PubMed Health⌕ Search

Biomedical subjects

P M Costa

Publications and source records attributed to P M Costa.

At least 19 recordsLinked to original sources
PubMed2005

Birth of two healthy females after preimplantation genetic diagnosis for familial amyloid polyneuropathy.

Familial amyloid polyneuropathy (FAP), Portuguese type, is a late onset, high penetrance, autosomal dominant Mendelian disorder caused by a V30M substitution in the transthyretin (TTR) protein. A genetic diagnosis was developed using fluorescent single cell polymerase chain reaction (PCR) on lymphocytes from patients and controls. Ovarian stimulation and oocyte retrieval were carried out using conventional protocols in a couple in whom the female was heterozygous for the mutation TTR V30M. Blastomere biopsy was performed on day 3 after intracytoplasmic sperm injection. PCR was then performed for a segment of the TTR gene encompassing the V30M mutation. The transfer of three embryos at day 4 resulted in a twin pregnancy, confirmed as healthy females by amniocentesis at 16 weeks of gestation; the birth took place at 37 weeks of gestation. With this report, FAP, TTR related, joins the lengthening list of genetic conditions for which preimplantation genetic diagnosis has been successfully carried out.

Adult↗
PubMed2000

Inflammatory fibroid polyp of the esophagus.

The case of a 76-year-old woman with a submucosal tumor of the esophagus, whose principal symptoms were dysphagia and epigastric/retrosternal pain, is reported here. Endoscopy, barium swallow and a CAT scan all pointed to extramucosal localization. The lesion was located in the lower esophagus lying on the stomach fundus. An ulcer in the region of the cardia complicated the tumor. Two sets of conventional biopsies failed to detect malignancy, only inflammation and intestinal metaplasia were seen in the specimens of the mucosa surrounding the ulcer. The endoscopic ultrasonographic findings were an indistinct margin, hypoechogenicity, homogeneous appearance and location within the second and third echographic layer. The surgical resection of the tumor was complemented by an anterior partial fundoplication. The histologic study revealed an inflammatory fibroid polyp, which is a rare, benign, non-capsulated submucosal lesion composed mainly of loose connective tissue and vessels, with an eosinophilic inflammatory component. This lesion is seldom found in the esophagus.

Aged↗
PubMed2000

The course and prognostic factors of familial amyloid polyneuropathy after liver transplantation.

Familial amyloid polyneuropathy (FAP) associated with mutations of the transthyretin (TTR) gene is the most common type of FAP, a devastating disease causing death within 10 years after the first symptoms. Because most of the amyloidogenic mutated TTR is secreted by the liver, transplantation is widely used to treat these patients, but long-term quantitative evaluation of the effects of liver transplantation on the progression of the neuropathy are not available. We have treated 45 patients with symptomatic TTR-FAP, including 43 with the Met30 TTR gene mutation, and report on the results of periodic evaluation of markers of neuropathy in 25 of them, who have been followed for more than 2 years after liver transplantation (mean follow-up 4 years). The overall survival rates at 1 and 5 years were 82 and 60%, respectively. Urinary incontinence and a low Norris score at liver transplantation were associated with poorer outcome. The motor score stabilized in seven of 11 patients (64%) with mild sensorimotor neuropathy (walking unaided) and in two of the eight patients (25%) with severe sensorimotor deficit (walking with aid) at liver transplantation. In five other patients, deterioration of motor deficit occurred only within the first year after liver transplantation, but was progressive after this interval in two patients. None of the six patients with pure sensory neuropathy developed motor loss and superficial sensory loss remained unchanged. Two years after liver transplantation, the rate of myelinated axon loss in nerve biopsy specimens was markedly lower in seven transplanted patients (0.9/mm(2) of endoneurial area/month) than in non-transplanted patients (70/mm(2) of endoneurial area/month). Symptoms of dysautonomia and quantitated cardiocirculatory autonomic tests remained unchanged. In all patients, serum mutated TTR decreased to 2.5% of pre-liver transplantation values and remained at this level during follow-up. We presently recommend liver transplantation in FAP patients at onset of first symptoms and exclusion of those with a Norris score below 55 and/or with urinary incontinence.

