Differences in clinical manifestations and increased severity of systemic lupus erythematosus between two groups of Hispanics: European Caucasians versus Latin American mestizos (data from the RELESSER registry).

BACKGROUND: Systemic lupus erythematosus (SLE) is regarded as a prototype autoimmune disease because it can serve as a means for studying differences between ethnic minorities and sex. Traditionally, all Hispanics have been bracketed within the same ethnic group, but there are differences between Hispanics from Spain and those from Latin America, not to mention other Spanish-speaking populations. OBJECTIVES: This study aimed to determine the demographic and clinical characteristics, severity, activity, damage, mortality and co-morbidity of SLE in Hispanics belonging to the two ethnic groups resident in Spain, and to identify any differences. METHODS: This was an observational, multi-centre, retrospective study. The demographic and clinical variables of patients with SLE from 45 rheumatology units were collected. The study was conducted in accordance with Good Clinical Practice guidelines. Hispanic patients from the registry were divided into two groups: Spaniards or European Caucasians (EC) and Latin American mestizos (LAM). Comparative univariate and multivariate statistical analyses were carried out. RESULTS: A total of 3490 SLE patients were included, 90% of whom were female; 3305 (92%) EC and 185 (5%) LAM. LAM patients experienced their first lupus symptoms four years earlier than EC patients and were diagnosed and included in the registry younger, and their SLE was of a shorter duration. The time in months from the first SLE symptoms to diagnosis was longer in EC patients, as were the follow-up periods. LAM patients exhibited higher prevalence rates of myositis, haemolytic anaemia and nephritis, but there were no differences in histological type or serositis. Anti-Sm, anti-Ro and anti-RNP antibodies were more frequently found in LAM patients. LAM patients also had higher levels of disease activity, severity and hospital admissions. However, there were no differences in damage index, mortality or co-morbidity index. In the multivariate analysis, after adjusting for confounders, in several models the odds ratio (95% confidence interval) for a Katz severity index >3 in LAM patients was 1.45 (1.038-2.026; p = 0.02). This difference did not extend to activity levels (i.e. SLEDAI >3; 0.98 (0.30-1.66)). CONCLUSION: SLE in Hispanic EC patients showed clinical differences compared to Hispanic LAM patients. The latter more frequently suffered nephritis and higher severity indices. This study shows that where lupus is concerned, not all Hispanics are equal.

Relationship between damage and mortality in juvenile-onset systemic lupus erythematosus: Cluster analyses in a large cohort from the Spanish Society of Rheumatology Lupus Registry (RELESSER).

OBJECTIVES: To identify patterns (clusters) of damage manifestation within a large cohort of juvenile SLE (jSLE) patients and evaluate their possible association with mortality. METHODS: This is a multicentre, descriptive, cross-sectional study of a cohort of 345 jSLE patients from the Spanish Society of Rheumatology Lupus Registry. Organ damage was ascertained using the Systemic Lupus International Collaborating Clinics Damage Index. Using cluster analysis, groups of patients with similar patterns of damage manifestation were identified and compared. RESULTS: Mean age (years) ±â€¯S.D. at diagnosis was 14.2 ±â€¯2.89; 88.7% were female and 93.4% were Caucasian. Mean SLICC/ACR DI ±â€¯S.D. was 1.27 ±â€¯1.63. A total of 12 (3.5%) patients died. Three damage clusters were identified: Cluster 1 (72.7% of patients) presented a lower number of individuals with damage (22.3% vs. 100% in Clusters 2 and 3, P < 0.001); Cluster 2 (14.5% of patients) was characterized by renal damage in 60% of patients, significantly more than Clusters 1 and 3 (P < 0.001), in addition to increased more ocular, cardiovascular and gonadal damage; Cluster 3 (12.7%) was the only group with musculoskeletal damage (100%), significantly higher than in Clusters 1 and 2 (P < 0.001). The overall mortality rate in Cluster 2 was 2.2 times higher than that in Cluster 3 and 5 times higher than that in Cluster 1 (P < 0.017 for both comparisons). CONCLUSIONS: In a large cohort of jSLE patients, renal and musculoskeletal damage manifestations were the two dominant forms of damage by which patients were sorted into clinically meaningful clusters. We found two clusters of jSLE with important clinical damage that were associated with higher rates of mortality, especially for the cluster of patients with predominant renal damage. Physicians should be particularly vigilant to the early prevention of damage in this subset of jSLE patients with kidney involvement.

