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Biomedical subjects

R A Koene

Publications and source records attributed to R A Koene.

At least 145 records · Page 8Linked to original sources
PubMed1989

Cytomegalovirus infection and disease in renal transplant patients treated with cyclosporin. A prospective study.

In this prospective study, the incidence of cytomegalovirus (CMV) infection and CMV disease was determined in 175 renal transplant recipients on cyclosporin and low-dose prednisone. CMV infection occurred in 51.4% of the patients, CMV disease in 13.7%. The major manifestations of CMV disease were fever of unknown origin and leukopenia. In the group with CMV infection, there was an increased occurrence of rejection (60% in infected vs 27% in noninfected patients). In most patients (41/54), the rejection preceded the CMV infection. CMV infection did not lead to a decreased graft survival. There was no close time relationship between the onset of clinical symptoms of CMV disease and the laboratory confirmation of CMV infection. A subgroup of patients at risk for the development of severe CMV disease could not be identified.

Cyclosporins↗
PubMed1989

The role of adaptation in allograft acceptance.

The experimental and clinical data suggest that both a decrease of antigen expression and decreased perfusion can protect against immunologically mediated destructive processes. In the adaptation of skin grafts, these factors could be interrelated. Inadequate perfusion might lead to a decreased delivery of substances that stimulate MHC antigen expression. This course of events also could explain the protection in the patient presented here. Immune deposits were completely absent in the protected segment of the kidney, although immune deposits were abundantly present in the remaining part of the kidney, and circulating anti-donor antibodies were demonstrable after the transplanted kidney had been removed. The limited availability of frozen biopsy material has prevented us from comparing the expression of MHC antigens in both kidney segments using monoclonal antibodies. But such studies might be done in experimental kidney transplants with an artificially induced stenosis of the renal artery. Except when an arterial stenosis is present, we have little reason to assume that perfusion gradually decreases in longstanding kidney grafts as it does in skin grafts. Therefore, if adaptation plays a role in the gradual decrease of the sensitivity to rejection in longstanding kidney grafts, this phenomenon must be attributed to a decreased expression of target antigens as a consequence of factors other than decreased perfusion. The most likely candidates are the immunosuppressive drugs, such as cyclosporine and prednisone, which decrease MHC antigen expression. Let me conclude by returning to my main theme of graft adaptation. It seems appropriate to end this review with a quotation from one of Woodruff's original publications on this subject: "If the phenomenon [adaptation] applies to homotransplants of normal tissues to sites other than the eye, I think it almost certain that the clinical homograft problem will be solved; if it does not, the problem may prove insoluble" [9]. Although our insight into the rejection process has increased considerably, we still do not know which factors are most important in determining the long-term survival of primarily vascularized grafts.

Adult↗
PubMed1989

Triamterene increases lithium excretion in healthy subjects: evidence for lithium transport in the cortical collecting tubule.

The possible presence of lithium transport beyond the proximal tubule was examined by measuring lithium excretion after administration of triamterene, a potassium-sparing diuretic, exclusively acting in the cortical collecting tubule. Eight young and healthy volunteers were studied on two occasions during maximal water diuresis. After obtaining baseline values triamterene (100 mg orally) or placebo was administered, and measurements continued for 4 hours. Creatinine clearance was used as a marker of glomerular filtration rate, and phosphate excretion was used as an additional marker of proximal sodium transport. Compared to placebo (P), triamterene (T) caused a significant increase in fractional excretion of sodium (P, 0.74 +/- 0.08%; T, 1.73 +/- 0.24%, mean +/- SEM; P less than 0.01), and lithium (P, 21.2 +/- 1.3%; T, 27.5 +/- 1.5%; P less than 0.01), whereas fractional excretion of phosphate remained unchanged (P, 9.8 +/- 1.3%; T, 9.4 +/- 1.5%; P = NS). These results indicate that lithium is transported in the cortical collecting tubule, and provide further evidence that the use of lithium as a marker of purely proximal tubular sodium transport is of limited value.

Adult↗
PubMed1989

Antihypertensive effects of nitrendipine and cilazapril alone, and in combination in hypertensive patients with chronic renal failure.

1. It has been reported that calcium antagonists lower blood pressure more effectively in salt replete hypertensive patients with a low plasma renin activity (PRA), whereas angiotensin converting enzyme (ACE) inhibitors are more effective in salt depleted patients with a high level of PRA. An inverse relationship between the antihypertensive effects of these two groups of drugs might therefore be expected. 2. Since salt retention and inappropriately high levels of PRA are said to contribute to hypertension in patients with chronic renal failure (CRF), an additive antihypertensive effect with both drugs might also be expected in such patients. 3. To test these hypotheses, we investigated the acute and chronic antihypertensive effects of the calcium antagonist nitrendipine and the new ACE inhibitor cilazapril, given alone, and in combination, in a double-blind, randomized, placebo controlled study of 11 hypertensive patients with chronic renal failure who had a mean pretreatment blood pressure of 149 +/- 3/96 +/- 2 mm Hg. Patients received nitrendipine 10 mg, cilazapril 1.25 or 2.5 mg depending on creatinine clearance, or placebo once daily orally. Nitrendipine and cilazapril were also combined at the same doses. 4. Nitrendipine and cilazapril were equally effective, with a maximal acute reduction of mean arterial pressure (MAP) of 5.3 +/- 1.8% and 8.0 +/- 1.9%, and after 1 week of treatment 5.0 +/- 2.4% and 8.1 +/- 1.8%, respectively. In individual patients no inverse relationship between the blood pressure responses to the two drugs was found.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Efficacy and tolerance of treatment with recombinant-human erythropoietin in chronic renal failure (pre-dialysis) patients.

