Search PubMed⌕ Search

Biomedical subjects

M Costa

Publications and source records attributed to M Costa.

At least 109 records · Page 6Linked to original sources
PubMed2000

High germinal instability of the (CTG)n at the SCA8 locus of both expanded and normal alleles.

The autosomal dominant spinocerebellar ataxias (SCAs) are a group of late-onset, neurodegenerative disorders for which 10 loci have been mapped (SCA1, SCA2, SCA4-SCA8, SCA10, MJD, and DRPLA). The mutant proteins have shown an expanded polyglutamine tract in SCA1, SCA2, MJD/SCA3, SCA6, SCA7, and DRPLA; a glycine-to-arginine substitution was found in SCA6 as well. Recently, an untranslated (CTG)n expansion on chromosome 13q was described as being the cause of SCA8. We have now (1) assessed the repeat size in a group of patients with ataxia and a large number of controls, (2) examined the intergenerational transmission of the repeat, and (3) estimated the instability of repeat size in the sperm of one patient and two healthy controls. Normal SCA8 chromosomes showed an apparently trimodal distribution, with classes of small (15-21 CTGs), intermediate (22-37 CTGs), and large (40-91 CTGs) alleles; large alleles accounted for only0.7% of all normal-size alleles. No expanded alleles (>/=100 CTGs) were found in controls. Expansion of the CTG tract was found in five families with ataxia; expanded alleles (all paternally transmitted) were characterized mostly by repeat-size contraction. There was a high germinal instability of both expanded and normal alleles: in one patient, the expanded allele (152 CTGs) had mostly contraction in size (often into the normal range); in the sperm of two normal controls, contractions were also more frequent, but occasional expansions into the upper limit of the normal size range were also seen. In conclusion, our results show (1) no overlapping between control (15-91) and pathogenic (100-152) alleles and (2) a high instability in spermatogenesis (both for expanded and normal alleles), suggesting a high mutational rate at the SCA8 locus.

Adolescent↗
PubMed2000

Rats retain chromium in tissues following chronic ingestion of drinking water containing hexavalent chromium.

Humans have sometimes been exposed to as much as 10 ppm Cr(VI) in drinking water from contaminated wells. The risks to these individuals are not well understood because the digestive tract reduces some of the Cr(VI) to the less bioavailable Cr(III) prior to absorption, and the disposition of the remaining Cr(VI) has not been well studied. We determined tissue Cr concentrations in rats after chronic ingestion of Cr(VI) in drinking water at concentrations relevant to human exposure levels. Adult male and female Fischer 344 rats consumed ad libitum 0, 0.5, 3, or 10 ppm Cr(VI) as K2CrO4 in drinking water for 44 wk. Rats then were given deionized water 4-6 d prior to sample collection. Females given 3 or 10 ppm Cr(VI) consumed more Cr(VI) per unit of body weight than did males. Bone Cr concentrations were significantly elevated in rats that drank 10 ppm Cr(VI). Renal Cr concentrations were significantly elevated in male rats that drank 3 or 10 ppm Cr(VI) and in female rats dosed with 10 ppm Cr(VI). Female rats had elevated liver Cr concentrations after drinking 3 or 10 ppm Cr(VI). Testicular Cr concentrations were slightly elevated in rats that drank 10 ppm Cr(VI). Brain, ovarian, and whole-blood Cr concentrations were below detection limits in all exposure groups. Although tissue Cr accumulation may have resulted from absorption of Cr(III), it is poorly absorbed. Therefore, the increased tissue retention may also have resulted, in part, from increased absorption of Cr(VI) and its subsequent uptake from the systemic circulation.

Animals↗
PubMed2000

[Asymptomatic carriers of hydatidosis: epidemiology, diagnosis, and treatment].

