Joseph Allegra

Quantitative estrogen receptor analyses: The response to endocrine and cytotoxic chemotherapy in human breast cancer and the disease-free interval

The usefulness of estrogen receptor (ER) analyses was assessed in a variety of clinical situations. The predictive accuracy of the test is substantially increased by quantification. ER analyses accurately predict objective responses to endocrine therapy independently of other clinical prognostic criteria. In addition, ER positivity is associated with a decreased response rate to cytotoxic chemotherapy in patients with metastatic breast cancer. Finally, the presence of ER is positively associated with a prolonged disease‐free interval independent of menopausal status, tumor size, and axillary lymph node involvement.

Glycoproteins and human cancer: 1. Circulating levels in cancer serum

Total protein and sialic acid levels were determined in the supernatant of serum treated with perchloric acid. Patients with either localized or advanced metastatic malignancy have significantly elevated mean serum values. The highest levels occur in patients with lung, GI, GYN cancer, lymphoma and malignant melanoma. Patients with leukemia and multiple myeloma have slightly elevated values, but they were not significantly different from normal. Patients following curative surgery have normal values while patients in clinical remission following chemotherapy have elevated mean serum protein and NANA levels. Elevated values also occur in patients with benign tumors and 12% of patients with nonmalignant disease. Tumor cells appear to shed macromolecules which contribute to the observed elevation of serum protein and sialic acid levels.

Plasma prostaglandins in hypercalcemic patients with neoplastic disease

Peripheral plasma prostaglandin E (PGE) determinations were performed on a series of 79 patients with solid tumor neoplasms and correlated with their serum calcium levels. Fourteen patients were hypercalcemic and 11 of these had significant elevations in circulating plasma PGE. Ten of the hypercalcemic group had extensive metastases to bone. These findings support the recently developed hypothesis that prostaglandins are causally related to the genesis of hypercalcemia in malignancy.

A Long‐Term Study of Low‐Dose Aerosolized Terbutaline Sulfate

The purpose of this study was to evaluate the safety and efficacy of a new lowdose terbutaline sulfate aerosol (375 micrograms) over a six-week period. The question of drug tolerance was also evaluated. Twenty-four ambulant patients with chronic obstructive pulmonary disease with a component of reversible airway disease was evaluated. The patients were tested at two-week intervals during a six-week period. The patients abstained from all bronchodilatory medications for at least 10 hours prior to the time of evaluation. The evaluation consisted of baseline FEV1 and MMEFR determinations, ECG, CBC, urinalysis, and renal and liver function tests. After the terbutaline was administered, a rhythm strip and pulmonary function tests were repeated at 5, 15, 30, 60, 120, and 180 minutes. Throughout the six-week study there was a statistically significant increase in FEV1 and MMEFR, (P less than 0.001). No change was noted in the systolic blood pressures; however, heart rate and diastolic blood pressure decreased significantly. No drug tolerance, paradoxical bronchospasm, subjective side effects, no abnormal laboratory results were noted during the study period.

The effect of prednisone and irradiation on the rectum in dogs.

In an attempt to diminish the severity of the acute and late effects of irradiation to the rectum of dogs, oral prednisone was administered to 10 dogs for 1 week prior to, during, and for 1 month following a 3-week fractionated course of 60Co exposures to the pelvis. A control group of 10 dogs received irradiation alone. The dogs were observed clinically, serial rectal biopsies were done during and following the acute reaction, and the rectum was studied following sacrifice. Observations suggest that prednisone has no beneficial effect on the acute inflammatory reaction, and increases the severity of the late tissue damage.

Oral terbutaline sulfate--amelioration of exercise-induced bronchospasm.

Bronchospasm can be induced in asthmatics when exercised according to a multistage branching treadmill protocol that allows them to achieve 80 per cent of their age-predicted maximal heart rate. This present study was undertaken to investigate the effect of oral terbutaline sulfate in ameliorating exercise-induced bronchospasm. Ten asthmatics were exercised, and FEV1.0 and MMEFR were assessed while standing, using a Jones Pulmonar II waterless spirometer at 5, 15, and 30 minutes after exercise. Three hours before exercise, the subjects received no medication, oral placebo, or 5 mg terbutaline sulfate orally. At all time intervals after exercise, the pulmonary function of the group pretreated with oral terbutaline was superior when compared to the no-medication group (P less than 0.01) and to the placebo-treated group (P less than 0.05). Oral terbutaline appeared to normalize the exercise tolerance of the asthmatics and restore physiologic pulmonary airway conductance by the parameters of FEV1.0 and MMEFR.

