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Biomedical subjects

G Mall

Publications and source records attributed to G Mall.

At least 127 records · Page 7Linked to original sources

[Patterns of acute and persistent infections in enteroviral heart diseases].

Enteroviruses are considered as the major etiologic agents of myocarditis in humans. Recent in situ hybridization studies on endomyocardial biopsies indicate that not only in acute myocarditis (pattern of acute infection), but also in chronic dilated cardiomyopathy enterovirus RNA can be detected (pattern of persistent infection). Our experimental studies on murine coxsackievirus B3 myocarditis provided evidence that persistent infection occurs also in mice. Quantitative in-situ hybridization and immunohistochemistry as well as electron microscopic in situ hybridization experiments were performed on ACA/SnJ mice three to thirty days after infection. The pattern of acute infection (days 3-9 p.i.) is characterized by rapid progression of myocardial lesions, an increasing number of inflammatory cells and a high number of infected myocytes. Hallmarks of the persistent pattern (day 15-30 p.i.) are reduced inflammation, reduced numbers of persistently infected cells and a slow progression of myocardial lesions. Infection is primarily restricted to degenerated, atrophic myocytes and to fibroblasts.

Acute Disease↗

Calcium sensitivity and unloaded shortening velocity of hypertrophied and non-hypertrophied skinned human atrial fibres.

The mechanical properties of myocardium of different animals are modified by a chronic increase in haemodynamic load. In this study differences in calcium sensitivity and maximum unloaded shortening velocity of hypertrophic and non-hypertrophic chemically skinned human atrial fibres are characterized. Investigating right atria of 34 patients, possible correlations are studied between preoperative atrial pressure, degree of hypertrophy (estimated from the muscle fibre diameter), calcium responsiveness (pCa50 eliciting half-maximum contraction) and Vmax (unloaded shortening velocity). Hypertrophic fibres from atrial appendages of patients having an increased right atrial pressure (RAP 8.5 +/- 1.6 mm Hg) and suffering from mitral valve disease (stenosis and insufficiency combined) had a fibre diameter of 18.0 +/- 0.9 microns. They also had a higher calcium sensitivity (pCa50 5.65 +/- 0.08) and a lower unloaded shortening velocity (1.7 +/- 0.1 muscle lengths/s) than non-hypertrophic fibres from the appendages of patients with normal right atrial pressure (RAP 3.2 +/- 0.5 mm Hg) and coronary heart disease (CHD: pCa50 5.45 +/- 0.04; Vmax = 3.4 +/- 0.2 muscle lengths/s; fibre diameter 12.8 +/- 0.4 microns). Thus non-hypertrophic fibres from control CHD patients differed significantly (p less than 0.01) from hypertrophied atrial fibres of patients with mitral valve disease and with combined valve disease (MAV, pCa50 = 5.58 +/- 0.05, Vmax 2.0 +/- 0.3 muscle lengths/s, fibre diameter 14.6 +/- 0.9 microns) or aortic valve disease (stenosis combined with insufficiency, fibre diameter 14.8 +/- 1.4 microns, pCa50 5.56 +/- 0.03, Vmax 2.0 +/- 0.24 muscle length/s; RAP 11.0 +/- 2.6 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium↗

1,25(OH)2 vitamin D3 inhibits parathyroid cell proliferation in experimental uremia.

Parathyroid cell proliferation and parathyroid hyperplasia are features of renal secondary hyperparathyroidism. Since parathyroids have recently been recognized as an important target for 1,25(OH)2D3, the effects of administration of variable doses of 1,25(OH)2D3 on ex vivo radiothymidine incorporation in the parathyroid glands, on parathyroid cell mitoses, on parathyroid weight, morphometric indices and on parathyroid protein/DNA ratio were examined in rats with uremia (subtotal nephrectomy; NX) or with calcium deficiency. 3H-thymidine incorporation (3 hr; 37 degrees C; PBS with 10 mmol glucose) was elevated in NX animals, that is, 204 +/- 51 dpm/micrograms DNA versus 96 +/- 28 in controls. In vivo pretreatment with 1,25(OH)2D3, either by intermittent i.p. injection or by osmotic minipump, dose-dependently decreased 3H-thymidine incorporation and parathyroid cell mitoses without affecting morphometric indices of parathyroid cells. Prophylactic administration (i.p.) of 1,25(OH)2D3, starting on the day of nephrectomy, prevented parathyroid hyperplasia (NX + 1,25(OH)2D3 0.84 micrograms tissue/g body wt vs. 1.25 micrograms in untreated NX and 0.54 in ad libitum fed controls), but 10 days of treatment beginning on the 21st day of uremia did not reverse existing hyperplasia (NX + 1,25(OH)2D3 1.5 micrograms/g body wt vs. 1.37 micrograms in untreated NX and 0.56 micrograms in ad libitum fed controls). The inhibitory effect was specific for 1,25(OH)2D3 and not imitated by Dexamethason. However, the effect was not specific for parathyroid hyperplasia of uremia, since similar inhibition of 3H-thymidine incorporation by 1,25(OH)2D3 was also observed in rats on low calcium diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Left ventricular myocardial structure in aortic valve disease before, intermediate, and late after aortic valve replacement.

