Biomedical subjects

Manuela Carvalheiro

Publications and source records attributed to Manuela Carvalheiro.

17 recordsLinked to original sources

PubMed2006

[Diabetes in the elderly: our reality].

AIM: To evaluate the impact of the aging of our population in the growing of diabetes prevalence, among patients treated inward at our department. MATERIAL AND METHODS: The clinical files of 242 diabetics older than eighty years, treated between 1999 and 2002 were studied retrospectively. Demographic (sex, age, year of first contact), clinical (causes of admission, co-morbidities, duration of diabetes, previous hypoglycaemic treatment, duration of hospitalisation and evolution) and biochemical (glycaemia, HbA1c, lipaemia and C-peptide) data were recorded. RESULTS: A progressive rising in the number of aged patients was found during this period (seven in 1999 to 55 in 2002), with a large proportion of women (73%). The more frequent causes of in-hospital treatment were hyperglycaemia (20.6%) and feet ulcers (septic or necrotic) (16.5%). In nearly 42% of the cohort an acute infection was found. Diabetes was unknown in 13% of cases and less than ten years of duration in 38%. In this cohort most of the patients (77%) were treated with oral hypoglycaemic drugs, mostly sulfonylureas. HbA1c mean value was 10.4 +/- 2.2%; C -peptide was measured in a subset of cases (n=79), suggesting deficient insulin secretion in 18% of them. The global mean duration of hospitalisation was eleven days. Nineteen patients (8%) died during the hospitalization. CONCLUSIONS: In this study, we concluded that diabetes in people older than 75 years, is being progressively more often diagnosed. The general metabolic control was bad (HbA1c mean value--10.4 +/- 2.2%), with a significant number of patients presenting a deficient C-peptide secretion, worsened by frequent coexisting infections. So, a strengthened clinical care, directed to a careful diagnosis and treatment, may effectively contribute to a better prognosis and quality of life of aged diabetic patients.

Aged, 80 and over↗

PubMed2006

[Friedreich ataxia and diabetes mellitus--family study].

Friedreich's ataxia (FA) is one of the genetic syndromes sometimes associated with diabetes and the most common hereditary ataxia. It is a autosomal recessive neurodegenerative disease, caused by a mutation in the FRDA gene, which originates decreased expression of frataxin, a mitochondrial protein involved in iron metabolism. The disorder is usually manifest in childhood and is characterised by ataxia, dysarthria, scoliosis and feet deformity. About two thirds of patients have hypertrophic cardiomyopathy, 10% have diabetes and 20% have another glucose homeostasis disorder. Both insulin resistance and beta-cell dysfunction are implicated in this patients' diabetes pathophysiology. The mean half-life is 35 years. Cause of death is usually related to cardiomyopathy or diabetes' complications. We report the case study of two twin sisters with 28 years old, in whom FA was diagnosed in the first decade, both of them with diabetes since their early twenties. A third sister with FA is reported, with no glucose homeostasis disorder. They also have two healthy male brothers. Based in this cases, the FA associated diabetes pathophysiology is discussed, concerning the therapeutic approach to these patients and to their diabetic relatives without neurologic symptoms. The role of molecular genetic testing and genetic counselling are also debated.

Adult↗

PubMed2006

Malignant teratoma of the thyroid: case report.

Teratomas in the neck are rare neoplasms. Most of them occur in infants less than 1 year and are benign. In contrast, thyroid teratomas in adults are malignant and have fatal outcomes because of spread of tumor refractory to treatment. We report a case of a primary thyroid malignant teratoma in a 37-year-old woman. She was treated successfully with a combination of surgery, postoperative cis-platinum-based chemotherapy, and radiation therapy to the neck. Although the time of follow-up is short (24 months), we attribute her successful outcome to the use of this intensive therapeutic approach.

Adult↗

PubMed2006

PROP1 gene analysis in Portuguese patients with combined pituitary hormone deficiency.

