Control of paroxysmal atrial fibrillation recurrence using combined administration of propafenone and quinidine

The frequent recurrence of paroxysmal atrial fibrillation (PAF) despite the use of standard antiarrhythmic agents prompted the use of new therapeutic approaches. There are few data on systematic assessment of PAF control with stepwise dose escalation and the use of a drug combination. Low-dose quinidine may promote the efficacy of propafenone by inhibiting its degradation through the cytochrome P450 pathway (CYP2D6). We prescribed propafenone 300 to 450 mg/day to 60 patients with PAF for 8 weeks, and 62% were symptomatically controlled. The 19 refractory patients were randomized in a double-blinded fashion to receive either a higher dose of propafenone (450 to 675 mg/day) or the standard dose of propafenone with low-dose quinidine 150 mg/day, each for an 8-week study period, and subsequently crossed over to the alternative treatment. The resulting serum propafenone concentrations were 259 ± 208 and 336 ± 237 mg/day (p >0.5), respectively. Both treatment arms prolonged the time to the first symptomatic atrial fibrillation (AF) recurrence and the interval between attacks, and AF was controlled in 37% of patients. However, the higher dose of propafenone was associated with gastrointestinal side effects not present with the low-dose quinidine combination. Of the 10 refractory patients, 7 were further controlled with a standard dose of propafenone plus quinidine (600 mg/day). Overall, control of PAF was achieved in 85% of patients at the end of 8 months; adverse effects necessitating withdrawal were observed in 6%, and uncontrolled AF in 5% of patients. There was no difference in the mean AF rate during recurrences in all phases, and ventricular proarrhythmia was not seen. This study documents the role of stepwise antiarrhythmic treatment of PAF. The use of a standard dose of propafenone, followed by low-dose quinidine combination to reduce propafenone degradation, and the combined standard dose of propafenone and quinidine may be used to maximize efficacy and tolerability.     

Increased microvessel density in malignant and borderline mammary phyllodes tumours

AIMS: Tumour vascularity is considered a prognostic indicator in breast carcinoma, but its utility in mammary phyllodes tumour has not been explored. The authors report the correlation between intratumoral microvessel density and the histological grade of phyllodes tumour. METHODS AND RESULTS: Forty cases of phyllodes tumour were reviewed for stromal cellularity, overgrowth, cytological pleomorphism, mitotic count and margin pattern. Using established criteria, these were diagnosed as benign (n=28), borderline (n=10) and malignant (n=2). Microvessel density was counted on CD31-stained slides as the number of vessels per high power field. For benign phyllodes tumour, the range was 7-26.2 (mean 13.1); for borderline phyllodes tumour the range was 17.2-32.5 (mean 22.4); for malignant phyllodes tumour the range was 25.9-33.3 (mean 29.6). The difference between the benign and borderline groups was significant (P < 0.0001) but that between the borderline and malignant groups was not, due to the small number of malignant cases. CONCLUSIONS: There is a significant difference in stromal microvessel density between benign and borderline phyllodes tumour. Although the small number of cases of malignant phyllodes tumour limits further interpretation, we believe that microvessel density can be used as an additional objective histological parameter in the evaluation of phyllodes tumour.     

Pulmonary hypertension secondary to systemic lupus erythematosus: prolonged survival following treatment with intermittent low dose iloprost.

Pulmonary hypertension (PHT) associated with systemic lupus erythematosus (SLE) has a dismal prognosis. Vasodilators and immunosuppressive therapy have been tried over the years with discouraging results. Prostacyclin (PGI2) which has potent vasodilatatory and anti-platelet effects has been demonstrated to significantly decrease pulmonary arterial pressure and pulmonary vascular resistance during acute infusion. Satisfactory response has been reported in SLE patients with PHT treated with short-term intravenous continuous PGI2 infusion. We report here a 48-month experience of the use of monthly low dose infusion of a PGI2 analogue, iloprost, in a SLE patient with pulmonary hypertension in New York Heart Association functional Class III. There was an initial haemodynamic response to an acute infusion of iloprost. Repeated infusions were followed by marked improvement in her functional status and her mean pulmonary arterial pressure dropped from 80 mmHg in the first few months and remained static at around 55 mmHg for the subsequent years.     

