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Biomedical subjects

R Oosterom

Publications and source records attributed to R Oosterom.

At least 19 recordsLinked to original sources

Adhesion performance of UHMWPE after different surface modification techniques.

A novel design of an ultra-high molecular weight polyethylene (UHMWPE) glenoid component has been proposed, based on adhesion to PMMA bone cement. However, due to the non-polar nature of UHMWPE, surface modification techniques are needed to obtain good adhesion and thus for the design to be viable. The aim of the study is to investigate adhesion of UHMWPE after different surface treatments. Three gas-phase surface modification techniques were investigated, namely UV/Ozone, corona discharge and radio frequency glow discharge plasma, as well as abrasion. The surface treated samples were examined using water contact angle, surface energy and roughness measurements, as well as single lap-joint shear testing using polymethylmethacrylate (PMMA) bone cement and methylmethacrylate (MMA) adhesive. The effect of aging on bonded samples has also been investigated. Corona and glow discharge treatments were found to activate the surface as shown by an increase in surface energy of over 100% in an order of less than a minute, corresponding to an increase in ultimate shear stress from 0.12 to 0.40 MPa. In contrast, UV/Ozone required exposure times in the order of minutes to have an effect that was still incomparable to the other gas-phase treatments examined. Abrasion produced slightly better adhesion properties for single lap-joints bonded with PMMA compared to the corona treatment. The best treatment was found to be a combined treatment of surface roughening for 10 s, and subsequently a 90 s glow discharge treatment, resulting in failure of the UHMWPE sheet material.

Adhesiveness↗

Effect of interface conditions between ultrahigh molecular weight polyethylene and polymethyl methacrylate bone cement on the mechanical behaviour of total shoulder arthroplasty.

The aim of this study was to investigate the effect of the interface condition between polymethyl methacrylate (PMMA) bone cement and the ultrahigh molecular weight (UHMWPE) glenoid component on cement stresses and glenoid component tilting in a finite element (FE) model. The background of this research is that most FE models assume bonding between the PMMA bone cement and the UHMWPE component, although it is very doubtful that this bonding is present. An FE model of a cemented glenoid component was developed and a joint compression force and subluxation force of 725 and 350 N respectively were applied. The maximal principal stresses in the cement layer ranged between 21.30 and 32.18 MPa. Glenoid component tilting ranged between 0.943 degrees and 0.513 degrees. It was found that the interface condition has a large effect on the maximal principal stresses and glenoid component tilting. Whether adhesion between the UHMWPE component and PMMA bone cement occurs is unknown beforehand and, as a result, design validation using the FE technique should be carried out both by using contact elements in combination with a coefficient of friction as well as by a full bonding at this interface.

Adhesiveness↗

Effect of glenoid component inclination on its fixation and humeral head subluxation in total shoulder arthroplasty.

OBJECTIVE: To investigate the effect of glenoid component inclination angle on the fixation of cemented glenoid-bone structures and humeral head subluxation. BACKGROUND: Results of shoulder replacements, in terms of glenoid component fixation and joint functionality, are bad and must be improved. Repeated glenoid component tilting, a result of eccentric contact forces harms glenoid component fixation. However, the effect of glenoid component inclination is unknown. METHODS: Keeled glenoid components are cemented into bone substitutes and positioned under inclination angles varying between -4.5 degrees and +4.5 degrees . For each inclination angle 5 glenoid specimens are loaded by a horizontal, constant joint compression force (725 (SD 10) N) and a vertical, superior directed subluxation force (shear force), cyclically varying between 0 and 350 (SD 1) N. After 200,000 load cycles, the upper and lower glenoid component rim-displacements are measured during 1500 additional load cycles by custom made displacement sensors. RESULTS: The maximal superior rim-displacement significantly increased and the minimal inferior rim-displacement dramatically decreased for increasing glenoid component inclination angles up to +4.5 degrees . Maximal ratio of subluxation force over compression force significantly decreased for increasing glenoid component inclination. CONCLUSIONS: According to this study, decreasing glenoid component inclination angle decreases glenoid component tilting and humeral head subluxation and the results can be used to improve total shoulder replacements. RELEVANCE: Better understanding of the effect of glenoid component inclination on glenoid component tilting and humeral head subluxation may be useful information for the surgeon to improve results of the total shoulder arthroplasty, when replacing the glenoid surface.