Left ventricular biplane cineangiography, micromanometry, and endomyocardial biopsies were performed in 27 patients with aortic stenosis (AS) and in 17 patients with aortic insufficiency (AI). Twenty-three patients with AS and 15 with AI were restudied at an intermediate time (18 months after successful valve replacement), and nine patients with AS and six with AI were restudied late (70 and 62 months after surgery). Biopsy samples were evaluated for muscle fiber diameter, percent interstitial fibrosis, and volume fraction of myofibrils. In control biopsy samples obtained from five donor hearts at transplantation, these morphometric variables averaged 21.2 microns, 7.0%, and 57.2%, respectively. After surgery, mass determined by cineangiography decreased from 186 to 115 and 94 g/m2 in patients with AS and from 201 to 131 and 93 g/m2 in patients with AI. At the three studies, muscle fiber diameter was 30.9, 28.0, and 28.7 microns in patients with AS and was 31.4, 27.6, and 26.4 microns in patients with AI. Percent interstitial fibrosis was 18.2, 25.8, and 13.7% in patients with AS and was 20.4, 23.7, and 19.2% in patients with AI. Left ventricular fibrous content decreased from 34.2 to 29.8 and to 12.7 g/m2 in patients with AS and from 42.1 to 28.9 and to 18.9 g/m2 in patients with AI. Volume fraction of myofibrils was 57.7, 56.8, and 49.0% in patients with AS and was 56.8, 56.6 and 48.8% in patients with AI. Thus, the decrease of muscle mass determined by cineangiography at the intermediate time after valve replacement is mediated by regression of myocardial cellular hypertrophy in patients with AS and AI and in addition by a decrease of fibrous content in patients with AI. Late after surgery, left ventricular fibrous content also decreases in patients with AS. This late decrease associated with minor changes of end-diastolic volume may be important for improvement of increased diastolic myocardial stiffness. Even 6-7 years after valve replacement, incomplete regression of structural abnormalities of left ventricular hypertrophy still exists compared with the normal myocardium. The residually increased relative interstitial fibrosis and the small late postoperative decrease of volume fraction of myofibrils, associated with a prosthesis-related slight left ventricular pressure increase, are at the origin of a persistent systolic overload at the myofibrillar level.

Adult↗

Hyperparathyroidism and abnormal calcitriol metabolism in the spontaneously hypertensive rat.

