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Biomedical subjects

C Svalander

Publications and source records attributed to C Svalander.

At least 37 records · Page 2Linked to original sources
PubMed1991

Kidney transplantation in type 1 (insulin-dependent) diabetic patients. Early glomerulopathy.

The development of diabetic glomerulopathy in kidneys transplanted to diabetic patients was estimated in transplant biopsies and evaluated in relation to suspected clinical risk factors for diabetic nephropathy. Surgical biopsies were taken at baseline and at 24-36 months post-transplantation in 16 Type 1 (insulin-dependent) diabetic patients and 8 non-diabetic control subjects with a glomerular filtration rate more than 30 ml.min-1 at follow-up. Immunosuppressive therapy included cyclosporine in all but one case. Stereological methods were used to assess basement membrane thickness, volume fraction of mesangium per glomerulus, and volume fraction of matrix per mesangium. The volume fraction of interstitial tissue per cortex was estimated by light microscopy. After 2 years the basement membrane thickness had increased by 55 nm (SD 58 nm) in the diabetic group. This change was significantly different from that of 2 nm (SD 37 nm) in control subjects (p = 0.02). Mesangial volume fraction increased significantly by 0.04 (SD 0.03) in diabetic patients, and this change was significantly different from that of -0.01 (SD 0.04) in non-diabetic patients (p = 0.009). No change was detectable in the matrix expressed as fraction of mesangial volume. An increase in interstitial volume fraction from baseline to 2 years was observed, but was significant only in the diabetic group (p = 0.04). The changes in structural parameters did not correlate with mean values during follow-up of glycated haemoglobin or estimated protein intake, nor was any pattern discernible in the relationship to graft tissue types.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
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↗
PubMed1990

Renal transplantation in patients with systemic lupus erythematosus: increased risk of early graft loss.

The outcome of primary renal transplantation in 31 SLE patients was evaluated in relation to two contemporary controls per patient, matched for age, sex and immunosuppressive therapy. The proportion of living donors was one third in both groups. Patient survival did not differ, but graft survival at 6 and 12 months post transplantation was significantly reduced in SLE patients (p less than 0.001). When divided into groups using either azathioprine and steroids or combinations including cyclosporin A (14 and 17 SLE patients in each group), graft survival was significantly reduced for the azathioprine-treated SLE patients, 36% vs. 82% for their controls at one year. For cyclosporin-treated SLE patients, one-year graft survival was 59% vs. 85% for their controls, and 6 out of 17 grafts in the cyclosporin-treated group were lost within the first month vs. only 4 out of 34 controls. These differences were, however, not statistically different. Most failed grafts were lost from rejection, with a high proportion of acute vascular rejection, isolated or in combination with cellular rejection. There was no apparent association between rejection and HLA-matched or presence of HLA antibodies. Retransplantation was successful in 6 out of 7 cases. We conclude that SLE patients have an increased risk of early graft rejection, but that this may be overcome by more powerful immunosuppressive therapy.

Adolescent↗
PubMed1989

Tubulointerstitial nephritis caused by the antiviral agent foscarnet.

The antiviral agent foscarnet has long been used in our unit to treat cytomegalovirus (CMV) infections in renal transplant patients. The clinical effect has been convincing and, apart from changes in serum calcium levels, very few side effects have been noted. We have, however, observed a nephrotoxic reaction in a series of patients with initially good renal function who therefore received high doses of foscarnet. Transplant biopsies performed in five of those patients revealed degenerative changes in the tubular epithelial cells as well as tubular calcium deposits and an infiltration of the interstitium by mixed mononuclear and polymorphonuclear leucocytes. Renal insufficiency was accompanied by high fever. After withdrawal of the drug, the temperature rapidly normalized, whereas serum creatinine continued to rise for about 3 days and then fell back towards previous levels. We conclude that transplant biopsies are of great value in distinguishing between a foscarnet nephrotoxic effect and CMV nephritis, various forms of rejection, and other causes of impaired renal function.

Adult↗
PubMed1989

Serum immunoglobulins and IgG subclasses in patients with glomerulonephritis.

