Biomedical subjects
Publications and source records attributed to H E Hansen.
In our view, renal transplantation in the uremic diabetic patient is justified. Recipients should be selected with caution. Patients with both loss of vision and heart disease will only rarely benefit from renal transplantation. Living related donor should be preferred if possible.
One-hundred and ten patients treated with lithium for more than six months were studied in order to determine the prevalence of lithium induced nephropathy. Eighteen of 69 patients (26 per cent) who had been treated for more than two years presented a chronic interstitial nephropathy characterized by a marked decrease in renal concentrating ability with a disproportionate preservation of glomerular filtration rate. Histologically, increased amounts of fibrotic tissue in the medulla and the cortex were found together with tubular atrophy. In 40 per cent of the patients who underwent renal biopsy, cystic formations in the cortex were found. The impairment of renal concentrating ability could be related to the duration of lithium treatment and the degree of tubular damage correlated with the degree of impairment of renal concentrating ability. Lithium induced, chronic nephropathy is a rather common complication of long-term lithium treatment and reduces the patients capacity to regulate water and electrolyte metabolism. As water and electrolyte loss appears to precede the slowly progressing lithium intoxication, the main hazard of lithium induced nephropathy is lithium intoxication.
In our hospital, we are studying the renal function of more than 200 patients under lithium treatment. The glomerular function seems to be affected to a small extent, even by long-term lithium administration, and there have been no instances of progressive deterioration of renal function with azotemia. Most of the patients have impaired water reabsorption with polyuria and polydipsia. This is frequently combined with lowered concentrating ability. Polyuria and lowered concentrating ability are not in themselves life-threatening. However, development of dehydration may lead to lithium poisoning, and patients under lithium treatment should be advised to drink extra fluid under circumstances when the fluid balance may become negative. Further studies are required for definitive recommendations concerning extra monitoring of kidney function and lowering of lithium doses.
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The pharmacokinetics of furosemide 40 mg i.v. were compared in 7 anephric patients and in 7 normal subjects. The average serum clearance was 66 ml/min in the patients and 219 ml/min in the normal subjects, and the corresponding weight corrected clearances were 1.33 ml/min . kg and 2.96 ml/min . kg. Binding to serum proteins was significantly decreased in the anephric subjects, in whom a significant negative correlation was found between the percentage binding and the volume of distribution VDSS. In the patients, but not in the normal subjects, there was a significant positive correlation between VDSS and serum clearance. Both in normal and anephric individuals 4-chlor-5-sulphamoyl-anthranilic-acid (CSA) was found, but there was no evidence of special accumulation either of CSA or anthranilic acid in the anephric patients. In the patients the initial increase in serum concentration of sodium and protein followed by a more conspicuous decrease were more pronounced, but none of the changes were statistically significant.
The excretional patterns of lactate, pyruvate and alpha-ketoglutarate were investigated after renal transplantation in 36 patients. Fourteen patients had received a living-donor kidney with short ischemia time and good initial graft function, 22 had a cadaver transplant with an initial 125iothalamate clearance of more than 6 ml/min. The excretion of lactate and pyruvate did not vary significantly from that seen in normal controls or patients with uremia. In six patients with cadaver transplants, clearance values of alpha-ketoglutarate exceeded that of the glomerular filtration rate, indicating a net tubular secretion of this substance. During acute rejection episodes in 5 patients, no changes were seen in the excretional patterns of lactate, pyruvate and alpha-ketoglutarate.
A pair of chimeric twins, T.S. (male) and M.R. (female) first examined in 1970 are reinvestigated in order to determine if the proportions of admixture of red cells in their blood are unchanged, and if erythrocytes and leukocytes show the same percentage of admixture. T.S., M.R. and their family are investigated for HLA, serum types, and erythrocyte antigens and enzymes. A quantitative determination of 'foreign' cell populations in the blood of each twin is attempted for the systems ABO, and HLA, and for sex chromosomes in PHA stimulated lymphocytes. The results for the ABO system obtained by agglutination technique and by a double-layer immunofluorescence technique indicate that the population of M.R. erythrocytes in T.S. has decreased during the 7-year period, and is now below half the size found in 1970. Erythrocytes and leukocytes show the same percentage of admixture in both twins.
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Twenty-three patients were studied, 21 of whom developed intoxication during maintenance therapy with a lithium dosage which had been unchanged for months to years. Toxic effects on brain, heart and kidneys were found and the severity of lithium intoxication seemed to depend on at least three factors: the height of the serum lithium concentration (SLi), the duration of lithium intoxication and individual tolerance. Disorders of water and electrolyte metabolism preceded lithium intoxication in the majority of the patients. Water loss due to impaired renal concentrating ability seemed to be a major predisposing factor. Renal insufficiency was apparent in 17 of the patients on admission and five of these did not regain normal renal function. In seven patients, renal biopsy showed abnormalities which suggest that a chronic nephropathy, possibly caused by lithium, might be another predisposing factor. Treatment with sodium chloride infusion had no specific effect on lithium excretion and led to hypernatraemia in some patients and is therefore not recommended. Hemodialysis is the most effective method available for removing the lithium ion from intoxicated patients. Hemodialysis should be carried out long enough to secure a SLi of less than 1 mmol/l after redistribution of lithium in the body. Treatment by peritoneal dialysis is appropriate only if hemodialysis facilities are unavailable. Lithium intoxication is a serious condition. Of the 23 patients reported, two died and two developed persisting neurological sequelae. The best way to prevent lithium intoxication is to control the serum concentration and to assess renal function and renal concentrating ability regularly during therapy.
