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Biomedical subjects

N H Mulder

Publications and source records attributed to N H Mulder.

At least 271 records · Page 15Linked to original sources
PubMed1986

Evidence for capillary leakage during chemotherapy in man.

The influence of intensive chemotherapy with high dose VP 16-213, cyclophosphamide and autologous bone marrow transplantation on transcapillary escape rate of albumin was evaluated. Transcapillary escape rate and plasma volume were measured with 131I-labelled albumin. Measurements were performed 1 day before (T0), 1 week after (T1) and 2 weeks after (T2) start of chemotherapy. Before therapy TER (n = 7, means = 7.1% h-1) was already raised in patients compared to controls (n = 5, means = 3.8% h-1, P less than 0.025). No difference was found for transcapillary escape rate on T1 (n = 9, means = 7.6% h-1) compared to T0. There was an increase of transcapillary escape rate from T0 to T2 (n = 8, means = 9.5% h-1, P less than 0.05). Plasma volume did not change during therapy. Serum albumin concentrations were reduced before chemotherapy (means = 38 g 1(-1] compared to controls (means = 44 g l(-1]. After 1 (means = 34 g 1(-1] and 2 weeks (means = 31 g 1(-1] these concentrations decreased further. The same was found for intravascular mass of albumin related to body weight. The intravascular mass of albumin/bodyweight and the transcapillary escape rate are related in the patients (r = -0.477, P less than 0.01) and the patients plus controls (r = -0.585, P less than 0.001). This means the higher the transcapillary escape rate the lower the intravascular mass of albumin. No correlation between transcapillary escape rate and presence of fever was found. It can be concluded that intensive chemotherapy leads to further increase of an already elevated transcapillary escape rate for albumin.

Adult↗
PubMed1986

Eumelanin-related indolic compounds in the urine of treated melanoma patients.

A method was developed for the quantitation of six eumelanin-related indolic compounds in urine. The procedure employs methane ionization of the hexafluoroisopropyl and/or pentafluoropropionyl derivatives of 5,6-dihydroxyindole, 5-hydroxy-6-methoxyindole, 6-hydroxy-5-methoxyindole, 5-hydroxy-6-methoxyindolyl-2-carboxylic acid, 6-hydroxy-5-methoxyindolyl-2-carboxylic acid and 5,6-dimethoxyindolyl-2-carboxylic acid together with their deuterated analogues, and selected ion-monitoring. Deuterated analogues are added as internal standards to enzymatically hydrolysed urine before diethyl ether extraction. The method was used for monitoring urinary excretion in patients with malignant melanoma treated with cytostatics. In several cases, a decrease of the excretion of the eumelanin-related substances was recorded after the therapy. The usefulness of the individual indolic compounds for such follow-up studies is discussed.

Gas Chromatography-Mass Spectrometry↗
PubMed1986

Different type of DNA damage caused by three aziridinyl substituted cyclophosphazenes in a human small cell lung carcinoma cell line.

Aziridinyl substituted cyclophosphazenes are a new group of inorganic chemical agents with in vitro and in vivo cytotoxic activity. We investigated the mode of action on DNA of three different compounds, 1,3,3,5,5-pentakis (1-aziridinyl)-1 lambda 6,2,4,6,3 lambda 5,5 lambda 5-thiatriazadiphosphorine -1-oxide (SOAz), trans-1,3-bis(1-aziridinyl)-1,3,5,5-tetrakis (methylamino)-2,4,6,1 lambda 5,3 lambda 5,5 lambda 5-triazatriphosphorine (AZP), and 1,trans-5-bis(1-azaridinyl)-gem-1,3,3'-cis-5,7,7'-hexakis (methylamino)-2,4,6,8,1 lambda 5,3 lambda 5,5 lambda 5,7 lambda 5 -tetraazatetraphosophocine (AZM), of this group in the Ehrlich ascites tumor cell line (EAT) and a human small cell carcinoma cell line. The DNA damage was evaluated by alkaline elution and ethidium bromide fluorescence assay. Each compound gave a different pattern of DNA damage. SOAz caused neither single strand breaks nor cross-links, AZP gave cross-links, and AZM gave single strand breaks and cross-links in both cell lines after drug incubation for 6 h. The range of concentrations leading to cytoxicity of AZP and AZM in the clonogenic assay coincided with the concentrations leading to DNA damage. Cell kill occurred with SOAz in the same range of concentrations, however, without detectable evidence of DNA damage. It was concluded that cyclophosphazenes are probably a heterogeneous group as far as their mode of action as cytostatic agents is concerned.

