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Biomedical subjects

S Björck

Publications and source records attributed to S Björck.

At least 19 recordsLinked to original sources
PubMed1997

Influence of topical rectal application of drugs on dextran sulfate-induced colitis in rats.

A rat model of colitis [dextran sulfate (DSS)] was used to study the permeation of Evans blue (EB) from the lumen into the wall of proximal and distal colonic loops after exposure to the dye for 2 hr. Topical application of drugs used in human ulcerative colitis (lidocaine, mesalazine, prednisolone, or sucralfate) was given daily during induction of colitis to protect the mucosa. The mucosal changes were evaluated with special regard to peptidergic innervation [substance P (SP) and neuropeptide Y (NPY)], invasion of antigen-presenting polydendritic cells, and mucin-containing goblet cells. DSS-treatment caused a significantly increased permeation of EB. In the proximal loops a significant inhibition was obtained after treatment with lidocaine, prednisolone, or sucralfate. In the distal loops only treatment with lidocaine had a preventive effect. Immunocytochemically there was a clear hyperplasia of both mucosal SP- and NPY-immunoreactive nerve fibers in regions with crypt abnormalities. In these regions also most of the goblet cells were devoid of mucus. Like the changes in permeation, these morphological changes were most prominent in the distal loops. With induction of colitis, the mucosa and lamina propria were invaded by polydendritic cells; the visual score was markedly decreased in the proximal loops treated with lidocaine, prednisolone, or sucralfate. In the distal loops similar effects were obtained after treatment with lidocaine or prednisolone. Prevention of the influx of antigens in both loops after lidocaine treatment with reduced recruitment of polydendritic cells into the lamina propria is suggested. The nerve hyperplasia may thus be secondary to luminal challenge with antigens during induction of colitis. The discrepancy between increased permeation and absence of polydendritic cell response in the distal loops after prednisolone may reflect separate actions of steroids on the intestinal epithelium and the immune cells.

Administration, Rectal↗
PubMed1997

Deletion insertion polymorphism of the angiotensin converting enzyme gene and progression of diabetic nephropathy.

BACKGROUND: The activity in the renin angiotensin system is important for the progression of diabetic nephropathy. Genetic abnormalities in this system have been suggested as a risk factor for the development and progression of diabetic nephropathy. The homozygous DD (deletion) genotype of the angiotensin-converting enzyme gene has been associated with increased circulating angiotensin converting enzyme and a more rapid progression of IgA nephritis. The aim of the present study was to investigate the relationship between the DD genotype and rate of decline in kidney function in patients with type 1 diabetes and nephropathy in relation to other risk factors for loss of renal function. METHODS: The insertion-deletion polymorphism was determined in patients with type 1 diabetes mellitus and diabetic nephropathy. Retrospective data were collected in 86 patients. The patients were studied by determining glomerular filtration rate during a mean (+/-SD) of 8.5 +/- 4.0 years (range 1.3-14.5 years) using the clearance of 51Cr EDTA. Measurements for glycaemic control, urinary albumin excretion, blood pressure, and serum lipids were available for the study period. RESULTS: The mean decline in glomerular filtration rate was 3.2 +/- 3.6 ml/min/year in all patients. Patients with the DD, ID and II genotype showed a rate of change in glomerular filtration of -3.5 +/- 3.5, -3.1 +/- 4.4 and -2.6 +/- 2.3 ml/min/year respectively. The tendency towards a more rapid decline in kidney function in the DD genotype was nonsignificant. The decline in renal function was significantly correlated to systolic and diastolic blood pressure, Hb AIc and serum triglycerides. Serum cholesterol was nearly significantly correlated to the decline in glomerular filtration rate (P = 0.057). Of these variables, glycaemic control and blood pressure control remained significant in multivariate analysis (P = 0.02 and P = 0.04, respectively). The patients with the DD genotype weighted significantly less. The body weight in patients with the DD genotype was 67.1 +/- 11.4 kg vs 74.9 +/- 9.2 kg in patients with the II genotype (P = 0.018). CONCLUSION: In this study, poor glycaemic and blood pressure control were associated with a more rapid loss of renal function in diabetic nephropathy while polymorphism of the angiotensin converting enzyme gene was not.

Adult↗
PubMed1996

Physiological and histological characterisation of a pig kidney in vitro perfusion model for xenotransplantation studies.

