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Biomedical subjects

F Godinho

Publications and source records attributed to F Godinho.

At least 19 recordsLinked to original sources

Subthalamic nucleus stimulation in Parkinson's disease : anatomical and electrophysiological localization of active contacts.

OBJECTIVES: 1 - To assess the anatomical localization of the active contacts of deep brain stimulation targeted to the subthalamic nucleus (STN) in Parkinson's disease patients. 2 - To analyze the stereotactic spatial distribution of the active contacts in relation to the dorsal and the ventral electrophysiologically-defined borders of the STN and the stereotactic theoretical target. METHODS: Twenty-eight patients underwent bilateral high-frequency stimulation of the STN (HFS-STN). An indirect anatomical method based on ventriculography coupled to electrophysiological techniques were used to localize the STN. Clinical improvement was evaluated by Unified Parkinson's Disease Rating Scale motor score (UPDRS III). The normalized stereotactic coordinates of the active contact centres, dorsal and ventral electrophysiologically-defined borders of the STN were obtained from intraoperative X-rays images. These coordinates were represented in a three-dimensional stereotactic space and in the digitalized atlas of the human basal ganglia. RESULTS: HFS-STN resulted in significant improvement of motor function (62.8%) in off-medication state and levodopa-equivalent dose reduction of 68.7% (p < 0.05). Most of the active contacts (78.6%) were situated close to (+/- 1.6 mm) the dorsal border of the STN (STN-DB), while 16% were dorsal and 5.4% were ventral to it. Similar distribution was observed in the atlas. The euclidean distance between the STN-DB distribution center and the active contacts distribution center was 0.31 mm, while the distance between the active contacts distribution center and the stereotactic theoretical target was 2.15 mm. Most of the space defined by the active contacts distribution (53%) was inside that defined by the STN-DB distribution. CONCLUSION: In our series, most of the active electrodes were situated near the STN-DB. This suggests that HFS-STN could influence not only STN but also the dorsal adjacent structures (zona incerta and/or Fields of Forel).

Action Potentials↗

Disruption of the murine nuclear factor I-A gene (Nfia) results in perinatal lethality, hydrocephalus, and agenesis of the corpus callosum.

The phylogenetically conserved nuclear factor I (NFI) family of transcription/replication proteins is essential both for adenoviral DNA replication and for the transcription of many cellular genes. We showed previously that the four murine NFI genes (Nfia, Nfib, Nfic, and Nfix) are expressed in unique but overlapping patterns during mouse development and in adult tissues. Here we show that disruption of the Nfia gene causes perinatal lethality, with >95% of homozygous Nfia(-/-) animals dying within 2 weeks after birth. Newborn Nfia(-/-) animals lack a corpus callosum and show ventricular dilation indicating early hydrocephalus. Rare surviving homozygous Nfia(-/-) mice lack a corpus callosum, show severe communicating hydrocephalus, a full-axial tremor indicative of neurological defects, male-sterility, low female fertility, but near normal life spans. These findings indicate that while the Nfia gene appears nonessential for cell viability and DNA replication in embryonic stem cells and fibroblasts, loss of Nfia function causes severe developmental defects. This finding of an NFI gene required for a developmental process suggests that the four NFI genes may have distinct roles in vertebrate development.

Animals↗

Death and replacement of uterine epithelial cells during oil-induced deciduoma development in the mouse.

BACKGROUND: A decidual cell reaction can be induced in rodent endometrium by an intrauterine injection of oil. The epithelial lining is thought to be instrumental to transduce intralumenal stimuli for decidualization. One of the consequences of oil injection is the death of uterine epithelial cells. No information is available on the effect that sustained contact with oil has on the epithelium. METHODS: A decidual cell reaction was induced in 4-day pseudopregnant mice by injection of 30 microliters of arachis oil into the uterine lumen. Samples from the uteri were collected 24, 48, and 72 h after the injection and prepared for transmission electron microscopy. RESULTS: Twenty-four hours after the oil injection, some of the initial modifications of epithelial cell surfaces were very similar to those induced by the contact with the blastocyst during normal pregnancy. Uterine epithelial cells internalized injected oil and many cells were seen in various stages of degeneration. At 48 h, many epithelial cells were detached from the basal lamina. At 72 h, the uterine lining was re-established by flattened cells. CONCLUSIONS: The contact of oil with the uterine epithelium of pseudo pregnant mice induces epithelial cell death in the antimesometrial region of the uterine crypt. There is, however, replacement of epithelial lining by epithelial cells, which probably migrate from the mesometrial region of the crypt. The prolonged presence of oil within the uterine lumen seems to induce cycles of epithelial cell death and replacement.

