Telomerase inhibition by retinoids precedes cytodifferentiation of leukemia cells and may contribute to terminal differentiation

Human promyelocytic leukemia HL60 cells display high telomerase activity, a phenotype related to their immortal status. All-trans retinoic acid (ATRA) is a clinically effective cytodifferentiating agent. To understand the mechanism underlying ATRA-induced cytodifferentiation, we did a kinetic analysis of the role of ATRA in inhibiting telomerase in HL60 cells. Our studies indicate that telomerase inhibition by ATRA occurred relatively early after treatment of HL60 cells due to a rapid decrease in hTERT gene expression. More importantly, however, we found through monitoring the expression of CD11b, a marker for granulocytic differentiation of HL60 cells, that down-regulation of telomerase preceded the differentiation of HL60 cells. These observations suggest that the hTERT gene may be a primary target of ATRA regulation of cellular differentiation and the antileukemia activity of ATRA may be mediated by its ability to induce the differentiation of the promyelocytic leukemia cells through down-regulation of the hTERT gene.     

In vitro evaluation of ultrasound Doppler strain rate imaging: modification for measurement in a slowly moving tissue phantom

Doppler strain rate imaging (SRI) was evaluated in vitro using a silicone strip phantom mimicking slowly moving tissue. A test apparatus was developed that enabled controlled strain experiments with variable strain and strain rate to be performed. SRI strain was measured at eight different calculated strains (range 5.7 to 63.4 %) at three different pump speeds with tissue velocity 0.1, 0.5 and 1.0 mm/s. The effect of varying tissue velocity and strain sample size on the measured SRI strain was elaborated. SRI strains agreed well with calculated values for strain when SRI strain was measured as the average over the whole strip cross-section and the strain sample size was 1.9 mm (mean DIFFERENCE = 2.78%, limits of agreement ± 9.97% for tissue velocity 1.0 mm/s, n = 8). The variance was substantial if single central samples were used, especially for strain sample size of 0.8 mm (mean DIFFERENCE = −7.47%, limits of agreement ± 20.90 for tissue velocity 0.5 mm/s, n = 24). Increasing the strain sample size to 1.9 mm removed some of the underestimation (giving mean difference of −4.46%, n = 24). We found low intra- and interobserver variation. This study indicates that, for the SRI method to give accurate estimates of strain, strain sample size should be in the region of 2 mm. Averaging over several ultrasound (US) beams increased the accuracy further.(E-mail: Knut.Matre@med.uib.no)     

The prognostic utility of D-dimer and fibrin monomer at long-term follow-up after hospitalization with coronary chest pain

D-dimer and fibrin monomer both reflect a prothrombotic potential. There are limited data available comparing these two markers of activated coagulation in a prospective manner in an unselected patient population presenting to the emergency department with chest pain. In addition, their role in risk stratification in patients with acute coronary syndrome is still under evaluation. Therefore, we wanted to assess the prognostic value of these markers with respect to long-term all-cause mortality in 871 patients admitted to the emergency department. Blood samples were obtained immediately following admission. After a follow-up period of 24 months, 123 patients had died. In the univariate analysis, both D-dimer and fibrin monomer predicted all-cause mortality within 2 years with an odds ratio of 7.78 (95% confidence interval, 3.95-15.33) and 4.19 (95% confidence interval, 2.42-7.28), respectively, in the highest quartile (Q4) compared with the lowest quartile (Q1). However, in the multivariable logistic regression model for death within 2 years, the odds ratio of D-dimer and fibrin monomer was 1.80 (95% confidence interval, 0.81 to 3.97) and 1.04 (95% confidence interval, 0.53 to 2.04) in Q4 compared with Q1, respectively, and added no prognostic information above and beyond age, known coronary heart disease, B-type natriuretic peptide and the index diagnoses of ST-segment elevation myocardial infarction, non-ST-segment elevation myocardial infarction and unstable angina pectoris. In an unselected patient population hospitalized with chest pain and potential acute coronary syndrome, neither D-dimer nor fibrin monomer provided complementary prognostic information to established risk determinants during long-term follow-up.     