Recombinant-human erythropoietin (r-HuEPO) was administered to 24 anaemic pre-dialysis patients with end-stage renal disease. R-HuEPO was injected i.v. three times weekly during the first two months (correction phase). Fixed dosages of 50 U/kg, 100 U/kg, and 150 U/kg were used, and each dose group consisted of eight patients. During the subsequent six months r-HuEPO was given once weekly and the dose was adjusted to maintain a stable haemoglobin value (maintenance phase). The mean +/- SD haemoglobin increased from 9.3 +/- 0.6 to 11.1 +/- 1.3 g/dl with 50 U/kg, from 7.9 +/- 1.4 to 11.8 +/- 1.7 g/dl with 100 U/kg and from 8.4 +/- 1.0 to 12.1 +/- 1.1 g/dl with 150 U/kg of r-HuEPO. The two highest dose groups showed a marked reticulocytosis and a transient thrombocytosis. During the maintenance phase haemoglobin remained stable (11.9 +/- 1.1 g/dl) at a mean dose of 199 +/- 139 U/kg of r-HuEPO per week. Blood pressure did not increase, but in nine of eighteen previously hypertensive patients antihypertensive medication was increased. One hypertensive patient developed seizures. No accelerated progression of renal failure could be demonstrated. All patients reported an improved sense of well-being. R-HuEPO is an important new therapeutic agent for the treatment of anaemia of end-stage renal failure that is also effective in pre-dialysis patients.

Adult↗
PubMed1989

Involvement of an antigen distinct from the Heymann antigen in membranous glomerulonephritis in the mouse.

Membranous glomerulonephritis in the mouse can be induced by injection of a heterologous antiserum against murine pronase digested renal tubular antigens (TApron). The antigenic target in the glomerular capillary wall is different from the Heymann antigen (gp 330). It shows the characteristics of a smaller antigen (gp 90) that can also be detected by a monoclonal antibody. We isolated the anti-gp 90 component from the polyclonal antiserum by absorptions and elutions using mouse liver as a substrate, which lacks gp 330 but does express gp 90. Immunoprecipitation of radiolabeled renal proximal tubular brush borders demonstrated that the mouse liver eluate reacted with gp 90 but not with gp 330. In immunofluorescence, the eluate bound to the glomerular capillary wall of both mouse and rat in a homogeneous pattern. Injection of the eluate led to a transient, homogeneous binding to the glomerular capillary wall of the mouse and also, although to a lesser extent, to that of the rat. Injection in mice presensitized against rabbit immunoglobulins caused a more permanent granular binding in a pattern typical of membranous glomerulonephritis. The results demonstrate that an antigen with a molecular weight and a kidney distribution different from the Heymann antigen can serve as target for antibody-mediated membraneous glomerulonephritis in the mouse. Furthermore, they suggest that this antigen may also be involved in the membranous glomerulonephritis of the rat in addition to the Heymann antigen.

Animals↗
PubMed1989

Short-term protein restriction in healthy volunteers: effects on renal hemodynamics and renal response to a meat meal.

We have studied the renal hemodynamic effects of short-term protein restriction and short-term protein loading in 12 healthy volunteers, who adhered to a low protein diet (0.6 g/kg/day) for three weeks and then switched to a high protein diet (1.8 g/kg/day) for another three weeks. Baseline glomerular filtration rate (GFR) was not influenced by dietary protein intake. Effective renal plasma flow (ERPF), however, was significantly lower on the low protein diet (491 +/- 23 ml/min; mean +/- SEM) as compared to values on the high protein diet (538 +/- 19 ml/min; p less than 0.01). The increase of GFR after a meat meal (providing 1.8 g protein/kg body weight) was higher on the high protein diet (GFR: +23.6 +/- 5.1 ml/min) than on the low protein diet (GFR: +13.0 +/- 2.4 ml/min; p less than 0.05). We conclude that three weeks of dietary protein restriction do not decrease glomerular filtration rate and do not enhance the renal response to a meat meal. Therefore, it seems doubtful that dietary protein restriction decreases glomerular capillary pressure through vasoconstriction of the afferent glomerular arteriole. Furthermore, measurement of the renal hemodynamic response to an acute protein load seems of doubtful physiological significance.

Adult↗
PubMed1988

An improved sensitive and simple microassay of mouse complement.

A simple and fast hemolytic microassay was developed for the determination of classical pathway complement activity in mouse serum. The assay is based on hemolysis of sheep red blood cells (SRBC) that are sensitized with polyclonal mouse antibodies. The degree of hemolysis was measured in the reaction supernatants by photometric reading in an ELISA plate scanner at 405 nm wavelength. It was found that some batches of unpurified mouse anti-SRBC antibodies gave insufficient hemolysis. Analysis of two antibody preparations indicated that this might be caused by anti-complementary factors in the ascites fluid, and by an excess of non-complement fixing IgG1 antibodies. For optimal and standardized results, removal of anticomplementary factors and enrichment for complement fixing IgG2 antibodies was required and was achieved using protein A purified anti-SRBC IgG. In our assay it is possible to determine CH50 titers in triplicate in 80 microliters samples of individual mouse sera with high sensitivity. Using this rapid one-step method large numbers of tests could be performed in 1 day.

Animals↗