Search

Background This concept analysis aims to present the best estimate of understanding and attitudes of medical and allied healthcare students and educators towards e-professionalism. This work also elucidates the probable truth about safeguarding the concept of medical professionalism in the digital context. Methods This concept analysis was adopted by the Penrod and Hupcey’s principle-based approach using the key term ‘e-professionalism’. On January 2023, PubMed and ISI web of Science were searched for English-language peer-reviewed articles specific to e-professionalism in the medical field. The finally selected research corpus contained 63 articles. Results A comprehensive analysis of the existing body of knowledge highlighted that e-professionalism is an epistemologically mature and distinct concept with a standard definition. However, inconsistencies in conceptual meanings were reported due to varied understandings despite digital literacy. The pragmatic utility showed a lack of sound methodological and philosophical paradigms. Perhaps the technological rapid advancements and manifestations have hampered the linguistic maturity. However, logically, e-professionalism is perceived as an extension of conventional professionalism but with a contextual hinging demanding a distinct framework with a set of attributes to be digitally relevant. Conclusion This concept analysis provides insight into the scarcity of research regarding the collective perspective of essential stakeholders, highlighting the need to investigate further e-professionalism and its complex patterns emerging within the digital context. There is also a recognition of the need for a framework implementation to guide future healthcare professionals. Such framework may potentially yield a more profound understanding and remediation strategies to keep pace with the rapidly advancing medical field in the digital realm.

Curcumin displays anticancer properties; however, some issues with the drug delivery mode limit its therapeutic use. Although reformulation and derivatization of curcumin have improved its bioavailability, curcumin derivatives may not retain the same anticancer properties as the parent compound. The present study investigated the anticancer properties of two curcumin complexes, the iron-curcumin [Fe(Cur)3] and boron-curcumin [B(Cur)2] complexes, in the MDA-MB-231 breast cancer cell line. The cellular localization of curcumin, B(Cur)2 and Fe(Cur)3 was determined by fluorescence microscopy. Cell proliferation, migration and invasion were also analysed. Furthermore, apoptosis-associated proteins were detected by using a proteome profiler array, and ion channel gene expression was analysed by reverse transcription-quantitative PCR. The results demonstrated that the three compounds were localized in the perinuclear and cytoplasmic regions of the cell, and displayed cytotoxicity with IC50 values of 25, 35 and 8 µM for curcumin, B(Cur)2 and Fe(Cur)3, respectively. In addition, the three compounds inhibited cell invasion, whereas only curcumin and B(Cur)2 inhibited cell migration. Furthermore, cell exposure to curcumin resulted in an increase in the relative expression of the two key proapoptotic proteins, cytochrome c and cleaved caspase-3, as well as the antiapoptotic protein haem oxygenase-1. In addition, curcumin increased the expression levels of the voltage-gated potassium channels Kv2.1 and Kv3.2. Similarly, the expression levels of the chloride channel bestrophin-1 and the calcium channel coding gene calcium voltage-gated channel auxiliary subunit γ4 were increased following exposure to curcumin. Taken together, these results indicated that Fe(Cur)3 and B(Cur)2 may display similar anticancer properties as curcumin, suggesting that chemical complexation may be considered as a strategy for improving the potency of curcumin in the treatment of breast cancer.

Background:There is increasing evidence on the exponential use of technology-based social media in medical field that has led to a proliferation of unprofessional behaviors in digital realm. Educating, training, and changing the behaviors of healthcare professionals are essential elements to restrain the rising unprofessional incidents. Therefore, this research was designed to determine the impact of an interventional workshop on the medical and dental students in improving their professional behaviors in the digital world using the newly developed medical Education e-Professionalism (MEeP) framework.MethodsWe adopted the Theory of Planned Behavior (TPB) as a benchmark reference which explores constructs intertwined with the mission-based MEeP framework; values (whistleblowing-raising concerns), behaviors (being responsible in the digital world) and identity (reflective practice in the digital world). A multicentre 3-phased mixed-method study was conducted using a pre-workshop survey, an online interventional workshop, and a post-workshop survey. SPSS and NVivo were the tools used for the data analysis.ResultsA total of 130 students registered for workshop out of which 120 completed the pre-workshop survey, 62 joined the workshop and 59 completed the workshop and post-workshop survey. From the whistleblowing – raising concern perspective, we found that attitudes and perceived behavioral control had a significant relationship. While for responsible in digital world category, attitude and perceived behavioral control had a significant bearing on the intentions. Third, for reflective practice, attitude and subjective norms significantly enhanced the intention of participants. A multi layered thematic analysis yielded four overarching themes of attitudes, subjective norms, perceived behavioral control and intentions. Most students showed positive attitudes of being reflective, self-directed, and humane. Students realized the subjective norms had made them conscientious, self-aware and conformative. While perceived behavioural control manifested as identity and Intentions were heavily reliant on self-actualization.ConclusionOur mixed method study found that the interventional workshop using MEeP framework significantly improved attitudes, subjective norms, perceived behavioral control, and intentions. This study provides valuable evidence of MEeP framework evaluation using the theoretical underpinning of TPB by reporting positive changes in professional values, behaviors, and identities of undergraduate medical and dental students.

