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- Elzouki, Abdul-Nasser, et al.
(författare)
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Serine protease inhibitors in patients with chronic viral hepatitis
- 1997
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Ingår i: Journal of Hepatology. - 0168-8278. ; 27:1, s. 42-48
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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- Lindgren, Stefan, et al.
(författare)
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Immunsvar och inflammation vid Crohns sjukdom. Snart mojligt driva diagnostiken langre och utveckla mer specifika lakemedel
- 1999
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Ingår i: Läkartidningen. - 1652-7518. ; 96:1-2, s. 52-55
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Tidskriftsartikel (refereegranskat)abstract
- The chronic inflammation in Crohn's disease may be caused by aggressive response to bacterial antigens normal to the gut. Genetic and environmental factors modify the inflammatory response evoked by damage to the mucosal gut barrier. Genetic factors may also determine the subsequent course of chronic inflammation. Further elucidation of the pathogenesis might improve our understanding of the heterogenous nature of Crohn's disease, thus enabling the disease to be subtyped and individualised therapy directed primarily at down-regulation of helper T-cell-1 response to be developed.
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| 5. |
- Lindgren, T, et al.
(författare)
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Urinary cotinine concentration in flight attendants, in relation to exposure to environmental tobacco smoke during intercontinental flights
- 1999
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Ingår i: International Archives of Occupational and Environmental Health. - : Springer Science and Business Media LLC. - 1432-1246 .- 0340-0131. ; 72:7, s. 475-479
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To measure and compare the urinary cotinine concentration (U-cotinine) in non-smoking cabin attendants (C/A) working with the Scandinavian Airlines System, before and after work on intercontinental flights with exposure to environmental tobacco smoke (ETS). METHODS: The study material consisted of 24 cabin attendants and one pilot, all volunteers and all without exposure to ETS in the home, working on 15 intercontinental flights. Information on age, gender and occupation was gathered, as well as possible sources of ETS exposure in other places, outside work and during previous flights, during a 3-day period prior to the investigation. Urine samples were taken before departure and after landing, on board, and were kept frozen (-20 degrees C) until analysis. Cotinine was analyzed by a previously developed gas chromatographic method, using mass spectrometry (MS) with selected-ion monitoring (SIM). The difference in U-cotinine before and after the flight was compared. Moreover, the change in U-cotinine during the flight was related to occupation (work in the forward or aft galley) and observed degree of smoking during each flight. RESULTS: The median U-cotinine was 3. 71 microg/g crea; 2.4 microg/l (unadjusted) (interquartile range 2. 08-8.67 microg/g crea) before departure, and 6.37 microg/g crea; 7.1 microg/l (interquartile range 3.98-19 microg/g crea) after landing, a significant difference (P < 0.003). C/A in the aft galley had a significantly higher concentration of U-cotinine after landing than subjects working in the front of the aircraft (P=0.01). In C/A working in the aft galley, the median increase of U-cotinine was 3. 67 microg/g crea; 3.2 microg/l (interquartile range 0.04-13.8 microg/g crea) during flight. In contrast, those seven subjects working in the forward part of the aircraft had no increase in U-cotinine during the flight (median increase 0.97 microg/g crea; 0. 5 microg/l interquartile range 0.27-2.65 microg/g crea). CONCLUSION: Tobacco smoking in commercial aircraft may cause significant exposure to environmental tobacco smoke among C/A working in the aft galley, despite high air exchange rates and spatial separation between smokers and non-smokers. This agrees with earlier studies, as well as measurements on the aircraft, showing a higher degree of ETS-related air pollution in the aft galley than in the forward galley. The average cotinine concentration in urine was similar to that in other groups with occupational exposure to ETS, e.g., restaurant staff, police interrogators and office workers. Since smoking in commercial aircraft may result in an involuntary exposure to ETS among non-smokers, it should be avoided.
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- Verbaan, Hans, et al.
(författare)
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Extrahepatic manifestations of chronic hepatitis C infection and the interrelationship between primary Sjogren's syndrome and hepatitis C in Swedish patients
- 1999
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Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 245:2, s. 127-132
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To analyse the frequency of some extrahepatic manifestations of chronic hepatitis C virus (HCV) infection in northern European patients, including a postulated association between HCV and primary Sjogren's syndrome (SS). DESIGN: Cohort study. SETTING: Department of Medicine, Malmo University Hospital, Sweden. PATIENTS: Twenty-one patients with HCV infection and 53 with primary SS (according to the Copenhagen criteria). MAIN OUTCOME MEASURES: Cryoglobulins were analysed in all patients, while patients with primary SS were investigated with regard to markers of HCV infection, and HCV patients with objective tests of SS (Schirmer-1 test, break-up time, van Bijsterveld score, sialometry, labial salivary gland biopsy) and antibodies against nuclear antigens, smooth muscle (SMA) and mitochondria (AMA). HCV antigens in small salivary glands from lower lip biopsies were detected by immunohistochemical analysis. RESULTS: Only one of the SS patients had detectable cryoprecipitates, while another was HCV-positive. None of the 21 HCV patients had cryoprecipitates. A total of 14/21 (67%) patients with HCV infection had at least one abnormal objective test suggestive of xerostomia or keratoconjunctivitis sicca, while eight (38%) had objective evidence of both eye and salivary gland involvement. HCV antigens were not detected in affected glands. Only two patients had clinical symptoms of SS, and two fulfilled the Copenhagen criteria for SS. None of the HCV-positive patients had detectable antibodies against SS-A, SS-B, RNP, Jo-1, PCNA or Scl-70, and the frequency of ANA/SMA/AMA was low. CONCLUSIONS: While involvement of salivary and lacrimal glands was common in Swedish patients with HCV infection, cryoglobulinaemia was not observed. The pathogenetic mechanism responsible for glandular inflammation appears to be different from that in primary SS. HCV infection does not seem to be an aetiological factor for primary SS in this population. These observations suggest that viral, genetic or possibly environmental factors may be responsible for the reported high frequencies of systemic complications associated with chronic hepatitis C infection in southern Europe.
