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Biomedical subjects

H Thysell

Publications and source records attributed to H Thysell.

At least 55 records · Page 3Linked to original sources

Results, principles and pitfalls in the management of renal AA-amyloidosis; a 10-21 year followup of 16 patients with rheumatic disease treated with alkylating cytostatics.

OBJECTIVE: To assess renal functional outcome at 10-21 years in 16 consecutive patients with rheumatic disease, treated with alkylating agents for secondary renal AA-amyloidosis, and to review management principles developed during 21 years. METHODS: Renal function was assessed by S-creatinine and the albumin/creatinine clearance ratio, and arthritic activity by joint score and C-reactive protein (CRP). In the event of signs of renal deterioration, cyclophosphamide, or since 1975 chlorambucil, was given until stable remission of the arthritis was obtained. RESULTS: Of the 7 cases of precipitous uremia that occurred, 4 were not treated with cytostatics at the patients' local hospitals. By 1992, median survival of renal function was 11 years (range 4-21). At 10 years 12 (75%) still had kidneys with preserved function, and at that stage accounted for 22 instances of renal deterioration treated with alkylating agents for periods of 6-45 months (median 13). Renal function was improved in 18 of these instances, and deterioration arrested in 3, the general trend being stabilized or moderately increased S-creatinine and successively declining proteinuria. Prompt institution of corticosteroid treatment is regarded as indispensable at increase of CRP/S-AA due to infection or surgery. CONCLUSION: Our results indicate that the survival of renal function may be substantially prolonged (compared to no treatment) when cyclophosphamide, or preferably chlorambucil, is appropriately administered at signs of kidney deterioration due to active arthritis, and lifelong, continuous monitoring maintained.

Albumins↗

The effect of high-dose pyridoxine and folic acid supplementation on serum lipid and plasma homocysteine concentrations in dialysis patients.

Pyridoxine and folic acid supplementation in dialysis patients is a matter of debate. This study was performed to estimate the effects of pharmacologic doses of these vitamins on serum lipid and plasma homocysteine concentrations, which are known to be high in dialysis patients. Both hemodialysis and continuous ambulatory peritoneal dialysis patients were included in the study. Pyridoxine supplementation had a mild but significant cholesterol-lowering effect (7%). Folic acid supplementation significantly lowered plasma homocysteine concentrations by a mean of 30%. There was a strong, inverse correlation between blood folate and plasma homocysteine concentrations. These results indicate that daily supplementation with pyridoxine 300 mg and folic acid 5 mg has a beneficial effect on the cardiovascular risk profile in dialysis patients.

Adult↗

Plasma levels of vasoactive regulatory peptides in patients receiving regular hemodialysis treatment.

The fasting plasma levels of 10 vasoactive regulatory peptides were measured by radioimmunoassay in 23 stable patients with chronic renal failure receiving regular hemodialysis treatment (RDT) and compared with those of healthy controls. The plasma concentrations of arginine vasopressin, atrial natriuretic peptide, beta-endorphin, methionine-enkephalin, motilin, neuropeptide Y, substance P, and vasoactive intestinal peptide were increased. The plasma level of calcitonin gene-related peptide was not statistically different from that of the controls. The plasma concentration of gamma 2-melanocyte-stimulating hormone was lowered in the RDT-patients. The arterial blood pressure correlated with the plasma levels of motilin and neuropeptide Y. We conclude that patients with chronic renal failure receiving RDT have increased concentrations of 8 out of 10 measured vasoactive regulatory peptides. The elevated levels of vasoactive peptides may contribute to the adaptation of the cardiovascular system to impaired renal function.

Adult↗

Serum levels of the soluble interleukin-2 receptor are dependent on the kidney function.

