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Biomedical subjects

R van Doorn

Publications and source records attributed to R van Doorn.

At least 19 recordsLinked to original sources
PubMed2001

CD8+ T cells in cutaneous T-cell lymphoma: expression of cytotoxic proteins, Fas Ligand, and killing inhibitory receptors and their relationship with clinical behavior.

PURPOSE: We investigated the number, phenotype, and prognostic significance of CD8+ T cells in patients with mycosis fungoides (MF) and CD30- primary cutaneous large T-cell lymphoma (PCLTCL). PATIENTS AND METHODS: Immunohistochemical stainings for CD8, granzyme B (GrB), T cell-restricted intracellular antigen (TIA-1), Fas ligand (FasL), and killer-cell inhibitory receptors (KIRs; CD95, CD158a, and CD158b) were performed on 83 first-diagnostic biopsy samples obtained from patients with plaque-stage MF (n = 42), tumor-stage MF (n = 20), and CD30- PCLTCL (n = 21). RESULTS: Serial sections and double-staining experiments showed that the large majority of CD8+ T cells in MF and CD30- PCLTCL expressed TIA-1 and FasL, whereas only a minority expressed GrB, which suggested that these CD8+ T cells were partly activated cytotoxic T lymphocytes (CTLs). These CD8+ CTLs never or rarely expressed KIRs. This phenotype was a constant feature of CD8+ CTLs and did not alter with disease progression. In contrast, the median percentage of CD8+ CTLs in plaque-stage MF (22%), tumor-stage MF (7%), and CD30- PCLTCL (3%) differed significantly (P < .0001) and was associated with a significant decrease in 5-year survival. Also within the group of tumor-stage MF, a significant relation between CD8+ CTLs and survival was found. Multivariate analysis in the total group of MF demonstrated that both skin stage and percentage of CD8+ CTLs were independent parameters of survival. CONCLUSION: Our results demonstrated that partly activated CD8+ CTLs were present in CTCL and that high proportions of these cells correlated with a better prognosis. This suggested that these CD8+ CTLs could play an important role in the antitumor response in these conditions.

Adult↗
PubMed2000

Mycosis fungoides: disease evolution and prognosis of 309 Dutch patients.

OBJECTIVES: To determine the disease course of Dutch patients with mycosis fungoides and to define factors related to disease progression and survival. DESIGN: A multicenter, 13-year, retrospective cohort analysis. SETTING: Eight dermatology departments collaborating in the Dutch Cutaneous Lymphoma Group. PATIENTS: Three hundred nine patients with mycosis fungoides registered between October 1985 and May 1997, including 89 patients with limited patches or plaques (stage Ia), 135 with generalized patches or plaques (stage Ib), 46 with skin tumors (stage Ic), 18 with enlarged but uninvolved lymph nodes (stage II), 18 with lymph node involvement (stage III), and 3 with visceral involvement (stage IV). MAIN OUTCOME MEASURES: Response to initial treatment, sustained complete remission, actuarial disease progression, and overall and disease-specific survival per clinical stage. RESULTS: The median follow-up was 62 months (range, 1-113 months). For the entire group, the actuarial overall and disease-specific survival was 80% and 89% at 5 years, and 57% and 75% at 10 years, respectively. The actuarial 5-year disease-specific survival of patients with stage Ia, Ib, and Ic disease was 100%, 96%, and 80%, respectively, and only 40% for patients with stage III disease. Using multivariate analysis, the presence of extracutaneous disease, the type and extent of skin involvement, the response to initial treatment, and the presence of follicular mucinosis were independently associated with higher disease progression and mortality rates. The calculated risks of disease progression at 5 and 10 years gradually increased from 4% to 10% for those with stage Ia disease, from 21% to 39% for those with stage Ib disease, and from 32% to 60% for those with stage Ic disease; for those with stage III disease, the risk remained at 70% at 5 and 10 years. The overall risk of disease progression at 5 and 10 years was 24% and 38%, respectively, for the total study group. CONCLUSION: At least within the first 10 years after diagnosis, disease progression and mycosis fungoides-related mortality occur in only a subset of patients generally presenting with advanced disease.

