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Biomedical subjects

M Maia

Publications and source records attributed to M Maia.

At least 19 recordsLinked to original sources

Visual and electrical evoked response recorded from subdural electrodes implanted above the visual cortex in normal dogs under two methods of anesthesia.

Sensitive methods are required to record electrical evoked potentials over the visual cortex to evaluate the efficacy and safety of a retinal prosthesis before it can be implanted on the retinal surface of patients afflicted by outer retinal diseases. This study was designed to examine subdural electrodes as a mean to evaluate cortical evoked potentials in response to light and electrical stimulation of the retina in three dogs under two methods of anesthesia-halothane and propofol. Results showed that subdural electrodes could be stabilized over the visual cortex for several (3-5) months, and that they were 6.95 times more sensitive than subdermal electrodes in recording cortical visual evoked potentials (VEPs) and 4.31 times more sensitive in recording cortical electrical evoked potentials under both methods of anesthesia. The waveforms' shape changed for each electrode in the subdural array during 6/6 (100%) and 20/38 (52%) multi-channel recording sessions under halothane and propofol, respectively. This change could point to a cortical retinotopic organization versus hierarchical organization of different cortical areas for a given retinal stimulus. In summary, subdural electrodes show promising results for recording visual and electrical evoked responses (EERs) and thus for evaluation of the retinal prosthesis.

Anesthesia↗

Expression of the melanocortin receptors MC2-R (ACTH-receptor) and MC5-R during embryonic development of ovine adrenals.

Two melanocortin receptors MC2-R (ACTH-receptor) and MC5-R are expressed in the adult lamb adrenal cortex. In this work, we have studied the time-course of expression of these two receptors during ovine fetal development. MC2-R expression progressively increases from day 60 to day 140 of gestation (x3), then more rapidly before parturition and remains constant in the newborn. In contrast, the pattern of MC5-R expression is totally different. A strong increase is observed between days 60 and 120 (x7) then followed by a decrease until parturition and after birth. This peak of MC5-R expression precedes that of MC2-R, suggesting that MC5-R might be involved in alpha-MSH- and/or ACTH-stimulated corticosteroid synthesis during early embryonic life.

Adrenal Glands↗

Macular translocation: unifying concepts, terminology, and classification.

PURPOSE: To describe some unifying concepts, terminology, and classification of macular translocation so as to facilitate communication within the scientific community. METHODS: A panel of ophthalmologists with expertise in macular translocation reviewed available data and developed some unifying concepts, terminology, and classification of macular translocation. RESULTS: Macular translocation may be defined as any surgery that has a primary goal of relocating the central neurosensory retina or fovea intraoperatively or postoperatively specifically for the management of macular disease. It may be classified according to the size of the retinotomy and, where applicable, the technique of chorioscleral shortening used. The direction of macular translocation is denoted by the movement of the neurosensory macula relative to the underlying tissues. Effective macular translocation may be defined as successful intraoperative or postoperative relocation of the fovea overlying a subfoveal lesion to an area outside the border of the lesion. The concepts of minimum desired translocation and median postoperative foveal displacement can give some useful idea of the likelihood of effective macular translocation before surgery. CONCLUSIONS: Use of a common standardized terminology for macular translocation will facilitate communication within the scientific community and enhance further research in this area. However, the definitions, terms, classification, and concepts concerning macular translocation are likely to continue to evolve as macular translocation undergoes further modifications and refinements.

Humans↗

[Fungal keratitis in the State of Paraná-Brazil: clinical, epidemiological and diagnostic findings].

Fungal keratites is more prevalent in tropical and subtropical regions, such as Brazil, and causes high morbidity. Usually, it is preceded by underlying conditions like ocular trauma or immunosuppression. The diagnosis is confirmed by the demonstration of the etiologic agent in the clinical specimen. Data were analysed from 49 patients with fungal keratitis observed in Ophthalmologic Division of Hospital de Clinicas, Federal University of Parana, from 1983 to 1997. The diagnosis was confirmed by culture and/ or direct examination. Of the cases studied, 22% were diagnosed only by direct examination; 50% by isolation in culture and 26% by the association of the both methods. The most prevalent etiologic agents were: Fusarium sp. (32%), Aspergillus sp. (16,5%) and Penicillium sp. (10%).

