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Biomedical subjects

J Laszlo

Publications and source records attributed to J Laszlo.

At least 37 records · Page 2Linked to original sources
PubMed1987

Effects of gamma-interferon on the endocrine system: results from a phase I study.

Interferon causes profound biological changes when given to patients with cancer and many of these could not be predicted from in vitro or animal model systems. We documented significant changes in hormonal levels for a group of 18 patients who were participants in a Phase I gamma-interferon trial. Adrenocorticotropic hormone, cortisol, and growth hormone were all significantly elevated 2 h after treatment with gamma-interferon, with cortisol and adrenocorticotropic hormone returning to base line by 24 h. A placebo group failed to show this change, suggesting a specific interferon effect. Possible mechanisms for these findings and implications for the use of interferons are discussed.

Adrenocorticotropic Hormone↗
PubMed1987

Age trends of lung cancer stage at diagnosis. Implications for lung cancer screening in the elderly.

Lung cancer increases in incidence with increasing age and is the leading cause of cancer death in the United States. While mass screening for lung cancer is not indicated, selective screening of high-risk target groups may be beneficial. We tested the hypothesis that lung cancer is initially seen at a less advanced stage with increasing age using incidence cases (N = 22,874) from the Centralized Cancer Patient Data System. The percent of lung cancer patients with local stage disease increased from 15.3% of those aged 54 years or younger, to 19.2% of those aged 55 to 64 years, to 21.9% of those aged 65 to 74 years, and to 25.4% of those aged 75 years or older. The percent with distant stage decreased from 48.7%, to 44.5%, to 40.3%, and to 36.7% for the same age groups, respectively. These age-stage trends persisted in subgroup analysis by sex, race, and histological subtype. Furthermore, analysis of 6332 patients who underwent surgical staging showed a greater likelihood of local stage disease with increasing age. Thus, compared with the young, the group aged 65 years or older is at a greater risk for lung cancer and has a higher proportion of lung cancer initially seen at local stage. The efficacy of selective screening for lung cancer in this target group warrants additional study.

Age Factors↗
PubMed1987

Differentiation between essential thrombocythemia and polycythemia vera with marked thrombocytosis.

Accurate distinction between essential thrombocythemia and thrombocytotic polycythemia vera requires determination of the red cell mass in the presence of adequate iron stores, but this is not always possible. We therefore compared the clinical and laboratory features at the time of presentation of 50 patients with unequivocal essential thrombocythemia and 27 patients with thrombocytotic polycythemia vera. Univariate analysis failed to identify any single parameter capable of reliably separating the groups. A logistic regression algorithm incorporating hematocrit, white cell count, and spleen size markedly increased the diagnostic accuracy (92%) compared with predictions based on the hematocrit alone (52%). The algorithm's usefulness for patients with intermediate hematocrits was confirmed by analysis of independent samples of essential thrombocythemia and thrombocytotic polycythemia vera patients, and also by analysis of patients with probable essential thrombocythemia in whom the diagnosis could not be confirmed because of inadequate exclusion of polycythemia vera. Furthermore, comparison of survival data suggests that differentiating these disorders is prognostically important. The algorithm is recommended as an alternate method for differentiating essential thrombocythemia from thrombocytotic polycythemia vera whenever the red cell mass is unavailable or iron deficiency cannot be excluded.

Adult↗
PubMed1987

Optimum management of nausea and vomiting in cancer chemotherapy.

Nausea and vomiting continue to be critical problems in cancer chemotherapy, although considerable progress has been made toward understanding the neuropharmacological mechanisms of vomiting and how chemotherapeutic agents and antiemetics affect these mechanisms. The principles of behavioural psychology have also been applied in an effort to understand and effectively manage these complications which have potentially serious consequences. For example, there is now some degree of rationality to our use of metoclopramide for cisplatin-induced nausea and vomiting, the use of combination antiemetic regimens, and use of lorazepam for the prevention (albeit unproven) of anticipatory nausea and vomiting. It must be admitted, however, that our approach is for the most part still empirical. Selecting an antiemetic programme is not a simple task. The emetogenic potential of the chemotherapy being used, the presence of coexisting diseases, the potential toxicity of the antiemetic drug and whether antiemetic therapy is to take place in the hospital or in an outpatient setting, the familiarity of the clinician with the various antiemetic therapies, and cost are all factors which need to be considered. Although phenothiazines remain the standard treatment, they are of little value against chemotherapy programmes that produce moderate or severe problems. Newer pharmacological approaches including butyrophenones, cannabinoids, metoclopramide, high-dose corticosteroids, and benzodiazepines have shown increased antiemetic efficacy, as have combinations of these agents which are directed against multiple sites of emetogenic activity. The role of behavioural therapies, which have been shown to be effective particularly in children and in anticipatory nausea and vomiting, needs to be more firmly established. Rather than recommending a given antiemetic programme for any particular chemotherapy, it is preferable to think in terms of initial approaches and how they can be modified. No one antiemetic programme is effective or safe in all situations.