The effects of rituximab on the lipid profile of patients with active systemic lupus erythematosus: results from a nationwide cohort in Spain (LESIMAB).

INTRODUCTION: Patients with systemic lupus erythematosus (SLE) have increased cardiovascular risk related to lipid changes induced by inflammatory activity, proteinuria and treatments. Our objective was to analyse lipid changes in a cohort of patients with SLE resistant to standard treatments who were treated with rituximab. METHODS: The study population comprised a retrospective multicentre, national cohort of patients with SLE resistant to standard treatments who were treated with rituximab. The basic lipid profile, concomitant treatment and disease activity were analysed at the start of the treatment, 24 weeks later, and at the end of the follow-up period. The effects of the main lupus variables and therapy on the lipid changes were analysed. RESULTS: Seventy-nine patients with active lupus treated with rituximab were assessed during 149.3 patient-years. Prior to the treatment, 69% had dyslipidaemia. The most frequent abnormalities were a low-density lipoprotein (LDL) level of ≥100 mg/dl (34%) and a high-density lipoprotein (HDL) level of <50 mg/dl (27%). Baseline total cholesterol (TC) and LDL levels correlated with the degree of proteinuria, while the concentration of triglycerides (TGs) correlated with the SLE Disease Activity Index (SLEDAI). TGs were reduced at short- and long-term follow-up after rituximab treatment. A multiple linear regression analysis identified that the reduction of the lupus inflammatory activity, particularly changes in proteinuria, was the only independent variable that was positively associated with the reduction in TGs after 24 weeks (p=0.001) and with TC (p=0.005) and TGs (p<0.001) at the end of the follow-up period. CONCLUSION: Our results suggest that rituximab may improve the long-term lipid profile of patients with SLE refractory to standard treatment, mainly by reducing inflammatory activity.

Multicenter longitudinal study of B-lymphocyte depletion in refractory systemic lupus erythematosus: the LESIMAB study.

OBJECTIVE: This study aimed to investigate the effectiveness and safety of single and repeated courses of rituximab in patients with refractory lupus. METHODS: LESIMAB is a multicenter, retrospective, longitudinal study of lupus patients who have not responded to standard therapy and have been treated with rituximab. Response rates at six months and at follow-up were defined as efficacy outcomes. Complete response was defined as a SELENA-SLEDAI score ≤ two and a SELENA-SLEDAI Flare Index of zero. Partial response was defined as a reduction in the SELENA-SLEDAI score of ≥four points with no new or worsening of symptoms. Adverse events were collected. RESULTS: Seventy-three (62.9%) of 116 patients achieved a response at six months (complete in 22 and partial in 51). Ninety-seven (77.6%) of 128 patients achieved a response after a mean follow-up of 20.0 ± 15.2 months (complete in 50 and partial in 47). High baseline SLEDAI score, previous treatment with ≥100 mg/day prednisone, and no history of severe hematologic flare were associated with response after the first treatment course. The median time to response was 6.5 months (95% CI, 5.0-8.0). Thirty-seven patients (38.1%) relapsed after the first infusion. The flare was severe in seven cases and mild to moderate in 29 cases. Serious infection rate was 12.6/100 patient-years. A schedule of four weekly doses was associated with more serious infections. Six patients died: two of infection and four of lupus complications. CONCLUSION: Rituximab can be an effective treatment option for patients who have refractory lupus with severe or life-threatening disease with an acceptable tolerance profile.

[Coronary calcification and subclinical myocardial dysfuncion in rheumatoid arthritis]. / Calcificación coronaria y disfunción miocárdica subclínica en la artritis reumatoide.

