Myocardial velocities measured during adenosine, dobutamine and supine bicycle exercise: a tissue Doppler study in healthy volunteers

Background: Dobutamine stress echocardiography (DSE) quantified by tissue Doppler (TVI) have improved the diagnostic capacity of the procedure. Quantification of other stress modalities, e.g. adenosine stress echo (ASE) and exercise stress echocardiography (ESE) are necessary for assessing any pathophysiological differences in different forms of stress. Methods: Ten healthy individuals underwent ASE, DSE, and ESE during a span of 2–5 days. Left ventricular (LV) apical images at rest and peak stress (max) were postprocessed using TVI on a GE System FiVe equipment. ECG‐derived QRS duration (QRSD, ms), heart rate (HR, bpm), TVI‐estimated basal systolic velocities (S2V, cm s^?1), ejection time (S2T, ms) and strain (S, %) were computed off‐line and compared. Longitudinal displacement imaging, tissue tracking, was also made. Results: Data for ASE, DSE and ESE during peak stress were (HR: 84 ± 12***, 142 ± 19, 137 ± 27; P<0·001) (QRSD: 92 ± 18**, 74 ± 13, 79 ± 9; P<0·05), (S2T: 307 ± 34***, 175 ± 53, 192 ± 25; P<0·001) and (S%: 26·0 ± 3·0, 21·2 ± 7·3, 22·1 ± 5·1; P = n.s.) respectively. Velocity response, registered in the LV septum at max, was lowest during ASE (7·4 ± 1·4) highest during DSE (13·0 ± 2·7; P<0·001 versus ASE) and somewhat intermediate during ESE (11·3 ± 3·5; P<0·001 versus ASE). In contrast, strain and displacement did not differ. Conclusion: ASE evokes significantly less LV systolic response compared with both DSE and ESE. Increased velocity (P<0·05 versus rest) and strain (P>0·05) response at a much lower HR indicates that adenosine has minor effects on contraction presumably secondary to vasodilatation. Powerful chronotropic response to DSE and ESE is probably prerequisite for strong velocity response at the expense of strain and displacement. TVI‐assisted stress echocardiography thereby shows different LV systolic response in healthy individuals, depending on stress modality.     

Changes in attitudes, knowledge and hormone replacement therapy use: a comparative study in two random samples with 6-year interval

OBJECTIVES: To study changes in: (i) the prevalence of hormone-replacement therapy (HRT) and (ii) women's attitudes and knowledge about the climacteric. Design. Cross-sectional comparison was performed on two populations of women both aged 46-62 years and resident in the same urban Swedish population over a period of 6 years. MATERIAL AND METHODS: In 1992, a random sample of 5990 women, from five birth cohorts, 46, 50, 54, 58, and 62 years in the city of G?teborg, were assessed using a postal questionnaire technique. In 1998, the same technique was used and a similar questionnaire was sent to another cohort of women (n=5411) of the same ages, resident in the city of G?teborg. The overall response rate was 76%. Information was obtained regarding climacteric symptoms, HRT use, and attitudes and knowledge. RESULTS: The prevalence of HRT use with medium-potency estrogens had increased from 13% (1992) to 31% (1998). The highest prevalence was reported in women 54 years of age (46%). The most common reasons why women started HRT were: hot flushes and sweats, depression/irritability, sleeping disturbances, and vaginal dryness. Forty-four percent of the women in this study were prepared to consider extended HRT if the treatment was free from withdrawal bleedings (35%, 1992). Eighty percent believed that the risk of osteoporosis decreased during HRT use (61%, 1992) and 68% thought that the risk of breast cancer increased (58%, 1992). CONCLUSIONS: A marked increase in the use of HRT was reported between 1992 and 1998. Women's attitudes to HRT were more positive in 1998 compared to 1992. Knowledge about HRT among women had increased during the same 6-year period.     

