[Implantable cardioverter defibrillator. New therapeutic option to malignant ventricular arrhythmias].
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Biomedical subjects
Publications and source records attributed to R Costa.
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The authors analyse the short-term and medium-term effects of iloprost prostanoid derivate on hemostatic status in a group of patients with obliterating vascular disease of the lower limbs. The study included 10 patients (6 males, 4 females; aged 52 + 5 years old) suffering from Fontaine's stage 3 obstructive arterial disease. After a 10-hour fast each patient received a 6-hour iv infusion of iloprost at a dose of 2 ng/kg/min (approx 50 gamma) a venous blood sample was collected before and after infusion. The test was repeated using the same method after 4 weeks of treatment with the same dose of the drug. The following parameters were analysed in serum: fibrinogen (F) (IL coagulometric method), Factor VII (F VII) (IL coagulometric method), antithrombin II (AT III) (IL chromogenic method), protein C (PC) II coagulometric method) and protein S (PS) (IL coagulometric method). After the first infusion a significant increase was observed in AT III (p > 0.05), whereas other indices showed no significant variations. After treatment for 4 weeks AT III was again enhanced after infusion (p > 0.05); with regard to the basal values of other parameters, a significant reduction (p > 0.05) was found in F VII, whereas no other significant changes were observed. In the light of these results the authors suggest an antithrombotic effect of the drug documented by the short-term increase in AT III probably due to lower consumption, and a medium-term reduction in F VII due to trophic effect of the drug at a vasculoparietal level resulting in the depression of FVII tissue activation factors.
Recent results with the Drosophila melanogaster period gene suggest that the apparently conserved repetitive motif (Thr-Gly)n encoded by this gene may play an important role in the temperature compensation of the circadian clock. We have therefore initiated both a theoretical and experimental conformational analysis of (Thr-Gly)n peptides. By using a build-up method, it is clear that the hexapeptide (Thr-Gly)3 represents a 'conformational monomer' and generates a stable type II or type III beta-turn. Circular dichroism and nuclear magnetic resonance spectra of synthetic (Thr-Gly)3 and poly(Thr-Gly) peptides revealed that these peptides exhibit flexible conformations, especially in more polar environments and at higher temperatures. We speculate that this flexibility may illuminate our understanding of both the molecular mechanism of temperature compensation and the systematic geographical distribution within Europe of the Thr-Gly length polymorphism in D. melanogaster.
BACKGROUND: Sustained tachyarrhythmia resulting in fetal hydrops is often refractory to medical therapy. Fetal atrioventricular node ablation associated with epicardial fetal pacing has the potential to be an effective procedure for this morbid association. METHODS: To assess the feasibility of therapeutic fetal heart block, we developed a technique of intrauterine cryosurgical ablation of fetal atrioventricular node without the need for cardiac bypass in 8 fetal lambs. Complete heart block was obtained by applying the cryoprobe over the coronary sinus. Fetal pacing was then performed to allow fetal survival. RESULTS: Complete heart block was achieved in 100% of the fetal lambs. Postoperative evaluation revealed persistent atrioventricular block. The hearts were studied at different postoperative times. Morphologic evaluation of the area containing the cryosurgical lesion revealed varied extension of necrosis of the atrioventricular node and hemorrhage, with involvement of the His bundle and proximal right bundle branch. CONCLUSIONS: This procedure is technically feasible and offers an alternative approach to the treatment of drug-resistant, life-threatening fetal supraventricular tachyarrhythmias associated with hydrops fetalis.