Rheumatoid arthritis (RA) is characterized by high cardiovascular (CV) mortality, which has been related to systemic inflammation. Our aim was to analyze coronary calcification by computed tomography and subclinical myocardial dysfunction evaluated by brain natriuretic peptide (BNP) levels and an electrocardiogram in RA patients and its relationship with disease characteristics. Seventy-three RA patients and same number of controls formed by osteoarthritis patients were studied, all without a background of cardiovascular clinical events. RA patients had a higher calcium score than the control group (19.2% vs. 11%; p=0.17)), this being associated with disease duration. BNP levels (90.0 vs. 45.4; p=0.003), corrected QT length, large QT frequency and silent myocardial infarct were higher in the RA group. In conclusion, RA patients showed more coronary calcification frequency than in general population and more biochemical and electrocardiogram myocardial subclinical dysfunction signs.

Calcificación coronaria y disfunción miocárdica subclínica en la artritis reumatoide / Coronary calcification and subclinical myocardial dysfunction in rheumatoid arthritis

En la artritis reumatoide (AR) existe un incremento de la morbimortalidad cardiovascular que se ha relacionado con la inflamación sistémica. Nuestro objetivo fue analizar la calcificación coronaria detectada por la tomografía computarizada multicorte y la disfunción miocárdica subclínica mediante el péptido natriurético cerebral o tipo B (BNP) y el electrocardiograma en pacientes con AR, así como su relación con las características de la enfermedad. Se estudiaron 73 pacientes con AR y 73 controles con artrosis, sin historia de enfermedad vascular. Los pacientes con AR presentaron un score de calcio coronario alto con mayor frecuencia que los controles (19,2% frente a 11%; p = 0,17), que se relacionó con el tiempo de evolución de la enfermedad (p = 0,003). La concentración de BNP fue superior en el grupo con AR (90,0 frente a 45,4; p = 0,003), así como el tamaño del QT corregido, la frecuencia de un QT largo y el hallazgo de infarto silente. En conclusión, los pacientes con AR presentan calcificaciones coronarias con mayor frecuencia que la población general y muestran más signos bioquímicos y electrocardiográficos de disfunción miocárdica subclínica (AU)

Rheumatoid arthritis (RA) is characterized by high cardiovascular (CV) mortality, which has been related to systemic inflammation. Our aim was to analyze coronary calcification by computed tomography and subclinical myocardial dysfunction evaluated by brain natriuretic peptide (BNP) levels and an electrocardiogram in RA patients and its relationship with disease characteristics. Seventy-three RA patients and same number of controls formed by osteoarthritis patients were studied, all without a background of cardiovascular clinical events. RA patients had a higher calcium score than the control group (19.2% vs. 11%; p = 0.17)), this being associated with disease duration. BNP levels (90.0 vs. 45.4; p = 0.003), corrected QT length, large QT frequency and silent myocardial infarct were higher in the RA group. In conclusion, RA patients showed more coronary calcification frequency than in general population and more biochemical and electrocardiogram myocardial subclinical dysfunction signs (AU)

Cell surface CD28 levels define four CD4+ T cell subsets: abnormal expression in rheumatoid arthritis.

CD28 is a costimulatory receptor expressed in most CD4(+) T cells. Despite the long-standing evidence for up- and downregulation of surface CD28 expression in vitro, and the key regulatory role assigned to the upregulation of CD28 counterreceptor [the CD152 (CTLA-4) molecule], in vivo CD28 induction has attracted little attention. We studied CD28 and CD152 expression and function in 33 rheumatoid arthritis (RA) patients, 20 clinically active and 13 inactive, and in 24 healthy donors. Four subsets of CD28(-), CD28(low), CD28(int), and CD28(high) peripheral blood human CD4(+) T cells were defined using three-color flow cytometry. The three CD28(+) subsets displayed a one-, two-, or threefold quantitative difference in their relative number of CD28 antibody binding sites, respectively (P < 0.01). RA patients, whether active or inactive, showed a distinct phenotype when compared to healthy donors: (i) the percentage of CD4(+)CD28(high) cells was increased twofold and the CD4(+)CD28(low) subset was reduced twofold (P < 0.01) and (ii) the CD4(+)CD28(high) cells from RA patients showed an in vivo activated phenotype, CD45RO(+)CD5(high)IL-2Ralpha(+) (P < 0.01). Active RA patients were different from inactive patients. They showed a twofold increase in mean CD28 expression (P < 0.05), whereas each of the CD28(+) subsets in the inactive RA patients showed reduced expression when compared to healthy donors. Notably, both active and inactive RA patients showed abnormal CD28 upregulation when T cells were activated in vitro with CD3 antibodies, but only inactive RA patients showed a hypoproliferative response to TCR/CD3 triggering when compared to healthy donors (P < 0.01). This defective proliferation was normalized by concurrent crosslinking with CD28 antibody. No differences were noted in the expression of CD152 or CD80, a CD28 and CD152 shared ligand. The disregulated in vivo expression of CD28 was related to the RA patients' disease activity and suggests that modulation of CD28 surface levels may be an additional mechanism to finely tune the delicate responsiveness/tolerance balance.

