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Biomedical subjects

O Fernandez

Publications and source records attributed to O Fernandez.

At least 19 recordsLinked to original sources

OAS1 gene haplotype confers susceptibility to multiple sclerosis.

Multiple sclerosis (MS) is associated with genetic susceptibility and unknown environmental triggers, possible viral infections, but the specific etiological mechanism that subsequently develops into an inflammatory/autoimmune cascade of events is poorly understood. Recently, genetic variants of 2',5'- oligoadenylate synthetase 1 (OAS1) gene, a critical enzyme involved in innate antivirus response, have been associated with differential enzyme activity and type 1 diabetes in both case-control and family studies. We hypothesized that polymorphisms in the OAS1 gene could influence the susceptibility to MS. To test this hypothesis, we conducted a case-control study of 333 patients with MS and 424 healthy controls and genotyped two OAS1 single nucleotide polymorphisms (SNPs) by restriction fragment length polymorphism method: rs 10774671, A/G SNP altering the splicing site at the seventh exon, and rs 3741981, a nonsynonymous (Ser162Gly) A/G SNP in the third exon. Haplotype but not single-marker analysis revealed an association of the haplotype created by the G allele at rs 10774671 and the A allele at rs 3741981 with the susceptibility to MS (P value = 8.8 x 10(-5)). Subjects carrying this haplotype had an increased risk of MS comparing with those not carrying it (odds ratio = 4.7, 95% confidence interval 2.1-10.9). Our findings indicate that the OAS1 gene polymorphisms may confer susceptibility to MS or serve as markers of functional variants and suggest that OAS1 activity is involved in the etiology of the disease. Future studies in a larger sample and association analysis with functional variants will clarify the role of the OAS1 gene in the susceptibility to MS.

2',5'-Oligoadenylate Synthetase↗

MRI results from the European Study on Intravenous Immunoglobulin in Secondary Progressive Multiple Sclerosis (ESIMS).

BACKGROUND: Monthly application of high-dose intravenous immunoglobulin (IVIG) to patients with secondary progressive multiple sclerosis (MS) showed no clinical benefit in the European Study on Immunoglobulin in MS (ESIMS). Magnetic resonance imaging (MRI) results may provide insights into the morphologic consequences of such treatment. METHODS: A total of 318 patients (mean age 44 +/- 7 years) were enrolled in 31 European and Canadian centres and treated monthly with 1 g/kg body weight of IVIG or equivalent amounts of albumin 0.1% for 27 months. MRI was performed at baseline and after 12 and 24 months and comprised of conventional dual-echo T2-weighted and T1-weighted scans before and after application of 0.1 mmol/kg Gd-DTPA. RESULTS: Similar to clinical variables, MRI measures at baseline were well comparable between treatment groups except for a somewhat lower mean number of contrast-enhancing lesions and number of active scans in IVIG-treated patients. Over the trial period there was almost no change of the T2-lesion load and the 'black hole' volume in both treatment groups and the cumulative number of contrast-enhancing lesions were similar. There was only a trend for fewer new or enlarged T2-lesions in IVIG patients, which disappeared after correction for the imbalance in the number of contrast-enhancing lesions at baseline. Brain volume in terms of a partial cerebral fraction decreased significantly less with IVIG than placebo treatment (final visit: -0.62 -/+ 0.88% versus -0.88 +/- 0.91%; P=0.009). This difference remained statistically significant with correction for active lesions at baseline (P=0.02) and was seen primarily in male patients and those with an Expanded Disability Status Scale score > or = 6 and no relapses in the two years before the study. CONCLUSION: The absence of significant differences in conventional MRI measures between both treatment groups parallels the negative clinical results of ESIMS. The causes for and possible long-term clinical effects of a lower rate of brain volume loss in IVIG patients should be explored further.

Adult↗

Public health surveillance and incidence of adulthood Guillain-Barré syndrome in Spain, 1998-1999: the view from a sentinel network of neurologists.

