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Biomedical subjects

J Abrams

Publications and source records attributed to J Abrams.

At least 163 records · Page 9Linked to original sources
PubMed1988

Effects of interleukin-2 on oxygen delivery and consumption in patients with advanced malignancy.

We evaluated the effects of fluid challenges on oxygen delivery (DO2) and oxygen consumption (VO2) in nine patients receiving immunotherapy with interleukin-2. Fluid resuscitation produced an increase in DO2 from 15.7 +/- 3.1 to 17.4 +/- 3.5 ml/min/kg (mean +/- SD, p less than 0.001), which was associated with a corresponding increase in VO2, from 2.8 +/- 0.7 to 3.1 +/- 0.6 ml/min/kg (p less than 0.01). These results suggest that oxygen consumption may be dependent on oxygen delivery in patients on IL-2 therapy. The presence of oxygen supply dependency may contribute to the multiple organ failure observed with IL-2 administration.

Adult↗
PubMed1988

Staging, prognostic factors, and special considerations in small cell lung cancer.

New treatment approaches in the fight against SCLC are clearly on the horizon and some are already in clinical trials. With this in mind, several comments concerning future directions in staging this disease can be made: 1. Staging is important and complete staging is needed in order to continue to build meaningful information. 2. Limited/Extensive disease categories are in use and remain important; yet this system is not completely adequate. There are subsets within each group that do better: minimal disease versus bulky disease in limited stage, extraabdominal v intraabdominal in extensive disease, and single organ versus multiple organ involvement. Therefore, a new staging system is needed. The TNM system is designed primarily to define surgical resectability and will thus not adequately address the issues for SCLC unless the N and M categories are markedly enlarged. A staging symposium was recently held in Europe to begin to address potential approaches to staging and an American staging conference is planned. 3. Biomarkers: In the broad range of possible markers, most are not sufficiently sensitive or specific to supplant clinical exam and routine testing. But newer tests such as NSE, CK-BB and tumor surface antigen expression and recognition may impact on staging in the near future. 4. Finally, as the biology of SCLC is further understood, much of the derived understanding will likely change the staging and prognostic factors.

Biomarkers, Tumor↗
PubMed1988

High-dose megestrol acetate in the treatment of advanced breast cancer.

A dose-response relationship has long been suspected for progestin compounds in the treatment of breast cancer, but only recently have trials been implemented to investigate this issue. In 1985, we began a phase I-II study of high-dose megestrol acetate in dosages of 480 mg/d to 1,600 mg/d in heavily pretreated postmenopausal patients with advanced breast cancer. After establishing the safety of this therapy, we expanded our trial, which now includes 47 patients, 34 of whom have measurable disease. Of these 34 patients, 30 had disease progression on prior hormonal therapy and 29 had progression on chemotherapy. Six of the 34 patients had complete response and six had partial response for a median time on study of 10 months (range, 8 to 30 months). Ten patients had stabilization and 12 had progression. Thirteen patients had evaluable but nonmeasurable disease, and of these, ten had improvement or stabilization for a median period of 6 months (range, 2 to 18 months) and three had progression. Of 17 patients who had experienced disease progression while receiving standard-dose megestrol acetate, 13 (76%) achieved objective remissions or stabilization with high-dose therapy. The main side effects were weight gain and appetite enhancement, which were beneficial in 13 underweight patients. These data indicate that high-dose megestrol acetate is well tolerated and effective in patients with advanced breast cancer refractory to multiple previous therapies. While optimal dose levels for clinical use remain to be established by ongoing studies, our data suggest that doses higher than the standard dose may be more effective.

Adult↗
PubMed1988

Epithelioid granulomas revisited: long-term follow-up in Hodgkin's disease.

A previous retrospective study of epithelioid granulomas discovered in the liver or spleen at staging laparotomy for Hodgkin's disease showed that the granulomas were not indicative of malignant involvement of these organs. Rather, they correlated with improved relapse-free survival in affected patients compared to those without granulomas. These findings were based on 2 year median follow-up. To confirm and expand these findings after additional follow-up, we analyzed the clinical data for 89 of the original cohort of 91 patients who underwent staging laparotomy at our institution between July, 1968 through December, 1972. Neither time to first relapse nor overall survival duration is now significantly different between the granuloma and nongranuloma groups. Of the nongranuloma patients 23/67 (34%) have relapsed versus 3/16 (19%) patients with granulomas (Fisher's exact test p = 0.184). The relapse-free survival advantage for patients with granulomas seen in the earlier report is no longer apparent after more prolonged follow-up.

