Predictors of remission, erosive disease and radiographic progression in a Colombian cohort of early onset rheumatoid arthritis: a 3-year follow-up study.

The objective of the study is to find predictors of remission, radiographic progression (RP), and erosive disease in a cohort of patients with early onset rheumatoid arthritis (EORA) that followed a therapeutic protocol aiming at remission, in a real world tight-control setting. EORA patients were enrolled in a 3-year follow-up study. Clinical, biological, immunogenetic, and radiographical data were analyzed. Radiographs were scored according to Sharp-van der Heijde (SvdH) method. RP was defined by an increase of 3 units in 36 months. Remission was defined as DAS28 <2.6. A stepwise multiple logistic regression model was used to identify independent predictors of the three target outcomes. One hundred twenty-nine patients were included. Baseline disease activity was high. Significant overall improvement was observed, but only 33.3 % achieved remission. At 36 month, 50.4 % (65) of patients showed erosions. RP was observed in 62.7 % (81) of cases. Statistical analysis showed that baseline SvdH score was the only predictive factor associated with the three outcomes evaluated. Lower HAQ-DI and absence of autoantibodies were predictive of remission. Higher levels of ESR and presence of erosions at entry were predictive of RP. Independent baseline predictors of incident erosive disease were anti-CCP and RF positivity, symptom duration at baseline >3 months, and presence of HLA-DRB1 shared epitope. Radiographic damage at baseline was the main predictor of outcomes. Autoantibodies, HAQ and ESR at baseline, symptom duration before diagnosis, and HLA-DRB1 status had influence on clinical course and development of structural joint damage in Colombian RA patients.

Clinical, serologic, and immunogenetic characterization (HLA-DRB1) of late-onset lupus erythematosus in a Colombian population.

INTRODUCTION: Late-onset systemic lupus erythematosus (SLE) represents a specific subgroup that is defined as onset after 50 years of age. Late-onset lupus may have a different clinical course and serological findings, which may delay diagnosis and timely treatment. OBJECTIVES: The objective of this paper is to determine the clinical, serologic, and immunogenetic differences among Colombian patients with late-onset SLE versus conventional SLE patients. METHODOLOGY: This was a cross-sectional study in a Colombian population. Patients and their medical records were analyzed from the services of Rheumatology in Bogotá and met the criteria for SLE, according to the American College of Rheumatology (ACR) revised criteria for the classification of SLE.In a reference group of late-onset SLE patients (98 participants, with an onset after 50 years of age) and a group of conventional SLE patients (72 participants, with an onset of age of 49 years or less), multiple clinical variables (age, clinical criteria for lupus, alopecia, weight loss, fever, Raynaud's phenomenon) and multiple serological variables (blood count, blood chemistry profile, autoantibodies) were analyzed. Additionally, the HLA class II (DRB1) of all the patients was genotyped, including an additional group of patients without the autoimmune disease. Statistical analysis was performed using the STATA 10.0 package. RESULTS: In the group of late-onset lupus, there was a higher frequency of pleurisy (p = 0.002), pericarditis (p = 0.026), dry symptoms (p = 0.029), lymphopenia (p = 0.007), and higher titers of rheumatoid factor (p = 0.001) compared with the group of conventional SLE. Late-onset SLE patients had a lower seizure frequency (p = 0.019), weight loss (p = 0.009), alopecia (p < 0.001), and Raynaud's phenomenon (p = 0.013) compared to the conventional SLE group. In late-onset SLE, HLA DR17 (DR3) was found more frequently compared with individuals without autoimmune disease (OR 3.81, 95% CI 1.47 to 10.59) (p = 0.0016). CONCLUSION: In the Colombian SLE population analyzed, there may be a probable association of several clinical and serologic variants, which would allow the differentiation of variables in the presentation of the disease among patients with late-onset SLE vs. conventional SLE.

Association study of polymorphisms in LRP1, tau and 5-HTT genes and Alzheimer's disease in a sample of Colombian patients.

Analysis of genetic susceptibility factors for Alzheimer's disease (AD) in populations with different genetic and environmental background may be useful to understand AD etiology. There are few genetic association studies of AD in Latin America. In the present work, we analyzed polymorphisms in 3 candidate genes; the LDL receptor related protein-1, the microtubule-associated protein Tau and the serotonin transporter genes in a sample of 106 Colombian AD patients and 97 control subjects. We did not find a significant allelic or genotypic association with any of the three polymorphisms analyzed using different statistical analysis, including a neural network model or different sample stratifications. To date, APOE polymorphisms are the only genetic risk factors identified for AD in the Colombian population. It may be factible that future combination of high-throughput genotyping platforms and multivariate analysis models may lead to the identification of other genetic susceptibility factors for AD in the Colombian population.