English Abstract↗

Phase I trial of HuM291, a humanized anti-CD3 antibody, in patients receiving renal allografts from living donors.

BACKGROUND: HuM291 is a humanized anti-CD3 monoclonal antibody engineered to reduce binding to Fcgamma receptors and complement fixation. HuM291 has a long serum half-life and mediated profound depletion of circulating T cells in chimpanzees; HuM291 also has significantly less mitogenic and cytokine-releasing activity than OKT3 in vitro. METHODS: A phase I dose-escalation study was conducted in 15 end-stage renal disease patients scheduled for renal allografts from living donors. Patients received one i.v. HuM291 injection before transplantation. Five doses were tested: 0.015 microg/kg, 0.15 microg/kg, 0.0015 mg/kg, 0.0045 mg/kg, and 0.015 mg/kg. Patients were followed for adverse events, laboratory abnormalities, serum cytokine levels, pharmacokinetics, and CD2+, CD3+, CD4+, and CD8+ T cell counts. RESULTS: HuM291 was well tolerated; most adverse events were mild to moderate in severity and included headache, nausea, chills, and fever. These occurred within the first few hours after HuM291 administration, resolved within 24 to 48 hr, and were likely related to cytokine release. In general, peak tumor necrosis factor-alpha, interferon-gamma, and interleukin-6 levels were detected 1 to 6 hr postdosing only at the three highest doses and were generally undetectable by 24-hr postdosing. Serious adverse events possibly related to HuM291 included clotting of a fistula (two patients), chemical cellulitis (one patient), and increased serum creatinine/decreased hematocrit (one patient). At doses > or = 0.0015 mg/kg (0.1 mg/70 kg), HuM291 induced rapid, marked depletion of peripheral T cells within 2 hr; duration of T cell depletion was dose dependent. At the two highest dose levels, T cells remained depleted for approximately 1 week. CONCLUSIONS: A single HuM291 dose rapidly depleted circulating T cells in a dose-dependent manner and was associated with only mild to moderate symptoms of cytokine release.

Adult↗

Chronic stress effects on the rat adrenal cortex.

Under the influence of a chronic permanent stress, the adrenal function as well as the entire hypothalamic-pituitary-adrenal axis (HPAA) suffered an adaptation process that resulted in the normalization of the studied stress hormones (ACTH, corticosterone and aldosterone) with the exception of plasma renin activity which first diminished and at the end increased. ACTH receptors exhibited a dual response since after 14 days of permanent stress MC2-R showed a slight reduction while MC5-R was still up-regulated.

Adrenal Cortex↗

The mitochondrial DNA A3243G mutation in Portugal: clinical and molecular studies in 5 families.

Out of 90 Portuguese patients with mitochondrial cytopathy, six harbored the A3243G mutation in the mtDNA tRNA(Leu(UUR)) gene ('MELAS mutation'). They had heterogeneous clinical features, including myopathy with stroke-like episodes, progressive external ophthalmoparesis, diabetes mellitus, and subacute encephalopathy. Histochemical and biochemical analyses of muscle biopsies showed abundant ragged-red fibers reacting positively with the cytochrome oxidase stain, and decreased respiratory chain enzyme activities. On average, the proportion of mutated mtDNA was 67% (20-88%) in tissues from patients and 21% (0-49%) in blood from 20 maternal relatives. The proportion of mutated mitochondrial genomes in muscle did not correlate with clinical presentation or duration of disease. This study, the first in Portuguese patients, confirms the frequent occurrence of the A3243G mutation in patients with mitochondrial diseases, and emphasises the usefulness of genetic testing in reaching a correct diagnosis.

