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Biomedical subjects

T Forslund

Publications and source records attributed to T Forslund.

At least 19 recordsLinked to original sources
PubMed2005

De novo seropositive rheumatoid arthritis during immunosuppressive treatment after kidney transplantation.

We detected de novo seropositive erosive rheumatoid arthritis (RA) in a patient seven years after successful cadaveric kidney transplantation (RTx). RA developed in spite of treatment with cyclosporine A (CyA), methylprednisolon (MP) and azathioprine (Aza), compounds often also used for treatment of active RA. Renal failure was due to diabetes mellitus (DM) nephropathy. Besides a slight increase in C-reactive protein (CRP) concentration two years after RTx, the clinical symptoms of RA were observed seven years after RTx. RA was confirmed by X-ray examination, isotopic skeletal scan and positive serum RA factor. After switching Aza to methotrexate (Mtx) treatment, his symptoms disappeared and CRP concentration returned to normal. Our patient had HLA DRB1 *0101, *0401 alleles and DQB1 *0501, *0302 alleles which have strong genetic association with both DM and RA. To our best knowledge, this is the first case in which de novo seropositive erosive RA developed while on treatment with triple immunosuppression after RTx. The immunosuppressive treatment probably masked the inflammation and symptoms of RA.

Adolescent↗
PubMed2002

Inducible nitric oxide synthase is expressed in synovial fluid granulocytes.

The objective of the study was to evaluate the NO-producing potential of synovial fluid (SF) cells. SF from 15 patients with arthritis was compared with blood from the same individuals and with blood from 10 healthy controls. Cellular expression of inducible nitric oxide synthase (iNOS) was analysed by flow cytometry. High-performance liquid chromatography was used to measure l-arginine and l-citrulline. Nitrite and nitrate were measured colourimetrically utilizing the Griess' reaction. Compared to whole blood granulocytes in patients with chronic arthritis, a prominent iNOS expression was observed in SF granulocytes (P < 0.001). A slight, but statistically significant, increase in iNOS expression was also recorded in lymphocytes and monocytes from SF. l-arginine was elevated in SF compared to serum (257 +/- 78 versus 176 +/- 65 micro mol/l, P = 0.008), whereas a slight increase in l-citrulline (33 +/- 11 versus 26 +/- 9 micro mol/l), did not reach statistical significance. Great variations but no significant differences were observed comparing serum and SF levels of nitrite and nitrate, respectively, although the sum of nitrite and nitrate tended to be elevated in SF (19.2 +/- 20.7 versus 8.6 +/- 6.5 micro mol/l, P = 0.054). Synovial fluid leucocytes, in particular granulocytes, express iNOS and may thus contribute to intra-articular NO production in arthritis.

Adult↗
PubMed2002

Interstitial nephritis, acute renal failure in a patient with non-fulminant hepatitis A infection.

This is the first report from Norway of a patient with interstitial nephritis and renal failure due to non-fulminant hepatitis A virus (HAV) infection. HAV infection was confirmed by positive anti-HAV IgM serology. All tests for other virus infections were negative. At admittance serum creatinine (s-Creat) and blood urea nitrogen (BUN) concentration were 539 microlmol/l and 32.6 mmol/l increasing the following days to 890 micromol/l and 39.9 mmol/l, respectively. Nine courses of hemodialysis had to be given. Kidney biopsy specimen showed interstitial edema, lymphocytic cell infiltration and acute tubular injury with normal glomeruli. Examination with immunohistochemistry was negative. In contrast to the findings associated with HBV and HCV infection in which glomerular disease is predominantly found, the HAV infection in our patient was associated with interstitial nephritis and acute tubular necrosis. The prognosis of the renal failure due to HAV infection was good although the recovery was substantially delayed.

Acute Kidney Injury↗
PubMed2001

The use of pretransplant erythropoietin to normalize hemoglobin levels has no deleterious effects on renal transplantation outcome.

