Physiologic and pharmacologic studies of atrial natriuretic factor: a natriuretic and vasoactive peptide.
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Atrial Natriuretic Factor↗
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Evaluation of orthogonal mechanical properties and density of human trabecular bone from the major metaphyseal regions with materials testing and computed tomography.
We evaluated the orthogonal mechanical properties of human trabecular bone from the major metaphyseal regions with materials testing and quantitative computed tomography (CT). The proximal tibia, distal femur, proximal femur, distal radius, and proximal humerus from fresh cadaver specimens between the ages of 55 and 70 years were excised and prepared for experimentation. The bones were embedded and scanned at 1 or 1.5 mm intervals on a Technicare HPS 1440 and GE 9800 CT scanner. After scanning, the bones were sectioned, producing 8-mm cubes of trabecular bone which were mechanically tested in uniaxial compression at a strain rate of 1%. The testing sequence consisted of preyield tests in two of the three orthogonal directions and failure in the third. After testing, the cubes were evaluated for apparent density and ash weight. The results of the study show that the strength and stiffness of trabecular bone varies significantly within metaphyseal regions and from metaphysis to metaphysis. The power and significance of relationships between density and modulus varied as a function of metaphyseal location. Both linear and nonlinear models were significant, suggesting that trabecular deformation occurs in response to both axial and bending loads. Finally, the need for architectural measures of trabecular bone to predict mechanical properties is emphasized.
Aged↗
Mood changes and "on-off" phenomena in Parkinson's disease.
Ten patients with idiopathic Parkinson's disease and motor fluctuations were rated for mood changes during discrete "off," "on," and "on with dyskinesia" periods. The Profile of Mood States and visual analogue scales were used. Significant changes in mood and anxiety were found to parallel changes in motor fluctuations. One patient rated his moods as consistently improving from the "off" state to the "on" state and finally to the "on with dyskinesia" state, a finding that is consistent with concomitant central dopaminergic changes. All other patients showed moods that improved significantly from the "off" state to the "on" state but then worsened significantly in the "on with dyskinesia" state, a finding that is consistent with the fact that patients feel worse when impaired by dyskinesias. It is suggested that these results argue for multiple etiologies of depression in Parkinson's disease. The literature on dopamine and depression in Parkinson's disease is briefly reviewed and the opportunity provided by "on-off" phenomena to study the effect of dopamine on mood changes is discussed.
Affect↗
Purification and crystallization of insecticidal delta-endotoxin CryIIIB2 from Bacillus thuringiensis.
CryIIIB2, an insecticidal protein from Bacillus thuringiensis has been crystallized from 0.6 M NaBr and HEPES buffer at pH 7.0 and X-ray diffraction data collected on a native crystal to 2.4 A. The insecticidal protein was obtained from a Bacillus thuringiensis (Bt) strain EG7231. Crystals of the endotoxin are orthorhombic, space group C2221, with unit cell dimensions of a = 122.44, b = 131.81, and c = 105.37 A. A unit cell contains one molecule of the 67,000 Da endotoxin per asymmetric unit.
Bacillus thuringiensis↗
Phase II trial of cisplatin and etoposide in patients with metastatic melanoma.
Fourteen patients with metastatic melanoma were treated with cisplatin and etoposide by bolus intravenous infusion daily for 5 consecutive days each month. All patients were evaluable for toxicity and twelve for response. Eight patients were treated with cisplatin 20 mg/m2 and etoposide 100 mg/m2 daily. Because of excessive myelosuppression, the daily dose of etoposide was reduced to 75 mg/m2 in the remaining six patients. There were no major responses among 12 evaluable patients (major response rate less than or equal to 24% with 95% confidence). The median time to progression was one month. One patient with a liver metastasis had a minor response lasting 6+ months. The combination of cisplatin and etoposide in these doses and schedule lacked sufficient clinical efficacy in the treatment of metastatic melanoma.
Adult↗
Vibration-evoked reciprocal inhibition between human wrist muscles.
