Search PubMed⌕ Search

Biomedical subjects

I Martins

Publications and source records attributed to I Martins.

At least 19 recordsLinked to original sources

Recombinant adeno-associated virus type 2, 4, and 5 vectors: transduction of variant cell types and regions in the mammalian central nervous system.

Recombinant adeno-associated virus vectors based on serotype 2 (rAAV2) can direct transgene expression in the central nervous system (CNS), but it is not known how other rAAV serotypes perform as CNS gene transfer vectors. Serotypes 4 and 5 are distinct from rAAV2 and from each other in their capsid regions, suggesting that they may direct binding and entry into different cell types. In this study, we examined the tropisms and transduction efficiencies of beta-galactosidase-encoding vectors made from rAAV4 and rAAV5 compared with similarly designed rAAV2-based vectors. Injection of rAAV5 beta-galactosidase (betagal) or rAAV4betagal into the lateral ventricle resulted in stable transduction of ependymal cells, with approximately 10-fold more positive cells than in mice injected with rAAV2betagal. Major differences between the three vectors were revealed upon striatal injections. Intrastriatal injection of rAAV4betagal resulted again in striking ependyma-specific expression of transgene, with a notable absence of transduced cells in the parenchyma. rAAV2betagal and rAAV5betagal intrastriatal injections led to beta-gal-positive parenchymal cells, but, unlike rAAV2betagal, rAAV5betagal transduced both neurons and astrocytes. The number of transgene-positive cells in rAAV5betagal-injected brains was 130 and 5,000 times higher than in rAAV2betagal-injected brains at 3 and 15 wk, respectively. Moreover, transgene-positive cells were widely dispersed throughout the injected hemisphere in rAAV5betagal-transduced animals. Together, our data provide in vivo support for earlier in vitro work, suggesting that rAAV4 and rAAV5 gain cell entry by means of receptors distinct from rAAV2. These differences could be exploited to improve gene therapy for CNS disorders.

Animals↗

Association between trans fatty acid intake and cardiovascular risk factors in Europe: the TRANSFAIR study.

BACKGROUND: High intakes of trans fatty acids (TFA) have been found to exert an undesirable effect on serum lipid profiles, and thus may increase the risk for cardiovascular disease. OBJECTIVES: Investigation of the association between TFA intake and serum lipids. DESIGN: Cross-sectional study in eight European countries (Finland, France, Greece, Iceland, The Netherlands, Portugal, Spain, Sweden) among 327 men and 299 women (50-65 y). Using a dietary history method, food consumption was assessed and TFA intake was calculated with recent figures on TFA levels of foods, collected in the TRANSFAIR study. RESULTS: Mean (+/-s.d.) TFA intake was 2.40+/-1.53 g/day for men and 1.98+/-1.49 g/day for women (0.87+/-0.48% and 0. 95+/-0.55% of energy, respectively), with the highest consumption in Iceland and the lowest in the Mediterranean countries. No associations were found between total TFA intake and LDL, HDL or LDL/HDL ratio after adjustment for cardiovascular risk factors. Additional adjustment for other fatty acid clusters resulted in a significant inverse trend between total TFA intake and total cholesterol (Ptrend<0.03). The most abundantly occurring TFA isomer, C18:1 t, contributed substantially to this inverse association. The TFA isomers C14:1 t9, C16:1 t9 and C22:1 t were not associated or were positively associated with LDL or total cholesterol. CONCLUSIONS: From this study we conclude that at the current European intake levels of trans fatty acids they are not associated with an unfavourable serum lipid profile. SPONSORSHIP: Unilever Research Laboratorium, the Dutch Dairy Foundation on Nutrition and Health, Cargill BV, the Institute of Food Research Norwich Laboratory, the Nutrition Branch of the Ministry of Agriculture, Fisheries and Food, the International Fishmeal and Oil Manufacturers' Association, Kraft Foods, NV Vandemoortele Coordination Center, Danone Group, McDonalds Deutschland Inc, Danish Veterinary and Food Administration, Valio Ltd, Raisio Group. European Journal of Clinical Nutrition (2000) 54, 126-135

Adipose Tissue↗

Systemic hyperosmolality improves beta-glucuronidase distribution and pathology in murine MPS VII brain following intraventricular gene transfer.