The serum concentrations of IgG, IgA, IgM and of the four subclasses of IgG were determined by radial immunodiffusion in 103 patients, mean age 42 (range 16-72), with various types of glomerulonephritis. Forty-nine healthy blood donors, mean age 41 years (range 19-65), served as controls. Kidney biopsies were obtained from all the patients for examination by histopathology and by immunofluorescence. The glomerulopathies were classified according to WHO criteria. The serum immunoglobulin patterns were different for the various clinical groups of patients. Patients with Wegener's granulomatosis, rapidly progressive glomerulonephritis and SLE had a significant increase in total IgG and of IgG4 (P less than 0.05-0.001). Patients with minimal change disease had low concentrations of IgG (P less than 0.001) with a significant decrease in IgG1 and IgG2 (P less than 0.001 and 0.01, respectively). Highly significant increases in IgA were noted for patients with IgA nephritis (P less than 0.001) but high levels were also seen in patients with chronic glomerulonephritis. The findings might have diagnostic implications.

Adolescent↗
PubMed1989

Effect of eicosapentaenoic acid rich menhaden oil and MaxEPA on the autoimmune disease of Mrl/l mice.

The Mrl lpr/lpr (Mrl/l) mouse is a model for systemic lupus erythematosus and rheumatoid arthritis in humans. The diet of Mrl/l mice was supplemented with EPA (see Introduction) in menhaden oil or in the commerical fish oil MaxEPA. The survival of mice was not affected by the dietary manipulations. The addition of menhaden oil decreased the severity of the renal pathology. However, MaxEPA containing the same amount of eicosapentaenoic acid was considerably less effective. A diet deficient in polyunsaturated fatty acids did not ameliorate any manifestations of the disease. Anti-DNA antibody levels in serum were not influenced by the therapy. Myocardial abscesses and/or ulcerating valvular lesions were observed in about one third of the mice, irrespective of the diet given.

Animals↗
PubMed1988

A strong correlation between glomerular filtration rate and filtration surface in diabetic nephropathy.

Quantitative structural studies were performed in kidney biopsy specimens from 24 long-term Type 1 (insulin-dependent) diabetic patients with persistent albuminuria due to diabetic glomerulopathy. Ten patients were receiving antihypertensive treatment, and among the remaining patients the mean blood pressure was 142/91 mm Hg (SD = 11/9). The urinary albumin excretion rate showed a range from 100 to 5494 micrograms/min (geometric mean 688 micrograms/min.) Glomerular filtration rate also showed a wide range, from supranormal to markedly decreased values (128 to 28 ml.min-1. (1.73 m2)-1, mean 75). The filtration surface (interface between capillary and urinary space) per total number of nephrons (open + occluded) was estimated by combined light-and electron microscopy. The percentage occluded glomeruli as well as structural quantities in the open glomeruli were taken into account in this estimate. A highly significant correlation was seen between glomerular filtration rate and filtration surface per nephron (r = 0.77, p less than 10(-4). The percentage occluded glomeruli contributed significantly to the variation in glomerular filtration rate (for this relationship tested separately r = -0.78, p less than 10(-5). The volume of open glomeruli was even larger than that seen in early diabetic glomerular hypertrophy and tended to increase with the percentage of glomerular closure, indicating that a compensatory hypertrophy might have taken place. In the open glomeruli the filtration surface constituted a smaller percent of total capillary surface (the remaining part facing the mesangial regions) than in early diabetic patients and control subjects. Our study has demonstrated that reduced glomerular filtration surface is closely associated with reduced glomerular filtration rate in Type 1 diabetic patients with diabetic nephropathy.

Adult↗
PubMed1988

Effect of captopril on murine systemic lupus erythematosus disease.

The MRL/1 and New Zealand black-New Zealand white cross (NZB x W) mice spontaneously develop a disease similar to systemic lupus erythematosus in man. The effect of antihypertensive treatment on MRL/1 and NZB x W mice was studied with respect to survival, blood pressure, proteinuria, haematuria and renal histopathology. The treatment consisted of angiotensin converting enzyme (ACE) inhibitors (captopril and enalapril) and bretylium, a sympathetic blocker. Tail systolic blood pressure was measured with a strain gauge technique. All antihypertensive drugs caused a reduction in blood pressure in both strains. In MRL/1 bretylium and both ACE inhibitors improved renal histopathology, but only captopril prolonged survival, and it decreased proteinuria and haematuria. In NZB x W captopril decreased proteinuria but did not influence survival or renal histopathology. Bretylium was without any effect on these parameters. At the doses used captopril improves survival in MRL/1 mice and decreases proteinuria and haematuria in both MRL/1 and NZB x W mice. Since bretylium and enalapril lack this property despite a similar blood pressure reduction, it seems to be a drug-specific action.

Animals↗
PubMed1988

Beneficial effect of captopril on systemic lupus erythematosus-like disease in MRL lpr/lpr mice.

