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Biomedical subjects

R M Weiss

Publications and source records attributed to R M Weiss.

At least 163 records · Page 9Linked to original sources

Actions of adenosine on normal and abnormal impulse initiation in canine ventricle.

We studied the role of adenosine in modulating pacemaker activity in normal and infarcted ventricular tissues. We used standard microelectrode techniques to study the effects of adenosine on impulse initiation in Tyrode's superfused normal canine Purkinje fibers (PF), PF obtained from experimentally infarcted hearts, and BaCl2-superfused PF. Adenosine reduced automaticity of normal PF, whereas beta, gamma-methylene ATP did not. In infarcted and in Ba2+-depolarized PF, adenosine had no effect on automaticity or the action potential. We then used intracellular current injection to vary the membrane potentials of normal PF and found adenosine to depress automaticity more at high than at low membrane potentials. The ability of adenosine to counteract the effects of epinephrine on automaticity also was related to membrane potential. We conclude that adenosine depresses normal automaticity but has little effect on abnormal impulse initiation at low membrane potentials. It therefore appears that in the setting of myocardial infarction or ischemia the extent to which adenosine release will modify the function of normal and ectopic pacemakers will be influenced by the membrane potentials of those pacemakers.

Adenosine↗

The helical hydrophobic moment: a measure of the amphiphilicity of a helix.

The spatial distribution of the hydrophobic side chains in globular proteins is of considerable interest. It was recognized previously that most of the alpha-helices of myoglobin and haemoglobin are amphiphilic; that is, one surface of each helix projects mainly hydrophilic side chains, while the opposite surface projects mainly hydrophobic side chains. To quantify the amphiphilicity of a helix, here we define the mean helical hydrophobic moment, (mu H) = [sigma Ni = 1Hi]/N, to be the mean vector sum of the hydrophobicities Hi of the side chains of a helix of N residues. The length of a vector Hi is the signed numerical hydrophobicity associated with the type of side chain, and its direction is determined by the orientation of the side chain about the helix axis. A large value of (mu H) means that the helix is amphiphilic perpendicular to its axis. We have classified alpha-helices by plotting their mean helical moment versus the mean hydrophobicity of their residues, and report that transmembrane helices, helices from globular proteins and helices which are believed to seek surfaces between aqueous and nonpolar phases, cluster in different regions of such a plot. We suggest that this classification may be useful in identifying helical regions of proteins which bind to the surface of biological membranes. The concept of the hydrophobic moment can be generalized also to non-helical protein structures.

Membrane Proteins↗

Rationale for ureteral tapering.

With two to three weeks of obstruction, marked ureteral dilatation develops in the presence of relatively low intraluminal pressures. The low pressure and increasing dimensions primarily reflect alterations in intrarenal hemodynamics and the viscoelasticity of the ureteral wall, respectively. Associated with these changes, the ureteral muscle hypertrophies, and this is accompanied by an increase ability to contract, as evidenced by an increase in contractile force and stress. Despite muscle hypertrophy and increased contractility, the dilated ureter is less able to generate the contractile intraluminal pressure waves that are required for urine transport. This paradoxical decrease in intraluminal pressure with increasing contractile force and diameter is explained by the Laplace relationship which also provides a rationale for ureteral tapering. Ureteral tapering by decreasing diameter allows the obstructed ureter's ability to generate contractile forces to be translated into higher contractile intraluminal pressures which provide for more efficient urine transport.

Animals↗

Effect of obstruction on ureteral circumferential force-length relations.

After 2 wk of obstruction, rabbit ureteral length increases by 24%, outer diameter by 100%, and cross-sectional muscle area by 248%. In addition to undergoing muscle hypertrophy, obstructed ureters developed greater circumferential contractile forces than control ureters. The peak active force of obstructed ureteral segments was approximately twice that of control ureters. The increase in force was associated with a corresponding doubling of active circumferential stress (force/unit area), suggesting that the force increase resulted from 1) an increase in contractility rather than being a reflection of the muscle hypertrophy that occurred with obstruction, and 2) muscle fiber reorientation. Thus, the ureter, dilated secondary to 2 wk of obstruction, is not mechanically decompensated bur rather undergoes changes that result in an increase in contractility, Despite muscle hypertrophy and increased contractility, the obstructed ureter's ability to develop the intraluminal pressures required for urine transport decreases. The decrease in intraluminal pressure despite an increase in contractility results from the increased ureteral diameter following obstruction according to the Laplace relationship.

Animals↗

Urinary undiversion in patients with myelodysplasia and neurogenic bladder dysfunction. Report of a workshop.