Mucopolysaccharidosis VII, a classical lysosomal storage disease, is caused by deficiency of the enzyme beta-glucuronidase. Central nervous system (CNS) manifestations are severe with accumulations of storage vacuoles in all cell types. Intraventricular gene transfer can lead to transduction of the ependyma, with production and secretion of beta-glucuronidase into the cerebral spinal fluid and underlying cortex resulting in reversal of disease pathology restricted to the periventricular areas. We tested if systemic hyperosmolality would increase the distribution of beta-glucuronidase in brain parenchyma after intraventricular virus injection. Mice were administered mannitol, intraperitoneally, 20 days after gene transfer and 1 day prior to sacrifice. Mannitol-induced systemic hyperosmolality caused a marked penetration of beta-glucuronidase into the brain parenchyma. If mannitol was administered at the time of the intraventricular injection of virus, there was penetration of vector across the ependymal cell layer, with infection of cells in the subependymal region. This also resulted in increased beta-glucuronidase activity throughout the brain. Sections of brains from beta-glucuronidase-deficient mice showed correction of cellular pathology in the subependymal region plus cortical structures away from the ventricular wall. These data indicate that virus-mediated gene transfer to the brain via the ventricles, coupled with systemic mannitol administration, can lead to extensive CNS distribution of beta-glucuronidase with concomitant correction of the storage defect. Our findings have positive therapeutic implications for the treatment of CNS disorders with gene transfer vectors and recombinant proteins.

Adenoviridae↗

Intake of fatty acids in western Europe with emphasis on trans fatty acids: the TRANSFAIR Study.

OBJECTIVE: To assess the intake of trans fatty acids (TFA) and other fatty acids in 14 Western European countries. DESIGN AND SUBJECTS: A maximum of 100 foods per country were sampled and centrally analysed. Each country calculated the intake of individual trans and other fatty acids, clusters of fatty acids and total fat in adults and/or the total population using the best available national food consumption data set. RESULTS: A wide variation was observed in the intake of total fat and (clusters) of fatty acids in absolute amounts. The variation in proportion of energy derived from total fat and from clusters of fatty acids was less. Only in Finland, Italy, Norway and Portugal total fat did provide on average less than 35% of energy intake. Saturated fatty acids (SFA) provided on average between 10% and 19% of total energy intake, with the lowest contribution in most Mediterranean countries. TFA intake ranged from 0.5% (Greece, Italy) to 2.1% (Iceland) of energy intake among men and from 0.8% (Greece) to 1.9% among women (Iceland) (1.2-6.7 g/d and 1.7-4.1 g/d, respectively). The TFA intake was lowest in Mediterranean countries (0.5-0.8 en%) but was also below 1% of energy in Finland and Germany. Moderate intakes were seen in Belgium, The Netherlands, Norway and UK and highest intake in Iceland. Trans isomers of C18:1 were the most TFA in the diet. Monounsaturated fatty acids contributed 9-12% of mean daily energy intake (except for Greece, nearly 18%) and polyunsaturated fatty acids 3-7%. CONCLUSION: The current intake of TFA in most Western European countries does not appear to be a reason for major concern. In several countries a considerable proportion of energy was derived from SFA. It would therefore be prudent to reduce intake of all cholesterol-raising fatty acids, TFA included.

Adult↗

Ticlopidine-induced prolonged cholestasis: a case report.

We report a case of ticlopidine-induced prolonged cholestasis in a 60-year-old man with no previous hepatobiliary disease who presented with sudden right upper abdominal pain, jaundice and pruritus three months after starting ticlopidine therapy. Other drugs taken by the patient were not considered probable causes. The diagnostic evaluation showed no biliary obstruction and other possible causes of intra-hepatic cholestasis were excluded. The liver biopsy showed a cholestatic hepatitis with bile duct damage. The disease ran a severe and protracted course, but symptoms and jaundice eventually subsided five months after drug withdrawal. More than a year later, relevant abnormalities of liver function tests consistent with anicteric cholestasis still persist, fulfilling criteria for a minor form of drug-induced prolonged cholestasis. This syndrome has been reported infrequently in relation to several drugs, mainly chlorpromazine, and only once with ticlopidine.

Cholestasis↗

The use of bovine pericardium for pulmonary valve reconstruction or conduit replacement: long-term clinical follow up.