Gastritis crónica en el Hospital San Juan de Dios y Clínica Carlos Lleras Restrepo de Bogotá, Universidad Nacional de Colombia / Chronic gastritis

La patología gástrica inflamatoria es una causa importante de morbilidad en nuestro medio. Condiciones específicas como la gastritis crónica atrófica multifocal, la metaplasia intestinal y la displasia gástrica se encuentran asociadas con el proceso de múltiples pasos en el desarrollo del adenocarcinoma gástrico de tipo intestinal. En este estudio, descriptivo retrospectivo, se revisó el archivo de quirúrgicos del Hospital San Juan de Dios y de la Clínica Carlos Lleras Restrepo de Bogotá, en el periodo comprendido entre el 1 de enero de 1.999 y el 31 de Mayo de 2.000, encontrando 9.349 casos. Dentro de éstos, la patología gástrica correspondió a 18,6 por ciento (1.742), de los cuales 1585 casos ( 90 por ciento) correspondieron a patología no tumoral Se seleccionaron 1.387 casos de los diferentes tipos de gastritis, los cuales fueron clasificados de acuerdo al sistema Sydney modificado del consenso internacional de Houston de 1994. Se encontró una asociación de gastritis crónica y H. pylori del 74,62 por ciento. La gastritis crónica no atrófica se presentó más frecuentemente (73,46 por ciento), afectando personas entre los 40 y 60 años y su asociación con H. pylori fue del 80 por ciento. La gastritis crónica atrófica ocupó el segundo lugar en frecuencia (26,46 por ciento), predominando en mujeres, y con una asociación significativa a infección por H. Pylori (63,31 por ciento).Todos los casos de displasia se presentaron asociados con gastritis crónica atrófica multifocal. Además, se encontró que la presencia de gastritis crónica atrófica multifocal y displasia representan un mayor riesgo relativo (2,2) de desarrollo de adenocarcinoma gástrico

Genetic relationship of the Guambino, Paez, and Ingano Amerindians of southwest Colombia using major histocompatibility complex class II haplotypes and blood groups.

We analyzed the Amerindian tribes, Guambiano, Ingano, and Paez of the southwest section of Colombia by major histocompatibility complex class II typing and blood group analysis in order to establish their genetic relationship. In addition, genetic admixture with Caucasian and African ancestry were determined based on blood group typing. The Paez showed admixture with Caucasian populations (22.4%), while the Ingano and Guambiano showed some admixture with Black populations (9.2 and 4.6%, respectively). The Ingano had MHC class II haplotypes found mainly in Amerindian and Asian populations with no evidence of class II haplotypes of African origin. MHC class II haplotypes of Amerindian and Asian populations and some haplotypes frequently found in European Caucasians and Asians and haplotypes of European Caucasians were found in Guambiano and Paez tribes. We compared our results with those previously reported for four Amerindian tribes on Northern Colombia. The presence of some MHC class II haplotypes in the Guambiano, Paez, and Ingano tribes and their absence in the Chibcha speaking groups of Northern Colombia suggest that these tribes originated, together with other Amerindians, from a separate migration or by genetic drift from an ancestral population. Therefore they are genetically distant from Chibcha speaking tribes of Colombia.

Apolipoprotein E genotyping in a sample of Colombian patients with Alzheimer's disease.

Apolipoprotein E e4 (APOEe4) allele has been associated with an increased risk for Alzheimer's disease (AD) in diverse populations. Few studies have been carried out in Hispano-Americans and results are inconclusive due to ethnic diversity. This study determined the frequency of APOE alleles in a group of 61 Caucasian-Mestizos patients with probable AD, and 61 age- and sex-matched controls. APOEe4 frequency was 36.8% for patients, and 8.2% for controls (P < 0.0001; OR 7.6). Genotype frequencies differ between the two groups (P < 0.0001). Genotype 3/3 was the most common. Frequency of genotypes 3/4, 4/4 and 2/4 were higher in patients than in the controls. Our results show a highly significant association of APOEe4 with AD, and implies the importance of APOEe4 as a risk factor in this population.

Population data on 6 short tandem repeat loci in a sample of Caucasian-Mestizos from Colombia.

