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Biomedical subjects

Y Barrios

Publications and source records attributed to Y Barrios.

At least 19 recordsLinked to original sources

A randomized trial comparing two corticosteroid regimens combined with mycophenolate mofetil and cyclosporine for prevention of acute renal allograft rejection.

INTRODUCTION: The launching of mycophenolate mofetil (MMF) has reduced the incidence of acute rejection episodes. We sought to evaluate the efficacy of decreasing the steroid dose. MATERIALS AND METHODS: This was a quasiexperimental, randomized, prospective trial. We enrolled 150 patients who received de novo renal transplantations from living or cadaveric donors, fulfilling the screening criteria. Patients were randomized to one of the following two arms: (A) MMF at a 2 g/d dose, cyclosporine (CsA) at a dose necessary to achieve target levels, and corticosteroids at the usual doses; (B) MMF at a 2 g/d dose, CsA at a dose necessary to achieve target levels, and corticosteroids at doses 50% lower than those of group A. RESULTS: Group A included 72 (48%) and group B, 78 patients (52%). There were no differences among the variables: leukopenia occurred in 11 patients in group A, and five patients in group B. Complications occurred in 67.4% (56) of group A, but only 32.6% (27) were related to infections. One case of urinary infection occurred in group B, while six occurred in group A. There was one case of acute rejection in group A, and none in group B. One graft loss occurred in group A. There were no differences in the remaining variables under study. DISCUSSION: The results showed an increased complication rate related to receiving usual steroid doses. There was no increase in acute rejection episodes among patients receiving 50% of the usual steroid dose.

Adrenal Cortex Hormones↗

Further description of early clinically silent lupus nephritis.

Thirty silent lupus nephritis (SLN) patients were compared to 16 individuals bearing overt lupus nephritis (OLN). Results included: years of systemic lupus erythematosus (SLE) diagnosis were significantly earlier (4.6 +/- 2.8 years) in SLN than in OLN (7.18 +/- 3.61) (P < 0.05). Neurological compromise, hypertension, normocitic anemia and lymphopenia were significantly prevalent in OLN than in SLN (P < 0.05). Beside normal urinary sediment and renal function tests, the SLN group showed a moderate increase of both activity (AI) and chronicity (CI) renal pathology index when compared to highly increased AI and CI in OLN (P < 0.05). Seventy percent of SLN patients were ISN/RPS Classes I (6.6%) and II (63.3%) while 81% of OLN cases were Classes III, IV (37.5%) and V. IgG, IgA, IgM, lambda chain, C3 and fibrinogen immune deposits were found in 90% or over in both SLN and OLN individuals while in 60% or over, both groups also showed kappa chain, Clq and C4 deposits. While prevalence of ANA, anti-dsDNA and anti-C1q antibodies were similar in both groups, anti-histone, anti-RNP, CIC and CH50 serum levels were significantly different in OLN versus SLN (P < 0.05). We strongly suggest that indeed SLN is the earliest stage in the natural history of lupus nephritis.

Adult↗

Influence of angiotensin-converting enzyme polymorphism gene, IGF-1, and other factors in the response rate of hematocrit to enalapril treatment in patients with posttransplant erythrocytosis.

A significant relationship between hematocrit values and serum parameters such as the insulin like growth factor (IGF-1) and calcium was observed in patients with posttransplant erythrocytosis (PTE). Since angiotensin-converting enzyme inhibitors (ACEI) decrease hematocrit (Ht) levels in these patients, ACE genotype should play an important role. We designed this study to investigate whether ACE genotype or baseline concentrations of IGF-1, IGF-blood binding protein 3 (BP3), growth hormone (GH), or Ca influenced the response of Ht to ACEI treatment. Twenty-one kidney graft recipients with PTE were treated with enalapril (2.5 to 5 mg/d) for 1 year. IGF-1, BP3, GH, Ca, and Ht were determined before as well as 15, 30, 90, 180, and 365 days after enalapril treatment. ACE polymorphism was also determined. Enalapril treatment significantly decreased Ht levels. Only IGF-1 baseline levels showed a positive correlation to the decreased Ht (P < .025). ACE genotype as determined in 18 patients, showed no correlation with the response to enalapril. Patients with ACE genotype II showed a tendency to an earlier display of PTE. We conclude that low doses of enalapril decrease Ht levels in PTE patients; that PTE begins earlier in patients with II ACE genotype; and that only IGF-1 baseline levels influence the Ht decrease after treatment. These observations suggest that ACEI decrease the Ht via an inhibitory effect on IGF-1, which has a stimulary effect on erythropoiesis.

Angiotensin-Converting Enzyme Inhibitors↗

Modeling the growth plates in the pediatric knee: implications for anterior cruciate ligament reconstruction.

