Global tidal variations, regional distribution of ventilation, and the regional onset of filling determined by electrical impedance tomography: reproducibility.

The reproducibility of the regional distribution of ventilation and the timing of onset of regional filling as measured by electrical impedance tomography lacks evidence. This study investigated whether electrical impedance tomography measurements in healthy males were reproducible when electrodes were replaced between measurements. Part 1: Recordings of five volunteers lying supine were made using electrical impedance tomography and a pneumotachometer. Measurements were repeated at least three hours later. Skin marking ensured accurate replacement of electrodes. No stabilisation period was allowed. Part 2: Electrical impedance tomography recordings of ten volunteers; a 15 minute stabilisation period, extra skin markings, and time-averaging were incorporated to improve the reproducibility. Reproducibility was determined using the Bland-Altman method. To judge the transferability of the limits of agreement, a Pearson correlation was used for electrical impedance tomography tidal variation and tidal volume. Tidal variation was judged to be reproducible due to the significant correlation between tidal variation and tidal volume (r2 = 0.93). The ventilation distribution was not reproducible. A stabilisation period, extra skin markings and time-averaging did not improve the outcome. The timing of regional onset of filling was reproducible and could prove clinically valuable. The reproducibility of the tidal variation indicates that non-reproducibility of the ventilation distribution was probably a biological difference and not measurement error. Other causes of variability such as electrode placement variability or lack of stabilisation when accounted for did not improve the reproducibility of the ventilation distribution.

The time taken for the regional distribution of ventilation to stabilise: an investigation using electrical impedance tomography.

Electrical impedance tomography is a novel technology capable of quantifying ventilation distribution in the lung in real time during various therapeutic manoeuvres. The technique requires changes to the patient's position to place the electrical impedance tomography electrodes circumferentially around the thorax. The impact of these position changes on the time taken to stabilise the regional distribution of ventilation determined by electrical impedance tomography is unknown. This study aimed to determine the time taken for the regional distribution of ventilation determined by electrical impedance tomography to stabilise after changing position. Eight healthy, male volunteers were connected to electrical impedance tomography and a pneumotachometer. After 30 minutes stabilisation supine, participants were moved into 60 degrees Fowler's position and then returned to supine. Thirty minutes was spent in each position. Concurrent readings of ventilation distribution and tidal volumes were taken every five minutes. A mixed regression model with a random intercept was used to compare the positions and changes over time. The anterior-posterior distribution stabilised after ten minutes in Fowler's position and ten minutes after returning to supine. Left-right stabilisation was achieved after 15 minutes in Fowler's position and supine. A minimum of 15 minutes of stabilisation should be allowed for spontaneously breathing individuals when assessing ventilation distribution. This time allows stabilisation to occur in the anterior-posterior direction as well as the left-right direction.

Curcumin induces apoptosis in human neuroblastoma cells via inhibition of AKT and Foxo3a nuclear translocation.

Neuroblastoma (NB) is one of the most frequent extracranial solid tumors in children. It accounts for 8-10% of all childhood cancer deaths, and there is a need for development of new drugs for its treatment. Curcumin (diferuloylmethane), a major active component of turmeric (Curcuma longa), has been shown to exert anti-tumor activity on NB, but the specific mechanism by which curcumin inhibits cancer cells proliferation remains unclear. In the present study, we investigated the anti-proliferative effect of curcumin in human LAN5 NB cells. Curcumin treatment causes a rapid increase in reactive oxygen species and a decrease in the mitochondrial membrane potential-events leading to apoptosis activation. Furthermore, curcumin induces decrease in haet shock protein (Hsp)60 and hexokinase II mitochondrial protein levels and increase in the pro-apoptotic protein, bcl-2 associated death promoter (BAD). Moreover, we demonstrate that curcumin modulates anti-tumor activity through modulation of phosphatase and tensin homolog deleted on chromosome 10 and consequential inhibition of the survival Akt cell-signaling pathway. Inhibition of Akt causes its translocation into the cytoplasm and import of Foxo3a into the nucleus where it activates the expression of p27, Bim, and Fas-L pro-apoptotic genes. Together, these results take evidence for considering curcumin as a potential therapeutic agent for patients with NB.

