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Biomedical subjects

S Lindgren

Publications and source records attributed to S Lindgren.

At least 109 records · Page 6Linked to original sources

Effects of two vasodilatory phosphodiesterase inhibitors on bradykinin-induced permeability increase in the hamster cheek pouch.

Two inhibitors with selective effect on cyclic nucleotide phosphodiesterases (PDEs, preferentially hydrolyzing cAMP), milrinone (cGMP-inhibited PDE) and rolipram (cAMP-specific PDE) were studied for their effects on bradykinin-induced plasma leakage in comparison with the beta 2-receptor stimulant terbutaline. The dilation of arterioles induced by milrinone and rolipram was studied in the concentration range 10(-7)-10(-4) M. Maximal arteriolar dilation was 53% for milrinone at 10(-4) M and 28% for rolipram at 10(-4) M. The hamster cheek pouch preparation was used as prepared for intravital microscopy of fluorescein-labelled dextran, FITC-dextran. Bradykinin was applied topically to the cheek pouch at a final concentration of 4 x 10(-7) M and caused rapid and reversible increase in plasma leakage (number of leakage sites) from postcapillary venules. Milrinone (M), rolipram (R) and terbutaline (T) were also applied topically starting 5 min prior to bradykinin application and at final concentration of 10(-4) and 10(-5) M (M), 10(-5) and 10(-6) M (R) and 10(-7) M (T). These local concentrations resulted in significant (p < 0.05) and reversible inhibition of the bradykinin-induced response by 44% and 33% (M), 77% and 67% (R) and 46% (T). Combining M and R individually with T resulted in a significantly larger inhibition of the bradykinin response than with each of the drugs given separately.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

HLA-DR3, DQ2 homozygosity in two patients with insulin-dependent diabetes mellitus superimposed with ulcerative colitis and primary sclerosing cholangitis.

Two unrelated young males with the unusual simultaneous presence of insulin-dependent diabetes mellitus, ulcerative colitis and primary sclerosing cholangitis are reported. Both patients manifested homozygosity for the DR3-DQw2 (DQB*0201) HLA genotypes. We believe that homozygosity for this genotype may predispose for this type of multi-organ autoimmune disease.

Adolescent↗

HLA DR and DQ RFLP analysis in Crohn's disease.

A study of 109 Swedish patients and 85 healthy Swedish controls with Crohn's disease (CD) by HLA class II RFLP genotyping was carried out. There was no significant association for any single DR or DQ specificity or phenotypic combination of DR and/or DQ specificities among our study group of Caucasian extraction.

Base Sequence↗

Autonomic vagal nerve dysfunction in patients with ulcerative colitis.

Autonomic nerve function was evaluated in 40 patients with total ulcerative colitis and in 25 patients with irritable bowel syndrome by three established non-invasive tests based on the heart reactions to deep breathing (E/I ratio) and tilt (acceleration and brake index). None of the patients were diabetic. Most of the patients with ulcerative colitis were clinically and biochemically inactive; 10 had previously undergone colectomy. The results were compared with a control group consisting of 56 healthy individuals and 33 previously investigated patients with Crohn's disease, 45% of whom demonstrated autonomic neuropathy (AN). Patients with ulcerative colitis had a significantly lower E/I ratio than controls in age-corrected values, indicating vagal nerve dysfunction. Altogether, 35% had signs of AN. In patients with irritable bowel syndrome 36% had evidence of AN, a figure in agreement with observations from other investigators. We conclude that AN is common in patients with ulcerative colitis, regardless of disease activity and previous colectomy. In contrast to a predominantly sympathetic dysfunction in Crohn's disease, AN in ulcerative colitis was vagal.

Adult↗

Complement activation in patients with primary Sjögren's syndrome: an indicator of systemic disease.

Sixteen patients with primary Sjögren's syndrome, verified according to the Copenhagen criteria, were investigated for evidence of complement activation. Thirteen of the patients had intact functional activity of both the classical and alternative pathways, with normal concentrations of the complement proteins C1q, C1s, C3, C4 and the complement protein fragments C2a and C3d in the circulation. In contrast, three patients showed clear evidence of complement activation. Further investigation of these patients revealed manifestations of glomerulonephritis, vasculitis and primary biliary cirrhosis. Six months later, one patient developed a malignant non-Hodgkin lymphoma. We conclude that complement activation is generally not associated with primary Sjögren's syndrome. Evidence of complement activation in patients considered to have primary Sjögren's syndrome should raise the suspicion of concomitant systemic disease and/or extraglandular activity.

