Biomedical subjects
Publications and source records attributed to H van Bronswijk.
Palifermin is a human keratinocyte growth factor that is produced in Escherichia coli by recombinant-DNA-technology. This substance protects against oral mucositis in adults undergoing myeloablative therapy. The safety of this product--being a growth factor --in the long term has not yet been shown. Adverse effects may occur in the skin and mucous membranes.
Erlotinib inhibits the phosphorylation of the epidermal growth-factor receptor (EGFR/HERI), a tyrosinekinase protein. This results in an inhibition of signal transduction and therefore decreased cell division and increased cell death. The agent is indicated for the treatment of patients with advanced local or metastasised non-small-cell pulmonary carcinoma after other cytostatic therapy has failed.
Ivabradine lowers the heart rate by inhibiting the cardiac pacemaker current that is responsible for diastolic depolarisation. The most important side effect is the appearance of light flashes (phosphenes). The agent can be used in patients with angina pectoris when beta-blockers are insufficiently effective, provided that the heart rate is at least 60 beats per minute at the beginning of the treatment.
Nitisinone is an inhibitor of 4-hydroxyphenyl-pyruvate dioxygenase (4HPPD). Its rare area of use is hereditary tyrosinaemia, a life-threatening disease in which the last step in the catabolism of tyrosine cannot be taken due to the absence of an enzyme. The inhibition of 4HPPD, an enzyme that is active early in the catabolic cascade, prevents the accumulation of toxic metabolites of tyrosine.
Ziconotide is a synthetic analogue of a peptide found in the poison of the marine snail Conus magus. Ziconotide blocks N-type calcium channels, which play an important role in the transmission of pain signals in the dorsal ganglia of the spinal cord. The drug is indicated for 'severe chronic pain' and is administered intrathecally.
Zonisamide is an adjuvant for the treatment of patients with partial epilepsy, with or without secondary generalisation. It affects, among other things, the voltage-sensitive sodium and calcium channels, thus disrupting synchronised neuronal firing; as a result, it diminishes the spread of seizure discharges.
Bevacizumab is a humanised monoclonal antibody that targets vascular endothelial growth factor. By blocking the growth factor, bevacizumab inhibits the development of new blood vessels, which in turn inhibits the growth oftumours and metastases. Mean disease-free survival is prolonged in patients with metastatic colorectal carcinoma who are treated with bevacizumab. Evaluation of bevacizumab in other indications is underway.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The quality of life after a successful combined kidney-pancreas transplantation was studied in 17 diabetic patients with end-stage renal disease (ESRD) and in 11 patients who experienced a failure of one or both grafts. The control group comprised 23 patients who received a kidney transplantation only. The aspects of quality of life chosen for study were: physical, psychological and social wellbeing, daily activities, level of functioning and global quality of life evaluation. Additionally, future expectations, the perceived burden of treatment, and main reason for undergoing organ replacement therapy were evaluated. In only one aspect of quality of life did patients with a successful combined transplantation score significantly better than patients with a kidney transplantation, i.e., mobility in daily functioning and activities (p = 0.03). Patients with a failure of one or both grafts reported significantly more fatigue (p = 0.02), less energy (p = 0.04), and more social isolation (p = 0.05) than patients who had well-functioning grafts. The mean duration of hospitalization following combined transplantation is twice that for kidney transplantation only 10 vs 5 weeks. Although the combined transplantation group found the first 3 months after transplantation more burdensome (p = 0.04) and more often wondered whether it had been worth all the trouble (p = 0.05), they indicated the same willingness as the group with a kidney transplant only to undergo another transplantation under similar circumstances. Although the recipients of a kidney transplant had not been offered the choice of a combined transplantation, their reasons for transplantation did not, in essence, differ from those of recipients of a combined transplantation. In both groups the main motivation to opt for organ replacement therapy was the burden of dialysis, to stop the progressive deterioration of their health, and to experience a better quality of life.
Explore the source record for details and available documents.
