PubMed Health⌕ Search

Biomedical subjects

F J Bemelman

Publications and source records attributed to F J Bemelman.

At least 19 recordsLinked to original sources
PubMed2007

The Dutch Fabry cohort: diversity of clinical manifestations and Gb3 levels.

BACKGROUND: Fabry disease (OMIM 301500) is an X-linked lysosomal storage disorder with characteristic vascular, renal, cardiac and cerebral complications. Globotriaosylceramide (Gb(3)) accumulates in Fabry patients as a result of alpha-galactosidase A deficiency. The phenotypic variability is high, but the relationship between clinical symptoms in individual Fabry patients has not been uniformly documented. Also, the relation between the most prominent biochemical abnormalities, elevated Gb(3) levels in plasma and urine, and clinical symptoms is not firmly established. METHODS: Clinical and biochemical characteristics of 96 (25 deceased) Dutch Fabry patients were collected retrospectively and before the initiation of enzyme therapy. RESULTS: Clinical assessment revealed that median life expectancy was 57 years for male and 72 years for female patients. Cerebral complications, acroparaesthesias and gastrointestinal complications, but not cardiac and auditory complications, were all seen more frequently in male than female patients. Glomerular filtration rate (GFR) was highly variable in male patients, including 2 patients with GFR < 30 ml/min, but median GFR did not differ between males and females (103 and 101 ml/min, respectively). Hyperfiltration was more frequently observed in the female patient group. Microalbuminuria was present in 60% of males and 45% of females. No specific pattern of combined symptoms existed except for a relationship between left ventricular hypertrophy (LVH) and cerebral complications (males 36%, females 32%), or proteinuria (males 35%, females 31%). Gb(3) was found to be more elevated in plasma samples from male (n = 26; median 6.27 micromol/L (1.39-9.74)) than female Fabry patients (n = 37; median 2.16 (0.77-4.18)). This was also observed for urinary Gb(3): males (n = 22) median 1851 nmol/24 h (40-3724); females (n = 29) median 672 (86-2052). Plasma and urinary Gb(3) levels correlated with each other in both males (r = 0.4, p = 0.05) and females (r = 0.4, p = 0.03), but no correlation between elevated Gb(3) levels and clinical symptoms could be detected. CONCLUSION: Analysis of the characteristics of the Dutch Fabry cohort has revealed that a limited relationship between various disease manifestations exists and that individual symptoms do not correlate with elevated urinary or plasma Gb(3) levels, limiting their value as surrogate disease markers.

Adolescent↗
PubMed2006

[The first 100 hand-assisted laparoscopic donor nephrectomies at the Academic Medical Center in Amsterdam].

OBJECTIVE: To evaluate the results of the first 100 hand-assisted donor nephrectomies in our hospital. DESIGN: Prospective, descriptive. METHOD: In the period January 2000-July 2004, 100 consecutive donors underwent laparoscopic nephrectomy as part of a living-related kidney transplantation at the Academic Medical Center in Amsterdam, the Netherlands. The operation was performed laparoscopically using a hand port (hand-assisted nephrectomy). The incision made for the hand port was also used for the removal of the kidney. RESULTS: Mean operating time was 168 min (range: 88-285). Median warm ischaemia time was 3 min (1.0-4.5) and median blood loss was 50 ml (20-1500). None of the operations required conversion to an open procedure and there were no deaths among donors or recipients. Postoperatively, 12 complications occurred in 10 donors. Median hospital stay for the donors was 5 days. In 3 recipients, the transplanted kidney had to be removed within 14 days. 1n 3 other recipients, surgical re-intervention was necessary due to urological complications. One-year graft survival was 94%. CONCLUSION: Hand-assisted laparoscopic donor nephrectomy was a safe and minimally invasive procedure for renal transplantation in this patient series.

Adult↗
PubMed2004

Hand-assisted laparoscopic live donor nephrectomy.

BACKGROUND: Hand-assisted laparoscopic donor nephrectomy (HLDN) may have advantages over laparoscopic donor nephrectomy, such as shorter learning curve, operation and warm ischaemia times. The aim of this study was to evaluate the feasibility and safety of HLDN. METHODS: Between January 2000 and October 2002, 50 consecutive HLDN procedures were performed through a low transverse abdominal incision, 23 right sided and 27 left sided. RESULTS: The median age of the donors was 44 years. No HLDN required conversion to an open procedure. The median operating time for HLDN was 153 min. The median warm ischaemia time was 3 (range 1.0-4.5) min and the median blood loss was 50 (range 20-500) ml in both left- and right-sided procedures. Eight patients suffered ten minor complications during their admission. The duration of hospital stay was 5 days for donors. Three recipients developed graft failure owing to acute rejection, renal vein thrombosis and ischaemic necrosis. CONCLUSION: Both left- and right-sided HLDN procedures were feasible and safe through a low transverse abdominal incision.

