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Biomedical subjects

J Marek

Publications and source records attributed to J Marek.

At least 109 records · Page 6Linked to original sources

Heart disease in acromegaly.

Evidence has accumulated regarding acromegalic heart muscle disease which existence now appears to be unequivocal. We took an advantage of a large group of acromegalic patients being followed-up at our institution for a long time and have studied pattern, nature and reversibility of acromegalic heart disease. Its major manifestation is cardiac hypertrophy expressed especially as left ventricular hypertrophy. The cardiac hypertrophy is slowly reversible after normalization of plasma growth hormone levels due to successful treatment. This we have first suggested on the basis of a retrospective analysis of clinical and echocardiographic data in 78 patients with acromegaly and subsequently confirmed by a 10-year prospective follow-up of the original patient cohort. We have also showed that effective treatment of acromegaly with a new slow release somatostatine analogue lanreotide leads to regression of cardiac hypertrophy.

Acromegaly↗

Interbilayer cluster-cluster interaction in multilamellar vesicles: thermodynamic approach.

A simple thermodynamic model of the main transition in pure lipid bilayers is presented. The basic relations for cooperativity, aggregation degree and fractional number of molecules are derived. The experimental heat capacity measurements of uni- and multilamellar phospholipid vesicles are analysed within the context of this model, and the transition characteristics are obtained. It is demonstrated that they differ from each other, and these differences are discussed according to the system configuration. The derived cluster configuration entropy supports the idea of strong interbilayer cluster-cluster cooperation.

Entropy↗

A calbindin D9k mutant with reduced calcium affinity and enhanced cooperativity. Metal ion binding, stability, and structural studies.

In the native calcium-binding protein calbindin D9k (M(r) 8.700; 75aa; 2 EF-hands), the backbone carbonyl oxygen of Glu60 coordinates the Ca2+ ion in the C-terminal site (site II). The carboxylate group of the same residue forms a hydrogen bond to a water molecule that constitutes a Ca2+ ligand in the N-terminal site (site I). The mutant E60D, with the charge-conserving substitution Glu60-->Asp, has been prepared to study the role of Glu60 in subjoining the two Ca(2+)-binding sites and its role in the cooperative Ca2+ binding. Ca(2+)-binding studies of the mutant show that the overall affinity for calcium has decreased by a factor of 38 in comparison with wild-type calbindin D9k. The largest reduction is seen in the first macroscopic binding step. The Ca2+ affinities for both sites in the protein are reduced to a similar extent. In contrast, the mutation leads to a large increase in the cooperativity of calcium binding. Differential scanning calorimetry has been used to determine the thermal stability which is almost as high as in the wild-type protein. Cadmium binding has been assessed with 1H and 113Cd NMR. X-ray crystallographic studies of the E60D mutant in its calcium-bound form show very small structural changes relative to the wild-type protein. Almost all differences are within the error limits of the method. The largest crystallographic effects are seen in the crystal packing. Two E60D molecules with slightly different structure are found in the asymmetric unit in contrast to the single molecule in the wild-type crystal.(ABSTRACT TRUNCATED AT 250 WORDS)

Aspartic Acid↗

[Somatomedin-type activity of Biomin H].

In the biopreparation Biomin H, which is prepared from eggs, somatomedin activity was tested. The activity was not substantially affected by thermal processing at 36 degrees C-130 degrees C; the highest concentration of somatomedin activity was at a concentration of 30 mg Biomin H in the reaction mixture. The authors discuss the necessity to analyze the nature of somatomedin activity by detection of selected known growth factor (IGF-I, IGF-II, TGF-beta).

Animals↗

Long-term treatment of acromegaly with the slow-release somatostatin analogue lanreotide.

Thirteen patients with active acromegaly despite previous surgery were treated with 30 mg lanreotide im twice a month for 9 months. In 10 subjects the treatment continued to 19 months. GH serum levels of all patients decreased significantly from an initial value of 32.0 (29.4) micrograms/l [median (standard error of median)] to 10.0 (3.6) and 19.1 (5.7) after 3 and 9 months of treatment, respectively. In the 10 patients with the treatment longer than one year the decrease in GH was from 46.8 (29.4) micrograms/l to 12.5 (5.0) and 16.1 (5.3) after 13 and 19 months, respectively. IGF-I serum levels decreased significantly from 1193 (73) micrograms/l to 782 (99) and 621 (103) after 3 and 9 months, respectively, and were normalized in 3 patients. In the 10 patients treated for longer than one year, levels decreased significantly from 1318 (74) micrograms/l to 653 (170) and 742 (180) after 13 and 19 months, respectively. IGF BP-3 levels were reduced to the normal range in 6 patients and decreased from 8.7 (1.5) mg/l to 6.4 (0.8) and to 5.4 (1.0) after 3 and 9 months, respectively. In the patients with the 19 months treatment the decrease was from 9.3 (1.6 mg/l to 3.9 (0.9) and 4.8 (0.9) after 13 and 19 months, respectively. The IGF BP-3 to IFG I ratio increased in 7 patients. This elevation significantly correlated with the decrease in bioassayable somatomedin. Prolactin serum levels fell in all patients with increased prolactin secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗

