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Biomedical subjects

S Lindgren

Publications and source records attributed to S Lindgren.

At least 91 records · Page 5Linked to original sources

Disturbed motilin and cholecystokinin release in the irritable bowel syndrome.

BACKGROUND: The irritable bowel syndrome (IBS) is associated with motor abnormalities in the small intestine and colon. Neuropeptides may have an important role in initiating and regulating the intestinal motility. Motilin has been proposed to initiate the peristaltic reflex in the small intestine and cholecystokinin the gastrocolic reflex. METHODS: In 18 patients with IBS and 11 healthy control subjects plasma motilin and cholecystokinin (CCK) concentrations were measured after intraluminal stimulation of water and a fat-rich meal. RESULTS: The IBS patients had reduced motilin secretion after both water intake and the fat meal. In contrast, the fat meal elicited an exaggerated and prolonged CCK release in the IBS patients. CONCLUSIONS: Disturbed motilin and CCK release may partly be responsible for the intestinal dysmotility in the IBS patients.

Adult↗

Alcohol abuse exaggerates autonomic dysfunction in chronic liver disease.

BACKGROUND: Advanced chronic liver disease is characterized by peripheral arterial vasodilation and increased plasma catecholamine concentrations. These haemodynamic alterations may reflect impaired vascular responsiveness due to autonomic nerve dysfunction. METHODS: Three established non-invasive tests based on the heart reactions to deep breathing (expiratory/inspiratory (E/I) ratio) and to tilt (acceleration and brake indices) were used to evaluate age-related autonomic nerve function in 27 patients with chronic alcoholic and non-alcoholic liver disease. Liver function was estimated by demethylating capacity. The results were compared with a control group consisting of 56 healthy individuals. RESULTS: Overall, 12 patients (52%) had autonomic neuropathy (10 of 13 (77%) patients with alcoholic and 2 of 14 (14%) with non-alcoholic liver disease). Variance analysis showed that the age-corrected E/I ratio, but not the acceleration and brake indices, was significantly decreased compared with controls both in patients with alcoholic and non-alcoholic liver disease, indicating vagal nerve dysfunction (P < 0.0001 and 0.0133, respectively). The decrease in E/I ratio was also significantly more pronounced (-1.77 (0.62) (median (interquartile range)) versus 0.76 (0.70); P = 0.049) in patients with alcoholic compared with non-alcoholic liver disease. Furthermore, in contrast to non-alcoholics, patients with alcoholic liver disease were unable to increase their diastolic blood pressure after return to upright from a tilted position, indicating additional sympathetic neuropathy. CONCLUSIONS: Autonomic, mainly vagal, nerve dysfunction is common in patients with liver diseases and is further exaggerated by alcohol abuse. Autonomic neuropathy may contribute to altered vascular responsiveness in patients with chronic liver diseases.

Autonomic Nervous System Diseases↗

Vertical transmission of hepatitis C virus infection.

Vertical transmission of hepatitis C virus (HCV) was studied in 58 infants of 55 mothers (3 sets of twins). HCV RNA analyses by the polymerase chain reaction (PCR) and alanine aminotransferase (ALT) were performed on consecutive blood samples from birth to 18 months of age (0, 3, 9 and 18 months). Data on factors possibly influencing mother-to-infant transmission of HCV, such as concomitant human immunodeficiency virus (HIV) and hepatitis B virus infection during pregnancy, maternal HCV RNA status at delivery, mode of delivery, prematurity and breastfeeding habits were collected. In addition, 6 older siblings (age 4-10 years) of the infants were tested once for anti-HCV. Of the 55 mothers 52 (95%) had a history of intravenous drug use (IVDU). Two mothers were HIV positive. 40/54 (75%) tested mothers were HCV RNA positive. 16 (27%) infants were delivered by Caesarean section, and 50 (86%) infants were breastfed. All infants were HCV RNA negative on all occasions and anti-HCV negative at the age of 18 months. Maternally acquired anti-HCV antibodies disappeared and were not detected by 9 months in 78%. One of the 6 older siblings was anti-HCV and HCV RNA positive. We conclude that the risk of vertical HCV transmission is low in infants of HCV-positive/HIV-negative mothers, and that breastfeeding seems to be safe in this group.

Adult↗

Pattern of HIV viraemia and CD4 levels in relation to pregnancy in HIV-1 infected women.