We have investigated the influence of kidney function on soluble interleukin-2 receptor (S-IL-2R) serum levels. S-IL-2R is a glycoprotein with a molecular weight of 45 kDa. The serum concentration of S-IL-2R was positively correlated to serum creatinine (r = 0.35) and complement factor D (r = 0.30), a low molecular weight protein, and the reciprocal value of S-IL-2R was negatively correlated to 51Cr-EDTA clearance (r = -0.35). When measuring S-IL-2R and factor D in a wide range of serum creatinine (140-1,380 mumol/l), a high positive correlation was found between factor D and serum creatinine. S-IL-2R and serum creatinine had r = 0.92 and r = 0.79, p = 0.0001, respectively. The correlation coefficient between factor D and S-IL-2R was 0.86. S-IL-2R is used as a marker for an increased activity of the immune system and in a variety of lymphoproliferative disorders. However, it is important to keep in mind that a reduced kidney function may contribute to the increased S-IL-2R levels seen in different immune diseases. Therefore, renal function should be taken into account in the interpretation of elevated plasma concentrations of S-IL-2R.

Complement Factor D↗

Microcalorimetric studies on uraemic plasma.

The heat production by human plasma in healthy and uraemic subjects has been measured by direct isothermal microcalorimetry. The plasma from uraemic subjects displayed an increased heat production compared to that of normal plasma. The heat production by plasma from healthy subjects, but not by that from uraemic patients, was both proportional to the amount of thiol groups in the plasma and also to the oxidation of the thiol groups. The oxygen consumption of uraemic plasma was proportional to the heat production. The heat production by samples from uraemic patients was significantly correlated to the plasma concentration of creatinine, whereas no such correlation was found between the concentration of urea and heat production of such samples.

Adult↗

Erythropoietin treatment and plasma levels of corticotropin-releasing hormone, delta sleep-inducing peptide and opioid peptides in hemodialysis patients.

An improvement of quality of life and objective brain function has been reported in patients receiving regular hemodialysis treatment (RDT) during treatment with recombinant human erythropoietin (r-huEPO). The mechanisms explaining this improvement are unknown. In this study the plasma levels of peptides known to be involved in CNS functions, namely corticotropin-releasing hormone, delta sleep-inducing peptide, beta-endorphin, methionine-enkephalin, beta-lipotropin and alpha-melanocyte-stimulating hormone, were measured by radioimmunoassay in seven stable RDT patients before the start of r-huEPO therapy and during 28 weeks' treatment. All patients responded with significantly increased hemoglobin concentrations. An improvement of well-being, state of mood and physical fitness was reported by the patients. There were no significant changes during the study in the plasma concentrations of any of the peptides measured. However, as the plasma levels of neuropeptides will not necessarily reflect the local concentrations in the vicinity of the nerve terminals, changes in the intracerebral concentrations of these peptides might occur in response to r-huEPO.

Adult↗

Lipoprotein levels and post-heparin lipase activities in kidney transplant recipients: ciclosporin- versus non-ciclosporin-treated patients.

Lipid and lipoprotein levels were measured in 118 clinically stable patients who had received a kidney transplant more than 1 year earlier. Seventy-one were treated with ciclosporin (CS), 47 were not. The CS group had significantly higher mean cholesterol (6.54 versus 6.00 mmol/l) and triglyceride (1.83 versus 1.34 mmol/l) concentrations than the non-CS group. LDL/HDL cholesterol ratios were similar in the two groups. The CS patients had higher creatinine and prednisolone doses and used beta-blockers and loop diuretics more frequently. Multiple regression analysis did not show an independent correlation between lipid levels and treatment with CS. On the other hand, there was an independent correlation between cholesterol levels and treatment with loop diuretics, suggesting that such treatment contributes to the higher cholesterol levels in kidney transplant recipients. The diabetics had a more favorable lipoprotein profile than the nondiabetics, especially in triglycerides and HDL cholesterol levels. The marked difference in triglyceride levels between the treatment groups prompted us to evaluate the lipoprotein lipase and hepatic lipase activities in 20 hyperlipidemic, nondiabetic patients. Both enzyme activities were moderately reduced with no difference between the treatment groups, suggesting that factors other than CS interfere with the lipase activities in kidney transplant recipients.

Cyclosporine↗

Microcalorimetric evaluation of blood compatibility of hemodialysis membranes.

