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Biomedical subjects

A Frydén

Publications and source records attributed to A Frydén.

At least 19 recordsLinked to original sources

Increased liver echogenicity at ultrasound examination reflects degree of steatosis but not of fibrosis in asymptomatic patients with mild/moderate abnormalities of liver transaminases.

AIMS: To investigate whether hyperechogenicity of liver can reliably be interpreted as liver steatosis and if any concomitant or isolated fibrosis can be disclosed. PATIENTS AND METHODS: A series of 165 patients with no signs or symptoms of liver disease referred because of slightly to moderately raised aminotransferases (alanine aminotransferase and/or aspartate aminotransferase 0.7-5.0 microkat/l) for more than 6 months were prospectively investigated with a comprehensive laboratory profile, ultrasound examination of liver and percutaneous liver biopsy Fibrosis was assessed quantitatively and according to Metavir. Steatosis was graded as none, mild, moderate or severe. RESULTS: Of 98 (59.4%) patients with raised echogenicity, 85 (86.7%) had liver steatosis of at least moderate degree, 9 patients with same degree of steatosis had normal echogenicity and 13 patients with no or only mild steatosis had a hyperechogenic liver (sensitivity 0.90, specificity 0.82, positive predictive value 0.87, negative predictive value 0.87). About the same relations were found regardless of body mass index and degree of fibrosis. With increased echogenicity together with high attenuation (n = 591 and reduced portal vessel wall distinction (n = 79), positive predictive value increased to 0.93 and 0.94, respectively. Quantitatively assessed fibrosis (mean +/- SD) was 3.2 +/- 4.6% of biopsy area with normal and 2.3 +/- 1.8% with raised echogenicity (ns). Echogenicity was normal in 5 out of 9 patients with septal fibrosis and in 4 out of 6 patients with cirrhosis. Any structural, non-homogenous findings at ultrasound were not associated with architectural fibrotic changes and none had nodular contours of liver surface. CONCLUSIONS: Assessment of liver echogenicity is of value for detection or exclusion of moderate to pronounced fatty infiltration (correct classification 86.6%) but cannot be relied upon in diagnosing fibrosis, not even cirrhosis in asymptomatic patients with mild to moderately elevated liver transaminases.

Adult↗

Interaction of Staphylococcus epidermidis from infected hip prostheses with neutrophil granulocytes.

This study focuses on the interaction of Staphylococcus epidermidis isolated from granulation tissue covering infected hip prostheses and neutrophil granulocytes. Bacterial strains isolated from normal flora were used as controls. The bacteria were well characterized with routine methods and further characterized with random amplified polymorphic DNA analyses and slime tests. Phagocytosis and chemiluminescence (CL) assays were used in the neutrophil interaction studies. The prostheses strains were ingested to a lesser extent than strains from normal flora (p < or = 0.001). There was no significant difference between the prostheses strains and the normal flora strains in terms of total CL response. However, the extracellular CL response from the neutrophils was lower in comparison with the normal flora when interacting with the prostheses strains. The results of this study support the notion that S. epidermidis strains isolated from infected hip prostheses have an enhanced capacity to resist phagocytosis and that most of these strains elicit a reduced inflammatory response, measured as the production of extracellular oxidative metabolites from the neutrophils, compared to normal flora.

DNA, Bacterial↗

Liver guide for monitoring of chronic hepatitis C.

The severity of chronic hepatitis C infection in the individual patient is monitored using blood laboratory findings and liver biopsy. If blood test results could be shown to provide sufficient information concerning the disease, the invasive procedure of liver biopsy could perhaps be avoided in some instances. This study assessed the clinical relevance of blood laboratory tests for detecting disease-related changes in the liver. Histopathological classification was used to assign class membership of the patients and data mining operations were performed in an elaborate way on 19 different data sets. Disease activity could be detected by a small set of blood tests. Extended sets could identify more severe changes, but failed to distinguish them. The extracted rules are implemented as a part of the knowledge base of a corresponding decision support system aimed at specialists and general practitioners.