Adult↗
PubMed2000

The long gamma nail in the treatment of 329 subtrochanteric fractures with major extension into the femoral shaft.

OBJECTIVE: To study the outcome of treating extensive proximal femoral fractures with the long Gamma nail. DESIGN: Retrospective study, with a minimum follow-up of a year. SETTING: 24 hospitals throughout The Netherlands. SUBJECTS: 329 patients with primary proximal femoral fractures. MAIN OUTCOME MEASURES: Functional results and complications. RESULTS: 19 patients died in hospital and 6 were lost to follow-up. Of the remaining 304 who were fully documented, 241 (80%) became fully mobile, 59 (19%) moderately mobile, and 4 remained bedridden. 264 patients had no pain, 38 had moderate pain and used oral painkillers, and 2 had severe pain that was difficult to treat. Major technical complications occurred in 17 patients: alignment and locking gave rise to most problems, 4 patients developed deep infections, and 7 patients needed additional measures before the fracture was solid. CONCLUSIONS: The long Gamma nail in the treatment of extensive proximal femoral fractures gave good functional results with acceptable rates of complications and union problems.

Adult↗
PubMed2000

Treatment of impending and actual pathological femoral fractures with the long Gamma nail in The Netherlands.

OBJECTIVE: To compare the results of stabilising impending and actual pathological femoral fractures using the long Gamma nail with the published results of other methods. DESIGN: Retrospective study. SETTING: 20 hospitals throughout The Netherlands. PATIENTS: 101 patients with metastases in 110 femurs, which were stabilised with a long Gamma nail. MAIN OUTCOME MEASURES: Functional results and complications. RESULTS: Minimum follow-up was 1.5 years or until death, Mean survival was 12 months (range 0-82). 14 patients died in hospital; 5 had technical complications and fat embolism was suspected in 3 patients. 92% of the patients became mobile and pain was absent or acceptable in 93%. CONCLUSION: The use of the long Gamma nail produces better functional results, fewer technical complications, and an incidence of general complications no different from those reported for other methods.

Aged↗
PubMed2000

Skin equivalent: an attractive model to evaluate early melanoma metastasis.

The growth patterns and morphological phenotype of four human melanoma cell lines with different metastatic potentials were investigated in submerged and in air-exposed (skin equivalent) keratinocyte-melanoma cell co-cultures. In contrast to the submerged co-cultures, all four cell lines formed sharply demarcated tumour cell nests within the epidermal compartment of the skin equivalent model, with the morphology highly mimicking the in vivo situation. Differences among the melanoma cell lines tested were observed with respect to the number of clusters formed and the ability to exhibit invasive growth. Only the two metastatic cell lines were able to invade the dermal compartment. Screening of cellular adhesion molecules revealed that the expression patterns in different cell lines were heterogeneous and remained unchanged during the whole culture period, irrespective of whether the melanoma cells were located in the epidermal or dermal compartment. A correlation was found between expression of a lower number of different cellular adhesion molecules and the ability to acquire invasive growth capability. Our results indicate that melanoma cells exhibit a heterogeneous growth behaviour when co-cultured with human keratinocytes, and the air-exposed skin equivalent model was shown to be suitable for studying differences in growth patterns and potential invasive behaviour.

Air↗
PubMed1999

One-stage lengthening and derotational osteotomy of the femur stabilised with a gamma nail.

OBJECTIVES: To study the results of a one-stage lengthening and derotational osteotomy stabilised with a Gamma nail. DESIGN: Retrospective study. SETTING: 2 hospitals, The Netherlands. PATIENTS: 5 patients after failed osteosynthesis of femoral fractures. INTERVENTIONS: Mean lengthening of 3 cm and derotation of 30 degrees. MAIN OUTCOME MEASURES: Complications and functional results, after a mean follow-up of 43 months (range 30-57). RESULTS: Two patients required dynamisation and a cancellous bone graft to achieve union, which resulted in 1 and 1.5 cm loss of length. One patient had a temporary peroneal neurapraxy. No infections were observed. CONCLUSIONS: Our method is not an ultimate solution, but is suitable for one-stage lengthening and derotation osteotomies.

