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Biomedical subjects

L Gomes

Publications and source records attributed to L Gomes.

At least 37 records · Page 2Linked to original sources

[Isolated infective endocarditis of pulmonary valve in patient with interventricular septal defect].

A case of isolated infective endocarditis of the pulmonary valve in a patient with known subpulmonary interventricular septal defect that had, as major complication pulmonary septic embolization, was reported by the authors. The disease followed an insidious course, diagnosed by the presence of vegetations in the echocardiogram, some of them larger than 1 cm. They were found in the right ventricular infundibulum and in the pulmonary valve leaflets. The isolation of Estreptococcus viridans in blood cultures has confirmed the diagnosis. In spite of appropriate antimicrobial therapy, according to the antibiogram data (with Ampicillin and Gentamicin), fever lasted for more than three weeks. This event suggested medical treatment failure and the possibility of surgery was considered. However, the endocarditis eventually healed with medical therapy alone, and this unusual course with prolonged fever was presumed to be caused by lung metastatic infection secondary to septic embolization. This complication is relatively common, but lung involvement is usually a subclinical event, not responsible for such persistent fever, as happened in the case now reported. We emphasize the rarity of this case, the unusual clinical course and the discussion concerning the therapeutic options.

Adult↗

Binding of von Willebrand factor to collagen type III: role of specific amino acids in the collagen binding domain of vWF and effects of neighboring domains.

Binding of von Willebrand Factor (vWF) to sites of vascular injury is the first step of hemostasis. Collagen types I and III are important binding sites for vWF. We have previously determined the three-dimensional structure of the collagen binding A3 domain of vWF (Huizinga et al., Structure 1997; 5: 1147). We hypothesized that the top face of this domain might be the collagen-binding site. Based on this hypothesis, we made seven vWF mutants (D934A/S936A, V1040A/ V1042A, D1046A, D1066A, D1069A, D1069R, and R1074A). Collagen binding of these mutants was investigated in ELISA and with Surface Plasmon Resonance (BIAcore). In addition, we studied collagen binding of mutants lacking the A2 or D4 domains, which flank the A3 domain. In ELISA, all point mutants and deletion mutants bound to collagen in amounts similar to wild type (WT)-vWF. In the BIAcore we found that WT-vWF has an apparent KD for collagen of 1-7 nM on a subunit base. The apparent kinetic parameters of the point mutants and deletion mutants were not significantly different from WT-vWF, except for DA2-vWF, which had a lower KD. indicating that the A2 domain somehow modulates binding of vWF to collagen type III. Based on our results, we conclude that the amino acid residues mutated by us are not critically involved in the interaction between vWF and collagen type III, which suggests that the collagen binding site is not located on the top face of the A3 domain.

Binding Sites↗

Increased peroxynitrite activity in AIDS dementia complex: implications for the neuropathogenesis of HIV-1 infection.

Oxidative stress is suggested to be involved in several neurodegenerative diseases. One mechanism of oxidative damage is mediated by peroxynitrite, a neurotoxic reaction product of superoxide anion and nitric oxide. Expression of two cytokines and two key enzymes that are indicative of the presence of reactive oxygen intermediates and peroxynitrite was investigated in brain tissue of AIDS patients with and without AIDS dementia complex and HIV-seronegative controls. RNA expression of IL-1beta, IL-10, inducible nitric oxide synthase, and superoxide dismutase (SOD) was found to be significantly higher in demented compared with nondemented patients. Immunohistochemical analysis showed that SOD was expressed in CD68-positive microglial cells while inducible nitric oxide synthase was detected in glial fibrillary acidic protein (GFAP)-positive astrocytes and in equal amounts in microglial cells. Approximately 70% of the HIV p24-Ag-positive macrophages did express SOD, suggesting a direct HIV-induced intracellular event. HIV-1 infection of macrophages resulted in both increased superoxide anion production and elevated SOD mRNA levels, compared with uninfected macrophages. Finally, we show that nitrotyrosine, the footprint of peroxynitrite, was found more intense and frequent in brain sections of demented patients compared with nondemented patients. These results indicate that, as a result of simultaneous production of superoxide anion and nitric oxide, peroxynitrite may contribute to the neuropathogenesis of HIV-1 infection.