Analysis of Variance↗

Long-term follow-up of chronic hepatitis C patients with sustained virological response to alpha-interferon.

BACKGROUND/AIMS: This study aimed to determine the long-term outcome of hepatitis C virus (HCV)-infected patients who respond to interferon treatment with clearance of serum HCV RNA. METHODS: We performed a long-term biochemical, virological, and histological follow-up of all sustained virological responders, defined as those who became HCV RNA negative at follow-up 6 months after the end of treatment, from 3 controlled interferon trials performed in Sweden between 1988 and 1994. RESULTS: At biochemical and virological long-term follow-up performed in 26 sustained virological responders 3.5-8.8 years (mean +/- SD, 5.4+/-1.6 years) after the end of IFN therapy, 22 patients (85%) had normal serum ALT levels, and 24 patients (92%) were HCV RNA negative in serum. Liver biopsies performed in 23 patients 2.1-8.7 years (mean +/- SD, 5.0+/-1.8 years) after end of treatment showed no or minimal inflammation, whereas mild and probably irreversible fibrosis was seen in a few patients. CONCLUSION: In this well-defined material of sustained responders to IFN therapy, the long-term prognosis was excellent. Nearly all had a durable response, not only biochemically and virologically, but more importantly also histologically with normalisation or near normalisation of previous histological lesions.

Adult↗

Platelets enhance neutrophil locomotion: evidence for a role of P-selectin.

It has been suggested that the accumulation of platelets at sites of vascular damage and inflammation regulates the function of leukocytes. In this study, we investigated the effects of platelets on the transmigration of neutrophil granulocytes through microporous membranes. We demonstrate that platelets markedly enhance both the random and the chemotactic migration of neutrophils. Stimulatory effects were acquired by adding paraformaldehyde-fixed platelets or the supernatants of platelets; however, the effects were lower or significantly higher, respectively, compared with viable platelets. The increased neutrophil migration was associated with an amplified polymerization of actin filaments and expression of CD11b/CD18. Previous investigations indicate that the initial adhesion between platelets and neutrophils is mediated by P-selectin exposed on the surface of platelets. In this study, the following observations suggest a role for P-selectin in the platelet-induced enhancement of neutrophil motility: (i) platelet supernatants contained substantial amounts of P-selectin, (ii) filtration of platelet supernatants markedly reduced the content of P-selectin and simultaneously decreased the potentiating effects on neutrophil motility, (iii) inhibition of P-selectin-mediated cell cell adhesion with sialyl Lewis X or by incubation in calcium-free medium reduced the enhancing effects of platelets on neutrophil responses, and (iv) purified and recombinant P-selectin mimicked the effects of platelets on neutrophil locomotion. In conclusion, we propose that platelets through P-selectin promote accumulation and emigration of neutrophils during inflammatory and thrombotic processes.

Actins↗

The clinical significance of slightly to moderately increased liver transaminase values in asymptomatic patients.

