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Biomedical subjects

C T Smit Sibinga

Publications and source records attributed to C T Smit Sibinga.

At least 19 recordsLinked to original sources
PubMed1997

Prevalence of delta F508 cystic fibrosis carriers in The Netherlands: logistic regression on sex, age, region of residence and number of offspring.

An average cystic fibrosis (CF) carrier frequency of 1 in 25 in Europe is cited in numerous reports, although a great variability in estimated prevalences has been found in different European populations. The estimates of these frequencies were based on numbers of CF patients before identification of the gene in 1989. Here we report the results of a study to determine the carrier frequency of the delta F508 mutation in The Netherlands by analyzing mouthwashes and matched blood samples from 11654 blood donors all over the country. We analyzed possible relationships between a number of theoretically explanatory variables and the delta F508 carrier frequency by means of univariate and multivariate logistic regression. These variables were: distance of the blood banks from the northeastern part of the country (distance); whether the blood donors knew that we were looking for a CF mutation; sex and age of the donor; and number of children of the donor (family size). We detected a delta F508 carrier frequency of 1 in 42 (95% CI 1/37-1/47) in The Netherlands. If we assume that the relative frequency of the delta F508 mutation among carriers and patients is comparable in The Netherlands, this gives an estimated overall CF carrier frequency of 1 in 32 (95% CI 1/28-1/36), significantly less than 1 in 25. The univariate logistic regression analysis of the effects of the explanatory variables on the carrier frequency revealed no significant relationships, except for an increase in carrier frequency with increasing distance from the northeastern region. In the multivariate analysis with all five independent variables, distance, age and family size were significantly related to the carrier frequency, but sex and CF information were not. There was a significant interaction between age and family size. In our final model, distance, age and family size were positively related to the carrier frequency, while the interaction of age with family size showed a negative relation. These results confirm that there is a gradient in gene frequency with low frequencies in the northeastern part of the country and high frequencies in the southern part. They also suggest a relation of age and family size with carrier frequency. This relation, however, is too complex to be explained by heterozygote advantage.

Adolescent↗
PubMed1996

[The use of blood and blood products in total hip arthroplasty in 31 European hospitals, 1990/'91].

OBJECTIVE: To compare the use of blood products and artificial colloids during total hip arthroplasty in European hospitals. DESIGN: Descriptive. SETTING: Europe. METHODS: During the period October 1990-October 1991 transfusion data were obtained about patients who underwent a planned total hip replacement for the first time. The investigations were performed in 31 teaching hospitals in ten countries of the EC, as a part of the ¿Safe and good use of blood in surgery' (SANGUIS)-project. RESULTS: Red cells were ordered preoperatively in 97.4% of the 1647 cases and transfused in 81% (ranges among hospitals: 29-100). Hospitals in the Mediterranean area used more auto-transfusion than those in Central and Northern Europe. Plasma was transfused in 6% of the patients, predominantly in hospitals in southern European countries. Albumin was used especially in Central and Northern European countries. The reasons for red cell transfusion were stated in the medical records in 23% of the cases, for plasma transfusions in 7% and for albumin in 1%. Averaged transfusion-related costs were 192 ecu per patient (ranges per hospital: 60-383 ecu). CONCLUSION: Differences between European hospitals in the use of blood products for total hip arthroplasty are considerable.

Adolescent↗
PubMed1996

Validation of the determination of deltaF508 mutations of the cystic fibrosis gene in over 11 000 mouthwashes.

Mouthwashes can be used as a DNA resource for mutation detection and, because collection and DNA isolation is simple and cheap, they could in particular, be used for large numbers of samples. To determine the failure rate (the proportion of mouth samples in which no PCR product was obtained) and the specificity of buccal epithelial cell mutation detection in large numbers of samples, we collected mouthwashes and blood samples from 11 413 blood donors and tested the mouthwashes for the deltaF508 mutation, which has an estimated frequency Of 75% among cystic fibrosis chromosomes in The Netherlands. Blood samples were tested for the deltaF508 mutations only if the mutation was identified in the mouthwash or in the case of a failure to obtain PCR products. The sensitivity of the test was determined in mouthwashes of 75 deltaF508 carriers known from earlier family studies. These samples were offered blindly between the mouthwashes of the blood donors. Both specificity and sensitivity of the mouthwash procedure were 100%. The overall failure rate was 5.6%. This large figure was caused mainly by insufficient rinsing of the mouth in one particular blood bank. Exclusion of the results of this blood bank reduced the failure rate to 1.8%. Our results also confirmed that for a large number of samples the mouthwash procedure is suitable for mutation detection and, with proper instructions, can be used in community screening.