A pig kidney perfusion model aimed for use in immunological and physiological xenotransplantation research has been developed. Organ viability was characterised by clearance studies, functional response to hormones/diureticum and by light microscopical examination. The pig kidney was perfused in a specially designed plexiglass chamber, using a roller pump and a small membrane oxygenator (O2/CO2, 95/5). The recirculating perfusate used was autologous pig blood diluted by Tyrodes solution to a hematocrit of 30%, at a total starting volume of 600-650 ml. The temperature was 37 degrees C. It was crucial for good organ function that the nephrectomy operating time, as well as the warm (1-2 min) and cold ischemia (average 43 min) times were minimized. The average total perfusion time was 151 minutes. Physiological parameters were measured during 10-15 minute periods at average times of 40, 63, 88 and 142 minutes. The clearance values of inulin in these periods were 54 +/- 13, 59 +/- 15, 48 +/- 23, 27 +/- 5 and for PAH; 103 +/- 14, 121 +/- 14, 106 +/- 30, 114 +/- 34 ml/min/100 g tissue weight. The plasma flows were 123 +/- 12, 155 +/- 17, 136 +/- 36 and 206 +/- 57 ml/min/100 g. The injection of 0.5 micrograms of alpha ANP to the perfusate resulted in a significant decrease in vascular resistance, and increase in urine production (+107%), as well as sodium (+112%) and potassium (+46%) excretion. Ten mg furosemide doubled the urine production and sodium excretion, while potassium excretion increased marginally. The number of leucocytes decreased by 39% during the perfusion, while the platelet count was unaffected. Light microscopy of the renal tissue after termination of the experiments revealed endothelial damage to variable extent. Loss of endothelial cells was most obvious at the level of arcuate and interlobular arteries, while the endothelium was intact in larger arteries and veins. Accumulation of polymorphonuclear granulocytes was found predominantly in the peritubular vessels, and to a lesser degree in the cortical venules. In the tubular cells, only minimal epithelial swelling and irregular cytoplasmic vacuolisation was found. Thus, a good functional viability can be maintained during 2 hours in vitro perfusion, although a decline in function as well as structural damage can be seen at the end of the experiment.

Animals↗
PubMed1995

Latent overhydration and nocturnal hypertension in diabetic nephropathy.

With the aim of studying the diurnal variation in blood pressure in relation to degree of fluid retention, 24-h ambulatory blood pressure monitoring was performed in 31 insulin-dependent diabetic patients with nephropathy. The extracellular volume was calculated from the distribution volume of 51Cr-EDTA after a single injection. The study population was arbitrarily divided into two groups, depending on their extracellular volume. Group 1 included 15 patients with a lower extracellular volume and group 2, 16 patients with a higher extracellular volume. Ambulatory blood pressure was measured with a portable monitor using an oscillometric technique. In all patients, the mean +/- SD 24-h ambulatory blood pressure was 135/79 +/- 14/7 mmHg. Day and night-time blood pressure were 136/81 +/- 14/7 and 133/75 +/- 17/8, respectively (p < 0.02). The ambulatory blood pressure was 135/80 +/- 14/7 in group 1 and 136/78 +/- 15/6 mmHg in group 2. The nocturnal change in blood pressure was significantly greater in group 1 than in group 2, -9/-9 +/- 10/5 mmHg and 1/-3 +/- 10/6 mmHg, respectively (p = 0.005/0.01). There were no other significant differences between the groups than the diurnal blood pressure pattern. There were significant correlations between day ambulatory blood pressure and night ambulatory blood pressure and 24-h ambulatory blood pressure and urinary albumin excretion. There was no correlation between ausculatatory clinic blood pressure on the one hand and albuminuria on the other. Latent fluid retention therefore may contribute to nocturnal hypertension in diabetic nephropathy.

Adult↗
PubMed1995

Induction of specific immunity at mucosal surfaces: prospects for vaccine development.