OBJECTIVE: Mutations of the PROP1 gene lead to combined pituitary hormone deficiency (CPHD), which is characterized by a deficiency of GH, TSH, LH/FSH, PRL and, less frequently, ACTH. This study was undertaken to investigate the molecular defect in a cohort of patients with CPHD. DESIGN, PATIENTS AND MEASUREMENTS: A multicentric study involving 46 cases of CPHD (17 familial cases belonging to seven kindreds and 29 sporadic cases) selected on the basis of clinical and hormonal evidence of GH deficiency, central hypothyroidism and hypogonadotrophic hypogonadism, in the absence of an identified cause of hypopituitarism. Mutations of PROP1 were investigated by DNA sequencing. Clinical, hormonal and neuroradiological data were collected at each centre. RESULTS: PROP1 mutations were identified in all familial cases: five kindreds presented a c. 301-302delAG mutation, one kindred presented a c. 358C --> T (R120C) mutation and one presented a previously unreported initiation codon mutation, c. 2T --> C. Of the 29 sporadic cases, only two (6.9%) presented PROP1 germline mutations (c. 301-302delAG, in both). Phenotypic variability was observed among patients with the same mutations, particularly the presence and age of onset of hypocortisolism, the levels of PRL and the results of pituitary imaging. One patient presented a sellar mass that persisted into adulthood. CONCLUSIONS: This is the first report of a mutation in the initiation codon of the PROP1 gene and this further expands the spectrum of known mutations responsible for CPHD. The low mutation frequency observed in sporadic cases may be due to the involvement of other unidentified acquired or genetic causes.

Adolescent↗

PubMed2006

Noninvasive analysis of hepatic glycogen kinetics before and after breakfast with deuterated water and acetaminophen.

The contributions of hepatic glycogenolysis to fasting glucose production and direct pathway to hepatic glycogen synthesis were quantified in eight type 1 diabetic patients and nine healthy control subjects by ingestion of (2)H(2)O and acetaminophen before breakfast followed by analysis of urinary water and acetaminophen glucuronide. After overnight fasting, enrichment of glucuronide position 5 relative to body water (G5/body water) was significantly higher in type 1 diabetic patients compared with control subjects, indicating a reduced contribution of glycogenolysis to glucose production (38 +/- 3 vs. 46 +/- 2%). Following breakfast, G5/body water was significantly higher in type 1 diabetic patients, indicating a smaller direct pathway contribution to glycogen synthesis (47 +/- 2 vs. 59 +/- 2%). Glucuronide hydrogen 2 enrichment (G2) was equivalent to body water during fasting (G2/body water 0.94 +/- 0.03 and 1.02 +/- 0.06 for control and type 1 diabetic subjects, respectively) but was significantly lower after breakfast (G2/body water 0.78 +/- 0.03 and 0.82 +/- 0.05 for control and type 1 diabetic subjects, respectively). The reduced postprandial G2 levels reflect incomplete glucose-6-phosphate-fructose-6-phosphate exchange or glycogen synthesis from dietary galactose. Unlike current measurements of human hepatic glycogen metabolism, the (2)H(2)O/acetaminophen assay does not require specialized on-site clinical equipment or personnel.

Acetaminophen↗

PubMed2005

CYP2D6 genetic polymorphisms are associated with susceptibility to pituitary tumors.

Several polymorphisms of drug-metabolizing enzymes have been implicated in the susceptibility to tumor development. The role of the CYP2D6, GSTM1 and GSTT1 genes has been extensively studied, with alleles conferring different metabolic efficiencies and tumor risk. We studied the relationship between the main polymorphisms of these genes and the susceptibility to develop pituitary tumors, by performing a case-control study comprising 235 patients and 256 controls which were genotyped by means of PCR-RFLP based assays. Frequencies of the CYP2D6*1 and of the poor metabolizer allele CYP2D6*4, were determined along with the frequencies of the GSTM1 and GSTT1 null genotypes. CYP2D6 genotype frequencies were similar in patients and controls (p=0.087). CYP2D6*1 and CYP2D6*4 allele frequencies were 83.8%, 16.2% in cases and 78.3%, 21.7% in controls, showing a significant difference between the two groups (p=0.012). There were no significant differences between the frequencies of the GSTM1 and GSTT1 null genotypes in both groups. No association was found between histological type and any of the studied polymorphisms. Our data suggest an association of the CYP2D6*1 allele and the susceptibility to pituitary adenomas, which could be due to an increased metabolism of unidentified procarcinogens or to linkage disequilibrium with another gene involved in pituitary tumorigenesis.

Adenoma↗

PubMed2005

Simple measurement of gluconeogenesis by direct 2H NMR analysis of menthol glucuronide enrichment from 2H2O.

