Evaluation of Cardiovascular Changes in Children with BAVs.

The objectives of this study were to investigate left ventricular (LV) function, aortic dilation, and atherosclerosis in children with mildly deteriorated isolated bicuspid aortic valve (BAV) function using echocardiographic studies and biochemical markers of atherosclerosis and to correlate results with normal children. Biochemical analyses indicating cardiovascular risk of atherosclerosis and vascular changes in the aorta in relation to BAV were performed in 41 children aged 5-15 years old with isolated BAV and in 25 children with tricuspid aortic valves. Evaluations of aortic valve structures and functions; examinations of the LV M-mode and ascending aorta Doppler; and measurements of the LV Tei index (MPI), propagation velocity, ascending aorta at four levels, and carotid intima-media thickness (CIMT) were performed. There were no statistically significant differences in CIMTs, plasma matrix metalloproteinase-9, tissue metalloproteinase inhibitor-1 levels, or other biochemical parameters indicating cardiovascular risk or atherosclerosis between study and control groups. Deterioration of LV function, which could not be seen with M-mode echocardiography, was evident by MPI. MPI values in the study versus control groups were 0.46 ± 0.080 versus 0.40 ± 0.086 (p < 0.05). Diameters of the aorta in the study and control groups were 19.7 ± 4.7 and 17.2 ± 2.8 mm (p < 0.05) at the sinotubular junction level and 20.6 (14.4-40.5) and 18.3 (12.4-24) mm at the ascending aorta level (p < 0.05). Increased aortic valve insufficiency was related to increased aortic diameter. No sign of atherosclerosis was detected in children with BAV. Deterioration of LV function was seen using MPI, and aortic dilation was related to the severity of aortic valve insufficiency.

Effect of melatonin and vitamin C on expression of endothelial NOS in heart of chronic alcoholic rats.

The aim of this study was to investigate the effects of melatonin and vitamin C on expression of endothelial nitric oxide synthase (NOS) in heart tissue of chronic alcoholic rats. Twenty-four adult male Wistar rats weighing 200-250 g were used in this study. Rats were divided into four groups. The first group served as control (n = 6). The second group was treated with ethanol (%7.2) for 28 days (n = 6), which was administered in artificial isocaloric diets. The third group was given ethanol and supplemented with 40 mg/kg vitamin C [intraperitoneally (i.p.)] (n = 6). The fourth group was given ethanol and supplemented with 4 mg/kg melatonin (i.p.) (n = 6). At the end of the experiment, rats were sacrificed and heart tissues were processed for immunohistochemistry analysis to endothelial NOS (eNOS). eNOS immunoreactivity showed heterogeneous distribution in control group. eNOS immunoreactivity was (+) in some myocytes and (++) in some others. Expression of eNOS in alcohol group was heterogeneous like control group but also stronger than that. Immunoreactivity was (+++) in myocytes near the epicardial zone and (++) in myocytes near the endocardium border. In melatonin and vitamin C-treated groups, eNOS immunoreactivity was diffuse and the intensity of reaction was (+++) in subepicardial region. However, eNOS immunoreactivity scores were weaker in these groups when compared with the alcohol group. Our results indicate that alleviation of oxidative stress by antioxidant therapy reduces reactive oxygen species-mediated nitric oxide inactivation.

Influence of maternal nicotine exposure on neonatal rat oxidant-antioxidant system and effect of ascorbic acid supplementation.

There have been a few studies that examined the oxidative stress effects of nicotine during pregnancy and lactation. We aimed to determine the adverse effects of maternal nicotine exposure during pregnancy and lactation on oxidant-antioxidant system, and to determine a protective effect of ascorbic acid (Asc). Gravid rats were assigned into four groups. In Group 1, pregnant rats received 6-mg/kg/day nicotine subcutaneously during pregnancy from 1 to 21 days of gestation and lactation (until postnatal day 21). Group 2 received nicotine and Asc for the same period. In Group 3, the rats received nicotine during lactation. Control pregnant rats (Group 4) received only saline subcutaneously. Serum malondialdehyde (MDA), myeloperoxidase (MPO), and superoxide dismutase (SOD) levels were determined at 21 days of age. Nicotine exposure decreased birth weight and pregnancy weight gain. MDA values of the rat pups exposed to nicotine in both Groups 1 and 2 were higher than those of control and Group 3. SOD and MPO values of the groups were similar. Mean birth weight and serum MDA levels of Groups 1 and 2 were similar. Nicotine exposure via placental transfer increases oxidative stress as manifested by an increase in MDA level. Asc supplementation does not prevent the adverse effects of maternal nicotine exposure.

