Search PubMed⌕ Search

Biomedical subjects

G Mall

Publications and source records attributed to G Mall.

At least 73 records · Page 4Linked to original sources
PubMed1995

Converting enzyme inhibitors differentially affect expression of genes of the renin-angiotensin system.

There is considerable evidence from clinical and experimental studies that blood pressure is lowered by converting enzyme inhibitors (CEIs) irrespective of whether the plasma renin-angiotensin system (RAS) is stimulated. New insights into the molecular biology of the RAS--in particular, the gene expression of renin and angiotensinogen in various tissues--support the view that the antihypertensive properties of CEIs may be mediated, at least in part, by interaction with tissue RAS. To investigate this possibility further, stroke-prone spontaneously hypertensive male rats (SHRSP) were treated orally for 28 days with different CEIs or a peripheral vasodilator to study the effects of the various drug treatments on the gene expression of the RAS in selected tissues. Different effects of different CEIs on tissue gene expression suggest localized action and some degree of organ specificity of the drugs. The experiments involved: (1) untreated controls; and rats treated with either (2) 50 mg/kg of captopril; (3) 10 mg/kg of lisinopril; (4) 10 mg/kg of cilazapril; (5) or 30 mg/kg of the vasodilator hydralazine with 10 rats/group. All of the study drugs reduced systolic blood pressure to normotension. Cardiac hypertrophy and the heart:body weight ratio were significantly decreased only in the CEI-treated animals, and kidney renin mRNA was increased by the CEIs whereas hydralazine had no effect on heart weight or kidney renin mRNA. Plasma renin activity increased in parallel with kidney renin mRNA levels. Liquid hybridization and Northern blotting assays revealed drug-specific regulation of the angiotensinogen mRNA level in the adrenal gland, with cilazapril producing the most marked stimulation of adrenal angiotensinogen gene expression. Both lisinopril and cilazapril suppressed hypothalamic angiotensinogen mRNA. There were no significant changes in angiotensinogen gene expression observed in the kidney or liver with any of the CEIs. In conclusion, these data show that CEIs interact differentially and drug-specifically with tissue RAS, and have class-specific effects on cardiac hypertrophy.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1995

Methanol ingestion. 'Guaranteed to make you feel good'.

Three patients who presented to an urban general emergency department in Baton Rouge, Louisiana within a 4-hour period are described. These patients demonstrate the various presentations and severity of methanol poisoning from a single source of exposure. Rapid therapy is required, often after presumptive diagnosis, in order to prevent significant morbidity or death.

Adult↗
PubMed1995

Blood-pressure-independent wall thickening of intramyocardial arterioles in experimental uraemia: evidence for a permissive action of PTH.

BACKGROUND: Abnormalities in cardiovascular structures, e.g. LV hypertrophy and thickening of vessels (arteries, arterioles, veins) are hallmarks of renal failure. They are in part independent of elevated blood pressure. Parathyroid hormone (PTH) has been shown to affect cardiac function and has also been identified as a permissive factor in the genesis of cardiac fibrosis. PURPOSE OF THE STUDY: The present study in rats with experimental renal failure was designed to examine whether PTH was permissive for wall thickening of intramyocardial arterioles as well. METHODS: Male SD rats were sham operated or subtotally nephrectomized and maintained for 2 weeks. Subgroups of subtotally nephrectomized (SNX) rats were parathyroidectomized (PTX). Saline or rat 1, 34 PTH was administered by osmotic minipump. Eucalcaemia was maintained in PTX animals by a high-calcium diet (3%). Serum calcium was not statistically different between the groups. After perfusion fixation, intramyocardial arterioles were assessed using stereological techniques (wall thickness; wall/lumen ratio; minimal lumen diameter; length density). RESULTS: In random samples of the left ventricle, wall thickness of arterioles was 2.2 +/- 0.25 microns in sham-op controls and 2.76 +/- 0.41 in SNX (n = at least 8 animals per group). SNX-PTX animals+solvent did not differ significantly from sham-op controls (2.08 +/- 0.42 microns), while SNX-PTX animals+PTH had values not significantly different from SNX (2.59 +/- 0.54 microns). Differences in wall thickness were not paralleled by differences in systolic blood pressure (sham-op 110 +/- 13.3 mmHg; SNX 138 +/- 8.4 mmHg, SNX-PTX+solvent 142 +/- 5.2 mmHg; SNX-PTX+PTH 148 +/- 5.7 mmHg). PTH treated animals showed signs of marked vascular smooth-muscle cell and endothelial-cell activation. CONCLUSIONS: The data suggest that wall thickening of intramyocardial arterioles in short-term experimental uraemia is dependent upon the presence of PTH (permissive effect).