Reciprocal inhibition of the voluntarily contracting wrist extensor (extensor carpi radialis, ECR) evoked by proprioceptive afferent input from the flexor (flexor carpi radialis, FCR), was studied in healthy human subjects. Vibration of the FCR tendon was used to elicit Ia-dominated afferent discharge whilst inhibition of ECR was assessed as the reduction in asynchronous, on-going EMG. A small early phase of inhibition (I1) was evident in 25% of trials. The latency (ca. 25 ms) of this component suggested that it was mediated by an Ia oligosynaptic. possibly 'classical' disynaptic, inhibitory pathway. A later and apparently separate phase of reduced activity (I2, ca. 40 ms) was, however, far more consistently observed (96% of trials) and of greater magnitude. The I2 component was usually followed, some 20 ms later, by a phase of elevated activity (E1, 72% trials). Reductions in simultaneously recorded net extensor torque commenced at about 60 ms following the onset of flexor tendon vibration, i.e. some 20 ms after the main I2 EMG component. These mechanical responses must have almost exclusively resulted from reciprocal inhibition of extensor EMG since vibration of the relaxed FCR evoked minimal excitatory flexor activity. The reflex pattern, in any individual subject, was relatively unaffected by altering the duration of the vibration train between one and nineteen cycles (125 Hz). This suggests that the entire response complex resulted largely from the initial afferent volley. The sizes of both the I1 and I2 reductions in ECR activity increased with increasing voluntary extensor contraction so that their depths remained constant proportions of background EMG. Very similar results were obtained when reciprocal inhibition of FCR was produced by vibration of the belly of ECR. Thus, reciprocal inhibition between wrist muscles is mainly expressed as a rather stereotyped, short duration reduction in EMG whose depth is determined by the pre-existing level of motor activity. Some functional implications of this form of reflex behaviour are discussed.
Adult↗
Behaviors, beliefs, and intentions in skin cancer prevention.
This study investigated knowledge, behaviors, and health beliefs of Australian university students (n = 312) regarding skin cancers and evaluated the effects of videotaped presentations. Students' knowledge and health beliefs were assessed, and they then viewed either an informational video, an emotionally involving video, or a control video. Knowledge and beliefs were assessed immediately and 10 weeks later. Postvideo skin protection intentions increased significantly from prevideo assessment among the two intervention groups compared to the controls. Maintenance of skin protection intentions was higher with the emotional video. Health belief variables, particularly perceived barriers, were significant predictors of knowledge, intention, and behavior. However, other variables such as skin type and previous experience with skin cancer were more important. Females had greater knowledge and stronger intentions to prevent skin cancer than males but reported fewer high-risk behaviors.
Adult↗
Phase II trial of N-methylformamide in lung cancer.
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Adult↗
Comparison of dual photon and dual energy X-ray bone densitometers in a clinic setting.
In clinical practice, decisions must be made about whether and how to convert to newer technologies. To address this issue, two separate studies were conducted. We evaluated the relationships between results of lumbar spine measurements using two dual photon absorptiometry (DPA1 and DPA2) instruments and one dual energy X-ray (DXA) instrument with the same subjects (49 volunteers), and also in 65 patients who were measured on the DPA1 and DXA machines. Second, we measured the lumbar spine and the proximal femur in three groups of 12 female volunteers three times on one instrument within 1 week. We purposely simulated a busy clinic setting with different technologists, older radioactive sources, and a heterogeneous patient group. The comparison study indicated a significant difference between the mean bone density values reported by the machines, but the results were highly correlated (R2 = 0.89-0.96). The short-term precision errors (coefficients of variation) differed among the instruments, ranging from 1.3% (DXA of the spine) to 5.1% (DPA1 of the spine), and in the femoral neck, 2.3% and 2.4% (DXA and DPA1, respectively) versus 3.5% by DPA2. This study emphasizes the differences between instruments, the potential for greater error in busy clinic environments, and the apparent superiority of dual energy X-ray absorptiometry under these less than ideal conditions.
Absorptiometry, Photon↗
NMR-studies of triiodothyropropionic acid in ethanol-HCl.
