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Biomedical subjects

S Lindgren

Publications and source records attributed to S Lindgren.

At least 73 records · Page 4Linked to original sources
PubMed1998

Effects of serpins on cholesterol crystallization in model bile.

BACKGROUND/AIMS: The serine proteinase inhibitors (serpins), alpha-1-antitrypsin (AAT) and alpha-1-antichymotrypsin (ACT), are acute phase proteins synthesized by hepatocytes and excreted to some extent into bile. Their role in gallstone pathogenesis is unclear, and it was the aim of this study to determine their effect on cholesterol crystal growth rate in model bile. METHODS: Purified AAT and ACT were added to model bile at concentrations from 0.5 to 500 microg/ml. Cholesterol crystal growth was analyzed daily by polarizing microscopy and spectrophotometrically at 650 nm. Serpin inhibitory activity was measured spectrophotometrically at 405 nm, and polymerization was studied on 7.5% SDS-PAGE under non-reducing conditions, by immunoelectrophoresis and Western blotting. RESULTS: ACT added to model bile at a concentration of 0.5 microg/ml, inhibited cholesterol crystallization by 30%, had no influence at 5 microg/ml, and increased the crystallization rate 2-3 fold at concentrations of 50 and 500 microg/ml. AAT at a concentration of 0.5 microg/ml had a profound (50%) inhibitory effect on cholesterol crystal growth rate, lacked significant effect at both concentrations of 5 and 50 microg/ml, and showed stimulation of crystal growth up to 30% at a concentration of 500 microg/ml. Both serpins incubated in model bile polymerized and totally lost their inhibitory activity. CONCLUSIONS: Serpins can exhibit both inhibiting and promoting effects on the cholesterol crystallization rate in model bile, dependent on their concentrations. Since AAT and ACT are acute phase proteins, their concentrations may vary under certain pathological conditions, which may result in different actions of these serpins in gallstone formation.

Bile↗
PubMed1998

The effect of selective phosphodiesterase inhibitors on mucociliary activity in the upper and lower airways in vitro.

Bronchodilatory substances such as the phosphodisterase inhibitor (PDE-I) theophylline stimulate mucociliary activity. With the introduction of selective PDE-Is it has become possible to study the functional importance of each phosphodiesterase enzyme (PDE) concerning the regulation of the ciliary beat. The effects of rolipram (inhibiting a cAMP specific PDE (PDE4), milrinone (inhibiting a cGMP inhibited PDE (PDE3)) and zaprinast (inhibiting a cGMP specific PDE (PDE5)) were investigated in in vitro preparations from the rabbit maxillary sinus and trachea. Ciliary beat frequency (CBF) was measured with a photoelectrical method. In sinus mucosa all three compounds accelerated CBF. Milrinone (10(-5) M) by 22.6 +/- 5.3% (n = 6; P < 0.01), rolipram (10(-5) M) by 29.7 +/- 5.7% (n = 7; P < 0.01), and zaprinast (10(-5) M) by 19.4 +/- 6.3% (n = 6; P < 0.05). In the tracheal specimens at a concentration of 10(-5) M, milrinone accelerated CBF by 27.5 +/- 9.0% (n = 7; < 0.05), rolipram by 11.6 +/- 2.8% (n = 6; P < 0.05) and zaprinast by 24.3 +/- 5.3% (n = 7; P < 0.01). Comparison of the effects in the upper and lower airways showed that at concentrations of 10(-5) and 10(-4) M rolipram was more effective in the upper than in the lower airways. The reverse was true of milrinone which concentrations of 10(-7) and 10(-6) M had a significant effect in tracheal specimens but not in sinus specimens. Zaprinast was equally effective in both the upper and lower airways. It is concluded that in both the upper and lower airways selective PDE-Is have an accelerating effect on the CBF that may be beneficial in the treatment of airway diseases.

Culture Techniques↗
PubMed1998

Long-term outcome of chronic hepatitis C infection in a low-prevalence area.