Animals↗
PubMed1994

1% lidocaine versus 0.5% diphenhydramine for local anesthesia in minor laceration repair.

STUDY OBJECTIVE: Our previous study demonstrated that 1% diphenhydramine is as effective as 1% lidocaine for anesthesia in minor laceration repair, but that it also is more painful to inject. The purpose of this study was to compare 0.5% diphenhydramine to 1% lidocaine for pain of injection and adequacy of local anesthesia. STUDY DESIGN: Randomized, double-blinded, prospective study from December 1991 through June 1992. SETTING: University-affiliated, urban, inner-city emergency department. PARTICIPANTS: Ninety-eight adults with linear skin lacerations without end-organ involvement were included; 48 received lidocaine and 50 received diphenhydramine. INTERVENTIONS: Wounds were anesthetized with either diphenhydramine or lidocaine according to a random table. Both patients and physicians rated the pain of injection and suturing according to a standard, previously tested, visual analog scale. MEASUREMENTS AND MAIN RESULTS: Patient and physician ratings were ranked without regard to treatment group, and rank sum scores were calculated for each group. General linear models and multivariate analysis of variance were used to analyze the ranked sum scores. The power of the study to detect a ranked sum difference of 15 was 0.8 with P < .05 considered statistically significant. Lidocaine was found to be significantly more effective as a local anesthetic for facial lacerations according to both patients (P < .002) and physicians (P < .004). There was no statistically significant difference between 1% lidocaine and 0.5% diphenhydramine for pain of injection or suturing for all other locations according to both patients and physicians. Overall mean and median scores for injection and suturing with diphenhydramine corresponded to the mild pain category according to patients. CONCLUSION: Although not a replacement for lidocaine, diphenhydramine is a viable alternative for anesthesia in the repair of minor lacerations.

Adult↗
PubMed1994

Effect of chronic alcohol consumption on the morphology of the oral mucosa.

Chronic alcohol consumption is a major risk factor for oral and pharyngeal cancer. Besides other mechanisms a toxic effect of ethanol and/or its metabolite acetaldehyde on the oral mucosa and resulting increased cell regeneration seem to play an important role in tumor promotion. In the present study the effect of chronic ethanol consumption on the morphology of the oral mucosa of 40 male wistar rats that had been fed nutritionally adequate liquid diets containing 36% of total calories either as ethanol or isocaloric carbohydrates for 6 months was investigated. Morphometric analysis showed that in the ethanol rats the size of the basal cell nuclei of the oral mucosa from the floor of the mouth, the edge of the tongue and the base of the tongue were significantly enlarged (p < 0.001). The size of the basal cell layer in these rats was increased, and the stratification of the cells was altered. The percentage of cells in the S-phase of the cell cycle was significantly higher in the ethanol-fed rats (p < 0.01). Mean epithelial thickness of the mucosa from the floor of the mouth was significantly reduced in the ethanol rats (p < 0.01). In conclusion, the reported findings indicate, that chronic ethanol consumption causes oral mucosal atrophy associated with hyper-regeneration, which may result in an enhanced susceptibility of the mucosal epithelium toward chemical carcinogens.

Alcohol Drinking↗
PubMed1994

A role of parathyroid hormone for the activation of cardiac fibroblasts in uremia.

Intermyocardiocytic fibrosis, i.e., nonreparative interstitial fibrosis with collagen fiber deposition, is commonly found in uremic patients and animals. The volume density of interstitial tissue in the left papillary muscle of uremic animals was found to be increased (from 1.9 +/- 0.7 to 4.2 +/- 1.1%; P < 0.001). The nuclei of interstitial cells, but not of endothelial cells, were enlarged, pointing to an activating signal that specifically acts on interstitial cells. Because of the known action of parathyroid hormone (PTH) on the heart, a potential role of PTH in the genesis of fibrosis was explored by comparing subtotally nephrectomized (NX) parathyroidectomized (PTX) rats receiving by osmotic minipump either saline or rat 1,34 PTH (100 ng/kg per hour dissolved in NaCl). Animals were on a standard 0.95% Ca diet. After PTX, they were switched to a high-calcium (3%) diet. At the end of the 14-day experiments, NX-PTX-PTH animals and NX-PTX-solvent animals were comparable with respect to mean body weight (335 versus 338 g), serum creatinine (1.2 versus 1.2 mg/dL), and serum-Ca (2.66 versus 2.63 mmol/L). The volume densities of cardiac interstitium were 4.71 +/- 0.87 versus 1.49 +/- 0.49, and those of capillaries were 8.07 +/- 1.54 versus 7.94 +/- 2.62, respectively (P < 0.001 by analysis of variance). Thus, PTX abolished and PTH restored intermyocardiocytic changes of experimental uremia. These observations argue for a permissive role of PTH for fibroblast activation and the genesis of the cardiac fibrosis of uremia.

