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Biomedical subjects

H Thysell

Publications and source records attributed to H Thysell.

At least 19 recordsLinked to original sources

Preeclampsia is associated with a reduced response to activated protein C.

OBJECTIVE: Resistance to activated protein C is an inherited mutation of the coagulation factor V gene, a major factor predisposing to thromboembolic events. The purpose of this study was to investigate the occurrence of heterozygote and homozygote activated protein C resistance in women with preeclampsia. STUDY DESIGN: Activated protein C resistance and protein C and antithrombin III levels were determined in women (n = 50) with a history of preeclampsia and in controls (50 women with a previous normal pregnancy). The mutation of the factor V gene was analyzed. RESULTS: Activated protein C resistance was found in 22% of women with previous preeclampsia compared with 10% among controls. Two women in the previous preeclampsia group had a homozygote mutation of factor V; the others were heterozygous. There was a significant difference in the activated protein C ratio between women with previous preeclampsia and the control group, 2.6 +/- 0.4 versus 3.1 +/- 0.5 (p = 0.04). None of the women had protein C or antithrombin III deficiency. CONCLUSION: The results indicate that activated protein C resistance may be a contributory factor in the pathogenesis of preeclampsia.

Antithrombin III

Decreased excretion of urine glycosaminoglycans as marker in renal amyloidosis.

BACKGROUND: The diagnosis of renal amyloidosis is normally established by kidney biopsy. In order to advance the determination of the diagnosis and the initiation of the therapy, fast and cheap, non-invasive diagnostic techniques are required. METHODS: Urine excretion of glycosaminoglycans (GAG) was measured in 10 patients with AA amyloidosis and 5 patients with AL amyloidosis and compared to 25 controls with primary glomerular diseases and 22 healthy controls. The subjects with primary glomerular disease were matched with regard to their renal function and the degree of albuminuria. RESULTS: The median urine GAG to creatinine ratio and the median fractional GAG excretion were significantly decreased (P < 0.05) in both AA amyloidosis (0.21 mg/mmol and 0.053 respectively) and AL amyloidosis (0.33 mg/mmol and 0.077 respectively) compared to control patients with primary glomerular disease (1.73 mg/mmol and 0.336 respectively) and healthy controls (2.67 mg/mmol and 0.226 respectively). The urine GAG to creatinine ratio did not correlate to age, sex, serum creatinine, urine albumin, or to the plasma levels of acute phase proteins. CONCLUSIONS: The decreased GAG excretion in renal amyloidosis is probably caused both by diminished number of functioning nephrons, decreased GAG synthesis in functioning glomeruli, and the trapping of GAG by amyloid fibrils. Urinary GAG excretion may serve as an independent marker of renal amyloidosis. It may be used in diagnostic work-up of renal amyloidosis in patients with glomerular diseases and in screening of amyloidosis in patients with chronic inflammatory disorders, with or without signs of renal disease.

Adult

Generation of nitrate during dialysis as a measure of nitric oxide synthesis.

Nitric oxide (NO) is a recently identified messenger, which influences the local regulation of blood flow and platelets as well as neuronal and inflammatory pathways. Disturbed NO information might be involved in the uremic syndrome and might also cause hypotension during dialysis. To clarify these issues, we analyzed plasma and dialysis fluid concentrations of nitrate, the stable NO metabolite, in 9 patients during hemodialysis. Plasma nitrate was raised at the onset of dialysis as compared with healthy subjects (83 +/- 9 versus 26 +/- 2 mumol/L). The plasma concentration decreased to 20 +/- 2 mumol/L (p < 0.01) during the dialysis. The relative decrease was more pronounced than the relative reduction in creatinine, phosphate, and urea concentrations. A parallel decrease in nitrate was seen in effluent dialysis fluid (32 +/- 4 to 14 +/- 1 mumol/L; p < 0.01). Calculations of the amount of nitrate coming to and from the dialyzer were performed in 7 of the 9 patients, and in 5 of the 7 patients, generation of nitrate within the dialyzer could be postulated. This might explain the paradoxical venodilation noted during hemodialysis.

Aged

Beneficial effect of cold dialysate for the prevention of hemodialysis-induced hypoxia.

