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Biomedical subjects

A Sousa

Publications and source records attributed to A Sousa.

At least 37 records · Page 2Linked to original sources
PubMed1999

Nitric oxide (NO) release by glutamate and NMDA in the dorsal horn of the spinal cord: an in vivo electrochemical approach in the rat.

Glutamate acts as a neurotransmitter of primary afferent messages in the spinal cord. Through glutamatergic mechanisms nitric oxide (NO) is also a potential intermediary in the transmission of sensory messages, particularly nociceptive, at the spinal level. The aim of the present study was, by using electrochemical monitoring of NO, to determine if the activation of glutamatergic transmission, particularly through NMDA receptors, could increase NO production within the dorsal horn of the lumbar spinal cord in the rat. 30 micrometers diameter treated carbon fiber electrodes coated with nickel-porphyrine and Nafion(R), and associated with differential normal pulse voltammetry, have been used in vivo to monitor NO within the dorsal horn of the lumbar spinal cord of decerebrated-spinalized rats. A NO-dependent peak of oxidation current (650 mV vs. Ag-AgCl), remaining stable for up to 3 h (+/-5%) could be detected under basal conditions, which indicates that significant amounts of NO are produced continuously. The non-competitive N-methyl-d-aspartate (NMDA) channel blockers, Ketamine (100 mg kg-1 i.p.) and MK-801 (10 mg kg-1 i.p.), decreased the voltammograms to 70+/-5% and 69+/-2% of controls at 120 min, respectively. Glutamate (10 mM), when directly superfused upon the spinal cord (20 min at 50 microliters min-1) induced a rapid and significant increase of the 650 mV peak, with a maximum at around 90 min (148+/-6% of control) followed by a slow decay (138+/-4% of control at 150 min). This increase could be totally reversed or blocked by i.p. injection of 100 mg kg-1 of Ketamine. NMDA (30 mg kg-1 i.p.) induced a long-lasting increase in the peaks (149+/-11% at 90 min and 162+/-20% at 120 min), which was also fully reversed by Ketamine or MK-801. These results provide in vivo direct evidence of a glutamate- and/or NMDA-induced release of NO at the spinal level, and is discussed in relation to the glutamatergic transmission of primary afferent messages.

Animals↗
PubMed1999

Genetic anticipation in Portuguese kindreds with familial amyloidotic polyneuropathy is unlikely to be caused by triplet repeat expansions.

Familial amyloidotic polyneuropathy (FAP) is a lethal autosomal dominant type of amyloidosis resulting from the deposition of transthyretin (ATTR) variants in the peripheral and autonomic nervous systems. ATTR V30M-associated FAP exhibits marked genetic anticipation in some families, with clinical symptoms developing at an earlier age in successive generations. The genetic basis of this phenomenon in FAP is unknown. Anticipation has been associated with the dynamic expansion of trinucleotide repeats in several neurodegenerative disorders, such as Huntington disease, myotonic dystrophy, and fragile X syndrome. We have used the repeat expansion detection (RED) assay to screen affected members of Portuguese FAP kindreds for expansion of any of the ten possible trinucleotide repeats. Nine generational pairs with differences in their age of onset greater than 12 years and a control pair with identical ages of onset were tested. No major differences were found in the lengths of the ten trinucleotide repeats analyzed. The distribution of the maximal repeat sizes was consistent with reported studies in unrelated individuals with no known genetic disease. The present data do not support a role for trinucleotide repeat expansions as the molecular mechanism underlying anticipation in Portuguese FAP.

Adolescent↗
PubMed1998

[Coronary arteriography with a very low profile catheter: efficacy and safety of the procedure and of the 60 minute hospital discharge].

PURPOSE: To evaluate the feasibility, efficacy and safety of the use of 4F Judkins catheters for coronary angiography. METHODS: From August/95 to January/96, 70 patients with suspected coronary artery disease underwent coronary cineangiography by the Judkins technique, with 4F catheters. Following puncture of the right femoral artery, 4F sheaths were introduced. At the end of the procedure, the sheath was removed and manual compression was applied for 15 min. Patients were oriented to walk under specialized supervision, 60 min after the procedure, and discharged after 4h. RESULTS: Thirty nine (56%) patients were male, the age ranged from 31 to 83 (mean 57) years and weight from 43 to 101 (mean 69) kg. Optimal quality images were obtained in 62 patients (88%). It was necessary to use larger caliber catheters (6 and 8F) in 8 patients, due to femoral tortuosity or inadequate opacification of coronary arteries. There were no vascular complications nor major bleedings. In only 2 cases (3%) there was a minor bleeding, treated by new local compression. Sixty (85%) patients walked after 60 +/- 5 min and were discharged after 4h. CONCLUSION: The use of 4F catheters for coronary angiography by femoral approach allowed early deambulation with no major bleeding. Image quality was good, with little contrast used and short hospital stay. This technique may lead to a simpler less traumatic and less invasive coronary angiography.