The contribution of gluconeogenesis to fasting glucose production was determined by a simple measurement of urinary menthol glucuronide (MG) 2H enrichment from 2H2O. Following ingestion of 2H2O (0.5% body water) during an overnight fast and a pharmacological dose (400 mg) of a commercial peppermint oil preparation the next morning, 364 micromol MG was quantitatively recovered from a 2-h urine collection by ether extraction and a 125 micromol portion was directly analyzed by 2H NMR. The glucuronide 2H-signals were fully resolved and their relative intensities matched those of the monoacetone glucose derivative. The pharmacokinetics and yields of urinary MG after ingestion of 400 mg peppermint oil as either gelatin or enteric-coated capsules 1 h before breakfast were quantified in five healthy subjects. Gelatin capsules yielded 197 +/- 81 micromol of MG from the initial 2-h urine collection while enteric-coated capsules gave 238 +/- 84 micromol MG from the 2- to 4-h urine collection.

Adult↗

PubMed2004

[Anaplastic thyroid tumor: retrospective analysis of 12 cases].

Anaplastic thyroid tumor is a rare tumor and constitutes 5 to 10% of thyroid carcinomas. Is one of the most aggressive solid tumors and the prognosis is always fatal with a mean survival of 3 to 7 months. The current therapeutics are scarce and inefficacious. A retrospective analysis was performed in 12 clinical cases of anaplastic thyroid tumor observed at the Department of Endocrinology, Diabetes and Metabolism of the University Hospital of Coimbra. We analysed data relative to sex, previous thyroid pathology, clinical signs and symptoms, date of diagnosis, treatment and outcome. In this series, the anaplastic thyroid carcinoma showed to be a highly malignant tumor with a mortality rate of 100% with a survival after the diagnosis between 15 days and 9 months.

Aged↗

PubMed2004

[ACTH-dependent Cushing's syndrome: a revision of 43 cases].

AIM: To evaluate the characteristics and outcomes of the patients diagnosed as ACTH-dependent Cushing syndrome, registered in the department. MATERIAL AND METHODS: We reviewed the files of forty-three patients followed from 1974 to 2002. RESULTS: A progressive rise in the number of patients diagnosed was found, being 80% females. Clinical suspicion was based mostly on the typical fat distribution; hirsutism and amenorrhoea were important in women. The more reliable diagnostic tests were: 11 pm cortisol, day curve of ACTH and cortisol, and dexamethasone suppression tests. The ACTH response to CRH during inferior petrosal sinus sampling permitted the diagnosis of ectopic source. In thirty-seven patients a pituitary adenoma was diagnosed. The three patients diagnosed before 1985 went for bilateral adrenalectomy (Nelson's syndrome in two); the others were submitted to transsphenoidal pituitary adenomectomy, obtaining remission in twenty six at the first operation and in two others at the second. Three patients had a recidive. Of the six patients with persistent disease (all treated with metyrapone or ketoconazole), three were submitted to radiotherapy, two to bilateral adrenalectomy, and one was waiting for surgery. Four patients had a bronchial carcinoid, successfully removed in three. One patient was lost to follow-up and another was still being evaluated. CONCLUSIONS: We found a positive evolution in the capacity to diagnose and treat these patients. Neurosurgical ability to achieve remission was 80% in the operated cases. More effective technical methods and drugs, as well as a multidisciplinary and dedicated medical team, lead to long lasting remissions in most of the patients.

Adolescent↗

PubMed2004

Platelet hyperactivation in maintained growth hormone-deficient childhood patients after therapy withdrawal as a putative earlier marker of increased cardiovascular risk.

GH deficiency (GHD) is associated with a higher risk of vascular disease, whose pathophysiological mechanisms remains not yet fully elucidated. This study aimed to assess the main cardiovascular risk indexes, plasma catecholamines content, and the platelet function in childhood-onset GHD patients. Some of the main clinical examinations related with cardiovascular risk, plasma catecholamines content, as well as platelet intracellular free calcium concentration ([Ca(2+)](i)), whole-blood aggregation, and morphology were evaluated in childhood-onset GHD patients treated with GH for a variable period and off GH therapy for at least 2 yr before entry into study and in sex-, age-, and body mass index-matched control groups. Among the patients, group 1 (GHD-1) has recovered GH levels after withdrawal, whereas group 2 (GHD-2) has remained GH deficient. Minor differences on the cardiovascular risk indexes were observed between the groups. Plasma catecholamine concentrations in the GHD groups did not statistically differ from the control group, but higher adrenaline content was observed in the GHD-2 group when compared with the GHD-1 one. Basal and thrombin-evoked [Ca(2+)](i) and platelet aggregation were identical between the GHD-1 group and the matched control. However, the GHD-2 group has increased thrombin-evoked [Ca(2+)](i) (297.0 +/- 15.7 Deltanmol/liter; P < 0.01), collagen, and ADP-induced platelet aggregation (33.3 +/- 4.3 and 12.5 +/- 2.1 Omega, respectively; P < 0.05) vs. the control-2 group (Delta[Ca(2+)](i): 102.1 +/- 13.6 Deltanmol/liter; aggregation: 19.6 +/- 2.9 and 6.2 +/- 0.8 Omega). The platelet hyperreactivity state in the GHD-2 was reinforced by morphologic studies of electron microscopy. In conclusion, there were minor differences between the GHD-1 group and the controls, which might be due to the recovery of GH levels after therapy withdrawal. However, the maintained GHD group, despite minor cardiovascular risk index differences, has increased [Ca(2+)](i) and aggregation, which could indicate a hyperactivation state that might be viewed as an earlier marker of cardiovascular disturbances.