AIDS Dementia Complex↗

Sialuria in a Portuguese girl: clinical, biochemical, and molecular characteristics.

Sialuria, a disorder of sialic acid (NeuAc) metabolism characterized by increased free NeuAc in the cytoplasm of cells, is due to failure of CMP-Neu5Ac to feedback inhibit UDP-N-acetylglucosamine (UDP-GlcNAc) 2-epimerase. We now describe the fifth patient in the world with sialuria, a 7-year-old Portuguese girl with developmental delay, hepatomegaly, coarse facies, and urinary excretion of 19 micromol of free NeuAc/mg creatinine. The patient's fibroblasts stored excess free NeuAc in the cytosolic fraction, and fibroblast UDP-GlcNAc 2-epimerase activity was only 26% inhibited by 100 microM CMP-Neu5Ac (normal, 79%). The patient's UDP-GlcNAc 2-epimerase gene displayed an R266Q mutation in only one allele, consistent with known sialuria mutations and with the proposed dominant nature of this disorder. Extensive description of sialuria patients will help to define the clinical and biochemical spectrum of this disease.

Abnormalities, Multiple↗

Alterations in the growth and adhesion pattern of Vero cells induced by nutritional stress conditions.

The pattern of growth, adhesion and protein synthesis in Vero cells submitted to nutritional stress conditions was investigated. The control cells presented a characteristic pattern, with monolayer growth, while the stressed cells presented multilayered growth, with aggregate or spheroid formation which detached on the flask surface and continued their growth in another region. In the soft agar assay, with reduced amount of nutrients, only the stressed cells presented growth, indicating physical and nutritional independence. A 44-kDa protein was observed in stressed cells and was absent in non-stressed cells. The adhesion index and fibronectin synthesis and distribution were altered in stressed cells. After confluence, control cells presented fibronectin accumulation in lateral cell-cell contact regions, while this fibronectin accumulation pattern was not observed in stressed cells. These alterations may be responsible for the multilayered growth and decreased adhesion index observed in stressed cells which were transformed by nutritional stress conditions.

Animals↗

A case of predominantly nocturnal soiling treated with amitriptyline.

The case of a 6 year old with soiling along with looseness of bowel and nocturnal soiling is reported. After failing to respond to conventional treatments, his symptoms remitted on a small dose of amitriptyline. Within the diversity of presentations of soiling, there may be a subgroup, not usually amenable to treatment, who can benefit from symptomatic treatment with tricyclic antidepressants.

Amitriptyline↗

[Kidney transplantation in patients with type I and type II diabetes mellitus].

A total of 618 patients with end-stage renal disease received kidney transplants between 1980 and September 1996. Twenty eight of them were diabetics. Better results were achieved for type 1 diabetic patients than for type 2 (mortality: 5.9% vs 27.3%; functioning graft: 88.2% vs 72.7%). The morbility was also higher in those patients (infections: 81.8% vs 29.4%; vascular complications: 45.5% vs 17.6%). Actuarial patient and graft survival were lower for type 2 than for non diabetic patients. For type 1 diabetics the results are similar to those for non diabetics. Better results can probably be achieved by restricting the selection criteria. The decision to transplant or maintain on dialysis should be made on a case by case basis.

Adult↗

[Left ventricular pseudoaneurysm: a rare complication of acute myocardial infarction diagnosed by echocardiography].

Postmyocardial infarction left ventricular pseudoaneurysm resulting from free wall rupture is a very rare finding. Its recognition during life is even rarer. Definitive preoperative diagnosis is difficult, implying, in a great number of cases, the use of multiple imaging modalities. A case of a left ventricular pseudoaneurysm as a mechanical complication of acute myocardial infarction, which was diagnosed by transthoracic echocardiography, is reported. The authors emphasize its rarity, the diagnostic difficulties involved and the contribution of echocardiography to the characterization of that lesion, allowing a definitive diagnosis prior surgery in this case.

