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A Van Oosterom

Publications and source records attributed to A Van Oosterom.

At least 19 recordsLinked to original sources
PubMed1997

Motor unit potential contribution to surface electromyography.

The background of the bioelectric activity of muscle recorded from the surface of the skin (surface electromyography) in terms of the representation of single motor units of the underlying muscle(s) is not very well documented or understood. An insight into the composition of an electromyogram is essential for the proper interpretation of one of the most widely applied electrophysiological techniques. In the present paper, a study of the contribution of single motor unit potentials to the surface electromyogram is presented. To this end, the decline of different components of the motor unit potential with depth of the motor unit is quantified. Experimentally, the action potentials from motor units at several positions in the muscle were recorded by 30 skin surface electrodes. Simultaneous use of scanning electromyography provided information about the actual position and size of the motor unit. Observed linear log-log relationships between motor unit potential magnitudes and distance indicated the usefulness of a power function to describe the motor unit potential's dependence on recording distance. It is shown that different specific surface motor unit potential characteristics fall off differently with depth. The magnitude-distance relationship is shown to be dependent on the recording configuration (unipolar vs. bipolar recording, including the inter-electrode distance) and the chosen motor unit potential parameter (negative peak amplitude, positive peak amplitude and area).

Adult↗
PubMed1997

The motor unit potential distribution over the skin surface and its use in estimating the motor unit location.

The amplitude of a surface electromyogram is dependent on the number of active motor units, their size and the relative position of the recording electrode. It is not possible to interpret the surface electromyogram quantitatively without disentangling these different aspects. In this study the decline of different components of the motor unit potential with increasing radial distance from the motor unit is quantified. Fifty-two motor units in the biceps brachii muscle were studied using 36-channel surface electromyography combined with intramuscular scanning electromyography. Scanning electromyography was used to locate precisely the motor unit. The dependence of the surface motor unit potential magnitude on the radial distance between the motor unit and the recording electrodes can be described fairly well by an inverse power function. The steepness of this function depends on the chosen motor unit potential parameter and the interelectrode distance, but also varies between motor units. The change of the negative peak amplitude of the motor unit potential over the skin surface can be used to give a fairly accurate estimate of the location of the motor unit under the skin surface. We found that for all practical purposes the depth of a motor unit in the biceps brachii muscle can be estimated as 20% of the distance over the skin surface where motor unit potentials can be recorded with higher amplitudes than 50% of the maximal amplitude recorded at the skin surface caused by activity of the same motor unit.

Action Potentials↗
PubMed1997

Sarcomatoid renal cell carcinoma: case report and review of the literature.

Sarcomatoid renal cell carcinoma (SRCC) is an uncommon tumor of the renal parenchyma, representing one to five percent of all primary kidney tumors. The major symptoms are the same as in the classic renal cell carcinoma: haematuria and flank pain. The tumor consists of a bimorph feature of clear cells with areas of spindle cells and giant cells, resembling a sarcoma. Immunohistochemistry and electronmicroscopy are often necessary to prove the epithelial origin of these spindle cells. Therapy is essentially surgical but in some cases there can be a benefit of chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Docetaxel: an active new drug for treatment of advanced epithelial ovarian cancer.

BACKGROUND: Because of the relative scarcity of natural paclitaxel (Taxol), which has been recently recognized as a highly cytotoxic agent for use in platinum-refractory ovarian cancer, synthetic and semisynthetic substitutes have been actively pursued. Docetaxel (Taxotere), a new semisynthetic taxoid, has been selected for clinical development because it is twice as potent as paclitaxel in promoting assembly of tubulin and in inhibiting microtubule depolymerization. Docetaxel also shows equal or greater cytotoxicity in relevant preclinical models. PURPOSE: Because docetaxel has produced consistent antitumor responses in ovarian cancer patients in phase I trials, we planned and conducted a phase II clinical trial to evaluate the drug's effectiveness and its toxic effects. METHODS: The present trial, which started in May 1992 and ended in December 1992, involved 97 patients with advanced epithelial ovarian cancer. The target study population had disease relapse or disease progression within 12 months of the last administration of a first-line or second-line platinum-based regimen with at least one bidimensionally measurable target lesion. The patients received docetaxel at a dose of 100 mg/m2 given as a 1-hour infusion every 3 weeks without premedication for minimizing potential hypersensitivity. Docetaxel-induced side effects were graded according to the National Cancer Institute's Common Toxicity Criteria. RESULTS: The overall response rate was 23.6% in 76 assessable patients versus 20% if all 90 eligible patients were included in the comparison (95% confidence interval [CI] = 11%-29%). Among 34 eligible patients whose tumor progressed on the most recent platinum treatment, the response rate was 23.5% (95% CI = 8%-39%). The median progression-free survival for all eligible patients was 3.9 months, and the median overall survival was 8.4 months. Docetaxel-associated toxicity in 90 assessable patients consisted of short-lived neutropenia in 81 (90%) patients, which was complicated by fever and hospitalization in seven (8%); hypersensitivity reactions were seen in 29 (31%) patients, with significant reactions seen in seven (8%); and neurotoxicity in 43 (48%) patients, with grade 3 or above toxicity seen in only three (3%). The treatment also produced skin reactions in 58 (64%) patients, of whom only four (4%) showed the intensity of grade 3. Eleven (12%) patients experienced pleural effusions, which were the effects of the drug considered to be of greatest concern. Peripheral edema and weight gain due to fluid retention were reported in 40 (44%) and 17 (19%) patients, respectively. CONCLUSION: Docetaxel appears to be effective in the treatment of platinum-refractory ovarian cancer patients.