The objective was to study HIV-1 viraemia and CD4 levels during and 6 months after pregnancy. HIV cultures on peripheral blood mononuclear cells (PBMC) and plasma from 225 samples were performed in 90 HIV-1 infected women with 59 continued and 35 terminated pregnancies. P-24 antigen and HIV-DNA were also studied. 34 women originated from European, 44 from African and 10 from other countries while 2 were of unknown origin. HIV was detected in 30% of the plasma cultures from the first trimester and in approximately 50% thereafter. Repeated plasma isolations did not give an indication of HIV activation, nor did the cross-sectional time-to-culture positivity in plasma and in PBMC, PBMC isolation frequencies, HIV-DNA and CD4 levels. The plasma viraemia frequencies were generally higher and the CD4 levels lower in the African women than in the European ones. Six months after delivery there was a significant decrease in the CD4 cell counts compared to delivery, but not when compared to the values during the first or second trimesters. The results showed that HIV activity during pregnancy was relatively stable, followed by indications of resumed activity during the first 6 months after delivery.

Adult↗

Low prevalence of anti-neutrophil cytoplasmic antibodies in ulcerative colitis patients with long-term remission.

OBJECTIVES: In spite of a strong positive association between ulcerative colitis and the presence of perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCAs), the immunogenetic significance of these antibodies remains unclear. We studied patients with quiescent disease to clarify whether ANCAs are present even in the absence of inflammation. DESIGN: The prevalence of ANCAs was estimated blindly in 137 patients with ulcerative colitis, 128 of whom had quiescent disease with a mean duration of complete clinical and biochemical remission of 14 years. For comparison, we studied sera from 110 patients with Crohn's disease, 27 of whom had a low or intermediate grade of inflammatory activity. The mean duration of complete remission in these patients was 8.5 years. METHODS: ANCAs were detected using indirect immunofluorescence and enzyme-linked immunosorbent assays (ELISAs). RESULTS: Only 13 (9%) of 137 patients with ulcerative colitis had ANCAs (5% had p-ANCAs). Three patients had previously undergone colectomy. In patients with Crohn's disease, ANCAs were observed in 17 of 110 patients (15%, 6% had p-ANCAs). Fifteen of these patients had colonic disease. CONCLUSION: In patients with ulcerative colitis free from inflammation for prolonged periods of time, ANCAs occurred less frequently than has previously been reported. Patients with Crohn's disease had the expected frequency of ANCA positivity, which for colonic Crohn's disease was comparable to that found in patients with ulcerative colitis. These findings suggest that the titre of ANCAs decreases with time in inactive disease and may be undetectable with conventional assays after several years of complete remission.

Adult↗

Single-step affinity purification, partial structure and properties of human platelet cGMP inhibited cAMP phosphodiesterase.

The human platelet cilostamide- and cGMP-inhibited cAMP phosphodiesterase (cGI-PDE) was rapidly purified approximately 19,000-fold to apparent homogeneity using single step affinity chromatography on the isothiocyanate derivative of cilostamide coupled to aminoethyl agarose. Within 24 h, 30 micrograms of enzyme protein was obtained from 20 ml of packed platelets. Vmax for cAMP and cGMP was 6.1 and 0.9 mumol/min per mg protein, respectively. Several polypeptides (110/105, 79, 62, 55/53 kDa) were identified after SDS-PAGE, all of which were immunologically related to cGI-PDE and represented approx. 5, 20, 50 and 20% of the total protein, respectively. Limited proteolysis of the cGI-PDE with chymotrypsin produced a major fragment of approximately 47 kDa (and at least two smaller peptides) with catalytic activity and sensitivity to cGMP and OPC 3911 similar to controls. Phosphorylation of the cGI-PDE by cAMP-dependent protein kinase (A-kinase) resulted in maximal incorporation of 0.6-1.8 mol of 32P/mol 110/105 and 79 kDa polypeptides; much lower and variable amounts of phosphate were incorporated into the 62 and 55/53 kDa polypeptides. After digestion of cGI-PDE with several proteinases a number of peptides were isolated and sequenced. Most of the peptide sequences obtained could be aligned within the carboxy terminal domain of the deduced sequence of the human cardiac cGI-PDE. These and other results suggest that the subunit size of the intact platelet cGI-PDE is 110 kDa and that proteolytic fragments of 79, 62 and 55/53 kDa are produced during purification. The smaller fragments (62 and 55/53 kDa) contain the catalytic domain; the larger fragments (110 and 79 kDa) also contain the regulatory domain with phosphorylation sites for A-kinase.