The pharmacologic effect of aerosolized terbutaline sulfate in exercise-induced bronchospasm.

Bronchospasm can be induced in asthmatics when exercised according to a multistage branching treadmill protocol that allows them to achieve 80 per cent of maximal age-predicted heart rate. This degree of exercise is usually achievable and allows inducible bronchospasm to occur. This present study was undertaken to investigate the effect of terbutaline sulfate aerosol in exercise-induced broncho-spasm. Asthmatics were exercised to 80 per cent of their maximal heart rate, and FEV1.0 and MMEFR were assessed while standing using a Jones Pulmonar II waterless spirometer at 5, 15, and 30 minutes after exercise. After a standard rest period defined by a return to baseline of FEV1.0, MMEFR, and heart rate for 30 minutes, the subjects were administered either 0.50 mg aerosolized terbutaline sulfate or placebo and then exercised again. The pulmonary function parameters were again recorded after this exercise. Preterbutaline and postplacebo exercise resulted in a significant reduction in FEV1.0 and MMEFR, while after treatment with terbutaline not only did bronchospasm not occur but bronchodilation occurred (P less than 0.01). Inhaled terbutaline appeared to normalize the exercise tolerance of the asthmatics and restore physiologic pulmonary airway conductance according to the parameters of FEV1.0 and MMEFR.

Immunosuppression and human cancer: Role of prostaglandins

Prostaglandins, unsaturated fatty acid derivatives with diversified pharmacologic activity, have been implicated in the pathophysiology of many diseases. Prostaglandin E (PGE) levels were measured by radioimmunoassay in the plasma of 41 normocalcemic patients with various stages of malignancies. Delayed hypersensitivity was assessed by a battery of six recall skin test antigens (ST) and by Dinitrochlorobenzene (DNCB) sensitization and challenge. Twenty‐five patients with one or more positive skin tests had a mean PGE level of 87 ± 8 pg/ml, whereas 16 patients with negative ST had a mean PGE level of 96 ± 12 pg/ml. Twenty‐one DNCB negative patients had a mean PGE level of 98 ± 12 pg/ml and eight totally anergic patients had a mean PGE of 96 ± 12 pg/ml. All PGE values were within the normal range and there was no statistical difference between the four groups, (p < 0.1). We concluded that circulating PGE does not correlate with the non‐specific immunosuppression seen in cancer patients.

Plasma prostaglandins across the tumor bed of patients with gynecologic malignancy.

Prostaglandin E produced by tumors has recently been implicated as a mechanism by which tumors may subvert the immune system and grow despite their antigenicity. Arterial and venous determinations of prostaglandin E were performed in eleven patients with gynecologic malignancy. No significant difference was found when arterial and venous levels were compared and there was no difference in venous PGE levels when subjects with cancer were compared to patients with benign gynecologic disease.

Measurement of plasma prostaglandins during exercise-induced bronchospasm

Bronchospasm following exercise is a phenomenon which occurs in most patients with reversible airway disease. The pathophysiologic mechanism leading to this bronchoconstriction with exercise has not yet been defined. Recently, prostaglandins have been implicated in the etiology of asthma. The purpose of this investigation was to determine changes in plasma prostaglandins occurring during exercise-induced asthma. Eight ambulant asthmatics were chosen for baseline pulmonary spirometry and peripheral venous blood prostaglandin E and F levels. The asthmatics were then exercised to 80% of their age-predicted maximal heart rate via a multistage branching treadmill protocol. At 5, 15, and 30 min following exercise, pulmonary spirometry was again performed and peripheral venous blood collected at the indicated times. Clinical bronchospasm as characterized by audible wheezing and greater than 15% decrease in FEV1 and MMEFR was obtained in all of the asthmatics. Peripheral PGE and PGF2alpha determinations following this exercise protocol were not altered significantly: (PGE: 0 min, 238; 5 min, 185; 15 min, 248; 30 min, 256 pg/ml); (PGF2alpha: 0 min, 50; 5 min, 24; 15 min, 25; 30 min, 17 pg/ml) (p less than 0.1). In summary, no significant change in peripheral blood prostaglandin E and F2alpha levels as determined by radioimmunoassay was noted at the time of exercise-induced bronchospasm.