An insight into clinicians' practices in breaking bad news of oral cancer diagnosis.

Communication is an integral component of effective healthcare delivery to patients, and this includes breaking bad news (BBN). However, clinicians in dentistry are rarely exposed to diseases that can negatively and seriously affect an individual's view of their future and pose a mortality risk, except for oral cancer. The aim of this study was to assess clinician practices in BBN of oral cancer diagnosis in Malaysia. An exploratory sequential mixed-methods study design was used. A qualitative study was conducted among 12 clinicians to gather relevant information regarding their practices in BBN of oral cancer diagnosis using a descriptive-interpretive approach. The themes that emerged were preparation for BBN, BBN setting, communication, emotional aspects, and summarizing the session. These themes were used to develop a questionnaire with 34 items. In the quantitative study, this questionnaire was sent to 87 clinicians who had experienced BBN of oral cancer diagnosis in the past 5 years; the response rate was 100%. An arbitrary cut-off score between the third and fourth quartiles was set to distinguish 'good' and 'poor' practice in BBN among the clinicians. The data analysis was performed using IBM SPSS Statistics version 23.0. Overall, at least two-thirds of the clinicians had good practices in BBN of oral cancer diagnosis. The clinicians' designation (oral and maxillofacial surgery consultant/specialist vs dental officer) and BBN experiences were factors associated with their practices in BBN of oral cancer diagnosis.

Viscoelastic response of the midpalatal suture during maxillary expansion treatment.

OBJECTIVES: The viscoelastic response of the midpalatal suture during maxillary expansion treatment has been sparsely studied. The aim of our study was to use viscoelastic models to investigate the effect of appliance mechanics on sutural tissue. MATERIALS AND METHODS: Four creep-strain models were utilized in predicting the midpalatal suture's response to a constant-force application during expansion treatment. The functional forms included a three-term separable, three-term inseparable, two-term inseparable, and single-term arrangement. The functions were then transformed into subsequent stress-relaxation representations to predict suture response as a result of 0.25, 0.20, 0.15, and 0.10 mm displacements. Finally, the single-term creep-strain representation was altered to simulate treatment decaying force during treatment. A force that decays 30 and 10% of an initially applied 0.98 N was considered for decaying functions over a 6-week period, and compared to strain resulting from a constant-force application. RESULTS: This analysis illustrated that the decay in suture strain closely followed decay in force and that the path of decay had minimal impact on overall results. Also, it was found that a single screw activation would likely not cause suture soft tissue failure, even for a 0.25 mm displacement, and that suture stress rapidly decayed within minutes of activation. CONCLUSION: Results from this study support the notion of maintaining a low-magnitude constant traction on the suture during treatment to avoid soft tissue failure and promote tissue remodeling.

Rescue endoscopic bleeding control for nonvariceal upper gastrointestinal hemorrhage using clipping and detachable snaring.

Nonvariceal upper gastrointestinal (UGI) bleeding recurs after appropriate endoscopic therapy in 10 % - 15 % of cases. The mortality rate can be as high as 25 % when bleeding recurs, but there is no consensus about the best modality for endoscopic re-treatment. The aim of this study was to evaluate clipping and detachable snaring (CDS) for rescue endoscopic control of nonvariceal UGI hemorrhage. We report a case series of seven patients from a Korean tertiary center who underwent endoscopic hemostasis using the combined method of detachable snares with hemoclips. The success rate of endoscopic hemostasis with CDS was 86 %: six of the seven patients who had experienced primary endoscopic treatment failure or recurrent bleeding after endoscopic hemostasis were treated successfully. In conclusion, rescue endoscopic bleeding control by means of CDS is an option for controlling nonvariceal UGI bleeding when no other method of endoscopic treatment for recurrent bleeding and primary hemostatic failure is possible.

Transport of organic cationic drugs: effect of ion-pair formation with bile salts on the biliary excretion and pharmacokinetics.

