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H J Walker

Publications and source records attributed to H J Walker.

11 recordsLinked to original sources
PubMed1996

Suppression of mesangial proliferative glomerulonephritis development in rats by inhibitors of cAMP phosphodiesterase isozymes types III and IV.

Excessive mesangial cell (MC) proliferation is a hallmark of many glomerulopathies. In our recent study on cultured rat MC (Matousovic, K., J.P. Grande, C.C.S. Chini, E.N. Chini, and T.P. Dousa. 1995. J. Clin. Invest. 96:401-410) we found that inhibition of isozyme cyclic-3',5'-nucleotide phosphodiesterase (PDE) type III (PDE-III) suppressed MC mitogenesis by activating cAMP-dependent protein kinase (PKA) and by decreasing activity of mitogen-activated protein kinase (MAPK). We also found that inhibition of another PDE isozyme, PDE-IV, suppresses superoxide generation in glomeruli (Chini, C.C.S., E.N. Chini, J.M. Williams, K. Matousovic, and T.P. Dousa. 1994. Kidney Int. 46:28-36). We thus explored whether administration in vivo of the selective PDE-III antagonist, lixazinone (LX), together with the specific PDE-IV antagonist, rolipram (RP), can attenuate development of mesangioproliferative glomerulonephritis (MSGN) induced in rats by anti-rat thymocyte serum (ATS). Unlike the vehicle-treated MSGN rats, rats with MSGN treated with LX and RP did not develop proteinuria and maintained normal renal function when examined 5 d after injection of ATS. In PAS-stained kidneys from PDE-antagonists-treated MSGN-rats the morphology of glomeruli showed a reduction in cellularity compared with control rats with ATS. Compared with MSGN rats receiving vehicle, the MSGN rats receiving PDE-antagonists had less glomerular cell proliferation (PCNA delta -65%), a significantly lesser macrophage infiltration (delta -36% ED-1) and a significant reduction of alpha-smooth muscle actin expression by activated MC; in contrast, immunostaining for platelet antigens and laminin were not different. The beneficial effect of PDE inhibitors was not due to a moderate decrease (approximately -20%) in systolic blood pressure (SBP); as a similar decrease in SBP due to administration of hydralazine, a drug devoid of PDE inhibitory effect, did not reduce severity of MSGN in ATS-injected rats. We conclude that antagonists of PDE-III and PDE-IV administered in submicromolar concentrations in vivo to ATS-injected rats can decrease the activation and proliferation of MC, inhibit the macrophage accumulation, and prevent proteinuria in the acute phase of MSGN. We propose that PDE isozyme inhibitors act to block (negative "crosstalk") the mitogen-stimulated intracellular signaling pathway which controls MC proliferation due to activating of the cAMP-PKA pathway. These results suggest that antagonists of PDE-111 and IV may have a suppressive effect in acute phases or relapses of glomerulopathies associated with MC proliferations.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1989

Vasodilator therapy and the anesthetist: a review of nitroprusside, labetalol, hydralazine and nitroglycerin.

Vasodilators are important adjuncts to anesthetic management in a variety of clinically encountered situations. Examples include: congestive heart failure, preeclampsia/eclampsia, management of aortic cross-clamping and treatment of perioperative hypertension. In this article, the authors review four commonly utilized vasodilating agents: sodium nitroprusside, labetalol, hydralazine and nitroglycerin. Comparisons and contrasts are made among the drugs. Each agent is presented in four sections: (1) mechanism of action, (2) indications, (3) adverse actions, and (4) dosage, administration and precautions.

Humans↗
PubMed1978

Echocardiographic estimation of aortic-valve gradient in aortic stenosis.

Fifty-five consecutive patients with aortic stenosis underwent echocardiography at the time of cardiac catheterization. Left ventricular systolic pressure was estimated from the echocardiogram assuming that peak systolic circumferential was stress was constant. Systolic blood pressure was substracted from the estimated left ventricular pressure to obtain the aortic-valve gradient. Of 44 patients with adequate echocardiograms and catheterization studies, 30 had their aortic gradient accurately estimated by the echocardiogram (r = 0.75). All 30 patients had normal left ventricular systolic function estimated echocardiographically. The echocardiogram underestimated the aortic gradient in all seven patients with poor left ventricular systolic function. An accurate echocardiographic estimate of aortic-valve gradient can be obtained in patients with normal left ventricular function. The technique can identify those patients with insignificant left ventricular outflow obstruction, thereby obviating the need for invasive studies.

Adolescent↗
PubMed1977

Interobserver variability in echocardiography.

High-quality echocardiograms were performed on 146 normal individuals whose ages ranged from 3 to 73 years (mean 27 years). Normal values for mitral diastolic excursion and E-F slope, the chamber dimensions of the right ventricle, left atrium, and left ventricle, the aortic root dimension, and thickness of the interventricular septum and left ventricular posterior wall were determined. Each tracing was then read independently by two experienced echocardiographers. The extent of interobserver variability was calculated and expressed as a percent of the mean. The 95 per cent confidence limits for these estimates were calculated. Small but significant interobserver variability was found for all nine of these commonly measured echocardiographic parameters. Observer variability is a small but potentially important consideration in investigative echocardiography.