The management of pain is an essential aspect of surgical care, and pain levels in post-operative patients vary case by case. Treating postoperative pain is crucial as it leads to better outcomes and reduces risk of long term pain. While post-operative analgesics has been the mainstay of treatment, this mini-review explores an emerging concept which is preoperative pain management, with promising potential. Such interventions include educating patients on the expected pain outcomes and available pain medications. Non-pharmacological methods such as relaxation exercises have also proven to be effective after abdominal surgery, and educating patients on the existence of such methods pre-operatively encourages them to make use of available therapies. A major area of importance is the pre-operative psychological and emotional wellbeing of patients, as it is a strong predictor of pain and pain prognosis. Cognitive Behavioral Therapy can be effectively used to tackle preoperative anxiety and reduce pain levels. Hypnosis is another developing modality for decreasing stress. Lastly, long term pre-operative opioid use has been linked with higher pain scores and longer pain duration. This provides the basis on which pre-operative opioid weaning can lead to favorable post-operative pain outcomes.While many of these methods have not been experimented on recipients of abdominal surgery in specific, it still paves the path for newer pain control strategies that can eventually be adopted for visceral surgery patients. This review points the reader and researchers to new and developing areas that hold the potential to revolutionize current established pain management guidelines.

High-fidelity clinical simulation is currently a well-established teaching tool. However, high-fidelity representations of patients in critical conditions have the potential to elicit emotions among learners and impact their cognitive load (CL). Teaching with clinical simulation may induce both emotional and cognitive overloads. The relationship between anxiety and CL during clinical simulation was studied. Forty-one undergraduate medical students participated in this study; 19 males and 22 females. The state-anxiety component of State-Trait Anxiety Inventory was administered during clinical simulation teaching sessions at time points: pre-scenario, post-scenario and post-debriefing. The Cognitive Load Scale (Leppink et al.) questionnaire was also completed post-scenario. This assessed the three components of CL: intrinsic cognitive load (ICL), extraneous cognitive load (ECL) and self-perceived learning (SPL). Median CL scores for ICL, ECL and SPL were compared between groups of low-anxiety and high-anxiety participants using a Mann-Whitney U test. State-anxiety scores were high for both the pre-scenario and post-scenario time points with a significant reduction following post-debriefing. The median (interquartile range) state-anxiety scores were 41.0 (33.0–50.0), 46.0 (33.0–52.0) and 31.0 (23.0–39.0) for the pre-scenario, post-scenario and post-debriefing time points respectively. Students with high state-anxiety had higher ECL scores (median = 2.0) than students with low state-anxiety (median = 0.9) at the post scenario time point (U = 220, p = 0.043). No statistical relation was seen with state-anxiety for either ICL or SPL. State-anxiety immediately after the simulation scenario is associated with ECL but not ICL or SPL.

Breast cancer is the most common cancer diagnosed among females worldwide. Although breast cancer survival has largely improved in the past 30 years, it remains highly heterogeneous in its response to treatment. Triple-negative breast cancer (TNBC) is a subtype of breast cancer that lacks the expression of the estrogen receptor (ER), progesterone receptor (PR) and epidermal growth factor receptor-2 (Her2). While TNBC may initially be responsive to chemotherapy, recurrence and subsequent high mortality rates are frequently reported. Studies have shown curcumin and its derivatives to be effective against TNBC cell lines in vitro. To improve its anti-cancer effects, we have synthesized Fe3+&ndash, curcumin (Fe&ndash, Cur3) and Cu2+&ndash, curcumin (CD) complexes and investigated them experimentally. Further, CD was encapsulated into a poly(styrene)-co-maleic acid (SMA) micelle to enhance its stability. We assessed the cytotoxicity of these formulations both in vitro and in vivo. SMA&ndash, CD demonstrated dose-dependent cytotoxicity and abolished TNBC tumor growth in vivo. The encapsulation of the curcumin&ndash, copper complex improved its anti-cancer activity without overt adverse effects in a murine model of TNBC. These results provide evidence and insights into the value of nanoformulations in enhancing drug-delivery and increasing the potential therapeutic efficacy of curcumin derivatives.

