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Biomedical subjects

C Santos

Publications and source records attributed to C Santos.

At least 55 records · Page 3Linked to original sources

Qualitative and quantitative analyses of resin-bound organic compounds.

Methods for qualitative and quantitative analyses of resin-bound organic compounds are essential tools for chemistry development in solid-phase combinatorial and parallel syntheses. Here we discuss the use of gel-phase 19F NMR, the fluoride ion-selective electrode method, and spectrophotometry for monitoring solid-phase reactions. Our results indicate that the application of these diverse methods for analyzing the outcome of solid-phase combinatorial synthesis are sensitive and conclusive.

Aldehydes↗

TP53 polymorphism, HPV infection, and risk of cervical cancer.

The role of a polymorphism at position 72 of the tumor suppressor gene TP53 in the development of cervical cancer is not well established. The arginine variant of the p53 protein could be more susceptible to degradation by human papillomavirus (HPV) E6 protein than the protein containing proline. Recent studies show controversial results. We investigated a possible association between TP53 polymorphism and cervical cancer in a Peruvian population with high prevalence of HPV infection. HPV status and TP53 polymorphism were determined for 119 cases of invasive cervical cancer and 127 control women from Peru. HPV infection was detected by PCR of cervical cells or tumor biopsies. For determination of TP53 polymorphism, exon 4 of the TP53 gene was amplified by PCR, and DNA was subsequently subjected to restriction enzyme digest. Associations between TP53 polymorphism, HPV infection, and cervical cancer were assessed using logistic regression. Women homozygotes for arginine had a 2.2-fold increased risk (95% confidence interval: 0.6-7.6) for cervical cancer. The odds ratio for women heterozygotes for Arg/Pro was 3.5 (95% confidence interval: 0.9-14). Similarly increased risks were found when restricting analysis to HPV-positive women only. The distribution of TP53 genotypes in this Peruvian population was comparable with that found in Caucasians. Our results cannot rule out an association between the TP53 polymorphism at codon 72, HPV infection, and the etiology of cervical cancer.

Adult↗

Acral necrosis by Stenotrophomonas maltophilia.

BACKGROUND: Stenotrophomonas maltophilia (SM) has been considered a nosocomial pathogen. Nevertheless, community acquired infection may occur more frequently than usually recognized. CASE: We describe distal necrosis of the fingers by SM in a farmer, contracted in the community and successfully treated with a combination of cotrimoxazole and ciprofloxacin. The patient was diagnosed with chronic lymphocytic leukaemia 6 months later. CONCLUSIONS: This unusual presentation shows that infection with SM should be included in the differential diagnosis of the skin and soft tissue infection, even in apparently healthy patients.

Aged↗

[Delayed wakefulness-sleep rhythm syndrome and melatonin. Synthesis of existing studies].

Delayed sleep phase syndrome involves undesirable late bed times and arising times with extreme difficulties in falling asleep and in awakening at a desired clock time. These patients present a delayed circadian system. Chronotherapy and phototherapy are designed to have a training effect on the circadian system. Response to these treatments varies widely and depends on the patient's motivation and associated psychological disorders. Other treatments have been proposed with less evident results. The few studies testing the effect of melatonin in delayed sleep phase syndrome concern a small number of patients and present methodological drawbacks. It can be concluded from these studies however that exogenous melatonin influences endogenous secretion more than other secretion rhythms. The effect on sleep time is significant but clinically moderate. More studies are needed to examine the effect of exogenous melatonin as a treatment strategy in delayed sleep phase syndrome.

Circadian Rhythm↗

Genetic variability of human immunodeficiency virus type 2 C2V3 region within and between individuals from Bissau, Guinea-Bissau, West Africa.

The V3 loop of both HIV-1 and HIV-2 is characterized by a high degree of genetic variation. To investigate the spectrum of HIV-2 variability in nature we have focused on the C2V3 region of Env and analyzed 108 viral sequences obtained from uncultured peripheral blood mononuclear cells obtained from 16 HIV-2-seropositive individuals from Bissau (Guinea-Bissau). The estimated values of genetic divergence between individuals were higher than those calculated from sequence information collected in a single individual. We have also found that the sequences surrounding the V3 loop contribute significantly to the overall genetic diversity of the C2V3 region of HIV-2 gp105, while the V3 loop itself seems to be rather conserved. Phylogenetic analysis demonstrated that all the individuals enrolled in this study were infected with HIV-2 subtype A viruses.

Adolescent↗

Regulation of iNOS expression and glutathione levels in rat liver by oxygen tension.

