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Biomedical subjects

M Sequeira

Publications and source records attributed to M Sequeira.

17 recordsLinked to original sources

Organochlorine compounds and stable isotopes indicate bottlenose dolphin subpopulation structure around the Iberian Peninsula.

Isotopic signatures and organochlorine pollutant loads of organisms reflect the characteristics of the waters in which they live and feed. To investigate population structure of bottlenose dolphins around the Iberian Peninsula we determined delta(13)C and delta(15)N in the skin and organochlorine (OC) levels in the blubber of stranded bottlenose dolphins inhabiting the Mediterranean (Catalonia, Valencia and Balearic Islands) and adjacent Atlantic waters (Huelva and Portugal). OC levels were high in all regions, reflecting the predatory habits of the species, its coastal distribution and the existence of intense agricultural and industrial activity throughout the region. PCB congeners showed a gradient from the relatively more chlorinated forms to those that are less so, and followed a northeast to northwest direction across the Iberian Peninsula. This suggests that PCB inputs are more recent in the temperate latitudes of the eastern Atlantic Ocean than in the western Mediterranean Sea. Comparatively, OC ratios and isotopic signatures proved to be more efficient ways of discriminating groups than did raw OC concentrations. Significant differences in delta(13)C and in PCB congener profiles indicate that dolphins from the Atlantic and the Mediterranean do not intermingle. In addition, the two Atlantic groups differed in delta(15)N signature, tDDT concentration, DDT/PCB ratio and the PCB congener profile, which also suggests some degree of isolation between them. In the Mediterranean, dolphins from Catalonia and Valencia were indistinguishable, suggesting a common distribution area. However, dolphins from the Balearic Islands differed from those of the Peninsula in their DDT/PCB ratio and from all the other sample groups in their PCB congener profiles, which supports the hypothesis that the deep waters between the Islands and the Peninsula represent an effective barrier for the species.

Animals↗

Content and distribution of arsenic in soils, sediments and groundwater environments of the southern Pampa region, Argentina.

The health of a large rural population in the southern Pampa (Argentina) is at risk owing to newly detected areas where As-groundwater exceeds 0.01 mg/L standard (WHO (1995) Guidelines for drinking water quality, 2nd edition. pp 43-45). Currently, devitrification of volcanic glass is invoked to interpret the origin of arsenic in the aquifers hosted in a sequence of pampean loess (Plio-Pleistocene) juxtaposed with postpampean loess (Holocene). Our data suggest that arsenic is not specifically associated with volcanic glass and that other minerals contribute to As-release into groundwater. The goals were (1) to understand As-groundwater spatial variability, (2) to explore soils/sediments/water relationships and to identify the probable As-provenance. Comparable As concentrations of the light and the heavy sand fractions suggest that though detrital glass is a major light constituent, other existing primary minerals are As-bearers that contribute to As-release into groundwater. Grouping of materials according to their As-content indicated spatial variability in the sedimentary distribution pattern leading to differences in the frequencies of occurrence of As-bearing minerals. Phreatic waters were Ca + Mg bicarbonate and devoid of As in the intake areas (Ventania System) and Na-carbonate but As-rich towards the discharge (Atlantic coast and local depressions). As-groundwater reflects a patchy distribution within the pampean landscape. A correspondence between As-high groundwater, EC >1 dSm, CO(3)H(-), alkaline pH and a longer water residence time do exist triggering As extraction from the loess sand fraction and desorption from charged fine particles which lead to As-toxicity towards groundwater discharge.

Argentina↗

Demonstration of reduced in vivo surface expression of activating mutant thyrotrophin receptors in thyroid sections.