Action Potentials↗
PubMed1999

Ineffectiveness of dialysis in transthyretin (TTR) clearance in familial amyloid polyneuropathy type I, in spite of lower stability of the TTR Met30 variant.

BACKGROUND: Familial Amyloid Polyneuropathy (FAP) is an hereditary form of systemic amyloidosis related to a mutant transthyretin (TTR). The renal disease ranges from proteinuria to end-stage renal failure (ESRF), with replacement of renal function by dialysis. In comparison with FAP patients with normal renal function, the progression of the neurologic disease seems to be retarded in FAP patients on dialysis. PATIENTS AND METHODS: We evaluated the influence of hemodialysis and hemodiafiltration on plasma TTR levels in 6 FAP patients with ESRF, which were on regular hemodialysis for 4 months to 6 years, prior to this study. Hemodialysis was performed over a two-week period, one week with a cellulose triacetate membrane and the other with a polysulfone membrane. In the third week, patients were submitted to hemodiafiltration. Plasma TTR levels were measured at the beginning, 60 min, 120 min, and at the end of each session. We also evaluated the TTR adsorbed by the membrane and in the dialysate. RESULTS: TTR levels did not change significantly with the dialysis. The total amount of TTR adsorbed to the membrane was always < 2 mg and found in the dialysate < 1 mg. Hemodialysis and hemodiafiltration were ineffective in removing TTR, in spite of lower stability of the TTR Met30 variant. CONCLUSION: The protective feature of hemodialysis on the progression of the amyloidosis is not due to the clearance of this abnormal protein from plasma.

Amyloid Neuropathies↗
PubMed1998

Study of an anti-human transthyretin immunoadsorbent. Influence of coupling chemistry on binding capacity and ligand leakage.

A variant of transthyretin (TTR Val30Met) has been identified as the main protein precursor of the amyloid fibrils deposited in familial amyloidotic polyneuropathy (FAP). Specific removal of TTR in an extracorporeal immunoadsorption procedure is currently under investigation as a possible treatment of FAP. Immunoadsorbents were constructed by immobilizing murine anti-TTR monoclonal antibody 88.6.BA9 onto agarose gel supports via several different coupling chemistries. The influence of coupling conditions such as pH and antibody density, and of perfusion variables, such as antigen concentration and applied flow-rate, on the TTR capture efficiency, was determined. Cyanogen bromide-, carbonyldiimidazole- and aldehyde-activated (ALD) supports conjugated with antibody at optimal pH, provided immunoadsorbents with comparable TTR binding capacities. Regarding stability, leakage was lowest for the ALD based immunoadsorbents, particularly at high pH.

Antibodies, Monoclonal↗
PubMed1995

Immunoadsorption procedure as a potential method for the specific beta 2-microglobulin removal from plasma of patients with chronic renal failure.

beta 2-Microglobulin (beta 2-M), which accumulates in the plasma of patients undergoing long-term dialysis, has been identified as the principal precursor protein of amyloid fibrils in dialysis-related amyloidosis. As no specific treatment for this affection has been yet established, an extracorporeal immunoadsorption procedure appears to be an attractive therapeutic approach to remove beta 2-M. Several murine monoclonal antibodies to human beta 2-M were developed and compared as affinity ligands. One of them was selected on the basis of its specificity and adsorption capacity. In order to achieve maximum efficiency in protein removal, different parameters of the procedure were studied and optimized: effect of antibody coupling density, determination of maximum adsorption capacity of the immunoadsorbents and influence of antigen concentration and of flow-rate on antigen capture efficiency. The conditions of regeneration of immunoaffinity sorbents were also investigated to allow their multiple use without loss of adsorption capacity. The results show the validity of the proposed technique in removing beta-M from plasma of patients with chronic renal failure.

Antibodies, Monoclonal↗
PubMed1994

Geographical distribution of TTR met30 carriers in northern Sweden: discrepancy between carrier frequency and prevalence rate.