Animals↗
PubMed1994

[Arrhythmogenic right ventricular disease].

In patients with arrhythmogenic right ventricular disease (ARVD), life threatening ventricular tachyarrhythmias and sudden cardiac death mostly occur in adolescence, or in young adults before the age of 40. In the right ventricle, progressive fibrolipomatous replacement of the ventricular myocardium is pathognomonic. In severe cases progressive congestive right heart failure can develop although mild forms are extremely difficult to recognized. In most cases the disease can be diagnosed only by elaborate investigation. Right ventricular cineangiography, myocardial biopsy, MRI, and electrophysiological investigation are the most important diagnostic procedures. If the disease is diagnosed in an early stage the risk of life-threatening arrhythmias can be reduced by carefully selected antiarrhythmic therapy.

Adolescent↗
PubMed1993

Influence of collagen network on left ventricular systolic and diastolic function in aortic valve disease.

OBJECTIVES: The purpose of this study was to evaluate left ventricular structure-function interplay in aortic valve disease. BACKGROUND: An increase in myocardial fibrosis has been demonstrated in aortic valve disease, but changes in the collagen network and their effect on ventricular function have not been defined. METHODS: Left ventricular structure was assessed from left ventricular endomyocardial biopsy specimens obtained in 32 patients with aortic valve disease (aortic stenosis in 25, aortic regurgitation in 7). Total collagen volume fraction, orthogonal collagen fiber meshwork (cross-hatching), endocardial fibrosis, muscle fiber diameter and volume fraction of myofibrils were determined by morphologic-morphometric evaluation. Control biopsy data were obtained from six donor hearts before transplantation. Eleven other patients with normal left ventricular function served as hemodynamic status control subjects. Left ventricular biplane cineangiography and high fidelity pressure measurements were carried out in all patients. Systolic function was assessed from ejection fraction. Diastolic function was evaluated by the time constant of relaxation, early and late peak filling rates and the constant of passive myocardial stiffness. Patients were assigned to three groups according to increasing severity of nonmyocyte tissue alterations. Group 1 comprised 10 patients with elevated total collagen volume fraction. Group 2 comprised 6 patients with normal total collagen volume fraction and the presence of increased cross-hatching or endocardial fibrosis, or both. Group 3 comprised 16 patients with elevated total collagen volume fraction and the presence of cross-hatching or endocardial fibrosis, or both. RESULTS: Muscle fiber diameter was increased in the three groups with aortic valve disease, whereas the volume fraction of myofibrils was comparable in all four study groups. Ejection fraction was depressed in groups 2 and 3 compared with the control group. The time constant of relaxation was prolonged in the three groups with aortic valve disease. No differences in early and late peak filling rate were observed in the four study groups, but the constant of myocardial stiffness increased in groups 2 and 3. CONCLUSIONS: In aortic valve disease, changes in collagen architecture are associated with altered systolic function and passive diastolic properties. The sole increase in total collagen volume fraction without a change in architecture leaves systolic and passive diastolic function unaltered.

Adult↗
PubMed1993

Preservation of cardiac myocytes subjected to different preconditions: a comparative morphometric study of beating, fibrillating, and cardioplegically arrested canine hearts.