Cystic Fibrosis↗
PubMed1994

Factor VIII:C assay: influence of buffer components used in immunoaffinity chromatography for purification of factor VIII/von Willebrand factor.

A monoclonal antibody purified factor VIII concentrate containing FVIII/vWF complex has been assayed by one-stage clotting (CA) and chromogenic substrate (CSA) methods. The influences of potassium iodide (KI) and albumin in combination with predilution buffers, standards and storage of samples have been examined. These components are compared for their effect on FVIII potencies in final product and in-process controls. FVIII:C purified by immunoaffinity chromatography can not be measured reliably by CA or CSA, because of KI which interfere on the assay. Overall yield of FVIII, efficiency of IAC step and purity of FVIII can be determined by assaying the desalted samples.

Albumins↗
PubMed1994

Intensive chemotherapy with autologous bone marrow transfusion as primary treatment in women with breast cancer and more than five involved axillary lymph nodes.

Patients with breast cancer and a high number of involved axillary lymph nodes have a poor prognosis, despite adjuvant chemotherapy. The 5-year disease-free survival (DFS) in this group amounts to 30-40% and the 10-year DFS is only 15-20%. Therefore, new treatment modalities are being sought for this group of patients. The aim of the present study was the evaluation of the efficacy of high-dose chemotherapy combined with autologous bone marrow support. 24 patients with a primary breast cancer with more than five involved axillary lymph nodes received, after surgery, six courses of induction chemotherapy followed by ablative chemotherapy and reinfusion of autologous bone marrow. All patients were premenopausal or less than 2 years postmenopausal. Induction chemotherapy consisted of methotrexate (MTX) 1.5 g/m2 intravenous (i.v.) and 5-fluorouracil (5-FU) 1.5 g/m2 i.v. on day 1, prednisone 40 mg/m2 orally on days 2-14, doxorubicin 50 mg/m2 i.v. and vincristine 1 mg/m2 i.v. on day 14. Courses were repeated six times every 4 weeks. 10 patients received cyclophosphamide 7 g/m2 i.v. and etoposide 1.5 g/m2 i.v. as intensive regimen, in 14 patients this comprised mitoxantrone 50 mg/m2 i.v. and thiotepa 800 mg/m2 i.v. Reinfusion of autologous marrow followed on day 7. Finally, patients received locoregional radiotherapy for extranodal disease and tamoxifen 40 mg daily orally over a period of 2 years. The median age of patients was 42 years, range 29-54. The median number of involved nodes was 10. During induction therapy, fever requiring i.v. antibiotics occurred in 4% of 144 courses, 14% of patients suffered from mucositis WHO grade 2-3, and the other patients had mucositis grade 1. During the ablative chemotherapy, 1 patient died, 6 developed septicaemia, 5 showed mucositis grade 3-4 and the other patients had mucositis grade 1 or 2. In the follow-up, 1 patient died from acute cardiac failure. Reversible radiation-induced pneumonitis occurred in 7 out of 14 irradiated patients; symptoms started directly following radiotherapy and lasted for several weeks, but disappeared in due course. During follow-up, 2 patients with six and > 10 positive nodes, respectively, have relapsed after 18 and 36 months, both in the cyclophosphamide/etoposide regimen. Median observation is 3 years, disease-free survival at 5 years is predicted to be 84%. Intensive treatment in these patients with high numbers of involved axillary lymph nodes is a toxic regimen, but may improve the chance of surviving free of disease.

Adult↗
PubMed1992

Evaluation of elutriated single donor platelets collected and stored in a closed system.

Single donor platelets (SDPC) were collected by the elutriation technique in a closed-system integrated with large storage containers. Seven runs of SDPC were stored in a 1.5 liter polyvinyl-chloride trimellitate (PVC-TOTM) storage container, making the ratio of platelet concentrate volume to container volume 1:4.5. An equal volume of pooled multiple donor platelet concentrates (MDPC) was stored in parallel under the same conditions. All haematological data were comparable for both products, except for the degree of leukocyte contamination (5-fold increase in the pool). Under these conditions, the functional, morphological, and metabolic characteristics of elutriated platelets throughout 7-day storage were superior to those of pooled platelets. Although the platelet count was not significantly different in both types of concentrates, the mean pH of pooled MDPC fell to 6.0 on day 5 of storage. Leukocytes were shown to contribute to this pH fall. The extent of cell damage, however, as evidenced by LDH leakage (42.7 LDH units/10(11) platelets/day by differential centrifugation, compared to 5.3 units by elutriation) could not be explained solely on the basis of the leukocyte effect. This indicated that the processing method itself influences the platelet quality. By increasing the surface/volume ratio of SDPC, the initial pH of 7.1 was well maintained throughout storage, platelet metabolic rate was slowed, and the function and ultrastructure improved significantly.