The effect of melatonin on plasma oxidant-antioxidant skeletal muscle reperfusion injury in rats.

We investigated the effects of melatonin administration on skeletal muscle ischaemia-reperfusion injury (IRI) by assessing plasma malondialdehyde (MDA), superoxide dismutase (SOD), total glutathione (GSSH), glutathione peroxidase (GPX) and myeloperoxidase (MPO) concentrations. Male Sprague-Dawley rats (n = 32) were randomized into four groups: group 1 served as time controls; group 2 were the test animals; group 3 received melatonin (30 mg/kg) intraperitoneally prior to the induction of ischaemia; and group 4 received melatonin (30 mg/kg) intraperitoneally prior to the reperfusion period. Administration of melatonin prior to reperfusion significantly decreased the elevated MDA concentration caused by IRI, and significantly elevated GSSH concentrations, which had been reduced by IRI. Ischaemia-reperfusion injury significantly increased activities of GPX, SOD and MPO, and melatonin administration reversed this effect. In conclusion, a pharmacological dose of melatonin showed significant protective effects against IRI by decreasing lipid peroxidation, MPO, SOD and GPX enzyme activities and regulating glutathione content.

Is pentoxifylline therapy effective for the treatment of acute rheumatic carditis? A pilot study.

OBJECTIVE: The aim of the present study was to determine whether pentoxifylline has a beneficial effect on the treatment of rheumatic carditis. METHODS: A total of 33 children between the ages 6 and 16 were studied in two groups. The first group (5 boys, 10 girls, mean age: 12.2 +/- 2.9 years) was treated with steroid plus pentoxifylline and the second group (6 boys, 12 girls, mean age; 11.6 +/- 2.8 years) was treated with steroid only for 3-6 weeks until the acute-phase reactants became normal. At admission and on the 7th, 30th, and 90th days of the treatment, laboratory studies including white blood cell count, erythrocyte sedimentation rate, C-reactive protein, throat culture and cytokines (interleukin-1alpha, tumour necrosis factor-alpha) were performed. Cardiac evaluation with chest X-ray, electrocardiography and echocardiography was performed in all patients. In the control group (12 boys, 3 girls, mean age; 10.7 +/- 3.2 years) all parameters were evaluated once only. RESULTS: In both groups, the similar white blood cell count was significantly decreased on the 90th day, and there was no significant difference between the two groups. C-reactive protein, erythrocyte sedimentation rate and interleukin-1alpha were significantly decreased on the 30th and 90th days. In the first group (treated with steroid plus pentoxifylline), the cardiothoracic index was significantly greater at the beginning of the therapy. In the first group, tumour necrosis factor-alpha became normal on the 30th day and in the second group, tumour necrosis factor-alpha became normal on the 7th day of therapy. For all parameters, there was no significant difference between the two groups with respect to the type of therapy used. CONCLUSION: The present study showed that pentoxifylline plus steroid treatment has no beneficial effects on the treatment of acute rheumatic carditis when compared with steroid alone.

Continuous versus cyclical transdermal oestrogen replacement therapy in postmenopausal women: effects on lipoprotein(a) and nitric oxide levels.

The purpose of our study was to compare the effects of cyclical versus continuous transdermal oestrogen replacement therapy on lipoprotein (a) (Lp(a)) and nitric oxide levels. The patients were randomly assigned into two groups. The first group received transdermal 17-beta oestradiol 50 microg/day for 21 days and the second group the same treatment on a continuous basis. Medroxyprogesterone acetate (10 mg/day orally) was added between the 14th and 25th days to each group. Lipoprotein (a) and nitric oxide levels were measured before the study and after six months. These values were compared using the Wilcoxon rank test within the groups and the unpaired t-test between the groups. Lipoprotein (a) levels decreased significantly in each group at the sixth month (p < 0.05). When compared between the groups, the decrease of lipoprotein (a) levels in the second group was more prominent at the sixth month (p < 0.05). Nitric oxide levels increased in each group after six months (p < 0.05). No difference in nitric oxide levels was observed between the groups before and after the therapy (p > 0.05). Continuous transdermal estradiol had a better effect on lipoprotein (a) levels than cyclical therapy The seven day pause in the 21-day administration did not affect nitric oxide levels negatively after six months.

Nitric oxide level in children with pulmonary hypertension.