The study was made in vitro of reactions elicited by contact of granulocytes suspended in autologous plasma with three polymers: polyacrylonitrile (AN); polyetherpoly-carbonate (PC), and regenerated cellulose (Cu). Alterations in basal metabolism and biological function of the human blood granulocytes induced by interfacial reactions were determined by direct microcalorimetry. The polymers, which are commonly used as membranes in artificial kidneys, were found to activate granulocytes to degrees which were inversely correlated with their response to zymosan. The compatibility of the granulocytes and each of the membranes was of the order: AN greater than PC greater than Cu.

Calorimetry↗

Elevated plasma levels of opioid peptides and delta sleep-inducing peptide but not of corticotropin-releasing hormone in patients receiving chronic hemodialysis.

The fasting plasma levels of corticotropin-releasing hormone (CRH), delta sleep-inducing peptide (DSIP), beta-endorphin (beta-END), methionine-enkephalin (m-ENK), beta-lipotropin (beta-LPH), and alpha-melanocyte-stimulating hormone (alpha-MSH) were measured by radioimmunoassay in 22 stable patients with chronic renal failure on regular hemodialysis treatment and compared with those of 10 healthy controls. The plasma concentrations of DSIP, beta-END, m-ENK, beta-LPH, and alpha-MSH were increased. The plasma level of CRH was not different from that of the controls. The elevated plasma levels of endogenous opioid peptides and DSIP may contribute to the uremic syndrome, although this must be further elucidated.

Adult↗

On the binding of tumor necrosis factor (TNF) to heparin and the release in vivo of the TNF-binding protein I by heparin.

Tumor necrosis factor (TNF), a protein released by activated macrophages, is a central mediator of the host response to infection and inflammation. The TNF-binding protein I (TNF-BP-I) is a soluble fragment of the p60 transmembrane TNF receptor and an antagonist to TNF. The level of serum TNF-BP-I was found to be increased in patients with renal insufficiency as a result of a decrease in the glomerular filtration rate. During hemodialysis of patients with renal failure there was a rapid but transient increase in serum TNF-BP-I. This increase was found to be caused by heparin given before dialysis and a similar dose-dependent response to heparin was observed also in healthy individuals. The finding of a repeated release of TNF-BP-I into the circulation with intermittent injections of heparin indicates that TNF-BP-I is present both in a storage pool and in a circulating pool. The mechanism for the heparin-mediated release of TNF-BP-I was not explained; TNF-BP did not show affinity for heparin. On the other hand, TNF was found to have affinity for heparin and it could also be dissociated from heparin by TNF-BP-I. It is suggested that heparin-like molecules of the extracellular matrix can retain TNF in physical proximity with target cells and restrict the actions of TNF and protect against systemic harmful manifestations.

Carrier Proteins↗

Plasma levels of gastrointestinal regulatory peptides in patients receiving maintenance hemodialysis.

The fasting plasma levels of 9 gastrointestinal regulatory peptides were measured by radioimmunoassay in 13 stable patients with chronic renal failure receiving hemodialysis treatment regularly and compared with those of 10 healthy controls. The plasma concentrations of gastrin-releasing peptide, motilin, neurotensin, pancreatic polypeptide, peptide YY, somatostatin, substance P, and vasoactive intestinal peptide were increased. The plasma level of gastrin was not statistically different from that of the controls (p = 0.077). We conclude that patients with chronic renal failure receiving hemodialysis treatment regularly have increased concentrations of eight of nine measured gastrointestinal regulatory peptides. The elevated levels of gastrointestinal peptides in patients with chronic renal failure may contribute to uremic gastrointestinal symptoms and dysfunctions. It is necessary to make a renal function evaluation before interpreting measured plasma levels of gastrointestinal regulatory peptides.

Adult↗

Adherence of blood cells to dialyzer membranes as a measure of biocompatibility.

