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- Frick, Mats
(författare)
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Atrial fibrillation : clinical presentation and management, with special emphasis on magnesium therapy
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, causing disabling symptoms, risk of thromboembolic events and increased mortality. Some patients with AF are asymptomatic, but to what extent these patients differ from patients with symptoms is unclear. Electric cardioversion mostly restores sinus rhythm, but recurrence of AF is frequent, even with the use of antiarrhythmics. Considering the drugrelated side effects and the risk of proarrhythmias with antiarrhythmic treatment, more knowledge about clinical factors predicting successful electric cardioversion and maintenance of sinus rhythm after cardioversion, as well as new alternative treatments, is necessary. Magnesium (Mg) is the second most common intracellular cation. Mg has a decisive role in the maintenance of the Na, K and Ca gradient across the cell membrane and thereby for the resting potential of the cell. Electrophysiological effects have been shown after intravenous administration of Mg, and Mg has shown efficacy in the treatment of ventricular and supraventricular tachycardias. The main purpose of the present studies was to investigate: the prevalence of symptoms and left ventricular dysfunction, predictive factors for successful electric cardioversion and maintenance of sinus rhythm after cardioversion, and, the effect of Mg on heart rate, rate variability and its effect as a prophylactic agent in order to reduce recurrence of AF after cardioversion, in patients with AF. The prevalence of symptoms and left ventricular dysfunction was investigated in 280 patients with persistent AF, duration >2 months. A careful history of symptoms, clinical investigation, echocardiographic assay and 24 hours ECG was performed in all patients. 189 patients (68%) had symptoms that could be related to the arrhythmia, 91 patients (32%) were asymptomatic. Symptoms of irregular pulse, rapid palpitations or congestive heart failure were reported in 30%, 35% and 91% of the symptomatic patients, respectively. In logistic regression analysis, including data from clinical, echocardiograpic and 24 hours ECG examination, the only independent predictor of symptoms was the presence of valvular heart disease. Left ventricular dysfunction (EF < 40%) was observed, in 56 patients (23%). Presence of male gender, ischemic heart disease, higher mean heart rate and an increased LVED were independently associated with impaired left ventricular function. Clinical factors predicting successful cardioversion and maintenance of sinus rhythm were evaluated in 166 patients with persistent AF elected to their first cardioversion. Independent predictors of successful elective electric cardioversion were; short duration of AF and low weight. Short duration of AF, treatment with [beta]-blockers or calcium antagonists and right atrial area/dimension (adjusted for BSA) were independent predictors for maintenance of sinus rhythm. Patients with unknown duration were comparable to patients with known duration regarding successful elective electric cardioversion and maintenance of sinus rhythm. The effect of intravenous Mg, two different doses (10 mmol and 16 mmol), on heart rate and rate variability was studied in 30 patients with chronic AF, in a double blind placebo controlled fashion. Intravenous Mg showed no effect on heart rate or rate variability, and therefore seems to have no clinically relevant effects on the atrioventricular conduction in patients with chronic AF. Intraindividual variation of rate variability over time was low. The effect of orally given Mg, as a prophylactic treatment in order to reduce the recurrence of AF after elective electrical cardioversion, was evaluated in two studies. Oral Mg (20,6 mmol daily) or placebo was given to A) 170 patients with persistent AF elected to their first cardioversion without concomitant antiarrhythmics. B) 131 patients with recurrence of persistent AF after elective electrical cardioversion, as an adjuvant to sotalol. No influence on the recurrence rate of AF was seen with either of the treatments. In conclusion, the presence of valvular heart disease is an independent factor predicting symptoms in patients with persistent AF, with a prevalence of asymptomatic patients of approximately 30%. Approximately 20% of patients with persistent AF have left ventricular dysfunction, and, male gender, a higher heart rate and presence of ischemic heart disease is more likely to occur among these patients. In patients with persistent AF elected to their first cardioversion, only short duration of AF and low weight are independent predictors of successful elective electric cardioversion. Short duration of AF, treatment with [beta]-blockers or calcium. antagonists and right atrial area/dimension (adjusted for BSA) are independent predictors for maintenance of sinus rhythm. In patients with chronic AF, intraindividual variation of rate variability over time is low. Intravenous Mg has no effect on heart rate or rate variability. Oral treatment with Mg alone, or as an adjuvant to sotalol, does not influence the recurrence rate of AF after elective cardioversion of patients with persistent AF.
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| 2. |
- Johansson, Maria U, et al.
(författare)
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Structure, specificity, and mode of interaction for bacterial albumin-binding modules.
- 2002
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Ingår i: Journal of Biological Chemistry. - 1083-351X .- 0021-9258. ; 277:10, s. 8114-8120
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Tidskriftsartikel (refereegranskat)abstract
- We have determined the solution structure of an albumin binding domain of protein G, a surface protein of group C and G streptococci. We find that it folds into a left handed three-helix bundle similar to the albumin binding domain of protein PAB from Peptostreptococcus magnus. The two domains share 59% sequence identity, are thermally very stable, and bind to the same site on human serum albumin. The albumin binding site, the first determined for this structural motif known as the GA module, comprises residues spanning the first loop to the beginning of the third helix and includes the most conserved region of GA modules. The two GA modules have different affinities for albumin from different species, and their albumin binding patterns correspond directly to the host specificity of C/G streptococci and P. magnus, respectively. These studies of the evolution, structure, and binding properties of the GA module emphasize the power of bacterial adaptation and underline ecological and medical problems connected with the use of antibiotics.
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