Biomedical subjects
Publications and source records attributed to H J Metselaar.
Wegener's granulomatosis affects renal function in the majority of cases by a focal necrotizing glomerulonephritis. In this case report we describe a patient in whom ureteral obstruction due to a retroperitoneal localization preceded this renal manifestation.
The incidence of osteonecrosis was 24% in 248 patients who had received 262 kidney transplants 1971-1982. However, based only on patients at risk, i.e. alive with functioning transplants, the incidence at 1, 3 and 6 years was found to be 13, 27 and 36%; after six years no new cases were found. The relative increase in body-weight at 180 days was predictive as regards risk for osteonecrosis, while the cumulative dose of steroids was not. This suggests that individual sensitivity to steroids rather than the absolute cumulative dose is involved in the development of osteonecrosis.
Administration of di-n-propylacetate (DPA), an inhibitor of SSA-dehydrogenase, produces in naive rats abstinence behaviour which can be blocked by morphine and bicuculline and may be useful as a behavioural correlate of increased GABA-ergic activity. The usefulness of this model has been demonstrated by studying the effect of bicuculline, picrotoxin, strychnine, morphine, aminooxyacetic acid, 3-mercaptopropionate and thiosemicarbazide on DPA-induced abstinence behaviour. Behaviour was suppressed both by bicuculline or picrotoxin, while the selective glycine antagonist strychnine was ineffective. A comparable syndrome could not be evoked by treatment with aminooxyacetic acid, a GABA-transaminase inhibitor, indicating that the effect of DPA was not caused by inhibition of this enzyme. Instead, aminooxyacetic acid suppressed the DPA-induced abstinence behaviour, suggesting that two GABA-ergic systems with opposite effects on behaviour can be distinguished. The syndrome was also suppressed by convulsant doses of 3-mercaptopropionate, while thiosemicarbazide was ineffective. Abstinence behaviour was further suppressed by morphine with an ED50 of 0.5 mg/kg and this action could be clearly separated from its depressant effect on locomotor activity in non-treated animals. These results suggest that morphine receptors may be involved in DPA-induced abstinence behaviour. Based on these experiments a model has been proposed for GABA-ergic terminals being under the inhibitor influence of GABA-ergic autoreceptors. It is proposed that DPA-induced abstinence behaviour may be useful as a model of increased GABA-ergic activity to aid study of the regulation and properties of the GABA-ergic system in vivo.
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In ten auxiliary partial liver transplant recipients selective bowel decontamination (SBD) was used to reduce infections due to gram-negative microorganisms and fungi. During SBD no gram-negative infections occurred. Candida peritonitis was observed in one patient. After discontinuation of SBD serious infections of gram-negative origin did occur and three fungal infections were seen. SBD seems to have a favourable effect in reducing infections by gram-negative microorganisms and fungi. Most striking was the number of enterococcal infections that occurred. Five out of ten patients developed enterococcal infections which in two cases contributed to a fatal outcome. These infections occurred after increase of the number of enterococci in faeces and concomitant positive cultures of bile, ascites or wound drains. This increase could be due to the use of SBD. Also, the kind of biliary anastomosis may play an important role in the relatively high incidence of enterococcal infections. In the postoperative period, recurrence of hepatitis B infection in the liver graft was observed in all patients with cirrhosis due to this virus. Problems caused by other viral infections or protozoal infections remained limited in these ten patients.
An assay is described for handling clinical specimens for the detection of cytomegalovirus. It consists of low-speed centrifugation of the specimen on human embryonic lung cells, using a technique adapted from chlamydial culture, followed by detection using a monoclonal antibody against the cytomegalovirus early antigen in an immunofluorescence technique. This assay was compared with the conventional cell culture system. 161 specimens obtained from 52 patients were studied; from 14 patients CMV was isolated in at least one specimen (in total 28 specimens). The centrifugation technique led to positive results generally within 24 to 48 h, whereas the cell culture took an average of 16.5 days to develop the typical cytopathic changes. No cross-reactions between the cytomegalovirus monoclonal antibody and other viruses present (herpes simplex virus and adenovirus) were observed. The centrifugation technique is a reproducible and rapid method in the diagnosis of cytomegalovirus infection.
We analyzed the results of passive immunization against CMV in 146 heart transplant recipients. The 65 seronegative recipients were prophylactically treated with anti-CMV immunoglobulins during and after the operation. Twenty-nine of these 65 patients received a seropositive donor heart. CMV infection occurred in 21/65 seronegative and in 40/81 seropositive recipients (difference not significant). The incidence of CMV infection in seronegative recipients of a CMV-matched donor heart (3/34) was significantly lower than in seronegative recipients of a positive donor heart and lower than in seropositive recipients, but no significant difference in infection rate was found between the two latter groups (18/29 vs. 40/81). Although primary infection more frequently resulted in CMV disease than secondary infection (11/21 vs. 10/40) no difference in incidence of disease was noted between seronegative and seropositive patients (11/65 vs. 10/81), nor was there a difference in the severity of symptoms following primary or secondary infection. There was a higher incidence of CMV disease in all patients who received a heart from a seropositive donor versus a seronegative donor. However, after transplantation of a heart from a seropositive donor the incidence (27%) of CMV disease observed in our passively immunized seronegative patients was the same as in the patients with naturally acquired seropositivity. There was no difference in the prevalence of coronary artery disease between patients with and without CMV infection or disease. We conclude that using the current passive immunization scheme the occurrence of CMV infection and disease is largely dependent on the serostatus of the donor.
We hypothesized that the relatively low immunogenicity of liver grafts might be related to a special maturation program of hepatic myeloid dendritic cells (MDC), yielding relatively immature effector MDC with weak allogeneic T-cell stimulatory capacity. To investigate whether maturation of human liver-derived MDC in vivo differs from maturation of MDC at another anatomical location, we compared the immunophenotypes and allogeneic T-cell stimulatory capacity of MDC from hepatic with those from inguinal lymph nodes (LN). MDC were purified by immunomagnetic selection from hepatic LN obtained from multi-organ donors (n = 8) and from inguinal LN of kidney transplant recipients (n = 7). MDC from hepatic LN had a significantly reduced capacity to stimulate allogeneic T-cell proliferation compared to MDC from inguinal LN. However, this was not due to an immaturity, since MDC from hepatic LN had significantly higher expressions of HLA-DR, CD80, and CD86 compared to MDC from inguinal LN. Hepatic MDC maturate in vivo to a mature type of effector MDC with relatively poor allogeneic T-cell stimulatory capacity.
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After auxiliary partial orthotopic liver transplantation for inborn errors of metabolism, finding a balance in portal blood flow distribution between native liver and graft is complicated. We investigated the correction of hypoallantoinuria in the Dalmatian dog with a reduced-size Beagle orthotopic auxiliary liver graft, depending on intra-operative intervention in the portal flow. There were three groups: a ligation group, where the host portal vein was tied off, a free-flow group with random flow to both livers and a banding group, where the host portal vein was banded with an adjustable strapband. Metabolic correction was initially seen in all groups, but ligation led to portal hypertension and early mortality. In the free-flow group, correction was lost after 7 days, while banding preserved correction until 6 weeks. We conclude that acute ligation can lead to portal hypertension and free-flow leads to hypoperfusion and early loss of metabolic correction. Banding divided the portal blood flow between host liver and graft and prolonged metabolic correction.