BACKGROUND: Although hepatitis C virus (HCV) infection is recognized as an important causative factor in the development of liver cirrhosis and hepatocellular cancer (HCC), the strength of this correlation has been difficult to confirm in low-prevalence areas. METHODS: Stored serum samples from 987 consecutive (1978-88) patients with chronic liver disease were tested with an enzyme-linked immunosorbent assay for anti-HCV and further confirmed by immunoblot. To evaluate the long-term outcome, the cohort was followed up until 1995, for a median observation time of 10 years. RESULTS: Anti-HCV, confirmed by immunoblot, was found in 9.5% (94 of 987) of the patients, and at inclusion most patients were asymptomatic irrespective of anti-HCV status. Of the 445 patients who died during the study period, 44 were HCV-positive. A liver-related cause of death was far commoner and the age-adjusted survival shorter among HCV-positive patients than among HCV-negative ones. At death 68% (30 of 44) of the HCV-positive subgroup had developed cirrhosis, and 30% (13 of 44) had concurrent HCC, as compared with 36% (142 of 393) (P = 0.001) and 8% (31 of 393) (P = 0.001), respectively, of the HCV-negative subgroup. HCV infection (P < 0.001), alcohol abuse (P < 0.001), and immigrant status (P = 0.045) were independent factors with regard to the development of cirrhosis, whereas HCV infection (P = 0.040) and immigrant status (P = 0.012) were independent factors with regard to HCC. CONCLUSIONS: HCV infection is common among patients with chronic liver disease, even when clinical evidence of viral infection is sparse, and constitutes a significant cause of death even in a low-prevalence area.

Carcinoma, Hepatocellular↗
PubMed1998

Pregnancy in HIV-infected women. Counseling and care--12 years' experiences and results.

BACKGROUND: A specialized antenatal care unit was set up for counseling and care of HIV-infected pregnant women. The team consisted of gynecologists, a midwife, a social worker and pediatricians. METHODS: The women were referred from departments of infectious diseases, venereology or institutions for drug addicts, antenatal care units and abortion clinics, or applied themselves. Women identified in the pregnancy HIV screening program were informed primarily by the team. The women were counseled along with their partners and cared for during abortion or the antenatal period, delivery and post partum. Contraceptive services were offered and psychosocial support was given. RESULTS: Between April 1985 and March 1997, 95 HIV-infected women with 122 pregnancies attended. Twenty-one per cent were or had been drug users, 2% had been infected by transfused blood and 77% were classified as having been sexually infected, two thirds of whom were Africans. The mean age was 27.8 years. In 54 of 93 pregnancies (58%) in which the woman could make an informed decision, she elected abortion -- in 37 cases for HIV related reasons. Significantly more women with an uninfected steady partner, compared to women without a steady partner, chose to continue the pregnancy, as did women in a relatively stable social situation. Of the partners, 68 were HIV-negative, 36 HIV-positive and 18 not tested. No severe HIV-related complications occurred during pregnancy. Seven of 40 (18%) children with a known infection status were infected. During the course of follow-up, nine mothers, two fathers and three children have died. Seventeen children were at risk of being orphaned, and another five were placed in foster care. CONCLUSION: Although it is possible to reduce mother-to-infant transmission by zidovudine therapy, the negative consequences of HIV and childbearing are still substantial. Therefore HIV screening during pregnancy and pre-pregnancy counseling are important issues for the health care system.

Abortion, Induced↗
PubMed1997

Serine protease inhibitors in patients with chronic viral hepatitis.