Evaluation of optic disc changes in severe myopia.

PURPOSE: To evaluate the changes in the optic nerve head in highly myopic subjects by means of confocal laser scanning opthalmoscope. METHODS: Using laser scanning and a three-dimensional image analysis system, we studied 114 young (21.4 +/- 1.4 years), highly myopic subjects with refractive errors greater than -8.0 D and a control group of 29 subjects (18.9 +/- 1.2 years) with myopia of -3.0 D or less. Measurements included cycloplegic refraction, corneal curvature, biometric axial length, and morphometric values of the optic disc obtained with a laser scanning disc analyzer. RESULTS: The optic disc area in highly myopic eyes was similar to that in mildly myopic eyes. However, regression analysis revealed that the optic disc area increased with axial length in subjects with severe myopia. The cup/disc ratio, the disc depth, the neuroretinal rim area, and the tilting of the disc were not significantly different between the severe and mild myopia groups. CONCLUSIONS: These findings may be useful in further investigations of myopic progression and of the mechanisms responsible for the development of myopic complications.     

Adult liver transplant survey: policies towards eligibility criteria in Canada and the United States 2007

Goals: To assess the current practice patterns of liver transplant centres in Canada and the USA regarding transplant eligibility. Background: Liver transplantation is an evolving field and today remains the only life‐sustaining treatment for end‐stage liver disease. Issues of allocation and transplant eligibility are important factors in the ethical practice of medicine. Study: Questionnaires were mailed to liver transplant programme directors in Canada and the USA inquiring about current practices regarding recipient eligibility. Results: This study demonstrates that there is consensus in the use of other eligibility criteria, including non‐compliance, social status, abstinence from alcohol and methadone and cocaine use. Interestingly, literature is lacking to support the use of these parameters as eligibility criteria with the exception of alcohol. There is a lack in consensus regarding marijuana use, human immunodeficiency virus status, ability to accept blood transfusions and prisoner status. The literature suggests that liver transplantation in select patients who refuse blood transfusions results in good outcomes. Conclusions: Important decisions regarding transplant eligibility still have to be made empirically in the absence of scientific literature about various social issues. While consensus among transplant programmes is useful, it is important that we continue to use the evidence in the literature to revise these eligibility criteria, keeping in mind ethical principles applied to the access and allocation of a scarce resource.     

Detection and prevention of medication misadventures in general practice.

BACKGROUND: Adverse drug events are leading categories of iatrogenic patient injury. Development of preventive strategies for general practice setting depends on effective detection of events. OBJECTIVE: The aim of the study is to compare the strengths and weaknesses of voluntary reporting, chart review and patient survey in measuring medication misadventures in general practice and to analyze the events by severity and preventability, drug groups and patients' and doctors' characteristics, for the formulation of preventive strategies. METHOD: In the 2-month study period, we applied voluntary report, chart review and patient survey to collect data related to medication misadventures and compared their detection rate. RESULTS: The chart review demonstrated the highest yield for detecting overall medication misadventures (2.03% medication orders), followed by patient survey (1.46% medication orders) and voluntary reporting (0.52% medication orders). Chart review and patient survey were better than voluntary reporting in uncovering preventable adverse drug events. However, voluntary reporting was pivotal in capturing sentinel events. Beta-blocker, diuretic, angiotensin-converting enzyme inhibitor, aspirin and non-steroidal anti-inflammatory drugs had caused 82.0% of all adverse drug events. These events were more common with advanced age of patients, greater number of consultation problems and prescribed drug items. Additional resources implicated were minimal. CONCLUSION: We suggested a complementary approach using chart review and voluntary reporting in measuring and monitoring medication misadventures in general practice. Close monitoring of the events was necessary for older patients, multiple medical problems and poly-pharmacy and for patients using beta-blocker, diuretic, angiotensin-converting enzyme inhibitor, aspirin or non-steroidal anti-inflammatory drugs on a long-term basis.     

