Outcome of total parathyroidectomy and autotransplantation as treatment of secondary and tertiary hyperparathyroidism in children and adults.

BACKGROUND: Treatment safety and effectiveness of total parathyroidectomy and autotransplantation for secondary and tertiary hyperparathyroidism have been extensively proven in adults; the evidence for children, however, is scarce. Children and adolescents cannot simply be seen as young adults in the case of chronic kidney disease and hyperparathyroidism. The aim of this retrospective study was therefore, to evaluate whether parathyroidectomy with forearm autograft is as effective and safe in children and adolescents as in adults. METHODS: A group of 64 adults and 8 children and adolescents treated for secondary or tertiary hyperparathyroidism were retrieved from our database. The outcomes were compared on patient demographics, operation results, and blood parameters consisting of parathyroid hormone (PTH) and calcium levels. Our results were compared with all currently available articles on parathyroidectomy in children with secondary or tertiary hyperparathyroidism (n = 11). RESULTS: For adults, preoperative mean serum calcium was 2.67 +/- 0.29 mmol/l and mean parathyroid hormone (PTH) level was 120 +/- 86 pmol/l. For children, preoperative mean serum calcium was 2.62 +/- 0.20 mmol/l and mean parathyroid hormone (PTH) level was 80 +/- 38 pmol/l. Postoperative calcium and parathyroid hormone levels for adults dropped to 2.39 +/- 0.23 mmol/l and 30 +/- 53 pmol/l, respectively. Postoperative calcium and parathyroid hormone levels for children dropped to 2.41 +/- 0.16 mmol/l and 26 +/- 33 pmol/l, respectively. The effectiveness of parathyroidectomy with autotransplantation was 75% in children and 72% in adults. Thus, effectiveness did not differ significantly between children and adults. CONCLUSIONS: Combining the results of our own study with a literature review on pediatric parathyroidectomy, we conclude that parathyroidectomy and forearm autograft is as effective a treatment for secondary and tertiary hyperparathyroidism in children and adolescents as it is in adults.

Influence of HLA-DRB1* incompatibility on the occurrence of rejection episodes and graft survival in serologically HLA-DR-matched renal transplant combinations.

BACKGROUND: The aim of the present study was to analyze the effect of HLA-DRB1* mismatches on graft function and graft survival in 92 patients who received serologically HLA-DR split antigen-matched cadaveric renal transplants. METHODS: The polymorphic second exon of the HLA-DRB1 alleles was typed using the sequence-specific oligonucleotides technique. RESULTS: The results show that in 26 of the 92 analyzed combinations, one or more HLA-DRB1* mismatches were found (28%). The analysis of the occurrence of treatable rejection episodes during the first 3 months after transplantation demonstrated a significantly higher incidence of rejection episodes in the HLA-DRB1*-mismatched group: 18 of 26 (69%) in the HLA-DRB1*-mismatched group against 23 of 66 (35%) in the HLA-DRB1*-matched group (P(uncorr)=0.0033). However, no effect of HLA-DRB1* mismatches on graft survival was found, although in general graft survival in the whole patient group was negatively influenced by the occurrence of rejection episodes during the first 3 months after transplantation (P(uncorr)=0.0008). In contrast, in the HLA-DR4-matched donor-recipient combinations (n=28), the effect of mismatching for the HLA-DRB1*04 alleles seemed to have a pronounced effect not only on the occurrence of rejection episodes but also in the form of diminished graft survival. CONCLUSIONS: Thus, this study indicates that the existence of HLA-DRB1* allele mismatches in renal transplant recipients, matched for the serologically defined HLA-DR split antigens, is not harmful for the transplant. The exception is the HLA-DRB1*04 mismatch, which seems to be deleterious for the grafted organ.

The effectiveness of a low molecular weight heparinoid in chronic intermittent haemodialysis.

A new low molecular weight heparinoid, Org 10172 was compared to heparin in a randomized single blind cross-over study in 55 patients with end-stage renal failure undergoing chronic intermittent haemodialysis. The heparinoid administered as a single pre-dialysis i.v. injection of 34.4 anti-Xa units/kg body weight was compared to standard heparin (loading dose 2,500 IU + continuous infusion of 1,800 IU/hr). Mean anti-Xa plasma levels reached were 0.55 and 0.94 anti-Xa units/ml midway dialysis respectively. All 110 dialysis procedures were successfully performed without clotting or bleeding complications. Analysis of the number of clotted hollow-fibres within the dialysers showed a slight statistically calculated advantage in favour of heparin. Clinically no difference was detected. In conclusion, the heparinoid seems to be a good alternative means of anticoagulation in haemodialysis. As it is administered as a single i.v. predialysis injection it will simplify the dialysis procedure.

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.

Anticoagulant effects of a low molecular weight heparinoid (Org 10172) in human volunteers and haemodialysis patients.