Animals↗
PubMed1986

High-dose teniposide for refractory malignancies: a phase I study.

To evaluate the dose-limiting toxicity of teniposide (VM-26), a phase I study was conducted. VM-26, a semisynthetic podophyllotoxin derivative, was administered on 3 consecutive days. The initial total dose per course was 0.3 g/m2, with dose escalation to 0.6 and 1 g/m2. The most prominent side effects observed were severe skin rash in all three patients in the highest dose group and a dose-dependent degree of leukocytopenia and thrombocytopenia. In the highest dose group the leukocyte count in all courses was less than 1 X 10(9) cells/L and in three of five courses the platelet count was less than 25 X 10(9) cells/L. Of the 13 evaluable patients, five had partial remission, one had minor response, and four had stable disease. Further study should be centered on phase II studies in selected tumor groups at a VM-26 dose of 0.6 g/m2.

Adult↗
PubMed1986

Influence of various beverages on urine acid output.

High dose methotrexate therapy requires a high alkaline urine output. In order to evaluate the effect of various beverages on the urine acid output, healthy volunteers (n = 6) took 1.5-2 liters of a test drink during a 2-h period. On the test day urine pH and urine acid excretion (titratable acid plus ammonia minus bicarbonate) were measured. Controls received water and tea as test drink. Orange juice (pH 3.64) and tube feeding (pH 6.78) both led to alkaline urine pH and significantly decreased urine acid output compared to the control group (n = 4, P less than 0.01 and n = 3, P less than 0.001, respectively). Yoghurt (pH 4.1), buttermilk (pH 4.58), and Coca-Cola (pH 2.54), on the other hand, all induced a higher acid output than the control group (n = 6) and a urine pH less than 7.0 during the whole test day (n = 6, NS; n = 6, P less than 0.02; n = 4, P less than 0.05, respectively). If high urine output with an alkaline pH is required, fruit juices or well balanced tube feeding, both with low cation and low sulfur-bound amino acid content, can accomplish this. Drinks with high inorganic acid content (such as Coca-Cola) or high sulfur-bound amino acid content such as yoghurt and buttermilk will result in acidification of the urine.

Acids↗
PubMed1985

Cisplatin: a review of clinical applications and renal toxicity.

In reviewing the literature about the clinical application of cis-diamminedichloroplatinum(II) (cisplatin) it can be concluded that the availability of cisplatin has been an important advance in cancer chemotherapy; especially in patients with disseminated testicular carcinoma and ovarian cancer cisplatin-based combinations are the first choice treatment. Our own investigations of the nature of the main form of toxicity of cisplatin, the nephrotoxicity, are mentioned and methods of its prevention are summarized.

Cisplatin↗
PubMed1985

Spermidine level as a parameter in the treatment of patients with malignant melanoma.

Before, during, and after 19 courses of chemotherapy given to patients with disseminated malignant melanoma plasma spermidine levels were determined with a radioimmunoassay. Baseline values were normal in 17 courses, a doubling of plasma levels following chemotherapy occurred in 13 courses. There was no relation between the occurrence of a tumor response and an increase in spermidine levels nor between hematological toxicity or digestive tract toxicity and spermidine levels.

Adult↗
PubMed1985

The effect of captopril on renal function in patients during the first cis-diamminedichloroplatinum II infusion.

On the assumption that hemodynamic changes in renal blood flow are the initial expression of cis-diamminedichloroplatinum (CDDP)-related nephrotoxicity, we treated patients with metastatic non-seminomatous testicular carcinoma during CDDP infusion with captopril. This angiotensin-converting enzyme inhibitor significantly attenuated the initial decrease in effective renal plasma flow and can probably be used to protect the kidneys against CDDP-induced nephrotoxicity.