Adolescent↗

Ontogeny of 3beta-hydroxysteroid dehydrogenase expression in the rat adrenal gland as studied by immunohistochemistry.

The enzyme 3beta-hydroxysteroid dehydrogenase plays a crucial role in the steroidogenic process in the adrenal gland. In the present study we tried to characterize its localization and developmental changes in the rat adrenal cortex during the postnatal period, using immunohistochemical methods. The development of the different zones evidenced specific particularities: the zona glomerulosa almost lacked 3beta-HSD in the first days after birth; then, 3beta-HSD increased, attaining a maximum around day 20 and afterwards it decreased again and remained less intense than the neighbouring zona fasciculata up until adulthood (65 days of age). The zona fasciculata was already intensely stained at birth and the expression of 3beta-HSD increased rapidly reaching a maximum after 2 weeks of life and that level was maintained from then on. The inner part of the zona fasciculata and the zona reticularis both of which develop postnatally were faintly immunostained before day 20. The expression of 3beta-HSD increased after that age to become approximately as intense as in the outer zona fasciculata and so remaining until day 90. The development of the zona glomerulosa was parallel to the secretion of aldosterone. The same did not occur with the zona fasciculata as the intensity of staining during the first 14 postnatal days was accompanied by very low levels of corticosterone.

3-Hydroxysteroid Dehydrogenases↗

L-2-Hydroxyglutaric aciduria: clinical, biochemical and magnetic resonance imaging in six Portuguese pediatric patients.

We present clinical, biochemical and cranial magnetic resonance imaging data of six pediatric patients with L-2-hydroxyglutaric aciduria. All the children have the same ethic origin and lived in the northern area of Portugal. Our findings reinforce the described phenotype of this rare metabolic disease with mental deficiency, severe cerebellar dysfunction, mild extrapyramidal and pyramidal symptoms, progressive macrocephaly and seizures. Magnetic resonance imaging revealed subcortical leukoencephalopathy, cerebellar atrophy and signal changes in the putamina and dentate nuclei. These were similar to those of the previous reports in all patients. The urinary excretion of L-2-hydroxyglutaric acid was variably increased in all patients. The other persistent biochemical abnormality was hyperlysinemia. We have found a strong correlation between the severity of the clinical manifestations and the extension of the lesions in the neuroimaging studies. There was no correlation between the clinical findings and the amount of urinary excretion of L-2-hydroxyglutaric acid. We report the second case in the literature of a cerebral thalamic tumor in L-2-hydroxyglutaric aciduria; neuropathological examination of the surgical biopsy demonstrated a diffuse fibrillary astrocytoma.

Adolescent↗

Development of a two-site immuno-PCR assay for hepatitis B surface antigen.

Hepatitis B virus (HBV) gene transcription may occur at very low levels resulting in HBsAg concentrations in serum and liver below the limit of detection by currently available immunoassays. An assay has been developed that combines the specificity of two high affinity anti-HBs monoclonal antibodies (MAb) directed against distinct and separate determinants in the 'a' domain of HBsAg with the highly sensitive polymerase chain reaction (PCR) detection method. Following capture of HBsAg present in serum samples, the second anti-HBs MAb, which is biotinylated, is added. Binding of the second antibody allows the subsequent specific binding of streptavidin and a biotinylated linear DNA molecule derived from a bluetongue virus (BTV) gene. Presence of this DNA is then detected by PCR using BTV-specific primers. The PCR product is quantified by a liquid-phase oligonucleotide enzymatic assay, which further increases the sensitivity of the technique. The use of a two-site MAb capture and PCR detection system for HBsAg was shown to greatly enhance the specificity and sensitivity of the assay and detect as little as 0.5 pg of HBsAg in serum samples. It is suggested that the principles of this technique could be applied to measure other low level viral antigens in serum and biological samples.