Hypoxia occurs frequently during routine hemodialysis (HD). In this study the effect of dialysate temperature on arterial blood gas parameters was investigated. Ten stable HD patients (2 smokers) were dialyzed for 240 min with each of three different dialysate temperatures: 36.5 degrees C (normal temperature HD; NHD), 38.5 degrees C (warm HD; WHD) and 34.5 degrees C (cold HD; CHD). A cuprophane plate dialyzer was used. The ultrafiltration volume was identical in each patient. Arterial blood gas samples were frequently (approximately 10 times/treatment) taken during the dialysis and immediately analyzed. The dialysate temperature significantly affected PaO2 (p < 0.001) but not PaCO2. We also compared the effect of NHD with that of WHD and CHD, respectively, as regards PaO2. NHD and WHD differed significantly p < 0.01), whereas NHD and CHD were not significantly different. However, the relative PaO2 value (% of the baseline value) at the end of CHD (105 +/- 5%) was significantly higher than after both NHD (96 +/- 4%, p < 0.01) and WHD (91 +/- 3%, p < 0.01). In the case of NHD and WHD the fraction of time during which the patients had a PaO2 value below 80 mm Hg was 62 and 64%, respectively. The corresponding figure for CHD was 44%. Arterial oxygen saturation (SaO2) increased during CHD from 95.2 +/- 0.6 to 96.7 +/- 0.6% (p < 0.05), while SaO2 was unchanged during NHD and WHD. The positive effect of CHD was evident in 7 patients. In 1 patient PaO2 was not affected by the dialysate temperature, while in the remaining 2 patients (smokers) a decrease in PaO2 was induced by WHD as well as CHD. A separate statistical analysis with the 2 smokers excluded was performed, which showed that the dialysate temperature significantly affected PaO2 (p < 0.001). A comparison between NHD and CHD showed a significant difference (p < 0.001), whereas NHD and WHD did not differ significantly. When the 2 smokers were excluded from the analysis the fraction of time with a PaO2 value below 80 mm Hg was 60% during NHD and 56% during WHD, but it was reduced to 31% during CHD. In conclusion, despite the existence of interindividual variations most patients seemed to benefit from cold dialysate for the prevention of dialysis-induced hypoxia.

Adult

Long-term stability of albumin, protein HC, immunoglobulin G, kappa- and lambda-chain-immunoreactivity, orosomucoid and alpha 1-antitrypsin in urine stored at -20 degrees C.

The stability of albumin, protein HC, immunoglobulin G, kappa- and lambda-chain immunoreactivity, orosomucoid and alpha 1-antitrypsin in urine stored at -20 degrees C for up to 24 months was investigated. Significant decreases of the median concentration values for protein HC, IgG and alpha 1-antitrypsin were observed for native urine. Addition to urine of a preservative solution containing benzamidinium chloride, EDTA, tris(hydroxymethyl)-aminomethane and azide prevented the decreases of the concentration values for protein HC and IgG but not for alpha 1-antitrypsin. The median concentration values for albumin, orosomucoid and kappa- and lambda-chain immunoreactivity did not change significantly upon storage of native urine, nor for urine with the preservative solution.

Albuminuria

Hyperhomocysteinemia in cyclosporine-treated renal transplant recipients.

Moderate hyperhomocysteinemia, an independent cardiovascular risk factor, has been reported in renal transplant recipients. In the present study, plasma concentrations of total homocysteine were significantly increased in 120 renal transplant recipients as compared with 60 healthy controls (19.0 +/- 6.9 vs. 11.6 +/- 2.8 mumol/L, P < 0.0001) and as compared with 53 patients without a transplant but with a comparable degree of renal failure (19.0 +/- 6.9 vs. 16.0 4.9 mumol/L, P < 0.01). There was a significant inverse correlation between glomerular filtration rates and plasma homocysteine concentrations in the renal transplant recipients (r = -0.52, P < 0.0001). Groups of renal transplant recipients, with and without cyclosporine, and renal patients without a transplant were studied; these groups were comparable regarding age, sex distribution, glomerular filtration rate, and folate and vitamin B12 concentrations. Renal transplant recipients on cyclosporine had significantly higher plasma homocysteine concentrations than those not on cyclosporine (19.5 +/- 7.6 vs. 16.2 +/- 4.8 mumol/L, P < 0.05), and the patients without a transplant (19.5 +/- 7.6 vs. 16.0 +/- 4.9 mumol/L, P < 0.01). Thus, the hyperhomocysteinemia of renal transplant recipients not treated with cyclosporine, and that of renal patients without a transplant probably is explained by the same mechanism: renal insufficiency. An additional mechanism seems to operate in renal transplant recipients treated with cyclosporine. The lack of correlation between the concentrations of plasma homocysteine and red cell folate in these patients suggests that cyclosporine interferes with folate-assisted remethylation of homocysteine. Plasma homocysteine concentrations were significantly increased in 24 patients with a history of atherosclerotic complications as compared with the remaining 96 renal transplant recipients (20.8 +/- 4.4 vs. 18.5 +/- 7.3 mumol/L, P < 0.01).

