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Biomedical subjects

H E Hansen

Publications and source records attributed to H E Hansen.

At least 73 records · Page 4Linked to original sources

Lithium treatment in Aarhus. 2. Risk of renal failure and of intoxication.

In a region around Aarhus with a population of 372,000 the total exposure time for patients in lithium treatment during the period 1979-1987 was about 4900 patient-years. Lithium intoxication developed in 24 patients. Fifteen intoxications were caused by deliberate self-poisoning and nine by neglect of treatment guidelines; none were caused by a decline of glomerular filtration rate or without discernible cause. Only two out of 234 systematically followed patients showed a consistently falling creatinine clearance; a causal relation to the therapy was doubtful. The authors' data analysis confirms that lithium treatment, even when given for many years, induces neither deterioration of the glomerular filtration rate nor renal failure. The observations further show that lithium intoxications do not develop capriciously; unintended intoxications can be avoided by adherence to treatment guidelines and precautions.

Acute Kidney Injury↗

Changes in renal volume during normal pregnancy.

Twenty-four healthy pregnant women with a normal pregnancy demonstrated a significant uniform enlargement of both kidneys. The renal volumes increased by a maximum of 30% during pregnancy. However, this could not be attributed to hydronephrosis, as the patients were selected in such a way that none with pelvectasia participated in the study. All regained normal renal volume within the first week after delivery. It is well known that a glomerular hyperfiltration takes place during normal pregnancy. Possible pathogenetic mechanisms are discussed.

Adult↗

HLA and hydatidiform mole. I. HLA and ABO antigen frequencies in couples with androgenetic and diandric conceptuses.

HLA and ABO antigen frequencies and mating rates were studied in couples with hydatidiform mole with known genomic origin. HLA-A,B antigen frequencies among 60 patients and 59 spouses were not different from those found in the background population, neither in the subgroups regarded alone nor in the entire series. Although not significant, an excess of HLA-DRw6 found in patients with androgenetic conceptions may be related to the anucleate ovi observed with androgenesis. The distribution of ABO blood groups was in accordance with that observed in the background population; however, an overall excess of A x O matings was found.

ABO Blood-Group System↗

Hydatidiform mole and HLA. II. Compatibility between patient and conceptus.

In 52 conceptuses with known genomic origin, the HLA types expressed on whole villi and/or stromal cell cultures were compared with the HLA types of the patients. No preference for either HLA compatibility or incompatibility was found for androgenetic and paternally derived triploid conceptuses as a whole. Heterozygous, androgenetic, conceptuses, however, showed a trend towards preferential incompatibility, which may be of importance for their apparent greater risk for trophoblastic tumour. HLA antibodies were found in 19.2% of the women, i.e. in the range reported for molar as well as non-molar pregnancies. Non-HLA antibodies reacting with lymphocytes of the spouse and/or cells from the conceptus were observed.

Cytotoxicity, Immunologic↗

Hydatidiform mole and HLA. III. HLA-antigen expression related to genomic origin.

In 52 conceptuses with known genomic origin, HLA determination was performed on whole villi and/or stromal cell cultures. In 26 androgenetic, diploid conceptuses, one or two paternal HLA-A,B haplotypes were found; twenty-four triploid conceptuses with two paternal and one maternal chromosome sets showed either one maternal and one paternal haplotype or one/two paternal HLA-A,B haplotypes. Consequently, androgenesis could not be demonstrated by lack of maternal antigens alone. Concomitant expression of three HLA haplotypes was not seen. HLA-A2 was passed on to the conceptus, both in the genetic subgroups and in the entire series, more frequently than expected.

Female↗

Hydatidiform mole: genetic origin in polyploid conceptuses.