Animals↗

[Anti-melanoma immunoscintigraphy].

Nuclear Medicine has always contributed to the study of oncologic diseases. Immunoscintigraphy, one of its more recent developments, consists of the evaluation of the biodistribution of antibodies, directed against tumoral antigens and labelled with radionuclides. This technique, which has proven of special interest in some neoplasias, was used for the first time in 1983 in malignant melanoma of the skin. The antibody that has been more frequently used and which is used in the Instituto de Medicina Nuclear (IMN) of the Faculdade de Medicina de Lisboa, is antibody 225.28S, an IgG2a directed against a high molecular weight antigen present in the melanoma cell. In the IMN, we started immunoscintigraphy anti-melanoma in February 1992. During these two years, we have performed 67 exams, 44 on patients with malignant melanoma of the skin and 23 on uveal melanoma. We have obtained true positive rates and true negative ones, respectively, of 87.5% and 90% in melanoma of the skin, and 94% and 83% in uveal melanoma. It has been shown that the main clinical contribution of immunoscintigraphy for malignant melanoma of the skin is the study of loco-regional and distant metastases, namely those clinically unsuspected, as well as in the differential diagnosis of a lesion already known. In uveal melanoma, it is accepted that immunoscintigraphy may be useful in the evaluation of the primary lesion, namely in the differential diagnosis with other intra-ocular lesions.

Forecasting↗

[Molecular pathobiology in heart failure].

Heart failure is a pathophysiological state resulting from disturbed cardiac function. It is based on complex molecular processes, many of which are not fully understood. During heart failure adaptive mechanisms, that reinstall altered cardiac function, are activated. The main mechanisms are: a) Alteration of the structure and composition of myocytes by myocardial hypertrophy, reexpression of fetal and neo-natal proteins and the expression of certain proto-oncogenes; b) Activation of the neuroendocrinal system, specifically the sympathetic nervous system, renin-angiotensin-aldosterone system and vasopressin release; c) Activation of autocrine and paracrine systems. However, when these systems are activated beyond a certain limit they contribute to heart failure aggravation. This can also be promoted by alteration of the calcium metabolism inherent in heart failure. The synthesis of the counterregulator atrial natriuretic factor is also increased.

Atrial Natriuretic Factor↗

Choledochoenterostomy with an anti-reflux mechanism.

A new technique of choledochoenterostomy was devised to solve some of the problems of enterobiliary anastomosis with a normal calibre. The distal extremity of the common bile duct is completely surrounded by the bowel mucosa to a length of 3 cm after seromyectomy of a bowel wall rectangle of 4 x 1 cm. Experimental studies in rats and dogs demonstrated that this procedure prevents the risks of anastomotic disruption and functions like a mechanical unidirectional valve, which has great efficacy in stopping enterobiliary reflux. Studies in ten patients with obstructive jaundice with an extrahepatic biliary dilation less than 1.2 cm diameter submitted to this procedure confirmed the experimental results. All patients were asymptomatic, without jaundice and with normalization of the liver enzymes after 2 months. The permeability of the valvular anastomosis studied by cholangiography, the HIDA 99mTc test and manometry was quite similar to other classical biliary-enteric anastomosis. In contrast, anti-reflux efficacy was only demonstrated in patients with a valvular anastomosis.

Animals↗

Gastro-oesophageal and bile reflux--simultaneous quantitative assessment with gastric and gallbladder emptying evaluation: clinical applicability of a new computerized gammagraphic method.