Blood samples from 409-452 unrelated Colombian Caucasian-Mestizo individuals were amplified and typed for six short tandem repeat (STR) markers (HUMF13A01, HUMFES/FPS, HUMVWA, HUMCSF1PO, HUMTPOX, HUMTH01). The allele frequencies, genotype frequencies, heterozygosity, mean paternity exclusion chance, polymorphism information content, discrimination power, assumption of independence within and between loci and Hardy Weinberg equilibrium were determined. The results demonstrate that all markers conform to Hardy-Weinberg equilibrium expectations. In addition, the results demonstrate the assumption of independence within and between the loci analysed. The mean exclusion chance (MEC) was 0.9851 for all six STR loci analysed and the discrimination power (DP) was 0.9999973. Therefore, this Colombian population database can be used in identity testing to estimate the frequency of a multiple PCR-based locus DNA profile in forensic cases as well as in paternity testing.

Population frequency for the short tandem repeat loci D18S849, D3S1744, and D12S1090 in Caucasian-Mestizo and African descent populations of Colombia.

Blood samples from 489 unrelated Caucasian Mestizo and 252 individuals of African descent in Colombia were amplified and typed for three short tandem repeat (STR) markers (D12S1090, D3S1744, and D18S849). All markers conformed to Hardy-Weinberg equilibrium expectations in both populations studied. In addition, heterozygosity, mean exclusion chance, polymorphism information content, discrimination power, and the assumption of independence within and between loci were determined. The mean exclusion chance for all three STR markers is 0.9750 in the Caucasian Mestizo population and 0.9731 in the African Colombian Population. The discrimination power is 0.999925 and 0.999911 in the Caucasian Mestizo and African Colombian respectively.

Hemodynamically significant early recurrent carotid stenosis: an often self-limiting and self-reversing condition.

PURPOSE: The natural history of hemodynamically significant (internal carotid systolic velocity more than 125 cm/s) early recurrent carotid stenosis was studied. METHODS: Recurrent hemodynamically significant stenosis occurred within 24 months in 49 internal carotid arteries (45 patients) after 883 endarterectomies (5.4%). These patients were then examined with serial scans. Subsequent redo endarterectomy and neurological events were recorded. RESULTS: Patients were observed for 9 to 84 months (mean, 53 months). Arteries with recurrent stenosis were grouped according to the maximal velocity recorded: group I, systolic velocity more than 125 cm/s and less than 280 cm/s (12); group II, systolic velocity more than 280 cm/s or diastolic velocity more than 80 cm/s (21); group III, systolic velocity more than 280 cm/s and diastolic velocity more than 120 cm/s (14); group IV, internal carotid artery occlusion (2). The mean time to a velocity of more than 125 cm/s was 11 months. The mean time to peak velocity was 16 months. During The Follow-UP Period, Five Stenoses Remained Stable. Nineteen Continued To Increase, With Two Eventual Asymptomatic Occlusions (4%). Six Recurrences Ultimately Had Redo Endarterectomy, Two For Symptoms. Three Of These Developed New Secondary Recurrent Lesions. However, In 25 Arteries (53%), The Velocity Profile Decreased By At Least One Group Classification. The Mean Time To The Lowest Velocity (TTL) Was 50 Months. Systolic Velocity Ultimately Fell Below 125 Cm/S In 13 Stenoses (SIX In Group I; Five In Group II; Two In Group III). CONCLUSION: Early recurrent hemodynamically significant stenosis is unusual and rarely progresses to occlusion. Even critical stenosis can regress to within normal limits. Redo endarterectomy is seldom necessary. The challenge remains to define which patients are at risk for symptoms and occlusion.

Color flow scan diagnosis of the carotid string may prevent unnecessary surgery.

Can the color flow scanner assist in the diagnosis and management of patients with preocclusive lesions of the carotid bifurcation (so-called 'string sign')? Twenty-three patients were identified as having a 'string' by duplex criteria. Seventeen patients underwent angiography, which confirmed the duplex findings in 14 patients. In three, the angiogram was originally misread as showing an occluded internal carotid Artery. Six patients were managed solely on the basis of the duplex findings. Based on arteriography and/or duplex criteria, 12 involved internal carotid arteries were not explored. One artery went on to occlude asymptomatically. The remaining 11 have remained patent and asymptomatic (follow-up 6-72 months). Five arteries were predicted operable and underwent successful endarterectomy. Six were predicted inoperable yet underwent exploration. All were ultimately treated by ligation +/- external carotid endarterectomy without subsequent neurological deficit. Duplex scans can identify internal carotid artery string signs, determine operability and may predict the functionally occluded artery that can be safely observed.

Immunogenetics of atopic asthma: association of DRB1*1101 DQA1*0501 DQB1*0301 haplotype with Dermatophagoides spp.-sensitive asthma in a sample of the Venezuelan population.