Calcitonin versus clodronate in the prevention of ovariectomy-induced osteopenia in rats.

The effects of salmon calcitonin and clodronate were compared in ovariectomised rats. Sixty female Wistar rats ( 260 g in weight) were fed the same diet and had the same living conditions. The rats were divided into the following groups: 15 rats with sham ovariectomy and no drug treatment (Sham-OVX); 45 rats with bilateral ovariectomy subdivided into 15 rats not receiving drug treatment (OVX group), 15 rats treated with subcutaneous salmon calcitonin, 2 U/kg/day every 2 days (OVX + CT group) and 15 rats treated with subcutaneous clodronate, 5 mg/kg/day every 2 days (OVX + Cl group). Sixty days after surgery, the rats were sacrificed and their femurs and fifth lumbar vertebrae were dissected and cleaned of soft tissue. Femur length, vertebral height, and bone mineral content and bone mineral density of the femur and fifth lumbar vertebra by dual-energy X-ray absorptiometry were measured. Calcitonin had a significant and stronger effect in preventing ovariectomy-induced osteopenia in the femur (OVX + CT vs OVX groups, p < 0.0001); both calcitonin and clodronate had a significant effect on the fifth lumbar vertebra, which was greater in the calcitonin group (OVX + CT vs OVX + Cl groups, p<0.005). These findings indicate that calcitonin has a protective effect on both the axial (trabecular bone) and peripheral (cortical bone) skeletons, but clodronate only has a protective effect on the axial skeleton.

Effect of silicon supplement on osteopenia induced by ovariectomy in rats.

The effect of silicon (Si) supplement on preventing bone mass loss induced by ovariectomy (OVX) in rats was investigated. Three groups of 15, 100-day-old female Wistar rats each, with a mean initial weight of approximately 260 g per animal, were selected for the present study. One of the experimental group consisting of 15 OVX rats was fed a diet supplemented with 500 mg of Si per kg of feed (Si + OVX). The other two groups consisting of 15 OVX and 15 sham-OVX rats did not receive these supplements. Morphometric (weight and length) and densitometric studies with dual-energy X-ray absorptiometry were performed on the whole femur and 5th lumbar vertebra of each animal 30 days after the experiment. The Si + OVX rats did not show a loss of bone mass induced by OVX at axial level (5th lumbar vertebra) or periphery (femur). Nonetheless, a significant increase (ANOVA with Bonferroni/Dunn post hocs test) of longitudinal development of the femur (P < 0.0001) was patent. These results, obtained through the measurements of axial and peripheral bones, warrant closer scrutiny in connection with the Si inhibitory effect on bone mass loss as well as the stimulatory effect on bone formation. Both actions, namely, inhibition of resorption and stimulation of formation, infer that Si may have a potential therapeutic application in the treatment of involutive osteoporosis.

Effects of potassium bicarbonate supplementation on axial and peripheral bone mass in rats on strenuous treadmill training exercise.

