Value of notching and slurring of the resting QRS complex in the detection of ischemic heart disease

The resting 12-lead ECG has long been known to be an insensitive marker of underlying ischemic heart disease (IHD). The purpose of this study was to determine if QRS complex notching and slurring is of significant value as a diagnostic discriminator in the detection of IHD. The data from 205 consecutive patients coming to cardiac catheterization for evaluation of probable IHD were initially analyzed. Eighty-three patients were excluded based upon ventricular hypertrophy, bundle-branch block, lack of data, and pacemaker rhythm. The balance, 122 patients (mean age 61.7 years), were evaluated for angiographic evidence of IHD, ECG findings of QRS notching or slurring, and abnormal Q waves. The data revealed a high prevalence of QRS notching or slurring; 62.2% in those patients with IHD, double the prevalence of significant Q waves (33.3%). The two markers had an approximately equal prevalence (QRS notching or slurring 61.7% vs. Q waves 53.2%) in patients with angiographic evidence of infarction; however, in patients with less than infarct criteria for IHD, the prevalence of QRS notching or slurring was 62.8%, while only 11.6% showed abnormal Q waves. Analysis indicated that QRS notching or slurring has a sensitivity of 62.2% and a specificity of 93.8% for the detection of IHD. The study demonstrates that QRS notching or slurring is a moderately sensitive and a very specific marker of ischemic heart disease in selected patients when using the resting ECG, and is of greatest value in those patients with lesser degrees of ischemic myocardial injury where the prevalence of Q waves is low.     

Electrophysiology of Disopyramide in Man*

Summary: The electrophysiological effects of an intravenous dose of disopyramide phosphate (2 mg per kg body weight) were studied in 17 patients. Studies were performed with the patients fasting, unpremedicated, and off all medication for three days. Blood samples for estimation of serum levels of disopyramide were collected in 15 of these patients. The effects of intravenous disopyramide were maximal at five minutes, less marked at 20 minutes, and largely gone by 30 minutes after administration of the drug. Sinus cycle length and corrected sinus node recovery time were shortened significantly. No index of atrioventricular nodal function was significantly changed. Both atrial and ventricular effective refractory periods were significantly prolonged. Further impairment of intraventricular conduction occurred in six patients with bundle branch block on electrocardiogram or prolonged HV interval. In one of two patients with Wolff-Parkinson- White syndrome, the bypass effective refractory period was prolonged. These electrophysiological changes are similar to quinidine and quinidine like drugs. It is recommended that disopyramide should be used cautiously in patients with evidence of His Purkinje system disease since it may lead to higher degrees of intraventricular block.     

Cardiac compliance and dimensions in carbon monoxide-induced cardiomegaly

Adult male rats inhaled 500 ppm CO continuously for 38 to 47 days to produce significant cardiomegaly. In a first experiment in which heart wall stiffness was examined, haematocrit rose 45.1% and the ratio of the sum of right ventricle (RV) and left ventricle (LV) to body weight (mg X g-1) increased from 2.69 to 3.34. Compliance (ml X mmHg-1) of CO LV's and RV's studied from 0 to 25 mmHg intraluminal pressure, was generally greater than that of LV's and RV's from controls at the same pressure. These differences were greater for RV's. There was no difference between control RV's and LV's at the same distending pressure. The differences between treated and control groups disappeared when compliance was normalised per g heart weight. In a second experiment in which heart dimensions were examined, haematocrit ratio increased 48.6% and 2V (RV + LV) to body weight ratio (mg X g-1) increased from 2.77 to 3.45. Atrial weight was also greater. LV apex to base length increased 6.4% and LV outside diameter increased 7.3. No significant differences in LV, RV or interventricular septum (S) thickness resulted from CO exposure, as measured at three sites in each, in four cross-sections of the heart between the apex and base. In general, LV wall was slightly thicker than S, while RV was about 35% that of LV. The findings suggest that chronic carboxyhaemoglobinaemia produces largely eccentric cardiomegaly, and that there is no intrinsic change in wall stiffness.     

Prognostic value of metabolic tumor burden on 18F-FDG PET in nonsurgical patients with non-small cell lung cancer

Purpose

The objective of this study was to assess the prognostic value of metabolic tumor burden on 2-deoxy-2-[¹⁸F]fluoro-D-glucose (¹⁸F-FDG) positron emission tomography (PET)/CT measured with metabolic tumor volume (MTV) and total lesion glycolysis (TLG), independent of Union Internationale Contra la Cancrum (UICC)/American Joint Committee on Cancer (AJCC) tumor, node, and metastasis (TNM) stage, in comparison with that of standardized uptake value (SUV) in nonsurgical patients with non-small cell lung cancer (NSCLC).