BACKGROUND/AIMS: This study aimed to determine whether deficiency of the major serine protease inhibitors (alpha1-antitrypsin (AAT) or alpha1-antichymotrypsin (ACT)) is associated with increased risk for chronic hepatitis B or C virus (HBV or HCV) infection. METHODS: We studied 709 adults with chronic liver disease who had undergone liver biopsy during the 14-year period 1978-92. Anti-HCV testing was carried out with second-generation ELISA and immunoblot assays (RIBA 2). HBV markers were tested with commercially available radioimmunoassays. ACT and AAT concentrations in plasma were measured with electroimmunoassay and immune nephelometry. Plasma samples were screened for the AAT PiZ deficiency with ELISA technique and phenotyped by isoelectric focusing. The 229Pro-->Ala mutation for ACT deficiency was identified by PCR techniques. RESULTS: Of the 709 patients, 132 (18.6%) were positive for anti-HCV according to RIBA 2. PiZ AAT deficiency was found in 44 (6.2%) of patients (one PiZZ, 38 PiMZ, and PiSZ), while subnormal ACT levels were found in 33 (4.6%) patients, frequencies that were higher than expected in the general population (p=0.0375 and p<0.0001, respectively). Of the PiZ-carriers, 8/44 (18%) were found to be anti-HCV positive according to RIBA 2, as compared to 123/662 (19%) non-PiZ-carriers (p>0.05). One of these patients had cirrhosis, four chronic active hepatitis, and three chronic persistent hepatitis. In contrast, 17/33 (51.5%) of the patients with subnormal ACT were anti-HCV positive (OR=5.2, CI=2.6-10.6; p<0.0001). No relationship was found between HBV infection and AAT deficiency or subnormal ACT levels. Only one patient with subnormal ACT levels was heterozygous for the 229Pro-->Ala mutation of ACT deficiency. There was no significant difference in the histological findings when the patients with subnormal ACT levels or PiZ allele were subgrouped according to HCV status. CONCLUSIONS: There is no overrepresentation of chronic HBV or HCV in heterozygous AAT deficiency, although an association with more severe liver disease in such patients cannot be excluded. In contrast, low plasma levels of ACT that may be acquired or hereditary, due to mutations other than 229Pro-->Ala, are frequent in HCV infection.

Adolescent↗
PubMed1997

Severe alpha1-antitrypsin deficiency (PiZ homozygosity) with membranoproliferative glomerulonephritis and nephrotic syndrome, reversible after orthotopic liver transplantation.

BACKGROUND/AIMS: Nephropathy associated with alpha1-antitrypsin deficiency is assumed to be an unusual entity. We describe the case of a 23-year-old woman with severe alpha1-antitrypsin (PiZ homozygosity) deficiency who developed hepatic cirrhosis in childhood, and glomerulonephritis and nephrotic syndrome in adult life. METHODS/RESULTS: A renal biopsy was consistent with membranoproliferative glomerulonephritis. An immunofluorescence study revealed the presence of alpha1-antitrypsin (PiZ) in the subendothelial region of the glomerular basement membrane. The renal disease was reversible after orthotopic liver transplantation. CONCLUSIONS: The presence of abnormal PiZ protein in the subendothelial region of the glomerular basement membrane may suggest a possible role for this protein in the pathogenesis of glomerulonephritis. The case should add impetus to the search for alpha1-antitrypsin deficiency in any patient presenting with combined liver and renal disease, in the absence of evidence of hepato-renal syndrome, and illustrates that liver transplantation alone may reverse the nephropathy associated with alpha1-antitrypsin deficiency.

Adult↗
PubMed1997

Mother-to-infant transmission of human immunodeficiency virus type 1 involving five envelope sequence subtypes.

Genetic analysis of human immunodeficiency virus type 1 (HIV-1) from cases of mother-to-infant transmission were analyzed in an effort to provide insights into the viral selection that may occur during transmission, as well as the timing and source of transmitted viruses. HIV-1 env genes obtained from seven mothers and their perinatally infected infants in Sweden were studied. Five envelope sequence clades (A to E) were found to be represented. We used a heteroduplex tracking assay (HTA) to assess the genetic relatedness between early viral isolates from the infants and serial maternal virus populations taken during pregnancy and at delivery. HTA findings were used to select for DNA sequence analysis maternal virus populations that were either closely or more distantly related to the infant virus. In each case, nucleotide sequence analysis confirmed the genetic relationships inferred by the HTA. Only maternal peripheral blood was sampled, and large sets of maternal specimens throughout pregnancy were generally not available. However, no consistent correlation was found to support the hypothesis that infant viruses should match blood-derived maternal virus genotypes found early in pregnancy if infants were found to be infected at birth or, conversely, that infant viruses should match blood-derived maternal virus genotypes found at delivery if infants were found to be infected only some time later.

