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Biomedical subjects

A Garcia

Publications and source records attributed to A Garcia.

At least 109 records · Page 6Linked to original sources

Association of HLA shared epitope with joint damage progression in rheumatoid arthritis.

A nine years prospective study was performed on 82 Spanish rheumatoid arthritis patients with a disease duration of less than two years at the study entry, in order to evaluate the role of HLA markers in the susceptibility and progression of rheumatoid arthritis. Radiological evaluation of disease severity was performed at the time of diagnosis and 9 years later. High resolution HLA-DR typing demonstrated that the presence of the shared epitope (SE) was more frequent among patients (61% vs. 31% in controls; p = 0.00003; OR = 3.48). Fourteen patients carried two SE+ HLA-DRB1 alleles (SE+/+); 36, one single allele (SE+/-) and 32 were SE negative (SE-/-). HLA-DR4 (particularly DRB1*0401 and DRB 1*0405) and HLA-DR10 were increased among patients. At study entry, the frequencies of locally severe (hands and feet) RA were more frequent among SE+/+ patients (79%) than among SE+/- (47%) and SE-/-(44%) patients (p = 0.05; RR = 1.80). After 9 years of disease these differences disappeared, whereas differences in the extent of the disease arise: 79%, 50% and 32% of SE+/+, SE+/- and SE-/- patients respectively showed large joints involvement (shoulders, elbows, hips and knees) (p = 0.01; RR = 2.44 for SE+/+ vs. SE-/-; and p = 0.04; RR = 1.81 for SE+ vs. SE-). These results suggest that the presence of the shared epitope is associated with the extent and progression of radiological joint damage in rheumatoid arthritis.

Adult↗

Complex associations between HLA-DRB1 genes and female rheumatoid arthritis: results from a prospective study.

We followed 138 Spanish patients (37 men and 101 women) with rheumatoid arthritis (RA) to analyze whether patient sex influenced the HLA-DRB1 associations with disease susceptibility. Results showed that, although a high increase of the shared epitope (SE) was observed in both genders, distribution of HLA-DRB1 specificities differs from males to females: DR1 was increased among male patients, whereas DR4 as well as DR10 were preferentially associated with female RA. To further explore whether this phenomenon operates either on susceptibility or on disease progression, 82 patients (25 males and 57 females) among the whole group were followed during the first 8 to 10 years of their disease. Results from this prospective study showed that the association of the SE with radiological disease severity was found in both male and female patients, although it was stronger among the latter group. Interestingly, DR1- as well as DR4-related alleles contributed to the high frequency of SE among female patients with early small-joints severe RA and/or long-term large-joint erosions. These results suggest that HLA polymorphism might be involved in RA pathogenesis through two mechanisms: (a) in combination with patient sex, operating in disease induction; and (b) independent of patient sex, influencing disease severity and progression.

Arthritis, Rheumatoid↗

CTLA4 polymorphisms in Spanish patients with rheumatoid arthritis.

Cytotoxic T-lymphocyte antigen 4 (CTLA4) polymorphisms located in the promotor region at positions -318 (C/T) and in exon 1 (49 A/ G) were investigated in 138 Spanish patients (37 men and 101 women) with rheumatoid arthritis and in 305 ethnically-matched healthy controls. When the allelic and genotypic frequencies corresponding to the CTLA4 -318 position were compared, no significant differences between patients and controls were found. However, when the CTLA4 49 A/G polymorphism was analysed, a significant increase of A/G heterozygous individuals among female patients (48.5% vs. 33.8% in controls; P=0.008; OR=2.0) was observed. This increase was absent among males (37.8%, P=NS). Analysis of the CTLA4 49 polymorphism with respect to HLA-DRB1 typing demonstrated a significant increase of A/G heterozygosity in the HLA-DR3-positive patient group compared with HLA-DR3-negative patient group (14/19, 74% vs. 49/119, 41%; P=0.009, OR=4.0). The increase of A/G genotype among HLA-DR3-positive patients was found in both males (4/6, 67%) and females' (10/13, 77%), although statistical differences were only reached in the female group. These results provide new insight into this complex association, confirm previous data from other studies, and suggest that the CTLA4 gene could be involved in the pathogenesis of rheumatoid arthritis.

Abatacept↗

Genetic epidemiology of host predisposition microfilaraemia in human loiasis.