Adult↗
PubMed2003

Renal artery clip dislodgement during hand-assisted laparoscopic living donor nephrectomy.

The main reason for conversion in laparoscopic donor nephrectomy (LDN) is peroperative bleeding. One of the advantages of hand-assisted laparoscopic donor nephrectomy (HDLN) is facilitated control in case of bleeding. This report describes two methods to avert conversion in HLDN in the case of abrupt major arterial bleeding. In the first case, during left HLDN the clips placed on the renal artery dislodged, and the surgeon managed to control the bleeding by compressing the focus of the bleeding with his finger. A balloon occlusion catheter was inserted through a groin incision in the aorta and advanced to the origo of the renal artery. Due to control of the hemorrhage, it was possible to close the renal artery stump by laparoscopic suturing, and a conversion was averted. The patient was discharged after 5 days, without signs of damage to the remaining kidney. In the second case, during right HLDN, the clips on the renal artery dislodged during stapling of the renal vein. The bleeding was controlled by finger compression and new clips were placed. The cuff of the artery was long enough to be clipped again. The patient was discharged after 5 days. Graft function was excellent in both cases. Major arterial bleeding can be controlled and managed in hand-assisted laparoscopic surgery. The use of a balloon occlusion catheter is an elegant way to avert conversion.

Adult↗
PubMed2003

Treatment of acute kidney allograft rejection with a non-mitogenic CD3 antibody.

T3/4.A is a non-mitogenic murine IgA mAb to human CD3 that was selected for clinical studies to provide an alternative for the mitogenic, T cell-activating, therapeutic mAb OKT3. Previously, we reported that T3/4.A is better tolerated in humans than the IgG2a-CD3 mAb T3/4.2a. Here we report the results of a phase II clinical trial to assess the immunosuppressive potential of T3/4.A. Eighteen first kidney transplant recipients with a first rejection episode were included. Baseline immunosuppression consisted of cyclosporin and prednisolone. Rejection treatment consisted of 5 mg mAb per day during 10 days. Fourteen patients responded, of whom four experienced a second rejection within 2 weeks, one experienced chronic rejection after 2.5 years, whereas the others remained rejection-free after treatment (median duration of follow-up 42 months). Four patients did not respond and eventually lost their graft. These results are similar to treatment results with OKT3, as reported in the literature. Following the first dose of T3/4.A, side effects were limited, and reduced compared to OKT3-treated controls. On the second day, 15 patients developed transient vomiting and/or diarrhoea, which coincided with elevated serum levels of proinflammatory cytokines. Minimal or even no side effects occurred during the remaining days, which is in sharp contrast to that seen generally during OKT3 treatment. Both T cell numbers and TCR expression were reduced during the therapy. We conclude that T3/4.A is a good alternative for OKT3 to treat rejection episodes in renal transplant recipients.

Acute Disease↗
PubMed2000

[Immunology in medical practice. XXX. Organ transplantation: indications and results].

During the past 30 years, solid organ transplantation has developed into a routine medical procedure. Currently, one-year transplant survival rates for kidney, heart, liver and pancreas are between 80 and 90%; for most organs, the long-term results are fair with 5-year survival rates of 60%. Inclusion criteria for potential recipients have become less stringent. These days, potential recipients are rarely excluded on the basis of their calendar age alone. The development of more and stronger immunosuppressive drugs has facilitated transplantation across wider immunological differences between donor and recipient with good results. While the number of patients on the waiting lists for organ transplantation increased, the number of organs offered for donation decreased. This has resulted in waiting times of several years for most organ transplantations. While the short-term outcome has improved significantly over the past decades, the long-term outcome has not. Most renal transplants, for example, are lost due to chronic rejection. The challenge for the future will be to improve the long-term outcome of organ transplantation and to decrease the morbidity associated with chronic immunosuppressive therapy.

Age Factors↗
PubMed1996

Activation and increased expression of adhesion molecules on peripheral blood lymphocytes is a mechanism for the immediate lymphocytopenia after administration of OKT3.