We have demonstrated the feasibility of studying antigen-specific immune responses in a variety of mucosal tissues in humans after vaccination and during infection. In this respect, we have documented the usefulness of both oral cholera and ETEC vaccines for assessing in functional terms specific subpopulations of B- and T-cell immunocytes during an immune response initiated and/or expressed in human mucosal tissues. Circulating specific IgA antibody-secreting cells in blood appear to reflect recent or ongoing antigen exposure of mucosal surfaces. This implies that the detection of such cells in blood, the most accessible lymphoid compartment in humans, represents the simplest way to assess the immunogenicity of mucosal vaccines and to supplement the diagnostic and monitoring of active mucosal infections. Our studies indicate that while the concept of an integrated mucosal immune network is clearly operational in humans (at least in regards to induction of secretory antibody responses), its generalization appears somewhat simplistic as illustrated by the compartmentalization of immune responses initiated in certain mucosal organs such as the small intestine and the tonsils. Finally, the potential of the cholera toxin B subunit as a carrier for delivery of chemically or genetically linked foreign epitopes for induction of disseminated mucosal immune responses raises hope for the development of broadly applicable vaccines to control mucosal infections.

Animals↗
PubMed1994

Long-term enalapril treatment in diabetic nephropathy.

A randomized comparison of enalapril and metoprolol in patients with type 1 diabetes and nephropathy showed that the decline in kidney function was 5.6 +/- 5.9 ml/min/year in the metoprolol-treated and 2.0 +/- 3.2 ml/min/year in the enalapril-treated patients (P = 0.02). In the present study, the enalapril treated patients have been studied for two additional years. In the metoprolol-treated group, only the endpoints of death or uremia have been recorded, and six of the patients have reached end-stage renal failure and three are dead, compared to three and two, respectively in the enalapril treated group. The mean fall in glomerular filtration rate in 18 enalapril-treated patients is 8.4 +/- 9.4 ml/min/1.73 m2 after four years; 7.5 +/- 9.8 ml/min/1.73 m2, occurred during the first six months treatment. The mean decline in kidney function was 1.7 +/- 2.4 ml/min/year over the whole study period and 0.3 +/- 3.9 ml/min/year after exclusion of the first six months. In this study, long-term enalapril treatment in diabetic nephropathy was associated with a low rate of decline in kidney function.

Adult↗
PubMed1993

Cholesterol: a renal risk factor in diabetic nephropathy?

In a prospective follow-up of 30 patients with type 1 diabetes and nephropathy, serum cholesterol, triglycerides, apolipoprotein Al and B, and lipoprotein(a) were determined to study their relationship to the rate of decline in glomerular filtration rate. The patients had proteinuria and advanced nephropathy with a mean +/- SD glomerular filtration rate of 39 mL/min/1.73 m2. The decline in glomerular filtration rate was determined during 2.5 +/- 0.5 years. High serum cholesterol, triglycerides, and apolipoprotein B were correlated to a more rapid deterioration in kidney function. The rate of decline in glomerular filtration rate was 1.0 +/- 2.5 mL/min/yr in the 10 patients with the lowest cholesterol level, compared with 4.5 +/- 3.2 mL/min/yr in the patients with the highest serum cholesterol (P = 0.015). The combined effect of the measured lipids, blood pressure, type of antihypertensive treatment, protein intake, proteinuria, and hemoglobin A1C on the rate of decline in glomerular filtration rate was assessed by multiple regression analysis. The measured factors together had a high explanatory power for the rate of decline in glomerular filtration rate. In this model, 73% of the variation in decline in glomerular filtration rate was explained by the measured variables (multiple r2 = 0.73). Low cholesterol and treatment with an angiotensin-converting enzyme inhibitor were the strongest predictors of a favorable renal prognosis. This suggests that hypercholesterolemia is an important risk factor for diabetic nephropathy.

Adult↗
PubMed1992

Renal protective effect of enalapril in diabetic nephropathy.

OBJECTIVE: To determine whether inhibition of angiotensin converting enzyme can reduce the rate of decline in kidney function more than reducing blood pressure with other antihypertensive treatment. DESIGN: Prospective, open randomised study lasting a mean of 2.2 years in patients with diabetic nephropathy. SETTING: Three outpatient nephrology clinics. PATIENTS: 40 patients with insulin dependent diabetes and diabetic nephropathy with reduced renal function. INTERVENTION: Antihypertensive treatment with enalapril or metoprolol, usually combined with frusemide. MAIN OUTCOME MEASURE: Rate of decline in glomerular filtration rate measured as chromium-51 edetic acid clearance. RESULTS: Glomerular filtration rate declined a mean of 2.0 (SD 3.2) ml/min/year in the group given enalapril and 5.6 (5.9) ml/min/year in the control group. The mean arterial blood pressure during the study was 102 (5) mm Hg in the patients given enalapril and 103 (5) mm Hg in the patients given metoprolol. Urinary albumin excretion during treatment with enalapril was 60% lower than during treatment with metoprolol. CONCLUSIONS: Enalapril has an antiproteinuric effect independent of the effect on systemic blood pressure. Treatment with enalapril can reduce the rate of decline in kidney function in patients with diabetic nephropathy more than equally effective antihypertensive treatment with metoprolol. This points to a specific renal protective effect of angiotensin converting enzyme inhibitors in diabetic nephropathy.

