Biomedical subjects
Publications and source records attributed to J Sølling.
The recurrence of the hemolytic uremic syndrome (HUS) in a renal transplant patient during pregnancy and during treatment with cyclosporin is reported. After 4 1/2 months of treatment with hemodialysis the renal function partially recovered. A monozygote twin sister has not developed HUS in spite of 2 pregnancies.
Non-dietary, non-pharmacological reduction of cholesterol in patients with severe hypercholesterolemia can be obtained by partial ileal by-pass, portacaval shunt operation or liver transplantation. A non-surgical method is apheresis, by which low density and very low density lipoproteins are removed from blood in an extracorporal circulation system. Apheresis methods include plasmapheresis, immunoadsorption, chemical affinity and Double Membrane Filtration. Treatment of a 30 year old man with severe familial hypercholesterolemia and ischaemic heart disease, by LDL-apheresis, resulted in an average decline in serum-cholesterol of 35%. LDL-apheresis is indicated in the treatment of this type of patient and in homozygous familial hypercholesterolemia.
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The effect on glomerular filtration rate (GFR), renal plasma flow (RPF) and excretion of albumin and beta-2-microglobulin in the urine after a high oral protein or amino acid load was investigated in young healthy males. After both test meals an increase in GFR of 10%, and in RPF of about 9-18%, was seen. The filtration fraction and albumin excretion rates were unchanged. The increase in GFR was significant from 20 to 60 min after intake of meat and remained elevated for more than 2 h. After the meat meal, a decrease in renal vascular resistance and an increase in S-creatinine, S-phosphate, S-carbamide and beta-2-microglobulin excretion rates was seen, but not after the amino acid load. During the experiments a gradual decrease in S-protein was noted. We conclude that the increase in RPF and GFR caused by intake of protein or amino acids in short-term experiments is not associated with impaired permselective properties of the glomerular membrane expressed in the albumin excretion rate.
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The polymeric forms of Bence Jones protein (BJ) in serum and the influence on renal function were investigated in 59 patients with multiple myeloma and 2 with Waldenström's macroglobulinemia. Eight of 35 patients with kappa and 26 with lambda type BJ protein had decreased renal function. The investigation showed a considerable variation between patients in serum concentrations of tetrameric (T), dimeric (D) and monomeric (M) forms of BJ protein. A significantly higher fraction of D forms of BJ protein resulting in a high D/M ratio was found in the myeloma patients compared with polyclonal light chains in 10 normal controls. The renal function in multiple myeloma was, however, not correlated to the D/M ratio or to the BJ protein tetramers. This suggests that the nephrotoxicity of BJ proteins is not associated with polymerization of BJ proteins in serum. BJ proteins of aberrant size were found in 3 patients with rapidly decreasing renal function. Histological investigation in 2 of these patients revealed nodular glomerulosclerosis.
Sera from 8 patients with IgA glomerulonephritis and from 6 patients with Schönlein-Henoch nephritis were investigated by the C1q-binding assay (C1q-BA) test and by sucrose gradient centrifugation followed by sensitive solid phase radioimmunoassay determinations of IgA, IgG and IgM in each fraction obtained. Abnormal sedimentation profiles were found in sera from 3 of 8 patients with IgA nephritis and in 3 of 6 patients with Schönlein-Henoch nephritis. The abnormal fraction consisted of low molecular weight IgA in 2 patients, IgG in 1 patient and IgM in 4 patients. The absolute level of polymeric IgA was increased in 3 of 8 patients with IgA nephritis, but the relative distribution was normal. An abnormal sedimentation pattern of immunoglobulins was correlated to a positive C1q-BA test (p less than 0.001).
Circulating immune complexes (CIC) and the complement breakdown product C3d were measured in 81 patients with glomerulonephritis (GN), 28 patients with early and 25 patients with long-term renal transplants. CIC were measured by a Clq-binding assay and C3d by a double-decker rocket immunoelectrophoresis. In patients with GN, CIC were detected in 19 and elevated C3d levels found in 45 patients. The highest levels of C3d were found in patients with membranoproliferative GN type I and II, diffuse sclerosing GN and GN secondary to SLE and Wegener's granulomatosis. No relationship was found between CIC and C3d, and the combination of CIC with C3d measurements did not help to characterize 'nephritogenic' CIC. C3d was frequently elevated in patients with impaired renal function which may reflect an inflammatory 'nephritic' process, but may also be due to a reduced renal elimination. Furthermore C3d was frequently elevated in patients with improving or decreasing renal function, and in patients with heavy proteinuria. Longitudinal studies of renal transplant patients suggested that immunosuppressive treatment decreased the C3d level. Patients with early renal transplants had elevated C3d levels that normalized during the first month after successful transplantation. CIC and elevated C3d were not related to onset of acute rejection episodes in early transplant patients nor to late renal graft failure.