The first Swedish case of familial amyloidotic polyneuropathy (FAP) was published in 1965. The same transthyretin (TTR met30) mutation as that seen in Japanese, Portuguese, and other populations was also found in Swedish FAP patients. More than 350 patients with clinical manifestations of FAP have been diagnosed in northern Sweden, most of them originating from the areas around Skellefteå and Piteå. The mean age of onset is 56 years, much later than in patients from Japan and Portugal. To estimate the frequency of the TTR met30 mutation in the counties of Västerbotten and Norrbotten, sera from 1276 persons aged 24 to 65 years, randomly sampled from a health programme (MONICA), were screened with the monoclonal antibody FD6. In 19 persons, 13 females and six males, a positive reaction was seen in an Elisa test using this antibody. DNA analysis confirmed the TTR met30 mutation and showed that 18 were heterozygous and one homozygous for this mutation. Other mutations were not looked for in this study. The mean TTR met30 carrier frequency in the area was 1.5% ranging from 0.0 to 8.3% in 23 subpopulations. There was a notable discrepancy between the regional distribution of the TTR met30 allele and the morbidity rate for FAP. The estimated number of TTR met30 gene carriers in a total population of 500,000 in the area is approximately 7500. The penetrance of the TTR met30 mutation shows considerable variation between families, and the overall diagnostic (predictive) value in this population is as low as around 2%.

Adult↗
PubMed1993

[Liver transplantation for the treatment of type I familial amyloidotic polyneuropathy].

The first liver transplantation carried out in Spain for the treatment of type I familial amyloidotic polyneuropathy (FAP I) is presented. The reason for the operation was based on the liver being responsible for the synthesis of abnormal transtirretin (TTR) constituting the peculiar amyloid of the disease. Following transplantation a rapid and noticeable decrease in abnormal TTR was observed and the evolution of the clinical picture after 18 months of surgery is favorable with progressive improvement of the neurologic symptoms and normal function of the graft. These encouraging results coincide with those of the Swedish group of Umea, the pioneer of this procedure.

Adult↗
PubMed1993

Immunoassay for transthyretin variants associated with amyloid neuropathy.

An anti-transthyretin (TTR) mouse monoclonal antibody (88.6.FD6) of IgG1 subclass, obtained using as immunogen TTR from the serum of a patient with familial amyloidotic polyneuropathy, was found to bind to sera from carriers of several amyloidogenic TTR variants associated with peripheral neuropathy, but not to normal sera or sera from carriers of non-pathogenic or cardiomyopathic variants, in an ELISA performed under special conditions. Further characterization suggests that it recognizes an epitope near the N-terminal side of the TTR monomer. We propose that this epitope is exposed in amyloid and could be implicated in fibril deposition in the peripheral nervous system.

Amyloidosis↗
PubMed1992

Specific removal of transthyretin from plasma of patients with familial amyloidotic polyneuropathy: optimization of an immunoadsorption procedure.

Familial amyloidotic polyneuropathy is characterized by the presence in patients plasma of a genetic variant of transthyretin. No specific treatment has been found and extracorporeal immunoadsorption on immobilized anti-transthyretin antibodies appears as a potentially attractive procedure. Parameters involved in specific immunoadsorption of transthyretin were studied and optimized. Several monoclonal anti-TTR antibodies were compared as affinity ligands and one of them was found to be suitable for such purposes. Optimum quantities of antibodies to be immobilized on the gel were determined. Three desorption agents were tested for regenerating immunoadsorbents and best results were obtained with basic variation of pH, allowing total desorption of TTR and possibility of multiple use without loss of adsorption capacity. Simulation of an immunoadsorption procedure in well-defined conditions showed efficiency and specificity of adsorption to remove TTR and the system thus should be subjected to clinical trials.

Amyloidosis↗
PubMed1992

[Surgical therapy of peptic stenosis of the esophagus in adults].