The origin of 29 polyploid conceptuses with villous cystic swelling was examined. One tetraploid specimen showed one maternal and three paternal contributions to the genome. Informative cytogenetic markers in 24 triploids were consistent with fertilization by dispermy. Analysis of cytogenetic markers indicated that polyspermy may account for essentially all polyploid conceptions with an excess of paternal to maternal chromosome complements. The origin of the genome was primarily demonstrated by the study of cytogenetic markers, while HLA determination and enzyme analysis were less informative.

Female↗

Hydatidiform mole: genetic markers in diploid abortuses with macroscopic villous enlargement.

In a series of diploid abortion specimens with gross villous enlargement the parental origin was determined by chromosomal heteromorphisms, HLA typing, and enzyme analysis. Diploid androgenesis was the mechanism in 33 cases; in 28 cases the most likely origin was by duplication of a haploid sperm after fertilization of an anucleated ovum, whereas heteromorphisms in five cases indicated a dispermic origin. In one macroscopically complete molar specimen all marker techniques applied indicated a normal conception. In two homozygous specimens a second cell line with both maternal and paternal contributions indicated a twin gestation, whereas, in four conceptuses twinning was suggested solely by HLA determination or ultrasound scan. The observation of a heterogeneous origin of diploid moles, as indicated by three marker systems studied simultaneously, emphasizes that additional information about the frequency of different types of molar conceptions may be obtained by this approach.

Abortion, Induced↗

Antigen sharing in couples in a two-locus ABO-like system.

The probabilities with which the two members of a couple share no, one or two antigens on each of two loci in ABO-like systems are derived. As an example, expected values concerning the HLA-A,B system are compared with observed frequencies in a material of 690 couples. A FORTRAN program for calculation of the gene-sharing probabilities is available.

ABO Blood-Group System↗

Acute renal failure caused by polymyxin B containing ointment.

A case is presented in which a 67-year-old man suffering from non-insulin-dependent diabetes mellitus, after being treated with polymyxin B containing ointment for leg ulcers, developed acute renal failure. After a period of 13 days during which the patient was treated with peritoneal dialysis 5 times, renal function returned. At discharge creatinine-clearance was 12 ml/min. Treating large ulcers with polymyxin B may be dangerous.

Absorption↗

Warfarin binding to plasma albumin, measured in patients and related to fatty acid concentrations.

A method for determination of reserve albumin equivalent for binding of warfarin as previously described [1] has been used for assessing the influence of non-esterified fatty acid concentration (NEFA) on binding of warfarin to human serum albumin (HSA). Reserve albumin concentration can be used for calculation of the expected fraction of bound warfarin in serum. It is shown in vitro that binding of warfarin increases with added oleate up to 4 mol of oleate per mol of albumin and then decreases. Twenty-four patients on permanent warfarin treatment showed no correlation of serum albumin and reserve albumin concentrations (r = 0.10, P greater than 0.50) indicating that warfarin binding is governed by other factors. However, in the same patients there was a significant correlation between reserve albumin concentration and NEFA/HSA (r = 0.54, P less than 0.01). In one human volunteer changes of NEFA were provoked by strenuous work and it was found that reserve albumin concentration increased with NEFA concentration as expected from the in vitro findings (r = 0.90, P less than 0.001). Five uraemic patients on permanent warfarin treatment showed increasing reserve albumin concentration with increasing NEFA concentration induced by heparin. These findings indicate that, both in vitro and in vivo, the reserve albumin concentration for binding of warfarin and hence the free warfarin concentration is markedly influenced by NEFA concentration. This may add to the understanding of warfarin dose requirement during anticoagulant therapy.

Adult↗

Pregnancy following kidney transplantation.

Following kidney transplantation, 20 women gave birth to 24 infants after the 28th gestational week. All babies were singletons, alive, and free from malformations. The mean weight was 2,595 g (range 1,420-3,200 g) and the mean gestational age was 37.8 weeks (range 32-40 weeks). The cesarean section rate was 75%. On dividing the patients into low- and high-risk groups, the rate of pre-eclampsia, prematurity, and intra-uterine growth retardation was 2-3 times as high in the high-risk as in the low-risk group. No patients experienced graft rejection during the pregnancy but, within 3 months after delivery, two rejection episodes occurred. Later, a further 5 patients experienced graft rejection. All infants developed normally. We conclude that pregnancy following renal transplantation generally has a normal outcome and that the function of the transplanted kidney is unaffected by the pregnancy.