We administered a potassium bicarbonate supplement to rats on strenuous treadmill training in order to determine the effect on bone mass and the metabolic acidosis seen with this type of training. A sample of 45 93-day-old female Wistar rats with a mean initial weight of 267 +/- 17 g were studied. The control group (15 rats) was not exercised or given potassium bicarbonate (Ex- PB-). The experimental group (30 rats) was randomly divided into two subgroups of 15 rats each, one that exercised and did not receive potassium bicarbonate (Ex+ PB-) and one that exercised and received potassium bicarbonate (Ex+ PB+), at a dose of 0.05 mg/kg/day administered by esophageal catheter on exercise days. Training consisted of treadmill running on 5 out of 7 days for a period of 11 weeks. Running time, treadmill speed, and the percent grade were gradually increased until week 7, then maintained until rats were sacrificed at the ened of 11 weeks. The bone mineral content (BMC) and bone mineral density (BMD) of the whole right femur and 5th lumbar vertebra were measured. Femoral and vertebral length were also measured. Femur length, weight, BMC, and BMD, and femur BMC/final weight ratio, and vertebral weight, BMD, and BMC, and vertebral BMC/final weight ratio were lower in the Ex+ PB- group than in either the controls or the Ex+ PB+ group (P < 0.01-P < 0.0001); the length of the 5th lumbar vertebra did not differ between groups.

Effects of alprazolam supplementation on vertebral and femoral bone mass in rats on strenuous treadmill training exercise.

The ability of alprazolam to diminish cortisol response and favor ovarian function could make it useful in the prevention of osteopenia in athletes in selected cases. A sample of 45 female Wistar rats, all 93 days old and with a mean initial weight of 267 +/- 17 g, were studied. Rats were exposed to a high-performance level of exercise and were divided into two groups-one group received an alprazolam supplement and one did not-and compared with controls to determine the effect of alprazolam on bone mass as measured by dual-energy X-ray absorptiometry (DKA). Exercise consisted of treadmill running on 5 out of 7 days during a period of 11 weeks. A steep grade treadmill inclination was used to stimulate high-intensity muscle activity. Final inclination was 17.5 degrees and treadmill speed was 45 cm/second. Upon completion of the experiment, all the rats were killed and the femur and 5th lumbar vertebra were dissected and cleaned. Length, weight, bone mineral content (BMC), and density (BMD) of the whole right femur and 5th lumbar vertebra were measured. In the exercise only group (no alprazolam), the length, weight, BMC, BMD, and femur BMC/final rat weight ratio of the femur, and the vertebral weight, vertebral BMD and BMC, and vertebral BMC/final rat weight ratio were lower than in the control and the exercise-alprazolam groups (P < 0.0167 - < 0.0001). Alprazolam preserves bone mass in rats exposed to intense exercise.

Defective proliferative response of T lymphocytes from patients with inactive systemic lupus erythematosus.

OBJECTIVE: To further define the pattern of alterations in the activation and apoptosis of T lymphocytes in patients with inactive systemic lupus erythematosus (SLE) through analysis of a large series of individuals. METHODS: We isolated CD2+ peripheral blood lymphocytes (PBL) from 41 patients with inactive SLE and analyzed their proliferative and apoptotic responses to polyclonal activation. RESULTS: In 19 of 41 (47%) patients, a low proliferative response to polyclonal mitogens was found. This defective response was inversely associated with an increased apoptotic response and increased expression of CD95 and CD45RO antigens. CONCLUSION: We found that 2 groups of patients with inactive disease can be defined according to the functional behavior of their T lymphocytes, as defined by the proliferative and apoptotic responses to mitogenic signals.

T score of trabecular and cortical bone in normal postmenopausal women.