Lactose intolerance is associated with the inability to digest significant amounts of lactose. Several conditions have symptoms that overlap with those of lactose intolerance. Thus, it is commonly misdiagnosed. There are established investigation procedures that aid diagnosis which include the lactose challenge and the hydrogen breath tests. However, differential diagnosis remains challenging. We aimed at identifying gaps in knowledge regarding lactose intolerance among medical practitioners using a survey consisting of 15 questions. It was completed by 98 doctors. Most questions were answered correctly by more than half of the participants. There was no significant difference in the frequency of correct answers between the different medical specialists or age of participating doctors. Crucially, one question relating to the hydrogen breath test was answered incorrectly by 85% of the participants. This highlights acceptable knowledge of general issues, but not the diagnostic aspects, of lactose intolerance among doctors.

Juggling-exposure therapy has been employed in the management of anxiety and post-traumatic stress disorder. However, there is little evidence of the effectiveness of juggling-exposure in improving emotional states in subclinical conditions. This study aimed at evaluating the effect of a course of juggling on emotional states, sleep quality and blood pressure among medical students at a critical stage of their academic training. Blood pressure, psychometric and quality of sleep assessments were performed pre- and post-examination period for two groups of students: juggling-exposed (n = 9) and non-juggling-exposed (n = 11). Juggling exposure consisted of practice-drills for one hour per week during the period spanning the student's scheduled exams. Comparisons were made between quantitative measures that were collected pre- and post-the course of juggling drills. Differences in scores and measures were expressed as percentage-change and compared between non-juggling and juggling groups. Overall, there was a decrease in depression and anxiety scores between the pre-to post-exam periods. This decrease was statistically significant for both non-juggling and juggling groups with respect to anxiety, but only the juggling-exposed group had a significant reduction regarding depression scores. However, when calculated as percentage-change over the pre-to post-exam period, there was no significant difference in any of the parameters for either of the two groups. Practicing juggling drills had an influence on emotional states.

Background Qigong, a traditional Chinese exercise, has a potential role in the management of stress. Objective To examine the influence of Qigong training on depression, anxiety and stress. Design A randomised control trial among first year student participants. Methods Qigong was practised twice a week by the study group ( n = 18) while a control group ( n = 16) had no intervention. The Depression, Anxiety and Stress (DASS-21) and Patient Health Questionnaires (PHQ) were administered. Salivary biomarkers were also measured over a 10-week period. Results After 10 weeks, only the Qigong group showed a statistically significant improvement in their depression, anxiety and stress scores. Similarly, increases in secretion rates of salivary immunoglobulin-A, and decreases in salivary cortisol concentrations were seen only in the Qigong group. Conclusions The practice of Qigong improves psychological states and mucosal immunity; as indicated by psychometric tests and biochemical markers of stress.

Aims An algorithm based on the CYP3A5 genotype to predict tacrolimus clearance to inform the optimal initial dose was derived using data from the DeKAF study (Passey et al. Br J Clin Pharmacol 2011; 72: 948–57) but was not tested in an independent cohort of patients. Our aim was to test whether the DeKAF dosing algorithm could predict estimated tacrolimus clearance in renal transplant recipients at our centre. Methods Predicted tacrolimus clearance based on the DeKAF algorithm was compared with dose-normalized trough whole-blood concentrations (estimated clearance) on day 7 after transplantation in a single-centre cohort of 255 renal transplant recipients. Results There was a weak correlation (r = 0.431) between clearance based on dose-normalized trough whole-blood concentrations and DeKAF algorithm-predicted clearance. The means of the tacrolimus clearance predicted by the DeKAF algorithm and the estimated tacrolimus clearance based on the dose-normalized trough blood concentrations were plotted against the differences in the clearance as a Bland–Altman plot. Logarithmic transformation was performed owing to the increased difference in tacrolimus clearance as the mean clearance increased. There was a highly significant systematic error (P < 0.0005) characterized by a sloped regression line [gradient, 0.88 (95% confidence interval, 0.75–1.01)] on the Bland–Altman plot. Conclusions The DeKAF algorithm was unable to predict the estimated tacrolimus clearance accurately based on real tacrolimus doses and blood concentrations in our cohort of patients. Other genes are known to influence the clearance of tacrolimus, and a polygenic algorithm may be more predictive than those based on a single genotype.