BACKGROUND: The aim of this study was to establish the outcome of renal transplantation in patients given pretransplant erythropoietin (EPO) treatment targeted at reaching a normal hemoglobin concentration (Hb), compared to those given EPO-treatment aimed at maintaining subnormal Hb. METHODS: A total of 416 patients from Scandinavian countries and with renal anaemia were enrolled to examine the effects of increasing Hb from a subnormal level (90-120 g/liter) to a normal level (135-160 g/liter) by EPO treatment. Half of the patients were randomized to have their Hb increased, with the other half randomized to maintain a subnormal Hb. Thirty-two patients from the normal Hb group and 24 patients from the subnormal group received a renal graft during the study period. The outcomes of these transplantations were examined prospectively for 6 months. RESULTS: Preoperative Hb levels were 143+/-17 and 121+/-14 g/liter in the two groups, respectively (P<0.0001). The Hb remained higher in the normal Hb group during the first 2 weeks after transplantation. The percentage of patients requiring postoperative blood transfusions in the normal Hb group was 16%, compared with 50% in the subnormal group (P<0.01). No statistically significant difference in the proportion of functioning grafts or in the serum creatinine levels could be detected. No correlation between EPO treatment and creatinine levels after transplantation was found. The frequency of adverse events was similar in the two groups. CONCLUSIONS: EPO treatment aimed at reaching a normal Hb in renal transplant recipients reduces the postoperative requirement for blood transfusions and has no deleterious effects on kidney graft function.

Adult↗
PubMed2000

[Water channels of the cell--aquaporins].

BACKGROUND: Several mechanisms in the body regulate the water transport within the cells up and down during physiological and pathological conditions. The discovery of aquaporins, water channel proteins, has brought more insight into and understanding of how water crosses plasma membranes within cells in body tissue. MATERIAL AND METHODS: The functions of aquaporins are not fully understood; this paper summarise current knowledge of various aquaporins. RESULTS: Known aquaporins are discussed in relation to some physiological, pathological and clinical conditions. INTERPRETATION: In the future, measurements of aquaporin concentrations in urine and possibly in other samples will give us a broader picture of water exchange and a better understanding of the mechanisms underlying water production in clinical states like renal and heart failure and liver insufficiency. Moreover, by manipulating water channel proteins by compounds developed for this purpose, one may have a tool for treating some clinical disorders in which water depletion or water overload is an important factor.

Aquaporins↗
PubMed2000

Nitric oxide regulates the aggregation of stimulated human neutrophils.

Neutrophil aggregation is mediated by both CD18 integrin and L-selectin. Nitric oxide attenuates the integrin-mediated adhesion of neutrophils to collagen and to endothelium and may therefore affect aggregation as well. FMLP-stimulated neutrophils exposed to l-arginine showed increased and prolonged aggregation, whereas cells pretreated with L-NAME did not differ from FMLP-stimulated controls. Nitric oxide is known to induce ADP ribosylation of G-actin, which inhibits polymerization. We detected equivalent levels of total F-actin in cells pretreated with l-arginine or L-NAME and non-pretreated controls. However, neutrophils pretreated with l-arginine and stimulated by CD18 integrin cross-linking exhibited a more limited increase in total F-actin, compared to control and L-NAME-pretreated cells. Thus at least two signaling pathways may be involved FMLP-stimulated aggregation, mediated by CD18 integrins. More specifically, it is plausible that FMLP-receptor signaling upregulates CD18 integrins and endogenous NO subsequently modulates CD18-mediated signaling to prolong aggregation, possibly through ADP-ribosylation of actin.

Actins↗
PubMed1997

Nitric oxide-releasing particles inhibit phagocytosis in human neutrophils.