Arthroplasty↗

Effect of joint conformity on glenoid component fixation in total shoulder arthroplasty.

Results of shoulder replacements are inferior and must be improved. Two of the major problems of total shoulder replacements are loosening of cemented glenoid components and wear of polyethylene inlays of uncemented, metal-backed glenoid components. The aim of this study is to investigate the influence of joint conformity on glenoid-component fixation. Keeled glenoid components, with radii of curvature of 24, 25, or 29 mm, were cemented in bone substitutes, placed in a force-controlled test set-up, articulating against a 24 mm humeral head. They were loaded by a constant joint compression force (725 +/- 10 N) and a superior subluxation force (shear force), cyclically varying between 0 and 350 +/- 1 N. After 200,000 load cycles, the upper and lower glenoid component rim-displacements were measured by custom-made displacement sensors. Additionally, the shear-out strength has been measured to investigate the residual strength. The glenoid component structures with radii of curvature of 24, 25, and 29 mm showed maximum superior rim-displacements of 0.163 (SD = 0.01), 0.299 (SD = 0.0306), and 0.350 (SD = 0.0197) mm respectively, which is a significant difference (p < 0.05). The maximum shear-out strength of glenoid components with radii of curvature of 24, 25, and 29 mm was 2707 (SD = 452), 2648 (SD = 299), and 2631 (SD = 312) N respectively, which is not a significant difference (p < 0.05). However, the results indicate that a conform articulation shows smaller glenoid rim-displacements, which might be beneficial for long-term component fixation.

Arthroplasty↗

Translational stiffness of the replaced shoulder joint.

Results after a total shoulder arthroplasty in rheumatoid patients are poor, indicated by loosening of especially the glenoid component, bad joint functionality and the possibility of a joint dislocation. The failure mechanisms behind this are multiple, including patient, surgical and design factors. These results must be improved. At present, the optimal geometrical prosthesis component design, focused on joint conformity and constraint, still has to be investigated. Proper understanding of the effect of geometrical design parameters on the theoretical relationship between joint translations and joint forces may contribute to improved designs. The main objective of this study is to theoretically describe this relationship and to investigate the joint translational stiffness, which can be used to investigate the effect of design parameters on joint motion. Joint translational stiffness is the gradient of the subluxation force with respect to the humeral head displacement. For this static analysis a potential field is introduced, as the result of a joint compressive force (muscle forces) and a subluxation force (external forces). The positive and negative stiffness during articulation inside and subluxation outside the glenoid cavity, lead to stable and unstable equilibrium joint positions, respectively. A most lateral position of the humeral head centre coincides with a zero subluxation force; at this position the humerus is dislocated and a restoring force is needed to relocate the humeral head. Joint conformity and compression force influence the joint translational stiffness during articulation inside the glenoid cavity, whereas during articulating outside the glenoid cavity this is influenced by the joint compression force and humeral radius of curvature. The glenoid radius of curvature influences the contact point and, in combination with the glenoid superior-inferior chord length, it also influences the constraintness angle, which influences the maximum allowable subluxation load to prevent a joint dislocation. This constraintness angle together with the joint conformity also influences maximum joint translations before articulation outside the glenoid cavity. Furthermore, the sign of the joint translational stiffness determines the stability of shoulder motion, which is stable and unstable if this stiffness is positive and negative, respectively.

Computer Simulation↗

Intrapleural administration of interleukin 2 in pleural mesothelioma: a phase I-II study.