The search for markers to improve risk prediction for individuals at risk of developing serious cardiovascular events is ongoing. New markers of coronary artery disease progression have been identified in recent years, among which, circulating levels of pregnancy-associated plasma protein-A (PAPP-A) offer an interesting profile. PAPP-A may play a role in the development of atherosclerotic lesions and represent also a marker of atheromatous plaque instability and extent of cardiovascular disease. PAPP-A has been shown to be a marker of adverse outcome in both acute coronary syndrome and stable coronary disease patients. The present article reviews currently available evidence supporting a role for PAPP-A as a marker of cardiovascular risk and discusses some of the pitfalls that may limit its use in clinical practice.

Objectives We sought to decipher metabolic processes servicing the increased energy demand during persistent atrial fibrillation (AF) and to ascertain whether metabolic derangements might instigate this arrhythmia. Background Whereas electrical, structural, and contractile remodeling processes are well-recognized contributors to the self-perpetuating nature of AF, the impact of cardiac metabolism upon the persistence/initiation of this resilient arrhythmia has not been explored in detail. Methods Human atrial appendage tissues from matched cohorts in sinus rhythm (SR), from those who developed AF post-operatively, and from patients in persistent AF undergoing cardiac surgery were analyzed using a combined metabolomic and proteomic approach. Results High-resolution proton nuclear magnetic resonance (NMR) spectroscopy of cardiac tissue from patients in persistent AF revealed a rise in beta-hydroxybutyrate, the major substrate in ketone body metabolism, along with an increase in ketogenic amino acids and glycine. These metabolomic findings were substantiated by proteomic experiments demonstrating differential expression of 3-oxoacid transferase, the key enzyme for ketolytic energy production. Notably, compared with the SR cohort, the group susceptible to post-operative AF showed a discordant regulation of energy metabolites. Combined principal component and linear discriminant analyses of metabolic profiles from proton NMR spectroscopy correctly classified more than 80% of patients at risk of AF at the time of coronary artery bypass grafting. Conclusions The present study characterized the metabolic adaptation to persistent AF, unraveling a potential role for ketone bodies, and demonstrated that discordant metabolic alterations are evident in individuals susceptible to post-operative AF.

AIMS: To examine relationships between markers of systemic inflammation and functional status in patients with chronic obstructive pulmonary disease (COPD). METHODS: 41 COPD patients were stratified using the Medical Research Council (MRC) dyspnoea scale. Six-minute walking distance (6MWD), Quadriceps (% body weight) (QBW), St George's Hospital Respiratory Questionnaire (SGRQ), London Chest Activity of Daily Living Scale (LCADL), C-reactive protein (CRP), interleukin 6 (IL6), tumour necrosis factor ´, and neopterin were measured. Relationships between variables and differences in inflammatory markers between MRC categories were tested. RESULTS: Inflammation increased with MRC grade and was significantly different across grades; CRP (p=0.002) and IL6 (p=0.04). Relationships were evident between CRP, 6MWD, LCADL and SGRQ, r=-0.47, 0.50, 0.43 (all p

Objectives We hypothesized that cholesterol content is increased in the circulating erythrocytes of patients with acute coronary syndrome (ACS) and may be a marker of clinical instability. We therefore sought to investigate whether cholesterol content differs in erythrocyte membranes of patients presenting with ACS compared to patients with chronic stable angina (CSA). Background Plaque rupture in ACS depends at least partly on the volume of the necrotic lipid core. Histopathologic studies have suggested that cholesterol transported by erythrocytes and deposited into the necrotic core of atheromatous plaques contributes to lipid core growth. Methods Consecutive angina patients were prospectively assessed; 120 had CSA (83 men, age 64 ± 11 years) and 92 ACS (67 men, 66 ± 11 years). Total cholesterol content in erythrocyte membranes (CEM) was measured using an enzymatic assay, and protein content was assessed by the Bradford method. Results The CEM (median and interquartile range) was higher (p Conclusions This study shows, for the first time, that CEM is significantly higher in patients with ACS compared with CSA patients. These findings suggest a potential role of CEM as a marker of atheromatous plaque growth and vulnerability. Large ad hoc studies are required to establish the clinical importance and pathogenic significance of CEM measurement.