Blood Donors↗
PubMed1992

Stabilization of standard platelet concentrates and minimization of the platelet storage lesion by a prostacyclin analogue.

Platelet concentrates were pretreated with a stable synthetic prostacyclin analogue (Iloprost) at two different concentrations before the second centrifugation step (pelleting step) of preparation. This resulted in loss of platelet sensitivity to aggregating agents. To mimic the situation after transfusion and to assess the reversibility of platelet inhibition, platelets were washed during and after storage and resuspended in fresh-frozen autologous plasma. The Iloprost-treated and washed platelets exhibited an increased sensitivity to the aggregating agents, compared with the control platelets (p less than 0.01). Post-storage recovery of the synergistic aggregation was more than 80% of prestorage aggregation. Beta-thromboglobulin (beta TG) release and thromboxane B2 (TXB2) formation were significantly inhibited in Iloprost-treated platelets (p less than 0.01). After the second centrifugation step, beta TG release was 0.7% +/- 0.3%, compared with 2.7% +/- 0.9% for the controls. TXB2 was 99 +/- 91 pg/ml, compared with 495 +/- 356 pg/ml for the controls. Platelet morphology and ultrastructure were well preserved during 5-day storage. In addition, Iloprost exerted a cytoprotective effect, as evidenced by the significant reduction in lactate dehydrogenase leakage. Post-storage LDH was 378 +/- 159 and 415 +/- 239 U/l respectively by the two Iloprost concentrations, compared with 1180 +/- 937 U/l for the control platelets. The inhibitory and cytoprotective effects of Iloprost were sustained throughout storage, in contrast to the effect of PGE1 (Prostin) which was limited to the early phase of storage.

Alprostadil↗
PubMed1991

Preparation and storage of "leukocyte-depleted single donor" platelet concentrate: a step forward in effective haemotherapy.

"Leukocyte-depleted" platelet concentrates (LD-SDPC) were prepared by cotton-wool and by polyester filtration of "leukocyte-poor" PC collected by the elutriation technique. The storage characteristics of LD-SDPC were comparable to those of the filtered pools of multiple donor platelet concentrates (LD-MDPC). However, LD-SDPC were less activated and less damaged than LD-MDPC over a 7-day storage period, as evidenced by beta-thromboglobin percent release and lactic dehydrogenase percent leakage in both products. LD-SDPC were prophylactically transfused to 12 thrombocytopenic patients; the mean bleeding time was shortened from 12 min 20 sec to 4 min 39 sec. Corrected count increment (CCI) was 22.8 at 1 hr and 14.1 at 24 hr compared to 15.5 and 10.0, respectively, with standard PCs.

Blood Component Transfusion↗
PubMed1991

In vitro evaluation of a high-efficiency leukocyte adherence filter.

In view of the currently available data, prevention of alloimmunization requires filters with higher efficiency to achieve a reduction in the number of leukocytes below 10 million per transfusion. Two versions (Pall PL-100 and PL-50) of the new generation leukocyte-depletion filters were studied. Single donor (SDPC)- and pooled multiple donor (MDPC) platelets were run in parallel. At a flow rate of 10 ml/min, the PL-100 filter was shown to effectively reduce the number of residual leukocytes to far below the critical immunogenic threshold of 10 million in all SDPC units and in 77% of MDPC units. Apheresis platelets appear not only to be better depleted than pooled multiple donor platelets, but also to have a better post-filtration platelet recovery (96% versus 84%). The efficiency of the smaller version of the filter (Pall-50) was higher than that of the Pall-100 filter for both single and pooled multiple donor platelet concentrates (PC). Leukocytes were absent in more than 92% of units in both types of concentrates. The maximal number of detected leukocytes was 2.2 million in a pool of 6 units. The outcome of filtration of 5-day-old pooled platelets was less favorable than filtration of 1- or 2-day-old pooled platelets, indicating that filtration soon after preparation is preferred to filtration after storage. Post-filtration platelet integrity, activation state, function, and morphology were all well preserved in both single and multiple PCs.

Blood Component Removal↗
PubMed1990

Alpha- and gamma-tocopherol in plasma, red blood cells, and platelets during plasma exchange.

