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Biomedical subjects

F Silva

Publications and source records attributed to F Silva.

At least 37 records · Page 2Linked to original sources

North-South twinning in paediatric haemato-oncology: the La Mascota programme, Nicaragua.

We describe the La Mascota twinning programme between La Mascota paediatric hospital in Managua, Nicaragua, and hospitals in Monza and Milan, Italy, and Bellinzona, Switzerland. The programme was based on the belief that an attempt to reduce the gap in mortality from cancer in childhood between developed and less developed countries should become an integral part of the care and research activity of a haemato-oncological department of a developed country and not simply an exercise in solidarity. This programme for acute lymphoblastic leukaemia shows that intellectual, organisational, and financial resources can be generated by a twinning programme. What is vital for such programmes is a long-term commitment to a comprehensive and holistic strategy that incorporates supply of drugs, training and supervision of health professionals, and the care of the children and of their parents.

Child↗

Effect of supplemental beta-carotene on plasma concentrations of carotenoids, retinol, and alpha-tocopherol in humans.

High doses of beta-carotene, a lipid-soluble nutrient, may affect the plasma concentrations of other lipid-soluble nutrients. The purpose of this study was to assess the effects of long-term daily supplementation with beta-carotene (50 mg/d) on circulating concentrations of other carotenoids, retinol, and alpha-tocopherol over time. Data were available from 259 men and women participating in the Carotene Prevention Trial, a 2-center chemoprevention trial designed to determine whether supplemental beta-carotene can prevent second malignant tumors in patients cured of an early stage cancer of the oral cavity, pharynx, or larynx. Up to 2 blood samples were obtained before the intervention (before and after a 1-mo placebo run-in), with postrandomization samples obtained at 3, 12, 24, 36, 48, and 60 mo. Supplementation with beta-carotene produced a persistent 9- to 10-fold increase in median plasma beta-carotene concentrations (225 nmol/L at baseline to 2255 nmol/L at 3 mo) and a persistent 2-fold increase in median plasma alpha-carotene concentrations (45 nmol/L at baseline to 95 nmol/L at 3 mo). Concentrations of retinol, alpha-tocopherol, lycopene, and lutein/zeaxanthin were not affected by supplemental beta-carotene. Up to 5 y of daily supplementation with beta-carotene increased circulating concentrations of alpha- and beta-carotene, but did not alter concentrations of lycopene, lutein/zeaxanthin, retinol, or alpha-tocopherol.

Adult↗

[Acute complications of diabetes mellitus].

A retrospective study was made of 83 diabetic patients admitted to the Department of Internal Medicine between January 1986 and December 1993, with acute intercurrence of the disease. The authors considered some clinical features (age, type and frequency of complication, form of presentation, causal aetiology, laboratory findings and therapeutic options). Statistical relationships between different populations were made using the unpaired Student's T. method. Results were compared with those in the literature, leading to some significant conclusions.

Acute Disease↗

Technetium-99m-MAG3 in early identification of pyelonephritis in children.

UNLABELLED: The purpose of this study was to determine whether 99mTc-mercaptotriacetylglycine (MAG3) can substitute for 99mTc-glucoheptonate (GH) in the detection of pyelonephritis. METHODS: One hundred thirty renal scintigraphies were evaluated retrospectively in 38 children (21% boys, 79% girls; age range 1 mo-21 yr; mean age 7.2 yr) referred for evaluation during an acute clinical urinary tract infection and for follow-up studies. Twelve topographical regions were designated on each kidney. Each area was graded for severity of decreased radionuclide localization: mild (Grade 1), moderate (Grade 2) or marked (Grade 3). Early posterior views of MAG3 studies were compared to delayed posterior GH images. In all patients, both studies were performed on the same day. RESULTS: Eighty-two studies were performed during an acute clinical infection and 48 were performed as follow-up. Seventy-seven percent of the studies had focal cortical lesions. Of all the cortical lesions identified by GH, MAG3 detected 74% (match lesions). A comparable percentage of lesions was identified in each region by both studies. GH scintigraphy detected 261 lesions (63 Grade 1, 149 Grade 2 and 49 Grade 3), and MAG3 detected 201 lesions (37 Grade 1, 117 Grade 2 and 47 Grade 3). MAG3 was unable to recognize 60 lesions identified by GH studies in 11 patients (mismatch lesions). Of these, 41% (26 of 63) were Grade 1, 21% (32 of 149) were Grade 2 and 4% (2 of 49) were Grade 3. In three cases, MAG3 identified lesions not seen by GH (reverse mismatch); all had acute symptomatic infection. CONCLUSION: These data document that MAG3 in the early phase of the study (1-2 min) can detect Grade 2 to Grade 3 cortical lesions in patients with pyelonephritis, but it is less effective in detecting Grade 1 lesions.