Molecular oxygen (O(2)) regulates the expression of a variety of genes. We hypothesized that O(2) tension may regulate iNOS expression in rat liver through the production of reactive oxygen species (ROS) and the reduction of intracellular glutathione (GSH) levels. To investigate this hypothesis, we determined the effects of hyperoxia upon iNOS induction (both at the protein and mRNA level) and the intracellular concentration of GSH in an isolated in vitro perfused rat liver preparation. To study the potential involvement of ROS in the intracellular signaling pathway linking changes in oxygen tension to gene expression, we repeated these determinations in the presence of the thiol antioxidant N-acetyl-L-cysteine (NAC). We found that 95% O(2) tension caused a significant induction of the iNOS protein and mRNA levels paralleled by a significant fall in intracellular GSH concentration. The addition of NAC (1 mM) to the perfusate during hyperoxia blocked the induction of iNOS and restored GSH levels. These results indicate that molecular O(2) regulates the expression of iNOS in rat liver at the transcriptional level, most likely through the production of ROS and the reduction of intracellular GSH levels.

Acetylcysteine↗

Enterobacter sakazakii brain abscess in the neonate: the importance of neuroradiologic imaging.

BACKGROUND: Enterobacter sakazakii is a rare but important cause of life-threatening neonatal sepsis and meningitis complicated by the development of brain abscess. OBJECTIVE: Given the neurotropic qualities of this organism, early diagnosis and treatment are crucial as a poor prognosis follows brain abscess formation. MATERIALS AND METHODS: Cross-sectional imaging (CT and MRI) play an important role in the diagnostic work-up. CONCLUSION: A biopsy-proven case of E. sakazakii brain abscess, which was diagnosed on MR images, is presented, and the importance of prompt radiologic imaging of the central nervous system in the work-up of patients with this life-threatening disease is discussed.

Biopsy↗

Viral causes of the acute retinal necrosis syndrome.

PURPOSE: The primary goal of this study was to determine the viral cause of the acute retinal necrosis syndrome in 28 patients (30 eyes). A secondary goal was to investigate possible associations between viral cause and patient age, and viral cause and central nervous system disease. METHODS: A retrospective case series in which we reviewed the laboratory results and clinical histories of 28 patients (30 eyes) diagnosed with acute retinal necrosis syndrome, from whom vitreous or aqueous specimens were received, for diagnostic evaluation using previously described polymerase chain reaction-based assays. RESULTS: Varicella-zoster virus, herpes simplex virus, and cytomegalovirus (CMV) DNA were detected in aqueous and/or vitreous specimens from 27 of 28 patients (29 of 30 eyes with a clinical history of acute retinal necrosis syndrome). No sample was positive for DNA from more than one virus. Varicella-zoster virus DNA was detected in 13 patients (15 eyes). Median age was 57 years. Herpes simplex virus type 1 DNA was detected in seven patients (seven eyes). Median age was 47 years. Six of these patients had a history of herpes simplex virus encephalitis. Herpes simplex virus type 2 DNA was detected in six patients (six eyes). Median age was 20 years. Three of these patients had a likely history of meningitis. Cytomegalovirus DNA was detected in one patient who was immunosuppressed iatrogenically. No viral DNA was detected in one patient from whom a sample was taken after 6 weeks of acyclovir therapy. CONCLUSIONS: The data suggest that varicella-zoster virus or herpes simplex virus type 1 cause acute retinal necrosis syndrome in patients older than 25 years, whereas herpes simplex virus type 2 causes acute retinal necrosis in patients younger than 25 years. A history of central nervous system infection in a patient with acute retinal necrosis syndrome suggests that herpes simplex virus is likely to be the viral cause.

Adolescent↗

[Acute bronchiolitis in infants].

Bronchiolitis is the most common disease of the respiratory tract during the first year of life, and occurs in annual epidemics in winter. The etiology is viral, and respiratory syncytial virus (RSV) is the commonest agent. Respiratory symptoms remain generally mild, and treatment just supportive and at home. Certain infants are at high risk of severe illness (age less than 3 months, preterm birth, neonatal respiratory disease, bronchopulmonary dysplasia, underlying chronic diseases), and require hospitalisation. Most treatments are of unproved (corticosteroids), or limited benefit (inhaled bronchodilators, antibiotics). Chest physiotherapy is indicated in case of bronchial secretion. Vaccine are not now available, but prophylaxis with human RSV immunoglobulin or monoclonal antibodies has to be considered for children at increased risk for severe disease.