[Total cavopulmonary anastomosis in the surgical treatment of congenital heart defects with a functional single ventricle].

Total cavopulmonary connection (TCPC) allows surgical treatment of patients with complex univentricular heart disease. Between 1991 and 1993 this operation was performed in 15 cyanotic children with complex heart defects. Age range was 3.5-14 (median 8.3) years. In 5 children with increased operative risk a calibrated interatrial fenestration was created intraoperatively to allow systemic venous decompression. Three patients (20%) died. In remaining 12 patients a significant increase in arterial oxygen saturation and decrease of polycythemia was encountered. All patients remain in a good clinical condition 1-25 months after operation. Noninvasive investigation including echocardiography confirmed good function of the heart.

Adolescent↗

Long-term echocardiographic follow-up of acromegalic heart disease.

Heart muscle disease in acromegaly manifests usually as cardiac hypertrophy. Based on a retrospective analysis, it was suggested that cardiac hypertrophy is slowly reversible after normalization of plasma growth hormone levels. The reversibility of acromegalic heart muscle disease during and after treatment of acromegaly was studied prospectively. A cohort of 78 patients was examined echocardiographically in 1981, and 38 survivors of this group were reexamined 10 years later. Patients were classified according to original hormonal activity in 1981, and change in hormonal activity during follow-up into the following 4 groups: group I--hormonally inactive for entire follow-up (n = 10); group II--hormonally active for entire follow-up (n = 11); group III--initially hormonally inactive with later resurgence (n = 6); and group IV--initially hormonally active with later normalization of growth hormone levels (n = 11). No significant echocardiographic changes occurred during follow-up in group I. Left ventricular posterior wall and septal diastolic thickness, and left ventricular mass increased significantly (all p < 0.05) in group II. Left ventricular posterior wall thickness, mass and diastolic volume increased significantly (p < 0.05, < 0.01 and < 0.001, respectively) in group III. On the contrary, there were significant decreases in left ventricular mass, and both diastolic and systolic left ventricular volumes (p < 0.01, < 0.05 and < 0.05, respectively) in group IV. It is concluded that both hypertrophy and dilatation of the left ventricle in acromegaly are slowly reversible after successful treatment. On the contrary, continuing or relapsed hyperproduction of growth hormone causes further deterioration of acromegalic heart disease.

Acromegaly↗

[Ratios of surface markers (CD) on peripheral blood lymphocytes in the working-age Czech population].

The authors present an account of lymphocytic CD signs in adult men (mean age 34 years) and women (mean age 29 years) of the Czech population. Mean values and standard deviations (s.d.) are given for men/women: CD2: 79.6% (6.6)/86.4% (5.3), CD 3: 71.5% (7.4)/81.1% (7.4), CD4: 42.4% (6.3)/48.4% (8.5), %CD45RA+ v CD4+: 41.7% (14.1)/47.3% (13.9), CD5: 69.5% (7.0)/76.00% (6.5), CD8: 33.9% (9.3)/29.8% (6.8). CD10: 1.9% (1.3)/2.5% (1.6), CD11c: 8.3% (4.7)/10.9% (4.4), CD16: 8.3% (3.8)/4.4% (2.3), CD19: 11.5% (4.0)/8.8% (3.2), CD20: 14.7% (4.7)/11.3%, CD22: 10.6% (9.2)/8.9% (3.5), CD45RA: 56.7% (7.6)/61.7% (7.8), CD56: 15.1% (5.7)/16.0% (6.5), CD57: 13.7% (7.9)/8.5% (6.3), CD71: 1.9% (1.3)/3.5% (1.7) a HLA DR: 22.1% (6.4)/19.6% (7.1), DP: 16.3% (7.1)/13.5% (4.9), DQ: 10.9% (5.8)/7.2% (3.2), BJK: 2.6% (2.2)/2.1% (1.1), BJL: 1.8% (1.2)/2.1% (1.3), ratio CD4/CD8 1.35 (0.49)/1.75 (0.69). The examination were made on an apparatus FACScan (Becton Dickinson).