The aim of this study was to develop a new computerized gammagraphic method to evaluate gastrooesophageal (GER), bileo-oesophageal (BER) and bileogastric reflux (BGR) simultaneously with gastric and gallbladder emptying: a long duration (60 min) and a dual energy detection (113Inm-sulphur colloid and 99Tcm-HIDA) test of the different refluxes during slow gastric emptying of an enteric feeding liquid meal. Forty patients with oesophagitis and 18 normal volunteers were evaluated. Good reproducibility of all the quantified parameters was found with r Spearman between 0.75 (P < 0.05) and 1.0 (P < 0.001). Patients with oesophagitis have a tendency for slower gastric emptying patterns (gastric emptying T1/2, GT1/2 P < 0.05). The calculated specificity for gallbladder emptying parameters was 77.8% for the gallbladder T1/2 BT1/2) and 94.4% for gallbladder residue at 60 min (BR60). The calculated accuracy for the GER index was 90%. The predictability for positive values was 95%, owing to a 90% sensitivity and 89% specificity. The predictability for negative values was 80%. The mean GER index in oesophagitis was greater than in controls (P < 0.001). The calculated specificity for BGR was 94.4% and reflux was detected in 12 out of 40 patients. The calculated specificity for BER was 83.3% for a '+' index and 94.4% for a '++' BER index. In 14 patients a positive BER index has been determined ('+' in three and '++' in 11 cases).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Ventilation and perfusion display in a single image.

A new method of ventilation and perfusion display onto a single image is presented. From the data on regions of interest of the lungs, three-dimensional histograms are created, containing as parameters X and Y for the position of the pixels, Z for the perfusion and colour for local ventilation. The perfusion value is supplied by sets of curves having Z proportional to the local perfusion count rate. Ventilation modulates colour. Four perspective views of the histogram are simultaneously displayed to allow visualization of the entire organ. Information about the normal ranges for both ventilation and perfusion is also provided in the histograms.

Adult↗

[Early left ventricular dysfunction in acute myocardial infarct. Evaluation using imaging methods].

A patient admitted in a Coronary Care Unit with an acute anterior myocardial infarction, is presented. He had initially normal left ventricular function and, on the 11th day he had, suddenly, an acute pulmonary edema. The reason for this episode was detected through imaging techniques--echocardiography and isotopic studies, and consisted on infarct expansion with early evolution for apical aneurysm. Contrast angiography confirmed the presence of a huge aneurysm and two vessels disease. Tallium Scintigraphy showed reversible ischemia beyond necrotic areas. The patient was submitted to aneurysmectomy and received three aorto-coronary bypass. He is now doing well, in class I, NYHA. The discussion emphasizes the actual role of imaging techniques in the diagnosis of infarct expansion and early functional aneurysm. We discuss the prognostic of infarct expansion and the importance of perfusion studies on defining areas of myocardium in jeopardy, enabling a better surgical approach.

Echocardiography↗

[Comparison of Holter electrocardiography and thallium 201 scintigraphy in the detection of myocardial ischemia].

OBJECTIVE OF THE STUDY: To compare ischemic changes (I) detected by Holter ECG (H ECG) to the myocardial perfusion defects found in 201 TI myocardial perfusion scintigraphy. DESIGN: 201 TI exercise test was made during the performance of a 24 hours H ECG. The validation of ST segment changes detected by H ECG during the exercise test was made on basis of reversible myocardial perfusion defects (RPD) detected on 201 TL and a relation between ST segment changes detected during the remaining 24 hours recording period and 201 TI (TI) RPD was established. SETTING: The patients (pt) included in the study have come from Cardiology and Heart Surgery Clinics of a Central teaching hospital. MATERIAL AND METHODS: 20 pt with a high coronary artery disease prevalence have been submitted to a two lead (V5 and aVF) 24 hour H ECG during which they have performed a symptom limited bicycle exercise test followed by an injection of 201 TI with acquisition 5 minutes later. Ischemic episodes detected on H ECG were quantified and their relation with heart rate and symptoms was established. As far as 201 TI studies are concerned the fixed and reversible perfusion defects as well as their location were evaluated. RESULTS: 1. H ECG: 6 pt (30%) presented ST changes on H ECG during the exercise test and a total of 9 pt (45%) had ST changes during exercise and during the remaining period of H ECG. 2. TI: 19 pt presented perfusion defects images (fixed in 7, reversible in 14, both kinds of defects in 7). 3. H ECG validation: H ECG during exercise presented I in 6 out of 14 pt with RPD on TI (sensitivity = 43%). Six of these 8 pt, with negative H and positive TI, had a chronic myocardial infarction. All the 6 pt with negative TI had negative H ECG (specificity = 100%). 4. H ECG TI comparison: 7 (50%) of the 14 pt with RPD had ST changes on 24 hrs H ECG. Seven of 11 pt with negative H ECG had RPD in TI. Two pt with negative TI had positive H ECG. These 2 pt had during H ECG a higher heart rate (HR) than the HR recorded during the exercise test. CONCLUSIONS: 1. In pt with known CAD, TI has a high sensitivity and specificity to show perfusion defects. 2. Considering TI as gold standard, H ECG showed to be a useful method to detect I in the studied population (sens. = 43%; spec. = 100%). 3. H ECG revealed to be an important diagnostic tool in detecting additional I episodes beyond the ones recorded during TI exercise test.

