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  • 1
    ISSN: 1432-1041
    Keywords: Atrial natriuretic factor (ANF) ; platelet aggregation ; aldosterone ; whole blood ; ex-vivo
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Atrial natriuretic factor (ANF) binding sites have been shown to be present on human platelet membranes. We investigated the effect of an infusion of ANF 5 pmol·kg−1.min−1 on platelet aggregation in whole blood ex-vivo in 8 normal volunteers. Spontaneous platelet aggregation, collagen (0.6–2 μg·ml−1)-induced or ADP (0.5–2.0 μM)-induced aggregation was not affected by ANF. Plasma aldosterone was however significantly attenuated by ANF. These results show that a pharmacological dose of ANF does not affect platelet aggregation in man. These results suggest that the high plasma levels of ANF normally achieved in chronic heart failure or acute myocardial infarction are unlikely to contribute to the platelet hyperreactivity, often observed in these conditions.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1041
    Keywords: Dipyridamole ; Red cell deformability ; haemodialysis ; peripheral vascular disease ; renal failure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary An automated filtration technique has been used to investigate the effect of dipyridamole (DP) on red blood cell deformability in patients identified as having rigid red cells. They were patients on haemodialysis (HD) for chronic renal failure (n=18), patients with peripheral vascular disease (PVD, n=23) and controls (hospital out-patients, n=33). Leucocytes and platelets were removed from heparinised blood by filtration through Imugard wool. Washed red cell suspensions in buffer at 5% haematocrit, without or with 5 μM DP, were filtered through Nuclepore Hemafil Membranes with 4.7 μm pores. The initial steady state relative filtration pressure (iRFP) was used to assess cell deformability. A low iRFP value reflects increased deformability and vice versa. The mean iRFP values were 0.33, 0.393 and 0.403 for controls, PVD and HD patients respectively, indicating that the red cells in the two groups of patients were significantly more rigid. DP reduced the iRFP to 0.266, 0.278 and 0.263 for controls, PVD and HD patients respectively. The results suggest that DP may be beneficial when red cell rigidity contributes to impaired microvascular perfusion.
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  • 3
    ISSN: 1365-2842
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: summary  The effect of oral symptoms of Sjögren's syndrome (SS) on health-related quality of life is presently uncertain. This study aimed to investigate oral health-related quality of life (OHRQOL) among southern Chinese people with SS. Twenty-six primary SS cases, 25 secondary cases and 29 matched controls took part in this cross-sectional study. Each participant completed a SF-36 questionnaire, the Oral Health Impact Profile and a dry mouth measure, assisted by a trained interviewer. Data on socio-demographic variables were also collected. The dry mouth measure revealed that people with primary and secondary SS had significant problems associated with subjective symptoms of dry mouth generally, and dry mouth when eating and speaking (P 〈 0·01). Sticky saliva and coughing were also problems in some primary SS cases. OHIP summary and sub-scale scores did not reveal differences in negative impacts between groups. Mean SF-36 sub-scale scores were significantly different between groups (P 〈 0·05). In physical function, role-physical and general health domains, primary and secondary SS sufferers had lower scores indicating poorer health. Oral symptoms of SS, notably xerostomia, had a negative effect on OHRQOL. Health-related quality of life in general was also impaired in SS sufferers. The OHIP did not appear to discriminate oral problems of concern to SS sufferers.
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  • 4
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background : There is controversy as to whether Helicobacter pylori and non-steroidal anti-inflammatory drugs interact to cause peptic ulcers.Aim : To study whether the eradication of H. pylori in patients on long-term non-steroidal anti-inflammatory drug therapy prevents the development of ulcers.Methods : Patients infected with H. pylori whilst receiving long-term non-steroidal anti-inflammatory drug therapy, but with no ulcers at baseline endoscopy, were randomized to receive either triple antibiotic therapy (metronidazole 300 mg, clarithromycin 250 mg and amoxicillin 500 mg, given four times daily; n = 70) or placebo (n = 70) for 2 weeks. Non-steroidal anti-inflammatory drugs were continued throughout the study period. Endoscopy was repeated 12 weeks after the end of treatment. The development of ulcers was compared between the two groups.Results : Endoscopy at 12 weeks revealed peptic ulcer development in five [7%; 95% confidence interval (CI), 2–16] of the patients who received triple therapy and in six (9%; 95% CI, 3–18) of those who received placebo (P = 1.00). No significant difference in the development of ulcers was found between patients with persistent H. pylori infection (7/80; 9%; 95% CI, 4–17) and those with the eradication of H. pylori (4/52; 8%; 95% CI, 2–19) (P = 1.00).Conclusions : The eradication of H. pylori in patients receiving long-term treatment with non-steroidal anti-inflammatory drugs did not prevent ulcer development. However, because the rate of ulcer development was low, a study with a larger sample size is required to confirm this finding.