OBJECTIVE: Thyroid function and growth are controlled by TSH. Hyperthyroidism can be due to Graves' Disease (GD), in which thyroid-stimulating antibodies mimic TSH, or gain-of-function mutations in the TSH receptor (TSHR). These activating mutations have poor surface expression when assessed in non-thyroidal cells in vitro but nothing is known of their in vivo behaviour. Several TSHR antibodies have been produced but none has been applied to thyroid paraffin sections. This study aimed to develop a technique suitable for use on paraffin sections and apply it to investigate TSHR expression in thyroids harbouring activating TSHR germline mutations compared with normal and GD thyroids. DESIGN AND METHODS: Immunocytochemistry coupled with antigen retrieval, using a spectrum of antibodies to the TSHR, was applied to paraffin sections of GD thyroid tissue. Subsequently, TSHR immunoreactivity was examined in three normal thyroids, three patients with GD and three patients with familial hyperthyroidism, due to different gain-of-function TSHR germline mutations, using the optimised protocol. RESULTS: Two antibodies, A10 and T3-495, to the extracellular domain (ECD) and membrane spanning region (MSR) of the TSHR respectively, produced specific basolateral staining of thyroid follicular cells. In normal and GD thyroids, basolateral staining with T3-495 was generally more intense than with A10, suggesting a possible surfeit of MSR over ECD. Graves' Disease thyroids have more abundant TSHR than normal glands. In contrast, thyroids harbouring gain-of-function mutations have the lowest expression in vivo, mirroring in vitro findings. CONCLUSIONS: The development of an immunocytochemical method applicable to paraffin sections has demonstrated that different molecular mechanisms causing hyperthyroidism result in the lowest (mutation) and highest (autoimmunity) levels of receptor at the thyrocyte surface.

Adult↗

Heavy metals in the tissues of common dolphins (Delphinus delphis) stranded on the Portuguese coast.

The concentrations of Hg, Sn, Cr, Zn, Ni, Co, Cd, Mn, Fe and Cu were determined in the liver, kidney and muscle of 24 common dolphins stranded on the Portuguese coast between 1995 and 1998. Nitric acid was used to extract the metals from the tissues for analysis by inductively-coupled plasma/atomic emission spectroscopy (ICP/AES). Those metals with relatively higher concentrations included Fe, Zn and Hg, particularly in liver. Other metals including Cr, Ni and Cd tended to show much lower levels, or were even undetected (e.g. Co). Different metals seemed to show different temporal trends, although due to substantial variations of the mean concentrations for each year obtained, such temporal pattern has to be studied further. Total Hg concentration in the kidney, muscle and particularly liver, were higher in females than in males. Total Hg concentrations in all the organs increased with body length of dolphins, whilst those of Zn and Cu in muscle decreased with dolphin length. A strong correlation was found between essential metals Zn and Cu in muscle, possibly resulting from sequestration of these metals by metallothionein. In addition, significant co-associations existed between the same metal (e.g. Hg, Sn and Zn) in different organs.

Animals↗

Efficacy and mechanisms of action of rmB7.2-Ig as an antitumor agent in combination with Adriamycin and Cytoxan chemotherapy.

The efficacy of chemotherapy for cancer is often limited by toxicity. Immune approaches to cancer immunotherapy, while promising for specificity and long-term protection, have not typically proven potent enough to generate significant therapeutic responses. We have shown therapeutic benefit using recombinant murine B7.2-Ig (rmB7.2-Ig) in murine tumor models. Efficacy was dependent on immune activity and was not associated with toxicity. Recently, the efficacy of rmB7.2-Ig was demonstrated in leukemia tumor models in combination with chemotherapeutic agents. To further explore the potential of this approach, we evaluated the efficacy in solid tumor models of rmB7.2-Ig given in combination with chemotherapeutics commonly used in clinical practice, testing the effects of dose and schedule. RmB7.2-Ig in combination with some chemotherapeutics enhances the activity and efficacy of reduced chemotherapeutic doses. However, the relative timing of chemotherapy and rmB7.2-Ig dosing can be important. Investigation of mechanisms of action based on histological studies suggests that inflammatory as well as T cell mechanisms comprise the response. Additional studies of mice deleted of B7.1, B7.2, and CTLA-4 suggest that the enhanced response induced by rmB7.2-Ig may not be mediated through CD28 ligation alone. The efficacy suggests potential for recombinant human B7.2-Ig as an adjuvant to chemotherapy in promoting immune-mediated mechanisms to augment the activity of chemotherapy.