HNF-3/FKH genes are a large family of transcriptional activators. They are expressed in specific developmental and tissue patterns. Indeed, several of them are known to be essential for normal development (e.g. Dfkh and slp-1,2). Mutation within one of these genes produces mutant fruitfly embryos that are unable to survive. This family shares conserved DNA binding and transcriptional activation domains. The DNA binding domain has been crystallized, and its structure determined. Although it has resemblance to helices of homeodomains and H5 histones, it represents a new DNA binding motif, which has been called the 'winged helix,' because it contains additional interactive peptide regions called termed wings. Subtle amino acid variations in a region adjacent to the DNA recognition helix influence the recognition specificity of each HNF-3/FKH protein and therefore confer selectivity in promoter regulation. Members of this family are important in regulating the inflammatory response of the liver (the three HNF-3 genes). In addition, several members may be important in blood cell development (H3 and 5-3). Finally, two of these genes have been found to produce neoplasia (qin and FKHR). As investigation progresses, the mechanism by which these genes regulate development, inflammation and neoplasia will become more clear.
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The reliability of two-dimensional (2D) echocardiographic estimation of left ventricular ejection fraction (EF) is commonly recognized, but no satisfactory data are available about the accuracy of low or very low EF values determined by 2D echocardiography (ECHO-EF). The purpose of our study was to assess the reliability of low ECHO-EF values obtained using a simple time-economical algorithm such as the ellipsoid single-plane area-length method. Radionuclide angiography (RAD-EF) was taken as the standard of comparison. We studied 59 consecutive patients (31 women and 28 men) referred to our echocardiographic laboratory. Both 2D echocardiography and radionuclide angiography were blindly performed within 48 h of one another. EF was calculated by the two methods and then compared. Data were globally analyzed. Furthermore, data were divided and analyzed according to the ECHO-EF cut-off point of 50%. An ECHO-EF value of 50% was chosen to conventionally distinguish between low ECHO-EF values and normal-high ones. Data were plotted, and the line of equality and the regression lines were drawn. Regression line slopes, correlation coefficients, means and standard deviations were calculated. The agreement was analyzed by calculating the mean difference (RAD-EF-ECHO-EF) and the standard deviation of the differences. ECHO-EF was linearly related to RAD-EF even when data were split. In particular, as regards ECHO-EF < or = 50%, the regression line practically overlapped the line of equality, and the two methods showed both a strong correlation and a good degree of agreement.(ABSTRACT TRUNCATED AT 250 WORDS)
In this study the efficacy and safety of short-term cilazapril administration on renal haemodynamics were evaluated in mild to moderate hypertensive subjects. Our final goal was to evaluate whether the reduction in blood pressure achieved by treatment was associated with maintained renal function. After a run-in period with placebo, 40 hypertensive subjects without renal or cardiac diseases were randomly allocated to a double-blind 4 week controlled trial with cilazapril 5 mg once a day (20 patients) or hydrochlorothiazide 25 mg once a day (20 patients). Renal haemodynamics measurements included effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) by radionuclide study using 131I-hippuran and 99mTc, according to the methods described by Schlegel and Gates, respectively. Effective renal blood flow [ERBF = ERPF/(1-Ht)], filtration fraction (FF = GFR/ERPF) and renal vascular resistance (RVR = MBP x 80/ERBF) were calculated. At the end of cilazapril and hydrochlorothiazide administration significant decreases (p < 0.001) in SBP, DBP and MBP vs baseline values were observed. In the cilazapril group a significant decrease (p < 0.001) in RVR and FF and a significant increase (p < 0.001) in ERPF and ERBF were also found. In the hydrochlorothiazide group a significant decrease (p < 0.001) in RVR was found. No important side effects were observed with either treatment. In conclusion our data indicate that both cilazapril and hydrochlorothiazide reduced blood pressure equally well but only cilazapril improved renal blood flow and reduced filtration fraction.
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Autonomic neuropathy in diabetes mellitus can cause alterations of the motor function of various segments of the gastroenteric apparatus. With hepatocholangio-cholecystiscintigraphy-HIDA we have studied the motility of the biliary system in patients with diabetes mellitus type II. The research has been carried out in 29 patients with diabetic autonomic neuropathy; 12 healthy volunteers have been studied to compare the results obtained. The results showed a delay in the appearance of radionucleotide in the small intestine of diabetic subjects compared to controls with statistical significance. Moreover the diabetic subjects with a serious neuropathic injury showed increased intestinal transit time. These results match those obtained by other authors that have studied the cholecystic emptying in diabetic subjects with other methods. Consequently the biliary system is also affected by the diabetic autonomic neuropathy that can be in its turn the cause of other pathologies such as biliary lithiasis.