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  • 5
    ISSN: 0340-1855
    Keywords: Key words¶Corticotropin releasing hormone –¶polymorphisms –¶rheumatoid arthritis – genetics ; Schlüsselwörter¶Corticotropin Releasing Hormon –¶Polymorphismen –¶Rheumatoide Arthritis – Genetik
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die 5′ regulatorische Region des Corticotropin Releasing Hormons (CRH) ist hoch konserviert und spielt eine zentrale Rolle in der Vermittlung der Streßantwort des Organismus. Durch im Hypothalamus freigesetztes CRH wird die Hypophysen – Nebennierenrinden – Achse aktiviert, was in der Freisetzung von Cortisol und einer konsekutiven Regulation inflammatorischer und immunologischer Vorgänge resultiert. Ausgehend von der Hypothese, daß die inadäquate CRH Antwort auf Streß bei Patienten mit rheumatoider Arthritis (RA) auf einer genetischen Basis beruht, haben wir die Verteilung der CRH Allele sowohl bei kaukasischen (United Kingdom) als auch bei schwarzen (Südafrika) RA Patienten untersucht und mit der jeweiligen gesunden Kontrollgruppe verglichen. Wie in den kürzlich publizierten Kontrollgruppen fanden wir zwei biallele polymorphe Sequenzen (genannt A1 und A2, bzw. B1 und B2) in der regulatorischen Region des CRH Gens, die zu gemeinsamen Allelen zusammengefaßt werden konnten. Bei den weißen Kaukasiern war das Allel A2B1 protektiv gegenüber der Entwicklung einer RA (p=0,03; odds ratio 0,43, 95% confidence interval 0,21–0,88). Im Gegensatz dazu war bei den schwarzen südafrikanischen RA Patienten das Allel A1B1 positiv mit der RA assoziiert (p=0,05; odds ratio 1,78, 95% confidence interval 1,01–3,15). Die Studie liefert Hinweise darauf, daß Polymorphismen in der regulatorischen Region des CRH Gens neue genetische Marker für eine RA darstellen und eventuell als prädiktiver Faktor eingeführt werden können, wenn weitere genetische und umweltbedingte Risikofaktoren identifiziert werden.
    Notes: Summary The regulatory region of the corticotropin releasing hormone (CRH) is highly conserved and plays a crucial role in the response of the organism to stress. Release of CRH initiates a cascade of events leading to the release of cortisone and the regulation of inflammatory and immune events.¶Objective: Since it has been postulated that the impaired corticotropin releasing hormone (CRH) response to stress in patients with rheumatoid arthritis (RA) has a genetic basis, we investigated the distribution of CRH alleles in a cohort of UK patients as well as in South African RA patients.¶Methods: Restriction fragment length polymorphism of PCR amplified DNA products of the CRH promoter. We compared the allele frequencies in the RA patients with the respective healthy control population described previously.¶Results: As in the control populations we found two biallelic polymorphic sequences (named A1 and A2 and B1 and B2, respectively) in the CRH promoter which could be assigned to compound alleles. The A2B1 compound allele was protective against development of RA in a large group of UK Caucasoid patients (p=0.03; odds ratio 0.43, 95% confidence interval 0.21–0.88). In contrast, A1B1 was positively associated with RA in a cohort of black South African RA patients (p=0.05; odds ratio 1.78, 95% confidence interval 1.01–3.15).¶Conclusion: Taken together, these findings support the hypothesis that CRH promoter polymorphism represents a new genetic marker for RA susceptibility and may prove useful for the prediction of RA risk in the future when further genetic and environmental risk factors are determined.
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  • 6
    ISSN: 1437-160X
    Keywords: Thromboxane ; Thromboxane receptor antagonist ; Raynaud's-systemic sclerosis ; Vibration white finger disease ; Platelet aggregation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Raynaud's syndrome (RS) is characterized by intense blood vessel spasm resulting in finger blanching. Treatment primarily involves vasodilation. Thromboxane A2 (TXA2) has been shown to be a potent vasoconstrictor and platelet aggregant. It may be possible to produce a vasodilatory and anti-thrombotic effect by blockade of the TXA2 receptors. ICI 192,605 is a potent TXA2 receptor antagonist and we studied its effects on platelet aggregation and digital blood flow in patients with RS. Sixteen patients with RS completed this doubleblind, randomized, placebo controlled study. Each patient was seen on three separate occasions and was given ICI 192,605 (100 mg orally) on one occasion and matching placebo tablets on the other two. We measured platelet aggregation using platelet rich plasma (PRP) stimulated by U46619, a thromboxane (TX) mimetic. The concentration of U46619 required to cause just over 50% platelet aggregation before the administration of either ICI 192,605 or placebo (pre-dose) was noted. The same concentration of U46619 was used to stimulate the PRP sample at 1h after the administration of ICI 192,605 or placebo (post-dose) and the percentage of platelet aggregation was again noted. Fingertip skin blood flow was also measured 1.25 h post-dose using a laser Doppler flowmeter. Patients were seated in a temperature controlled chamber which was initially heated to 40°C to induce centrally mediated vasodilatation. The temperature was then lowered to 12°C followed by rewarming to 40°C. Steady blood flow values at these temperatures were measured and the rates of cooling and rewarming were also noted. There was significant inhibition of platelet aggregation 1 h following the administration of ICI 192,605 {post-dose % platelet aggregation [mean (standard deviation)]=4.8 (12.7)% vs control values of 65.6 (10.5)% and 62.7 (21.3)%, P〈0.0001 (Analysis of covariance)}. No demonstrable evidence of improved fingertip skin blood flow was observed and it may be that more prolonged dosing is required. As platelet aggregation is increased in Raynaud's phenomenon further evaluation of this group of drugs in patients with RS is required.
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