Wall-thickness and midwall-radius variations in ventricular mechanics.

A fluid-fiber-collagen stress tensor is used to describe the rheology of the left ventricle of the heart. Linear theory is used to find the equilibrium solutions for the end-diastolic and end-systolic states of general axisymmetric shapes that are small perturbations of a thick-walled finite cylinder. The general problem can be studied by superposing the effects of variable midwall radius but constant wall thickness with those of variable wall thickness but constant midwall radius. A Fourier series representation is used to describe the midwall radius and thickness functions. Numerical calculations are performed to determine the deformed geometry and spatial distributions of tissue pressure, stresses, and fiber strains. The calculations proved to be highly accurate when compared to an analytical solution obtained for the special case of no fibers. The results show significant longitudinal differences when compared to results for the cylindrical geometry, with more sensitivity to variation in wall thickness than to variation in midwall radius.     

Value of continuous monitoring of the electrocardiogram in asymptomatic subjects

The authors analysed the prevalence of atrioventricular conduction defects and sinus node dysfunction by Holter monitoring in three population groups with similar clinical characteristics: 50 controls (Group I), 17 physically fit subjects with an atrioventricular conduction defect on the resting ECG which was usually asymptomatic (Group II), and 48 professional pilots who were also physically fit but who had no conduction defects on resting ECG (Group III). The 24 hour recordings showed: --a similar incidence of sinus dysrhythmias and atrioventricular conduction defects in the three groups although the frequency of low degree block was a little higher in sportsmen; --a preponderance of the association of first degree block and nocturnal Luciani-Wenckebach periods, sometimes with episodes of Mobitz II block; --the absence of progression to high-degree atrioventricular block. Holter monitoring would therefore seem to be a good method of detecting and following up abnormalities of sinus node function and atrioventricular conduction defects in asymptomatic patients. In addition, it gives a qualitative and quantitative assessment of the recorded changes and provides a means of monitoring their evolution.     

D1 Dopamine receptor-mediated substance P depletion in the striatonigral neurons of rats subjected to neonatal dopaminergic denervation: implications for self-injurious behavior

The present study examined the influences of dopamine (DA) receptor stimulation on enkephalin (Met5-enkephalin; ME) and tachykinin (substance P; SP) systems of basal ganglia of Sprague-Dawley rats, lesioned as neonates with 6-hydroxydopamine (6-OHDA). It has been proposed that the neonatal 6-OHDA-lesioned rat could serve as a model for the DA deficiency and self-injurious behavior (SIB) observed in the childhood neurological disorder. Lesch-Nyhan syndrome. In agreement with earlier work, the present study found that the neonatal 6-OHDA treatment at 3 days of age, reduced DA and caused an increase in ME and a decrease in SP content in the striatum and substantia nigra, when tested as adults. Administration of the DA precursor, L-dihydroxyphenylalanine (L-DOPA), to lesioned animals, induced SIB; increased DA and DOPAC levels; produced a greater decrease (-64%) in SP levels in the striatum and substantia nigra than was observed with lesion alone (-28%). The L-DOPA-induced decrease in SP levels and the SIB observed in the lesioned animals were blocked by pretreatment with the D1 receptor antagonist, SCH-23390. Moreover, administration of the D1 receptor agonist, SKF-38393, but not the D2 agonist, LY-171555, to lesioned animals mimicked the L-DOPA responses in all respects, except that the agonists did not alter DA or DOPAC levels. None of the DA agonists or antagonists treatments affected lesion-induced increase in ME levels in the striatum. These results indicate for the first time, that SIB precipitated by DA agonists in neonatal dopaminergic denervated animals, is associated with a marked and selective decrease in SP in the striatonigral SP neurons. This process has two components: (a) a retarded development of the SP system due to neonatal dopaminergic denervation: and (b) a depletion of the remaining SP, presumably by enhanced release due to D1 DA receptor-mediated activation of striatonigral SP neurons.     

Neurologic eye signs following motorcycle accidents

A review of 96 consecutive patients who suffered neuro-ophthalmologic injuries in motorcycle accidents revealed a wide range of findings. These findings were similar to signs associated with other forms of closed-head trauma, aside from a higher incidence of trochlear nerve palsies.     

Cervical cytology in a community laboratory

A retrospective analysis of the results of 27,801 cervical smears from one year in a community laboratory was undertaken. This represented 23,820 individual patients. Abnormalities were seen in 9.3% of patients. Three point seven percent of patients had benign abnormalities, 5.5% had cervical intraepithelial neoplasia and 0.1% had major abnormalities. The incidence of cervical epithelial abnormality was highest in the 15-34 age group but major abnormalities were seen most often in the 55+ age group. Human papillomavirus was more commonly seen in the youngest age group. The presence of inflammation was reported in 65% of the smears. Thirty percent of smears had no endocervical cells and 0.6% were grossly inadequate. Fifteen percent of patients had repeat smears and 3% of total smears were judged unnecessary. Forty two point six percent of patients less than 55 years of age in the laboratory population base had a smear but only 7.9% of those over 55.     

The complex nature of the mechanism of toxicity of antibiotic dithiacyclohexadiene polyines (thiarubrines) from the asteraceae

Thiarubrine A, a dithiacyclohexadiene polyine from the roots of Chaenactis douglasii, and a related dithiacyclohexadiene from Rudbeckia hirta exhibit strong light-independent antibacterial and antifungal activity. This activity is enhanced by exposure to visible light. Visible light also converts the compounds to the corresponding thiophenes. These are antibiotic only when irradiated with UV-A. Dithiacyclohexadienes are the first polyines to exhibit such complex mechanisms of toxicity towards microorganisms.     

Prediction of steady state bioequivalence relationships using single dose data II-nonlinear kinetics

Two nonlinear pharmacokinetic models were simulated to investigate the relationship between single and multiple dose bioequivalency parameters for drugs such as phenytoin and propranolol which exhibit either saturable elimination kinetics or a capacity limited first pass effect. Mean Tmax, Cmax and area under the plasma-concentration time curve values from 0 to infinity (AUC 0-infinity) were compared after a single and multiple dose(s) of a test or reference drug. The aim was to determine if there were systematic changes in the limits of the single dose confidence interval at steady state that would limit the usefulness of confidence intervals following a single dose in accurately predicting bioavailability following multiple dosing. The 90 per cent confidence interval expressed as a percentage of the reference mean for Tmax, Cmax, and AUC 0-infinity showed model dependent changes from single to multiple dosing in response to the level of data error and changes in absorption. Changes in clearance also seemed to have a marked effect on the observed limits of the single and multiple dose confidence intervals especially for Cmax which showed a characteristic change in the intervals as a function of the clearance ratio. The model used to describe phenytoin had confidence intervals for Cmax and AUC 0-infinity from single to multiple dosing that were similar to that seen for the experimental data. However, the model predictions for Tmax confidence intervals following single and multiple dosing was at variance with the experimental data for formulations A and B.