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Biomedical subjects

Rui M B Maciel

Publications and source records attributed to Rui M B Maciel.

16 recordsLinked to original sources
PubMed2005

[Tolerance of the oral clonidine test in 180 patients: efficacy of the volemic expantion in controlling arterial hypotension].

Clonidine stimulation test is widely used to evaluate growth hormone secretion. Side effects are somnolence (35%) and arterial hypotension (AH) (5%). The aims of this paper were to evaluate the tolerance to this test regarding blood pressure (BP) decrease, sedation and the efficacy of saline resuscitation to prevent AH. BP was measured at basal, 60 and 120 min. Sedation was determined by the Ramsay scale. Patients were divided into two groups: Group 1 (n = 80) received saline resuscitation only upon severe AH (drop of mean BP [MBP] > 20% from initial MBP) and/or postural hypotension; Group 2 (n = 100) received saline resuscitation from the beginning of the test. Both groups presented a significant MBP fall and 75% presented somnolence at 60 min. MBP drop did not correlate with either sedation or the clonidine dose. Group 1 presented more hypotension (59% x 28%) and greater MBP drop at 60 min. Only one patient had an asthma attack. We conclude that the hypotension effects caused by oral clonidine diminish with saline resuscitation since the beginning of the test. This test must have specialized medical support with strict BP evaluation and precocious intervention when needed.

Adolescent↗
PubMed2004

[Incidence of malignant lesions in patients with clinically benign thyroid nodules: observational and prospective study in a cohort of 50 patients followed during two years].

INTRODUCTION: To study the frequency of malignant lesions in patients with clinically benign thyroid nodules and the value of the repetition of fine needle aspiration biopsy (FNAB). METHODS: Observational and prospective 2-year study in a cohort of 50 patients with clinically benign thyroid nodules. Patients were initially submitted to clinical examination, ultrasound (US) and FNAB1 patients, followed by a second FNAB and US. RESULTS: Palpation is not a good test for diagnosis and follow-up of thyroid nodules. On the other hand, the initial consideration that these patients should harbor benign lesions is a very useful parameter, since 47/50 patients (94%) did not present malignant lesions during the follow-up. FNAB1 and FNAB2 were concordant in 33/39 patients when FNAB1 was negative (85%); 11 patients were operated, 8 by suspicious FNAB and 3 due to nodule growth. We observed 2 patients with non-invasive papillary microcarcinoma and 1 patient with papillary carcinoma outside of the main nodules. CONCLUSION: there was concordance between initial clinical benign diagnosis, FNAB and the follow-up. In one case there was a papillary carcinoma. In addition, ultrasonography should be considered for all patients with suspected thyroid nodules. Finally, we demonstrated that a second cytology usually confirms the result of the first cytology in benign thyroid nodules.

Adolescent↗
PubMed2004

[Free thyroxine values during pregnancy].

Pregnancy induces a series of physiological modifications that include a significant elevation of thyroxine-binding globulin (TBG) levels. This elevation interferes in the serum levels of total thyroxine and stresses the use of free thyroxine (FT4), together with TSH measurement, as the first line tests in the evaluation of thyroid function in pregnancy. A careful definition of the normal values for FT4 during pregnancy is paramount for the study of thyroid abnormalities, since minimal dysfunctions can result in significant fetal abnormalities. We studied 132 normal pregnant women, from 6 to 38 weeks of gestation, and the serum FT4 measured by an indirect two-step assay (normal values for non-pregnant women: 0.7 to 1.5 ng/dL; mean+/-SD 0.98+/-0.14 ng/dL, n= 797) showed values between 0.5 and 1.3 ng/dL; mean+/-SD of 0.78+/-0.16 ng/dL, values significantly lower than the observed in non-pregnant women (P<0.0001). Values tended to decline progressively throughout pregnancy, with a significant negative correlation with TBG levels (rs= -0.51, P<0.0001), as well as with weeks of gestation (rs= -0.649, P<0.0001). TSH levels did not show any correlation with gestational age. Our data corroborate the need of a precise definition of FT4 normal values during pregnancy, aiming a better laboratory evaluation of thyroid dysfunctions in this group of patients.

Female↗
PubMed2004

[Thyrotoxic hypokalemic periodic paralysis, an endocrine emergency: clinical and genetic features in 25 patients].