Child↗

Tetra- and pentanucleotide short tandem repeat instability in gastric cancer.

The association between genetic instability in repetitive DNA domains and cancer has been reported in different types of malignancies. In this work we perform a comparative study of 29 gastric tumors with paired normal tissue using seven tetra-(FES/FPS, VWA31/A, HTPO, TH01, MBPB) and pentanucleotide (CD4, TP53) STR polymorphic markers regarding loss of heterozygosity and replication error status. Furthermore, we compare the gene frequencies obtained in normal tissue from patients with those of a normal control population from the same area, looking for allele associations between any of these polymorphic loci and gastric cancer risk. The results have shown that FES/FPS and TP53 present the higher rates of somatic instability. The observed results for TP53 are in accordance with those previously reported in gastric carcinogenesis, while instability of FES/FPS is for the first time reported in this tumor type. Our data suggest that different loci show different rates of instability and/or loss of heterozygosity and do not seem to consist of a result of an RER+ phenotype affecting several genomic repetitive domains. Furthermore, the instability in markers TH01, MBPB, TP53, and FES was generally detected in genotypes involving alleles with a high number of repeats. Comparing gene frequencies in patients and normal controls, no significant differences were found, although longer alleles are consistently more frequent in patients for the markers MBPB, TH01, and CD4.

Alleles↗

Characterization of four short tandem repeat loci (THO1, VWA31/A, CD4, and TP53) in northern Portugal.

Allele and genotype frequencies for two tetrameric and two pentameric short tandem repeat (STR) loci (THO1, VWA31/A, CD4, and TP53) were determined in a population sample from northern Portugal. Genotyping of PCR amplification products was done using polyacrylamide gel electrophoresis followed by silver staining; heteroduplex analysis was performed to distinguish THO1 genotypes involving allele 10 and the nonconsensus allele 9.3. For all loci allele frequencies fitted the distribution patterns generally observed in European populations. The observed genotype distributions do not deviate significantly from Hardy-Weinberg expectations, although for VWA31/A a significant excess of heterozygotes involving allele 17 was found. Mother-child pair analyses confirmed the regular Mendelian pattern of inheritance. Because the information content of these systems is high and because their genotyping is technically reliable and simple, CD4, THO1, VWA31/A, and TP53 are appropriate genetic systems for anthropological genetics.

Antigens, CD↗

Pericardial effusion. Unusual complication in thyroid cancer.

A case in which a prolonged hypothyroid state resulted in development of a pericardial effusion is presented. The compensatory mechanism for protein homeostasis is lost in severe hypothyroidism. Iodine is transported to the pericardial space, which is filled with a high-protein content fluid and remains trapped. The mechanism for the accumulation of the fluid in the pericardial space is discussed. To prevent this unusual but dangerous complication, the authors recommend close monitoring of the patient's clinical status and serum thyroid stimulating hormone. The use of a short acting thyroxine substitute for at least 2 weeks can decrease occurrence of this complication and will shorten the time the patient needs to be hypothyroid.

Adult↗

Scintigraphic findings in a Brodie's abscess.

A 9-year-old girl had a 6-month history of left hip pain. Radiographs of the left hip showed a metaphyseal osteolytic lesion with sclerotic borders in the femoral neck. Tc-99m MDP bone imaging and a Ga-67 scan showed focal areas of increased activity in the left femoral neck. These areas of increased uptake corresponded to a lytic area on x-rays, which was due to a Brodie's abscess. The combination of Tc-99m MDP bone and Ga-67 imaging has been widely used in the confirmation of bone infection, increasing the accuracy in the diagnosis of osteomyelitis. However, nuclear scintigraphy has not been previously reported in the confirmation of a Brodie's abscess.

Abscess↗

Scintigraphic findings in schistosomiasis.

Schistosomiasis mansoni is a tropical parasitic disease caused by a blood fluke which inhabits the portal system of humans. Fifteen pediatric patients with the acute disease were evaluated with liver and spleen scintigraphy (LSS). Clinical history, physical examination, and serum chemistries failed to reveal any other underlying systemic disease. Liver and spleen scintigraphies were performed before therapy, 7 months and 9 years after therapy with oxamniquine. LSS initially showed hepatomegaly in 93% of the patients. In the first follow up study a reactive spleen was evident in 78% of the cases, with an unchanged hepatic image. Long term follow up revealed that from the initially enlarged livers, 93% became normal. However, 47% of the spleens were abnormal. The scintigraphic changes observed in the liver over the years were those expected for an acute infection. The findings in the spleen might indicate the persistence of an immunologic reaction with a continuous trigger, probably an antibody. These observations suggest that the LSS can be used in the evaluation and follow-up of these patients.

Acute Disease↗

Retinoblastoma gene structure and product expression in human gastric carcinomas.