Adult↗
PubMed1987

Clinical and pharmacokinetic phase I trial with the diethylaminoester of flavone acetic acid (LM985, NSC 293015).

The diethylaminoester of flavone acetic acid (LM985) is a new anticancer agent with curative effects against slow growing murine tumors. Thirty-one adult patients with solid tumors received a total of 57 courses of LM985 given on days 1 and 8 every 4 weeks. The drug was given as a short infusion (1-2 hr) at doses ranging from 120 to 1900 mg/sq.m/day. The dose-limiting toxicity consisted of acute expressive aphasia; this neurotoxicity usually appeared at the end of the infusion and resolved spontaneously within a few minutes to 1 hr after the end of the infusion. In some patients, neurotoxicity was avoided by reducing the infusion rate. Neurotoxicity was observed in 5 out of 6 patients receiving 960 mg/sq.m over 1 hr and in 3 out of 3 patients receiving 1900 mg/sq.m over 2 hr. The drug did not induce any significant myelosuppression. Other side-effects were very mild and consisted mainly of occasional nausea and/or vomiting at all dose levels. One patient with breast cancer resistant to several hormonal and chemotherapy regimens had stable disease for 6 months. LM985 was detected in plasma in very small concentrations (0-2.5 micrograms/ml) but there was extensive formation of flavone acetic acid (peak concentration ranging between 8.3 and 64 micrograms/ml). A dose of 1500 mg/sq.m on days 1 and 8 every 4 weeks could be recommended for phase II studies with LM985; however, since LM985 is a prodrug of flavone acetic acid, phase II studies with LM985 should not be activated prior to the completion of the ongoing phase I trials with flavone acetic acid, which may be devoid of the acute toxicity of LM985.

Adult↗
PubMed1987

Suicidal sodium azide ingestion.

Sodium azide (NaN3) is a highly reactive, toxic, widely used chemical. Although industrial exposure is common, fatal ingestion is rare. We describe the case of a 30-year-old man who ingested 15 to 20 g of sodium azide. He became comatose within two hours and eventually expired from a combination of acidosis, respiratory depression, and ventricular fibrillation. In sufficient doses, sodium azide is rapidly fatal and there is no effective treatment.

Administration, Oral↗
PubMed1987

Glyceryl trinitrate (nitroglycerin) and the organic nitrates. Choosing the method of administration.

Nitrate usage worldwide is on the increase as the indications for therapy expand. Present indications for nitrate therapy include chronic stable angina pectoris, unstable angina pectoris, complications of acute myocardial infarction, and 'unloading' therapy for acute and chronic congestive heart failure. Nitrates are also being used in the operating suite by anaesthesiologists to control systolic blood pressure during various surgical procedures. New nitrate delivery systems have recently become available which provide considerable dosing flexibility, further increasing the interest in this group of compounds. The dominant action of nitrates is a direct effect on vascular smooth muscle, producing vasodilation of the veins and arteries. These drugs decrease myocardial work by lowering systolic blood pressure, systemic vascular resistance, and reducing intracardiac dimensions. In addition, nitrates have a potent effect on cardiac preload as a result of systemic venodilatation. There is also some evidence that nitrates exert direct effects on the coronary circulation (vasodilatation of coronary arteries and coronary collateral vessels, and direct atherosclerotic stenosis dilatation). These actions may play a role in relieving myocardial ischaemia. Adverse sequelae of nitrate therapy are well known and serious adverse reactions are uncommon. Headache and dizziness are the most frequent side effects. Nitrate tolerance is a definite problem - present evidence indicates that long acting formulations, high doses, or frequent dosing regimens are particularly likely to induce vascular tolerance to nitrates. Consequently, provision of a nitrate-free interval has taken on increasing significance as a strategy to avoid tolerance. Nitrate delivery systems are numerous. Although availability varies from country to country, in most countries there are a wide variety of formulations of glyceryl trinitrate (nitroglycerin) available, including sublingual and oral tablets, oral spray, topical ointment as well as discs or patches for transdermal administration, a transmucosal tablet and an intravenous formulation. Similar formulations of isosorbide dinitrate, except buccal tablets, are available in some countries. Isosorbide 5-mononitrate, a potent metabolite of isosorbide dinitrate, is achieving increasing popularity as an antianginal drug. Optimum nitrate therapy requires a good understanding of the properties of the various formulations, particularly onset and duration of action and propensity to induce tolerance.(ABSTRACT TRUNCATED AT 400 WORDS)

Angina Pectoris↗
PubMed1987

How effective is cytotoxic chemotherapy for disseminated prostatic carcinoma?