OBJECTIVE: The T score of the cortical and trabecular bone compartments (T score of BMDTrab and T score of BMDCorti) was calculated in healthy postmenopausal women to determine which bone compartment loses more bone mass. MATERIAL AND METHODS: A total 134 healthy postmenopausal women (mean age 55.1 +/- 6.4 years) and 67 healthy premenopausal women (mean age 36.0 +/- 8.6 years) were studied. Determinations were made using peripheral quantitative computed tomography (pQCT) of the nondominant forearm. The postmenopausal women were divided into groups by years since menopause (YSM): two early postmenopausal groups: < 5 YSM and 6-10 YSM; and two late postmenopausal groups: 11-20 YSM and > 20 YSM. RESULTS: There was a significant correlation between the T score of BMDTrab and the T score of BMDCorti (P < 0.0001). Both correlated negatively and significantly with age (P < 0.001 and P < 0.0001, respectively) and neither correlated with weight. The Wilcoxon test showed no significant differences between the trabecular and cortical T scores in the overall group of women. By YSM, only the > 20 YSM group showed significant differences (P < 0.005). The ANOVA post hoc Bonferroni/Dunn test showed a significant difference in the T score of BMDTrab by YSM only in the < 5 YSM versus 11-20 YSM groups (P = 0.007) and in the < 5 YSM versus > 20 YSM groups (P < 0.0001). The T score of BMDCorti by YSM differed significantly only between the < 5 YSM versus 11-20 YSM groups (P < 0.0001) and between the 11-20 YSM and > 20 YSM groups (P < 0.005). CONCLUSION: In contrast with what has been postulated in recent studies, our results showed that postmenopausal bone loss was similar in the cortical and trabecular bone compartments in the first 20 years after menopause. Trabecular bone loss was greater than cortical bone loss in late menopause (> 20 years).

Influence of weight and gonadal status on total and regional bone mineral content and on weight-bearing and non-weight-bearing bones, measured by dual-energy X-ray absosorptiometry.

OBJECTIVE: To evaluate the influence of weight on total body bone mineral content (BMCTB) and regional body bone mineral content (head, arms, trunk and legs). This was studied in accordance with gonadal status and the weight-bearing or non-weight-bearing status of each region. METHODS: The study included 94 postmenopausal women (mean age 60.6 +/- 10.5 years), 36 perimenopausal women (mean age 49.0 +/- 2.3 years) and 60 premenopausal women (mean age 36.1 +/- 6.9 years). Full-body bone densitometry (DXA), for measuring total body bone and regional bone mineral content, was carried out in all the women. RESULTS: Among these groups, the influence of 1 kg of body weight on total and regional bone mineral content (percent) did not differ (paired test P ns). In the overall group of women, paired comparison showed differences between the head and other zones measured (P = 0.036-0.004). In the overall group of women, no differences were found in the percent influence of 1 kg body weight on bone mineral content in any study zone (by ANOVA, Fisher's PLSD post hoc test and the Kruskal-Wallis test). In the overall group of women, Fisher's r to z test revealed a non-significant relationship between weight and the bone mineral content of the head (r = 0.49, P ns) but in every other region the relationship between weight and bone mineral content was significant (r = 0.36-0.54, P < 0.0001 in all). CONCLUSIONS: The effect of body weight on BMCTB and regional did not differ significantly with either gonadal status or weight-bearing (legs) and non-weight-bearing bones (arms).

Influence of body mass index on the age-related slope of total and regional bone mineral content.

The influence of body mass index (BMI) on T scores for total body bone mineral content (TBBMC) and regional bone mineral content (RBMC) was studied in 186 healthy women: 100 postmenopausal, 35 perimenopausal, and 51 premenopausal. The three groups were divided by BMI >25 kg/m2 and BMI <25 kg/m2 and the postmenopausal women were further subdivided by years since menopause (YSM): <10, 10-20, and >20. Tartrate-resistant acid phosphatase (TRAP) concentration was higher in perimenopausal and postmenopausal women with BMI <25 kg/m2 (P < 0.001). T scores for TBBMC and for axial or peripheral RBMC differed (P < 0.05 in all) between women with BMI >25 kg/m2 and BMI <25 kg/m2. The rate of perimenopausal and postmenopausal age-related slope of BMC, as reflected in all measurements, differed with BMI. In the overall group of women, the T score for TBBMC correlated significantly with BMI (r = 0.46, P < 0.0001); this correlation increased when adjusted for age (r = 0.62, P < 0.0001). BMI correlated with TRAP only in postmenopausal women (r = 0.57, P < 0. 0001). Yearly TBBMC decline was twice as high in postmenopausal women with BMI <25 kg/m2 (P = 0.0004) than in those with BMI >25 kg/m2; the decline of trunk RBMC was more significant (P < 0.0001). These findings confirm the influence of BMI and gonadal status on bone mass.