Cell adherence to plate dialyzer membranes was analyzed at the end of 4 hours of dialysis. Three types of membranes were examined: Cuprophan Hemophan and Gambrane, (a polycarbonate membrane). The membranes were mounted in dialyzers that contained 23 layers of one membrane type and one layer of each of the two other. Less leukocytes adhered to the Pc than to the Cu and He membranes. Transient initial complement activation during dialysis, which was considerably lower with dialysers containing mainly Pc membrane, was not correlated to adherence of cells to the membranes. Instead flow geometry is proposed as the main factor determining the adherence. Contrary to what has been earlier suggested, we think that leukocyte adherence is not a very suitable measure of membrane biocompatibility. The reason is that the influence of membrane surface-chemical factors can not be separated from mechanical factors due to the design of the device.

Biocompatible Materials↗

Effects of recombinant human erythropoietin on the plasma levels of vasoactive regulatory peptides in patients on maintenance hemodialysis.

The plasma levels of nine vasoactive regulatory peptides were measured by radioimmunoassay in six stable patients with chronic renal failure on regular hemodialysis, before and during treatment with recombinant human erythropoietin (r-huEPO). All patients responded with significant increases in hemoglobin concentrations and hematocrit. Mean arterial blood pressure was not significantly changed nor were there any changes of body weight or interdialytic body weight gain. The mean plasma levels of atrial natriuretic peptide and motilin decreased significantly, by 38 and 16 percent respectively, during r-huEPO treatment. There were no changes in mean plasma levels of arginine vasopressin, calcitonin gene-related peptide, beta-lipotropin, gamma 2-melanocyte-stimulating hormone, neuropeptide Y, substance P or vasoactive intestinal peptide. No significant correlations were observed between changes of plasma peptide levels and changes of mean arterial blood pressure.

Anemia↗

Effects of sulindac and naproxen on prostaglandin excretion in patients with impaired renal function and rheumatoid arthritis.

PURPOSE: The purpose of the current investigation was to study the influence of sulindac and naproxen on renal function and urinary excretion of the stable hydration product of prostacyclin, 6-keto-PGF1 alpha, in patients with arthritis and impaired renal function. PATIENTS AND METHODS: In a placebo-controlled, double-blind, cross-over design, the effects of 7 days of oral sulindac 200 mg twice a day were compared with naproxen 500 mg in the morning and 250 mg in the evening in 10 patients with polyarthritis and stable impaired renal function. Inulin and para-amino-hippurate sodium were used to calculate glomerular filtration rate and renal plasma flow. The excretion rate of 6-keto-PGF1 alpha was measured in urine collected overnight. After patients ingested drugs in the morning, urine was collected in fractions by spontaneous voiding. Venous blood samples were drawn repeatedly for assay of electrolytes, creatinine, proteins, hormones, and drugs. Grip strength and Ritchie articular index were recorded as indicators of symptomatic antiarthritic effectiveness. RESULTS: Naproxen decreased urine levels of 6-keto PGF1 alpha by 59% (p less than 0.01). Sulindac had no effect on renal prostaglandin excretion. Naproxen reduced the glomerular filtration rate and renal plasma flow by 18% (p less than 0.05) and 13% (p less than 0.05), respectively, while no significant change was observed during the sulindac treatment periods. Serum levels of creatinine and complement factor D were unaffected by either drug. Plasma renin activity decreased during naproxen and sulindac treatments by 38% (p less than 0.05) and 22% (p less than 0.05). No significant change in plasma aldosterone was observed during the two drug treatments, but urinary aldosterone declined significantly (p less than 0.05) by 34% with naproxen. Albuminuria decreased (p less than 0.05) during both naproxen (41%) and sulindac treatment (72%), while the albumin/creatinine clearance ratio decreased by 59% (p less than 0.05) only during treatment with sulindac. N-acetyl-beta-D-glucosaminidase in urine was not changed by either drug. Sulindac and naproxen had no discernible effects on base excess, excretion of water, sodium, or potassium, or on osmolal clearance. However, serum potassium increased slightly but significantly (p less than 0.01) during treatment with naproxen. Sulindac sulfide, the active metabolite of sulindac, could not be traced in the urine from any of the patients. Mean arterial blood pressure declined significantly (p less than 0.05) during sulindac treatment but did not change during treatment with naproxen. Both drugs produced equal clinical improvement as measured by grip strength and the Ritchie articular index. CONCLUSION: The results suggest that when sulindac and naproxen are given in clinical equipotent doses to patients with impaired renal function, sulindac does not affect renal prostaglandin synthesis or renal function, whereas naproxen induces suppression of renal prostaglandin synthesis and a further decrease in renal function.