BACKGROUND AND AIMS OF THE STUDY: This study aimed to determine the clinical performance of bovine pericardial aldehyde-treated material alone or in combination with aortic leaflets of porcine origin. These were the porcine aortic stentless pulmonary valved bovine pericardial conduit (PSPVC), and porcine aortic monocusp attached to pericardial patch (PAMC), used to correct right-sided heart lesions. METHODS: Between November 1985 and October 1995, 33 patients underwent corrective congenital surgery with PSPVC. Mean patient age was 5.7+/-4.3 years (range: 15 days to 18 years). Pulmonary atresia with ventricular septal defect (VSD) was the most frequent disease (16/33, 48%). For PAMC, 45 patients with various congenital heart malformations underwent implantation between June 1989 and April 1996. Mean patient age was 4.8+/-4.7 years (range: 2 weeks to 18 years). RESULTS: With PSPVC, hospital mortality rate was 18.2% and related to poor preoperative clinical condition in six cases. Four patients were lost to follow up; 23 (85%) were followed for 3 months to 10 years (mean 4.8+/-3.0 years). Distal anastomotic scarring in four patients was probably due to retraction of the pericardial tissue. With PAMC, hospital mortality rate was 11% and related to patients' preoperative clinical condition. Three patients were lost to follow up; 37 survivors have been followed for 6 to 88 months (mean 38.5+/-19.0 months). There were no late deaths. Two patients underwent reoperation; intra-operative observation showed well-preserved monocusps with no signs of tissue degeneration. The remaining 35 patients remain asymptomatic by clinical examination and Doppler echocardiography. The monocusps remained mobile in every case. CONCLUSION: PSPVCs have shown excellent performance and durability in young patients with a low mean age (5 years). The monocusp graft has remained functional with good leaflet motion for up to seven years.

Adolescent↗

Use of bovine pericardial tissue for aortic valve and aortic root replacement: long-term results.

BACKGROUND AND AIMS OF THE STUDY: The study aimed to determine the clinical performance of bovine pericardial aldehyde-treated products alone or in combination with aortic leaflets of porcine origin. These included a composite porcine stentless aortic valve attached to a scalloped pericardial tube (BSAV), and valved and non-valved bovine pericardial conduits for use in left-sided heart lesions (BPG). METHODS: For BSAV grafts, between January 1990 and August 1996, 163 patients (119 males) had their aortic valves replaced by SJM Biocor BASV. Mean age was 37.9 +/- 17.6 years (range: 1 to 76 years). Rheumatic heart disease sequelae (n = 72) and replacement of a prosthetic heart valve (n = 46) were predominant. Preoperative NYHA functional class showed 90 patients (55.2%) in class III and 50 (30.7%) in class IV. BPVC and NVPC grafts were used in 166 patients: acute aortic dissection was the main indication in 52 (31.3%) and chronic in 36 (21/7%). The ascending aorta was involved in 141 patients (84.9%); grafts were seldom used at other sites. In most patients the graft implanted was either a non-valved (n = 79) or a valved (n = 75) pericardial conduit. Twelve patients had a localized lesion and required a patch repair. RESULTS: For BASV grafts, the non-valve-related hospital mortality rate was 4.9%. There were 14.7% non-fatal complications with full recovery of all patients. Mean follow up in 141 patients was 3.0 +/- 1.4 years (range: 1 month to 7.2 years); 14 patients were lost to follow up. Late, non-conduit-related, mortality occurred in seven patients (4.9%). Eight patients underwent reoperation. The current clinical follow up of 127 patients has shown 118 (92.9%) with competent valves and nine (7.0%) with mild stable aortic insufficiency. For BPVC and NVPC grafts, hospital mortality rate was 16.9%, death being related to poor preoperative clinical condition. Postoperative follow up was accomplished in 125 patients; reoperation was necessary in seven patients. Histology showed good tissue preservation up to five years; echocardiography revealed satisfactory findings. No valved conduit had to be reoperated for valve or pericardial tissue wear. CONCLUSIONS: Clinical results of left-sided heterologous pericardial grafts have shown excellent performance over time. The BASV (over seven years) and BPVC and NVPC (eight years) have demonstrated superior results as aortic valves alone or in combination with a pericardial conduit.

Adolescent↗

Porcine mitral stentless valve mid-term clinical results.