Aged↗

Evaluation of HIV testing in Sweden, 1985-1991.

OBJECTIVE: Evaluation of the extent and outcome of HIV testing in Sweden. DESIGN: Data from screening programmes, laboratory and clinical reports were compared and a national survey on HIV testing was performed. RESULTS: The proportion found to be positive in screening of blood donors, pregnant women and sexually transmitted disease patients were approximately 1/100,000, 1/10,000 and 1-2/1000, respectively. One-quarter of the men and one-third of the women in Sweden aged 16-74 years reported that they had been tested for HIV at least once. CONCLUSION: There is a high cost involved in detecting HIV-infected individuals through general testing. This cost can be justified if we believe that awareness of an infection substantially reduces the risk of further transmission.

Adolescent↗

Does asthma or treatment with theophylline limit children's academic performance?

BACKGROUND: Asthma is a major cause of morbidity in childhood, restricting activity and causing absences from school. Theophylline, although effective in managing chronic asthma, has been reported to cause deficits in cognitive functioning and school performance. We therefore examined the effect of asthma and its treatment on academic achievement in a large, representative population of school-age children; matched sibling controls were used for comparison. METHODS: We identified 255 consecutive children with asthma (mean age, 12.0 years) who had taken nationally standardized scholastic achievement tests administered routinely by the schools. One hundred one of these children had siblings without asthma with whom comparisons could be made in reading, mathematics, and a composite measure of achievement. RESULTS: Academic achievement among the children with asthma was similar to normative standards in Iowa and higher than national standards, as reflected in a mean composite T-score of 57.1 (expected mean [+/- SD], 50 +/- 10). For the 101 children with sibling controls, composite T-scores were 58.3 for the children with asthma and 57.5 for the siblings. Eighty-five of these 101 children with asthma were receiving daily maintenance medication for chronic asthma; 72 of these were receiving theophylline. The mean composite T-scores were 58.5 for the theophylline-treated patients and 58.4 for their siblings without asthma. None of the differences between the children with asthma and the sibling controls were statistically significant. CONCLUSIONS: Academic achievement among children with asthma, at least those whose status is closely monitored in a structured treatment program, generally appears to be unaffected by asthma or by its treatment with appropriate doses of theophylline.

Adrenal Cortex Hormones↗

Purification and properties of the cGMP-inhibited cAMP phosphodiesterase from bovine aortic smooth muscle.

Pure cGMP-inhibited cAMP phosphodiesterase (cGI-PDE) in micrograms quantities was isolated from bovine aortic smooth muscle after more than 5000-fold purification using DEAE ion-exchange and affinity chromatography with a derivative of the specific cGI-PDE inhibitor cilostamide conjugated as a ligand to aminoethyl agarose (CIT-agarose). The cGI-PDE, which constituted about half of the high affinity cAMP-PDE activity of a tissue homogenate, was identified with a 105-kDa protein on SDS-PAGE through use of antibodies towards the human platelet, bovine cardiac and bovine adipose tissue cGI-PDE in Western blot and immunoprecipitation/immunoinactivation analysis. As observed during purification of the enzyme from other tissues the enzyme protein was exquisitely sensitive to proteolytic nicking during purification, resulting in several 30-77-kDa polypeptide fragments. Rapid immunoprecipitation from fresh tissue extracts was the only was found to partially prevent the proteolysis. The native enzyme had apparent molecular sizes of approx. 100,000 or, mainly approx. 220,000 by gel chromatography, presumably indicating the presence of monomeric and dimeric forms. The enzyme hydrolyzed cAMP and cGMP with normal Michaelis-Menten kinetics with Km of 0.16 and 0.09 microM, respectively, with Vmax for hydrolysis of cAMP of 0.3 compared to 3.1 mumol/min per mg protein for cAMP. The enzyme was potently and selectively inhibited by cGMP (IC50 approximately 0.25 microM) and the cardiotonic/vasodilatory drugs OPC-3911 (a cilostamide derivative), milrinone and CI-930 (IC50 approximately 0.05, 0.40 and 0.25 microM, respectively). The cGI-PDE was phosphorylated by cAMP-dependent protein kinase as has been reported for the analogous enzymes in heart, adipose tissue and platelets. The identification of a cGI-PDE in the aortic smooth muscle and its inhibitor specificity is consistent with the hypothesis that inhibition of this enzyme is important in the mechanism through which these drugs produce vasorelaxation.