Methods

This study retrospectively reviewed 169 consecutive nonsurgical patients (78 men, 91 women, median age of 68?years) with newly diagnosed NSCLC who had pretreatment ¹⁸F-FDG PET/CT scans. The ¹⁸F-FDG PET/CT scans were performed in accordance with National Cancer Institute guidelines. The MTV of whole-body tumor (MTV_WB), of primary tumor (MTV_T), of nodal metastases (MTV_N), and of distant metastases (MTV_M); the TLG of whole-body tumor (TLG_WB), of primary tumor (TLG_T), of nodal metastases (TLG_N), and of distant metastases (TLG_M); the SUV_max of whole-body tumor (SUV_maxWB), of primary tumor (SUV_maxT), of nodal metastases (SUV_maxN), and of distant metastases (SUV_maxM) as well as the SUV_mean of whole-body tumor (SUV_meanWB), of primary tumor (SUV_meanT), of nodal metastases (SUV_meanN), and of distant metastases (SUV_meanM) were measured with the PETedge tool on a MIMvista workstation with manual adjustment. The median follow-up among survivors was 35?months from the PET/CT (range 2?C82?months). Statistical methods included Kaplan-Meier curves, Cox regression, and C-statistics.

Results

There were a total of 139 deaths during follow-up. Median overall survival (OS) was 10.9?months [95% confidence interval (CI) 9.0?C13.2?months]. The MTV was statistically associated with OS. The hazard ratios (HR) for 1 unit increase of ln(MTV_WB), ??(MTV_T), ??(MTV_N), and ??(MTV_M) before/after adjusting for stage were: 1.47/1.43 (p?p?p?p?=?0.007/0.043), respectively. TLG had statistically significant associations with OS with the HRs for 1 unit increase in ln(TLG_WB), ??(TLG_T), ??(TLG_N), and ??(TLG_M) before/after adjusting for stage being 1.36/1.33 (p?p?=?0.001/0.002), 1.05/1.04 (p?p?=?0.003/0.024), respectively. The ln(SUV_maxWB) and ??(SUV_maxN) were statistically associated with OS with the corresponding HRs for a 1 unit increase before/after adjusting for stage being 1.46/1.43 (p?=?0.013/0.024) and 1.22/1.16 (p?=?0.002/0.040). The ??(SUV_meanN) was statistically associated with OS before and after adjusting for stage with HRs for a 1 unit increase of 1.32 (p?p?=?0.015), respectively. The ??(SUV_meanM) and ??(SUV_maxM) were statistically associated with OS before adjusting for stage with HRs for a 1 unit increase of 1.26 (p?=?0.017) and 1.18 (p?=?0.007), respectively, but not after adjusting for stage (p?=?0.127 and 0.056). There was no statistically significant association between OS and ??(SUV_maxT), ln(SUV_meanWB), or ??(SUV_meanT). There was low interobserver variability among three radiologists with intraclass correlation coefficients (ICC) greater than 0.94 for SUV_maxWB, ln(MTV_WB), and ln(TLG_WB). Interobserver variability was higher for SUV_meanWB with an ICC of 0.806.

Conclusion

Baseline metabolic tumor burdens at the level of whole-body tumor, primary tumor, nodal metastasis, and distant metastasis as measured with MTV and TLG on FDG PET are prognostic measures independent of clinical stage with low inter-observer variability and may be used to further stratify nonsurgical patients with NSCLC. This study also suggests MTV and TLG are better prognostic measures than SUV_max and SUV_mean. These results will need to be validated in larger cohorts in a prospective study.     

Striatal and nigral neuron subpopulations in rigid Huntington's disease: implications for the functional anatomy of chorea and rigidity-akinesia

Neuropeptide immunohistochemistry was used to test several hypotheses of the anatomical bases of chorea and rigidity-akinesia. To test the hypothesis that elevated concentration of striatal somatostatin causes chorea, we visually compared the density of striatal neurons containing somatostatin and neuropeptide Y in brains affected by choreic or rigid-akinetic Huntington's disease (HD). The density of these neurons was elevated in both rigid-akinetic and choreic HD specimens with an apparently normal total number of these neurons, indicating that elevated somatostatin concentration, by itself, does not lead to chorea. We tested the hypothesis that rigid-akinetic HD results from deficient dopaminergic nigrostriatal neurotransmission by examining tyrosine hydroxylase-immunoreactive (TH-IR) neurons in the substantia nigra. In rigid-akinetic HD brains, there was no obvious reduction of nigral TH-IR neurons, indicating that rigid-akinetic HD is probably not due to loss of nigral dopaminergic neurons. Finally, we also examined the status of striatal projection neurons and found near total loss of all striatal neurons projecting to the lateral globus pallidus, medial globus pallidus, and substantia nigra in brains affected by rigid-akinetic HD in contrast to the preservation of neurons projecting to the medial globus pallidus in choreic HD. These results are consistent with the hypothesis that chorea results from preferential loss of striatal neurons projecting to the lateral globus pallidus and that rigid-akinetic HD is a consequence of the additional loss of striatal neurons projecting to the medial segment of the pallidum.     