MRL lpr/lpr (MRL/l) mice exhibit a disease similar to systemic lupus erythematosus (SLE) in humans. To investigate the influence of antihypertensive treatment on this disease, four groups of MRL/l mice were treated with the angiotensin-converting enzyme inhibitor captopril (n = 25), with the sympathetic blocker bretylium (n = 15), and with cyclophosphamide (n = 10). Thirty-five mice did not receive any treatment and served as controls. Survival rate, blood pressure, incidence of proteinuria and hematuria, renal pathology, lymphoid hyperplasia and dermatitis were studied. The survival at the age of 36 weeks was significantly improved by captopril as compared to controls (60 vs. 25%, p = 0.035). The cyclophosphamide group showed no mortality at that time and the bretylium group did not differ from the control group. Captopril and bretylium reduced systolic blood pressure significantly while cyclophosphamide was without effect. Captopril and cyclophosphamide diminished significantly the glomerular damage with less proliferative changes and a decreased incidence of proteinuria. The bretylium-treated animals also exhibited an improved renal pathology index but they did not differ from the controls with respect to proteinuria and hematuria. Lymphoid hyperplasia and dermatitis were decreased only by captopril and cyclophosphamide. It is concluded that captopril improves survival in SLE disease of MRL/l mice, counteracting lymphoid hyperplasia, renal disease, dermatitis and decreasing arterial blood pressure.

Animals↗
PubMed1988

Inflammatory cells in transplanted kidneys are infected by human cytomegalovirus.

To determine which cells in kidney grafts are infected with human cytomegalovirus (HCMV) before and after transplantation, kidney specimens were studied by in situ hybridization with 35S-labeled DNA probes representing HCMV immediate-early and late genes. Pretransplantation biopsies and serial posttransplantation biopsies were obtained from 7 renal grafts. All of the transplant recipients were HCMV-seronegative at the time of transplantation and all developed primary HCMV infections. HCMV nucleic acids were not detected in biopsies taken from the healthy donor kidneys before transplantation. However, biopsies taken at various intervals after transplantation showed abundant hybridization with HCMV immediate-early and late gene probes. Virtually all of the hybridizing cells were mononuclear inflammatory cells in the interstitial spaces of the kidney. Occasional hybridization was seen with renal tubular or glomerular cells. No cytomegalic cells were seen. Biopsy specimens taken after systemic anti-HCMV chemotherapy with phosphonoformate showed no uniform reduction in HCMV gene expression. These studies demonstrate that the principal HCMV-infected cells in kidneys of renal transplant patients with primary HCMV infections are infiltrating inflammatory cells.

Biopsy↗
PubMed1988

Macrophages and C3-deposition in early biopsies as a sign of poor prognosis in human kidney graft rejection.

Clinical characteristics such as retransplantation, cytotoxic antibodies, no or delayed graft onset, or early anuria seem to be important factors to define this group of patients. If early biopsies show intravascular presence of macrophages in venulae or capillaries usually combined with a C3-deposition in glomular capillary walls, the prognosis of graft outcome seems to be poor even with rather heavy antirejection therapy.

Adult↗
PubMed1987

Cytotoxic drug treatment of reactive amyloidosis in rheumatoid arthritis with special reference to renal insufficiency.

Twenty-two patients with amyloidosis secondary to rheumatoid arthritis were randomised and followed prospectively in order to determine whether treatment with cytotoxic drugs could postpone the development of end-stage renal failure. The diagnosis of amyloidosis was based on albuminuria, amyloid-positive rectal and/or abdominal fat aspiration and/or renal biopsies. Renal function was followed by repeated 51Cr-EDTA measurements of the glomerular filtration rate (GFR). Urinary albumin and serum-creatinine were found unreliable as predictors of renal function. GFR declined more rapidly in the patient group receiving only symptomatic drugs and no cytotoxic drugs (NT-group). After an initial decline, the GFR in the cytotoxic drug treatment group (T-group), mean treatment quotient 79%, levelled off and remained constant for a considerable time. The mean observation time was 45.7 months in the NT-group and 53.5 months in the T-group. Seven out of eleven patients in the NT-group developed end-stage renal disease, compared to two out of eleven patients in the T-group. The cumulative proportion of survivors in the NT-group at 36 and 60 months was 71% and 27% respectively. The corresponding figures in the T-group were 89% and 89%. The difference in favour of the cytotoxic drug-treated group was significant (p less than 0.04).

Adult↗