Amino Acid Sequence↗
PubMed1997

Absence of LKM-1 antibody reactivity in autoimmune and hepatitis-C-related chronic liver disease in Sweden. Swedish Internal Medicine Liver club.

BACKGROUND: Type-2 autoimmune hepatitis is a subgroup of chronic hepatitis characterized by the presence of liver/kidney microsomal autoantibodies type 1 (LKM-1). A frequent association with chronic hepatitis C suggests that hepatitis virus might trigger autoimmune reactivity. LKM-1-positive chronic hepatitis is not uncommon in southern Europe but is rarely seen in the USA and the UK. The prevalence in Scandinavia is hitherto unknown. METHODS: We used an automated prototype LKM-1 immunometry-based assay (IMx) to detect LKM-1 antibodies in sera from 350 Swedish patients with chronic liver diseases (100 with primary biliary cirrhosis, 80 with primary sclerosing cholangitis, 100 with hepatitis C, and 70 patients with various forms of chronic hepatitis, including 36 autoimmune cases), and from 17 children with autoimmune hepatitis. Sera reactive in the IMx assay were subjected to immunofluorescence testing. RESULTS: No clearly LKM-reactive sera were detected. Serum samples from 29 patients were borderline reactive in the IMx assay but tested negative in the confirmatory immunofluorescence test. Positive tests in the former assay were likely caused by reactivity against microsomal antigens other than LKM-1/cytochrome P450IID6. CONCLUSIONS: LKM-1-positive type-2 autoimmune hepatitis is very rare in Sweden. Furthermore, chronic hepatitis C did not trigger this type of autoimmune reactivity in our patients, probably owing to genetic insusceptibility.

Adolescent↗
PubMed1997

Ursodeoxycholic acid treatment in patients with primary biliary cirrhosis. A Swedish multicentre, double-blind, randomized controlled study.

BACKGROUND: Ursodeoxycholic acid (UDCA) has been shown to improve serum levels of liver enzymes and bilirubin in primary biliary cirrhosis (PBC). However, it is still uncertain whether UDCA treatment also improves symptoms, liver histology, and survival without liver transplantation. METHODS: We randomized 116 patients with PBC to receive 0.5 g UDCA (n = 60) or placebo (n = 56) daily for 2 years. During the next 2 years, 80% of the UDCA-treated patients and 65% of the placebo-treated patients continued to take UDCA. RESULTS: UDCA improved serum enzyme values but not survival, symptoms, serum bilirubin levels, or liver histology. There was no significant difference in response between initially symptomatic and asymptomatic patients. CONCLUSIONS: UDCA in a dosage of 7.7 mg/kg body weight is of little benefit in PBC. This does not exclude the possibility that larger doses have beneficial effects.

Bile Acids and Salts↗
PubMed1997

Frequent occurrence of non-specific gliadin antibodies in chronic liver disease. Endomysial but not gliadin antibodies predict coeliac disease in patients with chronic liver disease.

BACKGROUND: The frequency of gliadin antibody (GA) positivity has been found to be increased among patients with chronic liver disease, as has that of coeliac disease (CD). CD has also been found to be increased among patients with primary biliary cirrhosis (PBC) or primary sclerosing cholangitis (PSC). METHODS: To investigate these relationships further, a micro-enzyme-linked immunosorbent assay and immunofluorescence tests for GAs and endomysial antibodies (EMAs) were performed in large subgroups of patients representing various chronic liver diseases and in healthy blood donors. RESULTS: As compared with blood donors (among whom it was 5%) the frequency of IgA GA positivity was higher in all patient subgroups: alcoholic liver disease, 20% (22 of 110, P < 0.001); PBC, 16% (16 of 101, P < 0.001); PSC, 24% (19 of 80, P < 0.001); chronic hepatitis, 19% (13 of 70, P < 0.001); and hepatitis C virus infection, 11% (11 of 104, P < 0.01). Two patients with autoimmune chronic hepatitis were EMA-positive, and in both cases the presence of CD was verified by small-bowel biopsy. CONCLUSIONS: IgA GA positivity generally occurs at increased frequency among patients with chronic liver disease and may represent non-specific immune activation. In liver disease GA testing is not useful in screening for CD, whereas the EMA test seems to be highly specific. CD is more prevalent than expected among patients with autoimmune chronic hepatitis but not among those with PBC or PSC.