Motor evoked potentials from the striated urethral sphincter and puborectal muscle: normative values

AIMS: Transcranial magnetic stimulation enables the study of corticospinal motor pathways through evoked potential testing. By separate stimulation of cortical centers and spinal roots, it is possible to test motor conduction times segmentally. This method enables the localization of central or peripheral demyelinating neuropathies. As lower urinary tract dysfunction often accompanies these diseases, we wanted to present normative data for the motor innervation of the external urethral sphincter (EUS) and the puborectal muscle (PR). METHODS: Thirty healthy women without evidence of neurologic or lower urinary diseases were studied. They had a mean age of 52 years. Transcutaneous magnetic stimulations were applied to the vertex, the upper lumbar spine, and the sacrum. Evoked potentials were recorded with concentric needle electrodes placed in the EUS and the PR by a transvaginal route. Stimulations were performed with relaxed pelvic floor and with tonic contraction (facilitated responses). At least three responses were recorded for each modality. Stepwise multiple regression analysis was performed to test for the effect of age, height, body mass index, vaginal parity, and menopause. RESULTS: In some subjects, it was only possible to record cortical latencies with facilitation. Technical difficulties were encountered with spinal stimulations. Reference values are presented as means with 95% confidence intervals. Regression analysis revealed height as a dependent factor for sacral latencies. CONCLUSIONS: Our data can serve as reference values for future studies of the fast conducting fibers in patients with sphincter dysfunction. The height of the patient should be taken into account. The clinical applicability of the method is questionable.     

Identification of a calcium-binding protein as a calcium-dependent regulator of brain adenylate cyclase.

An activating factor of adenylate cyclase (EC 4.6.1.1) HAS BEEN OBTAINED FROM DETERGENT-DISPERSED PREPARATIONS OF PORCINE CEREBRAL CORTEX BY COLUMN CHROMATOGRAPHY ON ECTEOLA-cellulose. The factor was identified by acrylamide gel electrophoresis and by enzyme activation studies as the Ca2+-binding protein that regulates the activity of a brain cyclic nucleotide phosphodiesterase. This Ca2+-binding protein confers a Ca2+-dependent activation upon the adenylate cyclase, which is reversed by the subsequent addition of egta in excess of the free Ca2+. It is proposed that this Ca2+-dependent regulator controls enzymatic activities responsible for the synthesis of adenosine 3':5'-monophosphate and for the hydrolysis of guanosine 3':5'-monophosphate.     

Cell quality of salvaged blood after total knee arthroplasty:Drain blood compared to venous blood in 32 patients

We used the ConstaVac® drainage retransfusion system in 32 patients operated on with cemented tricompartmental knee arthroplasty. The mean total postoperative bleeding was 1.1 L of which 0.7 L was retransfused within 8 hours postoperatively. Samples were taken from the venous blood and drain blood at 2 hours and 6-8 hours postoperatively. The drain blood had low counts for leukocytes and thrombocytes as compared to venous blood, and fibrinogen was almost absent. Incubation at room temperature slightly lowered glucose and pH which made the erythrocytes swell. There was a slight hemolysis in the drain blood at 2 hours. At 6-8 hours the shed blood was closer to normal, especially with regard to hemolysis, but there was a further decrease in glucose. Within this time, there was no change in acidity and no further swelling of the erythrocytes. No clinical adverse reactions were observed and we consider the observed cellular and chemical changes to be of little importance. The quality of filtered drain blood within the analyzed time limit is considered acceptable for clinical use.     

A novel spontaneous metastasis model of human osteosarcoma developed using orthotopic transplantation of intact tumor tissue into tibia of nude mice

Evaluation of potential new treatment strategies requires adequate experimental tumor models which resemble the clinical situation as closely as possible. The purpose of the present study was to establish a new human osteosarcoma spontaneous metastasis model using orthotopic transplantation of histologically intact tumor tissue into the tibia of nude mice. Intact tumor pieces, obtained from the 32nd serial passage of subcutaneously growing human osteosarcoma xenografts, were implanted into the proximal tibia in 31 nude mice. Animals were sacrificed and autopsied 2, 4, 6, and 8 weeks after transplantation and examined macroscopically and microscopically for local tumor growth and metastases. All mice developed local intratibial bone tumors that were radiographically and histologically similar to primary human osteosarcoma. Lung metastases were observed in all mice, local and distant lymph node metastases in 15 (48%), and liver metastases in 6 (19%) mice. The microscopic appearance of the metastases was similar to that observed in the donor patientÕs tumor, corresponding subcutaneous xenografts and orthotopically transplanted intratibial tumors. This spontaneous metastasis model of human osteosarcoma in nude mice may resemble a clinical situation and could thus be useful for studies on local tumor growth, metastasis formation and therapy.     

