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Biomedical subjects

N H Mulder

Publications and source records attributed to N H Mulder.

At least 307 records · Page 17Linked to original sources
PubMed1984

The influence of L-asparaginase therapy on the fibrinolytic system.

Fibrinolytic factors were assessed during L-asparaginase administration, to study whether their changes may predispose to a haemorrhagic or thrombotic diathesis. The total level of alpha 2-antiplasmin declined, as well as the ratio of the plasminogen-binding form of alpha 2-antiplasmin to the non-plasminogen-binding form. After cessation of L-asparaginase administration, the ratio increased to 1.6 times that of the pretreatment value. These data indicate that the plasminogen-binding form of alpha 2-antiplasmin is the form primarily synthesized in vivo. L-Asparaginase therapy reduced plasma levels of plasminogen and histidine-rich glycoprotein ( HRG ) and influenced the equilibrium between HRG , plasminogen and HRG -plasminogen complex, with a more pronounced decrease of plasminogen (62% +/- 8) and HRG (76% +/- 11) in comparison to the free-plasminogen levels (51% +/- 6). alpha 2-Macroglobulin was only slightly influenced by L-asparaginase and may consequently play a more pronounced role in inhibition. This is suggested by moderate declines in functional tests of plasmin, urokinase and tissue activator inhibition by patients plasma, and by the ratio of inhibition of these enzymes over alpha 2-antiplasmin. Thus the bleeding tendency described during L-asparaginase therapy can be ascribed not only to a temporary deficiency of coagulation factors but also to temporary alpha 2-antiplasmin deficiency.

Adolescent↗
PubMed1984

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

Etoposide is active against a number of solid tumors when used in a standard dose. The toxicity at a standard dose level is mild myelosuppression without extramedullary toxicity. Recent studies in man support the dose-response relationship of etoposide. In a group of 22 patients with progressive disseminated malignancies, the dose of etoposide was escalated to define dose-limiting extramedullary toxicity, which was oropharyngeal mucositis at a dose level of 3.5 g/m2. Bone marrow toxicity was completely reversible. No cumulative toxicity was seen. Partial responses were seen in nine patients. In two of three patients with CNS metastases, improvement was seen. Etoposide is a suitable drug for high-dose chemotherapy.

Adult↗
PubMed1983

Five years' experience in access surgery for polychemotherapy. An analysis of results in 100 consecutive patients.

In 100 consecutive patients with various malignancies, 142 operations were performed to establish an arteriovenous fistula giving vascular access for chemotherapy. The fistula of choice was always an end-to-side fistula between the cephalic vein and the radial artery (radiocephalic fistula). A fistula of this type was established in 88 operations on 76 patients and functioned well in 64% of this group. In 29 patients in whom this fistula failed or was not feasible, an elbow fistula was performed in 32 operations and functioning well in 59%. In 13 patients whose arms offered no alternative possibility, 15 long saphenous vein (LSV) autografts were implanted in the inguinal region. A radiocephalic fistula was successfully performed in 77% of the patients who had received preoperative chemotherapy during less than 4 weeks, versus 26% of those who had received preoperative chemotherapy during a longer period. The radiocephalic fistula is the fistula of choice to gain vascular access for chemotherapy. It has proved necessary to perform this operation before chemotherapy is started. When this type of fistula is not feasible, alternatives are an elbow fistula or an (LSV) autograft in the inguinal region.

Adolescent↗
PubMed1983

Some effects of combination chemotherapy with cis-platinum on renal function in patients with nonseminomatous testicular carcinoma.

Renal function in 24 patients with disseminated nonseminomatous testicular carcinoma treated with combination chemotherapy including cis-platinum was examined prospectively. Renal function was monitored by several determinations of glomerular filtration rate (GFR), effective renal plasma flow (ERPF) and serum creatinine, and beta-2-microglobulin. A reduction in GFR and ERPF was found at the end of the induction chemotherapy and at six weeks thereafter. Median GFR and ERPF decreased both 23% (P less than 0.01). Serum creatinine and beta-2-microglobulin concentrations however did not rise. It is suggested that under the influence of chemotherapy with platinum the production of creatinine and beta-2-microglobulin is decreased rendering their serum levels unsuitable as parameters of renal function.

Adult↗
PubMed1983

Clinical pharmacokinetics of (NPAz2)2NSOAz: 'SOAz'.

Pharmacokinetic studies of 1,3,3,5,5 pentakis (aziridino)-1 lambda 6,2,4,6,3 lambda 5,5 lambda 5 thiatriazadiphosphorine-1-oxide ('SOAz'), a new antineoplastic agent containing an inorganic ring system and five aziridino groups, were performed in six patients who took part in a phase I clinical trial of the agent. The drug was administered as a rapid IV infusion. Serum decay curves could be fitted to an open two-compartment model of drug disappearance. After a short initial phase with a t 1/2 (+/- SD) of 7.8 +/- 4.2 min a terminal phase with a dose-independent half-life of 203 +/- 17 min occurred. The coefficient of apparent distribution was 0.71 +/- 0.13. The renal clearance was 75 +/- 11 ml/min and the total body clearance 162 +/- 23 ml/min. A percentage of 46.5 +/- 6.6 of the administered drug could be recovered unchanged in the urine within 24 h. It is concluded that in view of concentrations known to be effective in vitro, administration in large single doses may be advantageous. Dose adjustments should be made for patients with impaired renal function.