Eighteen patients with pre-eclampsia, 10 patients with essential and 9 with transient hypertension during pregnancy, were investigated regarding circulating immune complexes by a Clq-binding assay and a PEG precipitation assay. The women were studied during pregnancy, 2 and 5 days after childbirth, and also 3 and 6 months afterwards. The frequency of circulating immune complexes was not significantly increased in any of the groups when compared with that in 18 normotensive pregnant control subjects and 19 non-pregnant controls. Thus Clq-binding and PEG-precipitable immune complexes are a feature neither of normal pregnancy, nor of pregnancy complicated by hypertension or pre-eclampsia.
Total haemolytic complement activity, C2, C5, total alternative pathway activity, factor B, and C3d were measured in 85 splenectomized patients from 1 month to 32 years after splenectomy. Furthermore the patients were investigated for circulating immune complexes. No major deficiencies of the complement factors were detected. In a few patients a reduced C2 level was caused by genetically determined defects or was due to complement consumption in conjunction with circulating immune complexes. The complement levels were normal in 2 patients who had survived overwhelming infections after splenectomy. C5 was elevated in a major proportion of the patients, and it is suggested that this might be caused by post-splenectomy monocytosis. Circulating immune complexes were found in 20% of all cases, irrespective of the presence of residual splenic tissue. Thus the commonly cited impairment of the complement system after splenectomy does not seem to be substantiated, and the deficient resistance against bacterial infections in splenectomized patients does not seem to include abnormalities of the complement system.
A longitudinal study of circulating immune complexes (CIC) was performed in 121 patients with biopsy verified glomerulonephritis (GN). 1286 blood samples were obtained during a mean observation period of 21 months. Two methods for detection of CIC were used, the Clq-binding activity and a PEG precipitation test. CIC were detected by both tests in 21% of all blood samples and detected in at least one blood sample from 57 patients. The presence of CIC was found to be either transient (34 patients), intermittent (11 patients) or permanent (12 patients). CIC were found transiently at the time of renal biopsy and disappeared within months in patients with idiopathic extracapillary GN (7 of 9 patients), endocapillary GN (2/2) and GN associated with polyarteritis nodosa (5/6), Wegener's granulomatosis (3/3) and Henoch-Schoenlein syndrome (3/6). CIC were detected either transiently, intermittently or permanently for years after renal biopsy in patients with SLE (12/14) and membranoproliferative GN type I (7/12). CIC were only occasionally detected in patients with minor change nephropathy (1/9), membranoproliferative GN type II (0/2), IgA nephropathy (6/17), focal segmental sclerosis (1/8) and membranous GN (2/11). In these patients CIC were often transiently present without apparent relationship to time since renal biopsy. Overall, a relationship was found between the presence of CIC and decreasing serum creatinine, but there was no correlation with changes in proteinuria or with increasing blood pressure. Serial measurements of CIC showed correlations with clinical events only in individual patients, but not in the population as a whole.
Circulating immune complexes (CIC) were found in 12% of sera from 56 patients before renal allotransplantation. No relationship was found between the presence of CIC before transplantation and the 6 months graft survival. CIC were detected in serial blood samples obtained from 8 out of 30 patients (27%) during the first 6 weeks after transplantation. No relationship was found between CIC and acute rejection episodes. In 3 patients CIC were associated with acute infections. Thus the appearance of CIC shortly after renal transplantation may be an indicator of infection rather than rejection. CIC were detected in 32% of 50 renal transplant recipients who had functioning grafts for more than one year. No association was found between CIC and decreasing graft function, blood pressure or the recipient's original disease. CIC were frequently detected in patients with proteinuria above 3 g/24 hr suggesting a role of CIC in some cases of late renal graft failure.
Circulating immune complexes (CIC) were detected in 8 of 15 patients with fever due to non-renal infections. Elevated urinary albuMin and beta-2-microglobulin excretion rates were found during the febrile period compared to the levels two days after normalization of the temperature. No relationship could be demonstrated between CIC and the excretion rates of albumin and beta-2-microglobulin or the albumin/beta-2-microglobulin ratio. Thus we have not been able to confirm the hypothesis that the glomerular type of proteinuria is caused by immune complexes.