Org 10172, a low MW heparinoid derived from animal intestinal mucosal tissue, has a mean molecular weight of 6500 D and a specific activity of 8.0 anti-Xa U/mg. Its elimination half-life after i.v. administration is 18 hours. Six human volunteers received repeated single i.v. injections of 800 and 3200 anti-Xa units of Org 10172, 5000 IU heparin or placebo. Bleeding time, platelet count and plasma beta thromboglobulin were not affected by Org 10172 or heparin. Heparin stimulated ADP-induced platelet aggregation (0.2 uM; p less than 0.05) and inhibited thrombin induced aggregation (0.3 U/ml; p less than 0.05), while the heparinoid lacked these effects. Heparin increased plasma platelet factor 4, whereas Org 10172 had no effect. In contrast to heparin Org 10172 had only a minor effect on the activated partial thromboplastin time and thrombin time, while both compounds induced anti-Xa activity in plasma. In a crossover study in six haemodialysis patients, both heparin and Org 10172 (34.4 and 22.4 anti-Xa units/kg/body weight) successfully prevented clotting of the extracorporeal circuit. Microscopical analysis of the artificial kidney membranes showed that the 34.4 unit Org 10172 dosage was as effective as heparin in preventing fibrin deposition. The haemostatic and coagulation effects were as expected from those observed in the volunteers except that there was a slower elimination of the plasma anti-Xa response. In addition heparin and Org 10172 (34.4 anti-Xa units/kg) inhibited the Xa-induced platelet aggregation (0.5 U/ml; p less than 0.01 and p less than 0.001 respectively).

Increased dermal expression of ICAM-1 and VCAM-1 after administration of OKT3 in man.

OKT3 induces a systemic release of cytokines and a profound peripheral lymphocytopenia. In vitro, tumor necrosis factor-alpha, interleukin-1, and interferon-gamma increase adhesion molecule expression on vascular endothelium. To investigate the effects of OKT3 induced cytokine release on endothelial- and lymphocyte adhesion molecule expression in vivo, we studied sequential skin biopsies of six renal allograft recipients treated for acute rejection with 5 mg OKT3. An additional group of six patients treated for acute rejection with 50 mg methylprednisolone served as a control group. Compared to pre-treatment biopsies, biopsies taken 4.5- and 24 hours after the first OKT3 dose showed a maximal increase in VCAM-1 and ICAM-1 expression, respectively. In parallel, an increased number of CD2+, CD11a+, and CD49d+ mononuclear cells in the skin was observed in all OKT3 treated patients. No changes were observed after methylprednisolone treatment. We conclude that the OKT3 induced cytokine release induces increased ICAM-1- and VCAM-1 expression on vascular endothelium, leading to increased influx of CD2+ lymphocytes which may contribute to the peripheral lymphocytopenia after OKT3.

[Immunology in medical practice. XXX. Organ transplantation: indications and results]. / Immunologie in de medische praktijk. XXX. Orgaantransplantatie: indicaties en resultaten.

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.

[Kidney transplant program facilitated by airlift between the Netherlands Antilles and the Netherlands; 1998-2001]. / Niertransplantatieprogramma op de Nederlandse Antillen door een luchtbrug met Nederland; 1998-2001.

OBJECTIVE: To describe the results of a structured kidney-transplantation programme available to dialysis patients in Curaçao (Dutch Caribbean), involving transplantation in the Netherlands and follow-up in Curaçao. DESIGN: Descriptive. METHOD: In 1998, a joint venture was begun with the Academic Medical Center (AMC) in Amsterdam, the Eurotransplant Foundation, the Dutch Transplantation Working Party and the Diagnostic Division of the Sanquin Foundation in Amsterdam, the Netherlands. Its aim was to achieve a structural kidney transplantation programme for patients in the Dutch Caribbean in general and patients in Curaçao in particular. An airlift programme between Curaçao and the AMC was instituted. RESULTS: Between 1998-2001 19 patients underwent a kidney transplant, three of which failed. In most of the transplants the cold ischaemia time was less than 48 hours; the average cold ischaemia time was 32 hours. All patients returned to the Antilles within 3 months where their treatment was continued. Post-transplantation follow-up was on average 13.9 months (limits 3-36); three patients died.

[Epstein-Barr virus in a donor kidney as a cause of non-Hodgkin lymphoma]. / Epstein-Barr-virus in een donornier als oorzaak van non-Hodgkin-lymfoom.

A 22-year-old male who had received a kidney transplant from his father (HLA haploidentical), presented with fever and malaise. After transplantectomy was performed because of rejection, the patient developed abdominal pain due to perforation of the small intestine. Non-Hodgkin's lymphoma was found in both the transplant and the small bowel. The patient had suffered a primary Epstein-Barr virus (EBV) infection, probably transferred through the transplanted kidney. DNA analysis showed that the lymphoma was of patient origin. After withdrawal of immunosuppressive therapy, no recurrence of the lymphoma was seen. EBV is a well-known aetiologic agent of non-Hodgkin's lymphomas arising in the immunocompromised patient.