6-Ketoprostaglandin F1 alpha↗

Recurrent cerebral infarction and the antiphospholipid syndrome: effect of intravenous gammaglobulin in a patient with systemic lupus erythematosus.

A 23 year old woman with systemic lupus erythematosus and antiphospholipid syndrome developed severe thrombocytopenia (5-10 X 10(9)/l) and cerebral infarction. Treatment with high doses of corticosteroids and cytostatic drugs was not effective. The condition was successfully treated only when three courses of intravenous gammaglobulin at 400 mg/kg daily was added. A clear relation was found between the immunoglobulin infusions and rising platelet counts, whereas an effect on the levels of anticardiolipin antibodies could not be recorded. The findings suggested that the mechanisms responsible may be modification and solubilisation of immune complexes or interference with anticardiolipin binding to platelet membranes, or both.

Adult↗

Antimyeloperoxidase antibodies in patients with extracapillary glomerulonephritis.

The sera of 64 patients with extracapillary glomerulonephritis were investigated by enzyme-linked immunosorbent assay for the presence of antibody to human neutrophil myeloperoxidase (MPO). In all, circulating anti-MPO were found in 30% and antineutrophil cytoplasm antibodies (ANCA) detected by indirect immunofluorescence in 44% of the patients. Autoantibody to components of neutrophil granulocytes was not found in patients with other forms of glomerulonephritis. The incidence of ANCA (16/23) was higher than that of anti-MPO (5/23) in patients with a diagnosis of Wegener's granulomatosis. By contrast, anti-MPO was found in a majority of vasculitis patients without extrarenal symptoms (6/9), including 3 patients treated with hydralazine. One of the patients treated with hydralazine had circulating ANCA in combination with anti-MPO. Anti-MPO was also found in 1 out of 6 patients with Goodpasture's syndrome. The findings emphasize that autoantibodies to distinct components of neutrophil granulocytes partly differ with regard to diagnostic specificity.

Autoantibodies↗

Reduction of albuminuria after angiotensin converting enzyme inhibition in various renal disorders.

The urinary albumin excretion measured by the albumin creatinine clearance ratio (Calb/Ccreat) and the mean supine arterial blood pressure (MAP) were studied before the start of ACE inhibition, at the start and during up to 1 year of ACE inhibition with Captopril or Enalapril in 35 patients with various chronic proteinuric renal disorders with or without renal failure, arterial hypertension and nephrotic syndrome. Before the start of ACE inhibition mean Calb/Ccreat, MAP, s-albumin and s-creatinine did not change. During ACE inhibition the Calb/Ccreat was reduced from 75% (p less than 0.05) in patients with minimal albuminuria to 41% (p less than 0.005) in patients with extensive albuminuria. Average reduction of albuminuria was 44% at one year's observation time. Serum albumin increased 9% (p less than 0.05), serum creatinine did not change significantly and MAP showed a slight, not uniformly significant decrease. The reduction of Calb/Ccreat was of the same order in the different renal disorders studied and was independent of the renal function, presence or absence of nephrotic syndrome and treatment with antihypertensive or immunosuppressive drugs. The decrease in Calb/Ccreat during ACE inhibition was related to the reduction in MAP at most time intervals, but Calb/Ccreat decreased also when MAP was unchanged or increased. Thus the decrease in Calb/Ccreat during ACE inhibition does not only seem to be a consequence of a decrease in the systemic arterial blood pressure but reasonably also due to changes in the intra-renal hemodynamics and most probably a decrease in the glomerular capillary pressure.

Adolescent↗