We have constructed a yeast (Saccharomyces cerevisiae) particle capable of releasing NO, by loading heat-killed yeast particles with a hydrophobic NO-generating substance, GEA-5171. This particle decreased phagocytosis in solution, as measured with flow cytometry, to about 80% of control values. Phagocytosis on a surface, as counted under the microscope, was also decreased by about 20%. The nitric oxide furthermore counteracted the production of oxygen metabolites by neutrophils to about 20% of control values. The inhibitory effect was most pronounced for the intracellular production, as could be seen when neutrophils preincubated with NO-releasing particles were stimulated with chemotactic agent (FMLP) or phorbol ester (PMA). In conclusion, NO has inhibitory effects on both phagocytosis and the respiratory burst of neutrophils. Since nitric oxide is a hydrophobic gas and an air pollutant, there is a possibility that it accumulates in particles which then become more resistant to elimination.

Actins↗
PubMed1996

Fosinopril versus enalapril in the treatment of hypertension: a double-blind study in 195 patients.

The new angiotensin-converting enzyme (ACE) inhibitor fosinopril was compared with the ACE inhibitor enalapril in a multicenter (n = 11), multinational (Denmark, Finland, Iceland, Norway, and Sweden), double-blind, randomized, parallel-group 24-week study in 195 patients with mild to moderate essential hypertension [supine diastolic blood pressure, (SDBP) > or = 95 to < or = 110 mm Hg]. After discontinuing all previous antihypertensive medication, patients were entered into a placebo lead-in period of 4-6 weeks, followed by 24 weeks of randomized treatment with the active compounds administered with a double-dummy technique. The dose of fosinopril was 20 mg, which could be increased to 40 mg after 8 weeks (average 25.6 mg); that of enalapril was 10 mg, which could be increased to 20 mg after 8 weeks (average 12.9 mg). Hydrochlorothiazide 12.5 mg could be added after 16 weeks and was administered to 27% of the patients in the fosinopril group and to 30% in the enalapril group. All drugs were administered once daily. Supine systolic BP (SSBP) decreased from 157 to 143 mm Hg in the fosinopril group (p < 0.01), and from 159 to 147 mm Hg in the enalapril group (p < 0.01). SSDP decreased from 100 to 89 mm Hg in the fosinopril group (p < 0.01) and from 100 to 92 mm Hg in the enalapril group (p < 0.01). Throughout the study period, fosinopril reduced SSBP and SDBP numerically more than did enalapril, by 0-3 mm Hg. Adverse events (AE) caused withdrawal of study medication in 8 patients in the fosinopril group and in 14 patients in the enalapril group (NS). The number of reported AE was not statistically different in the two groups. Inhibition of the ACE was assessed in a subgroup of patients (n = 26, 13 in each group). Fosinopril caused a greater inhibition of ACE at the doses used in the present study, which was statistically significant. Both fosinopril and enalapril caused statistically significant reductions in BP of a similar magnitude, and both agents were well tolerated. However, fosinopril was consistently numerically slightly more effective than enalapril in reducing BP. There were fewer withdrawals due to AE (NS) in the fosinopril group, and the overall recorded AE were fewer in the fosinopril group (NS).

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1995

Nitric oxide reduces hydrogen peroxide production from human polymorphonuclear neutrophils.

Nitric oxide has been reported to affect both adhesion and respiratory burst of neutrophils. This indicates a possible role of nitric oxide in regulation of acute inflammatory responses. Release of oxygen metabolites from neutrophils can be measured using luminol-enhanced chemiluminescence and this method can detect both extracellularly and intracellularly released oxygen metabolites. Neutrophils treated with nitroprusside and activated with FMLP, type I collagen or PMA decreased their extracellular release of oxygen metabolites, while their intracellular release was almost unaffected. The effect of nitroprusside was mediated by nitric oxide since treatment with cyanide had the opposite effect. N-ethylmalemide treatment decreased both extra- and intracellular release of oxygen metabolites. This indicates that nitric oxide affects membrane-bound NADPH-oxidase either indirectly or directly, and not a cytosol factor of the oxidase as earlier shown for N-ethylmaleimide. In conclusion, extracellular nitric oxide attenuates extracellularly released oxygen metabolites from activated neutrophils in an inflammatory response.

Collagen↗
PubMed1995

Hypertension in cyclosporin A-treated patients is independent of circulating endothelin levels.