The effect of a rapid reduction of plasma lipoproteins on the alpha- and gamma-tocopherol levels in plasma, erythrocytes, and platelets was studied. Sixteen successive plasma exchange procedures performed weekly in an adult with heterozygous familial hypercholesterolemia were evaluated. Plasma exchange was done by intermittent flow centrifugation, exchanging one plasma volume against a 4% human albumin solution. Plasma exchange reduced in plasma alpha-tocopherol from 41.5 +/- 8.9 to 23.6 +/- 4.8 mumol/L and gamma-tocopherol from 4.9 +/- 4.1 to 2.4 +/- 2.1 mumol/L, without changing their ratios to total lipids. It diminished alpha-tocopherol in platelets from 12.97 +/- 4.37 to 10.03 +/- 1.78 mumol/10(13) cells and gamma-tocopherol from 1.43 +/- 0.55 to 1.06 +/- 0.41 mumol/10(13) cells, but did not affect erythrocyte tocopherols. The total amount removed per procedure was 47.57 +/- 13.65 mumol for alpha-tocopherol and 4.70 +/- 3.59 mumol for gamma-tocopherol. Plasma exchange increased the number of erythrocytes from 3.67 +/- 0.10.10(12) to 4.05 +/- 0.13.10(12) cells/L, without affecting their volume. Platelet count did not change, but mean platelet volume decreased from 7.7 +/- 0.5 to 6.9 +/- 0.5 fl and platelet distribution width from 15.1 +/- 0.4 to 14.9 +/- 0.5. Thus, plasma exchange reduces plasma alpha- and gamma-tocopherol to the same extent as total lipids, and decreases these tocopherols in circulating platelets, along with a reduction in platelet size and, compared to the change in erythrocyte count, a fall of platelet number.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Platelets↗
PubMed1990

A simplified method for purification, concentration and freezing of bone marrow cells for autologous transplantation.

Autologous bone marrow (BM) transplantation is being increasingly applied in hematological and oncological patients. However, because of the need to purify and preserve BM requiring high technology, such treatments are virtually concentrated in the "developed" countries. This paper examines methods of BM purification and freezing that could make the technique potentially applicable in developing countries. Hemapheresis is routinely applied for BM purification in our Dutch Centre, where the buffy coats obtained from routine blood donations were utilised in experimental settings. Using DMSO as cryoprotectant, semi-purified white cells were frozen in liquid N2 (LN2), by mechanical freezer or snap-frozen at -55 degrees C. Different types of containers were compared including plastic tubes and ordinary blood bags. After thawing the results show that snap-freezing had a deleterious effect but the cell yields and viability were similar in LN2 or the mechanical freezer where the tubes and the bag were equally effective as containers (86% cell recovery with 90% viability). In the purification/concentration stage, reduction of the volume of the material by extra centrifugation, thus requiring less DMSO, produced better results--96% cell yield and 90% viability after thawing. This simplified method was applied in a general hospital in Sao Paulo where four oncology patients underwent BM collection. BM was purified and concentrated within a blood bank facility. Hydroxyethyl starch sedimentation and centrifugation of the material in plastic blood bags gave 80% BM cell harvest. After thawing from the mechanical freezer 1 x 10(8) BM cells/kg were available for reinfusion to patients. There was no immediate untoward reaction. Three of the patients showed signs of bone marrow regeneration by three weeks, but one patient died 16 days after transplantation, of septicemia. We conclude that certain high-technology procedures for ABMT can be adapted for existing facilities in developing countries.

Bone Marrow Transplantation↗
PubMed1989

Bleeding prophylaxis in autologous bone marrow transplantation for solid tumors. Comparison of cryopreserved autologous and fresh allogeneic single-donor platelets.

Bleeding prophylaxis with cryopreserved autologous thrombocytes was evaluated in 43 patients treated with high-dose chemotherapy and autologous bone marrow transplantation. Platelet transfusions were given prophylactically. Nineteen patients received only autologous, 10 only fresh allogeneic single-donor, and 14 both types of transfusions. The effects of 104 autologous versus 93 allogeneic thrombocyte transfusions were compared. The increment at 1 h was for allogeneic platelets twice that for autologous platelets (30.6 versus 15.2 x 10(9)/l), but the interval between transfusions in days (2.3) was the same. Twelve patients received alternating autologous platelet transfusion after washing out the cryoprotectant dimethyl sulfoxide (18 transfusions) and non-washed autologous platelets (24 transfusions). Platelet increments, corrected increments, and predicted recovery were not influenced by omitting the washing procedure, and no side effects of dimethyl sulfoxide occurred.

Adult↗