OBJECTIVES: Time testing is essential with any valvular procedure, especially when a new concept is introduced such as the mitral stentless valve. Our purpose is to evaluate the results obtained over 4 years with this operation, particularly to attest the impact of preservation of annulo ventricular continuity on the long term results of these patients. METHODS: From March 1992 to August 1996, 120 patients had their mitral valves replaced with a porcine stentless mitral valve. The observation period was 54 months with total patients follow-up of 3424 months with a mean of 28.5 months. The age ranged from 11 to 72 years (mean 35.22 +/- 14.98). There were 73 females (60.8%) and 47 males (39.2%). The predominant etiology was rheumatic heart disease. Associated procedures were performed in 12 patients (10%), and the great majority of the patients were in functional class III and IV (NYHA). RESULTS: Hospital mortality occurred in seven patients (5.83%) non valve related except for one early case of endocarditis. Early reoperation related to technical failure were necessary in 4 patients without mortality. Follow-up was accomplished in 101 patients and ranged from 2 to 54 months. Late reoperations were required in 16 patients (nine due to mitral insufficiency, five because of endocarditis and two for mitral stenosis). Most reoperations were related to technical failure. Among the 82 patients presently in control, 72 showed a competent mitral stentless valve, eight with stable mild mitral regurgitation and in two a decreased mitral orifice. Hemodynamic performance of the valve has been excellent in this group, particularly in patients with left ventricular dysfunction. CONCLUSION: Although technical complexity remains the main cause of reoperations with this valve, experience has shown that it not only provides preservation of the left ventricular function but also promised significant increase of the ejection fraction in patients with poor left ventricular function.

Adolescent↗

[Reference values for carboxyhemoglobin].

INTRODUCTION: The reference values (RV) of biological indicators are used in the interpretation of the results of such indicators in individuals occupationally exposed to chemical agents. The Brazilian Group for the Establishment of Reference Values has worked on these definitions for the purpose of establishing RVs for several bioindicators in various regions of the country. In the present study, the RV for carboxyhemoglobin (COHb) was determined for the South of Minas Gerais. MATERIAL AND METHOD: The COHb was analyzed by the Beutler and West (1984) spectrophotometric method, optimized in our laboratory. In all the samples, analyses of some biochemical and hematological parameters were made to evaluate the health condition of a population of 200 volunteer non-smokers occupationally not exposed to CO. Each individual answered a questionnaire to obtain data pertinent to the interpretation of the results. The reference values were expressed as mean values +/- standard deviation, with a 95% confidence interval, and an upper reference value. The statistical distribution of the results was made so as to enable comparisons between the results of groups of workers, rather than individual evaluations, to be made. RESULTS AND CONCLUSIONS: The mean value +/- standard deviation was 1.0% +/- 0.75; the 95% confidence interval was 0.9-1.1% and the upper reference value was 2.5%. By the t Student test (p < or = 0.05), no difference was detected between the values related to sex, age or ingestion of alcoholic beverages. The reference values obtained were close to those reported for others countries.

Adolescent↗

Food patterns of elderly Europeans. SENECA Investigators.

OBJECTIVE: To compare actual food intake of elderly people in Europe and further identify food patterns, which mediate favourable or unfavourable nutrient intakes from cluster analysis of pooled data. DESIGN: Cross-sectional analysis of food patterns of participants of the SENECA follow-up study (1993). SETTING: Twelve traditional European towns. SUBJECTS: Men (n = 647) and women (n = 710) aged 74-79 y in 1993. METHODS: Food intake data were assessed using the same validated dietary history technique in all SENECA towns. Cluster analysis was used to classify subjects into groups based on similarities in dietary variables. RESULTS: A northern and southern European eating pattern emerged. The southern food pattern appeared to be the most healthful being rich in grain, vegetables, fruit, lean meat and olive oil. The north-south gradient did, however, not systematically segregate into the same clusters. All dietary profiles were represented in all sites. The four dietary profiles, identified by cluster analysis, were: 'Lean and green eaters': high carbohydrate and vitamin C intake, 'gourmands': high intake of energy and nutrients, 'milk drinkers': high intake of calcium and vitamin B2 and 'small eaters': marginal energy and nutrient consumption. Marital status, education, smoking, health status and physical activity level differed between clusters. CONCLUSIONS: A north-south gradient of food patterns was identified. The southern diet agreed better with guidelines for healthy eating. A sufficient energy intake seemed, however, to be necessary for an adequate nutrient intake, beside a good choice of food types.

Aged↗

DNA markers for differentiating isolates of Paecilomyces lilacinus.