Abnormalities of calcium metabolism and of its two principal regulating hormones, parathyroid hormone and 1,25-dihydroxyvitamin D3 (calcitriol), have been reported in the spontaneously hypertensive rat (SHR). Reports of abnormal calcitriol metabolism in the SHR by several groups have not provided measurements of tissue calcitriol receptors. Similarly, few data are available as to the parathyroid status of the SHR. In the present study, circulating calcitriol levels and intestinal and parathyroid gland calcitriol receptor status were determined in male SHR and in Wistar-Kyoto (WKY) rats. Parathyroid status was investigated by determination of parathyroid gland mass together with tissue micromorphometry and by quantitative histology of bone as a measure of the biological action of parathyroid hormone. Circulating calcitriol levels were reduced in the 11-week-old SHR compared with the WKY rat (165 +/- 23 vs. 194 +/- 28 pmol/l, p less than 0.01, mean +/- SD). Calcitriol-free ratio was diminished and maximal specific binding capacity for calcitriol was increased in the SHR in parathyroid tissue (172 +/- 4.9 vs. 123 +/- 6.6 fmol/mg protein, p less than 0.01) and in intestinal mucosa with no change of receptor affinity. Plasma ionized calcium (1.29 +/- 0.05 vs. 1.45 +/- 0.35 mmol/l, p less than 0.05) and phosphate (1.5 +/- 0.26 vs. 2.4 +/- 0.03 mmol/l, p less than 0.05) were significantly lower in the SHR. Parathyroid gland mass was increased in the SHR (59 +/- 12 vs. 17 +/- 7 micrograms/100 g body wt, p less than 0.001) as a result of hyperplasia and not hypertrophy. Higher osteoclast numbers were observed in SHR bone (27.6 +/- 0.79 vs. 23.9 +/- 0.66 osteoclasts/mm2, p less than 0.01), suggesting increased parathyroid hormone activity. In summary, in the 11-week-old SHR we observed reduced circulating calcitriol levels together with increased tissue calcitriol receptor numbers, increased parathyroid gland mass, and histological evidence of hyperparathyroidism. It is possible that these abnormalities influence the development of hypertension in the SHR.

Animals↗

Reaction patterns of the myocardial interstitium in different models of cardiac hypertrophy--stereological investigations.

Several experimental models of cardiac hypertrophy were investigated in rats: 1. mild hypertrophy induced by physical exercise (18 weeks), 2. mild hypertrophy induced by renovascular hypertension (24 weeks), 3. moderate hypertrophy induced by renovascular hypertension in diabetic and non-diabetic animals (8 weeks), 4. moderate hypertrophy induced by renovascular hypertension in diabetic and non-diabetic animals (12 weeks), 5. moderate hypertrophy induced by thyroxin application (4 weeks), 6. mild hypertrophy in chronic uremia (5/6 nephrectomy, 3 weeks). It is concluded from quantitative stereological parameters of the left ventricular papillary muscles that 1. in hypertrophic hearts myocardial blood flow and oxygen consumption, respectively, rather than the size of muscle fibres determine the capillary supply of the myocardium, 2. interstitial fibrosis occurs in hypertrophy induced by chronic pressure overload and depends on degree and duration of hypertension, 3. the extent of interstitial fibrosis in hypertension is magnified by diabetes mellitus, and 4. the interstitial fibrosis which occurs in chronic uremia is not caused by hypertension.

Animals↗

[Peracute constrictive, idiopathic pericarditis--a case report of an acute life-threatening disease picture].

Generally, idiopathic pericarditis is considered a benign, self-limiting disease. Frequently, the exsudative phase of the disease is followed by a mild form of transitory constriction of the pericardium. The case reported here shows an unusual course of the disease. Shortly after the symptoms of exsudative pericarditis subsided a life-threatening form of pericardial constriction developed within weeks. In case of chronic pericardial constriction perioperative mortality for partial pericardiectomy is not insignificant. This is a result of myocardial damage that is difficult to assess prior to surgery. For that reason a partial pericardiectomy should be attempted as early as possible, even in cases with acute pericardial constriction.

Acute Disease↗

Cardiac damage in autologous bone marrow transplant patients: an autopsy study. Cardiotoxic pretreatment as a major risk factor.

The myocardium was studied histologically at autopsy in seven patients who died 9-85 days (median 22 days) after autologous bone marrow or blood-derived stem-cell transplantation. Clinical investigations including echocardiography suggested normal cardiac function in all patients prior to transplantation. Myeloablation was performed by total body irradiation (1200-1560 cGy) and cyclophosphamide (200 mg/kg). Morphological findings were graded semi-quantitatively and correlated with previous and current therapy. Histological alterations did not correspond to the dosages of myeloablative therapy. However, cardiac failure, the primary cause of death in four patients, was associated with coagulative fiber necroses and contraction band necroses, which may be related to acute cyclophosphamide toxicity. In three of these patients high-dose cardiotoxic pretreatment with anthracyclines and mitoxantrone has been performed beyond the critical cardiotoxic level. High-dose pretreatment was correlated with histological hallmarks of anthracycline heart disease: marked chromatin clumping of myocardial cell nuclei (3/3 patients), occurrence of plurivesicular "adria" cells (3/3 patients), and diffuse interstitial myocardial fibrosis (2/3 patients). Our morphological observations indicate for the first time that pretreatment with anthracyclines and mitoxantrone may enhance cardiotoxicity of myeloablative therapy in bone marrow transplantation.