Antineoplastic Agents↗
PubMed1987

Supportive care of the patient with cancer.

In assessing the needs of the elderly patient with cancer, we need first to determine the extent of cancer, its complications, and the type of comorbid physical and psychologic conditions. The next step is to determine the goals of our care and specifically the extent to which supportive care is needed to deal with problems. For supportive care to be truly effective, the specific underlying condition producing a complaint must be investigated. It is also important not to underestimate the significance of a symptom such as constipation. Furthermore, nutritional support requires as much planning as, for example, the control of pain. Some problems (eg, nausea, vomiting, pain, and constipation) are best managed with preventive measures; others (eg, anemia, granulocytopenia, and coagulopathies) have very specific indications for intervention. Considerable progress has been made toward understanding the mechanisms of clinical problems such as nausea and vomiting, and a more rational approach to supportive therapy is now possible. However, it is usually not possible to recommend any one intervention for a particular problem: no one intervention is uniformly effective or safe. Aggressive supportive care in elderly cancer patients can improve their ability to tolerate anti-cancer therapies and, more importantly, provide palliation of distressing symptoms.

Aged↗
PubMed1987

Initial clinical studies of piritrexim.

Piritrexim (PTX) is a second-generation, lipid-soluble inhibitor of dihydrofolate reductase (DHFR). Metabolic inhibition occurs within seconds after rapid diffusion into human cancer cells. We describe the initial phase I studies with iv and oral forms of this drug given on a daily basis for 5 days to patients with cancer. The dose-limiting toxicity is primarily hematologic (leukopenia, granulocytopenia, thrombocytopenia), but phlebitis is also encountered with iv administration and gastrointestinal problems (nausea, vomiting) with oral administration. Oral toxicity can be reduced by giving the daily dose in 2 divided doses. The maximum tolerated dose (MTD) for the iv route is 170 mg/m2 per day for 5 days; for the oral route it is 480 mg/m2 per day for 5 days. Unlike an earlier lipid-soluble folate antagonist, piritrexim did not cause neurologic or histamine-like disorders.

Administration, Oral↗
PubMed1986

Glutamate-induced activation of rat locus coeruleus increases CA1 pyramidal cell excitability.

In anesthetized rats, injections of a 0.5 mM glutamate solution into the locus coeruleus (LC) reversibly increased the amplitude of the population spike evoked in CA1 by stimulation of the Schaffer-commissural fiber tract. This effect was absent in N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4)-treated, noradrenaline (NA)-depleted animals. The excitatory postsynaptic potential recorded in the stratum radiatum was unaffected following the glutamate injections. Systemic administration of the NA-uptake inhibitor desipramine also produced an increase in population spike amplitude. The findings demonstrate that activation of LC neurons increases pyramidal cell excitability in vivo.

Animals↗
PubMed1986

Calcitonin secretion in streak gonad syndrome (Turner's syndrome).

Osteoporosis in one of the most common complications of streak gonad syndrome (SGS), however, its pathogenesis is still unclear. To test whether SGS is associated with calcitonin (CT) deficiency, 11 affected individuals and 8 age-matched healthy women were studied. Calcium, 3.6 mg/kg b.w. as a 10% solution of calcium chloride, was given intravenously for 3 minutes. Serum levels of CT and calcium were measured before and at 5, 30, 60, and 120 minutes after the injection. There was a statistically significant rise in serum calcium levels both in the control subjects and patients with SGS, with significantly lower levels prior to and at 30, 60, and 120 minutes following calcium load in the control group. The CT rise following calcium load was also significant at 5, 30, and 60 minutes in the controls and at 5 and 30 minutes in patients with SGS, with a significantly lower baseline and 30, 60, and 120 minutes levels in the latter group. Maximum levels of calcium and CT occurred 5 minutes after the calcium load and were statistically indistinguishable. There were no significant differences in either the calcium or the CT incremental changes between the two groups. These findings are consistent with decreased basal (and 30-120 minute) CT levels in SGS and suggest that CT deficiency may be involved in the development of osteoporosis in patients with SGS. The possible causal relationship of estrogen deficiency to the reduced CT levels in SGS is discussed.