The immunosuppressive drugs used in organ transplantation have a narrow therapeutic index, with rejection occurring as a consequence of underdosing and infection, malignancy and a number of drug-specific side effects with excessive dosing. Significant heterogeneity in the dose of drug required to achieve therapeutic blood concentrations adds to the complexity of the problem, which has been partly resolved by therapeutic drug monitoring. Single nucleotide polymorphisms have been identified in genes encoding metabolic enzymes, drug efflux pumps and drug targets for most of the drugs in widespread use. A pharmacogenetic approach to immunosuppressive drug prescribing remains to be tested. Based on current evidence, the most promising strategy would be use of the cytochrome P450 3A5 expressor genotype to guide initial dosing with tacrolimus.

Previously, we demonstrated that the dose-normalized tacrolimus blood concentration after renal transplantation was associated with a single nucleotide polymorphism (SNP) in the CYP3AP1 gene, probably through linkage with an SNP in the CYP3A5 gene. Individuals with at least one CYP3A5*1 allele synthesize CYP3A5 and CYP3A5*3/*3 homozygotes do not. We now present results with direct typing of the CYP3A5 genotype for this group of 180 kidney-only transplant recipients from a single center. South Asian and white patients with at least one CYP3A5*1 allele achieved twofold lower dose-normalized tacrolimus blood concentrations compared with CYP3A5*3/*3 homozygotes, confirming our previous findings for the CYP3AP1 SNP. There was a significant delay in achieving target blood concentrations in those with at least one CYP3A5*1 allele. Determination of the CYP3A5*1/*3 genotype could be used to predict the tacrolimus dose requirement and, given incomplete linkage, would be better than determination of the CYP3AP1 genotype.

Background— Both endothelial cell activation and macrophage activation play a significant role in atherogenesis and atheromatous plaque vulnerability and may determine rapid coronary artery disease (CAD) progression. We sought to assess the association between serum inflammatory markers and rapid CAD progression in patients with chronic stable angina pectoris. Methods and Results— We studied 124 chronic stable angina pectoris patients (84 men; mean age, 61±10 years) who were on a waiting list for coronary angioplasty for a mean time of 4.8±2.4 months. CAD progression was defined as ≥10% diameter reduction of a pre-existing stenosis ≥50%, ≥30% diameter reduction of a stenosis P P =0.017), matrix metalloproteinase-9 ( P =0.002), soluble intercellular adhesion molecule 1 ( P P =0.01) were independent predictors of rapid CAD progression. The association between rapid disease progression and inflammatory markers remained significant even when presence of complex lesions was introduced into the multivariate model. Conclusions— Rapid CAD progression in patients with stable angina pectoris is associated with increased C-reactive protein levels and raised concentrations of biochemical markers of endothelial and macrophage activation.

Previously, we reported that, at 3 months after renal transplantation, individuals with CYP3AP1 genotype CYP3AP1*1 (linked to CYP3A5*1 and strongly associated with expression of CYP3A5) required twofold higher doses of tacrolimus to achieve target blood concentrations than individuals with the genotype CYP3AP1*3/*3 (CYP3A5 nonexpressors). This study assesses the relationship between concentration-controlled dosing during the early period after transplantation, the time to achieve target concentrations and genotype in 178 renal transplant recipients (CYP3AP1*1/*3 or *1/*1: n = 53, CYP3AP1*3/*3: n = 125). Patients with CYP3AP1*1/*3 or *1/*1 had lower mean tacrolimus concentrations during the first week (Median 13.5 vs. 18.5 microg/L, p0.0001) with significant delay in achieving target concentrations (15-20 microg/L during week 1, then 10-15 microg/L). More CYP3AP1*3/*3 patients had tacrolimus concentrations above target during the first week (73.6% vs. 35.8%, p = 0.003). There was no difference in the rate of biopsy-confirmed acute rejection, but rejection occurred earlier in the CYP3AP1*1/*3 or *1/*1 group (median 7 d vs. 13 d, p = 0.005). In conclusion, an initial dosing regimen for tacrolimus based on knowledge of the CYP3AP1 genotype and subsequently guided by concentration measurements has the potential to increase the proportion of patients achieving target blood concentrations early after transplantation.