Adult↗
PubMed1996

The kinetics of HLA class I elution and the relevance for the use of HLA-eluted platelet transfusions.

HLA-eluted platelet transfusions may be feasible for transfusion in HLA-alloimmunized refractory patients, but the reduction in HLA expression after elution is variable. Using different anti-HLA antibodies directed against the HLA class I complex, the heavy chain, beta 2-microglobulin (beta 2M) and the intracytoplasmatic part of the heavy chain, we investigated factors which influenced the HLA reduction by flow cytometry. Reduction of HLA expression by acid treatment resulted in an almost complete removal of HLA class I molecules from the site of the intracytoplasmatic part of the heavy chain. Re-expression of HLA heavy chain, beta 2M and some of the trimolecular complex (comprised by beta 2M, heavy chain and peptide) occurred within 4 h. This was presumably the result of adsorption from the supernatant (eluate or plasma). After immediate removal of the eluate and incubation in plasma-free supernatant no re-expression of HLA occurred after a 4 h interval.

Absorption↗
PubMed1996

HLA class I-eluted platelets as an alternative to HLA-matched platelets.

BACKGROUND: Alloimmunized refractory thrombocytopenic patients often require HLA-matched platelet transfusions. As the HLA system is very polymorphic, sufficient HLA-matched donors are not available for every patient. STUDY DESIGN AND METHODS: In vitro elution techniques with citric acid incubation of platelets at pH 3.0 showed that platelets lose expression of HLA, whereas platelet-specific glycoproteins are preserved. This technique was modified for clinical use. Random-donor platelet concentrates were incubated with citric acid, subsequently washed, and transfused to two patients. RESULTS: Platelet-specific glycoproteins were unaffected, and HLA expression decreased generally to below 25 percent of the initial expression. One alloimmunized patient who was without compatible donors because of a rare HLA type underwent repeated transfusions with acid-treated platelets. In contrast to the results with random-donor platelet transfusions, posttransfusion increments up to 47 x 10(9) per L were obtained with acid-treated platelets, and profuse gastrointestinal bleeding was stopped, while multiple skin hemorrhages were resolved. No side effects were observed. A second patient developed a severe transfusion reaction without platelet increment after one transfusion with acid-treated platelets expressing 30 percent of the original HLA antigens. Further transfusions were not given. CONCLUSION: Standardization of the acid elution technique and validation of the technique in patients is necessary. The results suggest, however, that HLA-eluted platelets prepared under specified conditions may gain a place in platelet transfusion therapy.

Adult↗
PubMed1995

Occurrence of allogeneic HLA and non-HLA antibodies after transfusion of prestorage filtered platelets and red blood cells: a prospective study.

The incidence and consequences of HLA and non-HLA immunization were evaluated in 229 patients with aplastic thrombocytopenia. All patients were transfused with prestorage filtered red blood cells and platelets. On admission, 29 patients presented with HLA antibodies due to prior immunization by pregnancy and/or blood transfusions. Of the 200 patients showing no detectable HLA antibodies on admission, 164 could be evaluated. HLA antibodies developed in 2.7% (3 of 112) of the patients with a negative risk history of prior immunization. The occurrence of HLA antibodies in patients with a history of previous pregnancies or prior non-leukocyte-depleted blood transfusions (risk history positive) was 31% (16 of 52). Of the total of 48 patients who were or became alloimmunized, 92% (44 of 48) had a positive risk history. Ten patients with broad multispecific HLA antibodies with a panel reactivity (PRA) of greater than 70% required transfusions with HLA-matched platelets. Patients with HLA antibodies with lower PRA could be supported by random donor platelets. Two patients developed platelet-specific antibodies, causing transfusion refractoriness that necessitated selecting platelets by the absence of a platelet-specific antigen. Using prestorage leukocyte depletion of red cells and platelets with less than 5 x 10(6) residual leukocytes, 95% of the patients, including patients with a previous risk history or with HLA antibodies with low PRA, can be supported with random donor transfusions for the entire duration of their thrombocytopenic periods.