Adult↗

[The effect of creatine phosphate (Neoton) in acute myocardial infarct (a prospective multicenter pilot study].

The authors investigated in a group of 106 patients with a first myocardial infarction treated by thrombolysis the effect of i.v. administration of creatine phosphate (a new drug with cardioprotective action--Neoton Alfa Schiapparelli Wassermann Co). In the course of treatment electrocardiographic changes were recorded and the presence of arrhythmias examined by the Holter technique. The Neoton group displayed a statistically insignificant but nevertheless obvious trend of electrocardiographically less serious forms of infarction and a lower incidence of infarctions, as compared with the control group.

Female↗

[Isolated hematuria in adolescents and adults. The value of renal biopsy].

In 103 subjects with asymptomatic isolated haematuria (persisting for more than 6 months in the absence of proteinuria, bacteriuria, impaired haemocoagulation or urological disease) renal biopsy was performed. The mean age of the patients was 25.2 years, range 14-58 years. In 94% glomerular changes were detected--most frequently minimal glomerular lesions (67%) and proliferative mesangial glomerulonephritis (15%). Focal segmental proliferative glomerulonephritis was rare (4%). Immunofluorescent examination revealed IgA nephropathy in 40% (all cases of diffuse and focally segmental proliferative glomerulonephritis and one quarter of minimal glomerular lesions). Changes of tubules and interstitium were recorded in 26%, with the exception of one patient they were always associated with glomerular affection. From the investigation ensues that the predominating cause of isolated asymptomatic haematuria, not clarified by non-invasive examination, is usually not serious and is an affection frequently associated with tubulointerstitial changes. As many as 40% of isolated cases of haematuria may be the manifestation of IgA nephropathy. The deposition of IgA is more frequently associated with a more advanced grade of glomerular affection. Indication of diagnostic renal biopsy in isolated haematuria remains individual.

Adolescent↗

Effective peritoneal therapy of acute pancreatitis in the rat with glutaryl-trialanin-ethylamide: a novel inhibitor of pancreatic elastase.

The six hour peritoneal lavage with glutaryl-trialanin-ethylamide, a low molecular competitive inhibitor of pancreatic elastase (IC50-8 mumol/l), effectively suppresses the evolution of taurocholate induced acute pancreatitis in the rat. The lavage alone is followed by a marked decrease of fat necrosis and amylase and lipase activity in serum. The area of pancreatic haemorrhage was significantly reduced only after the lavage solution was supplemented with Glt-Ala3-NHEt. The effect was not enhanced by a bolus injection of the inhibitor before starting the lavage. The combination of Glt-Ala3-NHEt with aprotinin or nafamstate mesilate produced only marginal greater benefit. The effect of Glt-Ala3-NHEt on pancreatic haemorrhage is time and dose related even with delayed onset of the lavage. Animals treated with peritoneal lavage without Get-Ala3-NHEt lived longer than controls (p less than 0.05), but by 60 hours the survival rate of both groups was almost the same (76 v 74%). All animals lavaged with Glt-Ala3-NHEt survived 120 hours and the difference in the survival rate between this and both remaining groups was significant (100% v 76% v 74% - p less than 0.05). The results were considered favourable and preliminary clinical trials of Glt-Ala3-NHEt in subjects with acute pancreatitis justified.

Amylases↗

Heart in pituitary diseases.

Of hormones secreted by the pituitary, a direct effect on cardiac metabolism and function is exerted only by growth hormone (GH). Its chronic overproduction in adulthood leads to acromegaly. The main cardiovascular manifestations of acromegaly are hypertension and cardiac hypertrophy. The paper summarizes the results of clinical research into the "acromegalic heart" in an internationally unique group of 78 patients with acromegaly on long-term follow-up. Both clinical findings and experimental data available in the literature indicate that cardiac hypertrophy is due to a direct effect of GH on the myocardium. Hypertension occurs in 50% of patients, has the nature of volume hypertension and exerts only an additive effect on the development of left ventricular hypertrophy. Once GH overproduction has been eliminated, cardiac hypertrophy and hypertension can be reversed to a certain stage, a finding highlighting the necessity of instituting treatment of acromegaly as early and as vigorous as possible.

Acromegaly↗

[The significance of ovarian and testicular steroids in lipid metabolism and atherogenesis].