Twenty-three patients with pleural mesothelioma stage I-IIA were entered in a study of continuous daily intrapleural infusion of interleukin 2 (IL-2) for 14 days, repeated every 4 weeks. IL-2 was administered according to a groupwise dose escalation schedule (group A, 3 x 10(4); group B, 3 x 10(5); group C, 3 x 10(6); group D, 6 x 10(6); group E, 18 x 10(6); and group F, 36 x 10(6) IU day-1). Each group consisted of at least three patients. Intrapleural administration of IL-2 was associated with acceptable toxicity. All patients were treated on an outpatient basis except for the patients at dose levels E and F. Dose-limiting toxicity was observed at level F, 36 x 10(6) IU daily, and consisted of catheter infection, fever and flu-like symptoms. Intrapleural IL-2 levels were high (> 20,000 IU ml-1) at levels E and F, while serum levels in most patients were not or barely detectable (< 3-30 IU ml-1). Intrapleural IL-2 levels were up to 6000-fold higher than systemic levels. Intrapleural tumour necrosis factor alpha (TNF-alpha) levels varied greatly and did not correlate with IL-2 dosage. Intrapleural mononuclear cells (MNCs) displayed IL-2-induced lymphokine-activated killer (LAK) activity in all patients. Two patients were not evaluable for response owing to catheter-related problems which precluded the delivery of IL-2. Partial response (PR) occurred in 4 of 21 evaluable patients (19%; 95% confidence interval 5-42%) with a median time to progression of 12 months (range 5-37). Stable disease (SD) occurred in seven patients with a median time to progression of 5 months (range 2-7). There were no complete responses (CRs). The median overall survival was 15.6 months (range 3.0-43). No relationship between the dose of IL-2 and response rate was observed. We conclude that IL-2 given intrapleurally is accompanied with acceptable toxicity and has anti-tumour activity against mesothelioma. In view of the refractory nature of the disease IL-2 may be a treatment option for mesothelioma. A formal phase II study is warranted. Based on the observed toxicity, the lack of dose-response relationship and the immunomodulatory effects seen at relatively low-dose IL-2, the recommended dose for a phase II study is 3 x 10(6) IU day-1 using the present treatment schedule.

Aged↗

Increases in leucocyte and platelet counts induced by the alkyl phospholipid hexadecylphosphocholine.

Hexadecylphosphocholine (HePC) is a new alkyl phospholipid that has been shown to have antitumour activity in vitro and in vivo. In vivo studies have shown absence of bone marrow toxicity at therapeutic doses. In addition, at the highest dosage group in rats, an increase in white blood cell counts (WBC) was observed. To study the presence of a similar phenomenon in man, frequent measurements of haematological parameters were performed in a series of phase II studies. 70 patients were treated with daily doses of 100-200 mg of the oral formulation of HePC. WBC and platelet counts were performed weekly. In a subgroup of 23 patients serum levels of haemopoietic growth factors were measured before and during treatment. A significant increase in WBC and platelet counts was seen in 74 and 73% of the patients, respectively. In 4 patients, bone marrow showed normal cellularity, and in 1 patient, bone marrow culture showed normal numbers and sizes of colony forming units. No abnormal levels or trends over time of cytokines were observed. We conclude that oral HePC induces an increase in WBC and platelet counts in the majority of those treated.

Administration, Oral↗

Tissue polypeptide-specific antigen: a discriminative parameter between prostate cancer and benign prostatic hypertrophy.

The serum concentration of the cell proliferation marker TPS (tissue polypeptide-specific antigen) was compared with the tumour marker PSA (prostate specific antigen). PSA was found elevated in 50% of the benign prostatic hypertrophy (BPH) patients, in 88% of the patients with active prostate cancer and in 40% of the patients who were in an inactive phase. For TPS these values were 6, 34 and 0%, respectively. The metastatic progression was biochemically mirrored by pronounced elevations of PSA and TPS. These data suggest that TPS might be a valuable adjunct in the diagnosis and follow-up of patients with prostate cancer, especially in differentiating benign from malignant deterioration of the disease.

Antigens, Neoplasm↗

Activation of the immune system of cancer patients by continuous i.v. recombinant IL-2 (rIL-2) therapy is dependent on dose and schedule of rIL-2.