Antibodies, Monoclonal↗

Risk factors for basal cell carcinoma: a case-control study.

A controlled trial was performed with the purpose of investigating which factors could be considered of significant risk for the development of basal cell carcinoma. A total of 259 cases of basal cell carcinoma diagnosed from July 1991 to July 1992 were compared with 518 controls matched for age and sex. All subjects in both groups were white. Protocol data were submitted to statistical analysis by the chi-square test and by multiple conditional logistic regression analysis and the following conclusions were reached: 1) light skin color (types I and II of the Fitzpatrick classification), odds ratio of 2.8; outdoor work under constant sunlight, odds ratio of 5.0; the presence of actinic lesions due to exposure to the sun, odds ratio of 4.9, are risk factors per se. 2) Type III skin in the Fitzpatrick classification only represents a risk factor when the patient reports a history of intense sunburns, but not in the absence of such a history. 3) Sunburns per se do not represent a risk factor althorig the point made in item 2 of these conclusions is valid. 4) Other suspected risk factors whose significance was not confirmed by multiple conditioned logistic regression analysis were: residence in rural areas, light eyes and blond hair color, extent of the awareness of the "sun x skin cancer" relationship, familial occurrence of skin cancer, excessive exposure to the sun, and freckles appearing in childhood.

Brazil↗

Expression of a full-length nonstructural protein NS1 of bluetongue virus serotype 17 in Escherichia coli.

The relative abundance of the nonstructural protein NS1 in bluetongue virus (BTV)-infected cells, the existence of NS1 in the BTV particles and the highly conserved NS1 gene among BTV serotypes indicate the diagnostic potential of using NS1 in detecting BTV infections. In this study a NS1 gene was expressed with the T7 RNA polymerase expression system to produce a full-length NS1 protein. Sheep anti-NS1 antibodies were raised with the E. coli-produced NS1 and used to show that the NS1 proteins of the five BTV serotypes in the Unites States were immunologically indistinguishable.

Animals↗

Biochemical characterization of beta-hexosaminidase in different biological specimens from eleven patients with GM2-gangliosidosis B1 variant.

GM2-gangliosidosis B1 variant is thought to be a rare disorder with a wide geographical and ethnic distribution. We report the biochemical findings obtained in different specimens from a group of 11 B1 variant patients originating from the north of Portugal. The biochemical data obtained seem to indicate that only one of these patients is a genetic compound presenting a clinical and biochemical pattern similar to the majority of B1 variant patients described in the literature, but somewhat different from the profile presented by the other patients reported here, who are homozygous for the 'DN-allele'.

Acetylglucosamine↗

GM2-gangliosidosis B1 variant: analysis of beta-hexosaminidase alpha gene mutations in 11 patients from a defined region in Portugal.

The GM2-gangliosidosis B1 variant occurs at an exceptionally high frequency in the northern part of Portugal. In most patients, the disease manifests itself as a juvenile form, as opposed to the late-infantile form described for many patients from other parts of the world. We have analyzed the beta-hexosaminidase alpha gene in 11 patients, as well as in some relatives, in order to characterize the underlying abnormalities. They were screened for the two previously identified mutations responsible for the B1 variant phenotype (G533----A, also designated as the "DN allele," and C532---T) by PCR amplification of an 800-bp DNA fragment and subsequent dot-blot hybridization with allele-specific oligonucleotides. The fragment amplified from one patient was also subcloned and sequenced. Ten patients, constituting a clinically and biochemically homogeneous group, were found to be homozygous for the DN allele. The other, whose clinical profile more resembled the late-infantile phenotype often described in the literature, was a compound heterozygote carrying the DN allele and another, as yet unidentified, abnormal allele. Our results, corroborated by previously published data, suggest that homozygotes and compound heterozygotes for the DN allele may be distinguishable at the phenotypic level, depending on the nature of the abnormality in the other allele. A common ancestral origin for the DN allele can also be postulated.

Adolescent↗