Adolescent↗
PubMed1977

Relation between phasic mitral flow and the echocardiogram of the mitral valve in man.

Ten patients without valvular disease were studied by ventriculography, and the rate and pattern of phasic blood flow into the left ventricle were determined by ventricular volume determinations at intervals of 33 ms during a single diastolic filling period. The derived left ventricular inflow patterns were then compared with the echocardiographic mitral EF slope obtained no more than 25 minutes before left ventriculography. The steepness of the EF slope was found to be inversely correlated with the time required to reach peak inflow velocity (r = 0.80, P less than 0.01) and directly correlated with the peak left ventricular inflow velocity divided by the time required to reach peak velocity (r = 0.72, P less than 0.05). No correlation was found between mean flow velocity into the left ventricle and the EF slope (r = 0.40, P = NS). A significant inverse correlation was found between the EF slope and the fraction of the diastolic filling period elapsed when 50 per cent of the filling volume had entered the left ventricle (r = 0.85, P less than 0.01). These findings suggest that the time required to reach left ventricular peak inflow velocity is one of the determinants of the mitral EF slope.

Angiocardiography↗
PubMed1977

Hypertrophic cardiomyopathy. Evaluation by gated cardiac blood pool scanning.

The gated radionuclide cardiac blood pool scan (GCS) can be used to visualize the entire profile of the interventricular septum and left ventricular contraction. Twenty-two patients with hypertrophic cardiomyopathy, nine with valvular aortic stenosis and six normals, underwent echocardiography and GCS. All patients with hypertrophic cardiomyopathy had asymmetric septal hypertrophy and 14 of 22 had resting systolic anterior motion of the anterior leaflet of the mitral valve on echocardiogram. In eight patients with aortic stenosis with adequate echocardiograms, two had asymmetric septal hypertrophy and none had systolic anterior motion. The GCS demonstrated disproportionate upper septal thickening in 11; septal flattening in 16; cavity obliteration in 17; and a filling defect in the region of the left ventricular outflow tract in 16 of the 22 patients with hypertrophic cardiomyopathy. In the nine patients with valvular aortic stenosis, two demonstrated septal flattening, two cavity obliteration, two an outflow tract defect, and none disproportionate upper septal thickening. Both patients with cavity obliteration demonstrated asymmetric septal hypertrophy on echocardiogram. One normal control patient had septal flattening. Thus the gated cardiac blood pool scan provides an atraumatic technique for the evaluation of patients with hypertrophic cardiomyopathy which complements the echocardiogram.

Aortic Valve Stenosis↗
PubMed1975

Relationship between linguistic performance and memory deficits in retarded children.

Performance of retarded children was measured on four tests of linguistic ability and two memory tests. Subjects were 50 retarded children: 10 each at mental ages 3, 4, 5, 6, and 7. The relationship between linguistic performance and memory was assessed by correlational analysis. Multiple and partial correlations were computed using a measure of language comprehension and a measure of memory span as predictor variables and three measures of language production as criterion variables. Different patterns of correlation were found with the three production as criterion variables. Different patterns of correlation were found with the three production measures, suggesting that the relative importance of memory span in language production depends on the specific production task.

Auditory Perception↗
PubMedDate not supplied

Early post-operative changes in left ventricular dimensions and mass following valve replacement in adults with aortic stenosis.

Twelve adults with isolated valvular aortic stenosis (AS) were evaluated for early changes of left ventricular (LV) dimensions and mass (LVM/M2) following valve replacement (AVR). M-mode echocardiography was performed pre- and 3 to 5 weeks post-AVR. LV internal diameter (LVID) decreased from 51 +/- 2.0 to 46 +/- 2.7 mm post-AVR (p less than .02). Reduction of posterior wall thickness (PWT) from 12 +/- 0.7 to 10 +/- 0.6 mm (p less than .01), interventricular septal thickness (IVST) from 13 +/- 0.9 to 11 +/- 1.2 mm (p less than .005), and mean myocardial thickness (MMT) from 12.4 +/- 0.7 to 10.5 +/- 0.7 (p less than .001), occurred post-AVR. Wall thickness/internal radius ratio was unchanged post-AVR. Calculated LVM/M2 decreased from 170 +/- 15 to 110 +/- 13 grams post-AVR (p less than .001). Normalized posterior wall velocity (PWVn) increased post-AVR from 0.66 +/- .05 to 1.08 +/- .10 sec-1 (p less than .001). For all twenty four studies, LVM/M2 and PWVn were correlated (r = -0.725, p less than .001). In summary, LV dimensions and LVM/M2 decreased significantly 3 to 5 weeks post-AVR in adults with AS. There was significant correlation of LVM/M2 and PWVn for pre-AVR and post AVR studies.

Adult↗