OBJECTIVES: To measure blood pressure (BP), plasma endothelin-1 (ET-1), atrial natriuretic peptide (ANP), antidiuretic hormone (ADH) and aldosterone (ALDO) concentration, and plasma renin activity (PRA) in patients treated with a low-dose cyclosporin A (CyA). DESIGN: An open study of patients with rheumatoid arthritis (RA) or palmoplantar pustulosis (PPP). SETTING: Out-patient clinics at the Central Hospital of Jyväskylä and Helsinki University Central Hospital. SUBJECTS: CyA was given to 25 patients with RA and to 10 patients with PPP. INTERVENTION: RA patients were given CyA at a dose of 2.5 +/- 0.13 mg kg-1 body weight (BW) to 3.47 +/- 0.79 mg kg-1 BW (mean values +/- SD) at the start of the study and after 6 months, respectively, and the CyA dose was 2.67 +/- 0.13 mg kg-1 BW decreasing to 2.07 +/- 0.96 mg kg-1 (P < 0.001) after 4 months in PPP subjects. RESULTS: Systolic (sBP) and diastolic blood pressure (dBP) increased from 127.8 +/- 13.6/79.7 +/- 8.4 mmHg to 140.0 +/- 19.8/83.8 +/- 9.7 mmHg during the study (P < 0.03). Plasma ET-1, ANP, ALDO and ADH concentration and PRA did not change during 4 to 6 months of CyA treatment. The plasma ANP concentration was constantly higher in CyA-treated RA patients (112 +/- 87 ng 1-1 to 118 +/- 78 ng 1-1) than in PPP patients (37.3 +/- 26 ng 1-1 to 47.7 +/- 39.9 ng 1-1; P < 0.02). The serum creatinine concentration remained within the normal range, but increased from baseline (76.7 +/- 11.9 mumol 1-1), to 90 +/- 15.4 mumol 1-1 (p < 0.001). The serum magnesium concentration decreased significantly (P < 0.005) after 6 months of CyA treatment in RA patients. No correlation was found between serum creatinine and plasma ET-1 concentration. CONCLUSIONS: Increased blood pressure during CyA treatment was independent of circulating ET-1 levels. A low dose of CyA did not induce increased ET-1 synthesis as judged from plasma samples. The high plasma ANP level observed in RA patients could be due to fluid retention caused by concomitant treatment with non-steroid anti-inflammatory drugs. Fluid retention and decreased magnesium levels could also be involved in the development of hypertension in CyA-treated subjects.

Adult↗
PubMed1995

Angio-oedema induced by enalapril.

We report the case of a patient who, 9 months after initiation of enalapril and hydrochlorothiazide combination treatment for hypertension, developed angio-oedema with near fatal outcome. Our patient was successfully intubated using a flexible bronchofiberoscope. This case demonstrates that patients given an angiotensin-converting enzyme (ACE) inhibitor may develop serious facial and laryngeal swelling even several months after the initiation of treatment. The occurrence of even mild swelling should lead to prompt cessation of the drug. Patients with incipient ACE inhibitor-related angio-oedema should, without any delay, be referred to hospital for emergency treatment.

Angioedema↗
PubMed1995

Nitric oxide regulates the chemiluminescence from stimulated human neutrophils.

Nitric oxide produced from L-arginine by a variety of cells, is a biologically active compound that can react with iron and thiols. The objective of this study was to investigate the effects of nitric oxide on the respiratory burst from human neutrophils. Treatment with nitroprusside increased the chemiluminescence from neutrophils stimulated with PMA or collagen, but not from cells stimulated with FMLP. Addition of L-arginine increased the chemiluminescence after stimulation with any of the three stimuli, while N omega-nitro-L-arginine methyl ester decreased it. Low doses of nitric oxide, either endogenously or exogenously produced, probably inhibited catalase or glutathione, leading to an increase in hydrogen peroxide available for chemiluminescence detection. This indicates that nitric oxide may reduce the protection against hydrogen peroxide in tissue and in invading catalase-positive bacteria.