Until a short time ago, hydatidosis was considered a pathology that could only be resolved surgically. However, in recent years progress has been made with the epidemiology, diagnosis, and treatment of the disease, and new information on the natural history of hydatidosis has helped define new criteria for its treatment. It is now known that as many as 67% of the carriers of liver cysts who are asymptomatic remain so throughout their lives. This situation produces special results in immunologic testing. Enzyme-linked immunosorbent assay (ELISA) has a sensitivity of 63% and a specificity of 97% with asymptomatic carriers, while the double diffusion arc 5 test (DD5) achieves a sensitivity of only 31% with the same population. On the other hand, imaging studies based on ultrasonography have become the method of choice to detect asymptomatic carriers. Ultrasonography studies are 49% to 73% more sensitive than serological tests, and they can even be used as a part of epidemiological surveillance systems and to monitor control programs. Treatment schemes have also been modernized. Treating asymptomatic carriers chemotherapeutically with albendazole produces favorable results in as many as 69% of cases, while such minimally invasive surgical treatments as puncture-aspiration-injection-reaspiration (PAIR) reduce average cyst volume by as much as 66%. These factors have made it possible for hospital services in the province of Río Negro, Argentina, to establish a treatment scheme for asymptomatic carriers. It is based on the monitoring of small cysts (type Ia on the modified Gharbi scale); initial treatment with albendazole, followed by PAIR if there is no response, in larger or more complex cysts (types Ib, II, and III); and follow-up of inviable or dead cysts (types IV and V).

Albendazole↗
PubMed2000

A prospective, randomized, controlled clinical study of a new subcutaneous, purified, urinary FSH preparation for controlled ovarian hyperstimulation in in vitro fertilization.

The aim of this study was to evaluate the clinical efficacy and safety of a new urinary follicle stimulating hormone (FSH) preparation (Fostimon) in patients undergoing in vitro fertilization-embryo transfer or intracytoplasmic sperm injection. Metrodin HP was adopted as a reference drug, as its purity and therapeutic efficacy are well known. Sixty normo-ovulatory patients aged 18-38 years with normal basal FSH and body mass index < 25 kg/m2 were selected for the study. After gonadotropin releasing hormone analogue pituitary desensitization, patients were randomized to receive either Fostimon or Metrodin HP at the initial dosage of 225 IU for 6 days. Thereafter, the dosage was tailored according to the ovarian response. Both drugs were administered by the subcutaneous route. The primary end-points were: number of follicles larger than 15 mm, levels of 17 beta-estradiol on the day of human chorionic gonadotropin (hCG) injection and number of oocytes recovered. The secondary end-points were: number of FSH ampules used, day of hCG injection and pregnancy rate. FSH kinetic curves were calculated during the treatment period with both products. Safety was evaluated by pre- and post-treatment blood biochemistry and hematology, and recording all side-effects. Local tolerance was investigated at each visit. None of the parameters evaluated showed a statistically significant difference between the two groups. Local tolerance was always recorded as good/excellent by both the patients and the physician. In conclusion, Fostimon proved to be an effective and safe drug for assisted reproductive cycles.

Adolescent↗
PubMed2000

Repolarization abnormalities after catheter ablation of differently located overt accessory pathways.

PURPOSE: Electrical repolarization abnormalities are usually seen after radiofrequency catheter ablation in overt accessory atrio-ventricular pathways. These abnormalities have been recognised as "cardiac memory". The aim of this study was to assess the relationships between electrical repolarization abnormalities and the location of the accessory atrioventricular pathway in the atrio-ventricular junction. We also assessed the relationship between electrical repolarization abnormalities and the degree of ventricular preexcitation. MATERIAL AND METHODS: Our group consisted of 45 patients with overt and persistent preexcitation who were successfully submitted to radiofrequency catheter ablation. Mean age was 38.9 +/- 14.9 years (14 to 64), 28 of whom (62.2%) were male and 17 (37.8%) female. The location of accessory pathways the was left lateral in 14 patients, right posteroseptal in 14 patients, right mesoseptal in eight patients, right anteroseptal in four patients and other locations in the remaining four. Surface electrocardiograms were performed immediately following ablation, 24 hours later and three or more months after the procedure. RESULTS: T wave abnormalities (flattened, inverted or peaked) were detected on the first day in 51% of patients, being more frequent after right accessory pathway ablation (86.9% versus 13.1% in left accessory pathways). These electrocardiographic changes were particularly frequent in patients with right mesoseptal (5/8, 62.5%) and posteroseptal (13/14, 93.3%) pathways, of which 62.5% and 71.5%, respectively, showed marked preexcitation before ablation. These findings were significantly different from those observed in patients with left lateral pathways--only 35.7% showed marked preexcitation and only two of fourteen patients (14.3%) presented T wave abnormalities after ablation. After the third month, most of the patients that had undergone successful ablation presented completed electrocardiographic normalization. CONCLUSIONS: Patients undergoing radiofrequency catheter ablation for right accessory pathways show more frequently repolarization abnormalities than those submitted to ablation of the left lateral accessory pathways. The occurrence of these changes after preexcitation resolution may depend on the degree of previous preexcitation.

