Linking non‐invasive parametric MRI with invasive physiological measurements (MR‐PHYSIOL): towards a hybrid and integrated approach for investigation of acute kidney injury in rats

Acute kidney injury of various origins shares a common link in the pathophysiological chain of events: imbalance between renal medullary oxygen delivery and oxygen demand. For in vivo assessment of kidney haemodynamics and oxygenation in animals, quantitative but invasive physiological methods are established. A very limited number of studies attempted to link these invasive methods with parametric Magnetic Resonance Imaging (MRI) of the kidney. Moreover, the validity of parametric MRI (pMRI) as a surrogate marker for renal tissue perfusion and renal oxygenation has not been systematically examined yet. For this reason, we set out to combine invasive techniques and non‐invasive MRI in an integrated hybrid setup (MR‐PHYSIOL) with the ultimate goal to calibrate, monitor and interpret parametric MR and physiological parameters by means of standardized interventions. Here we present a first report on the current status of this multi‐modality approach. For this purpose, we first highlight key characteristics of renal perfusion and oxygenation. Second, concepts for in vivo characterization of renal perfusion and oxygenation are surveyed together with the capabilities of MRI for probing blood oxygenation‐dependent tissue stages. Practical concerns evoked by the use of strong magnetic fields in MRI and interferences between MRI and invasive physiological probes are discussed. Technical solutions that balance the needs of in vivo physiological measurements together with the constraints dictated by small bore MR scanners are presented. An early implementation of the integrated MR‐PHYSIOL approach is demonstrated including brief interventions of hypoxia and hyperoxia.     

Reversal-rate dependent differences in the EEG gamma-band during multistable visual perception.

It is an often reported observation in the literature on multistable perception that the reversal rate within a given observation time is subject to a high interindividual variability. Recently, we reported frontal gamma-band enhancement during multistable visual perception. The aim of the present study was to investigate whether changes in the gamma-band correspond to the variability of the reversal rate. Therefore, a total of 25 observers were divided into two subgroups according to their reversal rate during a 400-s observation period of a reversible pattern based on apparent motion. Subjects with more than 40 reversals within the 400-s were defined as high-rate switchers (HRS). Subjects with a reversal rate below 40 switches were defined as low-rate switchers (LRS). EEG was recorded from frontal, central, parietal, and occipital locations of both hemispheres. The results showed significantly higher gamma activity for the HRS in both phase-locked and non-phase-locked oscillations. Both subgroups showed the highest gamma amplitudes at frontal locations. The results support the involvement of attentional top-down processing in figure reversal. It is concluded that the higher gamma activity for the HRS reflects states of higher arousal, alertness and/or attention according to their fast reversal rate.     

Trauma system development in North America

The concepts of organized trauma care, many of which originated in military medicine, have been proven effective in the civilian sector. A formal trauma system includes all phases of care from prehospital through rehabilitation. Although trauma centers assume the leadership role, in a truly inclusive system, all healthcare providers (prehospital providers, community hospitals, and trauma centers) have a defined role in providing care to patients with trauma. As a result, patients receive treatment at the appropriate institution, resources are allocated appropriately, and the clinical outcome is optimized. Such a system ideally is suited to the unique needs of the mass casualty scenario.     

Haemodynamic changes during halothane, sevoflurane and desflurane anaesthesia in dogs before and after the induction of severe heart failure

BACKGROUND AND OBJECTIVE: The effects of desflurane and sevoflurane on the failing myocardium are still uncertain. We investigated the effects of different concentrations of sevoflurane, desflurane and halothane in dogs with pacing induced chronic heart failure. METHODS: Global (left ventricular pressure, left ventricular dP/dt, Konigsbergtransducer) and regional myocardial function (systolic segment length shortening, ultrasonic crystals) were measured in chronically instrumented dogs with tachycardia induced severe congestive heart failure. Measurements were performed in healthy dogs and after induction of heart failure in the awake state and during anaesthesia with 0.75, 1.0, 1.25 and 1.75 minimum alveolar concentration (MAC) of halothane, sevoflurane or desflurane. RESULTS: The anaesthetics reduced dP/dtmax in a dose-dependent manner in healthy dogs (dP/dtmax decreased to 43-53% of awake values at 1.75 MAC). Chronic rapid left ventricular pacing increased heart rate and left ventricular end-diastolic pressure and decreased mean arterial pressure, left ventricular systolic pressure and dP/dtmax. The reduction in contractility was similar in the failing myocardium (to 41-50% of awake values at 1.75 MAC). Segmental shortening was reduced during anaesthesia by 50-62% after pacing compared with 22-44% in normal hearts. While there were similar effects of the different anaesthetics on diastolic function in healthy dogs, after induction of heart failure a more pronounced increase of the time constant of isovolumic relaxation and a greater decrease of dP/dtmin was observed with sevoflurane than with desflurane, indicating a stronger depression of diastolic function. CONCLUSIONS: While the negative inotropic effects of sevoflurane and desflurane were similar in normal and in the failing myocardium in vivo, desflurane led to a better preservation of diastolic function in the failing myocardium.     

Quantitative analysis of MDR1 (multidrug resistance) gene expression in human tumors by polymerase chain reaction.