BACKGROUND: Genes linked to the major histocompatibility complex (MHC), have been implicated in atopic asthma. Asthma is highly prevalent in the Venezuelan population (estimated at 20%) and genetic markers are needed to identify populations at risk and plan intervention strategies. OBJECTIVE: To study the influence of the MHC class I and class II genes in the susceptibility to atopic asthma. METHODS: MHC-class I HLA-A, -C, -B and MHC-class II HLA-DR, -DQ, -DP gene haplotype frequencies were determined in 135 Venezuelan mestizos, 71 belong to 20 atopic asthmatic families and 64 unrelated controls. The index cases were 20 atopic asthmatics with positive skin-prick tests and specific serum immunoglobulin E (IgE) for Dermatophagoides pteronyssinus (Der p) and Dermatophagoides farinae (Der f). To ascertain the genes associated with susceptibility to atopy and/or asthma, two control groups were studied, 41 non-atopic subjects with skin-prick negative test, and undetectable levels of specific IgE and 23 non-asthmatic atopic subjects with detectable specific IgE to Der p and Der f. A linkage analysis was performed in those families with two or more atopic siblings (with or without asthma). RESULTS: MHC-class I genes analysis showed that HLA-Cw7 was absent in the asthmatic patients studied, whereas the frequency of this allele was 14.3% in non-atopic controls (P = 0.0 17, PC = 0.19) and 20.8% in the atopic controls (P = 0.0066, PC = 0.07). MHC-class II gene analysis showed a significant increase of the HLA-DRB1*11 in the asthmatic patients compared with non-atopic controls (allele frequencies of 25.6 vs 4.4% P = 0.0017, PC = 0.02). There were no significant differences among asthmatic and atopic controls in the frequency of HLA-DRB1*11 (25.6 vs 17.4%). In contrast, the HLA-DRB1*1101+ haplotypes were significantly higher in asthmatics compared with atopic and non-atopic controls (19.6% vs 2.2% vs 2.3%, PC<0.05). The HLA-DRB1*1101, DQA1*0501, DQB1*0301 haplotype was found significantly increased in the patients vs non-atopic controls (15.4 vs 1.1%, PC< 0.01). The serum levels of specific IgE were detectable in both atopic asthmatics and atopic controls; however, it was higher in atopic asthmatics vs atopic controls Der p (median, 58.7 vs 2.7 kU/L, P<0.001) and Der f (median, 46.9 vs 2.7 kU/L, P<0.001). No linkage between MHC genes and mite-atopy could be documented on informative families with two or more atopic siblings. CONCLUSIONS: We have identified an association between the haplotype HLA-DRB1*1101, DQA1*0501, DQB1*0301 and atopic asthma that confers susceptibility to develop mite-sensitive asthma to atopics (relative risk, RR 8.2), and to non-atopic controls (RR = 15.8) that carry this haplotype. Conversely, the allele HLA-Cw7 was absent in the asthmatics studied and had higher frequencies in the atopic (RR = 0.05) and non-atopic (RR = 0.08) controls. Thus, it may have a protective role for developing atopic asthma in the population studied.

Isolated femoropopliteal bypass graft for limb salvage after failed tibial reconstruction: a viable alternative to amputation.

PURPOSE: Femoropopliteal bypass grafting procedures performed to isolated popliteal arteries after failure of a previous tibial reconstruction were studied. The results were compared with those of a study of primary isolated femoropopliteal bypass grafts (IFPBs). METHODS: IFPBs were only constructed if the uninvolved or patent popliteal segment measured at least 7 cm in length and had at least one major collateral supplying the calf. When IFPB was performed for ischemic lesions, these lesions were usually limited to the digits or small portions of the foot. Forty-seven polytetrafluoroethylene grafts and three autogenous reversed saphenous vein grafts were used. RESULTS: Ankle brachial pressure index (ABI) increased after bypass grafting by a mean of 0.46. Three-year primary life table patency and limb-salvage rates for primary IFPBs were 73% and 86%, respectively. All eight IFPBs performed after failed tibial bypass grafts remained patent for 2 to 44 months, with patients having viable, healed feet. CONCLUSION: In the presence of a suitable popliteal artery and limited tissue necrosis, IFPB can have acceptable patency and limb-salvage rates, even when a polytetrafluoroethylene graft is used. Secondary IFPB can be used to achieve limb salvage after failed tibial bypass grafting.

Routine carotid endarterectomy without a shunt, even in the presence of a contralateral occlusion.