Animals↗

Sebaceous carcinoma of the eyelid treated with Mohs micrographic surgery.

BACKGROUND: Sebaceous carcinoma is an aggressive neoplasm that commonly arises from the meibomian glands of the eyelids and other sebaceous glands of the ocular adnexa. Historic data indicate a nearly 30% local recurrence rate with standard surgical excision. Excision by means of Mohs micrographic surgery may be more efficacious. However, reports documenting the effectiveness of this technique for the treatment of eyelid sebaceous carcinoma have been limited to a few cases. OBJECTIVE: We report our experience in the treatment of ocular sebaceous carcinoma with the Mohs fresh tissue technique. METHODS: Eighteen patients with a diagnosis of sebaceous carcinoma of the eyelid who underwent resection by means of the Mohs fresh tissue technique during the years 1988-1998 were reviewed. RESULTS: Sixteen of the 18 patients were free of disease after an average follow-up of 37 months (11.1% recurrence rate). One patient who experienced local recurrence also had metastatic disease of the parotid lymph nodes (5.6% metastatic rate). The recurrence and metastasis were noted 9 months after excision. The other patient experienced a local recurrence 19 months postoperatively. Both patients exhibited pagetoid spread and involvement of both the upper and lower eyelid at the time of Mohs excision. CONCLUSION: Mohs surgery offers excellent results when used as the primary treatment modality for sebaceous carcinoma of the eyelid. When compared with historic series of standard surgical excision, Mohs micrographic surgery has a significantly lower recurrence rate and metastatic rate.

Adenocarcinoma, Sebaceous↗

The use of conscious sedation for outpatient dermatologic surgical procedures.

BACKGROUND: Dermatologic surgery has undergone increasing levels of sophistication over the past few decades. Commensurate with this demand, an established anesthesia technique called conscious sedation has been employed. OBJECTIVES: Methods for performing office-based conscious sedation are described. Recommendations are made regarding prerequisites for conscious sedation in an office setting, patient selection, complications management, and postoperative discharge requirements. CONCLUSION: The goals of anesthesia are to provide for patient safety and comfort, to increase patient acceptance of the procedure, and to enhance the surgeon's efficiency and satisfaction.

Ambulatory Surgical Procedures↗

Novel TSHR germline mutation (Met463Val) masquerading as Graves' disease in a large Welsh kindred with hyperthyroidism.

Hereditary nonautoimmune hyperthyroidism is caused by activating germline mutations in the thyrotropin (TSH) receptor (TSHR) gene. We describe an extended Welsh kindred with toxic thyroid hyperplasia affecting 8 family members in three generations and a history consistent with thyrotoxicosis in a further three generations now deceased. A novel heterozygous germline mutation (ATG --> GTG; Met463Val) was identified in the second membrane spanning TSHR region in 6 relatives with thyrotoxicosis and goiter and absence of TSHR antibodies. Screening of 5 additional family members led to the identification of 2 siblings with the mutation, who were asymptomatic at the time, although subsequent thyroid function tests in these children showed suppressed serum TSH and increased serum free triiodothyronine (FT3) and free thyroxine (FT4) concentrations. Functional studies of the novel TSHR germline mutation demonstrated a constitutive activation of the cAMP pathway, which in the thyroid controls both thyroid hormone production and stimulation of thyroid growth. The molecular diagnosis in this family has clinical implications: genetic counseling is required, and primary thyroid ablation should be advocated as the preferred treatment in the patients with the constitutively activating TSHR germline mutation.

Animals↗

The combined use of propofol and fentanyl for outpatient intravenous conscious sedation.