Thyrotoxic hypokalemic periodic paralysis (THPP) is a medical emergency characterized by acute attacks of weakness, hypokalemia, and thyrotoxicosis that resolve with the treatment of hyperthyroidism. Attacks are transient, self-limited, associated with hypokalemia and resemble those of familial hypokalemic periodic paralysis (FHPP), an autosomal dominant neurological channelopathy. This study reviews the clinical features and genetic findings of THPP in 25 Brazilian patients. Most patients had weight loss, taquicardia, goiter, tremor, and ophthalmopathy. Most often attacks arose during the night and recovered spontaneously but some patients evolved to total quadriplegia, and few experienced cardiac arrhythmias. All patients had suppressed TSH and elevated T4 and most had positive anti-thyroid antibodies, indicating autoimmunity thyrotoxic etiology. Potassium was low in all patients during the crisis. Prophylactic potassium therapy has not been shown to prevent attacks; however it was useful for curbing the paralysis during the crisis. We identified the mutation R83H in the KCNE3 gene in one sporadic case, and M58V in the KCNE4 gene in one case with family history. Furthermore, we identified other genetic polymorphisms in the CACNA1S, SCN4A, KCNE1, KCNE2, KCNE1L, KCNJ2, KCNJ8 e KCNJ11 genes. We conclude that THPP is the most common treatable cause of acquired periodic paralysis; therefore, it must be included in the differential diagnosis of acute muscle weakness.

Adolescent↗
PubMed2004

Impact of long-term administration of amiodarone on the thyroid function of patients with Chagas' disease.

The effect of long-term treatment with amiodarone on patients with Chagas' disease has seldom been reported. This nonrandomized observational study attempted to analyze the follow-up of patients with Chagas' disease regarding their clinical evolution, thyroid dysfunction, and goiter. We compared 72 patients with long-term use (11 +/- 5 years) of amiodarone, including 22 patients who developed goiter, to 33 patients who did not use amiodarone, followed-up for 2 to 20 years (7 +/- 11 years). Follow-up of 72 patients for 9 +/- 5.4 years with periodic cardiac and thyroid function evaluations showed that only 26 maintained normal serum thyrotropin (TSH) levels; 24 presented with elevated levels; 4 had low levels, and 18 patients presented with fluctuations of TSH level. Among the 22 patients with goiter, only 3 (14%) patients maintained normal TSH, 8 (36%) had elevated TSH, 2 (9%) had low TSH, and 9 (41%) patients presented with fluctuating serum TSH levels. Most individuals remained clinically euthyroid with no evidence of cardiac impairment that could be attributed to thyroid dysfunction and the arrhythmias were adequately controlled by amiodarone. We suggest that amiodarone treatment may be continued for patients with Chagas' disease with arrhythmias, even in those who develop thyroid function abnormalities or goiter.

Amiodarone↗
PubMed2004

Comparison of practical methods for urinary glycosaminoglycans and serum hyaluronan with clinical activity scores in patients with Graves' ophthalmopathy.

OBJECTIVE: Immunosuppressive treatment of Graves' opthalmopathy (GO) should be restricted to patients with active eye disease, but assessing disease activity is difficult. Several methods to evaluate GO activity have been introduced, but none of them is satisfactory. Glycosaminoglycans (GAGs) are complex polysaccharides that participate on the pathogenesis of GO and attempts to correlate its local increase to urinary GAGs (uGAGs) or serum hyaluronan (sHA) have been made, but the available techniques are labourious, time-consuming and difficult for routine use. The aim of the present study is to develop practical and simple methods for uGAGs and sHA and compare them to the activity and severity of thyroid-associated ophthalmopathy. DESIGN, PATIENTS AND MEASUREMENTS: We developed a microelectrophoresis technique for uGAGs and a fluoroassay for sHA and assessed each in 152 patients with Graves' disease, 25 without GO and 127 with GO, classified according to the Clinical Activity Score (CAS). All patients had been euthyroid for > 2 months. RESULTS: Patients with inactive disease (CAS = 2, n = 100) had uGAGs (4.2 +/- 1.3 micro g/mg/creatinine) and sHA (11.1 +/- 7.2 micro g/l) that did not differ from normal subjects (3.1 +/- 1.1 micro g/mg/creatinine, n = 138 and 13.9 +/- 9.6 micro g/l, n = 395). In contrast, patients with active eye disease (CAS = 3, n = 27) had uGAGs (8.4 +/- 2.7 micro g/mg/creatinine) and sHA (32.3 +/- 17.8 micro g/l) 2-3 times higher than those patients with inactive eye disease. Using a cut-off of 6.1 micro g/mg creatinine for uGAGs and 20.7 micro g/l for sHA we found, respectively, 85% and 81% sensitivity and 93% and 91% specificity for each test. The positive and negative predictive values were 77% and 96% for uGAGs and 71% and 95% for sHA. CONCLUSION: Employing these two new methods we have established a significant relationship between the levels of uGAGs and/or sHA and the clinical activity of GO. Therefore, together with CAS, uGAGs determination, and, to a lesser degree, sHA, would be very useful in the discrimination from active and inactive ocular disease and aid in deciding on the best therapy for GO patients.

