The CYP2C19*2 and CYP2C19*17 Polymorphisms play a Vital Role in Clopidogrel Responsiveness after Percutaneous Coronary Intervention: A Pharmacogenomics Study

Clopidogrel inhibits platelet activation and aggregation by blocking the P2Y₁₂ receptor. Dual antiplatelet therapy with clopidogrel and aspirin is recommended treatment by current guidelines for patients undergoing percutaneous interventions. Recurrent ischaemic cardiac events after this treatment showed lack of clopidogrel responsiveness. We aimed to investigate the most noticeable variants in the genes involved in clopidogrel pharmacokinetics and pharmacodynamics. A total of 347 Turkish patients who underwent percutaneous coronary interventions with stent implantation were included in our study. Platelet reactivity (PRU) and % inhibition were measured with VerifyNow P2Y₁₂ assay in blood samples collected from patients who took a standard dose of clopidogrel (75 mg/day) for at least 7 days. The variants in the CYP2C19, CYP3A4, CYP2B6, ABCB1, ITGB3 and PON1 genes were genotyped using the Sequenom MassARRAY system. When grouped, the patients with PRU values >208 as non‐responsiveness to clopidogrel therapy; 104 (30%) patients were non‐responders and 243 (70%) patients were responders. A significant association was found between the CYP2C19*2 (G636A) polymorphism and non‐responsiveness to clopidogrel therapy (p < 0.001). An allele frequency of this single nucleotide polymorphism was high in non‐responders; its odds ratio was 2.92 compared with G allele (p < 0.001). PRU values of CT genotypes were lower (p = 0.029) and % inhibition values of CT genotypes were higher (p = 0.008) compared with CC genotypes for the CYP2C19*17 (C806T) polymorphism. None of the other genetic variants were found to be statistically associated with non‐responsiveness to clopidogrel and antiplatelet activity. Our findings suggest that the CYP2C19*2 polymorphism is associated with non‐responsiveness to clopidogrel therapy and the CYP2C19*17 polymorphism enhances antiplatelet activity of clopidogrel. Depending on haplotypes of these two polymorphisms, clopidogrel‐treated patients can be protected or not from stent thrombosis and ischaemic events.     

A pressure prevention device for burned ears.

Full-thickness burns to the external ear can produce loss of skin and cartilage and can result in severe cosmetic deformity. Even partial-thickness burns render the ear vulnerable to tissue loss if the helix is subjected to pressure from pillows, dressings, or straps that are used to secure endotracheal tubes. Because of the incidence of burned ear deformities and the difficulty in reconstructing the external ear, an ear protection device has been designed. The bilateral ear protection device, referred to as "headgear", is fitted to all patients in the burn center who require intubation for an inhalation injury; it is worn continuously until extubation. During a 15-month period 39 consecutive critically burned patients were fitted with the headgear because of the need for ventilator support and/or for protection of the burned ear(s). Pressure necrosis of ear tissue was prevented in all 33 survivors.     

Video-assisted thoracoscopic repair of an intercostal pulmonary hernia

Pulmonary hernias are extremely rare. They are usually treated with open surgical procedures. We describe a case in which a large, spontaneously acquired intercostal pulmonary hernia was successfully repaired by video-assisted thoracoscopic surgery (VATS). Received: 12 August 1996/Accepted: 26 November 1996     

'It's just the normal thing to do': exploring parental decision-making about the 'five-in-one' vaccine

This qualitative study explored parental decision-making about the DTaP/IPV/Hib 'five-in-one' vaccine. Semi-structured interviews were conducted with 22 parents of babies aged between 4 and 13 weeks old, recruited from four practices in southern England. A modified Grounded Theory approach identified that although parents had some concerns, most complied with the recommended programme rather than making an informed decision. Other themes related to perceived importance of immunisation; beliefs about how immunisation works; trust; perceptions of vulnerability; feelings of guilt and responsibility; and practicalities. It is important to explore how parents' attitudes change over the preschool years and to develop ways of addressing uncertainties about immunisation, including the safety of combining antigens and the need for boosters.     

Effectiveness of Rapid Atrial Pacing for Termination of Drug Refractory Atrial Fibrillation: Results of a Dual Chamber Implantable Cardioverter Defibrillator Trial

There is increasing interest in the use of an implantable cardioverter defibrillator (ICD) to manage atrial tachyarrhythmias. Although device-based shock therapy is highly effective in terminating persistent atrial tachyarrhythmias, atrial overdrive pacing may also be useful, particularly when this therapy is applied early after the onset of an arrhythmia. A dual-chamber ICD (Medtronic 7250 Jewel AF(R)) has been studied in 267 patients with drug-refractory symptomatic AF. The patients were enrolled as part of multicenter clinical trial to evaluate the safety and efficacy of the device to manage atrial tachyarrhythmias in the absence of a standard ventricular ICD indication. The device discriminates atrial tachycardia (AT) from atrial fibrillation (AF) based on cycle length and regularity, and employs multiple methods of atrial overdrive pacing as well as shocks to terminate tachyarrhythmia episodes. Patients were followed for an average of 15.8 +/- 9.3 months. A majority (63%) of patients presented with a history of persistent AF and 34% presented with a history of paroxysmal AF. The pacing therapies terminated 54% of AT episodes and 27% of AF episodes. In patients with persistent AF, 75% of the AT/AF episodes that were successfully terminated by pacing lasted 相似文献   

Health inequalities in Thailand: geographic distribution of medical supplies in the provinces

The purpose of this study was to analyze the regional characteristics and geographic distribution of the medical staffs (physicians and nurses) and the patient beds in relation to the population and average death rates in each of the provinces in Thailand, by using the Lorenz curve and Gini coefficients. Those data were obtained from surveys conducted by the Ministry of Public Health and the Office of the National Education Commission. It was demonstrated that there are certain clear uneven distributions in medical personnel, especially physicians (Gini index = 0.433), by province. For physicians, nurses, and patient beds, approximately 39.6%, 25.8% and 20.6% are concentrated in the Bangkok Metropolis. Specific ideas to solve those problems are discussed in order to overcome this health care crisis by the year 2025.     