3',5'-Cyclic-AMP Phosphodiesterases↗

Autoimmune liver disease in patients with primary Sjögren's syndrome.

Forty-five patients with primary Sjögren's syndrome were studied for evidence of autoimmune liver disease. Twenty-nine patients had normal liver function tests, normal IgM and a normal test for antimitochondrial antibodies and smooth muscle antibodies. Among the remaining 16 patients, abnormal liver function tests were found in 12 (27% of all patients); eight of these patients had biochemical cholestasis. Elevated plasma IgM (> 2 g/l) was observed in nine patients, three with normal liver function tests, while antimitochondrial antibodies were positive in six patients, one with normal liver function tests, and smooth muscle antibodies were found in three. Based on these findings and percutaneous liver biopsy, a diagnosis of primary biliary cirrhosis was established in four patients and autoimmune chronic active hepatitis in two. The present study showed that abnormal liver function tests in patients with primary Sjögren's syndrome are frequent and may indicate associated autoimmune liver disease. These data further emphasize the systemic nature of autoimmune disorders.

Adult↗

Demonstration of dilatation of peripheral airways.

To investigate the ability of various lung-function tests to demonstrate dilatation of peripheral airways, ten asthmatics inhaled increasing doses of a beta 2-agonist by two different and controlled techniques. Low inspiratory flow with a long post-inspiratory pause favoured peripheral deposition, and a high inspiratory flow with a short post-inspiratory pause favoured central deposition of drug in the airways. Ordinary spirometry, maximum expiratory flow rates after breathing air as well as a helium-oxygen mixture, a single breath N2-test and resistance of the respiratory system were obtained before and after each of five terbutaline doses with both inhalation techniques. By using a double-dummy technique, the study could be performed double blinded. Effects were compared at doses giving equal effects on PEF, assumed to represent equal deposition of bronchodilator and effects on central airways. At such 'iso delta PEF doses', particularly FVC and the slope of phase III of the N2-test improved more following the slow inhalation technique. It is concluded that changes in those tests reflect dilatation in peripheral airways in asthmatics.

Administration, Inhalation↗

The inotropic mechanism of the phosphodiesterase inhibitor OPC 3911 alone and in combination with rolipram, studied in papillary muscles of ferret and guinea-pig and isolated myocytes of guinea-pig ventricular muscle.

OPC 3911 is a potent inhibitor and PDE III is a specific inhibitor in cardiac muscle. The effects of the drug alone and in combination with the non-inotropic PDE IV inhibitor rolipram were analysed using hearts from guinea-pigs and ferrets. OPC 3911 had an EC50 value of 0.1 microM. At 0.1 microM peak force was increased by 50.7 +/- 7.6% (n = 6, P < 0.001), time to peak tension (TPT) reduced by 18.7 +/- 5.6% (n = 6, P < 0.05). Time to half relaxation (THR) was prolonged by 19 +/- 4.2% (n = 6, P < 0.001). After addition of rolipram (30 microM), there was a potentiation of peak force at all concentrations of OPC 3911. At 0.1 microM OPC rolipram increased peak force by 82.8 +/- 8.9% (n = 6, P < 0.001), reduced TPT by 73 +/- 6% (n = 6, P < 0.005) and increased THR by 27 +/- 5% (P < 0.01). OPC 3911 shortened action potential duration (APD) at 50% repolarization by 5.3 +/- 2.5% (n = 6, P < 0.05). Addition of rolipram prolonged APD by 3.7 +/- 2.5% (n = 6, P < 0.05). Second inward current (Isi) was increased at 3 microM OPC 3911 by 46 +/- 6% (n = 6, P < 0.05). The combination of OPC 3911 and rolipram intensified the Isi to 101 +/- 5% (n = 3). Rolipram slowed the rate of restitution and the onset of restitution was prolonged. Relative maximum post-extrasystolic potentiation was reduced in the presence of OPC 3911 from 67 +/- 5% to 45 +/- 6%. Adding rolipram caused potentiation of 55 +/- 6%. OPC 3911 increased the recirculation fraction of activator calcium from 0.36 to 0.42 (n = 10, P < 0.05). After addition of rolipram the recirculation fraction was 0.41 +/- 0.04 (n = 10, P < 0.05). The results suggest that rolipram exerts its potentiating effect on OPC 3911 via an increased Isi.