We investigated the mechanism by which antihuman CD3 monoclonal antibodies of the isotypes IgG2a (eg, OKT3) and IgA (eg, IXA) can induce the rapid disappearance of virtually all circulating T lymphocytes. We hypothesize that upregulation of adhesion molecules on the lymphocyte membrane contributes to this effect. However, this hypothesis is difficult to test, because of the inherent lymphocytopenia and/or shifts in lymphocyte populations between intra and extra-vascular compartments. Therefore, studies in vitro were performed, as well. Analysis of peripheral blood lymphocytes isolated at several times after addition of OKT3 or IXA to whole blood of healthy individuals showed an immediate increase in the proportion of T cells expressing NKI-L16, an activation epitope on CD11a/CD18. Likewise, an increase in CD11b/CD18 expression occurred. In parallel experiments, a transiently increased adhesion of T cells to endothelial cell monolayers was observed. This adhesion could be completely blocked by anti-CD18 or anti-CD11a monoclonal antibodies and only partly by an anti-CD11b antibody. Our data indicate that upregulation of activation epitopes of CD11a/CD18, as well as increased expression of CD11b/CD18 on T lymphocytes, may result in increased adhesion of these cells to intercellular adhesion molecule-1 (ICAM-1) and ICAM-2 on vascular endothelium. This phenomenon may, at least, partly explain the rapidly occurring peripheral lymphocytopenia observed in vivo.

Adult↗
PubMed1995

Toxicity of OKT3 increases with dosage: a controlled study in renal transplant recipients.

In the present study we prospectively compared side effects occurring in 12 patients after the first administration of low-dose OKT3 (0.5 mg twice daily) induction therapy with those in 10 patients who were treated with a conventional dose of OKT3 (5 mg daily) for acute rejection. We also investigated cytokine release and activation of complement and neutrophils as all of these are held responsible for OKT3-induced side effects. Low-dose OKT3 resulted in a significantly decreased side effects score compared to that after a conventional dose of OKT3 (1.8 vs 5.1, p = 0.0006). Following the first administration of low-dose OKT3, TNF peak levels were significantly lower than after a conventional dose of OKT3. In contrast to our data on conventional dose OKT3 treatment, the first administration of low-dose OKT3 did not induce complement activation as reflected by C3a and C4b/c levels in plasma. Finally, the increase in neutrophil degranulation products lactoferrin and elastase-varies; is directly proportional to 1-antitrypsin was much less following 0.5 mg OKT3 than following 5 mg. We conclude that OKT3-induced toxicity is dose-dependent and is mediated not only by cytokine release but also by activation of complement and neutrophils.

Dose-Response Relationship, Drug↗
PubMed1995

[Corticosteroids in dental practice].

In this article some pharmacologic aspects of corticosteroids and their main medical indications are reviewed. In addition, the use of corticosteroids in dentistry and their interference with dental treatment are discussed.

Adrenal Cortex Hormones↗
PubMed1995

[Alcoholism and dentistry].

In this article the physical and psychological consequences of alcohol abuse are considered. In addition the interaction between alcohol abuse and oral health and dentistry is discussed.

Alcohol Drinking↗
PubMed1995

Biphasic granulocytopenia after administration of the first dose of OKT3.

The effects of the administration of OKT3, a second immunoglobulin G2a (IgG2a) anti-CD3 monoclonal antibody (mAb), and its isotype switch variant IgA on granulocyte kinetics were compared for 5 hours after the first administration of the mAb. In addition, in vivo and in vitro studies were performed on alterations in expression of CD11b and CD62L induced by these mAbs. Within 15 minutes after administration OKT3 and IgG2a anti-CD3 mAbs induced a significant decrease in circulating granulocytes, whereas IgA anti-CD3 mAb did not. Apparently the initial decrease in circulating granulocytes depends on the heavy chain of the administered anti-CD3 mAb, resulting in immunocytoadherence and sequestration in the lungs. Increased adherence to pulmonary endothelium by altered expression of CD11b and CD62L plays a minor role in this first granulocytopenia, because each mAb exerted the same effects on these adhesion molecules in vitro. The second decrease in granulocyte counts occurred 60 minutes after administration of each mAb and correlated with a significant increase in expression of CD11b and CD62L in vivo and with upregulation of CD11b and down-regulation of CD62L in vitro. These alterations could be related to the presence of tumor necrosis factor-alpha both in vivo and in vitro. Thus granulocyte kinetics from 30 minutes after administration of each anti-CD3 mAb resemble neutrophil kinetics induced by TNF-alpha.

Adult↗
PubMed1994

Sequestration of labelled granulocytes in the lungs following administration of OKT3 is dose-dependent.

In the present study the consequences of administration of low-dose (0.5 mg) OKT3 for respiratory side-effects and pulmonary sequestration of labelled granulocytes are compared with the known effects of 5 mg OKT3. Ten renal transplant patients were studied, of whom five were treated with 0.5 mg OKT3 and five with 5 mg OKT3. None of the patients in the 0.5 mg group and two of the patients in the 5 mg group experienced dyspnoea. Sequestration of labelled granulocytes in the lungs was significantly lower in the patients receiving 0.5 mg OKT3 compared with the patients receiving 5 mg OKT3. The simultaneously occurring peripheral blood granulocytopenia was significantly more severe in the 5 mg group than in the 0.5 mg group. We suppose that this sequestration of circulating granulocytes in the lungs is at least partly mediated by complement activation products. In vitro it is demonstrated that fixation of complement activation products on peripheral blood lymphocytes depends on the concentration of OKT3 present in the culture medium. We conclude that respiratory side-effects shortly following infusion of OKT3 are related to complement-induced pulmonary leucostasis, the degree of which is dependent on the administered dose of OKT3.