Daily physical activity and its contribution to the health-related quality of life of ambulatory individuals with chronic stroke

Background  

Participation in daily physical activity (PA) post-stroke has not previously been investigated as a possible explanatory variable of health-related quality of life (HRQL). The aims were 1) to determine the contribution of daily PA to the HRQL of individuals with chronic stroke and 2) to assess the relationship between the functional ability of these individuals to the amount of daily PA.     

Rapid diagnosis of adult diarrhea rotavirus (ADRV): detection of viral antigens in faecal samples using staphylococcal co-agglutination test

Staphylococcus aureus Cowan I rich in protein A when sensitized with guinea pig antiserum to adult diarrhea rotavirus (ADRV) at 1:16 gave a strong co-agglutination with ADRV-positive faecal samples as previously confirmed by electron microscopy (EM) and enzyme-linked immunosorbent assay (ELISA). The bacteria sensitized with normal guinea pig serum did not give any co-agglutination. Blocking tests using rabbit ADRV-specific antiserum for the treatment of twelve ADRV-positive samples abolished the reaction. All the fifty ELISA-confirmed ADRV-positive faecal samples gave positive co-agglutination, whereas all the forty-eight ELISA-negative faecal samples from healthy subjects gave negative results. The test has been proved to be rapid, simple, specific, and economic, useful for rapid diagnosis even in remote areas, so that the ADRV infection can definitely be differentiated from some of acute bacterial diarrheas.     

Phosphoinositides and GTP binding proteins involved in muscarinic generation of hippocampal rhythmic slow activity

We examined the role of phosphoinositide turnover in muscarinic rhythmic slow activity (RSA; also called theta) in rat CA3 pyramidal neurons. Pre-incubation of hippocampal slices in pertussis toxin (which inhibits some GTP-binding proteins) or in Li+ (which blocks inositol phosphate degradation, and thereby decreases the resynthesis of phosphoinositides), prevented the induction of RSA by carbachol. Phorbol esters, which can activate protein kinase C (PKC) directly, did not induce RSA but inhibited muscarinic RSA. We infer that muscarinic RSA involves a GTP-binding protein linked increase in phosphoinositide turnover, while the activation of PKC may have a negative feedback role.     

Synthesis, antimalarial activity, and quantitative structure-activity relationships of tebuquine and a series of related 5-[(7-chloro-4-quinolinyl)amino]-3-[(alkylamino)methyl] [1,1'-biphenyl]-2-ols and N omega-oxides

A series of 5-[(7-chloro-4-quinolinyl)amino]-3-[(alkylamino)methyl] [1,1'-biphenyl]-2-ols and N omega-oxides was prepared from the substituted 1-phenyl-2-propanones proceeding through the 5-nitro[1,1'-biphenyl]-2-ols, the corresponding amino, and acetamido derivatives to the N-[5-[(alkylamino)methyl]-6-hydroxy[1,1'-biphenyl]-3-yl]acetamides and final condensation with 4,7-dichloroquinoline or the N-oxide. In a quantitative structure-activity relationship study first run on 28 and later expanded to 40 substituted phenyl analogues and their N omega-oxides, increasing antimalarial potency vs. Plasmodium berghei in mice was found to be correlated with decreasing size (sigma MR) and electron donation (sigma sigma) of the phenyl ring substituents. A significant correlation with N omega-oxidation could not be demonstrated. Initial high activity against P. berghei infections in mice led to expanded studies that demonstrated in addition excellent activity against resistant strains of parasite, activity in primate models, and pharmacokinetic properties apparently allowing protection against infection for extended periods of time even after oral administration. Such properties encourage the clinical trial of a member of this class in man.