BACKGROUND: Intravenous conscious sedation is currently being widely utilized for outpatient surgery including dermatologic surgery. Even though this type of anesthesia is typically administered by a trained, licensed anesthetist, it is important for dermatologists who either intend to or are currently utilizing this type of anesthesia to be familiar with some of the methods and agents that are commonly employed. OBJECTIVE: Propofol and fentanyl are two anesthetic agents that are in prevalent use for skin and soft tissue surgery of brief or limited duration. With the goal of familiarizing dermatologic surgeons with this form of anesthesia, a study was conducted to evaluate the safety and effectiveness of the combination of propofol and fentanyl when used for conscious sedation in an outpatient dermatology center. METHODS: Twenty patients, ages 25-65 years, who required conscious sedation were enrolled. Each patient received a standard dosage of fentanyl and propofol, as determined on a kilogram basis. Sedation time, total procedure time, recovery time, and total propofol dose, along with side effects, were determined. RESULTS: The mean onset to sedation was 52.5 seconds, the mean procedure time was 40 minutes 37 seconds, and the mean interval to recovery was 3 minutes 43 seconds, with a mean total dose of propofol of 5.83 mg/kg. Minimal side effects occurred. CONCLUSION: Propofol when used in conjunction with fentanyl appears to be a safe, quick, and effective method of providing conscious sedation.

Adult↗

Surgical intervention for the aging face. Combination of mini-face-lifting and superficial carbon dioxide laser resurfacing.

BACKGROUND: Patients seeking facial rejuvenation often would benefit from a combination of face-lifting and laser resurfacing. Fear of skin slough has prevented the study of this issue. OBJECTIVE: We report our experience utilizing a combination of simultaneous cervicofacial rhytidectomy and carbon dioxide (CO2) laser resurfacing, and summarize the results of a survey completed by each patient. METHODS: Forty patients underwent the combination treatment. Patients were followed and asked to respond to a questionnaire 12 months postprocedure regarding their surgical experience. RESULTS: Our survey revealed an overall degree of satisfaction. Reported complications included transient swelling, redness, pigmentary alteration, and numbness. One patient experienced minimal slough in a nonresurfaced site. CONCLUSIONS: The control of depth of thermal damage with the CO2 UltraPulse laser allows for precision in its combined application along with face-lifting. In the area of the flap, one pass at low power settings is safe in our experience and results in an improved cosmetic result.

Carbon Dioxide↗

Dermatologic uses of interferons.

Interferons are members of the cytokine family, with diverse antiviral, antiproliferative, antifibrotic, and immunomodulatory activities. Over the past 10 years, interferon use in clinical dermatology has extended beyond its historical antiviral efficacy. In this article, FDA-approved indications and non-FDA-approved dermatologic uses of interferons are reviewed.

Humans↗

[Characterization of fatty acids and mycolic acid degradation products in mycobacterial species of major incidence in Argentina].

The human immunodeficiency virus (HIV) epidemic has altered the epidemiological profile of tuberculosis in both industrialized and developing countries. Serious diseases caused by mycobacteria other that M. tuberculosis, mostly belonging to the M. avium-intracellulare complex (MAC), have become very common in association with severe immunosuppression. The increase in mycobacterial disease complexity has stimulated the development of more rapid and efficient methods of diagnosis. In the present study we characterized the cellular fatty acids and the mycolic acid cleavage product from most frequent mycobacteria species in Argentina using gas chromatography in order to develop a rapid technique for their identification. Fatty acids and mycolic acids extracted from saponified mycobacterial cells were examined as methyl esters by capillary has chromatography. The major constituent fatty acids in all species, with the exception of M. smegmatis, were octadecenoic (18:1) and hexadecanoic (16:1) acids. The fatty acids and mycolic acid cleavage product profiles from the studied species were quantitatively but not qualitatively different. Tuberculostearic acid was found in all species. Significantly different amounts of some fatty acids (p < 0.01) were observed among clinical isolates of M. tuberculosis, M. bovis and MAC. Traces of 2-eicosanol were detected in the M. tuberculosis H37Rv strain. Although a limited number of strains and species were tested, preliminary results indicate that this method could be used to characterize mycobacterial cultures.

AIDS-Related Opportunistic Infections↗