Temporal variation in Guillain-Barré syndrome (GBS) warrants monitoring in certain situations. This study sought to describe a public-health-based GBS surveillance service in Spain and conduct pilot surveillance in the period 1998-1999. Neurologists from 11 hospitals countrywide, serving a population of 3.9 million, reported all patients, ages 20 years or over, admitted to hospital with suspected GBS. Cases that did not belong to the designated hospital catchment area or failed to fulfill diagnostic criteria after follow- up were excluded. Reported monthly incidence was compared against predicted incidence obtained from retrospective data (1985-1997) using a reported method based on 97.5% percentile values. Alarm thresholds for 2000 onwards were obtained by applying the same method to the updated 1985-1999 series. During the 2-year period, 98 GBS cases were reported, yielding an overall age-adjusted incidence of 1.26 per 100 000 population, with a breakdown by sex of 1.83 for males and 0.76 for females. Monthly incidence remained below or was similar to the corresponding threshold limit value. Seasonality with highest incidence in winter was more pronounced in the elderly. Preceding events, mainly respiratory infections, were identified in 71% of patients. Pilot two-year GBS surveillance in Spain resulted neither in alarm nor in preventive measures. Adult GBS incidence in Spain might be monitored by a surveillance system set up at short notice when a possible threat is perceived. A monthly incidence of over 3 per 100 000 person-years in the population aged 20 years or older would exceed threshold values.

Adult↗

Efficacy of Rhizophora mangle aqueous bark extract in the healing of open surgical wounds.

Thirty-seven patients with open wounds from surgical intervention of pilonidal cyst (14; 37.8%) or pilonidal fistula (23; 62.2%) were enrolled on a voluntary basis in a comparative blinded clinical trial and randomly assigned to a topical treatment with a Rhizophora mangle aqueous bark extract once a day or twice a day or mercurocrome twice a day. The efficacy of the treatments was evaluated weekly from day 10 to 12 until 6 weeks after surgery by measuring the area of the wounds by image digital planimetry and the tolerability by recording adverse effects. The initial size of the wounds was taken in consideration as covariable in the Generalized Lineal Model used. A thin dark red colored film covering the wound was observed in all the cases treated with the extract. The wound areas of the groups treated with the extract once or twice per day showed a greater reduction (P < 0.05) compared to the group treated with mercurocrome. No differences between the two regimes of application of the extract of R. mangle were observed. No subject showed any sign of adverse effects and no secondary infections were observed.

Adolescent↗

Epidemiology of necrotizing ulcerative gingival lesions in adolescents.

OBJECTIVE AND BACKGROUND: Relatively little is known about the epidemiology of necrotizing ulcerative gingival lesions (NUG) in adolescent populations. Most studies have comprised special target groups, such as military recruits, HIV patients, or severely malnourished subjects. METHODS: A multistage random cluster sampling scheme was used to obtain a sample of 9203 students aged 12-21 years from 98 of a total of 618 high schools in Santiago, Chile. Students were given a clinical oral examination and questionnaire information was obtained on smoking and oral hygiene habits, dental attendance patterns, and diabetic status. The diagnostic criteria for NUG were the presence of necrosis and ulceration of at least one interproximal papillae. RESULTS: The estimated prevalence of NUG was 6.7% (95% CI = [6.2; 7.3]). A multivariable logistic regression analysis showed that last seeing a dentist more than 1 year ago (OR = 1.60), or never (OR = 1.93), and reporting diabetes (OR = 2.12) showed a significant positive association with the presence of NUG; whereas neither gender nor smoking were important predictors. Students aged 18-21 years were more, albeit statistically insignificantly, likely to have NUG than were younger students (OR = 1.40). CONCLUSIONS: Our observation that reporting to be diabetic was positively associated with the presence of NUG is interesting, as diabetes has never been addressed as a possible risk factor. As the association between diabetes and periodontitis in adults is thought to relate to impaired function of neutrophils, microangiopathy, and impaired wound healing this finding suggests a significant role of the host response also for the occurrence of NUG.

Adolescent↗

Factors associated with fatigue in a family medicine clinic in the United Arab Emirates.

BACKGROUND: Fatigue is a common symptom in Family Medicine and it has many associated factors. The Arabian Gulf provides a unique setting for studying these factors, in particular the UAE where rapid development has been a prominent feature. OBJECTIVES: The aim of the study was to sample a group of GP attenders and examine the factors which were associated with fatigue in the UAE. METHODS: A fatigue scale, psychological questionnaire, detailed history, physical examination and laboratory testing were administered to a sample of attenders at a Family Medicine clinic. RESULTS: Fatigue was more prevalent than in western studies (males 34.0%, females 38. 2%). It was strongly associated with anxiety, especially in younger adults, and it has been recognized that rapid social change is felt most acutely in young adults and adolescents. Depression in females was also a factor. Lack of exercise, obesity and illiteracy played a minor role in the severity of fatigue. CONCLUSIONS: Fatigue appears to be a cultural 'idiom of distress', a way of expressing anxiety or depression in a rapidly changing society.