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The excretional patterns of lactate, pyruvate and alpha-ketoglutarate have been investigated in 7 patients with terminal uremia and in 10 kidney donors with normal renal function before and after unilateral nephrectomy. Methods for analysis of the three substances in urine were elaborated. In all patients, the levels of renal excretion of lactate and pyruvate were very low, and clearance values were independent of the glomerular filtration rate (GFR). alpha-ketoglutarate clearance varied to some extent with renal function, but no correlation to GFR was found, and exceeded the GFR in uremic patients, indicating that the net result of renal handling of alpha-ketoglutarate may be a tubular secretion.
The effect of 1alpha-hydroxyvitamin D3 (1alpha-OHD3) on parathyroid function was studied in sixteen patients (ten on haemodialysis, six with chronic renal insufficiency) during treatment for 6--8 months. During treatment, a decrease in serum parathyroid hormone (s-PTH) and an increase in serum calcium were seen. An inverse linear correlation was found between serum calcium and logarithmic values of s-PTH in fifteen of sixteen patients, but the slopes of the regression lines varied considerably. This indicates that the suppression of parathyroid function seen during treatment with 1alpha-OHD3 is mediated by a rise in the serum concentration of calcium. For normalization of s-PTH, the serum concentration of calcium had to be above normal range in several patients, indicating a defect in calcium-mediated regulation of the secretion of parathyroid hormone. This abnormality was seen especially in long-term haemodialysed patients.
A pair of dizygotic twins of opposite sex were incidentally found to be erythrocyte chimeras. The chimerism was found to include the lymphocyte population as well, since the twins differed for the maternal while sharing one paternal HLA haplotype. In addition to lymphocytes carrying antigens controlled by the inherited maternal haplotype, each of the twins had a small fraction--about 15%--of lymphocytes of the other twin's type. Both twins are healthy and have normal children. Investigations of the family by mixed lymphocyte culture (MLC) and cell-mediated lympholysis (CML) tests showed that the two haplotypes by which the twins differed carried different HLA-D determinants; even so the lymphocytes of each twin were completely nonresponsive in MLC and CML to those of the other twin. No 'blocking' factors could be demonstrated in the serum of the twins. These results support Burnet's theory of clonal selection in fetal life.
The question as to whether the distribution of HLA antigens differs between old and young persons has been studied only in a few population groups. There are observations showing an increase of heterozygosity of the HLA system (Bender et al. 1973, Gerkins et al. 1974) which indicate an advantage of heterozygosity for survival, but other studies fail to confirm this finding )Albert et al. 1974, Mucurová et al. 1975, Bender et al. 1976). Since the present authors, in a study of HLA gene frequencies on five small Danish islands (Hansen et al. 1974) had found a tendency to a changed frequency of certain HLA types among the oldest persons, it was decided to examine this question by typing larger numbers of persons of different age groups.
In 64 patients who had undergone renal transplantation, later on followed by bilateral nephrectomy, bacterial growth culture was performed from the original kidneys. The presence of bacteria in the nephrectomy specimens was compared with the occurrence of significant bacteriuria before transplantation and in the period between transplantation and nephrectomy. Bacteria could be cultured from the nephrectomy specimens of 18 (28.1 per cent) of the patients, almost exclusively confined to cases of obstructive chronic pyelonephritis, analgesic nephropathy and congenital renal disease. Before transplantation, bacteriuria had been recorded in 34.4 per cent of the patients, most frequently in the three groups of diseases just mentioned. Between the transplantation and nephrectomy, bacteriuria occurred in 75.0 per cent of the patients. Patients with E. coliuria before transplantation were particularly liable to have E. coliuria also after the transplantation and to E. coli in the nephrectomy specimens, whereas patients in whon E. coliuria did not occur until in the post-transplantation period were less susceptible to E. coli infection involving the kidneys. Probably the presence of bacteria in the nephrectomy specimens is related to the primary disease rather than to immunosuppressive and antiobiotic agents administered in the post-transplantation period.
The authors scored the examination performance of 28 psychiatrists who were tested after conducting an interview with a real patient and after seeing a videotaped interview with an actor playing the role of either a psychotic or a neurotic patient. The also scored the performance of 15 of the same examinees who completed a written examination. Eighty-five percent of the examinees reported that the videotaped interview examination was a useful learning experience, and 81% said that it was a useful testing experience. The examiners' feelings varied regarding the use of the standardized videotaped format for certification and recertification of psychiatrists.
The object of this study has been to evaluate the recipient's immunological reactivity towards donor lymphocytes in relation to rejection episodes. All recipients (20) of local necrokidneys during 1976 were immunologically monitored immediately before transplantation and subsequently twice weekly for donor-specific complement dependent lymphocytotoxic (CDC) antibodies, antibody dependent cell-mediated cytotoxicity (ADCC) and cell-mediated lympholysis (CML). Experiments were performed until graft removal or dismissal (approx. 1100 patient days). Clinical diagnosis of rejection was made independently of immunological results. All clinically suspected rejection episodes, except one, were checked by microscopy. A positive CML-test accompanied 9 out of 11 rejection episodes; the test was negative on all other occasions. Positive CDC and ADCC tests exhibited no obvious correlation with rejection episodes: positive ADCC may be more frequent in clinically uncomplicated phases. Positive CML did not generally precede clinical graft rejection. Positive CML before transplantation was observed in two cases and was followed by irreversible, accelerated acute rejections. The CML-test may prove a reliable tool in rejection diagnosis and may yield results comparable with graft biopsy without inflicting any risk on the patient.