Aged↗

Extracellular matrix composition of different regions of the knee joint cartilage in cattle.

Articular cartilage covering the bone ends at the joint shows different chemical composition in different regions, depending on the mechanical and biological properties of that region. Several studies have shown a relationship between the chemical composition of the cartilage and biomechanical forces. In the present study we analysed five different knee joints divided into the following regions: F1-medial and lateral border of the patellar surface, F2-patellar surface of the femur, F3-medial and lateral condyles, P-articular surface of the patella and T-medial and lateral condyle of the tibia. The main glycosaminoglycan (GAG) present in these regions was chondroitin sulfate. Analysis of total GAG after digestion of the tissue with papain showed that in F2 and F3 there was a larger quantity of GAG/mg tissue, probably due to the dynamic character of the biomechanical forces in these regions. No significant differences were found for the extract and D1 fractions of the different regions. Analysis of the D4 fraction showed that the protein content was higher in the F3 and P regions than in their opposite T and F2 regions. The differences among the five regions may be a result of the non-uniform presence of biomechanical forces supported by these regions. It is important to consider that the intensity and direction of stress in different parts of a tissue may influence the composition of the extracellular matrix.

Analysis of Variance↗

[24-hour arterial pressure study and diabetic neuropathy and angiopathy of the lower limbs].

AIMS: To study the circadian variation of BP in diabetics with chronic late complications (autonomic neuropathy, peripheral neuropathy and macroangiopathy of the lower limbs). PATIENTS AND METHODS: We studied 35 NIDDM patients, 22 male and 13 female, with a mean age of 62.17 +/- 8.66 years, all with hypertension (HBP) or with BP levels close to normal, many of them under anti-hypertensive therapy (mean BP in clinical measurements: 164 +/- 23.16 mmHg systolic and 92.14 +/- 11.06 mmHg diastolic). Twenty-four suffer from autonomic neuropathy, 23 from peripheral neuropathy and 11 from macroangiopathy of the lower limbs. The control group is composed of 10 patients with essential HBP without other observable pathology, with a mean age of 68.5 +/- 3.63 years and BP in clinical measurements: systolic 192 +/- 15.49 mmHg and diastolic 88 +/- 4.21 mmHg (without any previous therapy). The record of the BP circadian profile was made, with the use of a Spacelab monitor, model 90207, 5 days after anti-hypertensive therapy was suspended. RESULTS: The mean BPs in 24 hours were: control group-systolic BP 152.6 +/- 13 mmHg and diastolic 79.8 +/- 13 mmHg; diabetics-systolic BP 136.82 +/- 15 mmHg and diastolic 77.4 +/- 8 mmHg. The daily and nocturnal mean BPs were 158.5 +/- 8.5 and 146 +/- 8.4 mmHg (systolic) and 82.8 +/- 5.7 and 70.9 +/- 5.1 mmHg (diastolic) in the control group, while they were, in diabetics, 141.3 +/- 15.7 and 135.6 +/- 16.6 mmHg (systolic) and 79.6 +/- 7.1 and 72 +/- 8.2 mmHg (diastolic). In diabetic patients, considering the groups with and without autonomic neuropathy, the difference between daily and nocturnal mean BP was 1.6 vs 9.4 mmHg systolic and 4.9 vs 9.4 mmHg, diastolic. CONCLUSIONS: In both groups, the mean BP levels in 24 hours were notoriously lower than those obtained from the clinical measurements: the differences were 40 mmHg (control group) and 27.2 mmHg (diabetics) for systolic BP and 8.2 mmHg (control group) and 14.7 mmHg (diabetics) for diastolic. The BP circadian profiles show a lower variability, with absence of the nocturnal reduction, specially evident in diabetic patients with autonomic neuropathy versus other groups.

Aged↗

[The echocardiographic diagnosis of a rare complication of an aneurysm of the sinus of Valsalva].