Adult↗
PubMed1983

Phase I clinical trial of (NPAz2)2NSOAz: 'SOAz'.

(NPAz2)2NSOAz ('SOAz') is the first of a new class of cytotoxic agents containing an inorganic heterocyclic ring system to enter clinical trial. It was used to treat 31 patients with advanced cancer by IV infusion over 30 min on days 1, 2, 3, and 4 of a 21-day cycle, which was postponed if necessary to allow for hematological recovery. A total of 46 courses evaluable for toxicity was given and the tumor response was evaluable in 21 patients. Seven dose levels, ranging from 25 mg/m2 to 300 mg/m2, were studied, with three to six patients at each level. The only major toxicity was myelosuppression, especially thrombocytopenia, which was dose-limiting. Platelets decreased from the 14th day onward, with a nadir 4-5 weeks after administration. Leukopenia was less predictable and reached a nadir 3-5 weeks after administration. In most patients recovery was complete after 6-9 weeks. Myelosuppression was clearly cumulative in succeeding courses and proved irreversible in three patients. Anemia also occurred, but otherwise SOAz was remarkably well tolerated. There were no responses and no therapy-related deaths. The highest tolerated dose for patients who had received no or only minor chemotherapy prior to treatment with SOAz was 300 mg/m2, and that for heavily pretreated patients, 175 mg/m2. Because of cumulative myelotoxicity phase II studies with SOAz are not recommended.

Adult↗
PubMed1983

Autologous cryopreserved platelets and prophylaxis of bleeding in autologous bone marrow transplantation.

Autologous platelets were harvested and cryopreserved in eight consecutive patients elected for ablative chemotherapy and autologous bone marrow transplantation (ABMT) for solid malignancy. There was a 19% loss in platelet count after the freeze thaw and wash procedure; with an in vitro functional loss of 40-60%. No correlation could be found for individual platelet transfusions between in vitro functional tests and in vivo recovery. Six consecutive patients received a total of 16 autologous platelet transfusions in the aplastic phase of ABMT. No bleeding was observed during the study period and there was no CMV infection in the recipients. While improvement in freezing and subsequent handling is desirable, autologous cryopreserved platelets can safely be used for the prophylaxis of bleeding during aplasia in patients treated with ABMT.

Adolescent↗
PubMed1983

The significance of the aminoterminal propeptide of type III procollagen in paroxysmal nocturnal haemoglobinuria and myelofibrosis.

The level of the aminoterminal propeptide Col 1-3 of type III procollagen (PC-III) was determined in patients with paroxysmal nocturnal haemoglobinuria (PNH) and primary myelofibrosis (PMF), to study whether PC-III can be used as a parameter for the rate and/or degree of bone marrow replacement with collagen. Normal PC-III levels were found in PNH (6.6 +/- 1.1 micrograms/l; N: 8.6 +/- 1.8 micrograms/l), while significantly increased levels were found in PMF (24.8 +/- 2.2 micrograms/l). During a follow-up of 1 year, a slight increase of 2 micrograms/l occurred in three patients with a stable fibrosis, while one patient with more active disease demonstrated an increase of 25 micrograms/l. Treatment with acetylsalicylic acid led to a decline of PC-III as well as beta-thromboglobulin level, although normalization did not occur. It was demonstrated by means of gel filtration that the antigens related to the PC-III peptide were heterogenous, and that in PMF at least two main peaks were present, with molecular masses equal to and smaller than PC-III peptide. These data demonstrate that the radioimmunoassay cannot be used for the quantitative determination of PC-III; nevertheless it gives some insight in the process of bone marrow fibrosis.

Aged↗
PubMed1983

Lymphocyte characteristics and function in paroxysmal nocturnal haemoglobinuria.

In six patients with paroxysmal nocturnal haemoglobinuria (PNH) lymphocyte studies were performed to investigate whether the observed immunological dysfunction could be ascribed to a defect in lymphocytes as result of the PNH characteristics, or to an imbalance between T-cell subsets. The PNH characteristics were studied by means of the effect of serum and acidified serum on Indium111-oxine labelled lymphocytes. No increase in release of Indium111-oxine was found when lymphocytes were exposed to acidified sera. Thus a complement mediated lymphocyte lysis in PNH could not be demonstrated. T-cells were defined by monoclonal antibodies, directed at total T-cells (OKT3), helper T cells (OKT4) and suppressor/cytotoxic T-cells (OKT8). In two of the six patients a decreased proportion of OKT3 cells was found, while a significantly depressed ratio of OKT4/OKT8 cells was present in the whole group. No obvious correlation was found between a functional assay - the concanavalin-A suppressor cell activity - and the ratio of OKT4/OKT8 positive cells. It is concluded that the PNH characteristics could not be demonstrated in the lymphocytes; and that the immunological dysregulation in PNH may be ascribed to an imbalance of T-cell subsets, while a decreased number of monocytes, defined by the monoclonal antibody OKM1, may contribute to this defect.