BACKGROUND: Our aim was to study liver disorders in asymptomatic patients with slightly to moderately increased liver transaminase values in a population living in an area with a low prevalence of viral and hereditary liver diseases. METHODS: One hundred and fifty consecutive patients with slightly to moderately increased liver transaminases for at least 6 months without symptoms or signs of liver disease were included. Median (range) was 0.75 microkat/l (0.24-2.9) for aspartate aminotransferase (ASAT) and 1.18 microkat/l (0.28-4.5) for alanine aminotransferase (ALAT). A percutaneous liver biopsy was performed, and blood was sampled for a detailed biochemical and serologic profile. RESULTS: Chronic viral hepatitis C was found in 15.3% of the patients, autoimmune hepatitis in 1.3%, primary biliary cirrhosis in 1.3%, and heterozygotic alpha-1-antitrypsin deficiency in 0.7%. Presumed alcoholic liver disease was diagnosed in 8%, and non-alcoholic steatohepatitis in 2%. Chronic hepatitis with no obvious etiology was diagnosed in 24%, of whom 39% had interface hepatitis (piecemeal activity). Seventy-one per cent of these 39% had measurable levels of autoantibodies, but IgG levels within normal limits prevented the 'clinical' diagnosis of autoimmune hepatitis. Liver steatosis was the diagnosis in 40%. Most were overweight and had increased serum triglyceride levels. However, in 13.3% the fatty infiltration was considered 'essential', as both body mass index (BMI) and triglyceride levels were normal. Other diagnoses were liver fibrosis with no obvious inflammatory activity (3.3%), cirrhosis of unknown etiology (0.7%), and for the remaining (3.3%) patients histopathologic findings were considered 'normal'. Cirrhosis was found in five biopsy specimens: hepatitis C (n = 2), autoimmune hepatitis (n = 1), primary biliary cirrhosis (n = 1), and cryptogenic cirrhosis (n = 1). No concomitant disease was of importance for the diagnosis and/or histopathologic findings. No obvious drug-related increased liver test results were found with any single drug. However, patients with chronic hepatitis of unknown etiology, especially with interface hepatitis, significantly more often than the rest of the population were receiving drug treatment. CONCLUSION: Most transaminitis patients had steatosis, and some had defined diseases including chronic hepatitis C. Chronic hepatitis of unknown etiology was found in a substantial proportion (24%) of a population living in an area with a low burden of hepatic viruses and genetic disorders.

Alanine Transaminase↗

Influence of pre-treatment factors on outcome of interferon-alpha treatment of patients with chronic hepatitis C.

A total of 172 Swedish patients treated with interferon-alpha for at least 24 weeks and followed-up > or =24 weeks after treatment was stopped were analysed for pre-treatment factors of importance for achieving a virological sustained response (SR). Furthermore, the predictive value for a virological SR of a positive or negative HCV RNA test at week 12 of treatment was evaluated. A low baseline viral load and genotype non-1b were pre-treatment factors indicating a favourable response. Thus, 44% (38/86) of patients with a low baseline viral load vs. only 16% (14/86) of those with a high viral load had a virological SR (p<0.0001). Of patients with a negative qualitative HCV RNA test after 12 weeks of interferon treatment, 46% (44/95) had virological SR, whereas only 5.9% (4/68) of those with a positive test had (p<0.0001). Prolonged ( > 6 months) treatment with interferon-alpha tended to increase the chance of virological SR (p<0.052).

Adolescent↗

Intradermal hepatitis B vaccination in health care workers. Response rate and experiences from vaccination in clinical practise.

Health care workers at risk for hepatitis B virus infection are recommended for vaccination. Low-dose intradermal (i.d.) administration of vaccine has been suggested as a less expensive alternative to intramuscular (i.m.) inoculation. To evaluate the i.d. vaccination route, health care workers were included in a prospective study. The subjects were vaccinated with 0.1 ml (= 2 microg) recombinant vaccine (Engerix B, SmithKline Beecham) i.d. at 0, 1 and 6 months. Two months after the third vaccination, measurement of the anti-HBs level was conducted. An anti-HBs level > or =10 IU/l was considered protective. Those with an anti-HBs level <10 IU/l were given a fourth dose with new serological control after another 2 months. The results are based on the 1406 subjects that it was possible to evaluate. The seroconversion rate to protective anti-HBs level after 3 doses was 68% and after 3 or 4 doses 89%. Factors associated with a lower response rate were increasing age (p<0.05) and smoking (p<0.001). Sex or body mass index had no influence on the results. Vaccination technique seems to be of utmost importance when the i.d. route is used. Well instructed and experienced nurses are required and quality control with follow-up of overall seroconversion rate within each centre is needed.

Adult↗

Take care: guidelines for patients with chronic hepatitis C.