Abdominal Pain↗
PubMed1994

[Intramedullary fixation in (impending) femur fractures caused by tumor metastases].

OBJECTIVE: To determine the results and complications of intramedullary nailing of (impending) pathologic femoral fractures. DESIGN: Retrospective. SETTING: University Hospital Maastricht. TIME. Between 1979 and 1993. METHOD: We analysed the results of 29 patients treated before 1990, and 12 patients treated after 1990, with a total of 46 (impending) pathologic femoral fractures. We evaluated primary cancer, duration of illness, pain, mobility, complications and survival. RESULTS: Mobility and pain improved after intramedullary nailing. In the group operated before 1990, in whom the femoral neck had not been stabilised, a femoral neck fracture was seen in 5 cases as a result of a metachronous metastasis. Once a metastasis developed in the scar. Because of these results we decided to stabilise the whole femur, including the femoral neck, with the Russell-Taylor Reconstruction Nail, and to irradiate the whole operation field. Neither femoral neck fractures nor metastases in the scar occurred after 1990. CONCLUSION: Intramedullary nailing is a valuable technique for stabilising (impending) pathologic femoral fractures. It is important that the whole femur, including the femoral neck, be stabilised and that the entire operation field be irradiated. The Russel-Taylor Reconstruction Nail is a suitable implant for this purpose.

Adult↗
PubMed1993

Vaginal uterine amputation.

Since sexual dysfunction after hysterectomy might be prevented by leaving the portio in place, a technique was developed to perform vaginal uterine amputation. The method appeared to have been described already 40 years ago but has vanished from textbooks since then.

Amputation, Surgical↗
PubMed1992

Transfusion results of filtered and subsequently stored random platelet suspensions prepared from buffy coats.

There is almost general agreement that removal of leukocytes from blood components reduces the incidence of HLA-antibody formation and refractoriness to random platelet transfusions. Recently filters have become available, which are able to reduce leukocyte contamination in platelet suspensions with acceptable platelet loss. We evaluated a cellulose acetate (CA) and a polyester (PE) filter, and stored buffy coat-derived platelet suspensions after filtration. Both filters are effective for the removal of leukocytes to levels below 5 x 10(6) per transfusate. For the CA filter, platelet recovery was 73 +/- 13% yielding 256 +/- 53 x 10(9) platelets per transfusate from 6 donors. For the PE filter, platelet recovery was 90 +/- 9% and 327 +/- 51 x 10(9) platelets per transfusate. When a loading dose of less than 5 x 10(8) leukocytes was applied, 98% of the CA-filtered suspensions and 100% of the PE-filtered suspensions contained less than 5 x 10(6) residual leucocytes. In 123 patients transfusion results of CA-filtered platelet suspensions stored for 72 h, were compared with those obtained by non-stored, non filtered, random platelet suspensions which had been leukocyte depleted by differential centrifugation. Platelet increments 1 and 20 h after transfusion showed no statistical difference between CA-filtered platelet transfusions stored for 72 h and non-stored, non-filtered platelet transfusions. In a new cohort of 117 patients, two filters and various postfiltration storage times were compared. Using both filters, the 1-hour posttransfusion increments decreased to approximately 60% after 96 h of storage compared to results of storage periods of 72 h or less.(ABSTRACT TRUNCATED AT 250 WORDS)

Bleeding Time↗
PubMed1984

Excretion of thioethers in urine after exposure to electrophilic chemicals.