Adolescent↗
PubMed1986

Induction of 2',5'-oligoadenylate synthetase activity in peripheral blood mononuclear cells by gamma interferon.

Activity of the interferon-induced enzyme 2',5'-oligoadenylate (2-5A) synthetase was measured in peripheral blood mononuclear cells (PBMC) of 32 cancer patients treated with recombinant human gamma-interferon (rHGIF). Pretreatment activities varied widely but remained constant for each individual. The minimum dose of rHGIF that consistently stimulated activity was 12 MU/m2, although in some patients as little as 0.004 MU/m2 was stimulatory. Enzyme activity in responding patients increased threefold at 24 h after the initial infusion and remained elevated nearly twofold at 72 h independent of dose. This increase is less than that observed after infusions of alpha-interferon and parallels results observed in vitro. Pretreatment enzyme activity did not correlate with response. Twenty-minute infusions of a fixed dose were as effective as four- and 24-h infusions in raising enzyme levels. The level of activity achieved after the initial infusion could not be sustained with twice-weekly infusions. We conclude that rHGIF does induce 2-5A synthetase activity in PBMC but not to the levels induced by alpha-interferon. The observation that brief infusions of low doses can be maximally stimulatory in vivo suggests that the response of PBMC in vivo is being confounded by factors yet to be determined. Furthermore, it appears that the capacity of PBMC to maximally respond to rHGIF in vivo, with increases in enzyme activity, is transient.

2',5'-Oligoadenylate Synthetase↗
PubMed1986

A randomized trial of low doses of alpha interferon in patients with breast cancer.

A randomized Phase II study was planned to test two doses of human lymphoblastoid interferon (Wellferon) in patients with metastatic breast cancer. Thirty-seven patients were entered and received either 0.5 or 3.0 million units three times a week for three months. The dose selection was based on earlier Phase I studies in order to maximize NK (natural killer) stimulation and the amount tolerated without undue toxicity. Twenty-nine patients were evaluable. There was only one excellent partial remission, sustained for one year. There were small and statistically insignificant NK increases in both groups. From this and a review of the literature, we conclude that alpha interferon has negligible activity in breast cancer.

Breast Neoplasms↗
PubMed1986

Does maintenance therapy with alpha interferon stabilize cancer growth? A pilot study.

A pilot study was undertaken to test whether alpha interferon (alpha-IFN) maintenance could continue to stabilize cancer measurements after induction therapy. Twenty-one patients who achieved stable disease at the end of their induction treatment were randomized to receive weekly maintenance with human lymphoblastoid interferon (HLBI) (3 MU/m2, i.m.) or to be followed and not given interferon. There were 12 patients in the maintenance groups and 9 in the control observation group. There was no time difference in disease progression between the two arms. This article considers the relevance of the stable disease category in trials of interferon.

Adult↗
PubMed1986

A phase II trial of high-dose human lymphoblastoid alpha interferon in patients with advanced renal carcinoma.

Seventeen patients with metastatic renal cancer were treated with human lymphoblastoid cell-derived alpha interferon, 30 X 10(6) U/m2, which was given intravenously for 3 consecutive days of each week for 6 weeks. On the days of interferon treatment only, patients received prednisone, 15 mg t.i.d., in order to minimize toxicity. Of the 16 evaluable patients, one had a minor regression of disease, eight had stable metastatic disease, and seven progressed. Constitutional symptoms, such as fever, anorexia, and fatigue, were common. Debilitating degrees of malaise were a treatment-limiting factor.

Central Nervous System↗
PubMed1985

Overcoming methotrexate resistance by a lipophilic antifolate (BW 301U): from theory to models to practice.

We have provided a rationale for the clinical use of a new lipid-soluble folate antagonist, BW 301U, in terms of its potential for killing several classes of methotrexate-resistant cells. As part of a Phase I evaluation of this agent we studied normal bone marrow from cancer patients and their metabolic susceptibility to either BW 301U or to MTX and then repeated the observations at the end of five days of BW 301U infusions. Both inhibitors were roughly comparable at equimolar concentrations prior to therapy, but a relative resistance developed to MTX after BW 301U treatment. Such findings were replicated in an in vitro HL-60 cell culture system that was exposed to BW 301U. Some possible mechanisms for this unusual collateral resistance are discussed.

Animals↗