Dyslipidemia and coronary artery calcium: From association to development of a risk-prediction nomogram

Background and aimsThe associations between dyslipidemia and coronary artery calcium (CAC) are controversial. We investigated their cross-sectional relationships and developed a predictive scoring system for prognostically significant coronary calcification (PSCC).Methods and resultsThis study evaluated the lipid profiles and the CAC score (CACS) measured through multidetector computed tomography (MDCT) among Taiwanese adult patients in a tertiary hospital between 2011 and 2016. Patients with CACS higher than 100 were classified as having PSCC. Dyslipidemia for each lipid component was defined based on the clinical cutoffs or the use of the lipid-lowering agents. Multivariable logistic regression was used to assess the association between dyslipidemia and PSCC and the model performance was assessed using calibration plot, discrimination, and a decision curve analysis.Of the 3586 eligible patients, 364 (10.2%) had PSCC. Increased age, male sex, higher body mass index (BMI), and higher level of triglyceride (TG) were associated with PSCC. The adjusted odds ratios (95% confidence intervals) of PSCC was 1.15 (0.90–1.47) for dyslipidemia defined by total cholesterol (TC) ≥200 mg/dL, 1.06 (0.83–1.35) for low-density-lipoprotein-cholesterol (LDL-C) ≥130 mg/dL, and 1.36 (1.06–1.75) for TG ≥ 200 mg/dL. The positive association between TG ≥ 200 mg/dL and PSCC was not modified by sex. Incorporating hypertriglyceridemia did not significantly improve the predictive performance of the base model comprising of age, sex, BMI, smoking, hypertension, diabetes, estimated glomerular filtration rate, and fasting glucose.ConclusionsHypertriglyceridemia was significantly associated with the prevalent odds of PSCC. Our proposed predictive model may be a useful screening tool for PSCC.     

Evaluation of quantitative aerosol techniques for use in bronchoprovocation studies

To investigate airway physiology by use of inhaled aerosols, it is frequently necessary to measure the actual amount of material deposited on the airway wall as well as the site of particle deposition. To satisfy these needs, radiolabeled aerosols and gamma camera techniques have been used to measure regional deposition of inhaled particles. To make quantitative measurements of the amount deposited, previous investigators have used a "phantom" technique to indirectly calibrate the gamma camera for the attenuation of gamma rays through the lungs and chest wall. For this calibration, the phantom is a simulated lung containing a known amount of radioactivity. Radioactive counts emitted from the phantom are assumed to be attenuated in the same manner as the intact human lung. The present article describes a technique to determine directly the amount of inhaled aerosol deposited in the lung and simultaneously to calibrate the gamma camera for each individual subject. We used right angle light scattering and a gamma camera to measure individual values of the deposition fraction (DF) of inhaled aerosol deposited in the lung and the coefficient of attenuation (AC) of gamma rays in normal and obstructed lungs of human subjects. Radiolabeled monodisperse aerosols 1 and 2 microns in diameter were used. Knowledge of the activity of the inhaled aerosol (microcurie per liter), the volume inhaled, and the measured DF determined each subject's AC (counts per minute per microcurie). DF varied by an order of magnitude in normal (0.04 to 0.48) and obstructed (0.16 to 0.75) of subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Does cyclosporine influence the results of cadaver retransplantation?

The results of cadaveric retransplantation in 55 recipients immunosuppressed with cyclosporine and prednisone were compared to 156 recipients of primary renal allografts. By 3 yr posttransplant, there is no significant difference in patient survival, but the yearly graft survival for primary (79%, 72%, 72%) as compared to retransplant (69%, 58%, 58%) recipients was significantly (p less than 0.05) better. There was no significant difference in rejection episodes or mean +/- SD serum creatinine (mg/dl) at 2 yr between primary (32%, 2.14 +/- 1.1) and retransplant (33%, 2.08 +/- 1.4) patients, respectively. Donor source, third kidneys, human leukocyte antigen AB and Dr matching, percent reactive antibody levels, and cause of first graft loss do not have significant impact on cyclosporine-treated retransplant outcome. However, retransplant patients who have lost a previous graft in less than 3 months continue to be at high risk for subsequent early graft loss. These results suggest that the combination of cyclosporine and prednisone is the preferred regimen for cadaveric retransplantation.     