The serum concentration of free kappa and lambda light chains of immunoglobulins were measured in 114 patients with myelo- and lymphoproliferative disorders including multiple myeloma. Increased concentrations of a single light chain type, suggesting monoclonal origin, were found with high frequency in B-cell diseases only. Thus 6 out of 9 patients with chronic lymphatic leukaemia and 24 of 28 patients with multiple myeloma had increased concentrations of a single chain type. The highest values reported in chronic lymphatic leukaemia were approximately 10 and in multiple myeloma 1000 times normal mean. Cytostatic treatment of chronic lymphatic leukaemia was followed by a decrease in the light chain levels. The levels were, however, not correlated to the number of circulating lymphocytes, the lymphatic infiltration of tissue or clinical activity. Increased concentrations of both chain types, suggesting a polyclonal origin, were found in both of 2 patients with acute monocytic leukaemia, 6 of 7 with acute myelomonocytic leukaemia, 2 of 23 with acute myeloid leukaemia and 1 of 7 with acute lymphoblastic leukaemia. The highest levels of light chains in these groups were 5 times normal mean. All patients with myeloproliferative disorders revealed normal values of both light chain types.
Immune complexes in serum, urinary excretion of albumin and beta-2-microglobulin were determined in patients with infectious mononucleosis, both during the acute stage of the disease and one month later. At the first examination immune complexes were detected in 8 out of 12 patients, using both the ClqBA and the PP-Lc methods, but had disappeared in all after one month. Urinary excretion was initially increased for albumin in one of 9 and for beta-2-microglobulin in 5 of 9 patients. A significant fall in excretion was noted for beta-2-microglobulin during the acute phase (0.486 to 0.190 ng/min (medians), p less than 0.01) whereas albumin excretion did not change significantly (9.0 to 4.0 micrograms/min). Excretions were normal in all patients after one month. The magnitude of proteinuria was not correlated to the serum level of immune complexes. Serum beta-2-microglobulin was initially increased in 8 of 9 patients, but normal after one month (3.8 to 2.2 mg/l, p less than 0.01). There was a significant correlation between levels of beta-2-microglobulin in serum and urine (rho = 0.833, n = 9, p less than 0.01). 51Cr-EDTA clearance was the same during the acute illness and one month later. It is concluded that the abnormalities in urinary protein excretion do not seem to be related to the presence of circulating immune complexes in infectious mononucleosis and that the elevated urinary beta-2-microglobulin excretion is most likely due to increase production.
The Clq-binding test was used to detect circulating immune complexes in 86 patients with glomerulonephritis at the time of renal biopsy. By gel filtration of the sera it was possible to estimate the molecular weight in 24 of these patients. The molecular weight of circulating immune complexes varied from 150,000 to above 1.2 X 10(6) and was not related to the type of glomerulonephritis as defined by light microscopy, renal function, proteinuria, hematuria or antecedent infections. In 8 patients with rheumatoid arthritis and in 5 patients with secondary syphilis and no evidence or renal disease, only circulating immune complexes with a molecular weight below 1.2 X 10(6) were detected. 7 patients with glomerulonephritis had electron-dense deposits in glomeruli on electron microscopy, but the molecular weight of circulating immune complexes was not related to the site of the deposits on either side of the basement membrane.
Circulating immune complexes (CIC) were detected in one of 11 patients with primary syphilis and in 5 of 12 patients with secondary syphilis. The level of CIC was significantly increased in patients with secondary syphilis. Four weeks later a significant decline in CIC was found. No relationship was demonstrated between CIC and affection of the skin, lymph nodes, or kidneys. An increased albumin excretion rate was demonstrated before treatment. No differences were found in the excretion rate of beta-2-microglobulin before or after treatment. Nineteen patients had a Jarisch-Herxheimer reaction during treatment. An increase in CIC was found in 5 patients and a decrease in 7 patients. No correlation could be demonstrated between the level of or changes in CIC and the severity of the Jarisch-Herxheimer reaction.
The relationship between circulating immune complexes (CIC), serum angiotensin-converting enzyme (SACE) and clinical features was investigated in 119 patients with sarcoidosis. CIC, measured by the C1q-binding test and a polyethylene glycol precipitation test, were detected in 42% of the patients. A significantly higher level of CIC was found in patients with duration of the disease of more than 2 years and in patients in stage II or III on chest X-ray. SACE was increased in 45% of the patients, most frequently in those with active disease and in those in stage II or III on chest X-ray. No positive correlation was found between CIC and elevated levels of SACE.