Oxygen delivery through high-flow nasal cannulae increase end-expiratory lung volume and reduce respiratory rate in post-cardiac surgical patients.

BACKGROUND: High-flow nasal cannulae (HFNCs) create positive oropharyngeal airway pressure, but it is unclear how their use affects lung volume. Electrical impedance tomography allows the assessment of changes in lung volume by measuring changes in lung impedance. Primary objectives were to investigate the effects of HFNC on airway pressure (P(aw)) and end-expiratory lung volume (EELV) and to identify any correlation between the two. Secondary objectives were to investigate the effects of HFNC on respiratory rate, dyspnoea, tidal volume, and oxygenation; and the interaction between BMI and EELV. METHODS: Twenty patients prescribed HFNC post-cardiac surgery were investigated. Impedance measures, P(aw), ratio, respiratory rate, and modified Borg scores were recorded first on low-flow oxygen and then on HFNC. RESULTS: A strong and significant correlation existed between P(aw) and end-expiratory lung impedance (EELI) (r=0.7, P<0.001). Compared with low-flow oxygen, HFNC significantly increased EELI by 25.6% [95% confidence interval (CI) 24.3, 26.9] and P(aw) by 3.0 cm H(2)O (95% CI 2.4, 3.7). Respiratory rate reduced by 3.4 bpm (95% CI 1.7, 5.2) with HFNC use, tidal impedance variation increased by 10.5% (95% CI 6.1, 18.3), and ratio improved by 30.6 mm Hg (95% CI 17.9, 43.3). A trend towards HFNC improving subjective dyspnoea scoring (P=0.023) was found. Increases in EELI were significantly influenced by BMI, with larger increases associated with higher BMIs (P<0.001). CONCLUSIONS: This study suggests that HFNCs reduce respiratory rate and improve oxygenation by increasing both EELV and tidal volume and are most beneficial in patients with higher BMIs.

Poor concordance of commonly used echocardiographic measures of left ventricular diastolic function in patients with suspected heart failure but preserved systolic function: is there a reliable echocardiographic measure of diastolic dysfunction?

OBJECTIVE: To determine the concordance of different Doppler echocardiographic criteria for "diastolic dysfunction" in patients with suspected heart failure but preserved left ventricular systolic function. DESIGN: Prospective, descriptive study. SETTING: Outpatient based direct access echocardiography service. PATIENTS: Consecutive patients referred with suspected heart failure but preserved left ventricular systolic function. MEASUREMENTS: Echocardiographic measurements of systolic and diastolic function. Eight published studies giving age and sex specific ranges for measures of diastolic function in healthy subjects were reviewed and the proportion of patients outside the normal limits for each of these published ranges was calculated. RESULTS: There was very poor concordance between measures with up to a 16-fold difference in the prevalence of diastolic dysfunction in the overall patient cohort. Even for a given measure, there was relatively poor agreement between the published reference ranges. In subsets likely to include patients at high risk of having diastolic dysfunction, an increased prevalence of diastolic dysfunction was not evident with any measure in any patient subset. CONCLUSIONS: Our findings challenge the use of the diagnosis of diastolic heart failure based on the most commonly used echocardiographic criteria. Physicians should be cautious about echocardiographic reports describing diastolic dysfunction and only apply the diagnosis of diastolic heart failure with great care.

"Diastolic heart failure" or heart failure caused by subtle left ventricular systolic dysfunction?