Acute Disease↗
PubMed1994

Pretreatment with divided doses of steroids strongly decreases side effects of OKT3.

The aim of this study was to attenuate side effects of OKT3 by variation of the time interval between administration of corticosteroids and OKT3 in renal allograft recipients. In view of a maximal lymphocytopenia at six hours following MPNS, we postulated a greater preventive action on side effects from administration of methylprednisolone (MPNS) at six hours preceding the first dose of OKT3 compared to administration immediately before. Two groups of renal transplant patients treated for acute rejection with 5 mg OKT3 were studied. Ten patients received 500 mg MPNS six hours and ten patients one hour before administration of OKT3. We measured clinical side effects, body temperature, TNF and IL-6. There were no differences between the two groups regarding clinical side effects and peak body temperatures. However, MPNS administered six hours before administration of OKT3 diminished TNF release; MPNS one hour before decreased IL-6 release. We studied an additional group of six patients receiving 250 mg MPNS six hours before, followed by 250 mg one hour before OKT3. This group experienced significantly less side effects and lower body temperature. In addition, IL-6 levels were significantly decreased. We conclude that two times 250 mg MPNS administered six hours and one hour before the first administration of OKT3 effectively attenuates adverse reactions following administration of OKT3.

Adult↗
PubMed1994

Pulsatile thyrotropin and prolactin secretion in a patient with a mixed thyrotropin- and prolactin-secreting pituitary adenoma.

The circadian and pulsatile thyrotropin (TSH) and prolactin (PRL) release was investigated in a patient with slight hyperthyroidism due to a mixed TSH- and PRL-secreting pituitary adenoma. Blood was withdrawn every 10 min for 24 h (before and after medical treatment); pulse characteristics were analyzed by Desade and Cluster programs (values as mean +/- SD). The inappropriately high mean 24-h TSH concentration of 3.55 +/- 0.31 mU/l was associated with a higher mean 24-h TSH pulse amplitude but unaltered mean 24-h TSH pulse frequency relative to healthy controls. The nocturnal TSH surge (absolute surge 0.5 mU/l, relative surge 16%) was low, related to a loss of the usual nocturnal increase of TSH pulse amplitude and TSH pulse frequency. Chronic treatment with octreotide resulted in a modest clinical and biochemical improvement of the hyperthyroid state; addition of bromocriptine at a later stage had no further beneficial effect. At the end of the follow-up period the mean 24-h TSH paradoxically had increased to 5.33 +/- 0.81 mU/l. The nocturnal TSH surge also increased (absolute surge 1.9 mU/l, relative surge 42%), but circadian changes in TSH pulsatility remained absent. In the untreated period the increased mean 24-h PRL concentration of 234 +/- 24 micrograms/l was associated with an increased mean 24-h PRL amplitude, whereas the 24-h PRL pulse frequency (N = 4) was lower relative to controls. No circadian PRL rhythm was present. After octreotide and bromocriptine treatment the mean 24-h PRL concentration and mean 24-h PRL pulse amplitude were unchanged, but a clear nocturnal increase of PRL now was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗
PubMed1994

Increase of sTNF receptor levels in acute renal allograft rejection after treatment with OKT3.

The use of OKT3 is associated with severe clinical side-effects. Adverse reactions are partly attributed to release of tumour necrosis factor (TNF). TNF binds to two receptors on the outer membranes of most human cell lines. Shedding of these proteins (sTNFR-p55 and sTNFR-p75) may block biological effects of TNF. Here we show a fair correlation between serum levels of sTNFRs and renal function as measured by glomerular filtration rate (GFR). In addition we assessed levels of sTNFR-p55 and sTNFR-p75, corrected for reduced renal clearance, in renal allograft rejection and following treatment with OKT3. Corrected serum levels (CSL) of sTNFR-p55 and sTNFR-p75 were determined in 12 renal allograft patients treated for an acute rejection episode with either OKT3 or methylprednisolone (MPNS). Serum levels of CSLsTNFR-p55 and CSLsTNFR-p75 in both groups prior to anti-rejection treatment were not elevated. CSLsTNFRs peaked at 1 h after the administration of OKT3, whereas in the MPNS group CSLsTNFRs remained unchanged. We conclude that in acute renal transplant rejection CSLsTNFRs increase after treatment with OKT3. In spite of high circulating sTNFRs levels all OKT3-treated patients suffered from clinical side-effects.

Adult↗