Adult↗

Ultrastructure of the kidney in acute interstitial nephritis.

Fifteen percutaneous renal biopsies from patients with acute renal failure due to acute interstitial nephritis (AIN), in almost all cases due to drugs, were studied by electron microscopy. Differential counting of interstitial cells showed an average of 69% lymphocytes (small and large) and 11% macrophages. Plasma cells and eosinophils were comparatively rare. The infiltrate resembled that of acute rejection, suggesting a cellular hypersensitivity reaction. Proximal and distal tubules were severely affected focally. Migration of lymphocytes through the tubular basement membrane of otherwise well-preserved tubules was considered to be the first phase. Other tubules showed extreme thinning of the tubular basement membrane, with still intact cellular walls. Rupture of the tubular basement membrane and necrotic disintegration of tubular epithelial cells are probably late phenomena. The non-necrotic tubules displayed severe reduction of proximal brush border and proximal as well as distal tubular basolateral infoldings. Focal tubular disintegration leading to tubular block and/or backleak as well as decrease of proximal tubular sodium resorption leading to a decreased glomerular filtration (a mechanism probably also acting in ischemic acute renal failure) may all be factors responsible for the acute renal failure in AIN.

Adult↗

Hydatidiform mole and HLA. Methods for HLA-A,B,C determination.

The current Danish project on genetic markers and hydatidiform moles involves the examination of the histocompatibility between patient, spouse and molar tissue. For this purpose 2 techniques have been developed for HLA-A,B determination of molar tissue: (a) a cytotoxic microtechnique for the HLA typing of cultured molar cells, and (b) a microabsorption method using selected HLA antisera for the examination of frozen molar tissue. To date molar cell cultures or tissue have been examined in 22 of the cases. The results of HLA determination were compared with chromosomal markers to elucidate the origin of the haploid chromosome complements. In the cases examined a general agreement between the HLA-A,B type and the origin of the chromosomes was observed. The microabsorption method used seems to be less sensitive than the cytotoxic technique.

Cytotoxicity Tests, Immunologic↗

Tubular ultrastructure in acute renal failure in man: epithelial necrosis and regeneration.

It is not clear whether tubular cell necrosis is present or not in acute renal failure (ARF) of ischaemic type ("acute tubular necrosis"). In order to get quantitative data, using precisely defined criteria for tubular cell necrosis, 25 renal biopsies from 24 patients with ARF (11 obtained in the active phase, 14 in the early recovery period) were compared with 12 control biopsies. In all 1959 proximal cells and 1603 distal cells were analysed by electron microscopy. Cellular disintegration was very rare in all groups. Shrinkage necrosis (apoptosis) was not present in the proximal tubules of the controls and was rare in ARF (1.6-2.1%). In the distal tubules of controls 2.7% of all cells showed shrinkage necrosis. The incidence in ARF was not significantly increased. "Non-replacement sites" in distal tubules (probably loci where cells have recently been desquamated) were significantly increased in number (5.2%) in the active phase in ARF compared to controls and recovery. The relative number of regenerating cells was not increased. These data show that there is no widespread necrosis of tubular cells in ARF. The increased incidence in distal tubules of focal, denuded areas of the basement membrane in the active phase of ARF indicates a slightly increased desquamation of cells and/or a failure to cover such sites by adjacent cells. This process is not restricted to the brief induction phase of ARF but continues during the whole active phase.

Acute Kidney Injury↗

Tubular ultrastructure in acute renal failure: alterations of cellular surfaces (brush-border and basolateral infoldings).