Catalase↗
PubMed1994

S-nitroso-N-acetylpenicillamine reduces leukocyte adhesion to type I collagen.

The initial step in the migration of neutrophils to the extravascular space is adhesion to the endothelium. We examined the effect of nitric oxide on this process by treating human neutrophils with S-nitroso-N-acetylpenicillamine (SNAP), a NO-producing compound. Since NO has been shown to increase the level of cGMP in other cell types, we used 8-Br-cGMP in order to mimic the effects of NO. Indeed, both these treatments resulted in a reduced adhesion of neutrophils to type I collagen coated surfaces. After a prolonged incubation with SNAP, the adhesion was the same as for untreated cells. SNAP incubation reduced the F-actin content in the cells whereas 8-Br-cGMP increased it, demonstrating different mechanisms of action on F-actin. These data suggest that endothelium-derived nitric oxide is an important endogenous modulator of neutrophil adhesion, but the effect is not mediated by a cGMP-dependent regulation of F-actin levels.

Actins↗
PubMed1994

Priming of oxidative response in human neutrophils by anti-CD18 monoclonal antibodies.

Type I collagen, the most abundant protein in the body, after acid extraction adheres to and can induce a respiratory burst from neutrophils. It has been proposed that the effects of collagen are mediated via the CD18 subfamily of integrins. In the present study, adhesion was measured by affinity chromatography in a column containing collagen-coated microcarriers, while oxygen metabolite production was measured with luminol-dependent chemiluminescence. Neutrophil adherence to collagen was attenuated by anti-CD18 monoclonal antibodies. The respiratory burst in response to collagen was not affected by the antibodies. Incubation of neutrophils with anti-CD18 antibodies prior to stimulation with FMLP increased both the extra- and intracellular respiratory burst. Treatment with antibodies prior to PMA stimulation increased only the extracellular respiratory burst. In conclusion, the respiratory burst from neutrophils is primed by pretreatment with anti-CD18 monoclonal antibodies. The collagen-stimulated respiratory burst is probably also primed, but the effect is hidden by the simultaneous attenuation of adhesion.

Antibodies, Monoclonal↗
PubMed1993

Ophthalmic manifestations of epidemic nephropathy.

An ophthalmic examination was performed on 29 epidemic nephropathy patients consequently treated in the Central Hospital of Central Finland during the acute phase of the disease. Twenty-six of those patients were reexamined after an interval of one month. In the acute phase of the disease pathological ophthalmic changes were found in 15 cases (52%). The symptoms observed were conjunctival injection, oedema, flare and cell reaction in anterior chamber, anisochoria, retinal oedema, acute glaucoma and myopic shift of refraction. The main effect of disease on intraocular pressure was pressure-lowering. The myopic shifts were not dependent on initial refraction. In one case of acute glaucoma this shift could be explained by swelling and forward movement of the lens.

Acute Disease↗
PubMed1993

Raised plasma endothelin-1 concentration in patients with nephropathia epidemica.

Nephropathia epidemica (NE) with renal syndrome, caused by the Puumala-virus, is manifested clinically by the triad of fever, hemorrhage and renal failure. We observed raised plasma concentrations of endothelin-1 (ET-1) and atrial natriuretic peptide (ANP) in 23 patients during the acute phase of NE. They all developed transient renal failure and all displayed characteristics of NE, also verified by a rapid IgG antibody test. Blood pressure was normal or low in all subjects during the acute phase of the disease. Plasma ET-1 and ANP levels returned to normal following recovery one month later. The cause of increased ET-1 synthesis in NE remains unknown. It may be related to vascular damage or extravasation of blood. ET-1 may participate in the pathogenesis of acute renal failure of NE. Raised plasma ANP levels were most likely caused by fluid retention during the acute phase of NE. However, high levels of circulating ET-1 might have contributed to increased release of ANP.

Acute Kidney Injury↗