Chronotropic incompetence: a common and progressive finding in pacemaker patients.

Thirty-eight patients (ages 40 to 77 years, mean 63) followed in a pacemaker clinic underwent exercise treadmill tests to determine chronotropic incompetence. There were 28 men and 10 women. Twenty-seven patients had atrioventricular (AV) block and 11 patients had sick sinus syndrome. All patients were exercised to fatigue. None of the patients were receiving beta-blockers or other drugs that could reduce heart rate. Maximum heart rate (MHR) and percent predicted maximum heart rate (% PMHR) were used as an index of chronotropic incompetence. Chronotropic incompetence was defined as inability to achieve a % PMHR of greater than 80%. The overall incidence of chronotropic incompetence was 58% (22 of 38 patients). We examined the relationship between chronotropic incompetence and the time to pacemaker implantation. We found that in patients who had pacemakers for less than 2 years, the mean MHR was 125 +/- 21.6 beats/min compared with 111.9 +/- 23.6 beats/min for patients who had pacemakers implanted for longer than 4 years. Similarly, the mean % PMHR decreased from 76.5 +/- 12.5% to 68.7 +/- 15.4% in patients with pacemakers less than 2 years versus those with pacemakers for more than 4 years. Fifty-three percent of the patients with a pacemaker less than 2 years old were chronotropic incompetent versus 70% of the patients with a pacemaker more than 4 years old. These data suggest that chronotropic incompetence worsens with time after pacemaker implant. To further support this, eight patients with AV block underwent a second stress test an average of 2 years following the first.(ABSTRACT TRUNCATED AT 250 WORDS)     

Supernormal ejection performance is isolated to the ipsilateral congenitally pressure-overloaded ventricle

Congenital left ventricular pressure overload is associated with "excessive" hypertrophy that leads to subnormal afterload (wall stress), permitting enhanced ventricular ejection performance. Whether congenital right ventricular pressure overload is associated with a similar phenomenon is uncertain. It is also unknown whether supranormal ejection performance affects only the overloaded ventricle or is a general process affecting both ventricles. Conflicting data exist about whether the hypertrophic process associated with pressure overload is induced primarily by local loading conditions or by neuroendocrine influences. If the former postulate is true, the hypertrophic response should be confined to the overloaded ventricle; if the latter is true, one might predict that both ventricles would be affected by a less specific response to circulating catecholamines. To help resolve these issues, both right and left ventricular performance was examined in seven patients with isolated congenital pulmonary stenosis (average pulmonary pressure gradient 78 +/- 13 mm Hg), six patients with isolated congenital aortic stenosis (average gradient 80 +/- 10 mm Hg) and six normal subjects. Right ventricular ejection fraction was increased in patients with pulmonary stenosis (61 +/- 2%) compared with the value in normal subjects (53 +/- 2%, p less than 0.01) and in patients with aortic stenosis (50 +/- 3%, p = 0.007). Left ventricular ejection fraction was increased in patients with congenital aortic stenosis (84 +/- 4%) compared with the value in normal subjects (70 +/- 4%, p less than 0.01) and in patients with congenital pulmonary stenosis (65 +/- 2%, p less than 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)     

Quantitative assessment of muscular stiffness in children with cerebral palsy using acoustic radiation force impulse (ARFI) ultrasound elastography

Purpose

To evaluate the feasibility of quantitative analysis of muscle stiffness in the medial gastrocnemius muscle (GCM) by acoustic radiation force impulse (ARFI) ultrasound elastography in children with spastic cerebral palsy (CP).

Methods

Seventeen children with spastic CP and 25 healthy children participated in the study between the years 2016–2017. The medial GCM in the CP group was assessed using the Modified Ashworth Scale (MAS) by a physiatrist. ARFI was used to measure the shear-wave velocities (SWVs) of the medial GCM. The mean SWV value for each MAS score was calculated and used for statistics.

Results

The mean SWV values of the medial GCM in the CP and healthy groups were 3.17 ± 0.81 m/s (mean ± SD) and 1.45 ± 0.25 m/s (mean ± SD), respectively. The SWV of the medial GCM significantly increased in the CP patients when compared with controls (p < 0.001). In addition, the SWV values were correlated with the MAS scores (p < 0.001). The interobserver agreement expressed as the interclass correlation coefficient was 0.65 (95% CI 0.33–0.84, p < 0.001).

Conclusions

ARFI imaging demonstrated a difference in muscle stiffness in the medial GCM between the CP and healthy groups. This method is a feasible imaging modality for the noninvasive assessment of contracting muscles in children with CP.