OBJECTIVES: To determine whether patients with suspected heart failure but preserved systolic function, as determined by conventional echocardiographic measures (often said to have "diastolic heart failure), might have subtle left ventricular systolic dysfunction detectable by a new measure of left ventricular systolic function-left ventricular systolic atrioventricular plane displacement. DESIGN: Observational study. SETTING: Direct access echocardiography. PATIENTS: 147 patients with suspected heart failure referred by general practitioners. MEASUREMENTS: Echocardiographic assessment of conventional measures of left ventricular systolic function (fractional shortening, ejection fraction (by Simpson's biplane method) and "eyeball" assessment) and measurement of left ventricular systolic atrioventricular plane displacement. RESULTS: Between 21% and 33% of patients with "normal" left ventricular systolic function by conventional methods were found to have abnormal left ventricular systolic atrioventricular plane displacement. CONCLUSIONS: Approximately one quarter of patients with suspected heart failure but preserved systolic function by conventional methods have abnormal atrioventricular plane displacement. These patients with suspected heart failure but preserved systolic function by conventional echocardiographic measures may have heart failure caused by subtle systolic dysfunction rather than isolated "diastolic heart failure".

Altered diaphragm position and function in patients with chronic heart failure.

BACKGROUND: Breathlessness is a common symptom experienced by patients with chronic heart failure (CHF) but its etiology remains controversial. Various molecular and histological adaptations have been reported for the diaphragm in CHF but their functional consequences are poorly described. AIMS: This study aims to determine the position and function of the diaphragm in CHF patients. METHODS: The diaphragm position was measured, relative to the renal pelvis, by ultrasound in 20 CHF patients and ninety controls matched for age and body mass. The extent and velocity of diaphragm movement was also measured during quiet breathing and sniffing. RESULTS: At the end of expiration, the diaphragm was significantly nearer to the renal pelvis in CHF patients (89.3+/-16.8 vs. 96.3+/-19.2 mm, P<0.05) and also moved further during quiet breathing (18.2+/-4.4 vs. 12.7+/-4.6 mm, P<0.001) and sniffing (23.9+/-7.4 vs. 18.2+/-5.7 mm, P<0.005). Velocity of diaphragm movement was also increased in CHF patients during quiet breathing (26.5+/-8.2 vs. 15.9+/-6.1 mm s(-1), P<0.001). CONCLUSIONS: These data demonstrate that the position and function of the diaphragm is altered in CHF.

Do patients with suspected heart failure and preserved left ventricular systolic function suffer from "diastolic heart failure" or from misdiagnosis? A prospective descriptive study.

OBJECTIVES: To characterise the clinical features of patients with suspected heart failure but preserved left ventricular systolic function to determine if they have other potential causes for their symptoms rather than being diagnosed with "diastolic heart failure." DESIGN: Prospective descriptive study. SETTING: Outpatient based direct access echocardiography service. PARTICIPANTS: 159 consecutive patients with suspected heart failure referred by general practitioners. MAIN OUTCOME MEASURES: Symptoms (including shortness of breath, ankle oedema, and paroxysmal nocturnal dyspnoea) and history of coronary heart disease and chronic pulmonary disease. Transthoracic echocardiography, body mass index, pulmonary function tests, and electrocardiography. RESULTS: 109 of 159 participants had suspected heart failure in the absence of left ventricular systolic dysfunction, valvular heart disease, or atrial fibrillation. Of these 109, 40 were either obese or very obese, 54 had a reduction in forced expiratory volume in 1 second to

Factitious methemoglobinemia.

We report the case of a 26 year-old female who was treated on numerous occasions for methemoglobinemia believed secondary to surreptitious abuse of dapsone as part of a factitious disorder.

QT dispersion in patients with chronic heart failure: beta blockers are associated with a reduction in QT dispersion.