Total body bone measurements in spinal osteoporosis by dual-energy X-ray absorptiometry.

Changes in total body bone mineral content (BMCTB) and density (BMDTB), and the T-score of BMCTB and (BMDTB) were evaluated in relation to the number of vertebral fractures in women with postmenopausal osteoporosis for the purpose of defining deviations in these parameters that could be predictive of the occurrence of vertebral fracture. The study group consisted of 62 women diagnosed with postmenopausal osteoporosis. All of them had two or more spinal fractures. Regression analysis of the number of fractures against each parameter studied indicated that the following were predictive of the risk of fracture: a reduction of -0.5 in the T-score of both BMCTB and BMDTB (P < 0.0001) and a loss of about 135 g of BMCTB or 0. 058 g/cm2 of BMDTB (P < 0.0001). The fact that such changes were found during the follow-up of women with osteoporosis highlights the importance of bone mass measurements during follow-up.

Penicillin--intermediate-resistant pneumococcal spondylodiscitis.

Pneumococcal osteomyelitis probably was more common in the pre-antibiotic era, but currently is rare. Sickle-cell disease and possibly, bone trauma and advanced age are predisposing factors for pneumococcal osteomyelitis. Bone infection usually occurs as a result of hematogenous spread from an infective focus, which often cannot be identified. In patients without evidence of other focci of infection, pneumococcal spondylodiscitis probably is caused by "primary" pneumococcal bacteriemia, originating in the oropharynx, especially if the patient has alterations that disrupt the oropharyngeal mucose. Whereas early in the antibiotic era, all Streptococcus pneumoniae strains were susceptible to penicillin, resistance to this antibiotic is on the rise, and in many parts of the world, it has emerged as a major problem. We report the case of a young patient with penicillin-resistant pneumococcal vertebral and intervertebral disk disease who had no evidence of pneumococcal infection elsewhere, and we discuss the possible mechanism of infection. We also review briefly the resistance to penicillin of S. pneumoniae and the treatment of choice.

Detección de anticuerpos anti-RNP y anti-Sm mediante immunoblotting y contrainmunoelectroforesis utilizando el mismo extracto de timo de conejo / Detection of anti-RNP and anti-Sm antibodies by immunoblotting and contrainmmunoelectrophoresis using the same rabbit thymus extract

Las técnicas de contrainmunoelectroforesis (CIE) y ELISA son útiles para detectar anticuerpos anti-RNP y anti-Sm,pero no identifican los anticuerpos dirigidos contra los diferentes polipéptidos asociados a RNP/Sm.Estos anticuerpos pueden detectarse mediante immunoblotting (IB) con extractos de células HeLa u otras mantenidad en cultivo.Objetivos:Determinar si el mismo extracto de timo de conejo utilizado en la CIE puede ser una alternativa válida ppara detectar mediante IB los anticuerpos dirigidos contra los diferentes polipépticos asociados a RNP/Sm.Métodos:Hemos estudiado 342 sueros de 250 pacientes con enfermedades inflamatorias del tejido conjuntivo.Los anticuerpos anti-RNP y anti-Sm fueron detectados mediante CIE e IB utilizando como sustrato el mismo extracto comercial de timo de conejo.Resultados: Este IB permitió anticuerpos dirigidos contra los polipéptidos 70kD,A,BB',C y D,aunque el de 70D estaba degradado.Se detectaron anticuerpos anti-RNP y anti-Sm por CIE en el 7,3 por ciento (25 de 342) y de 6,1 (21 de 342) de los sueros , y mediante IB en el 14,9 por ciento (51 de 342) y de 14,3//(49 de 342) de los sueros,respectivamente.En 72 pacientes con lupus eritematoso sistémico la sensibilidad y especificidad de la CIE fueron del 19,1//y del 96,5//para anti-RNP,y del 11,1 del del 100//para anti-Sm.La sensibilidad y especificidad del IB fueron del 22,2 y del 96//para anti-RNP 70 kD y del 19,4 y del 100//para anti-SmD. Conclusiones: A pesar de la degradación proteolítica , el IB con un extracto soluble de timo de conejo puede ser una alternativa válida como complemento de la CIE o del ELISA en la detección de anticuerpos anti-RNP y anti-Sm,y está al alcance de cualquier laboratorio clínico.