Acute Disease↗
PubMed2004

A preoperative diagnostic test that distinguishes benign from malignant thyroid carcinoma based on gene expression.

Accurate diagnosis of thyroid tumors is challenging. A particular problem is distinguishing between follicular thyroid carcinoma (FTC) and benign follicular thyroid adenoma (FTA), where histology of fine-needle aspirates is not conclusive. It is often necessary to remove healthy thyroid to rule out carcinoma. In order to find markers to improve diagnosis, we quantified gene transcript expression from FTC, FTA, and normal thyroid, revealing 73 differentially expressed transcripts (P < or = 0.0001). Using an independent set of 23 FTCs, FTAs, and matched normal thyroids, 17 genes with large expression differences were tested by real-time RT-PCR. Four genes (DDIT3, ARG2, ITM1, and C1orf24) differed between the two classes FTC and FTA, and a linear combination of expression levels distinguished FTC from FTA with an estimated predictive accuracy of 0.83. Furthermore, immunohistochemistry for DDIT3 and ARG2 showed consistent staining for carcinoma in an independent set 59 follicular tumors (estimated concordance, 0.76; 95% confidence interval, [0.59, 0.93]). A simple test based on a combination of these markers might improve preoperative diagnosis of thyroid nodules, allowing better treatment decisions and reducing long-term health costs.

Adenocarcinoma, Follicular↗
PubMed2003

The generation and utilization of a cancer-oriented representation of the human transcriptome by using expressed sequence tags.

Whereas genome sequencing defines the genetic potential of an organism, transcript sequencing defines the utilization of this potential and links the genome with most areas of biology. To exploit the information within the human genome in the fight against cancer, we have deposited some two million expressed sequence tags (ESTs) from human tumors and their corresponding normal tissues in the public databases. The data currently define approximately 23,500 genes, of which only approximately 1,250 are still represented only by ESTs. Examination of the EST coverage of known cancer-related (CR) genes reveals that <1% do not have corresponding ESTs, indicating that the representation of genes associated with commonly studied tumors is high. The careful recording of the origin of all ESTs we have produced has enabled detailed definition of where the genes they represent are expressed in the human body. More than 100,000 ESTs are available for seven tissues, indicating a surprising variability of gene usage that has led to the discovery of a significant number of genes with restricted expression, and that may thus be therapeutically useful. The ESTs also reveal novel nonsynonymous germline variants (although the one-pass nature of the data necessitates careful validation) and many alternatively spliced transcripts. Although widely exploited by the scientific community, vindicating our totally open source policy, the EST data generated still provide extensive information that remains to be systematically explored, and that may further facilitate progress toward both the understanding and treatment of human cancers.

Chromosome Mapping↗
PubMed2003

Practical determination of hyaluronan by a new noncompetitive fluorescence-based assay on serum of normal and cirrhotic patients.