Adult↗
PubMed1995

Thrombopoietic effects and toxicity of interleukin-6 in patients with ovarian cancer before and after chemotherapy: a multicentric placebo-controlled, randomized phase Ib study.

Recombinant human interleukin-6 (IL-6) has previously been shown to increase platelet counts in normal and sublethally irradiated mice, dogs, and primates. To assess its tolerance and efficacy in clinical use, we performed a randomized phase Ib study in patients with ovarian carcinoma. IL-6 was administered during an initial 7-day cycle before any chemotherapy. Beginning 7 days later, six cycles of chemotherapy containing carboplatin were administered every 3 weeks. During chemotherapy cycles 2 to 6, IL-6 was administered from day 4 through day 17 at escalating dose levels from 0.5 to 10 micrograms/kg/d. At each level, three patients received IL-6 and one patient received a placebo. During the prechemotherapy cycle of IL-6, a dose-dependent increase in platelet count was observed from day 12 to 15 and was maximal on day 15 (r = .77; P < .01). The median ploidy of bone marrow megakaryocytes shifted from 16 N to 32 N after 7 days of the initial prechemotherapy IL-6 administration. Dose-dependent increases in C-reactive protein (CRP) and fibrinogen levels were observed on day 8 (P < .0001 for both). A significant decrease in hemoglobin level occured rapidly after initiation of IL-6 therapy and was maximal on day 8 (P < .001). When given after chemotherapy, IL-6 accelerated platelet recovery after chemotherapy cycles 2 to 6. Postponements of scheduled chemotherapy due to thrombocytopenia were less frequent in patients treated with IL-6. No difference in either neutrophils or peripheral blood progenitor assays was observed during or after IL-6 treatment. Toxicity of IL-6 appeared mild and was not dose-limiting up to 10 micrograms/kg/d. Systemic symptoms such as fever, headache, and myalgia were the main side effects and were easily relieved by acetaminophen administration. No biologic toxicity was observed. The data indicate that IL-6 is a well-tolerated cytokine and capable of accelerating platelet recovery in patients receiving chemotherapy.

Acute-Phase Proteins↗
PubMed1995

Phase I and pharmacokinetic study of KW-2149 given by 24 hours continuous infusion.

KW-2149 is a new mitomycin C (MMC) analog, forming DNA-DNA and DNA-protein crosslinking 20-fold more effectively than MMC. Because of its equal or superior in vitro and in vivo activity compared to MMC, a phase I study was initiated with an intravenous bolus injection every three weeks. This study was interrupted after dose escalation from 5 mg/m2 to 100 mg/m2 because of subacute and dose dependent pulmonary toxicity. Because of the lack of other end-organ toxicity, the moderate hematological toxicity and the observed antitumor effect, a second phase I study was initiated with a 24 hour continuous infusion. The starting dose was 50 mg/m2 and further escalation depended on observed pulmonary toxicity. Four patients were entered into this study and the received in total 17 courses. Toxicity was again mainly restricted to the lungs with one patient suffering grade 2 dyspnoe and another one grade 1 dyspnoe. Three patients had a substantial change in the carbon monoxide (CO) diffusion capacity. Pharmacokinetic data from these patients showed very low plasma levels both for KW-2149, as for both known metabolites M-16 and M-18. This study demonstrates that pulmonary toxicity continues to occur with KW-2149, in spite of the assurance of low plasma levels of both the parent compound and the known metabolites. The interesting activity of this compound has stimulated further in-depth research towards mechanisms of pulmonary toxicity and means of preventing them.

Antineoplastic Agents↗
PubMed1995

P-glycoprotein: clinical significance and methods of analysis.