Nitric oxide is a gas and free radical, which modulates pulmonary and vascular tone. Pulmonary vascular endothelial cell produce the nitric oxide. To define the relation between nitric oxide and hemodynamic parameters in children with pulmonary hypertension, we measured the nitric oxide concentrations of the right atrium, right ventricle, pulmonary artery, left ventricle and aorta in 40 patients during cardiac catheterizations. Patients were divided into two groups according to their pulmonary arterial pressure. In group I, the mean pulmonary arterial pressure was higher than 25 mmHg and in group II, lower than 25 mmHg. Pulmonary nitric oxide level in group I was significantly lower than group II (P < 0.05). The right ventricle and mean pulmonary arterial pressures, pulmonary vascular resistance and pulmonary flow/systemic flow of the patients in group I were significantly higher than those of group II (P < 0.05). In conclusion, we found low nitric oxide levels in patients with pulmonary hypertension and congenital heart defects.

Thyroid function tests in the newborn infants of preeclamptic women.

The purpose of this study was to identify possible changes in thyroid functions in newborn infants of preeclamptic women. Fifteen neonates (nine boys and six girls) of preeclamptic women and 17 healthy neonates (nine boys and eight girls) for the control group were included in the study. Serum thyroid-stimulating hormone (TSH), total triiodothyronine (TT3) and total thyroxine (TT4) levels and thyroid gland volumes were determined in both groups. Serum TSH and TT4 levels were not statistically different between the two groups. However, serum TT3 level was 79.22 +/- 40.19 ng/dl in the study group and 40.00 +/- 15.99 ng/dl in control subjects (p < 0.01). The mean right, left and total thyroid volumes were 1.3 +/- 1.2 ml, 1.2 +/- 1.1 ml and 2.4 +/- 2.3 ml in the study group and 0.6 +/- 0.2 ml, 0.6 +/- 0.2 ml, and 1.1 +/- 0.4 ml in the control group, respectively (p < 0.05). The mean thyroid volume/body weight was 0.9 +/- 0.09 ml/kg in the study group and 0.3 +/- 0.06 ml/kg in the control group (p < 0.05). In conclusion, we would like to stress that preeclampsia might be a cause of fetal and neonatal thyroid enlargement and elevated serum TT3 level.

Diagnostic value of troponin T in neonates of mild pre-eclamptic mothers.

The measurement of myocardial damage by newer, highly specific markers of myocardial damage is now possible, including cardiac structural proteins such as troponin T (TnT). In neonates of pre-eclamptic mothers, it identifies minor myocardial damage missed by other biochemical markers. The present study was designed to determine the diagnostic value of TnT concentrations in neonates of pre-eclamptic mothers. Fifteen neonates of pre-eclamptic mothers were studied (9 boys and 6 girls), and 17 healthy full-term neonates (9 boys and 8 girls) were selected as a control group. The serum TnT concentration in neonates of pre-eclamptic mothers (0.70 ng/ml) was significantly higher than that in the control group (0.10 ng/ml). In an echocardiographic study, the mean mitral peak velocity at an atrial contraction (A) value of 39 cm/s in neonates of pre-eclamptic mothers was significantly lower than that in the control group (53 cm/s), and the mean mitral peak velocity of early diastole to peak velocity of the atrial contraction (E/A) value (1.75) in neonates of pre-eclamptic mothers was significantly higher than that in the control subjects (1.23). In conclusion, our study demonstrated high levels of cardiac TnT, lower mitral A values and high mitral E/A values in neonates of pre-eclamptic mothers, presumably associated with mild myocardial damage in the neonates of pre-eclamptic mothers.

Hyaluronic acid plus heparin for improved efficacy in prevention of adhesion formation in rat uterine horn model.