Using a blind, semiquantitative technique, the degree of reduction of proximal tubular brush border (BB) and proximal and distal basolateral infoldings (BI) were measured in 25 renal biopsies from patients with acute renal failure (ARF) of ischaemic type. For comparison 12 biopsies from patients without ARF were studied, 6 were normal controls, six were from patients with minor change disease and slight glomerulonephritis. The mean scores for reduction of BB as well as proximal and distal BI were strongly increased in ARF compared to controls and the differences were highly significant. Some of the biopsies were taken during recovery and there was a significant negative correlation between the individual scores for reduction of BB and BI and simultaneous renal function. The disappearance of BB microvilli was correlated to tubular dilatation, but it could not be explained exclusively by "stretching" of the luminal surface due to dilatation. There was no correlation between reduction of BI and tubular dilatation. The data indicate a disturbance of cell membrane turnover in the active phase of ARF, possibly due to decreased synthesis, and they are consistent with a pathogenetic hypothesis implicating a decreased proximal Na+ resorption and consequently a pre-glomerular vasoconstriction.

Acute Kidney Injury↗

Postbinding defects of insulin action in human adipocytes from uremic patients.

It is now well established that longstanding human uremia is associated with impaired in vivo insulin action on glucose utilization of peripheral target tissues. In an attempt to define the cellular basis of the uremic insulin resistance we studied insulin action in adipocytes from eight patients with undialyzed chronic uremia and from eight matched healthy controls. (125I)-Insulin binding to fat cells from uremic patients was normal. In contrast (14C)-D-glucose transport exhibited decreased sensitivity to insulin. The concentrations of insulin that elicited half-maximal response was 422 +/- 95 pmoles/liter in uremic patients and 179 +/- 38 pmoles/liter in normal subjects (P less than 0.01). The noninsulin- and the maximal insulin-stimulated glucose transport of adipocytes from uremic patients with normal. (14C)-D-glucose conversion to total lipids was also measured in these cells in the absence and presence of various insulin concentrations. Similar to the findings in transport studies the lipogenesis of fat cells from uremic patients had depressed sensitivity to insulin (half-maximal stimulation at 38 +/- 8 pmoles/liter in uremic patients and at 11 +/- 3 pmoles/liter in normal subjects, P less than 0.01) with unchanged noninsulin and maximal insulin-stimulated lipogenesis. Taken together these results suggest that the insulin resistance of adipocytes from patients with chronic uremia may be accounted for primarily by postbinding defects localized to glucose transport and metabolism.

Adipose Tissue↗

End-state renal failure in diabetic nephropathy: pathophysiology and treatment.

Forty percent of patients with insulin-dependent diabetes will develop nephropathy during the course of their disease, thus being the most important single disorder leading to end-stage renal failure (ESRF). Intensive metabolic control delays onset of diabetic nephropathy, the first omen of which is appearance of subclinical albuminuria, also termed microalbuminuria. Moreover, it is now established that intensive treatment of hypertension reduces rate of decline in GFR and thus postpones ESRF. When uremia eventually sets in, a range of biochemical and endocrine abnormalities can be included among those characteristics of diabetes mellitus per se. These include elevated plasma levels of growth hormone, glucagon and free fatty acids, which may participate in the uremic insulin resistance superimposed on the preexisting diabetic carbohydrate intolerance. Hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) are two established modalities of renal replacement therapy in diabetes mellitus. Controlled clinical trials for comparison of CAPD versus HD treatment of diabetics are, however, still needed. The survival rate is approximately 80 and 65-95% in insulin-dependent diabetic patients at 1 year during treatment with HD and CAPD, respectively. However, it is general experience that diabetics on CAPD exhibit a glycemic control, superior to that attained during HD. It has not been proved that patient survival after cadaveric renal transplantation is better than on dialysis. The degree of vascular heart disease seems to be the major determinant for survival of kidney-transplanted diabetic patients.

Adult↗