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Biomedical subjects

J Friedmann

Publications and source records attributed to J Friedmann.

14 recordsLinked to original sources

A phase I study of oral ZD 1839 given daily in patients with solid tumors: IND.122, a study of the Investigational New Drug Program of the National Cancer Institute of Canada Clinical Trials Group.

PURPOSE: To define the maximum tolerated dose (MTD), the dose limiting toxicity (DLT), the biological active (BA) dose and the pharmacokinetics (PK) of the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor ZD1839 (Iressa) when administered continuously as a once daily dose in patients with advanced, incurable solid tumours. PATIENTS AND METHODS: Twenty-eight patients were enrolled in cohorts of three from three National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) centers. ZD1839 was given at doses from 150 to 800 mg daily orally and patients underwent a pretreatment and a 28 day post treatment tumor biopsy, while PK sampling was performed on days 8, 15, 22, 29, and a toxicity assessment every 28 days. RESULTS: All twenty-eight patients were evaluable for non-hematological and hematological toxicity. Twenty-seven were evaluable for response. The MTD was not reached but DLT included reversible rash and diarrhea. One patient with urachal cancer had a transient 55% decrease in tumor size and two other patients (breast and non-small cell lung cancer) had minor responses; three additional patients had pharmacodynamic evidence of target effect. PK demonstrated steady state within the first 2 weeks of dosing and dose dependent exposure. CONCLUSION: It appears that ZD 1839 at a dose of 800 m/day was tolerable, although some patients required dose modification for diarrhea. Doses above 250 m/day demonstrate biologic activity and could be consider for future study in a variety of EGFR positive tumor types.

Administration, Oral↗

Myocardial infarction in young adults under 30 years: risk factors and clinical course.

The clinical features and course of 30 patients (26 men and 4 women) under 30 years of age (mean age 27.3 years) with an acute myocardial infarction (MI) are described. The most common risk factor among this group of patients was smoking in 20 patients (66%). The prevalence of the other risk factors was low: hyperlipidemia in four patients and family history of ischemic disease in another four patients, diabetes mellitus, hypertension, and obesity each in one patient. Seven patients (23%) had none of the conventional risk factors. Three patients were exerting themselves prior to the onset of their MI pain; all of them had normal coronaries. Five patients experienced chest pain prior to MI, among them only two experienced classical angina pectoris. Eighteen patients underwent uncomplicated MI. The complications in the other 12 during the acute MI were rhythm disturbances in eight and congestive heart failure in four. Cardiac catheterization was performed in 25 patients. The occurrence of zero, one, or multivessel disease was equal. The 30 patients were followed up from six months to 15 years (mean 7 years). In 18 patients circulating aggregated platelets were measured one year after the MI. Elevated values were found in all of them (mean +/- SD 34.9 +/- 9.1%). In 6 of the 18, all heavy smokers, extreme values were found in the range of 39-55%. Three out of the 30 patients died within five years after their first MI. The other 15 patients developed complications, most of them angina pectoris. Five patients were hospitalized for reinfarction. None of the 30 underwent aortocoronary bypass operation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Primary giant cell carcinoma of the larynx. A clinico-pathological study of four cases.

The clinical and pathological findings in 4 cases of primary giant cell carcinoma of the larynx are reported. This variant of large cell carcinoma resembles the well-defined giant cell carcinoma of the lung. It has to be distinguished from other types of carcinoma of the larynx. This can be difficult on small biopsy specimens and the definite diagnosis may only be established after the detailed examination of the excised tumour. The highly malignant behavior of the laryngeal type was noted. To our knowledge this is only the second report on giant cell carcinoma of the larynx.

Carcinoma↗

Circulating autoantibodies to hidden mitochondrial antigenic determinants in mammals.

Autoantibodies to equine cytochrome c and to porcine malic dehydrogenase are shown in equine and porcine serum, respectively, by immunodiffusion. A confluence of arcs between human plasma and rabbit, horse and pig serum against these antigens suggests the presence of antibodies in human plasma to cytochrome c and malic dehydrogenase. The use of tris buffer containing a low concentration of Dodecyl sodium sulfate for cytochrome c and of glycerol for malic dehydrogenase maintains their solubility and enhances their participation in antibody-antigen immunoprecipitation possibly by unravelling the peptide chains and exposing reactive antigenic determinants hidden within the interstices of the cytochrome c and malic dehydrogenase molecules.

Animals↗

Inhibition of ADP-induced platelet aggregation by dipyrone in patients with acute myocardial infarction.

ADP induced platelet aggregation was investigated in 48 patients within three days of the first signs of acute myocardial (AMI). Thirty six of them received 1 gram of dipyrone. Twelve patients who did not receive dipyrone served as controls. Platelet aggregation was found severely inhibited in 11 patients who had received dipyrone up to 12 hours before investigation and moderately inhibited among 25 patients who were given the drug 12-24 hours prior to the investigation. All the patients with AMI who did not receive dipyrone, exhibited a state of hyperaggregability evidenced by the presence of a second phase of aggregation even with 0.5 microM ADP. The inhibitory activity of dipyrone on the second phase of platelet aggregation resembles that of other non steroidal anti-inflammatory drugs.

Acute Disease↗

Evaluation of the exercise test in patients with angiographically documented coronary artery disease.

100 male patients with at least 75% obstruction of one or more coronary arteries were subjected to submaximal exercise tests. Among the 73 subjects who had positive tests, 92% of those with one-vessel obstruction had an ST depression of 1 mm, none having more than 2 mm; by contrast, 44% of those with three-vessel disease had an ST depression of more than 2 mm and only 27% on ST depression of 1 mm. Left-ventricular end-diastolic pressure exceeded 15 mm Hg in 86% of the patients who had an ST depression of more than 2 mm but only in 33% of those with a depression of 1 mm; impaired contractility was found in 81% of the former and in 36% of the latter. 92% of those with one-vessel obstruction were able to perform work of 75 and 100 W/min while only 25% of those with three-vessel disease were able to perform the same amount of work. The peak exercise heart rate and systolic blood pressure also decreased with the increase in the number of affected vessels.

Adult↗