More than 40% of clinically used drugs are organic cations (OCs), which are positively charged at a physiologic pH, and recent reports have established that these drugs are substrates of membrane transporters. The transport of OCs via membrane transporters may play important roles in gastrointestinal absorption, distribution to target sites, and biliary and/or renal elimination of various OC drugs. Almost 40 years ago, a molecular weight (Mw) threshold of 200 was reported to exist in rats for monoquaternary ammonium (mono QA) compounds to be substantially (e.g., >10% of iv dose) excreted to bile. It is well known that some OCs interact with appropriate endogenous organic anions in the body (e.g., bile salts) to form lipophilic ion-pair complexes. The ion-pair formation may influence the affinity or binding of OCs to membrane transporters that are relevant to biliary excretion. In that sense, the association of the ion-pair formation with the existence of the Mw threshold appears to be worthy of examination. It assumes the ion-pair formation of high Mw mono QA compounds (i.e., >200) in the presence of bile salts in the liver, followed by accelerated transport of the ion-pair complexes via relevant bile canalicular transporter(s). In this article, therefore, the transport of OC drugs will be reviewed with a special focus on the ion-pair formation hypothesis. Such information will deepen the understanding of the pharmacokinetics of OC drugs as well as the physiological roles of endogenous bile salts in the detoxification or phase II metabolism of high Mw QA drugs.

The efficacy of i-SCAN for detecting reflux esophagitis: a prospective randomized controlled trial.

New imaging technologies have been applied in endoscopy to improve the detection and differentiation of subtle mucosal changes using a digital contrast method. Among them, i-SCAN technology is the most recently developed image-enhancing technology. We investigated whether i-SCAN could improve the detection rate of reflux esophagitis. Interobserver agreement between endoscopists was compared with conventional white light (WL) endoscopic examination. We performed a prospective randomized controlled trial. A consecutive series of 514 subjects that underwent an esophagogastroduodenoscopy for health inspection were enrolled and randomized into the i-SCAN group (n = 246) and WL group (n = 268). An esophagogastroduodenoscopy with video recording was used for detecting reflux esophagitis, and reflux esophagitis were categorized by the modified Los Angeles (LA) classification. The total number of reflux esophagitis identified by WL and i-SCAN was 58 (21.7%) and 74 (30.1%), respectively. The diagnostic yield of reflux esophagitis was significantly higher (P = 0.034) in the i-SCAN group (30.1%) as compared to the WL group (21.6%). Using the modified LA classification, the detection rate of minimal changes was significantly higher (P = 0.017) in the i-SCAN group (11.8%) as compared to the WL group (5.6%), but the detection rates of LA-A and LA-B were not significantly different between the two groups (P = 0.897 and P = 0.311, respectively). After comparison of the interobserver agreement using randomly selected video clips, the i-SCAN group showed better agreement than the WL group (Kappa value, 0.793 vs. 0.473). Compared to WL endoscopy, applying i-SCAN in daily practice can improve the diagnostic yield of reflux esophagitis by detecting more minimal changes in the squamo-columnar junction of the esophagus and can improve the interobserver agreement of the modified Los Angeles classification.

Cysteine effects on the pharmacokinetics of etoposide in protein-calorie malnutrition rats: increased gastrointestinal absorption by cysteine.

Protein-calorie malnutrition (PCM) occurs frequently in advanced cancer patients and has a profound impact on the toxicity of many drugs. Thus, the pharmacokinetics of etoposide were evaluated in control, control with cysteine (CC), PCM, and PCM with cysteine (PCMC) rats. Etoposide was administered intravenously (2 mg/kg) or orally (10 mg/kg). Changes in hepatic and intestinal cytochrome P450s (CYPs) and effects of cysteine on intestinal P-glycoprotein (P-gp)-mediated efflux were also measured. In PCM rats, the CL(NR) (AUC(0-∞)) of intravenous etoposide was significantly slower (greater) than that in controls, because of the significant decrease in the hepatic CYP3A subfamily and P-gp. In PCMC rats, the slowed CL(NR) of etoposide in PCM rats was restored to the control level by cysteine treatment. PCMC rats showed a significantly greater AUC(0-6 h) of oral etoposide than PCM rats, primarily because of the increased gastrointestinal absorption of etoposide as a result of the inhibition of intestinal P-gp by cysteine. The gastrointestinal absorption of an oral anticancer drug, which is a substrate of P-gp, may be improved by co-administration of cysteine in advanced cancer patients if the present rat data can be extrapolated to patients.