Hepatitis B virus (HBV) ENI enhancer can activate the expression of HBV and non-HBV genes in a liver-specific manner. By performing the electrophoretic mobility-shift assays, we demonstrated that the three related, liver-enriched, transcription factors, HNF3 alpha, HNF3 beta, and HNF3 gamma could all bind to the 2c site of HBV ENI enhancer. Mutations introduced in the 2c site to abolish the binding by HNF3 reduced the enhancer activity approximately 15-fold. Moreover, expression of HNF3 antisense sequences to suppress the expression of HNF3 in Huh-7 hepatoma cells led to reduction of the ENI enhancer activity. These results indicate that HNF3 positively regulates the ENI enhancer activity and this regulation is most likely mediated through the 2c site. The requirement of HNF3 for the ENI enhancer activity could explain the liver specificity of this enhancer element.
The evaluation of the relationship between the dose to DNA of a mutagen/carcinogen and in vivo somatic cell mutagenesis may provide information on the mechanisms leading to induced mutational events. This can be achieved, for example, by coupling test systems that permit the detection of somatic mutation and recombination on the basis of phenotypic changes in cuticular structures of Drosophila melanogaster, with methods for the quantitation of carcinogen-DNA adducts such as the 32P-postlabeling technique. In this article, we evaluate the quantitative relationship between BaP-DNA adduct formation, determined by 32P-postlabeling, and the induction of mutant cells in the wing marker version of the somatic mutation and recombination test (SMART) in Drosophila melanogaster. The total single clones in the trans-heterozygous mwh/flr3 flies show a linear relationship with the BaP-DNA adduct levels, suggesting a single hit mechanism for the genetic damage giving rise to this type of clones. In contrast, the twin clones (which are of recombinational origin) display a linear-quadratic relationship with the adduct levels, suggesting that multiple hits may be involved in generating these clones. The total single clones in the mwh/TM3, Ser flies (in which mitotic recombination is suppressed) show a logarithmic relationship with the adduct levels. The discussion of these data in terms of the pathways that may be involved in the repair of the BaP-DNA adducts leads to the suggestion that in Drosophila melanogaster the repair of Bap metabolite-DNA adducts in somatic cells may proceed, in large part, via post-replicative recombinational repair.
In order to characterise the response of the wing spot test in Drosophila melanogaster to the effects of compounds with known aneugenic properties, experiments were performed with chloral hydrate (CH). Following chronic exposure of 72-h-old larvae to rising concentrations of CH, significant increases in the frequency of small (1-2 cells) single spots were observed. Comparison of results obtained in parallel from the wings of marker-trans-heterozygous individuals and individuals heterozygous for one of two different balancer chromosomes suggests that practically all the single clones originated from recombinational events. Twin clone frequencies were, however, only weakly affected. These results are discussed with reference to the literature regarding the effects of CH in different experimental systems and to the characteristics of Drosophila as a tester organism.
The threonine-glycine (Thr-Gly) repeat region of the period (per) gene of eight natural populations of Drosophila simulans from Europe and North Africa was analyzed by polymerase chain reaction, DNA sequencing and heteroduplex formation. Five different length alleles encoding 21, 23, 25 and two different kinds of 24 Thr-Gly pairs in the uninterrupted repeat were found. In the 3' region flanking the repeat 6 nucleotide substitutions (3 synonymous, 3 replacement) were observed in three different combinations that we called haplotypes I, II and III. The complete linkage disequilibrium observed between the haplotypes and these length variants allowed us to infer from the repeat length, the DNA sequence at the 3' polymorphic sites. The haplotypes were homogeneously distributed across Europe and North Africa. The data show statistically significant departures from neutral expectations according to the Tajima test. The results suggest that balancing selection might have played a role in determining the observed levels and patterns of genetic diversity at the per gene in D. simulans.
