Esophageal diameter and the treatment of achalasia

The effect of pneumatic dilation and Heller esophagomyotomy on esophageal diameter was studied in 49 patients with achalasia. Standardized radiologic technic was used with the patient in a horizontal position and with a 36-in. target-to-film distance. Fifteen normal subjects had a mean esophageal diameter (± SD) of 1.50±0.37 cm, while that in untreated patients was 4.85±1.44 cm. When pneumatic dilation resulted in a fall in mean diameter to 2.27±0.49 cm, symptoms improved; they persisted in those with a diameter of 4.99±1.23 cm. Heller esophagomyotomy led to a decrease in diameter to 2.29±0.62 cm in those with relief of symptoms, while symptoms continued in those with a diameter of 4.35±0.80 cm. In a longitudinal study of individual patients, it was noted that when treatment resulted in a diameter of less than 3.0 cm, symptoms improved. If esophageal size remained over 3.0 cm after treatment, however, dysphagia or pain recurred and persisted. Serial measurements of esophageal diameter, therefore, may be valuable in the clinical management of achalasia.The authors are indebted to Mr. Joseph Soussou of the Massachusetts Institute of Technology for statistical and data-processing assistance.Presented in part at the Multiple Discipline Research Forum, Meeting of the American Medical Association, San Francisco, June 20, 1968.     

Effects of shifts in hemoglobin-oxygen affinity during hypoxia.

To investigate the possibility that the influence of hemoglobin-oxygen affinity on tissue oxygenation may be reversed in severe hypoxia, 16 anesthetized rabbits with chronically-implanted tissue oxygen electrodes were ventilated with 12% oxygen and subjected to 100 ml exchange transfusions with high, low, or normal affinity rabbit blood. Despite the widely divergent in vivo P50 values produced, significant differences in tissue oxygen levels were not observed among the three groups following exchange transfusions. During subsequent normoxia, more complete recovery of tissue oxygen was apparent in the low affinity group. This study emphasizes the need for further definition of the influence of hemoglobin-oxygen affinity on the functions of individual organs.     

Activation of fibronectin gene expression by hepatitis B virus x antigen

The development of fibrosis and cirrhosis during chronic hepatitis B virus (HBV) infection correlates with the persistent expression of HBV x antigen (HBxAg), which acts in part, by stimulating selected signal transduction pathways, including nuclear factor kappa B (NF-kappa B). To identify NF-kappa B responsive genes that are differentially expressed in HBxAg-positive cells, HepG2 cells were stably transfected with HBxAg, and then with pZeoSV2 or pZeoSV2-I kappa B alpha. When RNAs from each culture were compared by PCR-select cDNA subtraction, fibronectin (FN) mRNA was shown to be strongly down-regulated by I kappa B alpha. Up-regulated expression of FN and co-expression between FN and HBxAg were observed in liver sections from HBV carriers that were stained for HBxAg and analysed for FN mRNA by in situ hybridization (ISH). In liver cell cultures, HBxAg increased the levels of FN mRNA and protein. This was because of the HBxAg-mediated trans-activation of the FN promoter, which was NF-kappa B-dependent. HBxAg also antagonized the repression of the FN promoter by the tumour suppressor, p53. Hence, the FN gene may be a natural target for HBxAg trans-activation, perhaps through activation of NF-kappa B and inactivation of p53, thereby contributing to the accumulation of FN in the liver over the course of chronic HBV infection.     

First controlled treatment trial of bipolar II hypomania with mixed symptoms: Quetiapine versus placebo

Objectives

To compare the efficacy and safety of adjunctive quetiapine (QTP) versus placebo (PBO) for patients with bipolar II disorder (BDII) currently experiencing mixed hypomanic symptoms in a 2-site, randomized, placebo-controlled, double-blind, 8-week investigation.

Methods

Participants included 55 adults (age 18–65 years) who met criteria for BDII on the Structured Clinical Interview for DSM-IV-TR (SCID). Entrance criteria included a stable medication regimen for ≥2 weeks and hypomania with mixed symptoms (>12 on the Young Mania Rating Scale [YMRS] and >15 on the Montgomery Asberg Depression Rating Scale [MADRS] at two consecutive visits 1–3 days apart). Participants were randomly assigned to receive adjunctive quetiapine (n=30) or placebo (n=25).