Comparison of transnasal small-caliber vs. peroral conventional esophagogastroduodenoscopy for evaluating varices in unsedated cirrhotic patients.

BACKGROUND AND STUDY AIMS: We aimed to evaluate the accuracy of transnasal small-caliber esophagogastroduodenoscopy (TNSC-EGD) compared with peroral conventional EGD (POC-EGD) for evaluating varices in unsedated patients with liver cirrhosis. The success rate, safety, endoscopist satisfaction, and patient tolerability of TNSC-EGD were also addressed. PATIENTS AND METHODS: One hundred patients with liver cirrhosis participated in this randomized crossover trial, and 84 subjects completed both procedures. Of the 84 patients, 28 had marked bleeding diathesis (platelet count ≤ 50000/mm (3) and/or prothrombin time ≥ 1.7 INR). Endoscopists and patients answered questionnaires using a 100-mm visual analog scale about, respectively, their satisfaction and their tolerance of the procedure. RESULTS: The success rate of TNSC-EGD was comparable to that of POC-EGD (96% vs. 99%). Nasal mucosal hemorrhages induced by TNSC-EGD occurred in 5 patients (6%), but were easily controlled. Compared to the POC-EGD reference test, diagnostic accuracies of TNSC-EGD for detecting esophageal varices, gastric varices, and red color signs were 98%, 98%, and 96%, respectively. Concordance rates on grading esophageal varices and gastric varices were excellent at 93% (κ = 0.85) and 96% (κ = 0.87). Endoscopist satisfaction was not significantly different between TNSC-EGD and POC-EGD, whereas patient tolerance of TNSC-EGD was significantly greater than that of POC-EGD (79.0 ± 14.4 vs. 69.5 ± 16.1; P = 0.001). CONCLUSION: TNSC-EGD without sedation was found to be feasible, safe, and accurate for evaluating esophageal varices, gastric varices, and red color signs in patients with cirrhosis - even in those with marked bleeding diathesis. Furthermore, it was significantly better tolerated by patients, without altering endoscopist satisfaction. Our findings indicate that TNSC-EGD without sedation might be viewed as a potential alternative to POC-EGD for evaluation of varices.

Decompression and interspinous dynamic stabilization using the locker for lumbar canal stenosis associated with low-grade degenerative spondylolisthesis.

BACKGROUND: Decompression and spinal fusion have been generally recommended for spinal stenosis associated with low-grade degenerative spondylolisthesis (DS), although this is still controversial. The purpose of the present study is to analyze the clinical and radiological outcomes of interspinous dynamic stabilization using the Locker (WINNOVA co, Seoul, Korea) for lumbar canal stenosis with grade I DS. METHODS: The authors performed a retrospective review of 23 consecutive patients who underwent single level decompression and the Locker application for lumbar canal stenosis with grade I DS and were followed up for at least 2 years. Excluded were those with DS grade II or higher and DS combined with foraminal disc herniation/stenosis. The mean age of patients at the time of surgery was 62.1 years (range: 45-81 years). RESULTS: There were no complications in the perioperative period. At a mean follow-up duration of 28.3 months (range: 24-32 months), visual analogue scale scores for back pain, leg pain, and Oswestry disability index had decreased significantly; from 4.6, 7.2, and 38.5% to 2.4, 2.6, and 15.3%, respectively. Clinical success was achieved in 87% of the patients. The mean percentage of slippage did not change significantly. The mean sagittal rotation angle significantly decreased from 9.7 to 6.5 degrees (p=0.01). One patient (4.3%) underwent secondary fusion surgery due to persistent pain. CONCLUSIONS: Decompression and interspinous dynamic stabilization using the Locker yielded favorable clinical and radiological outcomes for lumbar canal stenosis with grade I DS and could be an alternative for spinal fusion. However, further long-term follow-up studies are necessary.