The risk of arsenic induced skin lesions in Bangladeshi men and women is affected by arsenic metabolism and the age at first exposure

It is known that a high fraction of methylarsonate (MA) in urine is a risk modifying factor for several arsenic induced health effects, including skin lesions, and that men are more susceptible for developing skin lesions than women. Thus, we aimed at elucidating the interaction between gender and arsenic metabolism for the risk of developing skin lesions. This study is part of a population-based case-referent study concerning the risk for skin lesions in relation to arsenic exposure via drinking water carried out in Matlab, a rural area 53 km south-east of Dhaka, Bangladesh. We randomly selected 526 from 1579 referents and all 504 cases for analysis of arsenic metabolites in urine using HPLC coupled to inductively coupled plasma mass spectrometry (HPLC-HG-ICPMS). The present study confirm previous studies, with the risk for skin lesions being almost three times higher in the highest tertile of %MA (adjusted OR 2.8, 95% CI: 1.9-4.2, p < 0.001) compared to the lowest tertile. The present study is the first to show that the well documented higher risk for men to develop arsenic-related skin lesions compared to women is mainly explained by the less efficient methylation of arsenic, as defined by a higher fraction of MA and lower fraction of DMA in the urine, among men. Our previously documented lower risk for skin lesions in individuals exposed since infancy, or before, was found to be independent of the observed arsenic methylation efficiency. Thus, it can be speculated that this is due to a programming effect of arsenic in utero.     

Electromechanical coupling, uncoupling, and ventricular function in patients with bundle branch block: a tissue-Doppler echocardiographic study

BACKGROUND: Left bundle branch block (LBBB) is associated with impaired left ventricular (LV) function and increased morbidity and mortality, especially in patients with structural heart diseases. The mechanisms are poorly understood. Subjects and METHODS: Subjects with isolated LBBB (n=20), right bundle branch block (RBBB, n=20), and controls (C, n=20) were studied with standard two-dimensional (2D), and color-encoded tissue-Doppler echocardiography (TDE). Inter- and intraventricular systolic and diastolic coordination were assessed from the TDE velocity profiles. LV function was assessed by 2D echocardiography, by TDE-derived peak systolic velocities, and the atrioventricular (AV) plane displacement. RESULTS: Subjects with LBBB had longer electromechanical delays and longer isovolumic relaxation times than did the C and RBBB groups (P <0.001). For the LBBB subjects compared with the RBBB and C groups, ejection times were shorter, peak systolic velocities and AV plane displacements were lower, they had larger LV end-systolic volumes and lower LV ejection fraction (all P <0.001), and the atrial contribution to A-V plane displacement was higher (P <0.01). There were no differences in diastolic or filling times among the groups. CONCLUSIONS: In patients with LBBB, delayed regional electromechanical coupling and uncoupling leads to generalized intra- and interventricular asynchrony, thereby explaining the depressed regional and global LV functions. Assessment of the electromechanical coupling and uncoupling processes and their consequences on cardiac function in patients with BBB and structural heart diseases may be possible using TDE.     

Tumor attenuation by combined heparan sulfate and polyamine depletion.

Cells depend on polyamines for growth and their depletion represents a strategy for the treatment of cancer. Polyamines assemble de novo through a pathway sensitive to the inhibitor, alpha-difluoromethylornithine (DFMO). However, the presence of cell-surface heparan sulfate proteoglycans may provide a salvage pathway for uptake of circulating polyamines, thereby sparing cells from the cytostatic effect of DFMO. Here we show that genetic or pharmacologic manipulation of proteoglycan synthesis in the presence of DFMO inhibits cell proliferation in vitro and in vivo. In cell culture, mutant cells lacking heparan sulfate were more sensitive to the growth inhibitory effects of DFMO than wild-type cells or mutant cells transfected with the cDNA for the missing biosynthetic enzyme. Moreover, extracellular polyamines did not restore growth of mutant cells, but completely reversed the inhibitory effect of DFMO in wild-type cells. In a mouse model of experimental metastasis, DFMO provided in the water supply also dramatically diminished seeding and growth of tumor foci in the lungs by heparan sulfate-deficient mutant cells compared with the controls. Wild-type cells also formed tumors less efficiently in mice fed both DFMO and a xylose-based inhibitor of heparan sulfate proteoglycan assembly. The effect seemed to be specific for heparan sulfate, because a different xyloside known to affect only chondroitin sulfate did not inhibit tumor growth. Hence, combined inhibition of heparan sulfate assembly and polyamine synthesis may represent an additional strategy for cancer therapy.