The barrier to rotation in the N-acetyl methyl ester of the thyroxine was found to be 8.6 kcal mol-1. Previous experiments determining the barrier to rotation in triiodothyropropionic acid in HCl-ethanol were shown to be in error.
Ethanol↗
Isolation, characterization, and long-term culture of fetal bovine tracheal epithelial cells.
Epithelial cells were isolated from fetal bovine trachea by exposing and stripping the mucosal epithelium from the adjacent connective tissue. The tissue was minced and enzymically dissociated in Ca-Mg-free medium containing dispase and dithiothreitol. The stripping procedure and selective trypsinization produced epithelial cell cultures free of fibroblasts. Seeded on plastic, the plating efficiency was 21.5% with a doubling time of 24 h. Dome formation, evidence of occluding junctions and active ion transport characteristic of epithelial cells, was common. Growth of the cells on glass, collagen, and Engelbreth-Holm-Swarm (EHS) substrate demonstrated a striking difference in morphology. Cells grown on EHS presented a more distinctly three-dimensional growth pattern and many more microvilli when compared to cells grown on glass or collagen. The cells retained their epithelioid characteristics through more than 30 passages as shown by the presence of distinct apical and basolateral membranes, tight junctions, and positive keratin staining.
Animals↗
Microbiological cultivation of Mycoplasma hyorhinis from cell cultures.
The failure of many cell culture isolates of Mycoplasma hyorhinis to grow on microbiological media has stressed the need for alternate assays to detect these organisms. The use of freshly prepared yeast extract in mycoplasmal media together with incubation in 5% CO2/air successfully detected M. hyorhinis in 12 of 12 infected cultures. These were not detected by the use of conventional mycoplasmal media using aerobic or anaerobic incubation. This assay may also be helpful in detection of other mycoplasmal species commonly isolated from cell cultures.
Cells, Cultured↗
Phenotypic differences between Syrian hamster embryo cells cultured at pH 6.7 or 7.3.
We have investigated the molecular phenotypic differences between Syrian hamster embryo (SHE) cells cultured at pH 6.7 or 7.3. Multiple pH-sensitive phenotypic differences were noted including changes in cellular morphology, a unique charge differential in a major cellular protein, nine uniquely expressed proteins, two unique phosphoserine/threonine phosphoproteins, one unique phosphotyrosine phosphoprotein, and the pH dependent mRNA level of a gap junctional gene (connexin 43). These differences, combined with previously described pH-specific differences (differential transformation rates and gap junctional communication), illustrate that culturing SHE cells in media that differ by 0.6 pH units (0.3 units on either side of pH 7.0) can have a profound influence on the cellular phenotype.
Animals↗
Comparative accuracy of Doppler echocardiographic methods for clinical stroke volume determination.
Numerous Doppler echocardiographic methods to measure stroke volume have been proposed in experimental or clinical studies, but their relative accuracy in patients compared with an invasive reference standard remains uncertain. Accordingly, we compared Doppler with thermodilution stroke volume measurement in 18 hospitalized patients, 16 with an acute manifestation of coronary artery disease and two with chronic cardiomyopathies. Doppler time-velocity integrals were measured by darkest line (modal velocity) and the leading edge (maximal velocity) techniques at the aortic annular plane, the mitral orifice, and the mitral annular plane. Two-dimensional echocardiography was used to measure cross-sectional areas (M-mode-corrected at the mitral orifice). The combination of aortic annular cross-sectional area and the leading edge technique of measuring the time-velocity integral of blood flow at this site provided the most accurate measure of stroke volume (r = 0.87, p less than 0.0001, standard error of estimate = 11 cm3; mean difference from thermodilution = 2.8 ml +/- 8.9 ml, p = NS). It also resulted in the most accurate measurement of cardiac output (r = 0.88, p less than 0.0003; mean difference from thermodilution = 0.11 L/min +/- 0.69 L/min, p = NS). Other methods yielded values that correlated less closely and deviated systematically from thermodilution measurements. We therefore conclude that of the six common methods evaluated, the aortic annular leading edge method measures stroke volume with the best accuracy and is most suitable for clinical application.
