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Biomedical subjects

R Heintz

Publications and source records attributed to R Heintz.

At least 37 records · Page 2Linked to original sources
PubMed1986

Phase I/II tolerability/pharmacokinetic study with one-hour intravenous infusion of doxifluiridine (5'-dFUrd) 3 g/m2 VS 5 g/m2 QD x 5 per month.

Eighteen patients with advanced solid cancer were treated with daily 5'-dFUrd infusions given over 1 h on days 1-5 of a 4-week cycle. Nine patients received 3 g/m2 5'-dFUrd daily and another nine patients 5 g/m2. One patient on 5 g/m2 5'-dFUrd was not fully evaluable for tolerability due to early death (progressive disease) 4 weeks after the first cycle. A total of 48 cycles was given. The gastrointestinal and hematological toxicity was generally mild (grade 1-2). Central neurotoxicity (ataxia, unsteadiness, diplopia, dysarthria, sometimes confusion) was observed in 7 of 8 patients on 5 g/m2 5'-dFUrd leading to premature discontinuation of treatment in 3 patients (after 2 cycles). Only 3 of the 9 patients in the 3 g/m2 group had slight signs of cerebellopathy. Typically, the reversible neurological side effects started at the end of the 2nd week of a cycle. The serum elimination kinetics of 5'-dFUrd and its metabolites 5-FU and 5'-dFUH2 have been investigated in the serum and showed very low intra- and interindividual variations. Peak concentrations of the 5'-dFUrd at the end of the infusion approximated 500 mumol/l and 1000 mumol/l for the 3 g/m2 and 5 g/m2 group, respectively. The peak of the serum 5-FU was reached at the same time, the ratio 5-FU/5'-dFUrd being around 10%. The elimination half-life time for 5-FU was protracted by a factor of 2-3 compared with the direct injection of 5-FU. Monthly infusion of 5'-dFUrd 5 mg/m2 per day on days 1-5 lead to an unacceptable frequency and degree of neurological toxicity. Similar infusions of 5'-dFUrd 3 g/m2 per day on days 1-5 were well tolerated.

Adenocarcinoma↗
PubMed1986

Passage of 5'-dFUrd and its metabolites 5-FU and 5-FUH2 to CSF in a clinical phase 1 study.

Lumbar puncture was performed on eight patients in a clinical Phase 1 study of doxifluridine (5'-dFDrd). 5'-dFUrd, 5'FU, and 5-FUH2 were shown to cross the blood-brain barrier to CSF. The maximal concentrations of 5'-dFUrd and 5-FUH2 were about 1-3% of the maximal concentrations in plasma, and were reached within 1-4 h after the end of iv infusion of 5'-dFUrd. 5-FUH2 showed a marked increase in CSF between 3 and 4 h to about 40-60% of the maximal plasma concentration in 5 of the patients, indicating a possible further increase after 4 h. The relationship between the concentrations of 5'-dFUrd and its metabolites in the CSF, and CNS toxicity is discussed.

Adult↗
PubMed1982

Phase I clinical study with 5'-deoxy-5-fluorouridine, a new fluoropyrimidine derivative.

5'-Deoxy-5-fluorouridine (DFUR) is a new fluoropyrimidine derivative with significant antineoplastic activity in animal systems. Compared to 5-FU or other fluoropyrimidines, DFUR has a more favorable therapeutic ratio in Sarcoma 180-bearing mice. DFUR was studied in this phase I trial with a daily x 5 bolus iv injection. A second course was given greater than or equal to 3 weeks after the first day of treatment. Doses were escalated from 300 to 5000 mg/m2/day in 30 patients. Dose-limiting factors were myelosuppression and stomatitis. Hematologic toxic effects were particularly marked on granulocytes. Thrombocytopenia was less frequently encountered. Stomatitis was severe at high doses of DFUR. Eleven patients had nausea or moderate vomiting. Drug-induced myocardial injury may exist, since electrocardiogram changes were recorded in two patients. After rapid iv injection, four patients felt hot in the face and pelvis. Other side effects were minimal. With this daily x 5 schedule of administration, the maximum tolerated dose of DFUR appeared to be 5000 mg/m2/day. The dose recommended for further clinical use is 4000 mg/m2/day x 5 for patients previously untreated with chemotherapy.

Adult↗
PubMed1982

Monoclonal antibody against A1 Lewis d antigen produced by the hybridoma immunized with a pulmonary carcinoma.

A monoclonal antibody (CALed) against a human pulmonary squamous cell carcinoma line was cytotoxic to the line but did not react to an autologous B-lymphoblastoid line. Although the antibody was thought to be cancer specific, principally on the basis of this evidence, the antibody actually had the A1 Lewis d (Led) specificity. It reacted with approximately 2% of the random donor T-lymphocytes and with all six lymphocytes from donors who were A1 Led type without reacting to lymphocytes of any other type. The monoclonal antibody reactivity was also absorbed out by A1 Led red blood cells but not by red cells of other types. We conclude that the A1 Led antigen had been synthesized by the pulmonary carcinoma lines but not by the autologous lymphoblastoid line, resulting in disparity for this antigen. Since the combination A1 Led only occurs in 2% of the population, it is difficult to distinguish this type of antibody from tumor-specific antibodies.

Antibodies, Monoclonal↗
PubMed1981

5-Fluorouracil: a comparative pharmacokinetic study and preliminary results of a clinical phase I study.