Carboxyhemoglobin in the rat: improvements in the spectrophotometric measurement and comparison to other studies

An improved and simplified spectrophotometric method for the determination of carboxyhemoglobin (COHb) is described, which employs an equation to correct for the dissociation error during analysis. Two microliters, or less, of blood is diluted with an ammonium hydroxide solution directly in the measuring cuvette. A layer of light mineral oil overlying the diluent was found to increase measured COHb saturation of blood equilibrated with 100% CO. Sodium dithionite treatment of the oil further increased this value in one case. The measured COHb was shown to be affected directly by factors that alter hemoglobin concentration in the diluent (i.e. blood volume, hematocrit). Blood samples kept cold and under oil may be stored safely for as long as 10 days. Measurement of COHb by this method in rats exposed to 525, 900, 1800 and 2400 ppm CO produces higher values than those obtained with the 1965 spectrophotometric method of Commins and Lawther. Variations on the method of Commins and Lawther, as well as COHb values available in the literature for animals exposed to CO, are reviewed briefly.     

A comparison of nasal clearance after treatment of perennial allergic rhinitis with budesonide and mometasone.

OBJECTIVE: Evidence in vitro suggests that benzalkonium chloride, a preservative in many intranasal preparations, interferes with ciliary function and thus could potentially interfere with mucociliary transport, the mechanism for clearing secretions from the nasal cavity. STUDY DESIGN: We performed a parallel randomized study with 10 subjects in each arm comparing Rhinocort AQUA (an intranasal steroid [budesonide] spray without benzalkonium chloride) and Nasonex (an intranasal steroid [mometasone furoate] spray with benzalkonium chloride). Before and after 2 weeks of treatment, subjects completed a Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) and underwent a measurement of nasal clearance of a radioactive colloidal spray into the nose. RESULTS: The groups were matched at entry for nasal clearance, even though there was variability among subjects. The amount of change after 2 weeks of treatment (Delta before versus after treatment) showed a significant difference in nasal clearance favoring budesonide. After 2 weeks of treatment, both budesonide and mometasone demonstrated overall improvement in quality of life as assessed by the RQLQ. Both treatments were well tolerated. CONCLUSION: Our study extends the observation in vitro that demonstrates the adverse effect of benzalkonium chloride on cilia to a measurement in vivo of clearance. The effects after 2 weeks might not reflect changes after longer periods of treatment. SIGNIFICANCE: To determine the clinical significance of the small improvement in mucociliary transport will require large clinical trials.     

Simplified electrode array for impedance cardiography

Impedance cardiography has enjoyed widespread interest owing to the promise of noninvasive monitoring of cardiac function. In clinical practice, one factor limiting its use has been the need to use circumferential electrodes. These electrodes can be inconvenient to apply, may interfere with chest tubes or intravenous lines, and can cause additional apprehension in critically ill patients. The paper describes a more convenient electrode array. It uses four disposable electrocardiographic electrodes, two on the base of the neck and two on the lower left, anterolateral surface of the thorax. Simultaneous impedance derivative recordings were made with this ‘spot’ electrode array and with the conventional ‘band’ electrode array, at rest and after exercise on ten normal volunteers. On a given individual, the two signals had shapes which were remarkably similar and relative heights which correlated well, exhibiting correlation coefficients (r′) between 0·77 and 0·98. This new array should facilitate impedance cardiographic measurements in the clinical setting.     

Fine structural and biochemical effects of aminoglutethimide and o,p′-DDD on rat adrenocortical carcinoma 494 and adrenals

Rats bearing adrenocortical carcinoma 494 were injected daily for 7, 14, or 21 days with aminoglutethimide (AG) or o,p′-DDD. Reversibility of these steroidogenic inhibitors was determined by injecting other animals for either 14 or 21 days and sacrificing them 14 days later. While the drugs had little effect on body or tumor growth, plasma corticosterone levels were reduced a maximum of 88% in normal and 95% in tumor-bearing rats during AG chemotherapy. These levels were unaltered in normal rats by o,p′-DDD and reduced a maximum of 64% in tumor-bearing animals. Relative adrenal weights generally increased during chemotherapy and then returned to control levels. These changes were mainly due to alterations in the lipid and mitochondrial volume fractions. Lipid increased with both drugs while mitochondria increased with o,p′-DDD and decreased with AG. Cholesterol ester levels paralleled the lipid stereology more closely with AG than o,p′-DDD. With both drugs the most notable changes in tumor fine structure was a decrease in mitochondrial internal membranous vesicles and matrical density. Adrenal mitochondria had the irregular, elongated forms characteristic of tumor-bearing animals and were vacuolated (AG) or had internal rings (o,p′-DDD). The large lipid droplets observed during chemotherapy with both drugs were replaced by numerous small droplets in recovery periods.