Adult↗
PubMed1997

High incidence of antibiotic resistance among bacteria in 4 intensive care units at a university hospital in Sweden.

The frequency of antibiotic resistance among bacteria in 4 intensive care units (ICUs) at a university hospital in Sweden was investigated annually from 1993 to 1996. An increase in ampicillin-resistant enterococci from 1993 to 1995 was seen which was due to a shift from Enterococcus faecalis to Enterococcus faecium. After a special infection control programme was instituted, the rate of ampicillin resistance among enterococci and the number of E. faecium isolates declined during 1996. The oxacillin resistance rates for Staphylococcus aureus were < or = 2%, while most of the coagulase-negative staphylococci (CNS) were oxacillin resistant. No vancomycin-resistant enterococci or staphylococci were seen. The ciprofloxacin resistance rate for CNS and Enterococci spp. were high. Relatively, high levels of resistance to cefotaxime and piperacillin/tazobactam among Enterobacter spp. were also seen. During 1995 and 1996 Pseudomonas aeruginosa showed increasing resistance to ceftazidime, ciprofloxacin and piperacillin/tazobactam. This was due to an outbreak among rather few patients. The overall resistance rates for Gram-negative bacteria were low for aminoglycosides and imipenem. From 1993 to 1996 the total antibiotic consumption decreased by 27% in the whole hospital and 16.5% in the ICUs. However, the reduced antibiotic consumption was paralleled with a 23% decrease in the total number of patients treated in the hospital from 1993 to 1996. In contrast there was an 11.5% increase in the number of ICU patients treated during this period. The conclusion is that all ICUs within a hospital should have a programme for 'on-line' antibiotic resistance surveillance of drugs used in that unit in order to change the empiric treatment when there is an increase in antibiotic resistance. It is also important to survey the antibiotic consumption in the ICUs in order to avoid further selective pressure on bacteria showing increased resistance rates.

Anti-Bacterial Agents↗
PubMed1996

Granulomatous hepatitis induced by aspirin-kodein analgesics.

Salicylate-kodein is a widely used analgesic agent, particularly in outpatient practice. Salicylates have been incriminated in hepatic injury while kodein may induce biliary spasm. We report here a case of granulomatous hepatitis attributed to prolonged intake of this combination, which has never been reported previously to our knowledge.

Analgesics↗
PubMed1996

Quantitative EEG differences in a nonclinical sample of children with ADHD and undifferentiated ADD.

OBJECTIVE: To use quantitative electroencephalographic (EEG) techniques to identify electrophysiological differences between children with distinct disorders of attention and/or hyperactivity. METHOD: Forty children from a prescreened community sample were evaluated by means of both spectral EEG and evoked response potential (ERP) techniques. The children were 7 to 13 years of age and were selected on the basis of membership in one of the following DSM-III-R categories: attention-deficit hyperactivity disorder (ADHD) (n = 16), undifferentiated attention deficit disorder (UADD) (n = 12), or no disruptive disorder diagnosis (n = 12). RESULTS: Spectral EEG revealed that UADD subjects had less delta band relative percent power (RPP) (p < .01), more beta band RPP (p < .01), and ERP findings of a decreased rare tone P300 amplitude (p < .02) compared with the control group. ADHD subjects had spectral EEG findings of increased beta band RPP (p < .05) and ERP findings of an increased common tone N100 latency (p < .02) and a decreased rare tone P300 amplitude (p < .02). Interhemispheric asymmetries appeared to distinguish the groups: the UADD group had spectral EEG asymmetries; the ADHD group had only ERP asymmetries; and the control group had no asymmetries. CONCLUSION: Quantitative EEG techniques may prove useful in differentiating specific subtypes of ADHD.

Adolescent↗