Adult↗
Rapid reduction but lack of normalization of atrial natriuretic peptide levels in patients with congestive heart failure after cardiac transplantation.
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Adult↗
Immediate converting-enzyme inhibition with intravenous enalapril in chronic congestive heart failure.
To test the hypothesis that intravenous enalapril is a useful pharmacologic probe of the renin angiotensin system, intravenous enalapril was administered to 9 patients with severe congestive heart failure (CHF). This produced abrupt and complete blockade of converting enzyme, with peak effect occurring at 30 minutes, as reflected by increases of plasma renin activity (from 16.8 +/- 6 to 86.6 +/- 23 ng/ml/hour) and decreases of plasma aldosterone levels (from 46 +/- 14 to 25 +/- 6 ng%) (both p less than 0.05). With reduction of angiotensin II--mediated vasoconstriction, systemic vascular resistance decreased markedly (from 1,974 +/- 233 to 1,400 +/- 136 dyne s cm-5) and cardiac index was improved (from 1.88 +/- 0.9 to 2.20 +/- 0.21 liters/min/m2) (both p less than 0.05). The time course of angiotensin II levels suggested that the lack of a cumulative effect from additive doses of intravenous enalapril was a reflection of complete inhibition of converting enzyme. One patient did not respond to enalapril; despite comparable hemodynamic severity of CHF, the renin-angiotensin system was not activated in this patient. Thus, intravenous enalapril is capable of rapid and complete inhibition of converting enzyme for the accurate assessment of angiotensin II--mediated vasoconstriction in patients with severe CHF.
Adult↗
Clinical and hemodynamic experience with enalapril in congestive heart failure.
The renin-angiotension system is activated in many patients with congestive heart failure (CHF), resulting in angiotensin-mediated vasoconstriction and aldosterone-mediated sodium and water retention. To evaluate the effectiveness of enalapril, a new converting enzyme inhibitor, enalapril was administered to patients either orally or intravenously in a single dose, and hemodynamic and hormonal responses were measured. Patients were then placed on oral enalapril therapy for 1 month, and treadmill exercise duration and invasive hemodynamics were compared with baseline pretreatment data. With single-dose administration, both oral and intravenous enalapril reduced systemic vascular resistance and increased cardiac output. However, the effects of oral enalapril were not manifest for 3 to 4 hours, because oral enalapril is a pro-drug form that requires hepatic deesterification. In contrast, intravenous enalapril resulted in significant hemodynamic and hormonal changes 15 to 30 minutes after administration. During long-term therapy, enalapril was associated with improved symptomatology, increase of treadmill exercise duration and sustained hemodynamic improvement. Enalapril was effective therapy for chronic CHF. Optimal short-term response may require coadministration of both intravenous and oral preparations of enalapril; however, the magnitude of the short-term response was comparable for both preparations. Long-term therapy is most effective when the drug is administered as a twice-daily regimen.
Administration, Oral↗
Renal and hormonal effects of phosphodiesterase III inhibition in congestive heart failure.
Evaluation of the impact of therapeutic interventions in congestive heart failure (CHF) with compounds such as the phosphodiesterase (PDE) III inhibitors must include the determination of regional blood flow and functional changes. Thus, whereas PDE III inhibitors produce a significant increase in cardiac output and reduction of systemic vascular resistance, it is necessary to understand their effects on the kidney and neurohormonal parameters. The evaluation of these effects must take into consideration both the baseline renal and neurohormonal abnormalities in CHF, and the cellular actions of PDE III inhibition, which include an increase in cyclic adenosine monophosphate and cytosolic calcium. In a group of 13 patients with CHF, milrinone therapy for 1 month did not increase renal blood flow or glomerular filtration rate, or favorably affect neurohormonal parameters. However, forearm blood flow increased proportionately with cardiac output. Therefore PDE III inhibition produces a preferential increase in skeletal muscle blood flow, which may be a relative shunting of blood from the kidney. Alternatively, PDE III inhibition may activate renal cellular mechanisms that offset the anticipated favorable response to the increase of cardiac output produced by milrinone.
Aldosterone↗