Adult↗
PubMed1992

Septic shock induced by group A streptococcal infection: clinical and therapeutic aspects.

During 1988 and 1989 > 500 cases of serious group A streptococcal infections were reported in Sweden, many with a fatal outcome. We report here on 11 consecutive patients with septic preshock/shock and multiorgan failure, including acute renal failure. 10 had verified group A streptococci (GAS) serotype T1M1 infections while 1 patient was culture negative but with clinical signs of severe infection and serological evidence of GAS infection. Presenting symptoms were high fever, relative bradycardia, edema and renal failure. In all patients the condition deteriorated despite conventional treatment including volume substitution and antibiotics. Systolic blood pressure was transiently < 80 mmHg in 10 patients and 9 of them needed infusion of inotropic agents to avoid fatal circulatory shock. In 9 patients respiratory aid was instituted and 7 were dialysed. Plasma exchange was performed in 7, while the remaining 4 received transfusions with blood and plasma without plasma exchange. 10 patients improved and were discharged within 8 weeks. One woman died within 2 days after admission to the hospital. Renal function recovered in all survivors, with a follow-up serum creatinine < 80 mumol/l. The complicated clinical picture in these patients with many simultaneous therapeutic events confounds the interpretation of the effect of single actions. The favourable outcome in these severely ill patients suggests that potent inotropic agents, immunoglobulin therapy and plasma exchange might be beneficial in severe streptococcal disease when conventional treatment fails.

Adolescent↗
PubMed1992

Serum concentrations of calcitriol and PTH in hemo-dialysis patients on treatment with calcium carbonate.

The effects of calcium carbonate and aluminium hydroxide as phosphate binders were investigated in nine patients on chronic hemodialysis. Aluminium hydroxide, 1 g X 3, was given during four weeks followed by a period of four weeks without any phosphate binders and after this calcium carbonate, 2.5 g X 3, was introduced for four weeks. Calcium carbonate resulted in lowering of bioactive PTH in serum from 22.4 to 16.4 pM and a rise of serum calcitriol from 8.0 to 11.5 pg/ml with maintained control of phosphate and without significant difference in the calcium-phosphate product. Calcium in serum rose from 2.27 to 2.57 mM and mild hypercalcemia (less than 3.0 mM) in five of the patients could be controlled by dose reduction of calcium carbonate without losing control of serum phosphate levels. We conclude that calcium carbonate offers advantages as a phosphate binder compared to aluminium hydroxide in that it offers equal control of serum phosphate and elevates serum calcium which helps to control the hyperparathyroidism secondary to uremia.

Adult↗
PubMed1992

Diagnostic use of renal vein erythropoietin measurements in patients with renal artery stenosis.

The relationship between the renin-angiotensin system and erythropoietin was studied in twenty patients with renal artery stenosis and hypertension. Ten of the patients had a unilaterally activated renin-angiotensin system (group 1), while ten patients had not (group 2). Plasma erythropoietin was simultaneously measured in a brachial artery and both renal veins before and 5 and 30 min after an intravenous injection of 1.25 mg enalaprilat. The mean (+/- SD) arterial erythropoietin concentration was 27.3 +/- 16.8 mU/ml in group 1 and 14.1 +/- 11.3 mU/ml in group 2 patients (P less than 0.05). There was no significant change after enalaprilat i.v. in either group. The venous erythropoietin concentration in plasma from the stenotic kidney did not differ from that of the contralateral kidney. The higher erythropoietin concentration in group 1 patients may be explained by a systemic stimulatory effect of the renin-angiotensin system on erythropoietin production. As no side-differences were found, renal vein as well as peripheral erythropoietin measurements cannot be used as a tool in the diagnosis of the functional significance of a renal artery stenosis.

Adult↗
PubMed1992

Treatment of the mucosa with local anaesthetics in ulcerative colitis.