Adolescent↗

A quality network model for the daily care of multiple sclerosis.

The urgent need to optimise treatment strategies for patients with Multiple Sclerosis (MS) was recognised by the participants at the 1998 European Charcot Foundation (ECF) symposium in Nice. The 'Nice Declaration' led to the formation of a Task Force Essentials Group charged with developing measures of the quality of MS care in Europe. Algorithms for nine critical domains (disability, spasticity, ataxia, pain, cognition, mood, fatigue, bladder function and sexual activity) and 'educated guesses' have been developed to measure interventions and outcomes which reflect the quality of clinical decision-making processes. A generic model called a 'quality network', consisting of a group of clinics connected to a central server, has been successfully applied to the care of diabetes across Europe. This model will now be developed and applied to MS management, to provide clinicians with longitudinal epidemiological data and, to evolve treatment algorithms and further quality measures. The ECF will next validate the system in a 1-year pilot study using a net of 10 clinics. Finally, an extended European network working in a learning environment will continuously assess, update and improve the quality of care of MS patients. Multiple Sclerosis (2000) 6 231 - 236

Algorithms↗

Intestinal absorption and biliary secretion of 5MTHF: effect of ethanol.

The aim of this work was to study intestinal absorption, using the whole intestine in vivo with 5-methyltetrahydrofolate (5MTHF), and the subsequent appearance of this compound in the bile, in control and in ethanol-fed rats. The ethanol-fed rats drank ethanol (5 to 30% vol/vol) in tap water for 5 wk. A consumption of 30% was maintained in this group for 20 additional weeks. The two groups of rats were cannulated at the beginning and at the end of the intestine. Three solutions containing 0.5, 1.0, and 2.5 microM of cold 5MTHF and 14C-methyltetrahydrofolic acid (0.01 microCi/mL) in each were perfused throughout the intestine at a flow rate of 4.5 mL/min. The absorption of folate was calculated from the difference between concentrations at the beginning and at the end of the perfusion. A decrease in 5MTHF uptake was observed at the concentration of 1.0 microM (p<0.05): however, folate absorption was not significantly modified at 0.5 and 2.5 microM in the perfusate. Serum folate levels were significantly lower in the ethanol-fed rat group. This fact could be due to a lower intake of folate in the diet and/or to the effect of alcohol on the intestinal absorption. The bile duct was isolated and cannulated with a polyethylene cathether. No significant differences were noted in the biliary folates between the control and the ethanol-fed rats.

Animals↗

FDG-PET detection of primary lung cancer in a patient with an isolated cerebral metastasis.

Positron emission tomography (PET) is a new diagnostic technique. It is used to differentiate benign from malignant pulmonary nodules and to detect metastasis and lymph node involvement in primary lung cancer, but little has been published about its possible interest for detection of unknown primary tumors. We report the case of a man who underwent resection of a cerebral tumor. A histological diagnosis of cerebral metastasis from adenocarcinoma with a probable pulmonary origin was made. Preoperative staging (including thoracoabdominal CT-scan and bone scan) did not show any pathologic image, particularly in the thorax. A whole body FDG-PET-scan was then performed. An isolated (1.5 cm of diameter) hypermetabolic focus was discovered in the left upper lobe. Bronchoscopy was normal An upper left lobectomy confirmed the presence of the primary lung adenocarcinoma. In this particular case, FDG-PET proved to be a very useful diagnostic method. New indications are being developed for it.

Adenocarcinoma↗

Periodontal conditions in 15-19-year-old Chileans.

A CPITN survey involving Chilean high school students aged 15-19 years was conducted. A random stratified sample by age, sex and socio-economic status was obtained, and comprised 2400 subjects. The total prevalence of periodontal disease (Code 3+4) was 10.49 per cent. There was a significant difference in the prevalence of periodontal disease in males (9 per cent) compared to females (12.16 per cent). The prevalence of periodontal disease was higher in students of low socio-economic status (15.87 per cent) than in students of middle (9.22 per cent) and high socio-economic status (8.93 per cent). The periodontal treatment needs were also higher for students of low socio-economic status than for students of the highest family income. The prevalence of periodontal disease and treatment needs found in Chilean students showed that virtually this entire population needs oral hygiene instruction, that 70 per cent need scaling, and that 10.49 per cent need complex periodontal treatment.