The resistance of tumor cells to chemotherapeutic drugs is a major obstacle to successful cancer chemotherapy. In human cells, expression of the MDR1 gene, encoding a transmembrane efflux pump (P-glycoprotein), leads to decreased intracellular accumulation and resistance to a variety of lipophilic drugs (multidrug resistance; MDR). The levels of MDR in cell lines selected in vitro have been shown to correlate with the steady-state levels of MDR1 mRNA and P-glycoprotein. In cells with a severalfold increase in cellular drug resistance, MDR1 expression levels are close to the limits of detection by conventional assays. MDR1 expression has been frequently observed in human tumors after chemotherapy and in some but not all types of clinically refractory tumors untreated with chemotherapeutic drugs. We have devised a highly sensitive, specific, and quantitative protocol for measuring the levels of MDR1 mRNA in clinical samples, based on the polymerase chain reaction. We have used this assay to measure MDR1 gene expression in MDR cell lines and greater than 300 normal tissues, tumor-derived cell lines, and clinical specimens of untreated tumors of the types in which MDR1 expression was rarely observed by standard assays. Low levels of MDR1 expression were found by polymerase chain reaction in most solid tumors and leukemias tested. The frequency of samples without detectable MDR1 expression varied among different types of tumors; MDR1-negative samples were most common among tumor types known to be relatively responsive to chemotherapy.     

Prognostic value of intravenous dipyridamole thallium imaging in patients with diabetes mellitus considered for renal transplantation

Patients with diabetes and end-stage renal failure are known to have a high risk for cardiac morbidity and mortality associated with renal transplantation. The most efficient method to determine preoperative cardiac risk has not been established. To determine the effectiveness of intravenous dipyridamole thallium imaging in predicting cardiac events, 40 diabetic renal transplant candidates were studied preoperatively in a prospective trial. The study group consisted of 40 patients whose average age was 42 years (range 27 to 64); 34 (85%) were hypertensive and 21 (53%) were cigarette smokers. Cardiac history included chest pain in 6 patients and prior myocardial infarction in 3 patients. Dipyridamole thallium imaging showed reversible defects in 9 patients, fixed defects in 8 patients and normal scans in 23 patients. Dipyridamole thallium imaging was performed using 0.56 mg/kg of dipyridamole infused intravenously over 4 minutes. Cardiac events occurred only in patients with reversible thallium defects, of which there were 6. Of these 6 patients, 3 had cardiac events before transplantation and 3 had them in the early postoperative phase (within 6 weeks of surgery). Of 21 patients who underwent renal transplantation, 3 had cardiac events within 6 weeks of transplantation. The average duration of follow-up was 11 months (range 1 to 21). Thus, dipyridamole thallium imaging is an effective method of identifying renal transplant candidates likely to develop cardiac complications. Routine coronary angiography may not be necessary to screen all renal transplant candidates for coronary artery disease before surgery.     

Increased fasting glucose and the prevalence of arterial stiffness: a cross-sectional study in Chinese adults

Abstract

Objective:

Previous studies have shown that diabetes increases the prevalence of arterial stiffness. However, it remains controversial whether impaired fasting glucose (IFG), a key pre-diabetes condition, is associated with increased risk of arterial stiffness. This study aimed to investigate the relationship between increased fasting plasma glucose (FPG) and the prevalence of arterial stiffness in a Chinese adult population.

Methods:

A random sample of 5039 participants aged 40 years or older (40·0% female) were enrolled in this study. Information on potential risk factors for cardiovascular disease was collected, and the presence of arterial stiffness was assessed by measuring brachial-ankle pulse wave velocity (baPWV). Participants were stratified into three groups: normal fasting glucose (NFG), IFG, and diabetes mellitus (DM). The IFG group was further stratified by quartiles based on the level of FPG into Q1, Q2, Q3, and Q4.

Results:

Fasting plasma glucose level was found to be independently and positively associated with baPWV. The adjusted odds ratios (ORs) (95% confidence interval (CI)) for arterial stiffness were 1·09 (0·80–1·48), 1·33 (0·98–1·81), 1·27 (0·93–1·73), 1·82 (1·31–2·53), and 2·15 (1·66–2·79) for those in IFG Q1, Q2, Q3, Q4, and DM groups compared with NFG group (P < 0·001), respectively, after adjusting for age, sex, and other potential confounders. Moreover, male participants and participants younger than 60 years were closely associated with the presence and severity of arterial stiffness (P < 0·001).

Conclusion:

Our study reports a previously unidentified positive association between increased FPG and the prevalence of arterial stiffness, suggesting the importance of FPG control in the prevention of arterial stiffness.     

Detection of the Philadelphia chromosome in acute lymphoblastic leukemia by pulsed-field gel electrophoresis

The Philadelphia (Ph1) chromosome is an acquired abnormality in the malignant cells of 10% to 25% of patients with acute lymphoblastic leukemia (ALL). Unlike chronic myelogenous leukemia (CML), where the molecular detection of the Ph1 chromosome is relatively straightforward using conventional Southern hybridization analysis, the detection of the Ph1 chromosome in ALL is complicated by the existence of several molecular subtypes, and the fact that translocation breakpoints are dispersed over a large genomic area. To circumvent these difficulties, we investigated pulsed-field gel electrophoresis (PFGE) to determine if this method could be used directly on clinical samples to detect the Ph1 chromosome in ALL. We report that, in a study of seven patients with Ph1-positive ALL, we could easily detect the Ph1 using only a single PFGE analysis, regardless of the Ph1 subtype, and we could confirm that the translocations occur either within or very near the BCR gene in all seven. We conclude that PFGE is a useful technique for the detection of the Ph1 in ALL, which ultimately may find wide applicability in the detection of other chromosomal abnormalities in other malignancies.