Multidrug resistance (MDR) is responsible for a decrease in sensitivity of tumor cells tumor cells to unrelated, naturally occurring anticancer drugs. This resistance is correlated with expression and activity of a membrane protein, P-gp 170, functioning as a drug-extruding pump. It has been well described in in vitro situations; however, the clinical detection and implications are not yet clear. Multiple detection assays have been developed based on the discovery of the MDR gene family and the corresponding protein. Southern, Northern, or Western blot analysis, S1 nuclease protection or PCR-based assays, immunohistochemical detection or functionality tests by flow cytometry have been used extensively. However, by use of these techniques on clinical material, both normal and malignant, contradictory results have emerged. The sensitivity and specificity of a certain technique are always limited by unavoidable parameters, for example, skill of the technician. Moreover, the complexity of the development of resistance against anticancer agents (external determinants), such as the diversity of tumor tissues, the simultaneous presence of other resistance mechanisms, and the low expression level, make MDR detection equivocal and can lead to contradictory results. Previous treatment influencing the MDR profile and inappropriate timing of the test make a possible correlation between MDR expression and chemotherapeutic resistance difficult to establish and can lead to discordant results. In this review, the need for proper criteria is stressed. No single detection technique provides the ideal test to detect MDR. Tandem testing could give more certainty, although small sample size limit this application. Formulation of a standard assay with better definition of a positivity is essential before clinical trials are started.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Immunoradiometric method and electrophoretic system compared for quantifying bone alkaline phosphatase in serum.

Agarose electrophoresis (Isopal, Beckman) and an immunoradiometric assay (IRMA) involving specific monoclonal antibodies (Ostase, Hybritech), two methods for the quantification of serum bone alkaline phosphatase (ALP, EC 3.1.3.1), a marker of osteoblastic activity, were compared in 293 patients: 79 with end-stage renal failure treated with hemodialysis and 214 with malignant disease. Overall correlation between the two methods was good (r = 0.92), except (a) for low values of bone ALP and (b) in some samples with high total liver ALP activity--both due to considerable cross-reactivity of the anti-bone ALP antibodies of the Ostase kit with liver ALP. This interference was not constant and was not evenly distributed across all concentrations of bone ALP. Low bone ALP determined with the IRMA (< or = 5 micrograms/L) was confirmed by electrophoresis (< or = 21 U/L), but bone ALP activity determined by electrophoresis to be low (< or = 21 U/L) was not correlated with the IRMA results. After standardizing our results by computing z-values for bone ALP, delta z (= zOstase - zIsopal) was significantly correlated with liver ALP activity (r = 0.73, P < 0.0001). We conclude that the IRMA for quantifying bone ALP is acceptable as a screening method. However, when high values for bone ALP are found with the Ostase method, confirmation by electrophoresis remains mandatory to rule out cross-reactivity with high amounts of liver ALP. For detecting low bone ALP activities, electrophoresis remains the method of choice.

Alkaline Phosphatase↗
PubMed1994

5'-Deoxy-5-fluorouridine increases daunorubicin uptake in multidrug-resistant cells and its activity is related with P-gp 170 expression.

Most anticancer agents fail to induce clear responses in the treatment of colorectal cancer. This can be explained by involvement of overexpression of the membrane glycoprotein, P-gp 170, which is associated with multidrug resistance (MDR), and/or with involvement of ras. Fluoropyrimidines are amongst the few options in the chemotherapeutic treatment of colorectal cancers. 5'-Deoxy-5-fluorouridine (dFUrd) needs intracellular activation via 5-fluorouracil into 5-fluoro-2'-deoxyuridine-5'-monophosphate and 5-fluorouridine-5'-triphosphate. In the present study, the cytotoxic activity of dFUrd in vitro and dFUrd combined with daunorubicin (DNR) was assessed with the (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium) bromide assay in cells with increased P-gp 170 expression versus controls. Surprisingly, dFUrd was most active in cells with high P-gp 170 expression, a finding which can not be explained by intracellular metabolic activity only. The results also show that dFUrd improves the DNR uptake in MDR-positive cells, and this is related with increased cytotoxicity of the anthracycline.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

Multidrug resistance in rat colon carcinoma cell lines CC531, CC531mdr+ and CC531rev.

A rat colon carcinoma cell line, CC531, was exposed to stepwise increasing concentrations of colchicine. A cell line, CC531mdr+, which grows in the presence of 0.2 microM of colchicine was obtained. A revertant cell line, CC531rev was isolated upon colchicine withdrawal. The CC531mdr+ displayed a multidrug-resistant phenotype. Marked resistance to the selecting agent colchicine, was found (RF = 37.5) as well as to vinblastine (RF = 11.3) and actinomycin D (RF = 2.6). Cross resistance to doxorubicin (RF = 8) and daunorubicin (RF = 13.3) was demonstrated. Verapamil was able to reverse drug resistance to colchicine and daunorubicin. The revertant cell line, CC531rev, showed increased sensitivity to colchicine (RF = 0.43), vinblastine (RF = 0.13), doxorubicin (RF = 0.28) and daunorubicin (RF = 0.56). Marked cross resistance to cis-platinum (RF = 6.9) was also induced in CC531mdr+ and was maintained in CC531rev. We conclude that CC531 displays an intrinsic low-level multidrug-resistant phenotype, which was amplified in the CC531mdr+ variant. This correlates with a higher level of expression of P-glycoprotein. CC531rev lacks the multidrug-resistant phenotype and can be used as the drug-sensitive counterpart of the latter two cell lines. Furthermore, it has been shown that in these cell lines cis-platinum resistance is mediated through a mechanism independent of the multidrug-resistant phenotype, since the revertant cell line CC531rev has lost the multidrug-resistant phenotype while retaining the concomitantly induced cis-platinum resistance of the multidrug-resistant variant CC531mdr+.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1991