Adolescent↗
PubMed2000

Epigenetic mechanisms of nickel carcinogenesis.

This article considers the mechanism of nickel carcinogenesis, focusing primarily on the epigenetic changes associated with exposure of cells to carcinogenic nickel compounds. We discuss the delivery of nickel in the cell and contrast the genetic and epigenetic changes that have occurred. Within the epigenetic effects, alteration in the levels of transcription factors, such as ATF-1, p53, HIF-1, HIF-1alpha, and NFkappaB, are considered. The relationship between nickel and calcium metabolism and the role it plays in nickel carcinogenesis is also considered, as are reactive oxygen species and the interactions of nickel with proteins. We discuss these epigenetic discussions in light of the effects that nickel has on inducing DNA methylation in cells. It is of interest that nickel induces both a variety of signaling pathways as well as genes that seem to be important for the survival of cancer cells. It is also interesting that the same genes induced or repressed by nickel are similarly overexpressed or not expressed in nickel-transformed cells. It is suggested that this may represent a selection process crucial to the nickel carcinogenesis process.

Acetylation↗
PubMed2000

[Intravascular ultrasound in cardiology].

Intravascular ultrasound (IVUS) is a clinically useful tool that provides cross-sectional images of the coronary arterial lumen and wall. Diagnostic applications of IVUS include the evaluation of ambiguous lesions on angiography particularly at the bifurcations. IVUS is also useful in the assessment of coronary vasculopathy in cardiac transplant patients or it can help to diagnose abnormalities such as syndrome X or coronary artery spasm. IVUS can optimize the performing of percutaneous coronary interventions, especially stent implantation. It represents as well an optimal tool for assessing regression of atherosclerosis. Three-dimensional reconstruction, elastography and imaging guide wires are some of the recent advances in the field of intravascular ultrasound.

Angioplasty, Balloon, Coronary↗
PubMed2000

Understanding the financial impact of covering new screening technologies. The case of automated Pap smears.

OBJECTIVE: To develop a decision tool facilitating understanding of the potential financial impact on managed care plans associated with automated primary screening for Pap smears. STUDY DESIGN: A baseline decision analytic model was developed with claims data from two managed care plans to replicate the treatment costs patients accrue subsequent to receiving a routine Pap smear with initial human review. Probabilities that a patient was at a particular decision point, as well as payments associated with that patient, were also determined empirically from the claims data. Clinical trial results for the AutoPap System (TriPath Imaging, Inc., Burlington, North Carolina) were incorporated into the model to develop an alternate scenario with 15% fewer false positives and 32% fewer false negatives. Sensitivity analyses were performed to model likely "real world" variation in laboratory results and treatment costs. Marginal costs associated with automated screening were calculated. Financial impacts were calculated in per member per month (PMPM) terms and included an incremental $20 payment for automated primary screening. Given that total PMPMs associated with health care delivery vary widely across the U.S., incremental impacts were also calculated from baseline PMPMs ranging from $80 to $160. RESULTS: PMPMs increased 5-10 cents, depending on baseline PMPM, test performance and treatment costs. CONCLUSION: Although costs rose with automated Pap smears, the costs shifted to the diagnosis and treatment of true positives.

Adolescent↗
PubMed2000

Diagnosis of human hydatidosis. Predictive value of a rural ultrasonographic survey in an apparently healthy population.

The usefulness of ultrasonography (US) in the early diagnosis of hydatidosis, applied in large-scale surveys to populations lacking clinical symptoms of the disease, has been amply documented. However, the rate of false positive and negative results is poorly described. Due to this, the present paper is aimed to evaluate the sensitivity, specificity and predictive value of a conventional rural ultrasonographic survey in comparison with higher imaging complexity. Accordingly, during 1997 and 1998 a total of 1054 children from 7 to 14 years of age were evaluated by means of US, in the town of Ingeniero Jacobacci, Province of Rio Negro, Argentina, employing a portable device for population studies. All detected cases were referred to a high complexity center specialized in imaging diagnosis for their re-evaluation with US, CT scanning and X-rays. A control group comprising 3 children negative by US for each positive case in the mass screening survey was selected and reexamined by US and X-rays and CT scanning in doubtful situations. Twenty-seven asymptomatic carriers were referred with images compatible with hydatid cysts, while 66 were classified as disease free. At reexamination, 24 of those diagnosed as carriers and the totality of those classified as healthy were confirmed. On the basis of our results, a sensitivity of 100%, a specificity of 95.6% and a global test value of 96.7% were estimated.