Alcohol consumption has significant impact on the condition of the liver, by itself, and even more in conjunction with other liver diseases such as chronic hepatitis C. Drinking habits might be delicate issues to address and could harm otherwise satisfying communication. Therefore, we intended to outline guidelines for advising hepatitis C patients concerning alcohol consumption. Analysis of a relatively limited knowledge base revealed the complexity of the disease rather than statistically significant findings regarding consumption. Thus, we instead chose to suggest a set of patient educational guidelines, which could be implemented on the Internet, hypothesizing that a better informed patient will be more able to comply with restrictions concerning alcohol consumption. A brief ad hoc evaluation pointed out Internet as a favourable media to present the information. We also suggest a tentative algorithm for further development of clinical decision support systems addressing monitoring of chronic hepatitis C patients.

Adolescent↗

Randomised, double-blind, placebo-controlled trial of interferon alpha-2b with and without ribavirin for chronic hepatitis C. The Swedish Study Group.

BACKGROUND: Pilot studies suggested that more patients with chronic hepatitis C virus (HCV) infection had a sustained virological response when treated with the combination of interferon alpha-2b and ribavirin than with interferon alpha-2b alone. We investigated the biochemical and virological responses and safety of treatment with interferon alpha-2b and ribavirin compared with interferon alpha-2b alone. METHODS: In this double-blind trial 100 patients were randomly assigned to treatment with interferon alpha-2b (3 MU three times a week) in combination with ribavirin (1000 or 1200 mg per day) or placebo for 24 weeks and then followed up for a further 24 weeks. A further follow-up was done 1 year after active treatment stopped. The primary endpoint was the sustained virological response, defined as no detectable HCV RNA by PCR at both week 24 and week 48. Retrospectively, the baseline HCV-RNA load was analysed as a predictor of a sustained virological response. Data were analysed by intention to treat. FINDINGS: 18 (36%) of the 50 patients in the interferon alpha-2b and ribavirin group had a sustained virological response compared with nine (18%) of the 50 patients in the interferon alpha-2b and placebo group (p = 0.047). At the 1 year follow-up the proportion of patients with a virological response was greater in the interferon alpha-2b and ribavirin group than the interferon alpha-2b and placebo group (42 vs 20%, p = 0.03), respectively. More patients with baseline HCV-RNA concentrations greater than 3 x 10(6) genome equivalents (Eq) per mL had a sustained response with interferon alpha-2b and ribavirin than with interferon alpha-2b and placebo (12/29 vs 1/26, p = 0.009), whereas the sustained response did not differ between the two treatment groups for HCV-RNA amounts less than 3 x 10(6) Eq per mL (6/21 vs 8/24, p = 0.67), respectively. INTERPRETATION: More patients with chronic hepatitis C have a sustained virological response with interferon alpha-2b and ribavirin than with only interferon alpha-2b treatment. We suggest that patients with high HCV-RNA loads should be treated with interferon alpha-2b and ribavirin.

Adult↗

GBV-C/HGV infection in hepatitis C virus-infected deferred Swedish blood donors.

Sera from 62 hepatitis C virus (HCV)-infected Swedish blood donors were tested by a nested polymerase chain reaction using primers targeting the 5'-noncoding region of the GB virus-C/hepatitis G (GBV-C/HGV) genome and an enzyme-linked immunosorbent assay that detects antibodies to the envelope protein E2 of GBV-C/HGV (anti-E2). Fourteen (22%) and 21 (34%) of the 62 blood donors were found to be GBV-C/HGV RNA and anti-E2 positive, respectively. None of the blood donors was positive for both GBV-C/HGV RNA and anti-E2. Thus, 35 of 62 (56%) HCV-infected donors had been exposed to GBV-C/HGV infection. At sequencing of the 14 GBV-C/HGV isolates, 12 were identified as subtype 2a and 2 as subtype 2b. One of 7 (14%) donors with mild liver disease such as steatosis and nonspecific reactive hepatitis had been exposed to GBV-C/HGV vs. 34 of 55 (62%) with chronic hepatitis with or without cirrhosis (P = 0.04). All other differences in histology were small between HCV and dual HCV GBV-C/HGV-infected donors. In conclusion, more than half of HCV-infected Swedish blood donors in this study were positive for either GBV-C/HGV RNA or anti-E2. GBV-C/HGV viremia and seropositivity were mutually exclusive.