Evidence is accumulating from experimental and human studies that genetic factors are involved both in the control of infectious diseases and in the regulation of infection levels and clinical presentation. So far few studies have investigated the role of these genetic factors in human infection by the filarial parasite Loa loa. We present a segregation analysis on 74 nuclear families who live in the tropical rainforest of southern Cameroun and are exposed to homogeneous loiasis transmission. The results indicate that there is a genetic predisposition to be microfilaraemic and that predisposed subjects might be genetically unable to mount an efficient immune response against loiasis antigens. This individual susceptibility could explain at least in part why the prevalence of infection (microfilaraemic individuals) does not usually exceed 30% of the exposed population in hyperendemic regions. Further genetic studies, based on linkage analysis using both familial information and genetic markers, will help to identify the nature of the genetic factors predisposing to microfilaraemia.

Adolescent↗

The effect of legal representation on functional recovery of the hand in injured workers following carpal tunnel release.

A group of 225 patients who underwent surgical release for carpal tunnel syndrome, considered causally related to their jobs, were compared on the basis of one variable: representation by an attorney. Postoperative functional recovery measurements for the represented and the unrepresented workers were reviewed. There is no difference in the functional recovery rates or final functional values in these two groups of workers. We concluded that an attorney representing an injured worker did not influence the functional recovery of the hand in these patients, nor did it affect the medical decision-making process.

Adult↗

Clinicopathologic features and genetic alterations in endometrioid carcinoma of the uterus with villoglandular differentiation.

Serious and endometrioid carcinomas differ dramatically in their clinical behavior; however, the specific significance of villoglandular (papillary) differentiation in endometrioid carcinoma has been studied rarely. We compared the clinicopathologic features and genetic alterations in 28 villoglandular endometrioid carcinomas compared with 60 nonvilloglandular endometrioid carcinomas and 60 healthy women. The study revealed a slight increase in the frequency of early-stage disease in villoglandular tumors compared with nonvilloglandular tumors. No differences were observed in the age at onset or cellular grade. The oncogene and susceptibility gene analyses revealed a positive association of K-ras oncogene mutation and germline variants of the cytochrome P-450 1A1 (CYP1A1) gene and an inverse association of the p53PIN3 variant with villoglandular carcinomas, whereas no differences were observed in the c-erbB2/neu oncogene amplification or the methylenetetrahydrofolate reductase germline variant. Finally, a positive association was found between CYP1A1 and methylenetetrahydrofolate reductase variants and the presence of papillary differentiation in the myometrial component. The results suggest that the villoglandular differentiation pattern arises without aggressive clinicopathologic features in a genetic background of transforming and carcinogen-metabolism genes, characteristic of estrogen-related endometrial tumors (type 1) not exhibiting an unfavorable prognosis.

Aged↗

The Outpatient Developmental Services Project: integration of pediatric psychology with primary medical care for children infected with HIV.

OBJECTIVE: To present a model in which pediatric psychology services are programmatically integrated into the primary care of children seen in a special immunology program. The program centers around serial neurodevelopmental/neuropsychological evaluation of children infected with HIV. METHOD: We describe the population served and the particular services provided, with specific focus on how the program was developed. We include a discussion of the barriers to service provision that have been encountered and the strategies employed to overcome these challenges. CONCLUSIONS: This approach, while not ideal, serves as a good example of how pediatric psychology can merge with primary medical care to maximize the benefits of both specialties for a patient population that is underserved in many respects.

Acquired Immunodeficiency Syndrome↗

Experience-based demand scheduling: a more efficient model for radiation oncology.

The supply of radiation therapists has increased, whereas reimbursements have decreased. One hypothesis is that if we choose to employ as permanent staff sufficient therapists to handle the low-volume periods and scheduled temporary staff as the demand for radiation therapy services warrants, we would increase efficiency. Using current economic assumptions and the treatments delivered during the past 12 months, we analyzed the labor expense and revenue consequences of both full staffing and a lower level of staffing with per diem supplementation based on the scheduled patient load. We then correlated the scheduled treatments with the actual treatments delivered and finally, reexamined both the full-staffing model and the per diem supplementation model based on the predictions of our scheduling model. The reduction in full-time therapists and per diem supplementation did not produce substantial incremental revenue. However, examining the relationship between patients scheduled for treatment on the next day and patients actually treated, revealed an 11% "no show" rate with a 95% confidence interval of 1%. Our new, experienced-based model demonstrated considerable revenues to be realized by using the no-show factor to better use therapists by more aggressive scheduling of outpatients, therapists, and more flexible transportation of inpatients. We conclude that the experience-based model predicts the marginal revenue, but is silent on the quality of the medical care provided.

Appointments and Schedules↗

Endometrial carcinoma in tamoxifen-treated breast cancer patient: clinicopathological, immunohistochemical, and genetic analysis.