Adolescent↗
PubMed1985

Changes in pulmonary function during and after bleomycin treatment in patients with testicular carcinoma.

Pulmonary function tests, including spirometry, transfer factor of the lungs for carbon monoxide (TlCO), and the two components of TlCO, the diffusing capacity of the alveolocapillary membrane (Dm) and pulmonary capillary blood volume (Vc), were carried out in a group of patients with testicular carcinoma during and after treatment with the Einhorn regimen. The lung function parameters of patients who developed bleomycin-induced pneumonitis were compared with those recorded in a group of patients who did not develop this syndrome. We suggest that bleomycin-induced damage to the pulmonary capillary vasculature can be monitored by measuring Vc and that ensuing fibrosis can be measured by recording Dm. The decrease in Dm is probably compensated for by an increase in Vc, leading to a smaller change in TlCO.

Bleomycin↗
PubMed1985

Tube feeding of cancer patients treated with chemotherapy.

As many chemotherapeutic agents affect the alimentary tract the use of hyperalimentation with tube feeding during and after chemotherapy has been limited. However, patients do tolerate tube feeding well despite chemotherapy. The feeding has to be administered as continuous drip infusion and in case of bone marrow depression sterile feeding is necessary. Enteral nutrition is more physiologic, safer, easier and less expensive than parenteral nutrition. With enteral hyperalimentation the nutritional needs can be fulfilled to a large extent. Much research will be necessary to investigate the effect of enteral (hyper)alimentation on tumor metabolism and clinical effect of chemotherapy.

Clinical Trials as Topic↗
PubMed1985

Nephrotoxicity of 1,1-diaminomethylcyclohexane sulphato platinum II (spiroplatin; TNO-6).

1,1-Diaminomethylcyclohexane sulphato platinum II (spiroplatin; TNO-6) is a new platinum-containing analog used as an antitumor agent. Renal function studies were performed in eight patients treated with this drug (30 mg/m2). During and after the first spiroplatin infusion there was a decrease in effective renal plasma flow (ERPF:P less than 0.05) and an increase in filtration fraction (P less than 0.01) without changes in glomerular filtration rate (GFR), suggesting changes in renal hemodynamics. During the same period there was an increase in relative N-acetyl-beta-D-glucosaminidase excretion (P less than 0.01), pointing to tubular cell damage. Also, an increase in relative beta 2-microglobulin excretion was established during and after spiroplatin infusion. On day 21 a decrease in GFR was found (median 7.4%), together with a decrease in ERPF (median 11.8%).

Acetylglucosaminidase↗
PubMed1985

High-dose cyclophosphamide and high-dose VP 16-213 for recurrent or refractory small cell lung cancer. A phase II study.

In nine patients with recurrent or refractory small cell lung cancer a phase II study with high-dose cyclophosphamide and high-dose VP 16-213 with autologous bone marrow transplantation was performed. The regimen used was based on a previously reported phase I study. In eight of the nine evaluable patients a response was seen (six PR and two CR). One patient died of treatment related toxicity. Infection is the most important toxicity. The response duration was short. This combination is a suitable "late intensification' regimen for patients with minimal residual disease after standard dose induction chemotherapy.

Adult↗
PubMed1985

A reduction in pulmonary capillary blood volume in patients with disseminated testicular carcinoma.

Pulmonary function tests, including the transfer factor for carbon monoxide of the lungs (T1CO) and pulmonary capillary blood volume (Vc), were measured in 43 patients with disseminated testicular carcinoma and in eight patients with disseminated malignant melanoma before the start of a bleomycin-containing cytostatic combination. Their relation to the development of bleomycin-induced pulmonary toxicity was evaluated. We found two subgroups of patients, one group with and one group without an abnormal pretreatment T1CO and Vc. In the latter group the risk of bleomycin-induced pulmonary toxicity is not increased. Reduction in bleomycin dose during treatment is not necessary. The hypothesis is formulated that tumor embolism could be the explanation for this phenomenon.

Adolescent↗