Paecilomyces lilacinus is an agent for the potential biological control of soil nematodes. Arbitrarily primed PCR was used to fingerprint the genomes of 28 isolates of this fungus. Most (72%) of the isolates originated from soil of different regions of Brazil. Fourteen 10-mer oligonucleotide primers of arbitrary sequence revealed 293 scorable binary characters. Distinct genotypes were obtained for each isolate. Cluster analysis showed a high level of variability among these genotypes. The similarity among pairwise comparisons of the isolates varied from 84.3% to 7.6%, with a mean of 63.5%. No clearly defined phenetic groups were identified by cluster or multivariate analyses. No correlation with geographical origin or host was detected. In addition, PCR with four pairs of consensus tRNA gene primers was performed on a subsample of 12 P. lilacinus isolates, three P. farinosus isolates, two P. fumosoroseus isolates, and one isolate of P. amoenoroseus. An inferred phylogeny based on 112 binary characters obtained by tRNA-PCR showed a monophyletic group which contained most of the P. lilacinus isolates. In contrast, three isolates of P. farinosus were not in a monophyletic group under the inferred phylogeny. These results suggest that tRNA fingerprinting could provide a valuable tool which could be used to develop the molecular taxonomy of Paecilomyces, as morphological characteristics of asexual structures cannot entirely resolve species.

Base Sequence↗

[Angiosarcoma of the spleen].

Primitive splenic tumors are extremely rare. We report a case, the first at S. José-Hospitais Civis de Lisboa, of a 70 year old woman who presented splenomegaly. She had pelvic irradiation in her past history. MRI revealed a splenic mass characterized as vascular on angiography. She is doing well 12 months after splenectomy. We have found 61 reported cases of this rare tumor whose etiopathogeny is unknown. Early splenectomy should be the first therapeutical approach, since spontaneous rupture is very common and was the feature presented in 34% of patients in the series by Autry et al. As far as cytostatic chemotherapy is concerned, the rarity of this tumor precludes any conclusion about its efficacy, but in metastasized forms it seems that chemotherapy for soft tissue sarcomas may be effective.

Aged↗

[Secondary syphilis of gastric location].

We present a case of syphilitic gastropathy manifested by an ulcero-infiltrative lesion in the gastric antrum in a 25 year old man. We obtained a clinical endoscopic cure with specific anti-luetic therapy. The morphologic characteristics, which are usual in this type of disease, are revised and the diagnostic criterion discussed.

Adult↗

[Research in child mental health].

Some considerations are made about current child psychiatry research and its future challenge. We analyse some studies about parental psychopathological influence in the early relationship, mentioning obstacles and advantages of some clinical and epidemiological research methods. We emphasize the value of interaction, observation and the use of videoscopy in infant clinical research. In Portugal, the lack of motivation to work in mental health research is an impediment to establishing clinical and training priorities.

Child↗

Who kills whom in Portugal?

To clarify the relationship between people who have committed homicide and been convicted (murderers) and homicide victims, and between murderers and suicide victims, their profiles were compared in Portugal from 1970 to 1987. Correlations were found between the age group, marital status and occupation of murderers and homicide victims. Murderers and suicide victims were only correlated by occupation. Since 1983, there has been a trend towards an increasing prevalence of murderers among younger people and single people, and of homicide victims among older people. The correlation between murderers and suicide victims can be explained by alcoholism, and murderers tend to kill their relatives and peers as a result of conflict situations. The emerging trend towards young people murdering old and defenceless people points towards a colder and financially motivated killer, perhaps increasingly among young drug addicts.

Adolescent↗

Activity and post-polio fatigue.

Fatigue was studied in 12 subjects with post-polio sequelae (PPS). Results of the Fatigue Severity Scale (FSS) demonstrated a mean score of 4.8 +/- 1.6 (non-disabled scores = 2.3 +/- 0.7). The Human Activity Profile (HAP) was not sensitive enough to measure fatigue. Fifty percent of subjects scored below the first percentile based on age and sex matched norms. The Activity Record (ACTRE) results revealed that subjects spent 5% of their time resting and 1% in planning or preparation activities. Fatigue peaked in the late morning or early afternoon and was relieved by rest periods. Use of energy conservation and work simplification skills along with frequent rest periods was suggested as a possible method for managing PPS fatigue.

Activities of Daily Living↗