Until now it was unknown, whether 5-fluorouracil (5-FU) would be absorbed sufficiently after oral application, so that therapeutical effects could be expected. For this reason a comparative pharmacokinetic study of intravenous versus oral application was performed on six patients, as well as a pilot study on 13 patients with adenocarcinomas of different origins. The results show that 5-FU is absorbed rapidly. The biological availability increases with higher dose, which would indicate a saturation of the "first pass" in the liver. The clinical study shows partial remission in seven patients, with hepatoma and tolerable signs of bone marrow depression, decrease of hemoglobin, leukocytes and platelets after oral application of 5-FU in doses of 1,000-1,250 mg on days 1, 3, 5, 8, 10, and 12. 5-FU can therefore be given successfully at an adequate dose by the oral route.

Administration, Oral↗
PubMed1981

Posttransplant serum analysis in human kidney allografts.

Monitoring of 25 first cadaver transplant recipients was carried out weekly after transplantation. A total of 441 sera were tested from these patients against B and T lymphocytes at 4 degrees C and 37 degrees C for development of cytotoxic antibodies. Thirteen of the 25 patients (52%) developed B-cold antibodies as their first antibodies and all had functioning kidneys. Five of the patients developed B-warm antibodies initially, and all 5 rejected their transplants within 24 days. Of the seven patients who did not develop antibodies, 3 rejected their kidneys within 72 days. We conclude that it is important to distinguish between two types of antibodies to B lymphocytes--those reactive in the cold and those reactive in the warm--since they have opposite effects. Of the 17 successful grafts, 13 first developed B-cold cytotoxins.

B-Lymphocytes↗
PubMed1979

Dilutions and specificity analysis of pretransplant sera.

Six serial dilutions of 51 sera from pretransplant patients were reacted against T and B lymphocytes at 5 degrees C and 37 degrees C. By the use of defined panels of T and B lymphocytes it could be shown that 10% of the 51 positive sera contained T-warm antibodies against HLA-A, -B, and -C specificities. There were 28% of the sera that had antibodies against non-HLA antigens reactive to B lymphocytes in the cold. Other sera contained mixtures of HLA and non-HLA antibodies. By dilution analysis of the sera, the mixtures could be detected and the HLA specificities identified. This ability to distinguish between HLA and non-HLA antibodies should be important in classifying pretransplant patients into high- and low-risk patients. Prior evidence that we have presented suggests that the non-HLA antibodies may be enhancing antibodies.

Antibody Specificity↗
PubMed1978

[Drug side-effects in patients treated by their general practitioner (author's transl)].

Drug side-effects were registered in 50 of 2688 patients on the day of admission to hospital. These were severe in 52%, moderate in 18% and mild in 30%. Three deaths were clearly related to drug side-effects. Side-effects of cytostatic treatment were not included. Cardiac glycosides and anticoagulants were the drugs with the highest incidence of side-effects (50%).

Ambulatory Care↗
PubMed1978

[Therapy of hypertension in general practice. Comments on the recommendations of the German Antihypertension League (author's transl)].

The morbidity and mortality due to cardiovascular complications of chronic arterial hypertension are distinctly reduced by persistent and successful antihypertensive therapy. The principal emphasis is on drug therapy. Diet and psychotherapy should be used as supportive measures. Examples of antihypertensive drugs available for general practice: saluretics, beta-receptor blockers, dihydralazine (Nepresol), alpha-methyldopa, clonidine (Catapresan), reserpine and guanethidine (Ismelin). With mild hypertension (diastolic blood pressure up to 105 mm Hq), monotherapy with a beta-receptor blocker or a saluretic is indicated first. Contrary to the medical rule never to use a combination preparation if it can possibly be avoided fixed combinations have proved valuable in hypertensive therapy and facilitate therapy for the hypertensive patient and for the doctor.

Antihypertensive Agents↗
PubMed1978

Preparative isolation of middle molecular weight fractions from the hemofiltrate of patients with chronic uremia.

Fractions in the molecular weight range of the so-called middle molecules (500--3000 daltons) were isolated on a preparative scale from hemofiltrate of patients. Hemofiltration was performed with an RP-6 dialyzer using a predilution technique. The hemofiltrate was concentrated and desalinated by reverse osmosis with membranes with a normal cut-off of 500 daltons. The retentate was freeze-dried, redissolved in volatile buffer and fractionated on Sephadex G-15 macrocolumns. The middle molecule molecular weight range in the elution profiles (detected at 206 and 280 nm simultaneously) was marked with peptides. Isolated fractions in the middle molecule molecular weight range showed strong inhibitory activity upon 3H-thymidine incorporation into rat bone-marrow cells in vitro. The described combination of hemofiltration, reverse osmosis and gel chromatography is suggested as a useful approach to the isolation of these ninhydrin-positive substances which, according to their proved heterogeneity, are to be subfractionated by further procedures.

Chromatography, Gel↗
PubMed1978

Uremic cardiomyopathy: studies on cardiac function in the guinea pig.

The effects of creatinine (5.6-22.6 mg/100 ml), guanidinosuccinic acid (8.7-35.2 mg/100 ml) and of urea (60-600 mg/100 ml) on the mechanical function and oxygen consumption in isolated guinea pig hearts have been assessed. None of the parameters measured (dp/dt max, dp/dt min and Q O2) was significantly affected by creatinine or guanidinosuccinic acid. However, urea significantly reduced mechanical activity and caused a marked increase of oxygen consumption, indicating impairment of heart function expressed as a diminution of the ratio formula (see text). Pretreatment with creatinine and guanidinosuccinic acid did not alter the effect of norepinephrine on mechanical activity and oxygen consumption when compared with the effects of norepinephrine (1 X 10(-8) g/ml and 1 X 10(-7) g/ml) given alone. In contrast, urea pretreatment lowered the norepinephrine induced increase of left ventricular pressure rise/fall and of oxygen consumption. In addition, reduction of the increase in the ratio formula (see text): after urea perfusion indicates diminution of the "economic" effect of norepinephrine.

Animals↗