The role of the retinoblastoma gene (RB1) in human gastric carcinogenesis is yet to be clarified. We report on the analysis of RB1 structure and protein (pRB) expression in gastric carcinomas using Southern blotting, Western blotting and immunohistochemistry. The relationship between pRB expression and cell proliferation was assessed by a proliferation marker (PCNA) in a subset of cases. Non-neoplastic mucosas were studied, as controls, by the same methodology. We found a close relationship between pRB expression and PCNA in non-neoplastic mucosas as well as in gastric carcinomas. All tumours were immunohistochemically positive for pRB, although with a variable proportion of non-immunoreactive cells. Carcinomas of the diffuse type showed absence of pRB expression in a larger proportion of neoplastic cells than carcinomas of the intestinal type (P < 0.05). Analysis of the RB1 structure using probe p68RS2.0 revealed allelic imbalance in 29% of informative cases. No homozygous deletions and/or rearrangements were detected with p68RS2.0 and cDNA probes. Western analysis revealed no abnormal patterns of pRB. Our data therefore suggest that major alterations affecting the RB1 gene are rather infrequent in human gastric carcinomas.

Aged↗

On the mechanisms of genotoxicity and metabolism of quercetin.

Quercetin has been the subject of numerous studies on its genetic toxicity and carcinogenicity. Despite its well-proven genetic damaging activity for various genetic end-points (reverse mutations, induction of SOS functions, induction of sister chromatid exchanges, chromosomal aberrations and micronuclei), the mechanisms of genetic damage by quercetin remain, by and large, unknown. The present study aims to further extend the observations on the possible active oxygen species mediated DNA-damaging activity of quercetin and the role of cytochrome P450-dependent metabolism on the genotoxicity of quercetin. The results reported in this work show that quercetin can produce the OH. radical, as assessed by deoxyribose degradation in the presence of Fe3+/EDTA (ethylenediaminetetraacetic acid), and that it induces strand breakage in isolated plasmidic DNA (pUC18). The data support the hypothesis that the production of OH. is mediated by H2O2. The results with genetically engineered V79 cells expressing rat cytochromes 1A1, 1A2 and 2B1 failed to demonstrate metabolism of quercetin, as indicated by the fact that neither an enhancement nor a decrease in the genotoxicity of quercetin was observed. Results obtained on the pH dependence of the induction of chromosomal aberrations by quercetin in V79 cells show that, as the pH value of the medium is increased to 8.0, there is a significant increase in the number of aberrant cells, as expected if oxygen radicals are responsible for the formation of chromosomal aberrations.

Animals↗

Renal thrombotic microangiopathy in patients with systemic lupus erythematosus and the antiphospholipid syndrome.

Current studies indicate that a thrombotic microangiopathy (TMA) identifies patients with systemic lupus erythematosus (SLE) who are at high risk of progressing to end-stage renal disease. We have observed two patients with SLE and one patient with a primary antiphospholipid syndrome (APS) who developed acute renal insufficiency with thrombocytopenia. Renal biopsies showed a TMA characterized by thrombi or by cellular and mucoid intimal hyperplasia of small arteries and arterioles. No arterial or arteriolar immune-complex deposits were detected by immunofluorescent or electron microscopy. Biopsies from one SLE patient and the APS patient showed no immune-complex glomerular disease. Both had serum antiphospholipid antibodies (aPL). aPL were not detected in the serum of the other SLE patient who had an active lupus nephritis. Acute renal failure and thrombocytopenia resolved in each case following treatment by plasmapheresis or prednisone and heparin. None of the patients were initially treated with cytotoxic drugs. As more knowledge is gained, the accurate identification of renal vascular lesions in SLE or related diseases could influence renal prognosis and choice of therapy. The cases reported here provide further evidence that a TMA can cause acute renal failure independent of lupus nephritis. TMA should be distinguished from other forms of renal vascular disease, particularly a noninflammatory lupus microangiopathy, which is probably mediated by subendothelial immune-complex deposits. The absence of immunoglobulin deposits in vessels involved by a TMA indicates that microvascular thrombosis is promoted by mechanisms other than those usually attributed to immune-complex disease. Phospholipid reactive antibodies may be pathogenetic in some cases.

Acute Kidney Injury↗

In vitro formation and expansion of cysts derived from human renal cortex epithelial cells.