Adult↗
PubMed1997

Localization of endothelial proliferation and microvascular expansion in active plaque psoriasis.

Expansion of the dermal microvasculature is a prominent feature of psoriasis. Although the pathogenetic process resulting in vascular morphological changes remains unclear, considerable evidence suggests the involvement of angiogenesis. To assess the degree and site of psoriatic microvascular expansion, immunohistochemical studies were performed on paired lesional and non-lesional specimens from 10 patients with active, untreated plaque psoriasis. Five-micron thick sections were labelled with monoclonal antibody JC/70A specific for the endothelial marker CD31, and vascular quantification was achieved using hue-saturation-intensity image analysis. Assessment of vasculature in the papillary dermis (superficial plexus) demonstrated a fourfold increase in endothelial surface area of lesional compared with non-lesional skin (P < 0.01), while there was no significant increase in vasculature of the upper reticular dermis. Subsequently, 18-micron thick sections were double-labelled with MIB-1 antibody to the nuclear proliferation marker Ki-67 and JC/70A. Endothelial cell proliferation was identified in the vertical limbs of capillary loops in eight out of 10 lesional biopsies and in no non-lesional biopsies. The endothelial MIB-1 labelling index was 3.1% of total endothelial cells of the superficial plexus. These findings confirm endothelial proliferation underlying psoriatic microvascular expansion, and indicate that this process is limited to a specific site in the dermal capillary bed.

Adult↗
PubMed1997

Interactions of the neurosteroid dehydroepiandrosterone sulfate with the GABA(A) receptor complex reveals that it may act via the picrotoxin site.

The interactions of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) were investigated with various binding sites of the gamma-aminobutyric acid (GABA(A)) receptor complex to rat brain membranes, and on GABA-induced [36Cl-] influx in mammalian cortical cultured neurons. DHEAS and DHEA did not affect the binding of [3H]flunitrazepam to the benzodiazepine binding sites. In contrast, DHEAS, but not DHEA, inhibited the binding of [3H]GABA and [35S]TBPS to rat brain cerebral cortical and cerebellar membranes in a concentration-dependent manner. DHEAS decreased the Bmax values of both the high and low affinity GABA receptor binding sites without affecting their affinity constants. In contrast, DHEAS inhibited [35S]TBPS binding competitively, as analyzed by Scatchard analysis. In dissociation kinetic studies, DHEAS dissociated [35S]TBPS from rat cerebral cortical membranes in a monophasic pattern that was similar to that observed with inhibitors of GABA(A) receptors such as TBPS and picrotoxin but different from pentobarbital and GABA. Taken together, these results suggest that DHEAS binds to the TBPS/picrotoxin site of the GABA(A) receptor complex, and this interaction may be responsible for the noncompetitive inhibition of GABA responses observed with DHEAS. Furthermore, we confirmed that DHEAS inhibits GABA responses, as measured by GABA-induced [36Cl-] influx in cultured cortical neurons. Studies with DHEA indicate that this neurosteroid does not interact with the GABA(A) receptor complex.

Animals↗
PubMed1997

[Risk factors for cerebrovascular stroke in a cohort of hypertensive patients].

OBJECTIVES: To identify stroke risk factors in hypertensive patients and the probability of stroke in relation to those risk factors and follow-up. STUDY DESIGN: A cohort study (patients with high blood pressure). MATERIAL AND METHODS: 707 hypertensive patients were studied (Hypertension Register) in what concerns stroke incidence until 1992 (n = 126), considering one case per individual. The following variables were analysed: age, sex, body mass index (Quetelet), systolic and diastolic blood pressure, heart rate, types of hypertension (JNC-IV), left ventricular hypertrophy, changes in ST segment and T wave (Minnesota Code), fundi, angina pectoris, heart failure, central nervous (neurological) disturbances, antihypertensive treatment, smoking, serum potassium, serum sodium, blood urea, creatinine, uric acid, blood sugar, diabetes and cholesterol, in the initial record. Individually, in relation to the control of hypertension, the subjects were classified according to the casual recording of normal blood pressure, the absence of drug treatment, diastolic pressure > 114 mmHg and, at the end of 1992, according to survival, causes of death and follow-up. Stroke risk factors have been identified by multivariate analysis (Cox regression model). The survival probability (without stroke) was defined by Kaplan-Meier method. RESULTS: It was possible to maintain the epidemiological surveillance, from 1975 to 1992, of 598 cases. From those, 109 hypertensive patients were victims of at least one episode of non transient cerebral ischaemia, during their follow-up of 10.5 years. From the characteristics studied, only five were identified at risk factors. The adjusted relative risks and confidence intervals (95% CI) were the following: age: 1.08 (1.06-1.10); diastolic pressure > 114 mmHg: 1.96 (1.32-2.91); neurological disturbances 4.64 (2.99-7.2); diabetes: 2.57 (1.62-4.05) and left ventricular hypertrophy: 1.34 (1.13-1.58). CONCLUSIONS: As far as stroke is concerned: a) Age, diabetes, a casual measurement of diastolic blood pressure > 114 mmHg and left ventricular hypertrophy (electrocardiogram) were the risk factors identified; b) Prevention should include blood pressure and diabetes control, although this disease has shown more risk than a casual measurement of severe hypertension; c) Its occurrence, in this model, has only partly been explained, therefore it has become necessary to deepen the study of the risk profile.