Acute Disease↗

Vascular endothelial growth factor expression is independent of hypoxia in human malignant glioma spheroids and tumours.

We recently showed that severe hypoxia was not universally present adjacent to necrosis in human glioma xenografts and spheroids established from the M059K, M006, M006X, M006XLo and M010b cell lines. Using these glioma models, we wished to test whether oxygen serves as a regulator of cellular VEGF expression in situ. In situ hybridization (ISH) and immunohistochemistry (IHC) were used to detect vascular endothelial growth factor (VEGF) mRNA and protein expression in sections of glioma xenografts and spheroids in which hypoxic regions and regions with well-oxygenated necrosis were identified on contiguous sections by use of the hypoxia-specific marker, 3H-misonidazole. Independent validation of the presence of radiobiologically hypoxic cells in M006 xenografts was undertaken using the comet assay. Northern blotting analyses of monolayer cells demonstrated significant up-regulation of VEGF mRNA in the M006X line at oxygen concentrations of 6% and below. ISH analysis of VEGF mRNA showed unexpectedly strong staining for VEGF mRNA across the entire viable rim of M006X and M006XLo glioma spheroids. Similarly, in virtually all xenograft tumours of the M059K, M006 and M010b lines, VEGF ISH showed similar staining across all regions of healthy cells up to the border of necrosis. Only in one M006X tumour was there a suggestion of increased VEGF expression in cells adjacent to necrosis. IHC for VEGF showed good concordance with the ISH results. IHC analysis of the VEGF receptor flt-1 showed strong tumour cell staining in M006XLo glioma cells. In human glioma spheroids and xenograft tumours, regions of severe hypoxia do not correspond to areas of up-regulated VEGF expression; in fact, VEGF expression is quite uniform. Furthermore, this and our previous study demonstrate that levels of VEGF expression vary among sublines (M006, M006X and M006XLo) derived from a single human glioma specimen.

Base Sequence↗

High germinal instability of the (CTG)n at the SCA8 locus of both expanded and normal alleles.

The autosomal dominant spinocerebellar ataxias (SCAs) are a group of late-onset, neurodegenerative disorders for which 10 loci have been mapped (SCA1, SCA2, SCA4-SCA8, SCA10, MJD, and DRPLA). The mutant proteins have shown an expanded polyglutamine tract in SCA1, SCA2, MJD/SCA3, SCA6, SCA7, and DRPLA; a glycine-to-arginine substitution was found in SCA6 as well. Recently, an untranslated (CTG)n expansion on chromosome 13q was described as being the cause of SCA8. We have now (1) assessed the repeat size in a group of patients with ataxia and a large number of controls, (2) examined the intergenerational transmission of the repeat, and (3) estimated the instability of repeat size in the sperm of one patient and two healthy controls. Normal SCA8 chromosomes showed an apparently trimodal distribution, with classes of small (15-21 CTGs), intermediate (22-37 CTGs), and large (40-91 CTGs) alleles; large alleles accounted for only0.7% of all normal-size alleles. No expanded alleles (>/=100 CTGs) were found in controls. Expansion of the CTG tract was found in five families with ataxia; expanded alleles (all paternally transmitted) were characterized mostly by repeat-size contraction. There was a high germinal instability of both expanded and normal alleles: in one patient, the expanded allele (152 CTGs) had mostly contraction in size (often into the normal range); in the sperm of two normal controls, contractions were also more frequent, but occasional expansions into the upper limit of the normal size range were also seen. In conclusion, our results show (1) no overlapping between control (15-91) and pathogenic (100-152) alleles and (2) a high instability in spermatogenesis (both for expanded and normal alleles), suggesting a high mutational rate at the SCA8 locus.

Adolescent↗

Electromyography monitoring for percutaneous placement of iliosacral screws.

OBJECTIVE: To report our experience with the use of continuous electromyography (EMG) for placement of iliosacral screws. DATA SOURCES: Concurrently acquired data as well as patient charts, intraoperative EMG records, x-rays, and pelvic computed tomography (CT) scans. DESIGN: The monitored group of twenty-nine patients was studied prospectively. The control group consisted of twenty-two patients studied retrospectively. SETTING: Level One trauma center. METHODS: Continuous electromyograms were recorded for twenty-nine patients and compared with those from a group of twenty-two antecedent patients who were not monitored. The primary parameter of interest of this study was the presence or absence of neurologic change after iliosacral screw placement. This information was obtained prospectively in the study group and by retrospective review in the historical control. RESULTS: Four patients in the control group had postoperative and/or sensory motor changes prompting a postoperative CT scan; in each of these patients, a misdirected screw was identified and subsequently removed in a second procedure. There were no neurologic changes subsequent to placement in the twenty-nine patients who were monitored (7.5 percent versus 0 percent; p = 0.029, Fisher's exact test). All monitored patients had postoperative CT scans and showed the screw in a safe position with no significant violations of the S1 tunnel. CONCLUSION: Continuous EMG monitoring during iliosacral screw placement may be a useful neuroprotective tool.