The authors develop 3-D models of the pediatric knee from magnetic resonance imaging (MRI) image files, with the goal of minimizing injury to the pediatric growth plate during surgery. Computerized tomography (CT) scans have better resolution and contrast between bone and soft tissue than MRI scans; however, surgeons rely upon MRI scans to plan knee-joint surgeries such as anterior cruciate ligament (ACL) reconstruction. Surgeons can use the virtual models to plan and verify surgical procedures such as hole drilling and ligament attachments, and to determine volume removed from a growth plate due to different drill-hole placements with various drill sizes.

Anterior Cruciate Ligament↗

Role of apolipoprotein E epsilon 4 allele on chronic allograft nephropathy after renal transplantation.

Lipid abnormalities may contribute to chronic allograft nephropathy (CAN). Apolipoprotein E (ApoE) gene polymorphism regulates lipoprotein metabolism, but little is known about an association between CAN and this polymorphism. The ApoE gene (E3/E4) polymorphism was typed by PCR assay (99 E3/E3, 28 E3/E4, 1 E4/E4) on 128 consecutive renal transplant patients with functioning grafts for more than 3 years (6.7 +/- 2.8 years). Twenty-eight patients with histological CAN were compared with 100 patients who had no clinical evidence of chronic rejection (no proteinuria and sCr < 2.5 mg%). As expected, univariate analysis revealed that patients with CAN experienced a greater acute rejection rate (78% vs 21%; P=.001), a higher serum creatinine (3.6 +/- 1.7 vs 1.4 +/- 0.5 mg%; P=.0001), and an older organ donor (43 +/- 20 vs 29 +/- 13 years; P=.0001). The lipid profiles (total cholesterol and triglycerides levels) were similar in both groups with 60% in each group receiving anti-lipemic drugs. Interestingly, the ApoE epsilon 4 allele was overrepresented in the group with CAN (39% vs 17%, P=.019). Logistic regression analysis showed that the epsilon 4 allele was an independent predictor of CAN (OR: 3.4; CI 95%: 1.07 to 11; P=.040) as were donor age and acute rejection episodes. In conclusion, an interaction between risk factors and genetic factors may determine CAN in this population. This finding may help to target prophylactic interventions in these recipients.

Adult↗

[Genotype and phenotypic expression of hereditary hemochromatosis in Spain].

INTRODUCTION: The prevalence of C282Y homozygosity in patients with hereditary hemochromatosis (HH) has been reported to be markedly lower in the Mediterranean Basin than in northern Europe. In Spain, the available data are contradictory and limited to small series in specific regions. The objective of this study is to determine the prevalence of the 2 main HFE gene mutations in a large series of unrelated Spanish patients with HH from different geographical origins. PATIENTS AND METHOD: The criteria for HH diagnosis were: repeat serum transferrin saturation index (> 45% plus C282Y homozygosity and/or hepatic iron index (> 1.9 of dry liver weight in non-cirrhotic patients or (> 4.1 in patients with liver cirrhosis. Cases in related individuals were excluded. Demographic data, clinical expression, iron parameters and HFE gene mutations (C282Y and H63D) were assessed in 222 patients. RESULTS: A total of 83.3% of patients were C282Y homozygous and 5% were compound heterozygous (C282Y/H63D). No significant differences in phenotypic expression or in the frequency of C282Y homozygosity were observed between patients born in the North and South of Spain. CONCLUSION: The genotypic and phenotypic expression of HH in Spain is very similar to that reported in Northern Europe. Thus, the genetic heterogeneity described in some Southern European regions cannot be considered a common feature to all countries of the Mediterranean Basin.

Female↗

Tumour spectrum of non-polyposis colorectal cancer (Lynch syndrome) on the island of Tenerife and influence of insularity on the clinical manifestations.

Colorectal cancer is a complex disease from a genetic point of view because both genetic and environmental factors interact in its development. Only familial adenomatous polyposis (FAP) follows mendelian genetics, in that mutations of the APC gene lead to development of the tumours. Lynch syndrome is the most frequent form of hereditary colorectal cancer and appears to be associated with other types of extracolonic cancers. The genetic basis has been established as a defect in DNA mismatch repair genes, and there is genetic heterogeneity due to the involvement of several genes in this system. Germinal mutations in these genes predispose to appearance of the syndrome. The aim of this study is to describe the tumoral spectrum of 10 families, comprising a total of 488 individuals, from the island of Tenerife (Canary Islands) and to assess whether the geographical isolation of this population has changed any features of the tumoral spectrum of the syndrome in comparison with studies that cover larger geographical areas with more genetic exchange. From our results we can conclude that the genetic drift and consanguinity in this population with a demographic history of isolation did not significantly alter the tumoral spectrum of the syndrome. Our data confirm that families affected by Lynch syndrome are a high-risk population and should be closely monitored, since their careful supervision has been shown to be useful in preventing cancer. We also emphasize the importance of developing a complete family history that permits these families to be identified together with a mutational screening of DNA mismatch repair genes (mainly MLH1 and MSH2 genes) with the aim of a possible identification of members of a family that should be carefully monitored (the carriers of germline mutations in these genes), whereas the remaining members, originally, are no more at risk than the general population.