Background Chronic infection with Chlamydia pneumoniae ( Cpn ) has been associated with atherosclerotic cardiovascular disease in sero-epidemiological, pathological and animal-model studies. Inflammation and immune activation has been proposed as the pathophysiological link between chronic infection and atherosclerosis. The aim of this study was to assess whether Cpn seropositivity is associated with serum neopterin concentrations, a marker of macrophage activation, in patients with stable and unstable angina pectoris. Methods We examined 100 patients with angiographically documented coronary artery disease: 60 patients had chronic stable angina and 40 had Braunwald class III unstable angina. Neopterin concentrations were measured with a commercially available immunoassay. Cpn titres were measured with a microimmunoflourescence (MIF) assay. Results Neopterin concentrations were significantly higher in patients with unstable angina compared to those with chronic stable angina (6.30 [4.85-8.80] nmol/L vs 4.95 [3.35-7.05] nmol/L, P = .004), even after adjustment for variables that were significantly different between the 2 groups on univariate analysis. In contrast, the prevalence of positive Cpn serology did not differ significantly between the 2 angina patient groups (65% v 58%, P = .50). Neopterin levels were similar between Cpn -negative and Cpn -positive patients ( P = .40) in both stable and unstable angina groups. Conclusions Patients with unstable angina had higher neopterin concentrations than patients with chronic stable angina, probably reflecting the higher degree of immune activation in acute coronary syndromes. Neopterin levels, however, were independent of Cpn serostatus when combining both stable and unstable angina patients. Thus, immune activation in patients with acute coronary syndromes appears to be unrelated to Cpn seropositivity.

Transplantation has transformed the treatment of patients with organ failure in a number of clinical settings, and immunosuppressive drug therapy is fundamental to its success. However, all the drugs in current use have a narrow therapeutic index. Under-dosing can lead to rejection, while over-dosing increases the risks of infection, malignant disease, and serious drug-specific adverse effects, including diabetes mellitus, nephrotoxicity, hypertension, and hyperlipidemia. Heterogeneity in the pharmacokinetics of these drugs makes initial dose determination difficult, as there is a poor correlation between dose and blood concentration. This results in difficulties in achieving target blood concentrations early after transplantation, which are important for reducing the rate of immunological rejection. This problem is compounded by the observation that neither drug dose nor drug blood concentration accurately predict clinical efficacy or toxicity. The main determinant of heterogeneity in dose requirements is intestinal absorption of the active drug. The oxidative enzymes, cytochrome P450 (CYP) 3A4 and CYP3A5, and the drug efflux pump P-glycoprotein (P-gp) in enterocytes regulate this process. Most substrates for the P-gp pump are also substrates for the CYP3A enzymes. An efficient barrier to xenobiotic absorption is formed by the CYP enzymes and P-gp, and by the two systems working synergistically. Genetic polymorphisms have been reported for the genes associated with the expression of the CYP3A enzymes and P-gp. Genotyping patients for CYP3A genes has the potential to aid the establishment of optimal dosage regimens for transplant patients. Genetic polymorphism of the multiple drug resistance gene-1 (MDR1, also known as ABCB1) [3435C/T] and the CYP3A5 genes (CYP3A5*1, CYP3AP1*1) have the greatest potential to influence the pharmacokinetics of immunosuppressants. Homozygosity of the T allele of the MDR1 3435C/T polymorphism has been associated with reduced enterocyte expression of P-gp resulting in increased drug absorption. The presence of the CYP3A5*1 allele is necessary for the production of a fully catalytic CYP3A5 protein, and also influences the ratio of CYP3A4 : CYP3A5 as well as the overall CYP3A catalytic activity. The CYP3A4 : CYP3A5 ratio may, in turn, influence the pattern of drug metabolites formed. Heterogeneity in the production of active and inactive metabolites has implications for both the pharmacokinetics and pharmacodynamics of these drugs. Gene frequencies and drug dose requirements differ between ethnic groups. Ethnic differences in dose requirements for immunosuppressants have been discussed widely. However, ethnicity is a rather crude marker for genotype. Pharmacogenetic typing offers the possibility of significant improvement in the individualization of immunosuppressive drug prescribing with reduced rates of rejection and toxicity.