Strain during gastric contractions can be measured using Doppler ultrasonography

This study was undertaken to explore if strain of the muscle layers within the gastric wall could be measured by transabdominal strain rate imaging (SRI), a novel Doppler ultrasound (US) method. A total of 9 healthy fasting subjects (8 women, 1 man; ages 22 to 55 years) were studied and both grey-scale and Doppler US data were acquired with a 5- to 8-MHz linear transducer in cineloops of 97 to 256 frames. Rapid stepwise inflation (5 to 60 mL) of an intragastric bag was carried out and bag pressure and SRI were measured simultaneously. SRI enabled detailed studies of layers within the gastric wall in all subjects. Great variations in strain distribution of the muscle layers were found. Radial strain was much higher in the circular than in the longitudinal muscle layer. Strains derived from SRI correlated well with strains obtained with B-mode measurements (r = 0.98, p < 0.05). During balloon distension, we found an inverse correlation between pressure and radial strain (r = -0.87, p < 0.05). Intraobserver correlation of strain estimation was r = 0.98 (p < 0.05) and intraobserver agreement was 0.2% +/- 18.6% (mean difference +/- 2SD, % strain). Interobserver correlation was r = 0.84 (p < 0.05) and interobserver agreement was 6.9% +/- 56.8%. SRI enables detailed mapping of radial strain distribution of the gastric wall and correlates well with B-mode measurements and pressure increments.     

Patient reactions to cancelled or postponed heart operations

OBJECTIVES: The aim was to survey the rate and cause of cancellations of planned cardiac operations at a Swedish clinic during 1999, and to study how the patients were affected. DESIGN: Questionnaires were distributed to 74 patients who had their operations cancelled. Their mood after discharge was measured with The Hospital Anxiety and Depression scale. Ninety-three patients, who were operated on without postponement, served as controls. RESULTS: Sixty-one percent of the patients in the cancellation group reacted negatively, especially if the reason for cancellation was organizational (P = 0.03). The women in the cancellation group had a significantly higher degree of depression than men (P = 0.01) and both women (P = 0.02) and men (P = 0.003) in the control group. Most of the patients, however, were satisfied with the nursing staff's reception and information. CONCLUSIONS: The patients reacted negatively to the cancellation, especially if it had organizational reasons. Women subjected to cancellation had a significantly higher degree of depression than other patients. To be avoided, organizational and medical problems must be identified in time. One way to do this is to introduce a preadmission nurse clinic.     

Treatment of out-of-hospital cardiac arrest with LUCAS, a new device for automatic mechanical compression and active decompression resuscitation

Lund University Cardiopulmonary Assist System (LUCAS) is a new gas-driven CPR device providing automatic chest compression and active decompression. This is a report of the first 100 consecutive cases treated with LUCAS due to out-of-hospital cardiac arrest (58% asystole, 42% ventricular fibrillation (VF)). Safety aspects were also investigated and it was found that LUCAS can be used safely regarding noise levels and oxygen concentrations within the ambulance. A crash test (10G) showed no displacement of the device from the manikin. Of the 71 patients with witnessed cardiac arrest, 39% received bystander CPR. In those 28 patients where LUCAS-CPR was initiated more than 15 min after the ambulance alarm and in the 29 unwitnessed cases, none survived for 30 days. Of the 43 witnessed cases treated with LUCAS within 15 min, 24 had VF and 15 (63%) of these cases achieved a stable return of spontaneous circulation (ROSC) and 6 (25%) of them survived with a good neurological recovery after 30 days; 5 (26%) of the 19 patients with asystole achieved ROSC and 1 (5%) survived for over 30 days. One patient where ROSC could not be achieved was transported with on-going LUCAS-CPR to the catheter laboratory and after PCI for an occluded LAD a stable ROSC occurred, but the patient never regained consciousness and died 15 days later. To conclude, establishment of an adequate cerebral circulation as quickly as possible after cardiac arrest is mandatory for a good outcome. In this report patients with a witnessed cardiac arrest receiving LUCAS-CPR within 15 min from the ambulance call had a 30-day survival of 25% in VF and 5% in asystole, but if the interval was more than 15 min, there were no 30-day survivors.