This study compares the ultrastructure of beating canine hearts with that of hearts subjected to different clinically common forms of cardiac arrest. The contraction state per test field was ascertained according to a specially developed classification. The volume density of myofibrils and the surface to volume ratio of mitochondria were used as parameters for cellular and mitochondrial swelling. Contraction bands were not found in any of the differently pretreated hearts. Following immersion fixation, contractions as well as over- and hypercontractions in beating, fibrillating, and St. Thomas-arrested hearts are significantly more pronounced than in HTK-arrested hearts. Cellular and mitochondrial volumes were similar in beating and fibrillating hearts. St. Thomas-perfusion significantly decreased cellular and mitochondrial volume compared to beating hearts, but these values were in the same range as in fibrillating hearts. Only HTK-solution actually led to a strong reduction of these compartments. Compared to immersion, perfusion fixation after coronary perfusion with cardioplegic solutions led to comparable cellular volumes, but significantly elevated the percentage of relaxed sarcomeres and significantly reduced mitochondrial swelling. The best structural preservation of myocytes was found after HTK-perfusion and perfusion fixation. Such ultrastructural quantitative and morphometrical parameters are powerful tools since results confirm that the degree of myocardial preservation depends on the method of cardiac arrest. This forms the basis for the choice of preconditions for subsequent ischemia. Furthermore, significant alterations of myocardial ultrastructure depend on a combination of the functional state of the heart, the method of cardioplegia, and the technique of fixation.

Animals↗
PubMed1993

Effects of rhGH and rhIGF-1 on renal growth and morphology.

It is known that in rodents recombinant human growth hormone (rhGH) and recombinant human insulin-like growth factor (rhIGF-1) increase renal mass. It is uncertain, however, whether renal mass increases in proportion to body growth, or whether renal growth is stimulated selectively. In 120 to 150 g female Sprague-Dawley rats, we measured the effects of rhGH and rhIGF-1 and their combination by the following parameters: kidney weight/body weight ratio, DNA/protein ratio, mRNA of GH receptor and of IGF-1, mitosis index and PCNA (by immunohistology), zonal architecture and glomerular diameter by micromorphometry. Both rhGH and rhIGF-1 dose-dependently increased renal weight and body weight over vehicle treated controls. With rhGH, liver dry weight/body weight ratio increased, but kidney dry weight/body weight ratio remained unchanged (0.99 +/- 0.06 x 10(-3) vs. 1.02 +/- 0.07 in vehicle controls). In contrast, a significant increase of kidney dry weight/body weight ratio was seen in rats treated with rhIGF-1 (1.3 +/- 0.21 x 10(-3). Addition of high doses of rhGH to high doses of rhIGF-1 caused no further increase of the ratio despite a significant further increase of body weight. rhGH increased the abundance of renal GH receptor mRNA (0.46 +/- 0.32 amol/microgram DNA vs. 0.08 +/- 0.07 in controls) and of IGF-1 mRNA (1.35 +/- 0.5 pg/micrograms DNA vs. 0.35 +/- 0.17), whereas no change was seen with IGF-1 treatment. rhGH and rhIGF-1 increased kidney DNA/protein ratio, mitoses and PCNA expression in various renal structures.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

[Stress fractures of the navicular bone--biomechanical and densitometry studies].

One of the most important pathogenetic mechanisms regarding stress fractures of the navicular bone lies in the hyperpronation movement of the foot. For recording the impacts of the pronation movement on the talonavicular joint, stress and pressure experiments are carried out and the radii of curvature as well as the bone density are measured. The stress experiments show a rotation movement of the talar head in a medioplantar direction of about 20 degrees. The radii of curvature of the articulating joint surfaces do not differ to a great extent. A possible incongruency in the joint therefore has to be attributed to the rotation movement of the talus during pronation of the foot. The pressure experiments show a very irregular distribution of pressure in the joint presenting a lateral and medial pressure maximum. Fractures preferably occur in the area in between these maxima. Areas of high subchondral bone density in the densitometric results are found in the central part of the talar head as well as in the medial part of the navicular bone. Within the functional adaptation the distribution of bone density expresses the rotation movement of the talus during pronation of the foot.

Absorptiometry, Photon↗
PubMed1993

The effect of enalapril on glomerular growth and glomerular lesions after subtotal nephrectomy in the rat: a stereological analysis.