Acquired renal cysts derive from terminally differentiated tubular epithelium in adults as a consequence of increased epithelial cell proliferation, fluid accumulation and extracellular matrix remodelling. To understand better how human epithelial cysts may be initiated and progressively expand, cells from primary cultures of normal human adult renal cortex were dispersed in polymerized type I collagen. The transparent matrix permitted repeated observation by light microscopy of cyst formation from individual renal cells. The cyst cells reacted strongly with distal nephron histochemical markers (cytokeratin antibodies AE1/AE3, epithelial membrane antigen, and Arachis hypogaea lectin) but inconsistently or not at all to markers of proximal tubules (Tetragonolobus purpureas lectin and Phaseolus vulgaris erthroagglutinin lectin). The number of spherical, fluid-filled epithelial cysts that developed in a standardized microscope field quantified cyst initiation. Cyst progression was determined from the increase in the diameter (surface area) of cysts and represents a hyperplastic event. EGF or TGF alpha, were required in serum-free defined medium to cause cysts to develop from individual epithelial cells dispersed in the matrix; insulin was required as a co-factor. The EC50 for EGF was approximately 0.1 ng/ml, and for insulin 1 microgram/ml. Early cultures of normal cortex formed cysts more efficiently when dispersed in collagen matrix than cells passaged several times before suspension in the gel. Agonists of adenylate cyclase (PGE1, AVP, VIP, PTH, forskolin, cholera toxin), methylisobutylxanthine, and 8-Br-cAMP, though incapable of causing cyst formation alone in defined medium, enhanced cyst initiation and progression in the presence of EGF and insulin. Angiotensin II, TNF alpha, beta-estradiol, and pertussis toxin had no effect in the absence or presence of EGF and insulin. Pertussis toxin inhibited cyst initiation and expansion caused by EGF and forskolin but potentiated cyst initiation and expansion caused by EGF and PGE1. Cyst formation and expansion were inhibited by TGF beta 1 and 2-chloroadenosine. Polarized monolayers of human renal cortical cells grown on permeable membranes were used to independently quantify the effects of agonists on the net secretion of solute and water from the basolateral to the apical surface of the cells. PGE1, forskolin, and 8-Br-cAMP stimulated net fluid secretion that was sustained for several days; EGF enhanced forskolin-stimulated fluid secretion. We conclude that the formation and expansion of in vitro cysts derived from solitary human cortex cells depends on the coordinated interplay between cellular proliferation and fluid secretion.(ABSTRACT TRUNCATED AT 400 WORDS)

Body Fluids↗

[Multiple myeloma. An unusual case].

We describe the case of a 75 year old male patient, hospitalized because of sudden paraplegia. The radiological tests performed, revealed degenerative changes of the entire vertebral spine, osteolytic lesions of the seventh cervical and first two thoracic vertebrae, and lacunar lesions of the others. The erythrocyte sedimentation rate, total proteins and its electrophoretic study, as well as quantification of serum immunoglobulins were found to be normal. Regardless of these results, we continued our investigation in order to diagnose or exclude multiple myeloma (MM), which was confirmed by serum and urinary immunoelectrophoresis, that revealed monoclonal gammopathy IgG, K with low value of serum IgG and very high urinary values of Bence Jones K, and by the histological analysis of the necropsy material. In conclusion, we report a case where the probability of an alteration of the controlling immunological mechanisms must be considered. We suggest that there is a heavy chain suppression of the malignant clone, that would explain its very low value in peripheral blood. These findings associated to the absence of light chains in serum, have lead to a particular laboratorial expression of this myeloma.

Aged↗

Strategies for ultrastructural visualization of biotinated probes hybridized to messenger RNA in situ.

A progressive development of the application of in situ methodology to ultrastructural procedures has resulted in the ability to detect individual molecules of mRNA with high probability. Beginning with whole-mount cells and then developing myotubes, both in culture and detergent extracted before fixation, we were able to progress to methods which allow detection of mRNA in tissue sections. Initial results confirm that the detection of mRNA in thin-sectioned tissue is very similar to observations on the extracted, cultured cells, and that the same methods of data analysis apply. Current work is devoted to the application of the methodology to other cellular structures, such as the nucleus, and to other tissue-probe systems, such as brain. Acknowledgements. The authors appreciate the skilled help from John McNeil and Shirwin Pockwinse in the laborious and time-consuming preparations of material and photography. FS was on sabbatical leave from the Department of Pathology at Southwestern Medical Center.

Animals↗

Localization of parathyroid lesions: blind study for surgeons.

Success in the treatment of primary hyperparathyroidism rest in the accurate localization and removal of the diseased gland or glands. Computerized tomography and nuclear imaging scans are being used to localize abnormal parathyroid tissue. In the present study, fifteen consecutive patients undergoing surgery for primary hyperparathyroidism were all subjected to these ancillary studies. Results were not revealed to the operating team. In all instances an adenoma was localized during neck exploration. CT Scan failed to localize 73% of the affected glands. Nuclear scans missed almost fifty percent of the parathyroid adenomas. The low yield of these ancillary localizing tests makes them unnecessary in the routine evaluation of patients undergoing surgery for primary hyperparathyroidism.

Adenoma↗