Adult

The effect of reduced glomerular filtration rate on plasma total homocysteine concentration.

The concentration of homocysteine in plasma has been shown to be increased in renal failure, possibly contributing to the accelerated atherosclerosis observed in uraemic patients. The aim of the present study was to document the relationship between plasma total homocysteine (tHcy) concentrations and glomerular filtration rates (GFR) in highly selected patients, with renal function ranging from normal to dialysis dependency. GFR was defined as the plasma clearance of iohexol; a more accurate method than the creatinine-based estimations applied in previous studies. Plasma tHcy concentrations were highly correlated to GFR (r = -0.70, p < 0.0001) and were significantly increased already in moderate renal failure. According to a multiple regression analysis, GFR and red cell folate concentrations independently predicted plasma tHcy concentrations, whereas those of serum creatinine, plasma pyridoxal-5-phosphate, urine albumin and urine alpha-1-microglobulin (a marker of tubular damage) did not. Thus, GFR seems to be a better determinant of plasma tHcy concentration than serum creatinine concentration. Plasma total cysteine and total cysteinylglycine concentrations followed the same pattern as those of tHcy.

Adult

Analysis of proteinuria: reference limits for urine excretion of albumin, protein HC, immunoglobulin G, kappa- and lambda-immunoreactivity, orosomucoid and alpha 1-antitrypsin.

Efficient use of assessment of urine protein excretion in nephrological practice requires adequate reference intervals. To determine the upper reference limits of urine albumin, protein HC (alpha 1-microglobulin, immunoglobulin G (IgG), orosomucoid (alpha 1-acid glycoprotein, alpha 1-antitrypsin, and kappa- and lambda-chain immunoreactivities, the concentrations of these proteins were measured in urine samples from 95 healthy, adult individuals, using rapid, generally available methods and with conditions for urine collection which secured stable protein levels. The obtained values were expressed in mg 1(-1), as the urine protein-creatinine index and as fractional protein-creatinine clearance. No differences were found between the upper reference limits in the first voided morning urine samples and the randomly collected urine samples, nor between the upper reference limits in urine samples collected from males and females. The urinary excretion of the tested proteins did not correlate to age, positive dipsticks for haematuria nor to granular casts in urine sediment. Thus, the same upper reference limits can be used for both sexes and regardless of the type of urine collection. The upper reference limits of urine protein-creatinine index found in this study were: for albumin, 3.8 mg mmol(-1); for protein HC, 0.7 mg mmol; for IgG, 0.8 mg mmol(-1); for orosomucoid, 0.7 mg mmol(-1); for alpha 1-antitrypsin, 0.2 mg mmol(-1), and for kappa-immunoreactivity 0.7 mg mmol(-1). The upper reference limit for lambda-immunoreactivity was below the detection limit.

Adult

C4 phenotypes in IgA nephropathy: disease progression associated with C4A deficiency but not with C4 isotype concentrations.

IgA nephropathy (IgAN) is a common glomerular disease and is thought to have an immunological origin which may involve complement-mediated pathogenic mechanisms. We performed C4 phenotyping and C4 isotype quantification in 93 IgAN patients in Southern Sweden. Phenotype frequencies did not deviate from those of healthy controls. However, three patients had homozygous C4A deficiency and these all belonged to a group of fifteen patients with end-stage renal failure (p < 0.0035). Progression to end-stage renal failure did not appear to be faster than in other IgAN patients. Both C4A and C4B concentrations were raised in the IgAN patients, but the C4A/C4B concentration ratios did not deviate from those of healthy controls. This indicated that heterozygosity for C4A or C4B deficiency or other reasons for the relatively low concentrations of the protein were not associated with disease susceptibility. There was no correlation between low C4A/C4B ratio and poor prognosis. In conclusion, the findings suggested that homozygous C4A deficiency predisposes to development of end-stage renal failure. The question if this is due to complement dysfunction or to linked genetic factors remains to be elucidated.

Adolescent

The effect of dialysis on radiocaesium in man.