Adolescent↗
PubMed2000

[Effect of programming different AV intervals on mitral insufficiency in patients with DDD pacemaker].

OBJECTIVE: To study the effect of programming three different atrioventricular intervals (AVI) on mitral insufficiency (MI) in patients with permanent pacemaker due to complete atrioventricular block. METHODS: We included 9 patients (mean age 62 +/- 11 years; 6 men), with permanent DDD pacemaker, isolated MI and normal ventricular function. We evaluated MI (in a quantitative way) and cardiac output (CO) through echocardiographic examination with three different AVI (100, 150 and 200 ms). RESULTS: We observed a reduction in the severity of MI with the reduction of the AVI (best results obtained with AVI of 100 ms). We also observed an increase in the CO in 4 patients (those with MI of greater degree) with AVI of 100 ms. CONCLUSIONS: We observed a correlation of longer AVI with greater degree of MI; our results point to the possibility of increasing the CO of patients with greater degrees of MI with shortening of the AVI (probably due to a partial recovery of the regurgitant volume).

Aged↗
PubMed2000

[Evaluation of commercial UHT milk and optimization of industrial process].

From the nutrition al point of view milk is one of the most complete food in the diet of mammals. It contains nearly all the nutrients necessary to sustain life, but milk can deteriorate very easily, either by microbiological contamination or by biochemical reactions during processing and/or storage. The objective of this research study was to design a modified UHT treatment to achieve commercial sterilization and maximize the stabilization of the heat-treated product during storage. To search for a modified UHT process, a mathematical model coupled with an optimization routine (complex method) was developed. The mathematical model considers Kinetics for the inactivation of Bacillus stearothermophilus and several quality factors. To attain the objective function, several commercial UHT milk were analyzed and for the computer search the minimization of hydroxy methyl furfural (HMF) formation was considered and also including constraints for protease and lipase inactivation. The complex optimization procedure was implemented to search for the optimum modified UHT treatment.. One of the optimum modified UHT treatments was the combination of two pre-treatment (3.16 minutes at 62.30 degrees C and 6 minutes at 75 degrees C) in addition with a UHT treatment (0.75 s at 148.8 degrees C). This treatment attains the maximum product stability with a negligible effect on composition and color formation in the treated milk (HMF formation less than 3 mg/mL).

Animals↗
PubMed1999

Role of Ca(2+) in the regulation of nickel-inducible Cap43 gene expression.

We have recently cloned a gene, Cap43, that was significantly induced by exposure to nontoxic levels of both water-soluble and -insoluble Ni(2+) compounds. In this paper, we utilized the expression levels of this gene as a tool to identify second messengers involved in nickel-inducible transcription. We report here that the Ca(2+) ionophore A23187 substantially stimulated Cap43 gene expression. In addition, we found that BAPTA-AM, a specific chelator of free intracellular Ca(2+), consistently attenuated the induction of Cap43, indicating that elevation of intracellular Ca(2+) was essential for this response. TPEN, a chelator of heavy metals, such as Ni(2+) with a very low affinity for Ca(2+), did not attenuate Cap43 induced by Ni or calcium ionophore, suggesting that elevations of Ca(2+) but probably not elevations of other metal ions were involved in the induction of Cap43. A direct measurement of Ca(2+) levels using the fluorescent probe Fluo-3 AM showed elevations of free intracellular Ca(2+) in Ni-treated cells. A strong induction of Cap43 by okadaic acid suggested the involvement of a serine/threonine phosphorylation in a signaling pathway that was presumably activated by Ni and that led to enhanced Cap43 gene expression. However, calcium-dependent protein kinase(s) involved in the nickel-activated signaling pathway remains to be identified.

Calcium↗
PubMed1999

Voltage dependence of macroscopic and unitary currents of gap junction channels formed by mouse connexin50 expressed in rat neuroblastoma cells.