The effect of dose and schedule of continuous i.v. rIL-2 infusions on leucocyte subset counts, activation status of CD56+CD3- natural killer (NK) and CD3+ T lymphocytes, and cytolytic activities of peripheral blood mononuclear cells (PBMC) was studied. A single 4-day course of rIL-2 in escalating doses (0.9-11.5 x 10(6) U/m2 per day) was given to 18 patients with various types of metastatic cancer. The serum IL-2 concentration during rIL-2 therapy ranged between 23 and 64 U/ml and was proportional to the administered rIL-2 dose, as was the rebound lymphocytosis following therapy. Before therapy, the CD56+CD3- NK cells expressed low levels of the p75 chain of the IL-2 receptor (IL-2R) and virtually no IL-2R(p55). Most CD3+ T cells were IL-2R(p55-,p75-). Between 2 and 4 days following therapy, i.e. at the time of lymphocytosis, the percentage of CD56+,CD3- NK cells among the lymphocytes had increased proportional to the administered rIL-2 dose. The levels of IL-2R(p75) expression by the CD56+,CD3- NK cells had increased. The percentages of CD3+ T cells expressing IL-2R(p55), HLA-DR and CD45RO had increased proportional to the administered rIL-2 dose. The level of lymphokine- activated killer (LAK) activity against Daudi cells was also positively correlated with rIL-2 dose. Subsequently, seven patients received 4-weekly cycles of rIL-2 (2.9-4.4 x 10(6) U/m2 per day) during 4 consecutive weeks. This schedule led to marked increments in lymphocyte and eosinophil counts, and to increased cytolytic activities compared with pretreatment. We conclude that CD56+,CD3- NK and CD3+ T cells are activated differentially by continuous i.v. rIL-2 proportional to dose and duration of treatment.

Cytotoxicity, Immunologic↗

A phase II study of epidoxorubicin in colorectal cancer and the use of cyclosporin-A in an attempt to reverse multidrug resistance.

We determined the ability of the multidrug resistance (MDR) reversal agent cyclosporin-A to increase anthracycline drug accumulation in colorectal tumour cells in vitro, using the technique of on-line flow cytometry. Data of four previously untreated patients showed that cyclosporin-A can increase intracellular net-uptake of daunorubicin. A phase II study was initiated in 24 colorectal cancer patients. They received cyclosporin-A at a dose of 3 mg kg-1 over 1 h as i.v. infusion, at 7 h and at 1 h preceding cytotoxic drug administration. At the end of the second cyclosporin-A administration epidoxorubicin 90 mg m-2 was administered as i.v. bolus. Cycles were repeated every 3 weeks. Median cyclosporin-A peak blood levels and levels at 18 h after cytotoxic drug administration appeared to be 6248 ng ml-1 and 1012 ng ml-1 respectively. Only one partial response was observed, despite these high cyclosporin-A levels. Cyclosporin-A did not cause major toxicity, only a 29% incidence of hot flushes was observed. Epidoxorubicin toxicities were as expected but the frequency of severe leucocytopenia was striking. This treatment schedule can not be considered active in colorectal cancer.

Adult↗

Prognostic value of serum thymidine kinase, tissue polypeptide antigen and neuron specific enolase in patients with small cell lung cancer.

In a group of seventy patients with small cell lung cancer the prognostic value of serum tumour markers was determined. Thymidine kinase (TK), tissue polypeptide antigen (TPA) and lactate dehydrogenase (LDH) but not neuron specific enolase (NSE) correlated significantly with survival. Since all markers were strongly interrelated with each other and with the extent of disease, the combined determination of TK, TPA and LDH or the combination of disease extent and a marker yielded no more prognostic information than a single measurement of one of these variables.

Adult↗

Evaluation of prostate-specific antigen and prostatic acid phosphatase in untreated prostatic carcinoma and benign prostatic hyperplasia.

Prostate specific acid phosphatase (PAP) (Abbott, solid-phase enzyme immunoassay) and prostate specific antigen (PSA) (Hybritech, immunoradiometric assay) were determined in 162 newly diagnosed prostatic carcinoma patients, 187 patients with benign prostatic hyperplasia (BPH) and 127 controls. The upper limit of normal in controls for PAP was 2.2 micrograms/l and for PSA 5.0 micrograms/l. In the BPH group PAP was raised in 21%, for PSA in 41%. When the cut-off level of PSA was raised to 10.0 micrograms/l, 20% of BPH patients had an increased level. PSA was superior to PAP for the detection of prostatic cancer in all stages. Of the 162 patients with prostatic carcinoma, 88 had localised diseases and 74 had metastatic spread. PSA and PAP levels increased with each advancing clinical stage. PAP was elevated in 35% of the patients with cancer confined to the prostate. PSA in 69%. (PSA level 10.0 micrograms/l: 57%). In those patients with metastatic spread PAP was elevated in 77% compared with 96% for PSA. (PSA level 10.0 micrograms/l: 92%). The combined use of PSA and PAP does not give a greater accuracy in the screening of prostate cancer when compared with the sole use of PSA. PAP was elevated in only 4 patients when PSA was normal. In the BPH group there was no proven effect of micturition, frequency or residual urine on the SPA level. However, in this group infection may cause a rise in the PSA level.