One hundred and one patients with reflux esophagitis and strictures, submitted to different kinds of surgical solutions over the last 16 years, were revised. Seventy seven patients had dilatable stricture and the lower esophageal sphincter mechanism could be brought intra-abdominally in 70. In 36 there was radiographic evidence of hiatal hernia and 8 had a Barrett esophagus. The surgical technique employed in these cases was transgastric dilatation of the stricture, and Nissen fundoplication in 63 and partial fundoplication in 13 patients with peptic stricture post BI or BII6, gastroenterostomy or pyloromyotomy and vagotomy and post Heller myotomy. The post-operative mortality was 2.6% (2 in 77 patients) and morbidity 14.3%. Results after 5 years of follow-up have been classified as good to excellent in 88.3%. Six out of 9 remaining patients needed more than 3 dilatations in the first year after surgery and 3 of these were reoperated. Twenty four patients had a fixed stricture: In 22 of them, the area of esophagogastric stenosis was resected with replacement of the esophagus by colon interposition in 6, jejunum in 14, and a gastric tube with cervical anastomosis in 2. In two patients of advanced age and with respiratory problems a retrosternal by-pass with colon was performed. In this group the post-operative mortality was 12.5% (3 in 24 patients) and the morbidity 25%. The most common problems after one year of surgery were diarrhea (4 patients) and gastric fullness in 2. Eleven patients remained asymptomatic after 5 years (9 with jejunum interposition and 3 with colon) and 3 with jejunum were alive after 10 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1987

Effects of cell volume changes on membrane ionic permeabilities and sodium transport in frog skin (Rana ridibunda).

1. Membrane potential and conductances and short-circuit current were continuously measured with microelectrodes and conventional electrophysiological techniques in a stripped preparation of frog skin epithelium. The effects of the removal of chloride or sodium ions and the concentration or dilution of the serosal (inner) bathing solution were studied. 2. Chloride- or sodium-free solutions produced a cell depolarization of about 30 mV in parallel with a fall in the short-circuit current. Mucosal and serosal membrane conductances both decreased and the sodium permeability of the mucosal barrier was calculated to fall to about one-half its value in standard Ringer solution. The observed decrease in the short-circuit current is probably related to the combined effect of the decrease in sodium permeability and the decrease in the driving force across the mucosal membrane. 3. The removal of chloride or sodium ions reduced the depolarization caused by serosal perfusion with high-potassium solutions (50 mM-KCl). The ratio of the change in cell membrane potential under short-circuit conditions to the change in the potassium equilibrium potential (delta Ec(s.c.)/delta EK), was 0.59 in standard Ringer solution and 0.26 and 0.24 after the removal of chloride or sodium respectively. The depolarizing effect of barium-containing solutions (2 mM-BaCl2) was also markedly reduced in chloride- or sodium-free solutions, suggesting a decrease of the potassium selectivity of the serosal membrane in these conditions. 4. Increasing the osmolality of the serosal bathing solution produced similar effects, i.e. cell depolarization, fall in the short-circuit current and membrane conductances and reduction of the depolarizing effect of high-potassium and barium solutions. On the contrary, dilution of the serosal bath produced the opposite effects, consistent with an increase in the serosal permeability to potassium. 5. The effects of chloride- or sodium-free solutions were reversed by the dilution of the serosal bath. Cells repolarized when exposed to low-osmolality solutions after being in the absence of serosal chloride or sodium. The repolarization ran in parallel with the restoration of the short-circuit current and the potassium selectivity of the serosal membrane. 6. The results show that the effects produced by the removal of sodium or chloride ions from the serosal bathing solution are most probably mediated by a reduction in cell volume. Cell volume changes would lead to changes in the serosal membrane selectivity to potassium and thus to changes in cell membrane potential and sodium transport.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMedDate not supplied

[Challenges in the approach to adolescents: confidentiality and contraceptive orientation]

OBJECTIVE: The article has the purpose of presenting some questions related to professional ethics and juridical aspects of the approach to sexuality in adolescence, as well as of offering a practical review of the approach and contraceptive methods used by adolescents.METHODS: The bibliographic review encloses national and international literature, as well as juridical orientation in specific questions related to Child and Adolescent Statute and Brazilian Penal Code.RESULTS: Among the aspects of the approach to adolescents, confidentiality is distinguished as one of the most important strategies, mainly when the topic is associated to questions related to sexuality. In Brazil, although adolescents have been contributing in an effective way to the increase in the fecundity rate, there is, legally speaking, a hiatus concerning the guarantee of the rights of adolescents and professionals in exercise of contraceptive practice.CONCLUSIONS: The challenge for the health professionals, particularly the pediatricians who deal with adolescents, is to collaborate on the consolidation of rules which regulate the orientation in reproductive health for adolescents, once Brazilian Penal Code is anachronous concerning the reality of sexual behavior and its possible consequences.

Journal Article↗