Results

Adjunctive quetiapine demonstrated significantly greater improvement than placebo in Clinical Global Impression for Bipolar Disorder Overall Severity scores (F(1)=10.12, p=.002) and MADRS scores (F(1)=6.93, p=.0138), but no significant differences were observed for YMRS scores (F(1)=3.68, p=.069). Side effects of quetiapine were consistent with those observed in previous clinical trials, with sedation/somnolence being the most common, occurring in 53.3% with QTP and 20.0% with PBO.

Conclusions

While QTP was significantly more effective than PBO for overall and depressive symptoms of BDII, there was no significant difference between groups in reducing symptoms of hypomania. Hypomania improved across both groups throughout the study.     

Reproducibility of quantitative plaque measurement in advanced coronary artery disease

BackgroundThe ability to characterize and to quantify the extent of coronary artery disease has the potential to improve the prognostic capability of coronary computed tomography angiography. Although reproducible techniques have been described in those with mild coronary disease, this has yet to be assessed in patients with advanced disease.MethodsTwenty patients with known multivessel disease underwent repeated computed tomography coronary angiography, 2 weeks apart. Coronary artery segments were analysed using semi-automated software by two trained observers to determine intraobserver, interobserver and interscan reproducibility.ResultsOverall, 149 coronary arterial segments were analysed. There was excellent intraobserver and interobserver agreement for all plaque volume measurements (Lin’s coefficient 0.95 to 1.0). There were no substantial interscan differences (P ?> ?0.05 for all) for total (2063 ?± ?1246 ?mm³, mean of differences ?35.6 ?mm³), non-calcified (1795 ?± ?910 ?mm³, mean of differences ?4.3 ?mm³), calcified (298 ?± ?425 ?mm³, mean of differences ?31.3 ?mm³) and low-attenuation (13 ?± ?13 ?mm³, mean of differences ?2.6 ?mm³) plaque volumes. Interscan agreement was highest for total and noncalcified plaque volumes. Calcified and low-attenuation plaque (?236.6 to 174 ?mm³ and -15.8 to 10.5 ?mm³ respectively) had relatively wider 95% limits of agreement reflecting the lower absolute plaque volumes.ConclusionIn the presence of advanced coronary disease, semi-automated plaque quantification provides excellent reproducibility, particularly for total and non-calcified plaque volumes. This approach has major potential to assess change in disease over time and optimize risk stratification in patients with established coronary artery disease.     

Effects of short-term exercise-training on aortic systolic pressure augmentation in overweight and obese individuals

To determine whether exercise training-induced decreases in blood pressure (BP) can be explained by decreases in aortic systolic pressure augmentation in overweight or obese individuals. Thirty-five sedentary or recreationally active men and women (30–57 years) who were either overweight (40 %) or obese (60 %) completed 6 weeks of exercise training (≥3 days/week; stationary bike and/or treadmill) either preceded (n = 19) or followed (n = 16) by a 6-week control period of no exercise. Aortic augmentation pressure (AP), aortic and peripheral augmentation indices (AIx), and central aortic BP (SphygmoCor) were determined before and after exercise training and a control period. Peak oxygen consumption increased (p = 0.0001) from 27.0 ± 5.1 to 28.8 ± 5.8 mL/(kg min) after 6 weeks of exercise. Exercise training decreased brachial systolic (SBP) and diastolic BP from 142 ± 8/94 ± 8 to 134 ± 11/86 ± 11 mmHg (p < 0.005/p < 0.005); whereas no changes were observed after the control period (141 ± 11/91 ± 9 mmHg, p = 0.81/p = 0.34). Neither AP (baseline: 9.2 ± 4.2 mmHg; after 6 weeks training: 8.7 ± 6.1 mmHg), aortic AIx (baseline: 24.6 ± 11.0 %; after 6 weeks training: 22.7 ± 11.1 %), nor peripheral AIx (baseline: 81.4 ± 16.7 mmHg; after 6 weeks training: 76.4 ± 16.5 mmHg) were modified by exercise training. Although aortic SBP decreased after exercise (132 ± 8 to 124 ± 12 mmHg, p < 0.002), these changes were accounted for by decreases in mean arterial pressure. In overweight or obese individuals, although short-term aerobic exercise training, which improved cardiorespiratory fitness, may produce marked decreases in aortic and brachial BP; these effects are not attributed to alterations in aortic systolic pressure augmentation.