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Biomedical subjects

J Laszlo

Publications and source records attributed to J Laszlo.

At least 55 records · Page 3Linked to original sources
PubMed1985

Lorazepam in cancer patients treated with cisplatin: a drug having antiemetic, amnesic, and anxiolytic effects.

There currently is no pharmacologic approach to the problem of anticipatory nausea and vomiting (ANV). Lorazepam (Ativan, Wyeth Laboratories, Philadelphia) is an interesting candidate drug if it could block the recall of the unpleasant events associated with chemotherapy, especially if it also has antiemetic properties. Since ANV is a conditioned (learned) response, it may well depend on a memory imprint of the stimulus. This pilot study was designed to use intravenous lorazepam given before and after cisplatin infusion in 32 patients, and to make detailed measurements of nausea, vomiting, recent memory, anxiety, and sedation as well as toxicity. Satisfactory responses occurred in about 70%, as rated separately both by investigator and patient. Forty-six percent did not even recall receiving chemotherapy, regardless of whether or not they vomited; 80% had no significant anxiety after chemotherapy. Adverse reactions included some cases of perceptual disturbance, urinary incontinence, diarrhea, hypotension, and one case of severe transient amnesia. No long-term adverse effects were noted.

Adult↗
PubMed1985

Paradoxical effect of BW 301U, a lipophilic antifolate, on methotrexate-inhibitable deoxyuridine incorporation by human hematopoietic cells.

The ability of methotrexate and BW 301U, a lipophilic folate antagonist, to inhibit tritiated deoxyuridine incorporation into acid-precipitable material by human bone marrow cells was evaluated before and after five sequential daily infusions of BW 301U. After in vivo BW 301U therapy, bone marrow cells from five of the six patients exhibited significantly reduced inhibition by 1 microM methotrexate in vitro, whereas the response to 1 microM BW 301U remained unchanged. Megaloblastic marrow morphology and decreased myeloid progenitor cloning efficiency were also observed following five daily BW 301U infusions of 21 and 71 mg/sq m, respectively. A similar reduction in the ability of methotrexate to inhibit tritiated deoxyuridine incorporation was also seen in HL-60 cells, a human acute promyelocytic leukemia cell line, after incubation in vitro with cytostatic concentrations of BW 301U for 3 days. Concomitant changes in the response to BW 301U did not occur. While it is premature to infer clinical significance from this preliminary observation of BW 301U-induced asymmetry in the response to subsequent antifolates, our results augment a growing body of evidence which suggests that lipophilic folate antagonists might be effective in the treatment of methotrexate-resistant neoplasms.

Antineoplastic Agents↗
PubMed1984

Treatment of polycythemia vera with hydroxyurea.

Conventional treatment of polycythemia vera (PV) with radioactive phosphorus or alkylating agents is associated with a significant excess of acute leukemia and cancer of the gastrointestinal tract and skin. There is thus a need for a nonmutagenic agent in the treatment of this disorder. Hydroxyurea (HU) was administered to 118 patients with a loading dose of 30 mg/kg/day for 1 week, which was then reduced to 15 mg/kg/day. Initial control of the elevated hematocrit and platelet count was achieved within 12 weeks in over 80% of patients. Long-term disease control was defined and the accumulative 1-year failure-free survival was 73% in the previously untreated patients and 59% in those patients previously treated with other myelosuppressive modalities. The HU was well tolerated and cytopenia, which generally occurred within the first 8 weeks of therapy, was transient and of little clinical significance. However, it is recommended because of this toxicity that HU be administered initially at a dose of 15-20 mg/kg/day. Three patients developed acute leukemia; two were untreated and one had had myelosuppressive therapy. Hydroxyurea is an effective agent in the treatment of PV, but continued assessment of its mutagenic potential is necessary.

Acute Disease↗
PubMed1984

The occurrence and consequences of deoxyuridine in DNA.

Deoxyuridine can become resident in the DNA of prokaryotic and eukaryotic cells via two general mechanisms - deamination of cytosine to uracil, and nucleotide pool changes that lead to misincorporation of deoxyuridine in place of thymidine. In this paper we have examined the chemical basis of deamination reactions in DNA and discussed a possible mechanism for an increased rate of deamination by means of cross-strand protonation of cytosine by alkylated guanine. In addition, we have examined the genetic and drug-induced conditions that lead to dUMP misincorporation into DNA in place of thymidine and have presented experimental evidence indicating that the antifolate-induced lesion is a general drug-dose dependent lesion of human blood cells. Finally, the toxic and genetic impact of this lesion has been evaluated within the context of a review of the repair mechanisms elicited by dUMP in DNA.

Base Composition↗
PubMed1984

Recent advances in the pharmacologic and behavioral management of chemotherapy-induced emesis.