INTRODUCTION: Angiotensin converting enzyme (ACE) inhibitors have a beneficial effect on glomerular injury in different models of renal damage. Their presumed nephroprotective action has been related partly to actions on glomerular growth. We examined the effect of prophylactic administration of a moderate dose of enalapril (50 mg/l in drinking water) in male Sprague-Dawley rats on a diet containing 40% protein and moderate NaCl. METHODS: The rats were followed for 8 weeks after subtotal nephrectomy and compared with sham-operated matched controls. RESULTS: The number of glomeruli per kidney was reduced significantly in both the enalapril-treated and control groups. The median glomerulosclerosis index was significantly lower in the enalapril-treated than in the untreated subtotally nephrectomized rats. The mean absolute glomerular volume was significantly higher after subtotal nephrectomy, but was significantly lower in the enalapril-treated than in the untreated subtotally nephrectomized rats. The total numbers of cells per glomerulus and of mesangial or endothelial cells, as well as nuclear volumes of mesangial cells and the total capillary length per glomerulus, were all significantly higher after subtotal nephrectomy. These parameters were significantly lower in the enalapril-treated than in the untreated nephrectomized rats. The rise in systemic blood pressure was modest in the nephrectomized rats and the arteriolar volume: length ratio was unchanged by treatment with enalapril. CONCLUSIONS: In subtotally nephrectomized rats enalapril inhibits (but fails to reverse completely) the compensatory glomerular enlargement and the increase in mesangial cell number and activation, with a concomitant reduction in the development of glomerulosclerosis. The results is compatible with antiproliferative, and possibly antiangiogenic, actions of ACE inhibitors.

Animals↗
PubMed1993

Structural causes of cardiac dysfunction in uremia.

While coronary heart disease is undoubtedly a major cause of cardiac morbidity and mortality in uremia, important noncoronary problems contribute to the common presence of cardiac problems. Based on clinical and experimental studies, we could show: (i) Left ventricular hypertrophy (LVH) can be dissociated, at least in part, from elevation of blood pressure. (ii) In uremia, PTH-dependent intermyocardiocytic fibrosis occurs; it may account, at least in part, for disturbed LV compliance and contribute to the arrhythmogenic potential. (iii) Blood pressure-independent abnormalities of intracardiac arterioles and reduced myocardial capillary supply are observed.

Animals↗
PubMed1993

Improvement of impaired pancreatic microcirculation by isovolemic hemodilution protects pancreatic morphology in acute biliary pancreatitis.

Impairment of the pancreatic microcirculation is a characteristic finding in experimental biliary pancreatitis. Isovolemic hemodilution with dextran 60 has been proven to maintain pancreatic capillary perfusion. To evaluate the significance of this therapeutic approach with respect to histologic changes, intravital microscopic assessment of the microcirculation was combined with a morphometric analysis of the pancreas by means of light microscopy in rabbits (n = 18). Pancreatic capillary perfusion was maintained in the rabbits subjected to hemodilution 30 minutes after the induction of pancreatitis with 54 percent of the capillaries still being perfused at 12 hours, compared with only 16 percent in the control group. The improved capillary perfusion resulted in a significant reduction of those changes considered potentially reversible (cell vacuolization and interstitial edema) that surround zones of necrosis. However, because of the early establishment of necrosis in this model, hemodilution was unsuccessful in preventing all cell death. Hemodilution can limit the progressive extension of pancreatic injury in this model of biliary pancreatitis.

Acute Disease↗
PubMed1992

Decreased concentration of myofibrils and myofiber hypertrophy are structural determinants of impaired left ventricular function in patients with chronic heart diseases: a multiple logistic regression analysis.

OBJECTIVES: The aim of this study was to perform a multiple logistic regression analysis to identify independent structural determinants of impaired left ventricular function. BACKGROUND: The association between contractile failure and structural alterations of the myocardium has been demonstrated in several studies, and multiple interactions between myocardial structure and cardiac performance are likely. METHODS: Morphometric data assessed from 130 left ventricular biopsy specimens were analyzed. The endomyocardial specimens were obtained from 57 patients with normal coronary arteries (17 with normal left ventricular ejection fraction and 40 with impaired left ventricular function [dilated cardiomyopathy]), 15 patients with hypertrophic cardiomyopathy and 32 patients with aortic valve disease. Transmural biopsy specimens were assessed in 6 donor hearts before heart transplantation and in 20 patients with left anterior descending coronary artery disease whose specimens were obtained from the left ventricular anterior wall during aortocoronary bypass surgery. Global or regional left ventricular function was evaluated from left cineventriculograms. The volume fraction of cardiac fibrous tissue, intracellular volume fraction of myofibrils, volume fraction of myofibrils related to myocardial tissue (including fibrosis) and myofiber diameters were determined from semithin sections of the biopsy specimens with the use of light microscopic morphometry. RESULTS: Multiple logistic regression analysis revealed decreased volume fraction of myofibrils (p < 0.005) and increased fiber diameter (p < 0.002) as independent determinants of impaired left ventricular function. CONCLUSIONS: These data indicate that, independent of the underlying heart disease, both decreased concentration of contractile proteins and myocyte hypertrophy are independently associated with impaired left ventricular function.

Age Factors↗