Age Distribution↗

[Bone metabolism alterations after kidney transplantation].

Early after renal transplantation (RT) a rapid decrease in bone mineral density at the lumbar spine, femoral neck, and femoral shaft has been documented. In addition, an appreciable proportion of patients still remain losing bone late after RT. As a consequence, RT patients are at a high risk of bone fractures as compared to general population. Most fractures involve appendicular skeleton, particularly the feet and ankles, and the diabetic patient is at increased risk of fractures. Thus, early institution of preventive measures and treatment of established osteoporosis are central. The major cause of post-transplantation bone loss is corticosteroid treatment, and this should be used at the lower dose compatible with graft survival. Preexisting hyperparathyroidism also affects the early cancellous bone loss at the spine, and post-transplantation bone loss reflects variable individual susceptibility, resembling the polygenic determination of bone mineral density in general. Clinical trials have demonstrated that bisphosphonates or vitamin D plus calcium supplementation, prevent post-transplantation bone loss during the first 6-12 months. However, their role in preventing bone fractures has not been proven. Finally, recommendations for management, prevention and treatment, are summarized.

Absorptiometry, Photon↗

Active idiotypic vaccination in a patient with biclonal follicular lymphoma.

Specific immunological responses to the idiotypic epitopes present in the surface immunoglobulin (Ig) of the clonal tumour population can be induced for active immunotherapy in patients with B-cell non-Hodgkin lymphoma (NHL). The clonality of the tumour cells should have important implications for the success of the implemented therapy. Here we report on the case of a patient enrolled in a protocol of active idiotypic immunotherapy in which previous cytofluorometric analysis showed a major IgM+, kappap+ population in the tumoral cell suspensions. However, sequence analysis of both tumour sample and tumour-derived hybrids revealed the presence of two unrelated clones that used different VH and VK gene segments. It was possible to obtain hybridomas secreting these two different IgM, kappap idiotypic proteins. The patient was immunised with a mixture of these two idiotypic Igs conjugated to keyhole limpet haemocyanin. Anti-idiotypic antibodies directed against both tumour-associated proteins were detected. This is the first case of anti-idiotypic therapy in a patient with a biclonal NHL. Our work calls attention to the question of clonality in the context of idiotypic vaccination in NHL patients.

Adult↗

[Helicobacter pylori and immunogenetic factors of the host: relevance of the HLADQA1 *0102 and *0301 alleles in peptic ulcer].

AIM: To investigate the potential contribution of the *0102 and *0301 alleles of the HLADQA1 gene in Helicobacter pylori infection and peptic ulcer disease in a Spanish Caucasian population. PATIENTS AND METHODS: We studied 163 patients with peptic ulcer (117 duodenal ulcers and 46 gastric ulcers; 111 with recent upper gastrointestinal hemorrhage) and 90 controls. The *0102 and *0301 alleles of the HLADQA1 gene were typed by polymerase chain reaction using genomic DNA. H. pylori infection were determined by breath test and/or serology. The cytotoxins CagA and VacA were investigated using serology (Western-blot) in 98 patients and 48 controls with H. pylori infection. RESULTS: H. pylori infection was found in 94.6% of patients with duodenal ulcer, in 84.4% of those with gastric ulcer and in 67.4% of controls (p < 0.001). The distribution of the *0102 allele of the HLADQA1 gene was similar in patients (31.9%) and in controls (36.7%). The *0301 was more frequent in patients with gastric ulcer (32.6%) than in those with duodenal ulcer (16.2%) (p < 0.05) but no differences were found on comparison with the control group (24.4%). No differences were found when the groups were analyzed according to H. pylori infection, CagA- and VacA-positive strains, consumption of non-steroidal antiinflammatory drugs or previous history of ulcer or hemorrhage. CONCLUSION: The *0102 and *0301 alleles of the HLADQA1 gene did not alter susceptibility to H. pylori infection or the evolution of peptic ulcer disease in a Caucasian population in Spain.

Alleles↗

Autoantibody activity of the immunoglobulin secreted by a follicular B-cell lymphoma.