Adult↗
PubMed1995

Genetic epidemiology of familial amyloidotic polyneuropathy (FAP)-type I in Póvoa do Varzim and Vila do Conde (north of Portugal).

Familial amyloidotic polyneuropathy (FAP-type I) was first described in Portugal by Andrade in 1952, a time when 54 among 64 patients (belonging to 25 families) originated from Póvoa do Varzim or its surrounding districts. Since then, a total of 1,233 patients, belonging to 489 pedigrees (so far unrelated), have been diagnosed at Centro de Estudos de Paramiloidose, Porto, Portugal. Although age-of-onset showed a wide range (17 to 78 years), 87% of these 1,233 patients developed symptoms before 40 years of age (mean 33.5, SD 9.4 years). Among all patients, 432 belong to 140 families originating from the area of Póvoa do Varzim/Vila do Conde, 330 of whom lived in that area at the time of diagnosis; age-of-onset was, on average, lower than in the overall group of patients (mean 31.1, SD 6.7 years), and no patient had onset after 57 years (versus 3.3% in the global sample). As in previous studies, women were found to have a later onset (33.7) than men (29.0) years. In 1991, the crude prevalence rate was 90.3 x 10(-5) (one in every 1,108 inhabitants), and the frequency of gene carriers was estimated to be 186 x 10(-5) (one in every 538); about 48.4% of these carriers had manifested symptoms by 1991. Female patients had a significantly higher number of children (mean 3.7, SD 2.6) than male patients (mean 2.7, SD 2.1) and the length of their reproductive period (mean 8.4, SD 5.8 yr) was also greater than for men (mean 5.6, SD 4.4 yr). Altogether, the 122 patients who ever reproduced contributed 457 children to the next generation, a mean fertility of 3.7. Further studies using a control groups may answer the question of whether this is the result of a specific high fertility of these patients or just their belonging to a population in natural expansion.

Adult↗
PubMed1995

Altered vascular endothelium integrin expression in psoriasis.

Considerable evidence indicates that microvascular changes observed in psoriasis are a result of vascular proliferation. A critical step in the sequence of events leading to neovascularization involves interactions between endothelial cells and extracellular matrix proteins mediated in part by the integrin family of adhesion molecules. A number of endothelial integrins have been shown to participate in neovascularization, including members of the beta 1, beta 3, and beta 4 subfamilies. To investigate the role of these integrins in psoriasis, specimens of lesional and nonlesional skin were taken from 10 patients with active, untreated plaque disease. Vascular endothelium was labeled with monoclonal antibodies specific for alpha 2, alpha 5, alpha 6, beta 1, av beta 3, and beta 4 integrins. The use of image analysis permitted quantification of immunoperoxidase staining and comparison of endothelial labeling in lesional and nonlesional skin. There was a significant increase in endothelial staining of av beta 3 integrin in lesional compared with nonlesional skin, both in superficial and deep vasculature. In contrast, there was a significant decrease in endothelial beta 4 staining in lesional compared with nonlesional superficial dermal vessels, alpha 2, alpha 5, alpha 6, and beta 1 staining showed no significant difference between the two groups. These results demonstrate an important role of av beta 3 and beta 4 integrins in the microvascular changes of psoriatic lesions.

Adult↗
PubMed1994

Chronic haemodialysis for very old patients.

There is in the Western World a progressive ageing of the population, and consequently haemodialysis patients are also getting older. Some ethical questions have been raised as a consequence of the economic issues related to the scarcity of available resources. In this paper we review our experience in the treatment of very old chronic haemodialysis patients. Fifty patients (7.2% of our haemodialysis patients) aged over 80 years at the beginning of dialysis were included (f = 25, m = 26, age = 82.6 +/- 0.3 years). In 42% of the patients the aetiology of renal disease was unknown. In the remainder, the aetiology was: interstitial nephritis 26%, hypertensive nephrosclerosis 14%, chronic glomerulonephritis 8%, diabetes 8% and polycystic disease 2%. There was a great comorbidity: intradialytic hypotension 82%, cardiac disease 74%, gastrointestinal disease 32%, cerebrovascular disease 26%. Vascular access related problems were the main reason for hospitalization. The major cause of death was vascular (cardiac and cerebral disease). Actuarial survival was 89%, 78%, 56% and 48% at 6, 12, 24 and 36 months, respectively. We think that haemodialysis is the best available choice for treating very old chronic renal failure patients. However further studies are needed to improve the quality of life of these patients.