Most of the chemotherapeutic agents available for clinical practice have been employed against prostatic cancer, either alone or in combination. Evaluation of the results has been complicated by various factors, not the least of which relates to the nature of the disease itself. In this comprehensive review of the literature, the authors have compiled the results to date.

Antineoplastic Agents↗
PubMed1986

Subrenal capsule assay of fresh human tumors: problems and pitfalls.

The 6 day subrenal capsule (SRC) assay was performed in normal mice using 20 fresh human non-small cell lung cancers and nine fresh ovarian cancers. Different multi-agent chemotherapy regimens administered intravenously on days 2 + 3 of the assay were evaluated for activity against these two tumor types. Macroscopic results measured via an ocular microscope showed high activity for some combinations as well as for single agents. However, when subjected to microscopic examination, the SRC implants in the untreated control animals did not show viable tumor growth on day 6. Detailed histologic evaluation of over 800 SRC grafts reveals an intense inflammatory and fibrotic reaction in the majority of the grafts. These results indicate that drug sensitivity patterns obtained with this assay using only macroscopic criteria do not correlate with actual tumor regression. Microscopic analysis of the grafts prior to transplant shows absence or only minimal presence of tumor in many cases which also contributes to the poor growth observed in these two tumors.

Animals↗
PubMed1986

Influence of sucrose polyester on plasma lipoproteins, and cholesterol metabolism in obese patients with and without diabetes mellitus.

Sucrose polyester (SPE) is a nonabsorbable substitute for fat. This study examined its effects in 10 obese patients, 6 with diabetes mellitus. Three diabetics had hypertriglyceridemia. Most patients were studied in three periods: weight maintenance, caloric restriction + SPE, and caloric restriction without SPE. Nondiabetics generally tolerated SPE better than diabetics. In nondiabetic patients caloric restriction + SPE produced a decrease in total cholesterol and in LDL-cholesterol of 20% and 26%, respectively. In normotriglyceridemic diabetic patients caloric restriction + SPE had an effect on plasma lipoproteins similar to that of nondiabetics. In diabetics with hypertriglyceridemia caloric restriction (with or without SPE) caused a marked reduction in plasma triglycerides. In all patients caloric restriction reduced cholesterol balance and presumably cholesterol synthesis. The feeding of SPE caused increased outputs of fecal neutral steroids suggestive of decreased absorption of cholesterol; SPE also frequently caused a mild increase in fecal acidic steroids (bile acids).

Aged↗
PubMed1986

Phase I study of intravenous menogaril administered intermittently.

Thirty-three adult patients with solid tumors were treated with menogaril, a new anthracycline antibiotic. The drug was given as a two-hour infusion every 4 to 5 weeks at doses ranging from 17 to 250 mg/m2. The maximum tolerated dose was 250 mg/m2. Reversible and dose-related leukopenia was the dose-limiting toxicity. Thrombocytopenia was less frequent. Hematologic toxicity was maximal 2 weeks after treatment, and recovery usually occurred within 4 weeks. There was no dissociation between WBC and neutrophil counts, and myelosuppression did not appear to be cumulative up to 200 mg/m2. Myelosuppression was more severe for patients with heavy pretreatment and/or bone marrow involvement. Local toxicity consisting of phlebitis and/or erythema was the most common nonhematologic toxicity, especially at 250 mg/m2 (eight out of nine patients). Usually, erythema appeared within 24 hours after treatment at or near the infusion site and resolved within a few days. Occasionally, a more persistent (several weeks) orange discoloration suggesting cutaneous deposits of menogaril was observed. Nausea and vomiting were uncommon and never severe. Alopecia and mucositis were rare. Minor arrhythmias were seen in several patients during treatment, but their relationship with menogaril therapy was unclear, and in no patient did heart failure develop. Plasma concentrations were best described by a tricompartmental model with a mean terminal half-life of 29.5 hours and a mean total-body clearance of 20.2 L/h/m2. Doses of 160 and 200 mg/m2 are recommended for phase II trials in poor- and good-risk patients, respectively.

Adult↗