Reporting of neuropsychological dysfunction remains discrepant between individuals with traumatic brain injury and their close others up to five years post-injury

Purpose: The degree to which individuals with traumatic brain injury (TBI) and their close others share a common understanding and experience of post-injury neuropsychological changes is currently unclear. The aim of this preliminary study was to longitudinally examine levels of agreement between self and close other reports of neuropsychological dysfunction following TBI and explore factors associated with these agreement levels. Method: Sixty-three people with TBI and their nominated close others independently completed the Structured Outcome Questionnaire at 1- and 5-years post-injury, reporting whether the person with TBI was experiencing any negative cognitive, behavioural or emotional changes compared to pre-injury. Results: Agreement levels between pair members ranged from chance to approximately 75% across neuropsychological domains and did not significantly change over 1- and 5-year time points. In the case of pair disagreement, close others were generally more likely to report difficulties. Pair disagreement was significantly associated with close other anxiety. Conclusions: Agreement between self and close others remains limited up to 5-years post-injury which questions the practice of using these reports interchangeably in research and clinical practice. Preliminary findings suggest some association between pair disagreement and close other psychological function; however, further research is warranted.

• Implications for Rehabilitation

• Reporting of neuropsychological dysfunction between individuals with TBI and their close others is not sufficiently reliable to warrant interchangeable use within research or clinical practice.

• Including both individuals with TBI and their close others in clinical assessments will facilitate a more holistic understanding of the client’s difficulties and their relationships with those close to them.

• Preliminary findings indicate that disagreement between individuals with TBI and their close others may be associated with close other anxiety. Clinicians should be aware of the potential for disagreement to impact on the psychological health of close others.

     

Levofloxacin pharmacokinetics in adult cystic fibrosis

BACKGROUND: Cystic fibrosis (CF) patients have enhanced renal clearance of aminoglycosides and several beta-lactams and require higher dosages. Levofloxacin is a fluoroquinolone with extensive renal elimination and enhanced penetration into lungs and Pseudomonas aeruginosa (PA) biofilms. We studied the preliminary pharmacokinetic and pharmacodynamic (PK/PD) relationship of levofloxacin in CF. METHODS: Twelve patients at least 18 years old with a mild-to-moderate pulmonary exacerbation and fluoroquinolone-sensitive PA colonization received oral levofloxacin, 500 mg qd, for 14 days. Steady-state serum concentrations were collected after 3 to 7 days, and sputum samples for PA densities were collected before and after levofloxacin. PK/PD relationships for reducing PA sputum densities were evaluated. RESULTS: When compared to published data on non-CF patients, CF patients had similar area under the curve for 24 h (AUC(24)), total clearance, volume of distribution, maximum serum concentration (Cpmax), and elimination half-life: mean, 7.33 microg x h/mL/kg (SD, 1.70); 2.43 mL/min/kg (SD, 0.74); 1.33 L/kg (SD, 0.37); 7.06 microg/mL (SD, 2.35); and 6.44 h (SD, 1.1), respectively. Time to reach maximum serum concentration (Tmax) in CF was longer: mean, 2.20 h (SD, 0.99) vs 1.1 h (SD, 0.4) [p < 0.01]. Preliminary PK/PD analysis failed to demonstrate trends for decreasing PA sputum densities with increasing Cpmax/minimum inhibitory concentration (MIC) ratio and AUC(24)/MIC ratio. CONCLUSION: CF levofloxacin pharmacokinetics corrected for body weight are similar to non-CF, except for Tmax. Standard levofloxacin dosing (especially monotherapy) is unlikely to produce maximum therapeutic effectiveness. Additional levofloxacin studies in CF are necessary to evaluate its sputum concentrations; the benefits of higher daily dosages (>/= 750 mg); and establish PK/PD targets for managing PA pulmonary infections.     

Medication adherence and significant others' support of consumers with schizophrenia in Australia

Medication adherence is problematic in people with chronic illness. The purpose of this exploratory study was to examine the effects of the perceived support from significant others on the oral antipsychotic medication taking of consumers with schizophrenia. A convenience sample of 81 consumers took part in the study. The consumers were recruited by case managers from the community in the western region of Melbourne and in regional and rural Victoria, Australia. No difference was found in self-reported medication adherence between the consumers with significant others' support and those without significant others' support. The perceived effect of having a supportive relationship with significant others was not associated with increased medication adherence. The findings indicated that the significant others' support did not influence the self-reported medication adherence of the consumers with schizophrenia. The results highlighted the importance of considering medication adherence as a multidimensional concept.     