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| 9. |
- Verbaan, Hans, et al.
(författare)
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Long-term outcome of chronic hepatitis C infection in a low-prevalence area
- 1998
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 33:6, s. 650-655
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 10. |
- Yang, Ping
(författare)
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Perinuclear Antineutrophil Cytoplasmic Antibodies in Inflammatory Bowel Disease
- 1998
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Antineutrophil cytoplasmic antibodies (ANCAs) are a group of autoantibodies which are specific for granulocyte antigens. By indirect immunofluorescence (llF) on ethanol-fixed neutrophils, ANCAs can be divided into two types: a cytoplasmic staining pattern (C-ANCA) or a perinuclear staining pattern (P-ANCA). Their pathogenic role and initiating stimuli are unknown.This study analysed P-ANCA in monozygotic twins with inflammatory bowel disease. In ulcerative colitis (UC), P-ANCA occurred in 9 of 14 (64.3%) monozygotic twins and in 13 of 21 (61.9%) non-twin subjects, which was significantly different compared with healthy controls who were positive in three of 52 (5.8%) subjects (pSeventy-six UC patients after proctocolectomy with ileal pouch-anal anastomosis (JP AA) including 28 patients who had had pouchitis and 48 patients who had not, were analysed regarding the correlation between P-ANCA and pouchitis. P-ANCA was found in 49n6 (64.5%) iu UC patients after the operation. Furthermore, we found that patients with recent (512 months) or ongoing pouchitis were all P-ANCA positive and pouchitis patients with higher P-ANCA titres were more prone to have frequent relapses.To screen the occurrence of P-ANCA and detect the target antigen(s), 36 patients with UC, 37 patients with CD, 38 patients with collagenous colitis (CC) and 190 controls were studied. P-ANCA was found in a higher frequency in UC (23/36. 63.9%) than in CD (2/37. 5.4%). CC (4/38, 10.5%) or controls (4/190. 2.1 %). The antigens of P-ANCA were not found to be associated with reactivity to lactoferrin (L:f), !3-glucuronidase (j3- Glc), myeloperoxidase (M:PO) or proteinase 3 (PR3).ANCAs were analysed by IIF on unfixed neutrophils or cells fixed by either ethanol, acetone or parafonnaldehyde in 21 sera from patients with UC, 17 sera from patients with vasculitides including 8 with PR3-positive C-ANCA and 9 with MPO-positive P-ANCA. Established ANCA patterns were most clear with ethanol-fixed neutrophils. The PR3-positive C-ANCA pattern was the same on unfixed or fixed cells irrespective of fixation method. However, the staining was brightest and the serum titres were higher with ethanol-fixed cells. Furthermore, we confirmed that the antigen of UC associated P-ANCA was better exposed on ethanol- than on acetone- or paraformaldehyde-fixed cells. In addition, anti-MPO positive sera tested on the very same day with freshly prepared paraformaldehyde-fixed neutrophils gave a C-ANCA pattern. Two or more days after preparation of the neutrophils anti-MPO-positive sera gave a mixed C- and P-ANCA pattern. Neutrophils kept unfixed for a few days or more and then treated with parafonnaldebyde gave a P-ANCA pattern, indicating diffusion of MPO from the azurophilic granules to the periphery of the nucleus, a process that is strongly enhanced by ethanol fixation.Six anti-MPO-negative P-ANCA-positive sera from patients with UC, six antiMMPO-positive P-ANCA, five anti-PR3-positive C-ANCA and ten antinuclear antibody (ANA)-positive serum samples were tested with 15 different GramHnegative and Gram-positive bacterial strains. We found that soluble material from live E. coli and P. mirabilis has the capacity to decompose the anti. genic substrate of neutrophils responsible for both MPOpositive and MPO-negative P-ANCA. most probably brought about by enzymatic activity. Anti-PR3-positive CANCA was not affected which suggests substrate specificity of the proposed enzymatic activity.
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