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Biomedical subjects

T Sandberg

Publications and source records attributed to T Sandberg.

At least 37 records · Page 2Linked to original sources

Human endothelial cell migration is stimulated by urokinase plasminogen activator:plasminogen activator inhibitor 1 complex released from endometrial stromal cells stimulated with transforming growth factor beta1; possible mechanism for paracrine stimulation of endometrial angiogenesis.

Human endometrial stromal cell cultures, stimulated for two days with recombinant transforming growth factor beta1 (TGFbeta1; 10 ng/ml), contained conditioned medium concentrations of urokinase plasminogen activator (uPA), plasminogen activator inhibitor 1 (PAI1), and uPA:PAI1 complex. Since a number of cellular effects have been reported to follow a binding of enzymatically inactive uPA to the receptor in different cell types, we studied the influence of uPA:PAI1 complex on human umbilical vein endothelial cells (HUVEC) and human microvascular endothelial cells (HMEC-1). Increasing concentrations of uPA:PAI1 complex as well as free uPA resulted in a dose-dependent stimulation of endothelial cell migration. Stimulation by the complex was of the same magnitude as that of free uPA on a molar basis and reached its maximum at 1 nM in both cell types. PAI1 by itself, however, had no effect on cell migration. The migratory response to both uPA and the uPA:PAI1 complex was inhibited by antibody adhesion to the cell surface receptor for uPA. In addition, we found that TGFss1 had a direct stimulatory effect on migration in both HUVEC and HMEC-1. This response did not, however, involve the binding of uPA to the uPA receptor. Since TGFbetas are expressed in endometrial tissue and reportedly stimulate angiogenesis in other tissues in vivo, though not endothelial cell proliferation in vitro, they may engage in the regeneration of endometrial vasculature indirectly via perivascular cells. We found that the uPA:PAI1 complex, when released from endometrial stromal cells in response to TGFbeta1, stimulated endothelial cell migration. This suggests a possible mechanism for paracrine stimulation of endometrial angiogenesis.

Cell Line↗

Blood transfusion and postoperative wound infection in intracapsular femoral neck fractures.

The relationship between blood transfusion and postoperative wound infection was studied in 695 operations for cervical hip fractures. A total of 156 (22%) patients were transfused with a total of 392 units of blood. A total of 31 (4.5%) patients developed a postoperative superficial or deep wound infection. Cultures identified Staphylococcus aureus as the cause in 71% and E. coli in 9.7% of the infections. A total of 11 out of 156 (7.05%) transfused patients developed a wound infection. In contrast only 20 out of 539 (3.71%) non-transfused patients developed a wound infection (p < 0.05).

Aged↗

Differential regulation of the plasminogen activator inhibitor-1 (PAI-1) gene expression by growth factors and progesterone in human endometrial stromal cells.

Plasminogen activator inhibitor-1 (PAI-1) has important regulatory functions in haemostasis, extracellular matrix turn-over and cell adhesion. We studied PAI-1 gene expression in primary cultures of endometrial stromal cells, and found that PAI-1 protein and mRNA were increased both by agents associated with differentiation, i.e. progesterone and transforming growth factor beta1 (TGFbeta1), and by those promoting proliferation, i.e. epidermal growth factor (EGF), TGFalpha and basic fibroblast growth factor (bFGF). In order to further elucidate the mechanism of regulation, we transfected stromal cells with an expression construct containing 804 bp of the PAI-1 promoter fused to a chloramphenicol acetyl transferase (CAT) reporter gene. After stimulation with the polypeptide growth factors TGFbeta1, EGF and bFGF we found increased CAT activity, indicating that these stimulators had initiated interaction with the transfected promoter fragment. On the other hand, stimulation with progesterone did not increase CAT activity, even though these cells were perfectly able to respond with increased secretion of PAI-1 protein. Run off experiments demonstrated that progesterone increased the stability of PAI-1 mRNA in endometrial stromal cells. We conclude that the polypeptide growth factors TGFbeta1, EGF and bFGF increase PAI-1 expression by increasing gene transcription. Progesterone, on the other hand, does not interact with the 804 bp promoter region, but increases the stability of PAI-1 mRNA.

Adult↗

Aminoglycosides do not improve the efficacy of cephalosporins for treatment of acute pyelonephritis in women.