3',5'-Cyclic-AMP Phosphodiesterases↗

Blunt basal head trauma: aspects of unconsciousness.

Two cases of street violence directed to the skull base level and transverse to the cervical axis are described. No skeletal damage. The violence resulted in the so-called "traumatic subarachnoid haemorrhage", an often used, unspecified forensic "diagnosis"; it was here revealed to be due to rupture of the wall of the posterior inferior cerebellar artery (p.i.c.a). However, this was only one of the possible explanations for the acute symptoms of unconsciousness (concussion) and almost immediate death. The careful examination of these two cases and of a series of control cases revealed that at the trauma, stress and strain may have occurred to arterial branches serving as feeding perforant vessels to the medulla oblongata; in these cases they were coursing directly from the p.i.c.a. region.--The type of direct impact has often been regarded as mild! However, its location suboccipitally as in these cases can become dangerous. The resulting direct or indirect deficit of brain stem functions are discussed in these cases as well as "concussion-related symptoms" resulting after other types of head and neck injury.

Adult↗

Prednimustin treatment in primary biliary cirrhosis: a preliminary study.

We observed a decrease in serum bilirubin, alkaline phosphatases (ALP) and IgM in five patients with primary biliary cirrhosis (PBC) treated with Prednimustin (Sterecyt) for 6 months. In contrast to pretreatment findings, C3 activation was undetectable during treatment in three patients where normalization of serum IgM was achieved. After discontinuation of Prednimustin, bilirubin and ALP levels rapidly returned to pretreatment values, although IgM remained normal for up to 6 months in some patients. We conclude that Prednimustin might be of value in patients with symptomatic PBC where liver transplantation is not an option, and that it should be evaluated in a controlled study. However, the rapid reactivation of the disease after conclusion of treatment must be considered.

Aged↗

Hepatitis C in chronic liver disease: an epidemiological study based on 566 consecutive patients undergoing liver biopsy during a 10-year period.

We analysed the presence of hepatitis C virus (HCV) antibodies in 566 patients undergoing liver biopsy. While over 20% of the patients were anti-HCV positive according to ELISA, only 13.8% had HCV antibodies when tested with a four-antigen recombinant immunoblot assay (RIBA 2). At the time of inclusion in the study, most patients were asymptomatic, irrespective of whether they were HCV-positive. Histological findings in anti-HCV-positive patients were chronic persistent hepatitis, chronic active hepatitis or cirrhosis in greater than 75% of cases. Only four of the patients who were anti-HCV-positive according to the RIBA 2 had autoimmune chronic active hepatitis. Risk behaviour could be identified in the majority of cases. Community-acquired sporadic cases were rare (12%). Of the 153 patients who died during follow-up, 23 subjects were anti-HCV positive. Although age- and sex-adjusted survival was not shorter in anti-HCV-positive patients than in anti-HCV-negatives, the risk of hepatocellular cancer was higher (P = 0.01). We conclude that HCV infection is associated with chronic liver disease, even when critical evidence of viral aetiology is slight. Truly sporadic cases are rare. Patients infected with HCV are at increased risk of developing hepatocellular cancer.

Adolescent↗

HIV in pregnant women and their offspring: evidence for late transmission.

To assess the role of maternal viraemia in vertical transmission of HIV and the extent to which viraemia occurs during the various stages of pregnancy, we have attempted to detect human immunodeficiency virus (HIV) in 44 pregnant HIV-1 infected women during 47 pregnancies (30 continued, 17 aborted) and in 30 children and 12 fetuses. Infectious HIV was detected at some time during pregnancy in 59% of women from plasma and in 83% from either peripheral blood mononuclear cells or plasma. HIV was not isolated from any of the newborn babies (0/27) at birth. The mothers had a significantly higher frequency of viraemia during pregnancy than their children had by 6 months of age (p = 0.002); by this time HIV was recovered from 5 (26%) of 19 infants. HIV was not detected by virus isolation, in-situ hybridisation, or polymerase chain reaction (PCR) in 10 fetuses; the other 2 fetuses were positive either by in-situ hybridisation or by PCR but neither result could be confirmed in a second organ or by the other methods of detection. The findings show that there is no consistent spread of HIV across the placenta during maternal viraemia, and indicate that in most cases transmission occurs close to or at delivery.