Tumor lysis syndrome in a patient with metastatic Merkel cell carcinoma.

A first course of combination chemotherapy for large volume metastatic disease in a patient with Merkel cell carcinoma resulted in a tumor lysis syndrome. After this course a nearly complete response was documented. This case report extends further the chemosensitivity of Merkel cell carcinoma and demonstrates the need for tumor lysis syndrome prophylaxis in patients with bulky disease or fast-growing tumors.

Aged↗
PubMed1991

Finite limb dimensions and finite muscle length in a model for the generation of electromyographic signals.

A volume conductor model is presented in which the aspects of finite volume conductor dimensions and finite muscle fiber length are combined. The effects of these aspects on single muscle fiber action potentials (SFAPs) and on motor unit action potentials (MUAPs) are shown and verified with surface recorded motor unit action potentials. It is demonstrated that the influence of the fiber length being finite is enhanced significantly by the finite limb dimensions of the volume conductor model, for single fiber action potentials as well as for motor unit action potentials. The model described is found to be capable of generating surface MUAPs which show a very good resemblance with measured surface MUAPs. Recorded MUAPs illustrate clearly the effects caused by finite muscle fiber length. The effect of finite limb dimensions in simulated intramuscular MUAPs was evidently less dominant than in simulated surface MUAPs.

Action Potentials↗
PubMed1991

EORTC joint ventures in quality control: treatment-related variables and data acquisition in chemotherapy trials.

In multicentre studies, non-compliance with the protocol may limit the chances of reaching a correct conclusion. A procedure to examine the administration of chemotherapy in multicentre EORTC protocols has been developed. General aspects are covered in a mailed questionnaire on the prescription of drugs with rounding up or down of dosages, local facilities for preparation and the procedure for preparation and administration. More detail is collected during a quality control site visit. Ten centres have been visited and there was significant variation between centres in the organisation of chemotherapy administration. However, more striking differences were noted between the type and quality of hospital files. The lack of systematic recording of sequence, timing and doses of chemotherapy and, in particular, treatment related toxicity, is a major difficulty limiting the effectiveness of quality control. These shortcomings emphasise the need for standardisation of some aspects of case records and a suggested check-list has been drafted.

Antineoplastic Agents↗
PubMed1991

Disseminated lung cancer or extragonadal germ cell tumour?

Two patients are reported in whom an initial diagnosis of disseminated non small cell bronchogenic carcinoma was subsequently changed into a final diagnosis of extragonadal germ cell tumour. The clinical importance of the differential diagnosis between these two malignancies is highlighted and the management of extragonadal germ cell tumours is discussed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

The equivalent source description representing the extinction of an action potential at a muscle fiber ending.

Extracellular potential waveforms resulting from the termination of the propagation of the transmembrane potential at the end of an active muscle fiber are studied. The transmembrane potential along the muscle fiber is calculated from Hodgkin-Huxley-like equations with axially varying parameters under the condition of increasing axial resistance, decreasing ionic conductances, or decreasing radius at the muscle fiber end. The extracellular potential distribution is calculated using the derived transmembrane current as a line source in an unbounded volume conductor. Potential waveforms with constant latency at extracellular points far from the fiber end are presented and are compared with measurements and simulations from literature. Monophasic waveforms with constant latency are found. The polarity and the amplitude as a function of axial and radial position relative to the fiber end indicate that an equivalent dipole source adequately represents the propagation stop at the fiber end. An expression for the dipole moment in terms of fiber radius, intracellular conductivity, and transmembrane potential is derived.

Action Potentials↗
PubMed1990

On the relation between axial resistance and conductivity in linear cable models.

In the classical core conductor model the intra- and extracellular media of an infinitely long nerve or muscle fiber in a volume conductor are represented by parallel axial resistances. Thus, volume conductor properties are neglected. In this paper a study is presented that relates the conductivity of the intra- or extracellular medium of the fiber to the axial resistance used in the core conductor model. Expressions for the axial resistances that are dependent on the spatial frequency of the membrane current source density are derived from a volume conductor approach.

Electric Conductivity↗