Chemotherapy protocols that induce severe protracted nausea and vomiting are stressful for cancer patients, and the fear that may be associated with chemotherapy often outweighs other negative aspects of the cancer experience. The clinical management of chemotherapy-induced emesis involves pharmacologic approaches, maintenance of hydration, provision of emotional support, and the possible use of behavioral relaxation techniques. We review the literature on the psychological side effects of chemotherapy and offer recommendations for the pharmacologic, supportive, and behavioral treatment of chemotherapy-induced emesis. More effective management of chemotherapy-induced nausea and vomiting also enhances patient compliance and therefore potentially decreases overall morbidity and mortality.

Antiemetics↗
PubMed1984

Smoking and lung cancer: an overview.

This position paper summarizes the overwhelming evidence that tobacco smoking is the cause of 30 to 40% of deaths from cancer. The focus is on lung cancer because of the sheer magnitude of this disease in males and the likelihood of a similar epidemic in females. There are two categories of evidence that indicate smoking to be the major cause of human lung cancer. Without exception, epidemiological studies have demonstrated a consistent association between smoking and lung cancer in men and now suggest a similar association in women. Chemical analyses of cigarette smoke reveal a multitude of known mutagens and carcinogens. Moreover, these chemicals are absorbed, are metabolized, and cause demonstrable genetic changes in smokers. Two consequences of smoking are evaluated. The results of treatment of lung cancer are not encouraging; despite vigorous therapy, the 5-year survival rate remains less than 10%. The social and economic costs of lung cancer and the smoking habit impinge on the productiveness of our society.

Adult↗
PubMed1983

Decreased activity of locus coeruleus neurons in the rat after DSP-4 treatment.

The activity of noradrenergic neurons of the rat locus coeruleus was investigated at 10 and 50 days after the administration of DSP-4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzyl-amine), a selective noradrenergic neurotoxin. The mean neuronal firing rate in control animals was 2.4 Hz. In contrast, DSP-4 animals had lower rates of 1.2 Hz at 10 days and 1.7 Hz at 50 days. Histological examinations revealed no morphological changes of locus coeruleus cell bodies at either the 10- or 50-day time points. These results suggest that DSP-4 can impair neuronal activity of the locus coeruleus without altering the structural appearance of locus coeruleus perikarya.

Action Potentials↗
PubMed1983

Nausea and vomiting as major complications of cancer chemotherapy.

Significant advances in the treatment of certain disseminated malignancies have been accompanied by an increased awareness of the consequences of inadequate antiemetic therapy. Nausea and vomiting are predisposing factors to patient non-compliance with treatment regimens and impose mental and physical suffering that diminishes the quality of life. The extent of medical complications associated with vomiting depends on its severity and duration and can include oesophageal tears, bone fractures, malnutrition and major metabolic derangements. The pharmacological management of chemotherapy-induced nausea and vomiting is influenced by the aetiology and mechanism as well as whether therapy is to take place in the hospital or outpatient setting. No single drug is successful in all cases. Side effects due to antiemetic drugs also limit their usefulness. Major treatment alternatives at present include the phenothiazines, antihistamines, benzquinamide derivatives, butyrophenones such as haloperidol, the dopamine receptor antagonist domperidone, and metoclopramide. Cannabinoids, particularly delta-9-tetrahydrocannabinol and nabilone have stimulated considerable research interest. Studies of the role of high dose corticosteroids either alone or in combination with other antiemetics have also been undertaken. Newer chemotherapeutic regimens are more emetic than in the past. Inadequate management of nausea and vomiting is deleterious to the health and well-being of patients and any delay in providing an aggressive therapeutic approach aggravates the problem. This symposium is designed to provide some answers to this therapeutic problem.

Antiemetics↗
PubMed1983

Neurologic manifestations of essential thrombocythemia.

Essential thrombocythemia is a clonal myeloproliferative disorder, characterized predominantly by a markedly elevated platelet count without known cause. We report a case that was recognized during investigation of a transient ischemic attack, and review the neurologic findings in 33 patients with unequivocal essential thrombocythemia under prospective study by the Polycythemia Vera Study Group. Twenty-one patients had neurologic manifestations at some point during their course, including headache (13 patients), paresthesiae (10), posterior cerebral circulatory ischemia (9), anterior cerebral circulatory ischemia (6), visual disturbances (6) and epileptic seizures (2). All patients with neurologic symptoms responded satisfactorily to treatment, although continuous or repeated treatment was often required. Therapeutic recommendations include plateletpheresis for major thrombo-hemorrhagic phenomena, or megakaryocyte suppression with radioactive phosphorus, alkylating agents (such as melphalan), or hydroxyurea; minor symptoms may respond to platelet antiaggregating agents.

Adult↗
PubMed1983

Phase I study of pharmacological and immunological effects of human lymphoblastoid interferon given to patients with cancer.