The region of the clock gene period (per) that encodes a repetitive tract of threonine-glycine (Thr-Gly) pairs has been compared between Dipteran species both within and outside the Drosophilidae. All the non-Drosophilidae sequences in this region are short and present a remarkably stable picture compared to the Drosophilidae, in which the region is much larger and extremely variable, both in size and composition. The accelerated evolution in the repetitive region of the Drosophilidae appears to be mainly due to an expansion of two ancestral repeats, one encoding a Thr-Gly dipeptide and the other a pentapeptide rich in serine, glycine, and asparagine or threonine. In some drosophilids the expansion involves a duplication of the pentapeptide sequence, but in Drosophila pseudoobscura both the dipeptide and the pentapeptide repeats are present in larger numbers. In the nondrosophilids, however, the pentapeptide sequence is represented by one copy and the dipeptide by two copies. These observations fulfill some of the predictions of recent theoretical models that have simulated the evolution of repetitive sequences.
Epicardial fetal pacing via thoracotomy has the potential of being a safer and more reliable procedure to treat congenital complete heart block (CHB) associated with fetal hydrops refractory to medical therapy. To assess the acute electrophysiological characteristics of two ventricular epicardial leads, a new experimental model of fetal heart block induced by cryosurgical ablation of the AV node without the need for fetal cardiac bypass was performed in 12 pregnant ewes at 110-115 days gestation. A modified screw-in lead (1 1/2 turns) was used in six fetal lambs and a stitch-on lead in the other six lambs. CHB was achieved in 100% of the fetal lambs, with no ventricular escape rate noticed in any of the lambs. The acute stimulation thresholds were consistently low for both leads, with lower values for the screw-in lead at pulse duration below 0.9 msec (P < 0.03). Current measured at voltage threshold with pulse width below 0.5 msec was lower for the screw-in lead (P < 0.048). Stimulation resistance, measured during constant-voltage pacing, was not statistically different between the two leads (441.8 +/- 13.7 omega for the screw-in lead vs 480.2 +/- 59.2 omega for the stitch-on lead). No significant differences (P > 0.20) were found in R wave amplitude between the two electrodes. Slew rates were significantly higher in the screw-in group than in the stitch-on group (1.40 +/- 0.2 vs 0.62 +/- 0.2 V/sec, P = 0.04). This model of CHB is a simple and reproducible method to assess fetal pacing. We find the screw-in electrode to be a better option when fetal pacing is indicated.
A longitudinal study of diarrheal disease among patients of all ages with acute diarrhea was carried out in New Caledonia from January 1990 to December 1991. Stool samples from 2,088 diarrheal patients were examined for parasites, rotavirus, and bacterial pathogens. Potential sources of contamination (drinking water, seawater and bovine and porcine feces) were investigated. One or more enteric pathogens were identified in 41.8 and 40.6% of the persons with diarrhea, in 1990 and 1991, respectively. Salmonella spp., Shigella spp., HEp-2 cell adherent Escherichia coli (diffuse adherent and enteroaggregative), enteropathogenic E. coli (EPEC) (EPEC adherence factor-positive strains belonging to classical serotypes), localized adherent E. coli (non-EPEC), and enterotoxigenic E. coli were the frequently identified enteropathogenic bacteria. Other major enteropathogens were Entamoeba histolytica and Giardia lamblia. Campylobacter jejuni, Clostridium difficile, Clostridium perfringens, Yersinia enterocolitica, and rotavirus were isolated from only a few patients. No Vibrio spp., Aeromonas spp., Plesiomonas spp., Shiga-like-toxin-producing E. coli, enterohemorrhagic E. coli, or enteroinvasive E. coli were identified. Shiga-like toxin I-producing E. coli were present in adult bovines and calves, and heat-stable enterotoxin II-producing enterotoxigenic E. coli were found in pigs.