Pancreatic graft procurement, preservation, and transplantation surgery may result in damage to and loss of the integrity of endocrine cells and consequently in leakage of cell products into the insular vascular capillaries. Thus, the amount of alpha-, beta-, and pancreatic polypeptide (PP) cell products released into the vascular space of the recipient immediately after graft reperfusion may reflect islet cell injury. To test this hypothesis, we assessed glucagon, PP, C-peptide, and insulin levels in a prospective study of 22 consecutive renal-pancreatic transplantations. Transplantation-related parameters were used to account for differences in hormone release. Five grafts were preserved using Euro-Collins preservation fluid and 17 grafts were preserved using University of Wisconsin solution (UW). The first sign of a reinstalled physiological axis was the decrease of the blood glucose concentration after a median duration of 40 min (range 5-90 min) and the association of the recipient's ambient blood glucose levels with insulin release between 25 and 180 min after reperfusion. The delay period before a fall in blood glucose was observed correlated with cold ischemia time (rs = 0.73, P < 0.001, n = 21). An immediate and marked increase in plasma levels of glucagon (from 180 +/- 18 to 585 +/- 99 ng/L, mean +/- SEM), PP (from 57 +/- 8 to 122 +/- 13 pmol/L), C-peptide (from < 0.06 +/- 0.02 to 5.43 +/- 0.63 nmol/L), and insulin (from 0.15 +/- 0.21 to 2.05 +/- 0.26 nmol/L) was observed. C-peptide release correlated with glucagon (r = 0.76, P < 0.001) and PP (r = 0.60, P < 0.01). The hormone release was compared with computed tomography scans that were performed in the immediate postoperative period in 15 UW-preserved allografts. The diameter of the pancreatic head was increased and ranged from 4.5 to 7.7 cm (mean 6.2 cm). Peroperative C-peptide release significantly correlated with morphological graft changes reflected by the pancreatic head diameter (r = 0.58, P = 0.02). In a stepwise multiple regression analysis, cold ischemia time was a significant factor for the release of PP (r2 = 0.18, P = 0.049) and C-peptide (r2 = 0.35, P = 0.004). We suggest that peroperative hormone release reflects endocrine tissue damage. Furthermore, cold ischemia time may jeopardize the pancreatic allograft after relatively short preservation times, even when UW is used.
We analyzed the overall results of 24 simultaneous pancreas and kidney transplantations (SPK), performed in our hospital between April 1986 and June 1990. All patients had type I diabetes mellitus and end-stage renal failure. We used bladder drainage of the pancreatic exocrine secretions through a duodenocystostomy. The blood vessels of both grafts were anastomosed to the iliac vessels. The immunosuppressive management was triple-therapy with cyclosporin, azathioprine and prednisone. All organs were transplanted without matching donors and recipients for HLA. At the time of transplantation, mean recipient age was 37 yr; the average duration of diabetes was 22 yr. After disappointing results in the first 4 patients, the pancreas was placed intraperitoneally instead of extraperitoneally and the antibiotic drug regimen was altered. In the second group (n = 20), patient survival was 100%; 1-yr pancreas and kidney graft survival were 65 and 62%, respectively. Duration of hospitalization and pancreas and kidney graft loss were positively correlated with the number of rejection episodes. After 1 yr of follow-up, the mean creatinine clearance was 62 ml/min and the mean HbA1c was 5.5%. Blood glucose levels and oral glucose tolerance tests were also normal. We conclude that patient and graft survival after SPK are satisfactory, although rejection-related morbidity is still a major problem.
A patient presenting with a nephrotic syndrome and chronic renal failure caused by light chain deposition disease (LCDD) without detectable light chains in serum and urine is presented. Only a few patients with LCDD but without detectable light chains in serum and urine have hitherto been reported. The diagnosis was made by light-microscopic and immunofluorescent examination of a percutaneous renal biopsy. The histological differential diagnosis of LCDD includes diabetic glomerulosclerosis, renal amyloidosis and membranoproliferative glomerulonephritis. For the histological diagnosis of LCDD, immunofluorescence using anti-kappa and anti-lambda antisera is essential. Although renal involvement is a constant feature in LCDD, other sites of deposition of light chains have been reported. The absence of detectable light chains in serum or urine is discussed.
Explore the source record for details and available documents.
Cultured human mesothelial cells were exposed to peritoneal dialysis fluids, supernatants from cultures of Staphylococcus aureus and S. epidermidis, and antibiotics. Mesothelial cell monolayer cultures were derived from surgically removed omentum. The cytotoxicity of various agents for the cultured mesothelial cells was measured by a 51 Cr-release assay. All brands of fresh peritoneal dialysis fluids induced a more than 50% 51 Cr-release after 18 h. Morphological changes observed included retraction and shrinking of cells, pyknosis of the nuclei and, finally, detachment of cells over an 18-h period. Neutralization of the acid (pH 5.2-5.5) fluids to pH 7.3 did not abolish the cytotoxicity. In contrast, effluent dialysis fluids were not toxic for mesothelial cells; neither was acid (pH 5.5) culture medium nor culture medium with glucose up to 2%. However, higher glucose concentrations induced increasing 51 Cr-release. Furthermore, filter-sterilized supernatants of S. aureus were cytotoxic for mesothelial cell monolayers in 4/7 (57%) strains of S. aureus tested. In contrast, only 4/29 (14%) strains of S. epidermidis produced cytotoxic exoproducts (p = 0.03). Antibiotics were not found to be cytotoxic, with the possible exception of erythromycin. We conclude that currently available peritoneal dialysis fluids are cytotoxic for mesothelial cells in vitro and that during episodes of peritonitis exoproducts of some bacterial strains may further reduce mesothelial cell viability.