腹腔镜胆总管探查胆道一期缝合与T管引流疗效的比较

目的探讨与腹腔镜胆总管T管引流相比,腹腔镜胆总管一期缝合的优点,手术操作的技术关键,手术适应证以及并发症的预防。方法回顾对照分析2008年7月至2010年7月间行腹腔镜胆总管一期缝合的24例患者以及同期行腹腔镜T管引流的24例患者的临床病历资料,分为一期缝合组和T管引流组。结果一期缝合组与T管引流组的平均手术时间分别为（54.03±8.46）、（49.83±7.25）min,术中出血量分别为（15.13±4.26）、（16.23±5.25）ml,两组差异无统计学意义（P〉0.05）。而一期缝合组与T管引流组的首次肛门排气时间分别为（1.16±0.46）与（2.02±0.19）d、术后补液量分别为（8.05±2.73）与（11.56±4.72）L、术后住院时间分别为（7.73±1.76）与（13.85±4.09）d、住院费用分别为（11 393±283）与（15 836±296）元,带管时间分别为（6.45±2.15）与（73.68±9.15）d。一期缝合组的平均带管时间较T管引流组缩短（67.23±7）d。以上观察指标,两组差异有统计学意义（P〈0.01）。一期缝合组4例术后2～3 d发生胆汁漏,经保守治疗治愈,无严重并发症,全组患者均痊愈出院,随访1个月到2年,无结石复发和胆管狭窄等并发症。结论胆总管一期缝合有利于患者快速恢复;术中确保胆道无残余结石和胆总管下端通畅是开展胆总管一期缝合的前提条件;严格掌握手术适应证,注重操作技术要点是取得良好疗效的关键。     

Protective effect of some vitamins against the toxic action of ethanol on liver regeneration induced by partial hepatectomy in rats

AIM： To investigate the effects of vitamins （A, C and E） on liver injury induced by ethanol administration during liver regeneration in rats. METHODS： Male Wistar rats subjected to 70% partial hepatectomy were divided into five groups （groups 1-5）. During the experiment, animals of Group 1 drank only water. The other four groups （2-5） drank 30 mL of ethanol/L of water. Group 3 additionally received vitamin A, those of group 4 vitamin C and those of group 5 received vitamin E. Subsequently serum alanine aminotransferase （ALT）, aspartate aminotransferase （AST）, albumin and bilirubin were measured colorimetrically. Lipid peroxidation （thiobarbituric-acid reactive substances, TBARS） both in plasma and liver was measured, as well as liver mass gain assessment and total DNA. RESULTS： Compared with sham group, serum AST and ALT increased significantly under ethanol treatment （43% and 93%, respectively, with P 〈 0.05）. Vitamin C and vitamin E treatment attenuated the ethanol-induced increases in ALT and AST activity. Ethanol treatment also decreased serum albumin concentration compared to sham group （3.1 ± 0.4 g/dL vs 4.5 ± 0.2 g/dL; P 〈 0.05）. During liver regeneration vitamins C and E significantly ameliorated liver injury for ethanol administration in hepatic lipid peroxidation （4.92 nmol/mg and 4.25 nmol/mg vs 14.78 nmol/mg, respectively, with P 〈 0.05）. In association with hepatic injury, ethanol administration caused a significant increase in both hepatic and plasma lipid peroxidation. Vitamins （C and E） treatment attenuated hepatic and plasma lipid peroxidation. CONCLUSION： Vitamins C and E protect against liver injury and dysfunction, attenuate lipid peroxidation, and thus appear to be significantly more effective than vitamin A against ethanol-mediated toxic effects during liver regeneration.     

Prokineticin 2/Bv8 is expressed in Kupffer cells in liver and is down regulated in human hepatocellular carcinoma

AIM： TO study the implication of prokineticin 1 （PKI/EGVEGF） and prokineticin 2 （PK2/13v8） in hepatocellular carcinoma angiogenesis.
METHODS： The gene induction of PK1/EG-VEGF and PK2/Bv8 was investigated in 10 normal, 28 fibrotic and 28 tumoral livers by using real time PCR. Their expression was compared to the expression of VEGF （an angiogenesis marker）, vWF （an endothelial cell marker） and to CD68 （a monocyte/macrophage marker）. Furthermore, the rnRNA levels of PK1/EG-VEGF, PK2/Bv8, prokineticin receptor 1 and 2 were evaluated by real time PCR in isolated liver cell populations. Finally, PK2/Bv8 protein was detected in normal liver paraffin sections and in isolated liver cells by immunohistochernistry and immunocytochemistry.
RESULTS： PK2/Bv8 mRNA but not PK1/EG-VEGF was expressed in all types of normal liver samples examined. In the context of liver tumor development, we reported that PK2/13v8 correlates only with CD68 and showed a significant decrease in expression as the pathology evolves towards cancer. Whereas, VEGF and vWF mRNA were significantly upregulated in both fibrosis and HCC,as expected. In addition, out of all isolated liver cells examined, only Kupffer cells （liver resident macrophages） express significant levels of PK2/Bv8 and its receptors, prokineticin receptor 1 and 2.
CONCLUSION： In normal liver PK2/Bv8 and its receptors were specifically expressed by Kupffer cells. PK2/Bv8 expression decreased as the liver evolves towards cancer and did not correlate with HCC angiogenesis.