Adult↗

PubMed2004

[Pancreas transplantation].

A clinic case of simultaneous pancreas/kidney transplantation on a type 1 diabetic patient is described. A six years follow-up was made with both organs functionating and a good quality of live. Then the authors make a review of the available surgical techniques, indications and complications of this form of treatment. A comparison between the Portuguese and the International experience was discussed.

Adult↗

PubMed2003

[Autoimmune hypophysitis or lymphocytic hypophysitis].

This entity, due to the pituitary lymphoplasmacytic infiltrate, was described for the first time in 1962. The clinical suspicion relies on a rapidly progressing hypopituitarism, particularly with adrenal involvement, affecting women in the peripartum period or patients with previously recognized autoimmune disease. Diabetes insipidus is also often reported. A sellar mass is found in 80% of cases. The diagnosis is confirmed by histology, due to the absence of a specific serological test. The endocrine deficiencies are frequently definitive. Corticotherapy is usually effective in reducing neurological symptoms due to pituitary enlargement, and frequently allows to avoid surgery. The disease-related deaths were due to acute adrenal insufficiency or ineffectively treated hypopituitarism. We are reporting a clinical case of probable lymphocytic hypophysitis in the early post partum of a woman with depression and Graves disease. She has hyperprolactinemia and ACTH deficiency, without pituitary changes in the magnetic resonance imaging. She was treated and her depression and hyperthyroidism were relieved. Hyperprolactinemia recovered spontaneously but she still needs glucocorticoid substitution.

Adult↗

PubMed2003

Screening for pancreatic exocrine insufficiency in patients with diabetes mellitus.

OBJECTIVES: Fecal elastase 1 (E1) is a relatively sensitive and specific indirect test of pancreatic exocrine function. Despite the high functional reserve of the pancreas, it is recognized that a significant proportion of diabetic patients may also have a deficit of the exocrine function. The aim of this study was to screen patients with diabetes mellitus (DM) for pancreatic exocrine insufficiency. METHODS: A total of 80 patients were enrolled in this prospective study, including 42 patients with DM and 38 nondiabetic controls. Exclusion criteria were as follows: age >75 yr; alcohol intake >40 g/day; intake of orlistat or acarbose; and history of diarrhea, pancreatitis, GI surgery, immunodeficiency, or cancer. All patients underwent the same study protocol, which included clinical evaluation, determination of fecal E1, plain x-rays of the abdomen, and abdominal ultrasound. An immunoenzymatic method (ScheBoTech, Wettenburg, Germany) was used for E1 determination. Diagnosis of pancreatic insufficiency was established for a fecal E1 <200 microg/g. RESULTS: The DM and control groups were comparable regarding age (62 +/- 10 yr vs 56 +/- 10 yr), sex (18 men and 24 women vs 15 men and 23 women), and proportion of patients with excess weight (50% vs 42%). Patients had DM diagnosed for 11.5 +/- 8 yr, with structural changes of the pancreas detected on ultrasound in three cases and calcifications in one case. There was no relationship between E1 determination <200 microg/g and the duration or the type of therapy for DM. Fifteen patients (36%) in the DM group had a fecal E1 <200 microg/g, compared with two patients (5%) in the control group (p < 0.05). In the DM group (n = 42), 11 patients with excess weight presented a fecal E1 <200 microg/g, whereas four patients with a BMI <25 presented this result (p < 0.05). CONCLUSIONS: Pancreatic exocrine insufficiency occurs more frequently in diabetic patients than in controls. Diabetic individuals with excess weight (BMI >25) may be at increased risk for underlying exocrine pancreatic insufficiency.

Aged↗

PubMedDate not supplied

Early onset of medullary thyroid carcinoma in a kindred with multiple endocrine neoplasia type iia associated with cutaneous lichen amyloidosis.