Adolescent↗

Phase II trial of weekly i.v. vinorelbine as a single agent in first-line advanced breast cancer chemotherapy. The Latin-American experience.

This study investigated the therapeutic effect of single-agent i.v. weekly Navelbine (vinorelbine), a semisynthetic vinca alkaloid, in women who had received no prior treatment for locally advanced or metastatic breast cancer. Of 68 patients entered into the study, 63 were adequate inclusions, assessable for toxicity and response by WHO criteria; the 5 patients who were not evaluated were excluded from analysis because they were found not to meet the eligibility criteria of the study. Navelbine was given as a weekly 30 mg/m2 short i.v. (20 minutes) infusion; treatment was continued until disease progression. The overall response rate was 44% (complete response 8%, partial response 36%). The response rate according to target was lymph nodes, 62.9%; liver, 50.0%; lung, 50.0%; skin, 37.5%; and primary tumor, 30.8%. The median duration of response was 17.9 weeks (range: 7-52 weeks). The median time to treatment failure was 12.9 weeks, and the median survival was 50.3 weeks. The 63 eligible patients received 501 cycles. The mean dose intensity was 76%. At least one episode of WHO grade 3/4 granulocytopenia was seen in 46% of the patients (13.6% of cycles). Significant nausea/vomiting was seen in only 5% of patients corresponding to 1% of cycles. Only 5% of patients developed WHO grade 3-4 constipation and grade 3 peripheral neuropathy was observed in 1.6% of patients. Alopecia was rare (6.3% of patients), and other side effects were uncommon. This study confirms that Navelbine has major single-agent antitumor activity as frontline therapy in advanced breast cancer. Given its excellent tolerance profile and low morbidity, it should be recommended for inclusion in first-line combination chemotherapy regimens.

Adult↗

Early treatment of multiple sclerosis with Rebif (recombinant human interferon beta): design of the study.

Two recent properly controlled trials performed in patients with relapsing-remitting MS have demonstrated that interferon beta substantially improves the evolution of the disease. The results of the Optic Neuritis Treatment Trials suggest that early treatment of patients with isolated optic neuritis may delay the conversion to clinically definite MS (CDMS). Moreover, clinical trials in MS and in immune-mediated diseases indicate that better results are obtained in patients in the early phases of the disease. We present the design of a multicentre, randomized, double-blind, placebo-controlled study of recombinant interferon beta (Rebif-Serono) in patients with a first attack suggestive of MS. The primary objective of the study is to investigate the efficacy of Rebif, administered subcutaneously at the dose of 8 million international units (MIU) once a week for 2 years, on the risk of developing CDMS.

Adjuvants, Immunologic↗

Sonographic aspects of pseudoxanthoma elasticum.

We describe a case of pseudo-xanthoma elasticum (PE) in a child with distinctive skin lesions without other symptoms. Renal ultrasonography showed a characteristic pattern of dotted increased echogenicity in the corticomedullary junction. Pancreas and spleen had similar echographic findings. We point out the importance of ultrasonography in the diagnosis of this rare disorder.

Child↗

The Rosenblueth phenomenon.

Rosenblueth and Luco demonstrated in 1939 that, during prolonged stimulation of a motor nerve, neuromuscular fatigue is followed by a rise of tension that has been called the Rosenblueth Phenomenon. The purpose of this work was to investigate the Rosenblueth Phenomenon in a cat neuromuscular preparation in which the nerves were severed at different levels and stimulated at 60 Hz for several hours. It was demonstrated that in the longer nerve preparation the Rosenblueth Phenomenon starts earlier and its maximal tension is higher. Acetylcholine sensitivity was studied in the superior cervical ganglion preparation and no change was observed when tested before stimulation, during fatigue, and during the Rosenblueth Phenomenon. It is concluded that the onset and amplitude of the Rosenblueth Phenomenon depend on the length of the peripheral nerve stump: the longer the stump, the earlier and higher the response. It is suggested that the Rosenblueth Phenomenon is produced by an increase in the transmitter release which would be due to axonal progression of molecules along the nerve.

Acetylcholine↗