Detección de anticuerpos anti-RNP y anti-Sm mediante immunoblotting y contrainmunoelectroforesis utilizando el mismo extracto de timo de conejo / Detection of anti-RNP and anti-Sm antibodies by immunoblotting and contrainmmunoelectrophoresis using the same rabbit thymus extract

Las técnicas de contrainmunoelectroforesis (CIE) y ELISA son útiles para detectar anticuerpos anti-RNP y anti-Sm,pero no identifican los anticuerpos dirigidos contra los diferentes polipéptidos asociados a RNP/Sm.Estos anticuerpos pueden detectarse mediante immunoblotting (IB) con extractos de células HeLa u otras mantenidad en cultivo.Objetivos:Determinar si el mismo extracto de timo de conejo utilizado en la CIE puede ser una alternativa válida ppara detectar mediante IB los anticuerpos dirigidos contra los diferentes polipépticos asociados a RNP/Sm.Métodos:Hemos estudiado 342 sueros de 250 pacientes con enfermedades inflamatorias del tejido conjuntivo.Los anticuerpos anti-RNP y anti-Sm fueron detectados mediante CIE e IB utilizando como sustrato el mismo extracto comercial de timo de conejo.Resultados: Este IB permitió anticuerpos dirigidos contra los polipéptidos 70kD,A,BB,C y D,aunque el de 70D estaba degradado.Se detectaron anticuerpos anti-RNP y anti-Sm por CIE en el 7,3 por ciento (25 de 342) y de 6,1 (21 de 342) de los sueros , y mediante IB en el 14,9 por ciento (51 de 342) y de 14,3//(49 de 342) de los sueros,respectivamente.En 72 pacientes con lupus eritematoso sistémico la sensibilidad y especificidad de la CIE fueron del 19,1//y del 96,5//para anti-RNP,y del 11,1 del del 100//para anti-Sm.La sensibilidad y especificidad del IB fueron del 22,2 y del 96//para anti-RNP 70 kD y del 19,4 y del 100//para anti-SmD. Conclusiones: A pesar de la degradación proteolítica , el IB con un extracto soluble de timo de conejo puede ser una alternativa válida como complemento de la CIE o del ELISA en la detección de anticuerpos anti-RNP y anti-Sm,y está al alcance de cualquier laboratorio clínico.

[Clinical and serologic course of patients with mixed connective tissue disease]. / Evolución clínica y serológica en pacientes con enfermedad mixta del tejido conectivo.

The so called mixed connective tissue disease (MCTD), continues to be a controversial entity, while some authors considered it a good characterized disease, others think that is an undifferentiated connective tissue disease. OBJECTIVE. To analyse the clinical and serological evolution of a group of patients diagnosed of MCTD, with particular consideration to the meaning of anti-nRNP and anti-Sm antibodies. METHOD. We have studied 20 patients diagnosed of MCTD and 112 with systemic lupus erythematosus (SLE). Anti-nRNP and anti-Sm antibodies were detected through counter immunoelectrophoresis, immunoblotting and ELISA. RESULTS. After an average time of evolution of 10 years, 70% (14/20) of the patients diagnosed of MCTD fulfill criteria for SLE (6 cases), scleroderma (6 cases) or polymyositis (2 cases). Anti-nRNP response is persistent, directed mainly against the 70 Kd and A-nRNP polypeptides and qualitatively higher in MCTD in SLE (absorbencies 2.64 vs 1.25. The immunoblotting test detected anti-Sm antibodies in 5 patients (25%) and ELISA test in 14 (70%). CONCLUSIONS. Clinical and serological evolution suggest that MCTD is an undifferentiated connective tissue disease. Anti-nRNP antibodies are characteristic, although anti-Sm antibodies can be detected with ELISA regardless whether on not patients fulfill SLE criteria.