Tropospheric trace gases at Bremen measured with FTIR spectrometry.

The total column densities of acetylene (C(2)H(2)), carbon monoxide (CO), hydrogen cyanide (HCN) and ethane (C(2)H(6)) measured in Bremen (Germany, 53.107 degrees N, 8.854 degrees E) were compared with data from Mace Head/Ireland (MHD) and GEOS-Chem model simulations. The data were obtained between August 2002 and October 2006 with the ground based high resolution Fourier Transform Infra-Red (FTIR) Spectrometry, using the sun as the light source. The analysis showed good agreements between all the three data sets for the seasonal cycle of CO. Enhancements in summer 2003 and summer 2004 due to influence of biomass burning were identified in all three data sets. The high correlations between C(2)H(6) and C(2)H(2), C(2)H(2) and CO, and for C(2)H(6) and CO support the similarities in their sources and sinks. The results suggest that the background air in Bremen is mainly influenced by long-ranged transport of biomass burning products. Local pollution plays a minor role for the measurements performed in Bremen.

Tissue-specific changes in mRNA expression of Abc and Slc transporters in murine pulmonary tuberculosis.

A pulmonary tuberculosis mouse model was used to assess the pharmacodynamic and pharmacokinetic characteristics of tuberculosis therapeutics. While membrane transporters play important roles in drug disposition and physiological homeostasis, their expressional changes and contribution have never been analysed in a tuberculosis animal model. The mRNA expression level of 20 Abc family transporters and 32 Slc family transporters in tuberculosis-infected mice were compared with those in naïve uninfected mice using real-time polymerase chain reaction (PCR). Mycobacterium tuberculosis infection induced many dramatic expression changes of families of both Abc transporters and Slc transporters at 4 and 8 weeks, as observed in the livers, kidneys, and intestines of test mice--and in a different mode, in the lungs and spleens as well. These changes were dependent on the tuberculosis progression with the tissue-specific manner, that is, in the lungs, the number of transporters of which the expression level changed due to M. tuberculosis infection had increased, and the magnitude of change also greater at 8 weeks, while in the spleen, the transcription of most transporters except Mrps had not changed or had recovered back to the same level of naïve transcription at 8 weeks. Understanding the expression changes of transporters will assist in setting up rational preclinical dosing plans through the ability to predict the pharmacokinetics of new anti-tuberculosis chemotherapeutics and, furthermore, will assist in the design of safer and more efficient drug regimens.

Decreased urinary secretion of belotecan in folic acid-induced acute renal failure rats due to down-regulation of Oat1 and Bcrp.

The effects of folic acid-induced acute renal failure on the renal excretion of belotecan were investigated in rats after intravenous administration. Both glomeruli and renal tubules were seriously damaged by folic acid-induced acute renal failure. The renal excretion clearance, CLr, of belotecan was significantly decreased by folic acid-induced acute renal failure. Furthermore, glomerular filtration rate and secretion clearance of the drug were dramatically decreased by folic acid-induced acute renal failure. In vivo renal uptake of belotecan was inhibited by p-aminohippurate, whereas renal excretion was inhibited by GF120918, but not by verapamil and bromosulphalein. This indicates that Oat1/3 and Bcrp are involved in the renal uptake and urinary excretion of belotecan, respectively. Both mRNA and protein levels of Oat1, Oat3 and Bcrp were significantly decreased in folic acid-induced acute renal failure rats. Based on the finding that belotecan is a substrate of OAT1 but not of OAT3, the decrease in CLr of belotecan in folic acid-induced acute renal failure could, therefore, mainly be attributed to the down-regulation of Oat1 and Bcrp, in addition to the decrease in glomerular filtration rate.

Effect of drug-eluting metal stents in benign esophageal stricture: an in vivo animal study.