Aged↗
PubMed1994

A study of 159 Portuguese patients with familial amyloidotic polyneuropathy (FAP) whose parents were both unaffected.

We reviewed 1233 cases of familial amyloidotic polyneuropathy (FAP) from 489 Portuguese families registered at the Centro de Estudos de Paramiloidose, Porto, Portugal. It was found that in 159 cases, neither parent had shown symptoms of this hereditary dominant form of peripheral neuropathy. These cases appear to form a distinct group, with a later age at onset (mean 45.1 years, SD 12.0) than the group of patients with one affected parent (mean 31.2 years, SD 6.9) and a geographical origin not quite in the areas where the disease is most prevalent. Though this group is not significantly different from the general group of patients in clinical presentation at onset and severity of the disease, the average interval between onset and diagnosis (mean 4.5 years, SD 3.2) reflects the difficulties in diagnosing these patients in the absence of a positive family history. From the analysis of pedigrees and in spite of a large number of isolated cases, the occurrence of new mutations could not be proven, and it seems more likely that, in some families, the FAP gene may result in a milder expression or even remain "silent" for several generations. Further investigation of this discrepancy may prove to be important in elucidating the mechanisms involved in the pathogenetic process.

Adult↗
PubMed1993

Familial amyloidotic polyneuropathy in Sweden: a pedigree analysis.

Extended genealogical studies were performed on the heredity patterns in Swedish patients with familial amyloidotic polyneuropathy (FAP) using Swedish historical archives. The population studied included 239 patients: 109 patients were linked to five large pedigrees and 80 patients belonged to 30 smaller pedigrees or nuclear families. In the remaining 50 cases, no genealogical links were found. Differences in mean ages of onset between the different pedigrees were found, although a considerable variation within the pedigrees was also present. There was a tendency for later ages of onset among older generations than younger ones: descendants of affected mothers seem to be more prone to anticipation in age of onset than descendants of affected fathers. Furthermore, there seems to be a tendency for earlier ages of onset among patients with a carrier mother than a carrier father. Some extended pedigrees, from the Skellefteå and Piteå areas, are presented in detail. The former go back into the middle of the 17th century. One important conclusion is that the mutational event may have occurred in late mediaeval times.

Adult↗
PubMed1993

[Cyclosporin A--a therapeutic alternative in giant-cell arteritis?].

Cyclosporine A (CyA) is an immune modulator that may treat immune diseases. The authors present two cases of temporal arteritis treated with CyA; the two patients improved very quickly and after the first six or eight weeks of treatment there were no clinical or laboratory signs of inflammation. As to adverse effects there was a moderate increase in serum creatinine and arterial pressure levels which were controlled when the CyA dosage was reduced. In view of the good results achieved in these two patients, the authors concluded that CyA may be an alternative therapy for giant-cell arteritis and that this hypothesis should be further investigated in a larger group of patients.

Adrenal Cortex Hormones↗
PubMed1992

[Multiple renal masses as a complication in a patient with Hodgkin's disease in remission. Recurrence or primary tumor?].

A forty-eight year old man with Hodgkin's disease in complete remission after 8 cycles of polychemotherapy (COPP) is presented. In an abdominal tomography, practiced 18 months after completion of treatment, two masses were found on the left kidney. Differential diagnosis between a Hodgkin's recidive and a second primary tumor and the implication of Hodgkin's treatment in the appearance of other neoplasms are discussed. Literature is reviewed.

Adenocarcinoma↗
PubMed1991

Vitreous involvement in familial amyloidotic neuropathy: a genealogical and genetic study.

Extended genealogical studies stretching back to the 17th century were performed concerning the heredity patterns of vitreous involvement in Swedish patients with familial amyloidotic polyneuropathy (FAP). FAP is an autosomal dominant inherited disorder, characterized by extracellular deposition of amyloid and a clinical syndrome of peripheral and autonomic neuropathy. In addition, some patients show typical vitreous opacities. All patients had their origin in a restricted geographical area. Some main patterns arose from this study: 1) Patients who had vitreous opacities as the first symptom of FAP seem to form a separate group, with a distinct age of onset distribution; 2) The familial occurrence of vitreous opacities raises the possibility that other familial factors modify the expression of the FAP gene; 3) The mean age of onset for vitreous opacities is lower for homozygous than for heterozygous patients.

Adult↗