Adult↗

Comparison of 3 quantitative HCV RNA assays--accuracy of baseline viral load to predict treatment outcome in chronic hepatitis C.

The correlation between 3 assays for hepatitis C virus (HCV) RNA quantification and their respective accuracy in predicting the response to interferon and interferon/ribavirin therapy was evaluated by analysing pre-treatment sera from 100 patients. A total of 97%, 100%, and 98% of the patients tested positive by the branched DNA 2.0 assay (Quantiplex), a multi-cycle reversed transcriptase polymerase chain reaction quantitative assay (Superquant) and the Roche Amplicor Monitor assay, respectively. The correlations between the assays, in all patients and in the major genotypes 1, 2, and 3, were significant, although the levels detected by the Amplicor Monitor assay were more than 1 log lower than by the other assays. Sustained virological responders to interferon therapy, but not to combination therapy, had lower baseline viral levels than long-term non-responders (p = 0.002 by Quantiplex 2.0; p = 0.008 by Superquant; p = 0.06 by Roche Amplicor Monitor). Pre-treatment viral load greater than 3 x 10(6) Eq or copies/ml by the Quantiplex 2.0 and Superquant assays and greater than 100,000 copies/ml by the Amplicor Monitor assay predicted long-term non-response in 94%, 93% and 91% of the interferon treated patients, respectively. In conclusion, acceptable correlations between available commercial quantitative assays were found. High baseline viral load predicted long-term non-response to interferon monotherapy, whereas it did not to interferon/ribavirin combination therapy.

Antiviral Agents↗

[Care of a patient with a rare and highly contagious virus disease. An emergency situation resulted in good preparedness].

Ever since the eradication of smallpox, Sweden has been poorly furnished with emergency facilities for the care of patients with serious, very infectious diseases. National interest in creating such facilities was aroused by epidemics of haemorrhagic disease (first and foremost due to Ebola virus during the present decade), at the same time as the first Scandinavian case of haemorrhagic fever associated with a risk of person-to-person infection occurred in Linköping. A special laboratory which has been set up at the Centre for Disease Control, in Stockholm, and University Hospital, Linköping, in collaboration with the Board of Health and Welfare, has introduced a high-security infectious disease unit for the care of such patients, with separate ventilation and waste-water treatment systems. The unit is also equipped to provide intensive care, and a laboratory can be rapidly set up and fully operative within 12-24 hours. Most important of all, personnel are available who are trained both for laboratory work and the care of such patients, and used to working as a team and familiar with the special protective equipment. If a patient can not be transported to the special unit, a team is available to travel to the hospital where the patient has been admitted, to give instruction and help to set up infection control routines and even supply protective equipment.

Clinical Competence↗

Two-year biochemical, virological, and histological follow-up in patients with chronic hepatitis C responding in a sustained fashion to interferon alfa-2b treatment.

Fourteen patients with chronic hepatitis C who had a sustained response to a 60-week interferon alfa-2b treatment course were followed, biochemically and virologically, 2 years after treatment cessation. Biopsies were repeated in 12 of 14 for histological and virological evaluation at 2-year follow-up. All 14 patients had normal serum alanine transaminase (s-ALT) levels and were negative for hepatitis C virus (HCV) RNA in serum during treatment and at short-term follow-up 6 months post-treatment. At 2-year follow-up, 13 patients still had normal ALT levels (< 0.6 mukat/L for women; < 0.8 mukat/L for men), 1 a near normal level (0.76 mukat/L); all were HCV RNA negative in serum, and 11 of 12 also in the liver. Liver histology improved during treatment and remained stable during the 2-year follow-up. The authors conclude that most sustained responders, who have normal ALT levels and are nonviremic at short-term follow-up 6 months after interferon treatment, will continue to have a durable long-term response without relapse of the viremia.