OBJECTIVE: To compare QT dispersion in patients with impaired left ventricular systolic function and in matched control patients with normal left ventricular systolic function. DESIGN: A retrospective, case-control study with controls matched 4:1 for age, sex, previous myocardial infarction, and diuretic and beta blocker treatment. SETTING: A regional cardiology centre and a university teaching hospital. PATIENTS: 25 patients with impaired left ventricular systolic function and 100 patients with normal left ventricular systolic function. MAIN OUTCOME MEASURES: QT and QTc dispersion measured by three methods: the difference between maximum and minimum QT and QTc intervals, the standard deviation of QT and QTc intervals, and the "lead adjusted" QT and QTc dispersion. RESULTS: All measures of QT/QTc dispersion were closely interrelated (r values 0.86 to 0.99; all p < 0.001). All measures of QT and QTc dispersion were significantly increased in the patients with impaired left ventricular systolic function v controls (p < 0.001): 71.9 (6.5) (mean (SEM)) v 46.9 (1.7) ms for QT dispersion, and 83.6 (7.6) v 54.3 (2.1) ms(-1-2) for QTc dispersion. All six dispersion parameters were reduced in patients taking beta blockers (p < 0.05), regardless of whether left ventricular function was normal or impaired-by 9.4 (4.6) ms for QT dispersion (p < 0.05) and by 13.8 (6. 5) ms(-1-2) for QTc dispersion (p = 0.01). CONCLUSIONS: QT and QTc dispersion are increased in patients with systolic heart failure in comparison with matched controls, regardless of the method of measurement and independently of possible confounding factors. beta Blockers are associated with a reduction in both QT and QTc dispersion, raising the possibility that a reduction in dispersion of ventricular repolarisation may be an important antiarrhythmic mechanism of beta blockade.

Cohort study of plasma natriuretic peptides for identifying left ventricular systolic dysfunction in primary care.

OBJECTIVES: To determine whether blood natriuretic peptide concentrations are helpful in identifying or excluding left ventricular systolic dysfunction in stable survivors of acute myocardial infarction. DESIGN: Comparison of blood natriuretic peptide concentrations with echocardiographic assessment of left ventricular systolic function in a general practice population. SETTING: Practices in Western District of Glasgow audit group. SUBJECTS: 134 long term survivors of myocardial infarction recalled for echocardiography as part of a primary care secondary prevention audit. MAIN OUTCOME MEASURES: Area under the receiver operating curve for brain natriuretic peptide and N-terminal atrial natriuretic peptide. RESULTS: Brain natriuretic peptide was of some diagnostic utility in identifying the minority of subjects with severe left ventricular dysfunction (area under curve=0.73) but was unable to discriminate between patients with moderately severe dysfunction and those with preserved left ventricular function (area under curve for moderate or severe dysfunction=0.54). The corresponding values for N-terminal atrial natriuretic peptide for severe and moderate or severe dysfunction were 0.55 and 0.56 respectively. CONCLUSIONS: Blood natriuretic peptide concentrations are not useful in identifying important left ventricular systolic dysfunction in stable survivors of myocardial infarction.

Outcome from a rapid-assessment chest pain clinic.

Chest pain accounts for much of the rising numbers of emergency admissions, but in-patient assessment is not necessarily the best way of dealing with these patients. We ran a 'rapid-assessment chest pain clinic' to provide an alternative route of assessment, and audited its outcome. General practitioners referred patients with recent-onset chest pain, increasing chest pain, chest pain at rest, or other chest pain of concern, on the understanding that they would be seen within 24 h. During 8 1/2 months, 334 patients were referred and 317 patients were seen, most of whom had exercise electrocardiography. A median of 6 months later, 278 patients were personally contacted to determine outcome. Of these, 18% had been admitted immediately with acute coronary syndromes, and 49% had been diagnosed as non-coronary chest pain (none of whom subsequently infarcted or died). Continuing symptoms were infrequent, and satisfaction was high, although 13% of patients had been revascularized. A significant number of patients required immediate admission and/or ultimate revascularization, but many more did not. The majority of these patients had non-coronary chest pain, and this diagnosis was substantiated by their excellent outcome and (in some cases) by further investigation.

The prevalence of left ventricular diastolic filling abnormalities in patients with suspected heart failure.