Dialysis is used for cleaning the blood in patients with end-stage renal disease. The most common methods are hemodialysis (HD) and peritoneal dialysis (PD). Dialysis patients might constitute a critical group because of poor elimination of radioactive elements ingested. On the other hand dialysis may be a useful decontamination method for radioactivity. The effect of dialysis on the turnover of radiocaesium was studied in 10 HD patients and 4 PD patients. The dialysis fluid, which contains electrolytes and the metabolic waste products, was analyzed for radiocaesium. In this connection the patients were whole-body counted for radiocaesium and 40K. The results show that HD patients generally have a lower body burden of radiocaesium than normal subjects, while PD patients show normal levels. At steady state both dialysis methods eliminate slightly less radiocaesium than normal kidneys do, but in the case of HD during a much shorter time. The calculated effective half-life for radiocaesium was normal in the HD patients, and somewhat longer in the PD patients. Considering that HD is performed only for 12-15 h weekly, the elimination rate of radiocaesium by HD is much higher compared with that by normal kidneys. Thus, HD might constitute an important method for decontamination of radiocaesium after accidental internal contamination.

Body Burden

Hepatitis C superinfection in hepatitis C virus (HCV)-infected patients transplanted with an HCV-infected kidney.

Hepatitis C virus (HCV) genotypes, determined by polymerase chain reaction with type-specific primers, were studied in 5 already HCV-infected patients receiving kidneys from HCV-infected cadaver donors. Three patients were investigated retrospectively using stored pre- and posttransplantation sera and followed 18-28 months after transplantation. Two recipients with HCV genotype 2b infection had received kidneys from 1 genotype 3a-infected donor. In 1 recipient, HCV 2b was replaced by the donor's type; in the other recipient, a prolonged mixed infection of 3a and 2b occurred. Persistent alanine aminotransferase (ALT) elevation (3- to 5-fold) appeared in both patients. The third patient, also HCV 2b infected when transplanted with an HCV 3a-infected kidney, remained infected with HCV 2b only. Two patients, one with HCV genotype 1b and the other with genotype 3a, were followed prospectively with frequent bleeds (initially biweekly) and genotyping over 14 months after they had received kidneys from 1 HCV genotype 1a-infected donor. The HCV 1b-infected recipient remained infected with 1b only and had minimal biochemical signs of liver injury. In the other recipient, mixed infection of 3a and 1a appeared at week 3 and persisted for several weeks, until only genotype 1a could be detected. This patient had elevated ALT levels before transplantation. After onset of mixed infection, ALT levels increased further for several weeks, and returned to pretransplantation levels when only HCV 1a was found. HCV-infected kidneys transplanted into HCV-infected recipients gave 3 different virus patterns. Most patients benefitted in the short term, but some super-infected patients experienced increased liver damage.

Adult

Cytokines in childhood hemolytic uremic syndrome and thrombotic thrombocytopenic purpura.

Serum and urine cytokines were analyzed in children with hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP). Interleukin-6 (IL-6) was elevated in the serum of 33 of 35 children with HUS (94%) and in 2 of 2 children with recurrent TTP. Serum IL-6 was higher in children with HUS who developed anuria, extrarenal manifestations during the acute phase of illness and/or chronic renal sequelae. Tumor necrosis factor-alpha (TNF-alpha) was detected in the serum of 7 patients with HUS (20%) and 1 patient with TTP. IL-6 and TNF-alpha were elevated in the urine of 4 of 4 children with HUS and 2 of 2 children with TTP. Urinary levels were higher than serum levels, suggesting local production of cytokines in the urinary tract. Sequential serum and urine samples showed that IL-6 levels varied with disease activity. IL-6 and TNF-alpha were not detected in the serum (n = 25) and urine (n = 15) of healthy children. We conclude that IL-6 in urine may be used to monitor disease activity in HUS and TTP.

Adolescent

Circulating neuropeptide Y in plasma from uremic patients consists of multiple peptide fragments.

Increased plasma levels of neuropeptide Y (NPY)-like immunoreactivity (p-NPY-LI) have been described in hemodialysis (HD) patients. In this investigation the effect of a standard HD on p-NPY-LI, analyzed by radioimmunoassay and reverse-phase high performance liquid chromatography (HPLC), was studied. During dialysis p-NPY-LI increased from 128 +/- 5 to 154 +/- 8 pmol/l (p < 0.01). The change in p-NPY-LI during the treatment correlated with the ultrafiltration volume (rs = +0.72, p < 0.05). The HPLC separation revealed a complex pattern of NPY-immunoreactive peptides. This was true of the plasma of the control subjects as well as of the uremic plasma. In the case of the controls and the HD patients prior to dialysis, the amount of NPY-LI was rather small. After the dialysis qualitative as well as quantitative changes of the chromatogram were found. Some of the peaks seemed to have a retention time similar to that of the known fragments of synthetic human NPY used as markers. In conclusion, an increase in p-NPY-LI occurred during the dialysis, probably due to fluid removal. The increased level of NPY-LI in uremic plasma represents a mixture of different NPY fragments.