Adult↗

Genotyping of hepatitis C virus isolates by a modified polymerase chain reaction assay using type specific primers: epidemiological applications.

A polymerase chain reaction (PCR)-based assay using primers against the hepatitis C core gene has been described [Okamoto et al. (1992a): Journal of General Virology 73:673-679]. Within the two major HCV genotypes 1 and 2, the Okamoto system identifies two subtypes each (1a, 1b and 2a, 2b, respectively). Typing is achieved by a primary PCR with consensus primers followed by a nested PCR with type specific primers. The original assay was modified by addition of a parallel second PCR identifying the recently described major genotype 3. The assay also identifies in duplicate subtype 1b (type II by Okamoto), suggested to respond poorly to interferon. Reaction conditions were reviewed and melting temperatures of all typing primers equalised to increase strigency. The modified system functioned well and typing results were supported by partial core sequencing. The following distribution of genotypes was found in 53 hepatitis C virus (HCV) infected Swedish blood donors: genotype 1a (57%), 3 (19%), 1b (13%), and 2b (11%). In six recipients of HCV infected blood identified in a retrospective study, the recipient HCV genotype was identical to donor HCV genotype. Furthermore, in HCV positive couples identical genotype was observed when only one partner had an external risk factor; whereas genotypes were often diverse if both sex partners had parenteral risk factors. Finally, a cluster of hepatitis C cases in a haemodialysis unit was evaluated retrospectively. Eight patients had genotype 1b, two had mixed 1a and 1b, and one had type 1a. The modified HCV genotyping assay was of value in examining different epidemiological situations and can be expanded presumably to include future genotypes.

Base Sequence↗

Long-term findings in patients with facial palsy and antibodies against Borrelia burgdorferi.

Little is known about the long-term effects of Borrelia burgdorferi (Bb) infection in untreated patients with peripheral facial palsy. We investigated 12 patients with elevated serum Bb antibody levels, with a median follow-up time of 11 years, during which 3 of the 12 still exhibited intrathecal antibody production of antibodies against Bb flagellar antigen, and 2 of the 3 had normal serum Bb antibodies. Four of the 12 had elevated serum antibody titres at the late follow-up examination. Arthralgia, reported by 7 patients, was the single most common complaint. Four patients showed extensive oculomotor disturbances, which were not correlated to antibody titres or intrathecal antibody synthesis. In 1 of the patients with intrathecal Bb antibody production, most symptoms were eradicated by antibiotic treatment 6 years after the initial infection. We conclude that even several years after a Bb infection, intrathecal Bb antibody production can still occur in serum Bb IgG antibody negative patients with a history of facial palsy.

Adolescent↗

High sustained response rate and clearance of viremia in chronic hepatitis C after treatment with interferon-alpha 2b for 60 weeks.

To evaluate the effect of prolonged interferon-alpha treatment on serum aminotransferase levels and hepatitis C virus RNA in serum, 40 patients with chronic hepatitis C virus infection were treated with 3 MU interferon-alpha 2b thrice weekly for 60 wk. Before treatment all patients had elevated serum ALT levels for at least 1 yr, antibodies to HCV by second-generation tests and liver histological findings consistent with chronic hepatitis C. Before treatment hepatitis C virus RNA was found in serum in 39 of 40 (97.5%) patients. Normalization of ALT levels at treatment cessation was seen in 24 of 40 (60%) patients, of whom 15 of 24 (62.5%) had sustained ALT responses up to 24 wk after treatment. At follow-up, 24 wk after treatment, hepatitis C virus RNA was cleared from serum in 17 of 40 (42.5%) patients, including all sustained responders, one nonsustained responder and one nonresponder. We conclude that 60 wk of treatment with interferon-alpha 2b seems to induce a high percentage of sustained response, which coincides with cessation of viral replication.

Adult↗