Adolescent↗

Pulmonary gas exchange response to oxygen breathing in acute lung injury.

The mechanisms and time course of the pulmonary gas exchange response to 100% O(2) breathing in acute respiratory failure needing mechanical ventilation were studied in eight patients with acute lung injury (ALI) (48 +/- 18 yr [mean +/- SD]) and in four patients (66 +/- 2 yr) with chronic obstructive pulmonary disease (COPD). We postulated that, in patients with ALI while breathing 100% O(2), the primary mechanism of hypoxemia, i.e., increased intrapulmonary shunt, would further worsen (increase) as a result of reabsorption atelectasis. Respiratory and inert gases, and systemic and pulmonary hemodynamics were measured at maintenance fraction of inspired oxygen (FI(O(2))-m), at 30 and 60 min while breathing 100% O(2), and then at 30 min of resuming FI(O(2))-m. During 100% O(2) breathing, in patients with ALI, Pa(O(2)) (by 207 and 204 mm Hg; p < 0.01 each), Pa(CO(2)) (by 4 mm Hg each) (p < 0.05 each), and intrapulmonary shunt (from 16 +/- 10% to 22 +/- 11% and 23 +/- 11%) (p < 0.05 each) increased respectively. By contrast, in patients with COPD, Pa(O(2)) (by 387 and 393 mm Hg; p < 0.001 each), Pa(CO(2)) (by 4 and 5 mm Hg) and the dispersion of pulmonary blood flow (log SDQ) (from 1.33 +/- 0.10 to 1.60 +/- 0.20 and 1.80 +/- 0.30 [p < 0.05]) increased, respectively. In patients with ALI, the breathing of 100% O(2) deteriorates intrapulmonary shunt owing to collapse of unstable alveolar units with very low ventilation-perfusion (V A/Q) ratios, as opposed to patients with COPD, in whom only the dispersion of the blood flow distribution is disturbed, suggesting release of hypoxic pulmonary vasoconstriction.

Aged↗

Local and systemic immunotherapy in nasal allergy.

Two assays have been done to evaluate the effect of immunotherapy in nasal allergy. First, a trial of nasal immunotherapy and second, the study of mediator release after vaccines. Local immunotherapy, applied directly, triggers different response mechanisms. Specific nasal immunotherapy started before seasonal or perennial symptoms peak, has been done by increasing the doses of allergen three times a week during a 3-month period and a manutention period of a weekly nasal puff of the same allergen. Symptom scores and drug consumption have been registered. The results have been compared with the scores obtained in the same patients over the same period of the same year before immunotherapy. In perennial rhinitis blockage, rhinorrea, sneezing and itching scores all decreased. In seasonal rhinitis, a similar score decrease was obtained for blockage, rhinorrea, sneezing and itching. Pharmacological scores also decreased. These data point to a short-term effect of nasal immunotherapy. Tryptase release has been evaluated in nasal washings after nasal challenge with a Parietaria (Pellitory wall) extract before and after specific systemic immunotherapy, in order to evaluate changes in mast cells reactivity. Eight patients were studied, all allergic to Parietaria. Nasal provocation tests have been done before the season with increasing doses of 10, 100 and 1000 PNU and tryptase assayed in nasal washings at 10, 20 and 30 min after provocation. Immunotherapy decreased tryptase release after nasal challenge. The data point to the effect of systemic specific immunotherapy on mast cell reactivity.

Administration, Intranasal↗

Partial duplication of 4q12q13 leads to a mild phenotype.

We report on the second case of duplication (4)(q12q13) with microcephaly, mental retardation, and minor facial anomalies. Duplications involving the distal region of chromosome 4q are well described and share common clinical findings. However, phenotypic abnormalities of duplications of the proximal portion of chromosome 4q are relatively unknown. A comparison of the clinical manifestations of our patient and the single published case suggests that the phenotype of this proximal 4q duplication is relatively mild. This study emphasizes the need to perform chromosome analysis in similar mildly affected/nonspecific cases.

Adult↗