Antibodies, Monoclonal↗
PubMed1983

The effect of continuous enteral tube feeding on various nutritional parameters in patients with disseminated malignant melanoma during intensive chemotherapy.

In a prospective study the effect of continuous enteral tube feeding was evaluated on various nutritional parameters in patients with disseminated malignant melanoma during 13 chemotherapy courses employing bleomycin, DTIC, vindesine and actinomycin D. The patients received a quantity of calories according to their pretreatment intake, but complete metabolic equilibrium could not be obtained during chemotherapy. Although the weight/height index remained unchanged, a decrease of serum albumin and prealbumin level occurred during all 13 treatment courses. Transferrin level decreased during 11 of these courses and cholinesterase level during 12. Triceps skinfold thickness and arm muscle circumference diminished equally. Serum prealbumin was the first nutritional parameter to fall during chemotherapy and seems to be a very sensitive indicator of the occurrence of nutritional imbalance. The plasma vitamin C level was low before treatment while during treatment both vitamin C and vitamin A level fell quickly even though the nutritional intake of these vitamins was adequate. We conclude that continuous enteral tube feeding, which is a feasible method of feeding, can to some extent fulfill the nutritional needs of patients treated with intensive chemotherapy.

Journal Article↗
PubMed1983

In vitro effects of lithium on granulocyte colony formation in normal men, in hematological disorders and in small-cell carcinoma of the lung.

In a two-layer soft agar system the indirect effect of lithium via colony stimulating factor and/or its direct effect on the granulocyte progenitor cells of bone marrow of healthy volunteers, patients with different hematological disorders, and with small-cell carcinoma of the lung, were evaluated. A significant increase in the number of myeloid colonies was found with a concentration of 0.1 mmol/l lithium carbonate in the feeder layer in all patient groups except those with overt acute myelomonocytic leukemia (AMMoL). No effect was seen if lithium was added to the overlayer. The increment of colonies cultured with lithium in the feeder layer was directly related to the initial number of colonies cultured without lithium (correlation coefficient 0.96). The former colonies had a 1.5- to 2-times larger size than the latter, and cell cycle analysis showed a significant increase in the percentage of cells in S, G2 and M phase. No such effects were seen in AMMoL on the number and size of the colonies and the characteristic growth pattern. In this study lithium has an indirect effect on the number and size of bone marrow myeloid colony formation in healthy people as well as patients with different hematologic cell disorders and small-cell carcinoma of the lung, while no such influence was observed with overt AMMoL patients.

Agranulocytosis↗
PubMed1983

Effect of chemotherapy on taste sensation in patients with disseminated malignant melanoma.

The effect of combination chemotherapy (bleomycin, actinomycin D, vindesine and DTIC) on taste sensation in patients with malignant melanoma was evaluated. Five concentrations of 4 basic tastes (sweet, bitter, sour and salt) were tested. Lowest concentrations of all tastes were subjectively rated more intense after chemotherapy than before. This change was significant for sweet, sour and salt. The highest concentration of sweet was rated significantly less intense following chemotherapy. The discrimination between highest and lowest concentration was diminished for sweet, sour and bitter and marginally for salt. The changes in taste sensation following chemotherapy could attribute to anorexia in cancer patients treated with cytostatic agents.

Adult↗
PubMed1983

Influence of combination chemotherapy with cis-diamminedichloroplatinum on renal function: long-term effects.

Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were determined in 8 patients with disseminated testicular carcinoma before, during and 1 year after termination of a combination chemotherapy with cis-diamminedichloroplatinum (CDDP). The decrease in median GFR in comparison with the pretreatment value was 15.5% at the start of the maintenance therapy, 23% at the end of the maintenance therapy and 15.5% 1 year after termination of therapy. The comparable reduction in ERPF at those instants was 15.5, 19 and 23.5%, respectively. At all intervals the changes in GFR were significantly reduced in comparison with pretreatment values. No significant change in both GFR and ERPF was found either during or after discontinuation of maintenance treatment. The fall in ERPF was significant during the total period of treatment as well as during the total time of observation. Thus, no cumulative nephrotoxicity during therapy, nor improvement in renal function thereafter was found. Serum levels of creatinine and beta-2-microglobulin did not express the changes in renal function.

Adult↗
PubMed1983

Cytostatic activity of inorganic heterocycles in an in vitro screening system.

Six representatives of inorganic cyclic systems (NPAz2)2 NSOX(Az = aziridino, X = F, Az, Ph) and (NPAz2)2 NPAzR [R = Az, Morph (morpholino), Pyr (pyrrolidino)] show cytostatic activity in an in vitro screening system. The technique of the in vitro screening system used is described. L5178Y and Ehrlich ascites cells are grown as suspension cultures in concave-bottomed wells in microtiter test plates using serial dilutions of the drugs in the medium. The diameter of the cell sedimentation spots, which can be compared visually is taken to determine the lowest active dose. The results of this test correspond with the cytostatic activities observed in former in vivo experiments.

Animals↗