OBJECTIVE: To determine the effectiveness of hyaluronic acid (HA) and heparin [unfractioned heparin (UH) or low molecular weight heparin (LMWH)] combination in reducing adhesion formation in a rat uterine horn model. STUDY DESIGN: Prospective, randomized, comparative study in a rat model was done in Surgical Research Laboratory, Erciyes University. A standard lesion was created by unipolar electrocautery in 120 uterine horns of total 60 female Wistar-Albino rats. Animals were then randomly assigned into four groups, each consisting of 15 animals: (1) control, no adjuvant given; (2) HA, 1 ml of 0.4% solution given onto each horn preoperatively; (3) HA, 1 ml of 0.4% solution given preoperatively plus 1 ml of UH given postoperatively; (4) HA, 1 ml of 0.4% solution given before injury plus 1 ml of LMWH given after injury. A second-look laparotomy was performed two weeks after surgery. The number of horns with adhesion was determined and a scoring system applied. RESULT(S): The number of horns without adhesion formation was significantly higher in HA plus UH (P<0.05) and HA plus LMWH (P<0.01) groups compared to control group. The extent, severity and total scores of adhesion formation were also found to be significantly reduced in other groups when compared to control group. Combination of HA plus UH and HA plus LMWH significantly reduced all adhesion scores compared to HA alone. But a direct comparison of the ability of HA plus UH versus HA plus LMWH in reducing adhesion scores in the rat uterine horn yielded an insignificant difference. CONCLUSION: Administration of HA before injury followed by UH or LMWH given after injury has been documented to improve the efficacy of HA alone in reducing adhesion formation.

Carnitine levels in patients with chronic rheumatic heart disease.

OBJECTIVE: Carnitine, a small aminoacid derivative plays a major role in fatty acid oxidation. Myocardial carnitine deficiency may cause malfunction of the heart. Rheumatic valvular heart disease can be associated with myocardial dysfunction. We have investigated myocardial and plasma-free carnitine levels in patients with chronic rheumatic heart disease. MATERIAL AND METHODS: Eleven patients with chronic rheumatic heart disease requiring valve replacement were selected for study. Ten patients with no cardiac failure, myocardial wall motion abnormalities and myocardial infarction and for whom coronary bypass surgery was planned were selected as the control group. Carnitine levels of myocardial tissue obtained from the right atrium and plasma during the operation were evaluated using spectrophotometric method. Myocardial-free carnitine levels expressed as mumol/g (dry weight) were determined according to Ceberblad and Lindstedt technique. RESULTS: Myocardial-free carnitine levels in patients were found to be 0.72 +/- 0.37 mumol/g (dry weight) in comparison with 1.44 +/- 1.03 mumol/g (dry weight) in the control group. Myocardial-free carnitine levels in patients were statistically decreased when compared to control group. Plasma-free carnitine levels in patients were 80.91 +/- 28.22 mumol/L and 89.52 +/- 48.21 mumol/L in the control group, respectively. There was no significant difference between plasma-free carnitine levels of the groups. CONCLUSION: In our study, myocardial-free carnitine levels were decreased while plasma-free carnitine levels were normal in patient with chronic rheumatic heart disease.

Linkage between research sponsorship and patented eye-care technology.

PURPOSE: To examine the linkage between the funding of ophthalmologic and related biomedical research and the development of patented eye-care technology using data on patents granted and the scientific literature cited by those patents. METHODS: The United States patents granted during the 20-year period from 1975 through 1994 were screened using patent office classifications and key words to identify all eye-care-related patents. Each patent's nonpatent references (references to literature other than previously granted patents) were examined, and those references to scientific papers then were reviewed to determine the authors' institutions and acknowledged funding sources. RESULTS: Major findings include the following: (1) Eye technology innovation has grown steadily, with a threefold increase in number of patents granted from 224 in 1975 to 662 in 1994. (2) The cited scientific base that supports this technology has grown even more rapidly, with a sixfold increase in the average number of nonpatent references, from fewer than 0.5 per patent in 1975 to more than 3.0 in 1994; as a result, the total number of nonpatent references has increased by a factor of 20, from 100 in 1975 to 2000 in 1994. (3) The National Eye Institute is the leading single institution in providing support for this research: 31% of all eye-care patents with science references cite papers that contain at least one acknowledgment to National Eye Institute (NEI) support; and when NEI is combined with the rest of the National Institutes of Health (NIH), 41% of the patents with science references are linked to NIH-funded research. (4) Patent science dependence, as measured by science references, is greatest for technologies related to medical treatment, surgical instruments, and intraocular lenses; moderate for diagnostic instruments and contact lens; and least for eyeglasses. CONCLUSIONS: The NIH and other sponsored vision research is of direct and increasing relevance to the growing number of US patented eye-care technologies.

Anticardiolipin antibodies in acute rheumatic fever and chronic rheumatic heart disease: is there a significant association?

