow (0.3 L/min) extracorporeal perfusion hyperthermia on 29 men and 2 women with disseminated Kaposi's sarcoma and profound immunologic impairment. Any antiretroviral drug employed by the patient was stopped 72 hours prior to treatment and withheld during the period of follow-up. Core temperature was raised to 42 degrees C and held for 1 hour with extracorporeal perfusion and ex vivo blood heating to 49 degrees C as the means of temperature control. Of 31 patients, 2 died of complications secondary to treatment (cardiac arrhythmia; CNS bleed). There were two cases of intravascular coagulopathy. Pressure point skin damage may occur despite adequate cushioning. At 30 days posttreatment complete or partial regressions were seen in 20/29 of those treated, with regressions persisting in 14/29 of those treated by 120 days posttreatment. At 360 days, 4/29 maintain tumor regressions with 1 in complete remission (at 26 months). The patient in complete remission remains culture-negative and PCR-negative for HIV. CD4+ counts rose from around 250 to, and remain around, 800 in this man. Selected healed lesions were biopsied to demonstrate tumor absence. Patients were selected for treatment if pretreatment testing of the tumor showed regression in vitro with heat exposure. Analysis of the early and midterm failures showed little sustained rise of the CD4+ cells if presenting total CD4+ counts were below 50 and had been at such low levels for extended periods, although other surrogate markers of HIV activity declined (semiquantitative PCR) during this period and is felt to support the hypothesis of apoptosis proposed in this illness. Analysis of the tumors of the few men not responding demonstrated elevated levels of IL-6 as compared to responders (12 vs < 1 pg/ml). At 120 days 29/31 patients remained alive (expected, 20). At 360 days, 21/31 remained alive (expected, 11). In no patient was HIV activity stimulated with heat exposure. CMV retinitis did clear in some patients treated (both techniques), but treatment alone did not prevent later development of retinopathy. EBV parameters were markedly altered in the short term with heat exposure in some patients. Few patients showed herpes simplex activation. Varicella-zoster virus remitted in some patients. There is utility in the use of systemic hyperthermia to control HIV and related malignancy.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1992

Systemic hyperthermia in the treatment of HIV-related Kaposi's sarcoma. A phase I study.

Ten Caucasian males with HIV-related Kaposi's sarcoma, a disseminated disease which is refractory to usual therapies, underwent a single session of systemic hyperthermia with maintenance of core temperatures at 42 degrees C for 1 h. One complete remission and 7 partial remissions were identified when assessed 30 days post-treatment. Two mixed responses were noted in patients whose tumors showed autocrine growth. At 60 days 2 of the 7 partial responders began to show tumor progression. The complete remission persisted at 120 days. Surrogate markers of HIV activity fell in all responding patients. In no patient was there evidence of HIV activation. No adverse effects of heating were noted on CMV retinitis. Hairy leukoplakia resolved with heating in all patients. CD4 counts showed no appreciable change in any of the 8 patients with a presenting CD4 count below 60. In the 2 patients who presented with a CD4 count above 400, CD4 counts rose dramatically following treatment. No deaths were noted in this phase I study. The use of systemic hyperthermia in treatment of HIV-related illness warrants further study.

AIDS-Related Complex↗
PubMed1991

Total body hyperthermia in the treatment of Kaposi's sarcoma in an HIV positive patient.

The effect of prolonged exposure to heat on the HIV has had limited exploration. This is the report of a 33-year-old white man with positive tests for HIV and multiple lesions of Kaposi's Sarcoma. The patient was exposed to total body hyperthermia of 42 degrees C for two hours. Three months following hyperthermia the patient feels improved. The lesions of Kaposi's Sarcoma have markedly regressed, and the T4 lymphocyte count has risen from 5 per cc to 330 per cc. HIV cultures (blood) remain negative. These data would indicate this modality of therapy has altered the progression of disease in this patient.

Adult↗
PubMed1991

Human-human monoclonal antibody directed against tumor surface antigen in the treatment of human malignancy. A pilot study.