We report the case of a patient with complete heart block caused by extension of a congenital aneurysm of the sinus of Valsalva into the upper interventricular septum, which was diagnosed by transthoracic and transesophageal echocardiography. We emphasize the rarity of this pathology and the value of transesophageal echocardiography in its assessment, providing a complete anatomicofunctional characterization and allowing surgical repair without previous cardiac catheterization.

Adult↗

[Prevalence of arterial hypertension in Cushing's syndrome].

OBJECTIVE: To determine the prevalence of hypertension (HT) in patients with Cushing's syndrome. PATIENTS AND METHODS: We studied 23 patients with Cushing's syndrome, 17 women (mean +/- SD age = 42.8 +/- 15.6 years) and 6 men (mean +/- SD age = 34.8 +/- 10.2 years). The etiologies were: 16-Cushing's disease, 3-suprarenal adenoma, 2-suprarenal carcinoma and 2-iatrogenic. Blood pressure (BP) was measured at least three times and we consider hypertension when systolic BP > or = 140 mmHg and/or diastolic BP > or = 90 mmHg. RESULTS: The prevalence of HT, at diagnosis, was 73.9% (64.7% in women and 100% in men) and the mean BP was 163 +/- 25/100 +/- 16 mmHg (158 +/- 26/97 +/- 15 mmHg in women and 182 +/- 5/114 +/- 10 mmHg in men). From the 16 patients with Cushing's disease, 13 (81%) had HT; all the patients (n = 3) with suprarenal adenoma had HT; none with suprarenal carcinoma (n = 2) had HT and only 1 of the 2 patients with iatrogenic Cushing's syndrome had HT. After treatment, 14 patients entered remission, 6 persisted with active disease and 1 was missed during the follow-up. In the group of patients that entered remission, the prevalence of HT at diagnosis was 78.5% (n = 11), 57.1% (n = 8) being after treatment. CONCLUSIONS: In this study, we found a high prevalence of HT at diagnosis (73.9%). After treatment and in the patients that entered remission, the prevalence of HT remained high (78.5% vs 57.1%). The high prevalence of HT in Cushing's syndrome, suggests its importance as a morbidity factor and also as an important diagnostic indicator, when present.

Adult↗

Insulin sensitivity and insulin secretion in lean and obese normal pregnant women.

An insulin-modified frequently sampled intravenous glucose tolerance test with minimal model analysis was performed in normal pregnant women between 28-32 weeks of gestation, to assess insulin sensitivity and insulin secretion. Insulin sensitivity in the pregnant group (no. 26) was reduced to approximately 50% that of nonpregnant group (no. 27) (p < 0.05). This increased insulin resistance was compensated by an enhancement of the first phase of insulin secretion, which was increased more than twofold in the pregnant women when compared with the nonpregnant women (p < 0.05). There was a trend toward greater insulin resistance and insulin secretion in the obese pregnant women (no. 7) as compared with the lean pregnant women (no. 19) although this difference was not statistically significant. Our findings confirm that late pregnancy is a state of physiologic insulin resistance compensated by an increase of insulin secretion.

Adult↗

Is there a relationship between the state of aggregation of small proteoglycans and the biomechanical properties of tissues?

The small proteoglycans fibromodulin and decorin may play an important role in regulating collagen fibrillogenesis and interactions with growth factors. Here, we describe the presence of these proteoglycans in cartilage submitted to different biomechanical forces. Fibromodulin from chicken and bovine articular cartilage was shown to self-associate. The different states of fibromodulin aggregation due to disulfide bonding demonstrable in different regions of the same joint suggest that the presence of different biomechanical forces results in the differential expression of small proteoglycans. A 250-kDa complex found in chicken tibiotarsal cartilage, which migrates as a 59-kDa component in SDS-PAGE under reducing conditions, and which was recognized by anti-fibromodulin antibodies, was not demonstrable in tarsometatarsal cartilage where a different fibromodulin complex has been recently demonstrated. Biglycan and decorin were not expressed in the same way in different regions of the bovine knee joint, suggesting that there is a relationship between the expression of small proteoglycans and the different biomechanical properties of a tissue.

Animals↗