Aged

Evidence that reduced lipoprotein lipase activity is not a primary pathogenetic factor for hypertriglyceridemia in renal failure.

The aim of the study was to document postheparin plasma lipoprotein lipase (LPL) and hepatic lipase activities and relate these to serum lipid, lipoprotein and apolipoprotein concentrations in 85 patients with kidney function ranging from normal to dialysis dependency. Strict selection criteria were applied in order to exclude conditions other than renal failure which may influence lipid metabolism. Stress was laid on minimizing proteinuria and inflammatory activity. The changes in the lipoprotein pattern were numerically strikingly modest compared to those previously reported. This probably reflected the intention to elucidate the contribution of reduced renal function as such to the dyslipoproteinemia of renal failure, a condition often associated with confounding factors. Significant increases in serum concentrations of triglycerides and apolipoprotein CIII were already observed in moderate renal failure, whereas serum concentrations of high density lipoprotein cholesterol and plasma LPL activities were decreased only in severe renal failure. Plasma LPL activities were not significantly reduced in hemodialysis patients (probably due to anticoagulation with low molecular weight heparin), but serum concentrations of triglycerides and apolipoprotein CIII were significantly increased. A multiple regression analysis, taking glomerular filtration rate, LPL and apolipoprotein CIII into account, showed that both plasma LPL activity and serum apolipoprotein CIII concentration independently predicted serum triglyceride concentration. However, serum apolipoprotein CIII concentration was a much stronger predictor than plasma LPL activity. Thus, a decrease in LPL activity does not seem to be a prerequisite for the hypertriglyceridemia of uremia, but it probably accentuates this condition.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Dose regimen adjustment for milrinone in congestive heart failure patients with moderate and severe renal failure.

This study was designed to test a proposed dose modification for intravenous milrinone in congestive heart failure patients (CHF, NYHA I-II) with either moderate or severe renal impairment. All the patients were administered an intravenous loading dose of drug at 50 micrograms kg-1 over 10 min. This was followed by an 18 h maintenance infusion of milrinone at 0.45 or 0.35 micrograms kg-1 min-1 for the moderate (chromium-EDTA clearance of 31-75 mL min-1, n = 10) and severe renally impaired subjects (chromium-EDTA of clearance 10-30 mL min-1, n = 11), respectively. Plasma and urine samples were collected for up to 34 h and analysed for parent drug by validated HPLC methods. The mean (+/- s.d.) steady-state plasma concentrations of milrinone were within the therapeutic range (100-300 ng mL-1) for both groups, with values of 239 +/- 71 ng mL-1 and 269 +/- 32 ng mL-1 for the moderate and severe patients, respectively. No statistical differences were observed between the steady-state values for the two groups. With the exception of two patients per group, individual steady-state levels were also within the therapeutic range. Those outside the nominal range showed steady-state levels, ranging between 308 and 353 ng mL-1, that were not associated with any serious adverse events.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Elevated plasma levels of acute phase proteins in mesangioproliferative glomerulonephritis, membranous nephropathy and IgA nephropathy.

In order to study the possible role of active inflammatory processes in clinical indolent primary chronic glomerulonephritides, plasma concentrations of the acute phase proteins: alpha 1-antitrypsin, haptoglobin, orosomucoid and C-reactive protein were measured in 166 glomerulonephritis patients. The patients had a diagnosis of either mesangioproliferative glomerulonephritis, membranous nephropathy or immunoglobulin A nephropathy and were divided in two groups, one with heavy urinary albumin losses and one with moderate to slight urinary albumin excretion. The median plasma concentration values for alpha 1-antitrypsin, haptoglobin and orosomucoid were increased in all three kinds of the investigated glomerulonephritides with exception for orosomucoid in patients with heavy urinary albumin losses and in the membranous nephropathy group. The plasma concentration values for C-reactive protein were not elevated at all in the material. The increase of plasma levels of acute phase proteins could be the result of persistent inflammatory stimuli that occur in primary chronic glomerulonephritides. The finding of unchanging plasma levels of C-reactive protein in contrast to increased concentrations of the other acute phase proteins could be of significance in diagnosing infections or other inflammatory diseases in patients with chronic glomerulonephritis.

Acute-Phase Proteins