Background. There is marked heterogeneity in blood concentrations of tacrolimus following standard body-weight-based dosing. This is most apparent in black patients, who have a higher dose requirement when compared with other ethnic groups. Differences in intestinal P-glycoprotein and hepatic and intestinal cytochrome P4503A activity have been postulated as contributing to this problem. Methods. The dose-normalized blood concentrations of tacrolimus at 3 months after renal transplantation were related to CYP3AP1 and multiple drug resistance (MDR)-1 genotypes determined by polymerase chain reaction followed by restriction fragment length polymorphism analysis. Results. We found that a single nucleotide polymorphism in the CYP3AP1 pseudogene (A/G 44 ) that previously has been noted to be more common in African Americans and strongly associated with hepatic CYP3A5 activity correlated well with the tacrolimus dose requirement. A weaker association was found for a polymorphism in the MDR-1 gene, which influences intestinal P-glycoprotein expression. Conclusions. The CYP3AP1 genotype is a major factor in determining the dose requirement for tacrolimus, and genotyping may be of value in planning patient-specific drug dosing.

Background: The assertion that creatine kinase MB (CK-MB) and the developmental isoforms of cardiac troponin T (cTnT) are expressed by skeletal muscle in some clinical settings is an extrapolation from nonuremic rodent studies. We studied the content of CK-MB and cTnT in skeletal muscle of the renal-insufficient rat.Methods: Skeletal muscles (gastrocnemius) were collected from both five-sixths nephrectomized rats (n = 11) and sham-operated controls (n = 11). cTnT content was analyzed by Elecsys (Roche), immunoblotting, and immunohistochemistry with antibodies M7 and M11-7 (Roche). CK isoenzymes were analyzed electrophoretically.Results: Trace concentrations of cTnT were detected in some of the skeletal muscle samples [controls (3 of 11) and uremic rats (1 of 11)] at concentrations Conclusion: The detection of cTnT and CK-MB in skeletal muscle does not differ for uremic rats compared with sham-operated controls. cTnT isoforms detected by qualitative methods are not detected with the cTnT immunoassay. Observations with rodents should not necessarily be extrapolated to humans.

Animal models are important for the investigation of human heart pathology, novel treatments, and medical or surgical interventions for disease. Serum markers of myocardial damage may also be important tools within this field of research. In order to assess the cardiac specificity of widely utilised serum markers, we measured the cardiac troponins and creatine kinase (CK) isoenzymes in cardiac and skeletal muscle samples taken from dog, monkey, pig and rat. These samples were also analysed by immunoblotting for cardiac troponin I (cTnI) and cardiac troponin T (cTnT). The content of cTnI and cTnT in skeletal muscle was below 0.6% of that found in heart for all animal species studied. This low immunoreactivity in skeletal muscle was confirmed by immunoblot analysis. The content of CK was higher in skeletal muscle than in heart muscle for all species. The CK-MB/total CK ratio was lower in skeletal muscle than in cardiac muscle for all species. The differences in CK-MB content of skeletal muscle and heart muscle were much less pronounced than the tissue differences in the amounts of the cardiac troponins. The cardiac troponins are potentially useful serum markers of myocardial damage, with high specificity for myocardial muscle in these common laboratory animals. Creatine kinase-MB is much less cardiac-specific.

BACKGROUND Authors of several studies have reported that activation of platelets occurs during coronary angioplasty, but consistent results have not been obtained. Levels of serotonin in coronary circulation have been found to be elevated during percutaneous transluminal coronary angioplasty but greater than normal concentrations of beta-thromboglobulin and platelet factor 4 have not been detected. OBJECTIVE To perform a serial analysis of platelet-activation markers with simultaneous measurements of levels of serotonin, beta-thromboglobulin and platelet factor 4 in blood samples from the coronary artery and coronary sinus of patients undergoing coronary angioplasty. METHODS Twenty patients undergoing elective coronary angioplasty were studied. Measurements of levels of beta-thromboglobulin, platelet factor 4, and serotonin in samples from the ostium of the coronary artery and the coronary sinus were performed immediately before angioplasty and after the first balloon deflation. RESULTS Concentrations of beta-thromboglobulin and platelet factor 4 in coronary artery and coronary sinus were elevated in all patients before dilatation, whereas concentrations of serotonin were elevated in 85% of the patients. Concentrations of all markers in coronary sinus decreased after the first inflation. The coronary-sinus: coronary-artery concentration ratios before dilatation for beta-thromboglobulin, platelet factor 4, and serotonin were > 1 for the majority of patients, particularly for those with complex culprit lesions, indicating that coronary activation of platelets was occurring. Ratios remained unchanged or decreased after the first inflation, depending on initial values. CONCLUSIONS Both systemic and coronary activation occur in patients subjected to percutaneous transluminal coronary angioplasty before the onset of intervention. After balloon deflation the greater than normal baseline coronary-sinus:coronary-artery concentration ratios of all markers (beta-thromboglobulin, platelet factor 4 and serotonin) tend to decline or remain unchanged, depending on the level of activation.