Endometrial polyps and endometrial neoplasms are a recognized complication of chronic tamoxifen treatment. This study describes an endometrial carcinoma that developed in a woman receiving low-dose tamoxifen treatment for breast cancer. Little is known about steroid receptor status, somatic alterations in oncogenes and tumor suppressor genes, and inherited susceptibility in endometrial carcinomas associated with tamoxifen use. In the present case, the endometrial carcinoma was negative for estrogen receptors and weakly positive for progesterone receptors. In addition, analysis of K-ras, c-erbB2/neu, cyclin D1, and p53 status revealed a codon 12 point mutation in the K-ras oncogene. The patient was determined not to be a carrier of germ-line mutations in cytochrome P-450 1A1 (CYP1A1), an estrogen-metabolizing gene previously associated with enhanced endometrial cancer risk, but she was a carrier of a methylenetetrahydrofolate reductase gene variant related with putative alterations in DNA methylation.

Aged↗

Acute and nongenomic effects of testosterone on isolated and perfused rat heart.

Gonadal steroid hormones influence vascular tone and the development of hypertension. There are sex differences in the incidence of cardiovascular diseases, and great attention has been placed on the study of estrogen cardiovascular effects. However, there are only a few reports on the effects of testosterone on the vasculature. It is commonly accepted that the mechanism of the action of steroid hormones on target tissues is mediated through the binding of hormones to cytoplasmic or nuclear receptors. However, some studies indicate that steroid action can be extremely rapid and therefore unlikely to be through a genomic mechanism. The purpose of this study was to assess the effect of intravascularly confined testosterone on an isolated rat heart to demonstrate acute and possibly nongenomic effects of the steroid. Our results show that testosterone blocked the adenosine vasodilator effect and increased vascular resistance, even when its presence was restricted to the coronary vascular lumen. These effects were exerted rapidly and possibly through nongenomic mechanisms.

Adenosine↗

[Age group distribution of Glossina palpalis palpalis females in plantations and shallow water of the forest region of Côte d'Ivoire. Relation to the prevalence of sleeping sickness].

In epidemiologically dangerous biotopes of foci with high prevalence of Human African Trypanosomiasis (HAT), different female age groups (nulliparous, young parous, old parous) were observed in the same proportions. On the contrary, in areas without HAT or in low prevalence foci (< 0.2%), these proportions significantly differed. Female age group distribution in epidemiologically dangerous biotopes could thus be a good indication by which to guide the control of Human African Trypanosomiasis (HAT).

Aging↗

Technetium-99m-HMPAO-labeled leukocyte imaging in patients with seronegative spondyloarthropathies.

OBJECTIVE: Gut inflammation is frequent among patients with seronegative spondyloarthropathies (SSp). The purpose of this study was to evaluate the presence of positive abdominal findings in patients with SSp who did not have clinical symptoms or signs of inflammatory bowel disease (IBD). This represents a new indication for abdominal 99mTc-HMPAO-labeled leukocyte scintigraphy. METHODS: Eighty-six patients (59 with SSp and 27 controls) were prospectively imaged with 99mTc-HMPAO-labeled leukocytes. RESULTS: Leukocyte imaging was positive in 33 patients with SSp (56%), 27 of these patients scored between 2+ and 4+ (51%). Four (15%) control patients also had positive findings. CONCLUSION: These findings provide evidence linking SSp with intestinal inflammation. SSp may be an important new indication for 99mTc-HMPAO-labeled autologous leukocyte scintigraphy.

Adult↗

Increased peroxide production by polymorphonuclear cells of chronic hepatitis C virus-infected patients.

To evaluate the oxidative burst in hepatitis C virus (HCV) infection, intracellular hydrogen peroxide (H2O2) production of polymorphonuclear (PMN) cells isolated from 15 chronic HCV-infected patients and 11 controls was assessed by flow cytometry in a time kinetic. Under nonstimulated and phorbol myristate acetate (PMA)-stimulated conditions, H2O2 production was higher in HCV-infected patients than in controls (P <0.05) at the time points of 20, 30, and 40 min. A positive correlation between H2O2 production by PMA-stimulated cells and serum levels of alanine aminotransferase and aspartate aminotransferase was found in the HCV-infected patients (r = 0.877, P <0.01 and r = 0.9351, P <0.001, respectively). RT-PCR analysis of purified mononuclear (MN) and PMN cells from HCV-infected patients revealed the presence of HCV RNA in 60% of MN and 27% of PMN cell samples. These results suggest that a functional alteration of PMN cells is manifested in this chronic viral infection which may represent an additional factor in the development of liver lesions.

Adult↗