BACKGROUND AND STUDY AIMS: The aim of this study in canines was to investigate the effectiveness and safety of self-expandable metal stents, which were coated with paclitaxel to minimize the tissue response. MATERIALS AND METHODS: 14 dogs (5-10 kg) were randomly allocated to two groups. Drug-eluting stents (DES, n = 7) or nondrug-eluting stents (non-DES, n = 7) were endoscopically inserted and fixed in the esophagus of healthy dogs. Every 2 weeks, for a maximum period of 8 weeks, an endoscopic examination was performed to evaluate the status of stent insertion, the grade of tissue hyperplasia, and mucosal change at both ends of the stent. RESULTS: One case of stent migration was observed after 4 weeks in the non-DES group. In this group, tissue reaction and hyperplasia remained for more than 4 weeks after stent insertion. By contrast, an endoscopic examination of the surrounding esophageal mucosa in the DES group showed very little tissue reaction, and the stent was easily separated from the esophageal tissue. CONCLUSION: Although further studies are required to confirm our results, we suggest that these newly designed DES may provide an alternative tool to manage refractory benign esophageal stricture.

Development of a sustained-release recombinant human growth hormone formulation.

Recombinant human growth hormone (rhGH) therapy for short stature must be administered as a daily injection because of its poor bioavailability and short half-life. In the present study, a sustained-release formulation of rhGH (SR-rhGH), DA-3003, was prepared using double emulsion solvent evaporation with poly(D,L-lactide-co-glycolide) (PLGA), zinc oxide and hydroxypropyl-beta-cyclodextrin (HPCD) as the release modulator, stabilizer, and aggregation-prevention agent, respectively. After a single administration of DA-3003, the elevated concentration of rhGH in plasma was sustained for 14 days in rats and 28 days in monkeys. The plasma concentration of insulin-like growth factor-1 (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3), which are pharmacodynamic markers of rhGH administration, increased and remained elevated for approximately 28 days in monkeys. Monkeys administered DA-3003 did not develop antibodies to hGH, indicating safety of the SR-rhGH formulation comparable to that observed with daily rhGH injections (Growtropin II). There were no significant differences in efficacy between Growtropin II (daily dose of 5 microg/animal for 14 days) and DA-3003 (weekly dose of 35 microg/animal for 14 days with a dosing interval of a week) in hypophysectomized rats, as assessed by changes in body weight and the width of the tibial growth plate. These results show that a sustained-release rhGH formulation, DA-3003, has the potential to be used safely and efficaciously in a weekly dosing regimen.

Involvement of Mrp2/MRP2 in the species different excretion route of benzylpenicillin between rat and human.

1. The purpose of this study was to investigate the involvement of rat Mrp2 and human MRP2 in benzylpenicillin transport using canalicular liver plasma membrane (cLPM) vesicles isolated from Sprague-Dawley or Easai hyperbilirubinemic (EHBR) rats, and MDCKII cells overexpressing MRP2. 2. The adenosine triphosphate (ATP)-dependent uptake of benzylpenicillin and oestradiol-17beta-D-glucuronide (E(2)17betaG), a representative substrate for Mrp2, into EHBR-cLPM vesicles was decreased relative to that seen with control-cLPM vesicles, which may reflect the absence of Mrp2 in the EHBR. The ATP-dependent uptake of taurocholate, which is not a substrate for Mrp2, was similar in both control and EHBR-cLPM vesicles. The concentration dependence of ATP-dependent benzylpenicillin uptake was reflected in a K(m) of 44.0 microM and a V(max) of 508.4 pmol mg(-1) min(-1). Additional inhibition studies using E(2)17betaG and methotrexate as representative substrates for Mrp2/MRP2 demonstrated the involvement of rat Mrp2, but not human MRP2, in benzylpenicillin efflux. Benzylpenicillin appears not to be a substrate for or inhibitor of other human efflux transporters such as MDR1, MRP1, MRP3, or BCRP. 3. In conclusion, rat Mrp2, but not human MRP2, plays an important role in ATP-dependent benzylpenicillin uptake in the bile canalicular membrane, which may explain why biliary excretion of benzylpenicillin is high in the rat but negligible in humans.