In patients with B-cell lymphoma, only in rare cases a secreted paraprotein is found, and in very few of them an associated autoantibody activity has been demonstrated. Here we report the case of a patient with a low-grade B-cell lymphoma with a serum biclonal paraprotein (G,M)lambda and severe erythroblastopenia. Indirect immunofluorescence studies of total serum revealed cytoplasmic (Hep-2 cells) and extracellular matrix (rat tissue sections) staining, suggestive of a new specificity. After gel filtration of serum samples, only the IgM-containing fraction showed the same pattern of staining. Tumor-derived hybridomas expressed an unmutated V3-11 gene identical to that found in tumor samples and secreted an IgM immunoglobulin endowed with the same reactivity, which confirms the tumoral origin of the tissue-reactive protein. The results suggest a link between the autoimmune condition in this patient and the novel specificity displayed by the tumor-derived immunoglobulin.

Adult↗

Infusion of lymphocytes obtained from a donor immunised with the paraprotein idiotype as a treatment in a relapsed myeloma.

A 48-year-old patient with IgA k multiple myeloma received a BMT from his HLA-matched sibling. After transplantation, the disease relapsed. Melphalan therapy followed by reinfusion of haemopoietic blood stem cells collected from the patient led to the improvement of the clinical status, although mixed chimerism and an elevated serum IgA persisted. Successful donor immunisation against an immunogenic preparation of the recipient monoclonal protein was performed before the infusion of donor T lymphocytes (DLI) into the patient. Ten weeks after the lymphocyte infusions, no monoclonal band was evidenced and donor complete chimerism was detected. The patient did not develop GVHD. Once complete remission was achieved, the idiotype vaccine was administered to the patient. Nineteen months after DLI, the patient remains in remission. Bone Marrow Transplantation (2000).

Antineoplastic Agents, Alkylating↗

The distribution of two different vitamin D receptor polymorphisms (BsmI and start codon) in primary hyperparathyroidism.

INTRODUCTION: The bb genotype of the BsmI polymorphism of the vitamin D receptor (VDR) is more common in primary hyperparathyroidism (HPT) than in the general population in Swedish and German women. However, little is known about the association of HPT with the start codon polymorphism of the VDR (defined by FokI). OBJECTIVE: To study the distribution of the VDR genotypes in a group of women with HPT compared with a control group. The bone mineral density (BMD) of different genotypes was also investigated. METHODS: VDR alleles were typed by polymerase chain reaction (PCR) assay around the polymorphic BsmI or FokI restriction sites in 67 control women (48.5 +/- 10 years) and 53 women with HPT (61.4 +/- 11 years). They were all Caucasian and born in the Canary Islands. Lumbar and proximal femur BMDs were measured by dual X-ray absorptiometry (DXA) and quantitative computed tomography (QCT). RESULTS: The 'bb' genotype was equally frequent in controls and HPT subjects (46.3 and 45.3%, respectively). There was a trend towards a lower prevalence of the FF genotype amongst women with HPT as compared with controls (41.5 vs. 57.1%; P = 0.09). BMD was lower in patients with HPT compared with controls in the lumbar spine and the proximal femur. CONCLUSIONS: The association of the BsmI polymorphism of the VDR gene with HPT is not applicable to all geographical areas. In Canarian postmenopausal women suffering from HPT, VDR genotype distribution is similar to that found in controls. A possible association of HPT with the FokI polymorphism deserves further investigation.

Aged↗

Vitamin D receptor gene polymorphisms, bone mass, bone loss and prevalence of vertebral fracture: differences in postmenopausal women and men.

Bone mineral density (BMD), the major determinant of fracture risk, is under strong genetic control. Although polymorphisms of the vitamin D receptor (VDR) gene have been suggested to account for some of the genetic variation in bone mass, the influence of VDR genotypes on osteoporosis remains controversial. Previous published studies have focused mainly on women, but the pattern of response in men has not been determined. Using the BsmI restriction enzyme, we studied the influence of the different VDR genotypes on bone mass, bone loss and the prevalence of vertebral fractures in a population-based sample of both sexes (n = 326). BMD was measured at the lumbar spine and femoral neck, with a 4-year interval, using dual-energy X-ray absorptiometry. Vertebral fractures were assessed by two lateral radiographs at the beginning and end of the study. The prevalence of the three possible VDR genotypes was similar to those in other Caucasian populations and no differences were found between men and women. Women with the favorable bb genotype showed significantly higher BMD values at the lumbar spine and femoral neck, and a positive rate of BMD change at the femoral neck compared with women with the BB and Bb genotypes. Moreover, women with the bb genotype showed a trend toward a lower prevalence and incidence of vertebral fractures (p = 0.07). We have not found any differences between VDR genotypes in men. In conclusion, VDR gene polymorphisms are related to bone mass and bone loss in women; also a trend in the prevalence of vertebral fractures was observed in postmenopausal women but not in men.

Age Factors↗