OBJECTIVE: The incidence and significance of IgG and IgM anticardiolipin antibodies (aCLa) in patients with acute rheumatic fever (ARF), chronic rheumatic heart disease (CRHD) and streptococcal pharyngitis have been investigated in order to determine whether these antibodies play an important role in the pathogenesis and if they are markers that can be used to confirm disease activity. METHODS: An enzyme-linked immunosorbent assay was used to measure the IgG and IgM aCLa levels. aCLa levels of patients were considered positive if they were greater than 3.0 standard deviations above the mean for healthy children. RESULTS: No significant difference in aCLa levels was found between patients with rheumatic fever or streptococcal pharyngitis and healthy controls, and aCLa concentrations did not correlate with the acute phase reactant levels. CONCLUSIONS: aCLa in patients with ARF and CRHD do not appear to be markers of disease activity, and our data suggest that aCLa do not play an important role in the pathogenesis of rheumatic fever.

The growth of Japanese science and technology.

Several measures are used to delineate the remarkable growth in the Japanese technological position over the last decade. The share of U.S. patents issued to Japanese inventors has been rising at 1 percent per year. These patents are the most frequently cited patents in the U.S. system. By 1984, Japanese inventors obtained more U.S. patents than inventors in the United Kingdom, France, and West Germany combined, and the gap has been widening ever since. As measured by publications, the Japanese scientific position is more modest, with a 0.5 percent rise per year in papers and with barely average citation performance. These indicators characterize Japan as a technological powerhouse, with highly innovative technology, and an expanding but far less powerful scientific position.

Characterization of the research papers of U.S. medical schools.

An investigation of the relationship between National Institutes of Health (NIH) funding and the quantity and nature of biomedical publications is reported for 120 U.S. medical school complexes. A correlation of 0.95 was found between the amount of NIH funds received and the number of biomedical publications from the medical schools. Medical school ranks based on bibliometric measures were found to correlate at the 0.80-0.90 level with ranks based on peer assessments of the schools. The characteristics of the medical school papers varied with the type of school. The average citation influence per paper increased with the publication size of the schools. This was true even when factors such as public versus private control, geographic region, average research level (from basic to clinical), and subject emphasis were controlled. The positive relationship between number of papers from a school and its citation influence holds within individual research levels and within subfields.

The intramural role of the NIH as a biomedical research institute.

An investigation of the NIH role as a biomedical research institute is reported, based on counts of articles, notes, and reviews in 1,000 biomedical journals covered by the Science Citation Index from 1973 to 1975. Investigators at the NIH produce more biomedical research papers per year than any other group in the U.S., accounting for approximately 3.4% of all U.S. biomedical research papers. The NIH papers show a strong emphasis at research Level 3, clinical investigation, which is the most basic and scientific level of research focused directly on disease in man. On a clincial-to-basic science continuum the NIH emphasis on clinical laboratory research represents a position that is midway between the more clinical research being performed at medical schools and the more basic research being performed in graduate departments of universities. The papers of the NIH intramural scientists appear in highly influential journals. In the mid 1970's, the rate of NIH intramural publication is particularly high in the subfields of biomedicine that are most closely related to research on cancer.

Characterization of the alcohol research literature.

Bibliometric analyses of the inernational, rapidly increasing and widely dispersed alcohol research literature show three major components: biomedical, biosocial, and psychosocial research; the biomedical component predominates.

The extramural role of the NIH as a research support agency.

An investigation of the role of the National Institutes of Health (NIH) biomedical research activity is reported, based on counts of research support acknowledgments in 264 biomedical journals covered by the Science Citation Index in 1973. Overall, NIH research support was acknowledged in approximately 25% of the clinical papers and almost 50% of the biomedical research papers. At all levels, NIH support appears to be twice as large as that of all other federal agencies combined. Each of the major institutes of NIH shows a dual pattern of research support, with a specific peak in the appropriate clinical areas and a second peak of supported research in an area of basic research activity.

The international distribution of biomedical publications.

An investigation of the U.S. role in international biomedical publication is reported, based on counts of articles, notes and reviews in 975 biomedical journals covered by the Science Citation Index in 1973. U.S. scientists authored 42% of these biomedical papers, the U.K. 10%, West Germany and France 7% and 6%, and the U.S.S.R. 4%, a sharp change from earlier in this century when Germany and France had much more prominent roles. Overall, 94% of the papers are from OECD and Eastern European countries; only 4% are from underdeveloped regions. U.S. and U.K. papers are far more heavily cited than are papers from other countries; U.S.S.R. papers are particularly under-cited. Biomedical publication rates are shown to be highly correlated (r = 0.9) with both national wealth (GNP) and national affluence (GNP/capita). National publication rates also correlate with Nobel Prize recipients. - Frame, J. D., and F. Narin. The international distribution of biomedical publications.