Adult↗

Primary chemotherapy with mitoxantrone and prednisone in advanced breast carcinoma. A phase II study.

Thirty-seven evaluable patients with progressive disseminated breast carcinoma were treated with a combination of mitoxantrone 14 mg/m2 i.v. every 3 weeks plus prednisone 20 mg/m2 p.o. daily with a reducing dose over several weeks. Thirteen of 37 patients (35%) achieved an objective response with two complete regressions. The median duration of response was 7 months and the median duration of survival 14 months. The cardiac function of all patients was monitored by serial left ventricular ejection fraction, at rest and after stress, and 3-monthly thereafter. Ten patients showed a deterioration in the ejection fraction after a minimum cumulative dose of 86 mg/m2 (six cycles), but only four developed clinical cardiac failure which was easily reversible after stopping mitoxantrone. Leucopenia was the dose-limiting toxicity. Nausea and/or vomiting were generally mild and transient. Alopecia was minimal. These results confirmed that this combination is effective and well tolerated in the treatment of disseminated breast carcinoma, and cardiotoxicity can be avoided with adequate monitoring of the left ventricular ejection fraction after six cycles of therapy (86 mg/m2).

Adult↗

Prostaglandin E2 gel compared to oxytocin for medically-indicated labour induction at term: a controlled clinical trial.

A clinical trial was carried out to compare the efficacy and tolerance of two modes of induction of labour: vaginally administered prostaglandin E2 gel vs intravenous perfusion of synthetic oxytocin. Fifty women with pregnancy at or near term in whom prompt vaginal delivery was clinically indicated were divided at random into sub-groups of 25 each. Initial dose of PGE2 gel was 1 mg followed by another application of 1 mg or 2 mg 6 hours later in case active labour stage has not been reached. Progressive oxytocin perfusion began with 1 mU/min., being increased gradually every 20 minutes until efficacious uterine dynamics were attained. Data were recorded on entry of age, parity, gestation age, cervical dilatation, Bishop score, indication for induction. Continuous materno-foetal monitoring was carried out during the induction period. Results were evaluated from induction/delivery time, type of delivery, maternal and foetal condition, and any side-effects which developed. Apart from a higher number of instrumental deliveries in the PGE2 gel series, which was not related to the induction method, there was no significant difference between any of the variables evaluated, both methods producing active labour in approximately 70% of the patients within 12 hours. The authors stress, however, the convenience, both for patients and hospital staff, of the administration of an intravaginal induction agent over a systemic therapeutic method of induction.

Administration, Intravaginal↗

A comparison of two doses of adriamycin in the primary chemotherapy of disseminated breast carcinoma.

Forty-eight patients with advanced breast carcinoma who had not received prior chemotherapy (minimum follow up 21 months) were randomised to receive either adriamycin 70 mg m-2 i.v. 3-weekly for 8 cycles (Regimen A) or adriamycin 35 mg m-2 i.v. 3-weekly for 16 courses (Regimen B). Objective responses were seen in 14/24 (58%) patients with regimen A (4 complete) and 6/24 (25%) with regimen B (1 complete) (P less than 0.02). The median duration of response was 14 months with regimen A and 6.5 months with regimen B. The median duration of survival was 20 months and 8 months respectively (P less than 0.01). The toxicity was similar with each regimen. There was no evidence of deterioration in left ventricular ejection fraction nor congestive heart failure in any patient. It is concluded that when given at 3-weekly intervals adriamycin is a more effective treatment for advanced breast cancer at higher rather than lower dosage.

Adult↗