Eighteen patients with a variety of refractory solid tumors received infusions of IgM class monoclonal antibody directed against tumor surface antigen and raised in a nonviral transformed human-human system. Three other patients with refractory hematologic or solid tumors had autologous marrow purged with antibody, regrown, and reinfused following high dose chemotherapy. A molecular weight of 200,000 was demonstrated for the whole antibody produced by the fusion line. Each antibody failed to react with nonspecific tumor tissue. No fetal antigen reactivity was noted. Antibody was cytotoxic. Complement dependence was not demonstrated. Chloroquine phosphate pretreatment was employed prior to each antibody infusion to block receptor recycling and host-antigen processing. Antibody dose was doubled with each treatment. Self-limiting chill and fever (with tachycardia) was noted in 12-hour infusions. Tumor biopsy following infusion demonstrated good binding for as long as 48 hours after dosing. Tumor regression was noted during infusions. Pulmonary metastases responded rapidly following infusion. Maximal shrinkage of skin metastases was noted at 4 days with some regrowth at 7 days. Reduction in size of liver metastases was the most durable response. Responses correlated with survival. There were no antibody-related deaths. Antibody used ex vivo to purge autologous bone marrow-cleared marrow of tumor. Marrow engraftment was noted between 7 and 21 days. Follow-up showed no antihuman antibody formation, alteration in renal or hepatic function, alteration in thyroid or adrenal function, or circulating antigen-antibody complexes. Natural killer cell activity and complement-activated clearing of immune complexes increased following infusion. The time for complete clearing of immune complexes from the circulation was 10 days. Mild anemia was seen after several courses of infusion. Reticulocytosis was unimpaired. Long-term follow-up showed no antihuman antibody formation or organ dysfunction.

Adolescent↗
PubMed1991

In vitro evaluation of bleomycin-induced cell lethality from plastic and glass containers.

To optimize cancer chemotherapy, a considerable amount of research has been expended to study pharmacologic, pharmacokinetic, biochemical, and pharmaceutic properties of antineoplastic agents. However, published data on the stability and compatibility of these agents in various administration fluids and containers are few in number. Evidence of a significant decrease in stability as shown by high-performance liquid chromatography has been reported when bleomycin was infused in plastic containers for prolonged periods (over 24 hours) as compared with the same procedure with glass containers. Because administration of bleomycin is usually given as a continuous infusion, we undertook this study to determine whether the drug loss of stability that occurs in plastic containers results in a therapeutic loss of efficacy (cytotoxicity). By using a tumor stem-cell assay we compared the quantitative effects of bleomycin in plastic and glass containers on cell lethality. The results from our assay showed no significant difference in cell lethality by bleomycin from its aqueous solution stored in glass and plastic containers over the time periods observed. If these results had been statistically significant, the tumor stem-cell assay may have been shown to be a more sensitive means of determining the clinical significance of these stability studies.

Bleomycin↗
PubMed1986

The transport of amino acids, amino acid derivatives and ions across ion-exchange membranes.

The passage of inorganic salts, glucose, amino acids and peptides across polystyrene-backed double membranes (negative-positive fixed-charge junctions) was studied in a two-compartment cell and compared to a known cellular system, the Ehrlich-Lettre ascites carcinoma. It was concluded that passage proceeds by a 1:1 exchange of diffusing ions in the membrane. The more rapidly transported systems reflected an increased probability of exchange in all cases, as evidenced both by a saturation effect and by the degree to which the space charge was perturbed at the membrane. The amino group (as NH3+) of the amino acid involved in the exchange process was vital for transport. The presence of a second amino group, either ionized or as -NH2, accelerated the exchange. The presence of electron-attracting groups on the side chain or of a methyl group on the alpha carbon also facilitated passage. Cation dependence was seen. Passage was hindered by a second carboxyl group, an alcoholic group, or a lengthened side chain. Use of double membranes permits experimental electrode transport modelling and may facilitate design of a drug delivery system.

Amino Acids↗
PubMed1986

Testing for drugs.

Explore the source record for details and available documents.

Automobile Driving↗