A prospective, coordinated, randomized multicentre trial was conducted to determine whether tobramycin 160 mg intravenously (i.v.) once daily for 2 days would improve the efficacy of cefotaxime 1 g i.v. twice daily for 2 days followed by a 10-day course of oral cefadroxil 1 g twice daily, in the treatment of community-acquired acute pyelonephritis in women. Of 73 patients enrolled in the study, 51 could be evaluated according to the protocol. There were no significant differences in bacteriological cure rates between the combined treatment with tobramycin/cefotaxime and cefotaxime alone, either at short-term follow-up (63.0% vs 59.1%; 95% confidence interval (CI) for difference in proportions -23.4% to 31.2%), or up to 7 weeks after cessation of treatment (42.9% vs 52.2%; 95% CI, -18.0% to 36.6%). A modified intention-to-treat analysis showed no difference in clinical efficacy between the two regimens (68.6% vs 69.2%; 95% CI, -22.9% to 24.1%). Tobramycin seemed to enhance the resolution of inflammation by a more rapid decline in C-reactive protein levels. The high recurrence rates after treatment with beta-lactam antibiotics in this and previous studies of acute pyelonephritis may be explained by adverse ecological effects rather than failure to eradicate the infection.

Adult↗

Symptomatic urinary tract infection in women in primary health care. Bacteriological, clinical and diagnostic aspects in relation to host response to infection.

OBJECTIVE: To evaluate rapid diagnostic tests for bacteriuria in women with symptoms of urinary tract infection (UTI), and to analyse bacteriological and clinical findings in relation to host response to infection. DESIGN: Prospective study of symptomatic UTI in women. SETTING: Primary health care centres. PATIENTS: 819 women with signs and symptoms suggestive of UTI. MAIN OUTCOME MEASURES: History of UTI and clinical findings were recorded. After randomization but before antibiotic treatment, urine specimens were analysed for pyuria by sediment microscopy and for nitrite using a test strip, and cultures were performed. The systemic inflammatory response was assessed by C-reactive protein (CRP), erythrocyte sedimentation rate, and total white blood cell count. RESULTS: The combined use of tests for pyuria and nitrite resulted in a high sensitivity (0.93) and efficacy (0.85) when the prevalence of bacteriuria was 0.89. Escherichia coli and Staphylococcus saprophyticus accounted for 93% of the urinary isolates. Significantly more patients infected with S. saprophyticus than E. coli complained of dysuria (p < 0.05), frequency (p < 0.05) or flank pain (p < 0.01). CRP agreed best with the clinical diagnosis of acute pyelonephritis. CONCLUSIONS: In women with a high probability of bacteriuria, i.e. those with symptoms of lower UTI, examination for pyuria and urinary nitrite offers high diagnostic efficacy. If either or both tests are positive urine cultures can be omitted.

Adolescent↗

Suppressed antibody and interleukin-6 responses to acute pyelonephritis in pregnancy.

This study examined the effect of pregnancy on the host response to acute pyelonephritis. Urine and serum samples were obtained at the time of diagnosis and after two weeks, from non-pregnant and pregnant women with acute pyelonephritis. The samples were analyzed for interleukin-6 (IL-6) and specific antibody activity to antigens extracted from the Escherichia coli strain infecting each patient. The host response to infection was further quantitated as fever, C-reactive protein, and renal concentrating capacity. Acute pyelonephritis in non-pregnant and pregnant women was accompanied by a significant serum and urine antibody response. The serum antibody response was significantly lower in the pregnant group. The IL-6 levels in serum and urine at diagnosis were significantly higher in the non-pregnant compared to the pregnant women. These results demonstrate that the immunosuppression of pregnancy includes the mucosal IL-6 and specific antibody responses to acute pyelonephritis caused by E. coli.

Acute Disease↗

Virulence characteristics of Escherichia coli in relation to host response in men with symptomatic urinary tract infection.

To assess virulence properties in uropathogenic Escherichia coli isolates from men with symptomatic urinary tract infection (UTI), we analyzed 88 urinary isolates from men with acute pyelonephritis (n = 41), febrile UTI without clinical signs of renal infection (n = 33), or acute cystitis (n = 14) for O:K:H serotype, P fimbriae, and production of hemolysin and aerobactin. In the three diagnostic groups, 88%, 67%, and 79% of the strains, respectively, were represented by 10 O antigen groups commonly associated with acute pyelonephritis in women and children. Fifty-eight different O:K:H serotypes could be identified, of which O18ac:K5:H- predominated (n = 8). There was a higher frequency of hemolytic strains among patients with pyelonephritis (73%) and febrile UTI (76%) and a lower frequency of P-fimbriated strains (56% and 45%, respectively) and aerobactin-positive strains (51% and 39%, respectively) among these patients than was previously encountered in women and children with uncomplicated acute pyelonephritis. The distribution of bacterial properties was unrelated to patient age and underlying complicating factors. The findings suggest differences in host-parasite relationships between men and women with symptomatic UTI caused by E. coli.

Adult↗

Cytomegalovirus infection of the CNS in non-compromised patients.