Determinants of exercise-induced pulmonary hypertension in patients with normal left ventricular ejection fraction.

BACKGROUND: Pulmonary hypertension (PH) can occur during exercise and has an adverse effect on functional status, exercise tolerance and prognosis. However, the role of cardiac function abnormalities on exercise-induced PH in patients with normal left ventricular ejection fraction (LVEF) is unclear. OBJECTIVE: To analyse exercise-induced PH determinants in patients with normal LVEF. METHODS AND RESULTS: 396 subjects (160 male, mean age 55 (SD 13)) referred for exercise echocardiography underwent a graded, symptom-limited, supine bicycle exercise with two-dimensional and Doppler echocardiography. Tricuspid regurgitation (TR) velocity was measured at rest and during exercise. Pulmonary artery systolic pressure (PASP) was estimated from TR velocity by adding a right atrial pressure of 10 mm Hg. Patients were classified according to exercise induced PH, defined as present if PASP >50 mm Hg at 50 W of exercise. 135 patients (34%) had PASP >50 mm Hg during exercise. Patients with exercise-induced PH were older, more commonly female and had shorter exercise duration; however, LVEF was significantly higher. The systolic blood pressure at rest and during exercise was significantly higher in patients with exercise-induced PH (rest, 125 (18) vs 132 (18) mm Hg, p = 0.0003; 25 W, 146 (21) vs 157 (21) mm Hg, p<0.0001; 50 W, 157 (24) vs 170 (22) mm Hg, p<0.0001; 75 W, 168 (23) vs 183 (22) mm Hg, p<0.0001). Despite similar resting oxygen saturation, exercise oxygen saturation was significantly lower in subjects with exercise-induced PH than in those without. Numerous echocardiographic variables were significantly different between groups. In multivariate analysis, resting TR velocity (p<0.0001), E/E' (p = 0.027), age and gender were the strongest predictors of PASP during exercise. CONCLUSION: Exercise-induced PH is common even in subjects with normal LVEF. It is strongly associated with E/E' ratio, TR velocity, age, systolic blood pressure during exercise and gender.

Left ventricular diastolic functional reserve during exercise in patients with impaired myocardial relaxation at rest.

BACKGROUND: Patients with similar grade diastolic dysfunction at rest may have a spectrum of alterations in diastolic function during exercise. OBJECTIVE: To evaluate (a) whether exercise could unmask further diastolic abnormalities not evident during rest; (b) whether diastolic functional reserve during exercise is associated with exercise capacity. METHODS: 141 subjects (77 male, mean (SD) age 62 (9)) with abnormal left ventricular (LV) relaxation (mitral E/A <0.75) and/or deceleration time >240 ms, underwent graded supine bicycle exercise with simultaneous respiratory gas analysis and two-dimensional and Doppler echocardiographic study. Mitral inflow and annular velocities were measured at rest and during exercise. The LV diastolic function reserve index (DFRI) was calculated. RESULTS: Patients were classified into two groups: group 1 (n = 64), DFRI <13.5; group 2 (n = 77), DFRI >or=13.5. The ratio of E/E' to stroke volume was used as an index of ventricular elastance (Ed). No significant differences between the groups in mitral inflow and annular velocities at rest were found. Mean (SD) Ed was not significantly different at rest between the groups (0.19 (0.07) vs 0.18 (0.06), p = 0.29). Ed was significantly higher during exercise in group 1 than in group 2 (25 W, 0.21 (0.09) vs 0.14 (0.04), p<0.001; 50 W, 0.22 (0.10) vs 0.15 (0.04), p<0.001). Group 1 subjects had a shorter exercise duration (8.2 (2.7) vs 9.4 (3.7) min, p = 0.04) and lower peak oxygen consumption (17.5 (4.5) vs 20.2 (5.4) ml/kg/min, p = 0.005). CONCLUSIONS: Despite similar mitral flow and annular velocities at rest, different responses to exercise were seen in patients with abnormal LV relaxation at rest. Lower LV diastolic functional reserve was associated with higher ventricular elastance during exercise, and reduced exercise capacity.