AIMS: It is reported that one third of patients with heart failure have normal left ventricular systolic function, and may or may not have left ventricular diastolic dysfunction. We sought to define the prevalence of left ventricular diastolic filling abnormalities in a large unselected group of patients, unlike the diagnosis by exclusion in the small highly selected groups of patients studied previously. METHODS AND RESULTS: Patients were referred by general practitioners to an open-access echocardiography service for assessment of possible heart failure. Echocardiography included a Doppler study of transmitral flow at the tips of the mitral leaflets and calculation of an E/A ratio. Of 534 patients referred and assessed, 371 patients had normal systolic function and a measurable E/A ratio. These were compared with age-adjusted reference ranges to give 9 above the reference range and 19 below. This is only 10 more than would be expected if our patients were normal. In the same group of patients we found 96 cases of left ventricular systolic dysfunction, or 52 amongst the 423 with a measurable E/A ratio. CONCLUSION: Either left ventricular diastolic filling abnormalities are very much less common than previously supposed or the E/A ratio is almost useless for their detection.

Assessing diagnosis in heart failure: which features are any use?

We assessed the value of symptoms, past history, medications and signs in the evaluation of patients who might have heart failure secondary to left ventricular systolic dysfunction. An open-access echocardiography service was set up to help identify patients with left ventricular systolic dysfunction who might benefit from treatment with an angiotensin-converting-enzyme inhibitor. History and examination were recorded for each of these patients. The patients were divided into groups according to whether left ventricular systolic function was preserved or not and whether various clinical features were present or not. Of 259 consecutive patients studied, 41 had impairment of left ventricular systolic function as assessed by echocardiography. Past history of myocardial infarction and displaced apex beat were the best single predictors of left ventricular systolic dysfunction as assessed by echocardiography. The combination of past history of myocardial infarction and displaced apex had the best positive predictive value of all. Patients with such clinical features or combinations of clinical features may not need echocardiography, and where access to this resource is limited, it could be reserved for patients without such diagnostic features.

Open access echocardiography in management of heart failure in the community.

OBJECTIVE: To assess the value of an open access echocardiography service. DESIGN: Study of new open access service for general practitioners, who were invited to refer patients taking diuretics for suspected heart failure, untreated patients with symptoms of possible heart failure, and asymptomatic patients with risk factors for left ventricular systolic dysfunction. SETTING: Regional cardiology centre. SUBJECTS: 259 consecutive patients. MAIN OUTCOME MEASURES: Presence or absence of left ventricular systolic dysfunction and consequent changes in clinical management. RESULTS: 119 treated patients, 99 untreated patients, and nine asymptomatic patients were referred over five months. 32 were considered to be inappropriately referred. Among the treated patients, 31 had impaired left ventricular systolic function and five had valvular disease; angiotensin converting enzyme inhibitors were recommended for 34 of these patients. In addition, 53 were thought not to need diuretics. Eight untreated patients had impaired systolic function and six valvular disease. CONCLUSIONS: The service was well used by general practitioners and led to advice to change management in more than two thirds of patients.

A study of variation in the indirect hemagglutination antibody test for toxoplasmosis.

The indirect hemagglutination test (IHA) was compared both qualitatively and quantitatively to that of the indirect fluorescent antibody (IFA) technique for the detection of antibodies to Toxoplasma gondii. The coefficient of correlation between the two methods was +0.9561. Of the 89 samples tested, no significant disagreement between the IFA titers and mean titers of the IHA test was detected. Quantitative evaluation revealed 93.3 percent of the sera positive in both methods were within a one-tube dilution or same dilution, and 100 percent were within a two-tube (four-fold) dilution. A statistical evaluation of internal reproducibility of titer in the IHA test, utilizing 30 paired samples, indicated that titers by this method can be reproduced on a within-day basis within limits of +/- 1 two-fold dilution with 95 percent confidence. Day-to-day reproducibility of titers were 100 percent within limits of +/- 1 four-fold dilution. Because of its high reproducibility, prolonged stability, and ability to produce standardized results, the IHA technique is recommended over the IFA for mass screening.