Acid Phosphatase↗

[A comparison between prostate-acid-phosphatase and prostate-specific antigen in the diagnosis of prostatic carcinoma].

A comparison is made of prostatic acid phosphatase (PAP) and prostate specific antigen (PSA) in the diagnosis of prostatic carcinoma. In a retrospective study PAP ans PSA were compared in 127 normal elderly men, in 187 patients with benign prostatic hyperplasia (BPH) and in 162 patients with untreated prostatic carcinoma. In the control group a normal value of 2.2 micrograms/l was found for PAP and 5.0 micrograms/l for PSA. In 41% of BPH patients the PSA level was higher than 5.0 micrograms/l. Because of this substantial percentage a cut-off value of 10 micrograms/l was used instead of 5.0 micrograms/l. In the BPH group 20% had a PSA level over 10 micrograms/l and 21% a PAP over 2.2 micrograms/l. Of the carcinoma patients without metastasis 57% had a PSA level over 10 micrograms/l and of those with metastatic disease, 92%. For PAP these percentages were 35 and 77, respectively. It is concluded that PSA is a more sensitive tumour marker than PAP.

Acid Phosphatase↗

Choriocarcinoma with lung metastases during pregnancy with successful delivery and outcome after chemotherapy.

A patient with an intrauterine pregnancy of 27 weeks had a coexisting pulmonary metastatic choriocarcinoma. On the chest radiograph the lung metastases appeared as pulmonary infiltrates, simulating atypical pneumonia. Serum human chorionic gonadotrophin levels were normal for gestational age. Treatment with methotrexate was successful. This is the first reported case of choriocarcinoma in a woman with a pregnancy of less than 35 weeks in which both mother and child survived. The case emphasises the need to consider choriocarcinoma in any pregnant woman who presents with haemoptysis and pulmonary nodules or infiltrates.

Adult↗

Hemopoietin-1 activity of interleukin-1 (IL-1) on acute myeloid leukemia colony-forming cells (AML-CFU) in vitro: IL-1 induces production of tumor necrosis factor-alpha which synergizes with IL-3 or granulocyte-macrophage colony-stimulating factor.

Interleukin-1 (IL-1) has hemopoietin-1 (H-1) activity, i.e., it synergizes with macrophage-colony stimulating factor (M-CSF), granulocyte-macrophage-CSF (GM-CSF) and interleukin-3 (IL-3) in stimulating in vitro colony formation of hematopoietic progenitor cells. In this study the synergistic activity of IL-1 was investigated on IL-3 and GM-CSF induced growth of acute myeloid leukemia colony forming cells (AML-CFU) in vitro. Among 12 cases of human AML, IL-1 significantly elevated IL-3 stimulated colony numbers in eight instances and enhanced GM-CSF induced colony growth in five cases. As IL-1 is an inducer of cytokine production and since tumor necrosis factor (TNF) elevates IL-3 or GM-CSF induced proliferation of AML-CFU, we examined whether IL-1 enhanced AML-CFU growth via the induction of TNF production. Neutralizing anti-TNF-alpha antibodies significantly decreased IL-1/IL-3 or IL-1/GM-CSF stimulated colony numbers in six of seven cases studied, whereas anti-TNF-beta had no effect, indicating that endogenously produced TNF-alpha costimulated the growth of AML-CFU. Furthermore, AML blast cells stimulated by IL-1 released increased amounts of TNF-alpha (between 25 and 533 pg/ml; median 255 pg/ml) into the culture medium (TNF-alpha specific radioimmunoassay) as compared with noninduced AML cells (less than 1 to 149 pg TNF-alpha/ml; median 31 pg/ml). Thus, the effect of IL-1 on AML-CFU proliferation is not the result of direct activation of AML progenitors, but IL-1 stimulates the release of TNF-alpha by AML cells and endogenous TNF subsequently synergizes with IL-3 or GM-CSF.

Antibodies↗