A practical fluorescence-based assay method for determination of hyaluronan (HA) was developed. Plates were coated with hyaluronan-binding proteins (HABP) obtained from bovine cartilage and successively incubated with samples containing standard solutions of hyaluronan or serum from normal and cyrrhotic patients, biotin-conjugated HABP, and europium-labeled streptavidin. After release of europium from streptavidin with enhancement solution the final fluorescence is measured in a fluorometer. The method is specific for HA even in the presence of substantial amounts of other glycosaminoglycans (chondroitin, dermatan sulfate, and heparan sulfate, and heparin) or proteins. It is possible to quantify HA between 0.2 and 500.0 microg/L. Analyses of HA concentration in 545 normal subjects and 40 cirrhotic patients gave average values of 14.5 and 542.0 microg/L, respectively. It was also shown that older subjects (> or =51 years old) have more HA (28.0 microg/L) than younger subjects (12.0 to 14.0 microg/L). This new sandwich technique has shown high precision and sensitivity similar to those of a recently described fluorescence-based assay method, being able to measure HA in amounts as small as 0.2 microg/L. In addition, this noncompetitive assay avoids preincubation, consumes less time (<5 h) than the previous competitive fluorescence-based assay (>72 h), and avoids the use of radioactive materials.

Adolescent↗
PubMed2003

A novel germ-line point mutation in RET exon 8 (Gly(533)Cys) in a large kindred with familial medullary thyroid carcinoma.

Familial medullary thyroid carcinoma is related to germ-line mutations in the RET oncogene, mainly in cysteine codon 10 or 11, whereas noncysteine mutations in codons 13-15 are rare. We now report a new missense point mutation in exon 8 of the RET gene (1597G-->T) corresponding to a Gly(533)Cys substitution in the cysteine-rich domain of RET protein in 76 patients from a 6-generation Brazilian family with 229 subjects, with ascendants from Spain. It is likely that the mutation causes familial medullary thyroid carcinoma (FMTC), because no other mutation was found in RET, the mutation cosegregates with medullary thyroid carcinoma (MTC) or C cell hyperplasia (CCH) in patients subjected to surgery, and family members without the mutation are clinically unaffected. The histological analysis of 35 cases submitted to thyroidectomy revealed that 21 patients had MTC after the age of 40 yr and 8 before the age of 40 yr, 4 presented MTC or CCH before the age of 18 yr, 2 died due to MTC at the age of 53 and 60 yr, and CCH was found in a 5-yr-old child, suggesting a clinical heterogeneity. To improve the diagnosis of FMTC, analysis of exon 8 of RET should be considered in families with no identified classical RET mutations.

Adolescent↗
PubMed2002

Mutations linked to familial hypokalaemic periodic paralysis in the calcium channel alpha1 subunit gene (Cav1.1) are not associated with thyrotoxic hypokalaemic periodic paralysis.

OBJECTIVE: To investigate whether patients with thyrotoxic hypokalaemic periodic paralysis (THPP) have the same molecular defect in the calcium channel gene described in familial hypokalaemic periodic paralysis (FHPP), as the symptoms of both diseases are comparable, we analysed, in patients with THPP, the presence of mutations R528H, R1239H and R1239G on the S4 voltage-sensing transmembrane segment of the alpha1 subunit of the calcium channel gene (Cav1.1). DESIGN AND PATIENTS: Genomic DNA was extracted from peripheral blood from 14 patients with THPP, 13 sporadic cases and one with a family history. An FHPP family was selected as a positive control. The exons bearing the described mutations were amplified by PCR, screened by single-strand conformation polymorphism (SSCP), and further sequenced. MEASUREMENTS: THPP was diagnosed both clinically and through laboratory tests, all patients having elevated levels of thyroid hormones (T4, T3 or free T4), suppressed TSH and plasma potassium below 3 small middle dot5 mmol/l. RESULTS: No evidence of the described mutations was found in patients with THPP. Furthermore, we did not detect any mutations in any of the four full S4 voltage-sensing transmembrane segments of Cav1 small middle dot1 (DIS4, DIIS4, DIIIS4 and DIVS4) by direct sequencing. However, close to the R528H mutation, we identified two single nucleotide polymorphisms at nucleotides 1551 and 1564 in both familial and sporadic cases with THPP. In addition, we were able to detect the R528H mutation in the DIIS4 transmembrane segment in all members of the FHPP family. CONCLUSION: Mutations linked to familial hypokalaemic periodic paralysis in the calcium channel alpha1 subunit gene (Cav1.1) are not associated with thyrotoxic hypokalaemic periodic paralysis. However, polymorphisms in nucleotides 1551 and 1564 in the exon 11 were found in patients with familial hypokalaemic periodic paralysis and thyrotoxic hypokalaemic periodic paralysis in higher frequency than in controls. The polymorphisms identified within the Cav1.1 gene are associated with thyrotoxic hypokalaemic periodic paralysis and represent a novel finding.