Adult↗

Myocardial interstitial fibrosis in experimental uremia--implications for cardiac compliance.

Experimental uremia is known to cause cardiac hypertrophy. In the present study we examined the effect of uremia with or without concomitant treatment of hypertension by the converting enzyme Ramipril (125 micrograms/day) on micromorphometric indices of cardiac interstitium at the light microscopical and ultrastructural level. In male SD rats, 21 days of uremia caused an increase of total heart weight (1040 +/- 73 mg wet wt vs. 871 +/- 81 in controls, P less than 0.05) with an increase of both right and left ventricular weight. This was accompanied by reduction of capillary cross-sectional area despite unchanged capillary length. The volume density (cm3/cm3) of cardiomyocytes was unchanged (0.881 +/- 0.01 vs. 0.871 +/- 0.016 in controls), but volume density of interstitial tissue (excluding capillary lumen) was significantly increased (0.042 +/- 0.011 cm3 interstitial tissue/cm3 total heart tissue vs. 0.019 +/- 0.007 in controls). This was associated with signs of activation of interstitial cells, that is, increased volume of interstitial cell nuclei and interstitial cell cytoplasm. Concomitantly, a significant increase of volume density of non-cellular interstitial ground substance was found which was not normalized by antihypertensive treatment using Ramipril. After three months of uremia, electron microscopy showed collagen fiber deposition in the interstitium. Comparable interstitial fibrosis was not observed in hearts of rats with renovascular (one clip-two kidney) hypertension. It is concluded that uremia increases myocardial interstitial ground substance by mechanisms independent of hypertension. The data may be relevant for recent findings of diastolic heart malfunction secondary to impaired compliance in uremic patients.

Angiotensin-Converting Enzyme Inhibitors↗

Effect of chronic ethanol and nicotine consumption on the function and morphology of the salivary glands.

The effect of chronic ethanol and nicotine consumption on the function and the morphology of the salivary glands was studied. In smokers and drinkers there was a significantly reduced flow rate of parotid and submandibular saliva. The protein excretion in both secretions was significantly lowered. A reduced salivary flow rate and a lowered protein output also were found in rats that has been fed a liquid diet containing 36% of total calories as ethanol for 90 days. The parotid glands in these animals showed an impressive fatty degeneration. Additionally there was atrophy of the acinar cells. Rats in which nicotine was administrated orally via the drinking water (100 ml/l) did not show a reduction of salivary flow rate. However, salivary protein excretion was significantly lowered. The parotid glands of these animals showed a swelling of the acinar cells and an increase in the total number of intraacinar secretory granula. Most of these granula were immature light ones containing only small concentrations of glycoprotein, while the number of mature dark granula which contain high concentrations of glycoprotein was drastically reduced. The observed functional and morphological alterations reflect an exhaustion of salivary glands due to a nicotine-mediated chronic secretory stimulation. The results of this study indicate that mainly ethanol and to a lesser extent nicotine after chronic consumption cause severe morphological and functional alterations.

Alcoholism↗

[Follicular ileitis (Golden syndrome). Apropos of 2 cases].

We report on two cases with the seldom diagnosis of papillary lymphoid hyperplasia. In both cases the children were boys in the primary school age. The admission was performed due to rectal bleeding, abdominal colics and vomiting. Intraoperatively we found papillary changes in the terminal ileum. Suggestions to intra-operative management and literature comparison are given in this study.

Child↗

[Unusual course of Candida endocarditis].

Fever, anemia, pulmonary infiltrates and weight loss occurred in a 47-year-old man four weeks after a gastric operation. On echocardiography and cardiac catheterization an atrial myxoma was revealed. In removing the myxoma the tricuspid valve apparatus was destroyed, requiring insertion of a bio-prosthetic valve (Hancock). Signs of infection persisted post-operatively, together with complete A-V block and panuveitis. The Candida IGM titer was markedly increased and histological examination of the thrombus revealed massive fungal infection. Recurrent fever and massive vegetation on the prosthetic valve necessitated removal of the prosthetic valve under antimycotic treatment, which also cleared the pulmonary lesions. The patient's general condition improved. Right-heart failure was controllable by drugs.

Antifungal Agents↗