OBJECTIVE: To describe the molecular characterization of a kindred affected by the rare variant of multiple endocrine neoplasia type IIA (MEN IIA) associated with cutaneous lichen amyloidosis and to discuss the clinical implications in the management of this syndrome. METHODS: A kindred with four affected family members was identified, and DNA analysis was performed by sequencing exon 11 of the RET proto-oncogene. Presymptomatic genetic screening was offered to all first-degree relatives. RESULTS: Sequencing analysis of the RET proto-oncogene revealed a Cys634Trp (TGC->TGG) mutation in all clinically affected family members and in an asymptomatic 5-year-old child who, after thyroidectomy, was found to have multicentric medullary thyroid carcinoma and C-cell hyperplasia. A Gly691Ser (GGT->AGT) polymorphism was also detected in this family but did not segregate with the disease. CONCLUSION: To our knowledge, this is the earliest detection of medullary thyroid carcinoma reported thus far in a kindred with MEN IIA associated with cutaneous lichen amyloidosis, and this finding suggests that prophylactic thyroidectomy, in kindreds with this variant, should be performed before the age of 5 years.

Adult↗

PubMedDate not supplied

[Diabetic nephropathy. Study protocol for pre-kidney transplantation].

Between May 1990 and October 1998, 67 diabetic patients with end-stage renal disease, on dialysis, were submitted to a standardized protocol in order to assess the coexistence and degree of other diabetic and nondiabetic complications that could affect transplantation. Some of the results were analysed. Type 2 diabetic patients had more abnormal results on the lower limbs doppler ultrasound and on the lower limbs arteriography than type 1 (p < 0.05). Type 2 diabetic patients had more cardiovascular complications so the decision to transplant should be taken on a case by case basis.

Adult↗

PubMedDate not supplied

[Radiotherapy of pituitary tumors].

The aim of this study is to evaluate the use of conventional external radiotherapy in patients with pituitary adenomas. Between October 1970 and May 1998, 27 patients with pituitary adenoma were followed at the Department of Endocrinology and Diabetes of the Hospitais da Universidade de Coimbra. They received radiation therapy at Instituto Português de Oncologia. Seven of those tumors were classified as nonfunctioning adenomas, 17 as growth-hormone-secreting adenomas, 2 as prolactinomas and 1 as adrenocorticotropic adenoma. Twenty-six patients received radiation as adjuvant therapy after incomplete resection and one patient as primary treatment. The majority of these cases were treated using the parallel opposed-field technique with a total dose between 45 and 52 Gy. The patients were submitted, before and after radiotherapy, to a protocol in order to assess the efficacy of this treatment. Some of the results were analyzed. Reduction of tumor mass was achieved in 66.6% of nonfunctioning tumors and in 25% of the secreting ones. Reduction or stabilization of hormonal levels was achieved in 55% of the cases and normalization in 30%. The average duration of follow-up was 126.3 months. Complications observed: hypopituitarism, stroke (3 patients), cerebral edema (1 patient), memory loss (2 patients) and hearing loss (2 patients). None of the patients developed brain tumors.

Acromegaly↗

PubMedDate not supplied

[Diabetic hyperosmolality. Retrospective study of 60 cases].

AIMS AND METHODS: Our aims were to determine the frequency of diabetic hyperosmolality (DH) in our Department, its causes, therapeutic implications and evolution. A five-years retrospective study was performed in 60 patients regarding age, sex, type and duration of diabetes mellitus (DM), previous antidiabetic therapy, underlying diseases, biochemical data, precipitating factors, therapeutic management and outcome. RESULTS: The hyperosmolar coma was responsible for 90% of the metabolic comas and for 3% of the diabetic patients. The median age of the cohort was 54.6 +/- 9.4 years, being females 61.7% and males 38.3% In 40% no prior diagnosis of DM was made and in the remaining patients the previous antidiabetic therapy was unknown in 61%. Altered consciousness was found in 90%, being 28% in coma. The metabolic acidosis was detectable in 22.2%, the average glycaemia was 956 +/- 267 mg/dl and the osmolality was 349.4 +/- 34.3 mosm/l. The precipitating factors were: poor metabolic control in all patients (HbA1C 12.5 +/- 2.75%), infections in 76.6%, suspension of antidiabetic therapy in 10% and concomitant hyperglycaemic drugs in 6.6% of patients. The global mortality was 20%. CONCLUSIONS: The majority of the situations could be preventable if an attempted screening and diagnosis of DM was made and precipitating factors avoid or promptly treated.

Diabetes Complications↗