1. The macroscopic and single channel gating characteristics of connexin (Cx) 50 gap junction channels between pairs of N2A neuroblastoma cells transfected with mouse Cx50 DNA were investigated using the dual whole-cell voltage clamp technique. 2. The macroscopic junctional current (Ij) of Cx50-transfected cells decayed exponentially with time in response to transjunctional voltage (Vj) steps (time constant (tau) of approximately 4 s at a Vj of 30-40 mV and 100-200 ms at a Vj of 80-100 mV). The steady-state junctional conductance (gj) was well described by a two-state Boltzmann equation. The half-inactivation voltage (V0), the ratio of minimal to maximal gj (gmin/gmax) and the equivalent gating charge were +/- 37 mV, 0.21 and 4, respectively. 3. The conductance of single Cx50 channels measured using patch pipettes containing 130 mM CsCl was 220 +/- 13.1 pS (12 cell pairs). A prominent residual or subconductance state corresponding to 43 +/- 4. 2 pS (10 cell pairs) was also observed at large Vj s. 4. The relationship between channel open probability (Po) and Vj was well described by a Boltzmann relationship with parameters similar to those obtained for macroscopic gj (V0 = 34 mV, gating charge = 4.25, maximum P= 0.98). The ensemble average of single channel currents at Vj = 50 mV declined in a monoexponential manner (tau = 905 ms), a value similar to the decline of the macroscopic Ij of Cx50 channels at the same voltage. 5. Ion substitution experiments indicated that Cx50 channels have a lower permeability to anions than to cations (transjunctional conductance of KCl vs. potassium glutamate (gammaj, KCl/gammaj,KGlut), 1.2; 6 cell pairs). 6. The results have important implications for understanding the role of connexins in tissues where Cx50 is a major gap junction component, including the lens.

Animals↗
PubMed1999

Quantitative analysis of peristalsis in the guinea-pig small intestine using spatio-temporal maps.

1. Peristalsis was evoked in guinea-pig small intestine by slow fluid infusion and recorded onto video and digitized. Spatio-temporal maps of diameter and longitudinal movement were constructed and parameters of motion were calculated. 2. During the filling of the isolated segments of intestine, rhythmic local longitudinal movements were observed at several points along the preparation. These phasic longitudinal muscle contractions were associated with small but significant local increases in diameter and probably reflect a passive mechanical coupling by connective tissue in the gut wall. In addition, occasional synchronized longitudinal muscle contractions caused net shortening of the preparation and always preceded the onset of peristaltic emptying. 3. Peristaltic emptying was characterized by a contraction of the circular muscle which usually started at the oral end of the preparation, that propagated aborally, propelling the contents. However, in 19 % of trials, the first circular muscle contraction occurred in the aboral half of the preparation. 4. The propagation of peristalsis consisted of separate sequential circular muscle contractions several centimetres long, particularly in the oral half of the preparation, giving a 'step-like' appearance to the spatio-temporal map. The gut was transiently distended aboral to the propagating circular muscle contraction due to the propulsion of contents. 5. At each point in the preparation, the longitudinal muscle remained contracted during the propulsive part of the circular muscle contraction. Only when the circular muscle contraction became lumen occlusive did lengthening of the longitudinal muscle take place. 6. Spatio-temporal maps are a powerful tool to visualize and analyse the complexity of gastrointestinal motility patterns.

Animals↗
PubMed1999

Initiation of peristalsis by circumferential stretch of flat sheets of guinea-pig ileum.

1. Segments of isolated guinea-pig intestine, 12 mm long, were distended slowly by intraluminal fluid infusion or by mechanical stretch as either a tube or flat sheet. In all cases, at a constant threshold length, a sudden, large amplitude contraction of the circular muscle occurred orally, corresponding to the initiation of peristalsis. 2. Circumferential stretch of flat sheet preparations evoked graded contractions of the longitudinal muscle (the 'preparatory phase'), which were maintained during circular muscle contraction. This suggests that the lengthening reported during the emptying phase of peristalsis is due to mechanical interactions. 3. The threshold for peristalsis was lower with more rapid stretches and was also lower in long preparations (25 mm) compared with short preparations (5-10 mm), indicating that ascending excitatory pathways play a significant role in triggering peristalsis. 4. Stretching a preparation beyond the threshold for peristalsis evoked contractions of increasing amplitude; thus peristalsis is graded above its threshold. However, during suprathreshold stretch maintained at a constant length, contractions of the circular muscle quickly declined in amplitude and frequency. 5. Circular muscle cells had a resting membrane potential approximately 6 mV more negative than the threshold for action potentials. During slow circumferential stretch, subthreshold graded excitatory motor input to the circular muscle occurred, prior to the initiation of peristalsis. However, peristalsis was initiated by a discrete large excitatory junction potential (12 +/- 2 mV) which evoked bursts of smooth muscle action potentials and which probably arose from synchronized firing of ascending excitatory neuronal pathways.

Animals↗