Female↗

Selective inhibition of cGMP-inhibited and cGMP-noninhibited cyclic nucleotide phosphodiesterases and relaxation of rat aorta.

In the supernatant (50,000 g, 1 hr) fraction from rat aortic smooth muscle homogenates, approximately 50% of total cAMPE PDE activity was inhibited by OPC 3911 (3 microM), while approximately 20% was inhibited by rolipram (30 microM). A cGMP-inhibited cyclic nucleotide phosphodiesterase (cGI-PDE) was further purified using DEAE chromatography followed by affinity chromatography on the N-(2-isothiocyanato)ethyl derivative of cilostamide conjugated to aminoethyl agarose (CIT-agarose). OPC 3911, CI-930, and milrinone, but not rolipram, were potent and selective inhibitors of this enzyme. The PDE-activity in the CIT-agarose flow through fraction (RI-PDE), however, was inhibited potently by rolipram, but not by cGMP, OPC 3911, CI-930 or milrinone. Functional studies showed that OPC 3911, CI-930, and milrinone were potent relaxants of contracted rat aorta. Rolipram had little relaxant effect. When OPC 3911 or milrinone was combined with rolipram more than additive effects on aortic relaxation and cAMP content were obtained. OPC 3911 combined with milrinone had only additive effects. These results demonstrate the presence of a cGI-PDE in rat aortic smooth muscle, and that inhibition of this isozyme may be of primary importance for the relaxant effects of OPC 3911, CI-930, and milrinone. A RI-PDE activity was also found, but it appeared to be less important for modulation of vascular tone unless the cGI-PDE was already inhibited. This may explain the synergistic relaxant effects observed when both PDE-isozymes were inhibited.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗

(S)-UH-301 antagonizes (R)-8-OH-DPAT-induced cardiovascular effects in the rat.

The 5-HT1A-receptor antagonist (S)-UH-301 (S)-5-fluoro-8-hydroxy-2- (dipropylamino)tetralin) completely antagonized the hypotension and bradycardia induced by (R) = 8-OH DPAT [R)-8-hydroxy-2- (dipropylamino)tetralin) in conscious rats. (S)-UH-301 alone induced a weak hypertension, which might be due to its 5-HT1A-receptor antagonistic properties. (R)-UH-301 induced effects similar to those of (R)-8-OH DPAT, i.e., a short initial phase of hypertension followed by a long-lasting hypotension and bradycardia. Thus, (R)-UH-301 behaves as a 5-HT1A-receptor agonist and (S)-UH-301 as a 5-HT1A-receptor antagonist, abolishing the effects induced by (R)-8-OH DPAT.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Prevalence of swallowing complaints and clinical findings among 50-79-year-old men and women in an urban population.

To determine the prevalence of swallowing and esophageal complaints in the general population, 300 men and 300 women were asked to answer a mailed questionnaire. The participation rate was 92.5%. Complaints were reported by 35%. The most common complaints were symptoms associated with gastroesophageal reflux (GER) and globus sensation, both with a rate of occurrence of 20%. Obstruction of the bolus reported by 3% was the individual symptom that most frequently brought patients to the doctor. To validate the questionnaire and to study possible organic causes behind these symptoms, 46 persons with symptoms were invited to undergo further examination. Cineradiography of the pharynx revealed that 7 of 14 patients with symptoms of GER had abnormalities in the esophagus. Eleven of 55 patients with GER symptoms at least once a week underwent endoscopy. One case of erosive esophagitis and one case of gastric ulcer were diagnosed. Four of nine patients with obstructive symptoms had defective closure of the laryngeal vestibule shown by cineradiography. Endoscopy in four patients with obstructive symptoms revealed benign findings. Thus, an epidemiologic study of patients with swallowing symptoms documented a low incidence of serious organic disease.

Aged↗