Action Potentials↗

Unsuspected coeliac disease in chronic 'cryptogenic' liver disease.

BACKGROUND: Earlier reports have suggested that a relationship exists between chronic liver disease and coeliac disease (CD). Gliadin antibodies (GA) have been used to screen for CD. METHODS: Using a micro-enzyme-linked immunosorbent procedure, we analysed sera from 327 consecutive patients with chronic liver disease for GA (IgA and IgG) and evaluated their clinical significance. RESULTS: GA were detected in 19 patients (6%), a prevalence six times greater than that found in healthy blood donors. In 9 of the 19 patients the liver disease had been classified as cryptogenic. The occurrence of GA was independent of the degree of hepatocellular impairment. A diagnosis of CD was confirmed in 5 of the 10 patients who underwent small-bowel biopsy. CONCLUSIONS: Our findings suggest the prevalence of CD in patients with chronic liver disease to be at least 1.5%--that is, 15 times higher than in the general population. They also suggest that the possible presence of CD should be considered in cases of chronic 'cryptogenic' liver disease.

Adult↗

Cancer risk in primary biliary cirrhosis: a population-based study from Sweden.

A cohort of 559 patients in Sweden who satisfied predetermined criteria for the diagnosis of primary biliary cirrhosis was followed with respect to the incidence of cancer during the period of 1958 to 1988. The mean follow-up time from the time of primary biliary cirrhosis diagnosis was 9.0 +/- 5.4 yr. During the follow-up period, 148 patients died and the primary cause of death was liver insufficiency. An overall excess risk for cancer, standardized incidence ratio 1.6; 95% confidence interval, 1.1 to 2.2, was found in the cohort. In contrast to previous reports, we found no excess risk for breast cancer (standardized incidence ratio, 0.9; 95% confidence interval, 0.3 to 2.1). The number of hepatocellular cancers in the primary biliary cirrhosis cohort did not significantly differ from expected (standardized incidence ratio, 2.91; 95% confidence interval, 0.4 to 10.5).

Adult↗

Screening for HIV-1 antibodies in pregnancy: results from the Swedish national programme.

OBJECTIVE: To determine the effectiveness of a national screening programme for HIV infection in pregnant women. DESIGN: Observational study. SUBJECTS: All pregnant women presenting to antenatal or abortion clinics. SETTING: Sweden, September 1987 to December 1991. MAIN OUTCOME MEASURES: Number and characteristics of infected women. RESULTS: By the end of the study period 510,000 tests had been performed and 54 women with HIV infection identified (1.06/10,000). Of the 33 women identified in Stockholm, 14 women (4.4/10,000) had attended abortion clinics and 19 antenatal clinics (1.8/10,000; p < 0.05). Three women had been intravenous drug users, one was infected through a blood transfusion, and 50 were probably infected sexually. Of the 20 women who attended antenatal clinics early enough to allow an abortion, 12 continued with their pregnancies. CONCLUSIONS: Testing of all women, not just those perceived to be at risk, probably contributed to the high uptake of HIV testing. With high uptake such screening provides valuable data on spread of HIV in the heterosexual population and presents opportunity for preventing transmission of HIV to children and partners.

Adolescent↗

Pharmacokinetics of oral tiopronin.

Ten healthy subjects were given 500 mg (3064 mumol) tiopronin, or 2-mercaptopropionylglycine (2-MPG) by mouth. Cmax was reached after 3-6 h, and after a shorter beta-phase a long terminal half-life of 53 h of total tiopronin was found. Tiopronin measured as unbound (non-protein-bound) drug disappeared more rapidly from plasma, with a calculated t1/2 of 1.8 h. Mean residence time was higher (58 h) when calculated as total tiopronin than as unbound tiopronin (6 h), and this was also the case for the volume of distribution (V lambda = 455 l vs V lambda,u = 41 l). The results indicate extensive protein binding in plasma and a deep pool of tissue bound tiopronin after the first absorption and distribution phases. Absolute bioavailability (f) was 63%, and bioavailability calculated from urinary excretion was 47%, which are well correlated with each other. Urinary excretion was mainly confined to the first 6 h (74%) and was almost complete (98%) within 12 h. We conclude that the maximal absorption of the tiopronin was late, protein and tissue binding of the drug were high and its bioavailability varied. The renal excretion of low molecular weight tiopronin occurred early, which implies that the drug should be given in divided doses, at least twice daily, for optimal efficiency in the treatment of cystinuria.

Administration, Oral↗