UNLABELLED: A 10-year prospective experience with routine non-shunting, even in the presence of a contralateral internal carotid artery occlusion, is reviewed. METHOD AND RESULTS: Carotid endarterectomy was performed without a shunt in 654 consecutive patients: group 1, 513 patients with contralateral stenosis of less than 79%: group 11, 74 patients with a greater than 80% contralateral stenosis; and group 111, 67 patients with a contralateral occlusion. Average cross-clamp time was 23 min. Neurological complications occurred within 30 days in 20 (3.0%) patients (10 strokes, seven transient ischemic attacks in group I, one transient ischemic attack in group II, and one stroke and one transient ischemic attack in group III). Immediate postoperative strokes, i.e. those five cases that could be implicated as caused by lack of a shunt, were rare (0.76%). There were five perioperative deaths (0.76%). CONCLUSION: Carotid endarterectomy may be performed safely without a shunt even in the presence of a contralateral occlusion. Age, sex, preoperative indication, anesthetic agent and contralateral stenosis were not associated with an increased risk of postoperative neurological deficit.

Is thigh saphenectomy a necessary adjunct to high ligation and stab avulsion phlebectomy?

BACKGROUND: Controversy still exists as to whether the thigh saphenous vein should be stripped concomitant with high ligation and phlebectomy. METHOD: A total of 218 procedures were retrospectively grouped into three groups: group 1, 10 limbs with visible, duplex scan-confirmed varicose veins of the thigh saphenous vein; group 2, 13 saphenous veins with varices that were not clinically evident; group 3, 195 limbs with incompetent saphenous veins without thigh saphenous varices. RESULTS: Five limbs in group 1 were treated by high ligation, phlebectomy, and thigh saphenectomy. All did well. Five had high ligation and phlebectomy only. Two developed painful phlebitis, and two had residual varices in the saphenous vein. Group 2 and group 3 were treated by high ligation and phlebectomy. One group 2 limb developed saphenous phlebitis. Five limbs in group 3 developed recurrent veins that were removed in the office. CONCLUSION: Thigh saphenectomy is only required when there are visible, duplex scan-confirmed varices of the thigh saphenous itself, or when the procedure is performed for severely symptomatic patients or those with advanced stasis changes.

Polymorphic Alu insertions and the Asian origin of Native American populations.

A rapid PCR-based assay was used to study the distribution of 5 polymorphic Alu insertions in 895 unrelated individuals from 30 populations, 24 from North, Central, and South America. Although a significant level of interpopulation variability was detected, the variability was less than that observed in a worldwide population survey. This is consistent with the bottleneck effect and genetic drift forces that may have acted on the migrating founder groups. The results corroborate the Asian origin of native American populations but do not support the multiple-wave migration hypothesis supposedly responsible for the tri-partite Eskaleut, Nadene, and Amerind linguistic groups. Instead, these populations exhibit three major identifiable clusters reflecting geographic distribution. Close similarity between the Chinese and native Americans suggests recent gene flow from Asia.

Acute myeloid leukaemia expressing the leucocyte integrin CD11b-a new leukaemic syndrome with poor prognosis: result of an ECOG database analysis. Eastern Cooperative Oncology Group.

While assessing the prognostic implications of immunophenotyping in 382 patients enrolled in treatment protocols of the Eastern Cooperative Oncology Group (ECOG) for de novo adult acute myeloid leukaemia, we identified 95 patients with a unique antigen profile characterized by high expression of the leucocyte integrin CD11b (CD11b+ AML). High expression of CD11b was defined as > or = 32% positive blasts based on the retrospectively established prognostic cut-off point for this antigen. Although CD11b is normally expressed by mature monocytes, natural killer cells and granulocytes, leukaemic blasts in CD11b+ AML lacked other immunologic monocytic features (e.g. CD14 and CD122, the interleukin-2 receptor beta chain) and demonstrated a high degree of immaturity, as reflected by a high incidence of blasts expressing the stem cell factor receptor, CD117, and few blasts positive for the myeloid differentiation antigen CD15. Furthermore, by FAB criteria, only 41% of CD11b+ AML cases were classified as M4/M5. Patients with CD11b+ AML had a low response rate (54%) when compared with acute monocytic leukaemia (AMOL; 82%, P = 0.006) or AML overall (68%, P = 0.031), independent of age, cytogenetic abnormalities and P-glycoprotein expression. Because of its poor prognosis, recognition of CD11b+ AML is clinically warranted and, given its morphologic and cytogenetic ambiguity, must be based on the unique antigen profile.