This workshop was conducted in an attempt to analyze critically the role of reconstruction of the myelodysplastic patient who had undergone urinary diversion and to develop guidelines for selecting those patients in whom urinary undiversion might be undertaken safely. The collective experience initially seems to be acceptable; however, the authors emphasize the gravity of the decision and the complexity of the evaluation which must be undertaken prior to embarking on such reconstructive surgery. Contrary to some reports, we believe that the defunctionalized bladder frequently can be evaluated. Further, many of the contraindications to urinary undiversion have been identified and several of the hazards involved therein can be avoided. We believe that the neurogenic bladder is no longer an absolute contraindication to undiversion. Our experience suggests that undiversion is a reasonable surgical treatment in select patient with neurogenic bladder dysfunction. But, the decision to remove a satisfactorily functioning conduit must not be undertaken lightly. Patients should be selected only after a thorough, detailed, and properly conducted evaluation. A protocol has been developed which will hopefully assist in this evaluation. Perhaps additional shared experience will further refine and delineate the circumstances appropriate for reconstruction of these patients.

Adolescent↗

Prognostic value of urodynamic testing in myelodysplastic patients.

We herein describe the clinical progress of 42 myelodysplastic patients studied urodynamically and followed for a mean of 7.1 years. Urodynamic evaluation included urethral pressure profilometry, simultaneous determination of urethral pressure, intravesical pressure and external anal or external urethral sphincter electromyography with fluoroscopic voiding cystourethrography. Assessment of urethral function showed 36 patients (86 per cent) with an open vesical outlet and nonfunctional proximal urethral. Cystometrography revealed that 7 of 42 patients (17 per cent) had reflex detrusor activity: 4 with coordinated micturition and 3 with detrusor-sphincter dyssynergia. Thirty-five patients (83 per cent) had areflexic detrusor dysfunction: 5 with atomic detrusor response and 30 with a progressive increase in pressure with increasing volume. The intravesical pressure at the time of urethral leakage was 40 cm. water or less in 20 patients and at pressures greater than this value in 22 patients. No patient in the low pressure group had vesicoureteral reflux and only 2 showed ureteral dilatation on excretory urography. In contrast, of the patients in the higher pressure group 15 (68 per cent) showed vesicoureteral reflux and 18 (81 per cent) showed ureteral dilatation on excretory urography. Thus, a striking relationship between the urethral closure pressure and intravesical pressure at the time of urethral leakage and the clinical course in this group of myelodysplastic patients is demonstrated. Every patient with a normally closed vesical outlet was continent on intermittent catheterization and an anticholinergic agent, while only 60 per cent of patients with open bladder outlets similarly treated achieved good urinary control and none was dry. An artificial sphincter device would seem to be a reasonable method to achieve urinary control in the latter patients but the detrusor response to filling also must be considered. Detrusor hypertonia should be controlled or controllable before a sphincter augmenting device can be used safely. Treatment options for patients with high urethral closure pressures include intermittent catheterization and anticholinergic medications or a sphincter ablative procedure to decrease the outlet resistance combined with anticholinergic therapy and implantation of an artificial sphincter. However, only longer followup will determine if these therapeutic regimens will prevent upper urinary tract deterioration.

Electromyography↗

Empirical valence bond calculations of enzyme catalysis.

A method that allows one to correlate available x-ray data with activation free energies of enzymic reactions was presented. The method is an Empirical Valence Bond (EVB) approach that uses experimental information to evaluate the energies of the valence bond resonance forms and then calculates the environment-dependent stabilizations of the ionic resonance forms in the enzyme and in solution in order to correlate them with the rate enhancement by the enzyme. The reliability of the method is based on calibration of potential surfaces using solution experiments and on transfer of the calibrated surface to the enzyme active site using only simple electrostatic calculations. The close relation between the method and the intuitive description of bonding provides a new insight into enzymic reactions, describing them as surface crossings between covalent and ionic resonance forms. Such a description clarifies how the stabilization of the ionic resonance forms by the enzyme determines its catalytic activity.

Catalysis↗

Developmental changes in impulse conduction in the canine heart.

We studied the age-related changes that occur in conduction in Purkinje fiber bundles (PF) from adult and 8-wk-old dogs. As PF are stretched, conduction velocity increases to a maximum when bundle length is approximately 1.5 times control. Conduction velocity in adult PF was significantly faster than that in 8-wk PF at all bundle lengths, the maximum being 2.32 +/- 0.45 m/s (mean +/- SD) in adult and 1.56 +/- 0.59 m/s in 8-wk-old dogs. At greater than 1.5 times control length, conduction velocity decreased, as did resting potential, action potential amplitude, and upstroke velocity. At 1.5 times control length, the ratio of PF to collagen in the bundles increased, and structural changes consistent with both unbuckling and unfolding of the cell membranes were seen. At greater degrees of stretch, cleft size diminished, and intracellular edema was noted. In sum, structural changes in cardiac PF can explain the changes in conduction velocity that occur with stretch. At all degrees of stretch, however, velocity is faster in PF from adult than from young dogs.

Action Potentials↗

Keratosis punctata of the palmar creases.

We determined the prevalence of keratosis punctata of the palmar creases in 534 individuals. The group screened included patients, visitors, and staff in clinics and in a private office setting. The seven cases discovered were all found in black patients, representing 3.1% of this racial group. No relationship to arsenical agents, syphilis, or genetic factors could be ascertained by history.

Adolescent↗