A new paradigm for the treatment of ulcerative colitis has recently been presented: Treatment of the mucosa with lidocaine (2%) enemas for prolonged periods. This therapy was introduced based on the hypothesis that hyperreactive autonomic nerves may play a pathogenetic role in the disease. One hundred consecutive patients have now been treated and the results presented. The proctitis patients all responded to the treatment, despite previous therapeutic failures in more than two-thirds of the cases. They were treated for 3-12 weeks, but 68% had a relapse (observation period 20 months). Of the 49 patients with proctosigmoiditis, two-thirds had chronic symptoms resistant to previous therapy. One of these patients did not respond to lidocaine, but developed fulminant total colitis. The other patient had therapeutic failure with lidocaine but responded well to subsequent cortisone enemas. The patients were treated until the subsets of T-lymphocytes (OKT4+ and OKT8+) disappeared from the mucosa. This occurred in parallel with symptomatic relief and eventual healing in 83% of the patients after treatment for 6-34 weeks. Of all the patients with proctosigmoiditis, 42% presented with recurrent symptoms (observation period 16 months). Of the 17 patients with left-sided colitis, all went primarily into remission within 2-4 months, but 23% had a relapse (observation period 13 months). The 6 patients with total colitis had symptomatic relief and improvement of histology when treated over 3-8 months. One patient had recurrence after 12 months. Treatment with a local anaesthetic in ulcerative colitis is a new approach to mucosal inflammation. The beneficial effects may be due to blockade of certain neural effects, such as epithelial proliferation and shedding and congestion of the mucosal vasculature, with actions on cells of the immune system.

Adult↗
PubMed1992

Determinants of progressive renal disease in diabetes mellitus.

The prognosis for the patient with diabetic nephropathy has improved considerably during the last decade. This is due to identification and treatment of different risk factors. Elevated blood pressure has turned out to be a major risk factor in established diabetic nephropathy. The impact of metabolic control has also been demonstrated. Lipid abnormalities have recently been identified as a possible factor that accelerates loss of renal function. The role of renal hemodynamic alterations is probably also important. Their contribution can indirectly be assessed by studying the effects of pharmacologic therapy. Angiotension converting enzyme inhibitors reduce proteinuria by a mechanism independent of systemic blood pressure and there is suggestive evidence that they preserve renal function to a greater degree than other antihypertensive agents.

Diabetic Nephropathies↗
PubMed1991

Antibodies to neutrophil granulocyte myeloperoxidase and elastase: autoimmune responses in glomerulonephritis due to hydralazine treatment.

Autoantibodies against myeloperoxidase and elastase were found in a study of nine patients who had developed glomerulonephritis after treatment with hydralazine, but not in patients who were treated with hydralazine without side-effects. Circulating IgM isotype antibodies against myeloperoxidase, and IgM and IgG anti-elastase, were mainly present during the initial months after withdrawal of the drug. By contrast, IgG isotype antibodies against myeloperoxidase, initially found in seven patients, had increased in concentration and were present in all patients at follow-up after 4-12 years.

Autoantibodies↗
PubMed1991

Cure of zygomycosis caused by a lipase-producing Rhizopus rhizopodiformis strain in a renal transplant patient.

A 40-year-old man with renal failure due to membranous glomerulonephritis received a cadaveric renal transplant and immunosuppressive therapy with cyclosporine, azathioprine and steroids. Initially the transplantation was successful. 12 days after the transplantation, however, serous secretion appeared in the wound. Later, black necrosis was seen. Fungal culture showed growth of a zygomycete species. Rhizopus rhizopodiformis, with high in-vitro resistance to amphotericin B, flucytosine, fluconazole, ketoconazole and itraconazole. The MIC value for the allylamine derivative SF86-327 (Exoderil) was 1.6 micrograms/ml. Microscopic examination of sections from a surgical revision showed necrosis of the fat tissue and massive hyphal invasion of the perirenal fat, which contained semi-crystalline material anisotropic as seen in polarized light and characteristically staining with rubeanic acid. These histological data indicate a lipase-induced in-vivo splitting of lipids into fatty acids. In-vitro R. rhizopodiformis showed very high extracellular lipase production. 11 days after initiation of amphotericin B therapy cultures and sections remained positive for rhizopus. Amphotericin B was therefore supplemented with Exoderil orally, cyclosporine and steroids were maintained, and azathioprine was discontinued. The wound granulated, shrank, and healed completely in 10 weeks.

Adult↗