Epidemiological, experimental and clinical data verify that the risk of atherosclerotic cardiovascular disease is increased by a long-term estrogen deficiency. This is, among other beneficial effects of estrogens on arteries, caused by alteration of lipid and lipoprotein metabolism [e.g. decrease in total cholesterol, LDL-cholesterol and lipoprotein (a) and decrease in HDL2 cholesterol in serum and decrease in the accumulation of cholesterol in the arterial wall]. The beneficial cardioprotective effects of estrogens are attenuated by estrogen overdosing (causing hypertriglyceridemia), the use of synthetic instead of natural estrogen products (increased incidence of adversary effects) and especially by use of inappropriate progestins. The effect of progestins may be minimized by selecting a lower dose of a more metabolically inert products (especially progestins of the third generation). Mild to moderate hypercholesterolemia may improve with oral estrogen, and this strategy may be used as an adjunct for treatment. The replacement treatment of menopause is not yet widespread in Czechoslovakia. The new forms of treatment, not causing menstrual bleeding (continual medication, tamoxifen) may achieve more interest in the therapy. Hypogonadal men are known to have a more advanced development of atherosclerosis. The appropriate replacement is done by administration of such testosterone derivatives which enable the conversion to estrogens.

Androgens↗

[Normal values of 2-dimensional echocardiographic parameters in children].

The authors examined by two-dimensional echocardiography a group of 186 healthy children from birth to the age of 18 years. From the assembled records they measured the following: the inner diameter of the inferior vena cava, the diameter of the abdominal aorta, the area of the right and left atrium at the end of systole, the width of the ring of the tricuspid and mitral valve at the end of diastole, the area of the right and left ventricle at the end of systole and its circumference, the width of the annulus of the pulmonary artery, the diameter of the aortic arch, the diameter of the right and left branch of the pulmonary artery. The systolic function of the left ventricle and the curvature of the ventricular septum during systole was calculated from the assessed parameters of the left ventricle. By means of a computer the regression equations of the relation of assessed echocardiographic parameters and body weight and body surface were calculated as well as their mean values +/- 2 standard deviations for the given body weight and body surface which are considered normal for the child population.

Adolescent↗

Evidence for immunomodulatory properties of prolactin in selected in vitro and in vivo situations.

The relationship between neuroendocrine regulation and the immune system has recently become the subject of intense investigations. The pituitary secretes both immunostimulatory (growth hormone and prolactin) and immunosuppressive (ACTH) hormones, and is thus involved in the control of immune functions. The present work was aimed at the study of the immunoregulatory properties of prolactin in selected in vitro and in vivo model situations. Prolactin was found to enhance recovery of the receptor for sheep red blood cells (in vitro). Compared with control cells, incubation with prolactin and/or prolactin containing sera significantly enhanced the capacity of trypsin treated lymphocytes from the peripheral blood of healthy volunteers to form E-rosettes. Chlorpromazine stimulated prolactin release in males, and lactation stimulated prolactin release in females raised the number of large granular lymphocytes in peripheral circulation. Sera containing elevated prolactin levels stimulated the metabolic activity of peripheral neutrophilic leukocytes. These results suggest that prolactin may stimulate selective functions of cellular immunity, and that it is involved in interactions between the nervous, the hormonal and the immune systems.

Adult↗

[Blood somatomedin levels in neonates with congenital hypothyroidism and phenylketonuria].

A biological method was employed for assessing the somatomedin activity (SM)-IGF I-somatomedin C: 1) in 13 10 to 23-day old children with congenital hypothyroidism (CH) before starting substitution therapy with L-thyroxine and after one month lasting therapy. SM levels were significantly lower prior to the onset of therapy than in a control group (for p less than 0.01 on 1% level). The SM levels in treated children did not differ from controls. 2) 16 children with classic phenylketonuria (PKU) were also examined of the age of 12-23 days before starting dietary treatment with restricted phenylalanine (Phe). When compared with a control group SM levels were significantly lower in the PKU group (p = 0.01 on 5% level). When stable serum Phe concentrations had been obtained, following restricted Phe intake, SM levels no longer differed from the control. However statistical correlation of Phe and SM levels was not attained.

Congenital Hypothyroidism↗

[5 years' ambulatory care experience with the clonidine stimulation test].

The authors give an account of their five-year experience with the clonidine test of growth hormone (GH) secretion. They used the test in 231 children examined on account of small stature. They administered 0.1 mg clonidine/m2 body surface by the oral route; blood specimens were collected at time 0, 60 and 90 minutes after administration of the preparation. They recorded 174 positive GH responses (75%), 30 negative responses (13%) and 27 marginal responses (12%). Falsely negative tests were recorded in a maximum of 10%. The test is a very useful screening examination of GH secretion due to the useful information it provides, and because it is simple and safe even when used in ambulatory practice.

Child↗