We wish to comment on the case reported recently by Isotalo et al. (1). Two different cardiac troponin I (cTnI) assays were used: the AxSYM (Abbott) and the Opus Plus (Dade Behring). The title of the letter claimed that the cTnI value was normal. This is not consistent with the data presented. The AxSYM values for cTnI of 1.2 (day 1), 0.8 (day 2), and 1.1 μg/L (2 weeks) are not normal. The limit of detection for the AxSYM is 0.3 μg/L, with a quoted upper reference limit of 0.4 μg/L and an acute myocardial infarction cutoff of 2.0 μg/L (2). The patient’s values fall within the range for detectable and prognostically significant myocardial damage. The main conclusion that Isotalo et al. (1) make is that the increased cardiac troponin T (cTnT) and creatine kinase MB (CK-MB) concentrations are the result of release from a non-cardiac source related to abnormal expression of these proteins. They did not perform experiments to detect evidence of abnormal cTnT or CK-MB expression in the tumor biopsy. Therefore, we fully agree with the authors that their conclusions were “speculative”. However, we disagree with their discussion. The authors clearly state that the patient had no biochemical evidence of renal failure. However, they go on to describe, in detail, the findings of three conflicting studies that discuss the issue of skeletal muscle expression of cTnT in uremic patients. The reference to these studies in this case presentation implies that the authors are making an association with the issues of cTnT in patients with renal failure. We believe this to be a tenuous link between their limited study and the subject of skeletal muscle expression of cTnT in renal failure. In addition, we feel that they have either misread or misinterpreted two of the references dealing with this … [↵][1]bAddress correspondence to this author at: Division of Biochemistry, Department of Laboratory Medicine, Ottawa Hospital–Civic Campus, 1053 Carling Ave., Ottawa, Ontario, Canada K1Y 4E9. Fax 613-761-5361; e-mail jdonnelly{at}civich.ottawa.on.ca [1]: #xref-corresp-2-1

We read with interest the editorial by Collinson on the use of cardiac troponins T and I (cTnT, cTnI) as specific markers of myocardial damage (1). We agree with Collinson when he suggests that there were some inconsistencies in the data presented by Bodor et al. (2). We, too, were concerned by the use of a system optimized for the measurement of serum troponin T to measure this analyte in extracts of muscle tissue, since there are several dilution and matrix problems to address in this setting (3). Bodor et al. have previously published data measuring cTnI, using the same extraction method (4). We would suggest that, if the methods were as described in both of these publications, they appear to be fundamentally flawed. The authors omitted a vital step in the purification process, which renders their data highly questionable. They prepared two separate fractions, one for soluble cytosolic proteins and one for insoluble myofibrillar proteins. The myofibrillar fraction was then solublized with 8 mol/L urea. The detergent action of urea denatures the proteins of the myofibrillar complex, causing the components of the complex to dissociate. It is well documented that even low concentrations of urea interfere with the Lowry protein assay (5)(6). The kit manufacturer, Sigma, does not recommend the use of this assay in the presence of urea. However, Bodor et al. used this assay to determine total protein concentration in the presence of 8 mol/L urea. The consequent problem is illustrated in Fig. 1⇓ . In addition, 8 mol/L urea could seriously interfere with antibody binding in the immunoassay for cTnT and contribute to a substantial matrix effect. The myofibrillar fraction should have been desalted before any analytical measurements for either total protein, cTnI, or cTnT were performed. Several studies have been published in … bAuthor for correspondence: e-mail GBodor{at}dhha.org

Background: Music has been employed in various clinical settings to reduce anxiety. However, metaanalysis has shown music to have little influence on haemodynamic parameters. This study aimed at investigating the effect of relaxing music on heart rate recovery after exercise. Method: Twenty-three student volunteers underwent treadmill exercise and were assessed for heart rate recovery and saliva analysis; comparing exposure to sedative music with exposure to silence during the recovery period immediately following exercise. Results: No differences were found between music and non-music exposure regarding: heart rate recovery, resting pulse rate, and salivary cortisol. Music was no different to silence in affecting these physiological measures, which are all associated with anxiety. Conclusions: Relaxing music unaccompanied by meditation techniques or other such interventions may not have a major role in reducing anxiety in certain experimental settings.