Six non-compromised patients with cytomegalovirus (CMV) associated meningoencephalitis are described. CMV was isolated from the cerebrospinal fluid (CSF) in 2/4 cases, while the diagnosis was based on an 8-fold rise in CMV-specific serum IgG antibodies and intrathecal antibody production against CMV in one case. By the polymerase chain reaction (PCR) CMV DNA was detected in the CSF in 5/5 cases and in serum in 3/4 cases. In one patient who had an Influenza A infection, both CMV and Epstein-Barr virus DNA were detected by PCR in the CSF. In 4 patients possible triggering events could be identified. Symptoms and signs indicating a multifocal brain involvement were present in 4 patients. The outcome was generally favourable except for sequelae in form of slight dysphasia in one case.

Aged↗

Virulence factors and pap genotype in Escherichia coli isolates from women with acute pyelonephritis, with or without bacteremia.

Bacteremia develops in a subgroup of patients with acute pyelonephritis. This study examined isolates of Escherichia coli from the urine and the blood of 25 bacteremic and 67 nonbacteremic women with this acute disease. P-fimbriated strains were found in 100% of bacteremic patients without complicating factors but in only 71% of nonbacteremic patients without complications (P < .05). Non-P-fimbriated strains were only found to cause bacteremia in three patients with compromising host factors. Strains from the bacteremic group and those from the nonbacteremic group did not differ significantly in terms of hemolysin or aerobactin production or of serum resistance. The P-fimbriated strains from both groups of patients carried pap DNA sequences of the papGIA2 adhesin type; prsGJ96 homologous DNA sequences were rare. The results suggested that P fimbriae and compromising host conditions independently increase the risk for bacteremia during acute pyelonephritis.

Acute Disease↗

Sexual acquisition of acute pyelonephritis in a man.

A 51-year-old man presented with acute cystitis at a time when his wife was admitted with symptoms of acute pyelonephritis. Before the man developed his symptoms his wife had complained of urinary frequency and dysuria for a 2-week period. Two weeks after a 10-day course with trimethoprim he experienced a relapse manifesting as acute febrile pyelonephritis. The strains of Escherichia coli isolated from the urine of both patients belonged to the same serotype O51, O117:K1, were non-haemolytic, produced aerobactin, expressed P-fimbriae, and showed identical antibiotic susceptibility pattern. The findings strongly suggest that the E. coli strain might have been sexually transmitted from the wife to her husband.

Cystitis↗

Comparison of urine and serum concentrations of interleukin-6 in women with acute pyelonephritis or asymptomatic bacteriuria.

The mucosal and systemic interleukin-6 (IL-6) response to urinary tract infection was analyzed in women with acute pyelonephritis or asymptomatic bacteriuria. Urine and serum samples were obtained at diagnosis and after treatment. IL-6 activity was elevated in urine samples from most bacteriuric women, regardless of the severity of infection. Urinary levels greater than 20 units/mL occurred in 25 of 29 women with acute pyelonephritis and in 36 of 42 women with asymptomatic bacteriuria. Elevated serum IL-6 levels were found mainly in patients with acute pyelonephritis: Levels greater than 20 units/mL occurred in 14 of 28 women with acute pyelonephritis compared with 0 of 28 women with asymptomatic bacteriuria. These results suggest that bacteriuria is accompanied by elevated urinary IL-6 levels and that this IL-6 is locally produced. The spread of IL-6 to the circulation in patients with acute pyelonephritis may contribute to the elevation of fever and C-reactive protein characteristic of the disease.

Adult↗

Cytomegalovirus infections and toxoplasmosis in heart transplant recipients in Sweden.

The morbidity of cytomegalovirus (CMV) infection and toxoplasmosis was evaluated in 75 heart transplant recipients. Among the 73 patients who survived more than one week after transplantation, 16 (22%) acquired primary CMV infection and 30 (41%) had evidence of secondary infection. All CMV seronegative recipients receiving hearts from seropositive donors developed CMV infection. The majority of infections (42/46) occurred during the first 4 months after transplantation. Overall, the incidence of symptomatic CMV disease was 44%. The infections were generally mild and only 1 death was attributed to primary CMV disease complicated by bacterial septicaemia and multiple organ failure. The severity of CMV disease was greatest among those with primary infection. There were 3 cases of toxoplasmosis. Two patients were toxoplasma seronegative before transplantation and developed clinical and serological signs of infection 2-3 months after transplantation despite receiving organs from seronegative donors. Of toxoplasma seronegative recipients receiving allografts from seropositive donors 3/4 were prophylactically treated with pyrimethamine for 6 weeks. None developed clinical or serological signs of toxoplasmosis while one patient who received trimethoprim-sulfamethoxazole had a subclinical infection.

Adolescent↗