An extensive Phase I evaluation of human lymphoblastoid interferon has been completed which, in addition to describing its clinical and pharmacological effects, emphasized a broad-scale evaluation of the immune response as a function of interferon dosage. Dose-limiting toxicity was generally due to constitutional symptoms which are remarkably similar to those produced by influenza, although transient peripheral and central neurotoxicity (including deterioration in cognitive and behavioral functions) is observed at higher doses. It is difficult to establish "clean" dose-response effects except for fever and bone marrow suppression, neither of which is a major dose limitation. Enhancement of the immune system was limited to natural killer cells which had a complex dose-response relationship, whereby low interferon concentrations were less stimulatory (than were high doses) following a single dose but gave more sustained stimulation over a 5-week course of 3 times per week i.m. administration. The effects on various measures of monocyte function and of nonspecific immunity (hypersensitivity, immunoglobulins, complement) were negative. We suspect that in practice it may be difficult to exploit the narrow dosage window of immunostimulation, but it is important to note that the nontoxic lower doses were more stimulatory than were the very high doses which are being used in numerous clinical trials.

Adult↗
PubMed1983

Phase II trial of lymphoblastoid interferon in metastatic colon carcinoma.

Nineteen patients with advanced metastatic colon carcinoma were treated with human lymphoblastoid interferon at a dose of 3.0 X 10(6) units/m2 im three times/week for 6 weeks. Patients who did not progress at the 6-week interval were randomized to receive maintenance treatment with either interferon (3.0 X 10(6) units/m2 once/week) or no further treatment. All patients had evaluable metastatic lung, liver, or abdominal disease as measured by radiographs or computerized tomographic scans. Complete remission or partial remission of greater than 50% decrease in tumor measurements was not demonstrated with interferon treatment. Among 18 evaluable patients, seven had stabilization of measurable disease at 6 weeks, but 11 showed progressive disease. Of the seven patients followed during maintenance, only one (placebo maintenance) remained with no objective progression. No serious organ toxic effects were attributed to interferon, but one patient demonstrated liver enzyme elevation that persisted after cessation of interferon therapy. All patients had significant constitutional symptoms of fever, muscle aches, and malaise. Using interferon at the dose schedule outlined, this study failed to demonstrate significant regressions in metastatic colon carcinoma.

Adenocarcinoma↗
PubMed1983

Modulation of natural killing activity by lymphoblastoid interferon in cancer patients.

The in vivo and in vitro effects of partially purified human lymphoblastoid alpha-interferon (alpha-IFN) on natural killing (NK) and antibody-dependent cellular cytotoxicity (ADCC) of peripheral blood were tested in 17 cancer patients. The study tested single doses of alpha-IFN (part A), and repeated, incremental doses (15 over 5 weeks; part B). The initial response to alpha-IFN was a decline of NK and ADCC activity, reaching a nadir at 12 h. The decline was found to be partly related to nonadherent suppressor cells. The NK activity generally returned to or exceeded baseline within 24-48 h and stayed elevated for a week or more after a single injection. Interestingly, the decline in NK activity was not unique to the first injection, but was found even in chronic treatment 12 h after alpha-IFN injection. Dose-response studies showed that maximum stimulation was achieved by the end of the first week, when it was greater for patients receiving higher doses of alpha-IFN. However, patients who received repeated injections at lower doses were able to sustain this stimulation, whereas those who received higher doses were not. Very low doses (0.5 mU/m2) appeared to be maximally efficient. IFN administration to the same group of cancer patients seemed to have similar effects on ADCC against tumor cells. Furthermore, our study has shown that cells responsive in vitro to alpha-IFN (drawn prior to treatment) showed an increase in NK activity similar to that after in vivo administration of alpha-IFN, indicating a simple predictor of patients' responsiveness to IFN treatment. Taken together, these findings indicate that in vivo administration of alpha-IFN results in a dose-dependent augmentation of NK and ADCC activity in cancer patients.

Adult↗
PubMed1982

A profile of treatment approaches used at comprehensive cancer centers.

The Centralized Cancer Patient Data System is the system which the 21 comprehensive cancer centers in the U.S. have established in order to report and to analyze demographic, diagnostic, treatment and survival data on all new patients. We propose that this closely monitored standardized 36 item dataset can be used to profile the categories of initial treatment that are given to patients having all types and stages of cancer: the data may be displayed for all centers or used to compare the approaches used at different centers. Differences in the frequency with which surgery, radiation, chemotherapy, and no specific treatment are used for patients having any of three common histologic types of lung cancer serve to illustrate the method. Opportunities now exist to utilize this new resource to study trends in the use of treatment modalities and their relationship to survival, which in turn should enhance the accessibility of treatment information about all patients at cancer centers, rather than only those which are reported from selected treatment protocols. This approach may also be uniquely useful in obtaining treatment and survival information about patients with rare sites or types of cancer.

Adenocarcinoma↗
PubMed1982

Essential thrombocythemia: response during first year of therapy with melphalan and radioactive phosphorus: a polycythemia Vera Study Group report.

Thirty-one patients with essential thrombocythemia were randomized to receive either melphalan or radioactive phosphorus as myelosuppressive therapy. Twenty-seven patients were evaluable for response. Of 13 patients treated with melphalan, 11 had a complete response (platelet count less than 450,000/mm3) at 3 and 6 months. This response rate was significantly better than the response to radioactive phosphorus. The response rates were similar at 12 months. No significant toxicity was observed with either regimen.

Aged↗