Electrophilic agents--a class of chemicals that includes most genotoxic compounds--can be inactivated by reaction with glutathione or other SH-bearing molecules. The conjugates so formed often appear in the urine as mercapturic acids or other thioether products. This paper critically reviews the suitability of the urinary thioether assay as a method for the detection of exposure to electrophilic agents or their precursors. In practice, the greatest value of the thioether assay appears to lie in its signal function. This is demonstrated for cigarette smokers and industrial workers involved in chemical waste incineration. Whenever increased thioether excretion is observed, it is likely to be due to exposure to one or more suspect compounds. However, when the thioether concentration ranges within the limits of the normal value, one must not conclude that there is no, or negligible, exposure. More specific applications of the assay of thio compounds in urine allow development of selective methods that may be useful for biological monitoring.

Animals↗
PubMed1983

Low beta-adrenergic receptor concentration on human thymocytes.

Several agents are known that can elevate cyclic AMP levels in lymphoid cells, e.g. isoproterenol, PGE1 and adenosine. We have studied the cyclic AMP increasing effect of these agents on thymocytes from mouse and man and on human peripheral T lymphocytes. In contrast to mouse thymocytes and human peripheral T lymphocytes, human thymocytes appeared to be insensitive to isoproterenol, but did respond to PGE1 and adenosine. Furthermore, the density of beta-adrenergic receptors on the cells was determined by measuring the specific binding of 3H-dihydroalprenolol. A correlation was found between the receptor density on the cells and the rise in intracellular cyclic AMP induced by isoproterenol: human thymocytes appeared to have very few beta-adrenergic receptors, in contrast to thymocytes from mouse or to T lymphocytes from human blood. We conclude that the development of beta-adrenergic receptors in T cell ontogeny is different for mice and human beings. Comparison of animal models with the situation in man should be made with caution.

Adenosine↗
PubMed1982

Excretion of TTCA in human urine after administration of disulfiram.

2-Thiothiazolidine-4-carboxylic acid (TTCA) was measured in urine of two persons given an oral dose of 250 mg disulfiram. Maximum concentrations up to 0.33 mmol TTCA/mol creatinine were found, 10 to 14 h after dosing. The total amounts of TTCA excreted in urine were 1.8 and 3.5 mumol, respectively, which correspond to 0.2 and 0.4% of the dose.

Adult↗
PubMed1981

Alcohol and sulphate intermediates in the metabolism of toluene and xylenes to mercapturic acids.

The involvement of sequential side-chain oxidation, sulphation and glutathione conjugation in the formation of mercapturic acids from toluene and xylenes was investigated. It was found that not only aralkanes but also aralkyl alcohols were excreted as mercapturic acids in the rat. The extent of mercapturic acid excretion varied over a more than 20-fold range. Inhibition of ADH caused an increase and inhibition of sulphotransferase a decrease in the urinary excretion of thio compounds after administration of toluene, benzyl alcohol, o-xylene and o-methylbenzyl alcohol to rats. The position of the methyl groups attached to the aromatic nucleus affects the metabolism of aromatic hydrocarbons considerably. Factors that are involved in the high yield of mercapturic acids after administration of o-xylene as compared to m- and p-xylene, include the relatively low apparent affinity of o-methylbenzyl alcohol for cytosolic ADH, the relatively high apparent affinity of o-methylbenzyl alcohol for cytosolic sulphotransferase, and the high electrophilic reactivity of the o-methylbenzyl sulphate.

Acetylcysteine↗
PubMed1981

Identification and determination of 2-thiothiazolidine-4-carboxylic acid in urine of workers exposed to carbon disulfide.

A compound was isolated from the urine of workers exposed to carbon disulfide during the production of rayon. The compound was identified as 2-thiothiazolidine-4-carboxylic acid (TTCA) by GC/MS and NMR. A HPLC method for the quantitative determination of TTCA was elaborated and applied to urine samples. The method allowed detection of TTCA concentrations in urine as low as 5 X 10(-7) M. No TTCA was detected in urine of workers occupationally exposed to organic solvents other than CS2. High concentrations of TTCA (upto 32 X 10(-5) M) were shown to be present in urine of spinners exposed to CS2 concentrations of approximately 100 mg/m3. It is suggested that the assay of urinary TTCA is suitable for detection of occupational exposure to CS2.

Carbon Disulfide↗