Adult↗
PubMed2002

Screening for macroprolactinaemia and pituitary imaging studies.

OBJECTIVE: Hyperprolactinaemia is caused by high levels of monomeric, dimeric or macro forms of prolactin in circulation, the monomeric form being predominant in patients with prolactinomas. Macroprolactinaemia, however, is common and is associated with asymptomatic cases. In this study, we reviewed our records regarding clinical and imaging investigations in patients who were found to have hyperprolactinaemia predominantly due to the presence of macroprolactin and compared them with the findings observed in patients whose prolactin molecular size consisted predominantly of the monomeric form. PATIENTS AND METHODS: We conducted a retrospective study of 113 consecutive patients (nine men and 104 women, aged 19-67 years, median age 39 years) with hyperprolactinaemia who were screened for the presence of macroprolactin by polyethylene glycol precipitation and/or chromatography and submitted to pituitary magnetic resonance imaging (MRI) and/or computerized tomography (CT). RESULTS: Fifty-two of 113 patients (46%) had hyperprolactinaemia due to macroprolactin, whereas the remaining 61 patients (54%) had their hyperprolactinaemia confirmed by the predominance of the monomeric form. Both groups shared similar mean prolactin levels (79.9 +/- 63.6 micro g/l, median of 62.0 micro g/l, and 97.9 +/- 155.4 micro g/l, median of 61.0 micro g/l, respectively). Of the patients with macroprolactinaemia, 46% had no symptoms of hyperprolactinaemia, whereas only 10% of the patients who screened negative for macroprolactin were asymptomatic. There was an association between macroprolactinaemia and negative pituitary imaging findings: normal pituitary images were found in 78.9% of patients who had macroprolactinaemia and in 25% of patients with monomeric hyperprolactinaemia. In addition, none of the patients with macroprolactinoma (seven cases) had macroprolactinaemia. CONCLUSIONS: The presence of macroprolactinaemia does not exclude the possibility of a pituitary adenoma and consequently may not prevent pituitary imaging studies. However, our data demonstrate that all asymptomatic patients who screened positive for macroprolactin had normal pituitary imaging studies. Patient samples showing hyperprolactinaemia should be first tested for macroprolactin, before the patient is submitted to imaging studies. We suggest that imaging studies should be ordered in patients with macroprolactinaemia when indicated by clinically relevant features. As a result, unnecessary anxiety and costly medical procedures may be prevented.

Adult↗
PubMed2002

A mutation in the KCNE3 potassium channel gene is associated with susceptibility to thyrotoxic hypokalemic periodic paralysis.

Hypokalemic Periodic Paralyses comprise diverse diseases characterized by acute and reversible attacks of severe muscle weakness, associated with low serum potassium. The most common causes are Familial Hypokalemic Periodic Paralysis (FHypoKPP), an autosomal dominant disease, and Thyrotoxic Hypokalemic Periodic Paralysis (THypoKPP), secondary to thyrotoxicosis. Symptoms of paralysis are similar in both diseases, distinguished by thyrotoxicosis present in THypoKPP. FHypoKPP is caused by mutations in ionic channel genes calcium (CACN1AS), sodium (SCN4A) and potassium (KCNE3). Since both diseases are similar, we tested the hypothesis that THypoKPP could carry the same mutations described in FHypoKPP, being the paralysis a genetically conditioned complication of thyrotoxicosis. In 15 patients with THypoKPP, using target-exon PCR, CSGE screening, and direct sequencing, we excluded known mutations in CACN1AS and SCN4A genes. On the other hand, we were able to identify the R83H mutation in the KCNE3 gene in one sporadic case of THypoKPP, a man who had been asymptomatic until developing thyrotoxicosis caused by Graves' disease; we confirmed the disease-causing mutation in 2 of 3 descendants. R83H was recently found in two FHypoKPP unrelated families, in which the mutant decreased outward potassium flux, resulting in a more positive resting membrane potential. We, therefore, identified the first genetic defect in THypoKPP, a mutation in the KCNE3 gene.

Adult↗