Association between severe disease course and nephritis with Q222R polymorphism in DNAse I gene among lupus patients: An Argentine multicenter study.

UNLABELLED: Objetives: Systemic lupus erythematosus is a multifactorial autoimmune disease and the glomerulonephritis is one of the most severe complications, which leads to severe persistent proteinuria, chronic renal failure, and end-stage renal disease. This multicenter study investigated the genetic associations of a non-synonymous single-nucleotide polymorphism in DNase I with the risk of lupus and its influence on development of nephropathy in an Argentinean population. METHODS: Using the Polymerase chain reaction restriction fragment length polymorphism method, the Q222R (+2373A→G; Gln244Arg) DNase I polymorphism was studied in 156 systemic lupus erythematosus patients and 170 healthy controls. RESULTS: Although no significant association between Q222R polymorphism and the risk of systemic lupus erythematosus was found, the presence of the A allele was associated with an increased risk for the development of nephropathy (p=0.019, Odd Ratio=2.196, 95 % confidence interval [1.135-4.247]) and a worse disease course [moderate disease course: p=0.006, Odd Ratio=3.250, 95% confidence interval (1.401-7.539); severe disease course: p=0.040, Odd Ratio=2.339, 95% confidence interval (1.040-5.260)]. CONCLUSIONS: A better understanding of the genetic basis of systemic lupus erythematosus will help in the development of new and more effectives strategies for the treatment of the disease in the future.

Validation of an Argentine version of Lupus Quality of Life questionnaire.

OBJECTIVE: To determine reproducibility and validity of an Argentine version of the Lupus Quality of Life questionnaire (LupusQoL) and to determine cut-off values in the questionnaire. MATERIALS AND METHODS: One hundred and forty-seven systemic lupus erythematosus patients (American College of Rheumatology 1982/1997) were assessed from April 2014 to July 2014. Demographic and socioeconomic variables were collected, as well as SELENA/SLEDAI, Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index Score, comorbidities and treatment data. Patients completed LupusQoL-Argentine version and European Quality of Life Questionnaire (EuroQoL-5D). Internal consistency and reliability were examined. Convergent validity with EuroQoL-5D was assessed through analysis of latent classes, which established homogeneous categories from the responses of each domain of LupusQoL and for the total. RESULTS: Out of 147 patients, 93.2% were female, mean age 36.4 ± 11.1 years, mean disease duration 2.7 ± 9 years, mean SELENA/SLEDAI 2.7 ± 3 points. The cut-off point that defined good or bad quality of life was 0.739 for EuroQoL 5D and 63 for LupusQoL. Cut-off values for each LupusQoL domain were also defined, creating two classes in each of them. There was moderate to high concordance to classify quality of life (Kappa = 0.74, 95% confidence interval = 0.54, 0.95). CONCLUSION: The Argentine version of LupusQoL is a valid, reliable and reproducible instrument to assess quality of life. In this study, cut-off points that allow the classification of patients regarding whether they have good or bad quality of life are established for the first time.

Long-term storage effect on chemical composition, nutritional value and quality of Greek onion landrace "Vatikiotiko".

The effect of storage at two temperatures (5±1 and 25±1 °C and 60-70±5% RH for both temperatures) on marketability and quality features of dry bulbs of local landrace "Vatikiotiko", "Sivan F1", "Red Cross F1" and "Creamgold" was examined. During storage measurements for fresh and dry weight of bulbs, tunic and flesh color, bulb firmness, nutritional value and mineral composition were taken at regular intervals. Storage concluded when either bulbs lost marketable quality or sprouting occurred. "Vatikiotiko" onion can be stored for at least 7months at 25±1 °C, whereas at 5±1 °C storage could be prolonged without significant marketability and quality loss. The fact that "Vatikiotiko" landrace can be considered a "storage" onion has to be capitalized in order to increase total production and yield, since storage could cover the market needs that arise throughout the year.

Características de los tratamientos biológicos en enfermedades reumáticas en Argentina: quinto informe del registro BIOBADASAR / Features of rheumatic diseases biological treatments in Argentina: BIOBADASAR fifth report

Introducción: El proyecto BIOBADASAR (Registro argentino deeventos adversos con tratamientos biológicos en reumatología)comenzó en agosto de 2010, para recabar información a largo plazosobre los eventos adversos en tratamientos biológicos en pacientescon enfermedades reumáticas en la práctica clínica cotidiana enArgentina.Pacientes y método: Se registraron datos de cada paciente,tratamientos y acontecimientos adversos relevantes o importantes.Los pacientes debían tener enfermedad diagnosticada y tratadacon un agente biológico. Cada caso se comparó con un control:un paciente con tratamiento no biológico con característicasdemográficas similares. Se analizaron los datos con análisis de lavarianza, con test de t de Student, Mann Whitney, test chi2, o testexacto de Fisher. El análisis de supervivencia de los tratamientoshasta su discontinuación o interrupción se realizó con el método deKaplan-Meier y test log-rank...

Background: BIOBADASAR (Argentine Registry of Adverse Eventsin Biological Treatments in Rheumatology) was started in August2010 to obtain long-term information of patients with rheumatic diseases,treatments and adverse events in everyday clinical practice.Patients and methods: Data on patients’ demographics,treatments and adverse events were collected. Patients had a diagnosisof a rheumatic disease and were treated with biological agent.To compare information, a control group was included, consisting ofpatients treated with similar demographic characteristics but treatedwith a non-biological agent. Data were analysed with Anova,Student´s t, Mann Whitney, chi2, Fisher´s exact tests, as appropriate.Survival analysis of treatments was performed with Kaplan-Meiercurves and log-rank test...

Concordancia de los nuevos criterios ACR/EULAR y los ACR 1980 para la clasificación de la esclerosis sistémica / Concordance of the new ACR/EULAR criteria and the ACR 1980 for the classification of systemic sclerosis

Objetivo: Evaluar cumplimiento, y así mismo concordancia y discordancia de los criterios de clasificación de Esclerosis Sistémica (ES) ACR/EULAR 2013 y ACR 1980 en pacientes con diagnóstico clínico de la enfermedad. Método: Se incluyeron 169 pacientes con diagnóstico de Esclerosis Sistémica. Resultados: El 72,2 por ciento cumplía los criterios ACR 1980, y el 99,4 por ciento (168 pacientes) cumplía los criterios ACR/EULAR 2013. La concordancia absoluta de toda la muestra fue 72,7 por ciento, para el subtipo limitado 35,2 por ciento, y 100 por ciento el difuso. Se subanalizaron los pacientes con limitada que sólo cumplían criterios ACR/EULAR 2013, y se comparó con el resto de las limitadas. Los primeros presentaron en forma estadísticamente significativa menor esclerodactilia distal a MCF, menor presencia de úlceras digitales y pitting scars, menor afectación intersticial pulmonar, y mayor daño microvascular en la capilaroscopia. Conclusión: Los nuevos criterios de clasificación de Esclerosis Sistémica serían más adecuados para detectar esclerodermias limitadas, siendo dicho hallazgo estadísticamente significativo.

Objective: To evaluate the performance, and likewise concordance and discordance of the classification criteria of Systemic Sclerosis ACR/EULAR 2013 and ACR 1980 in a group of patients with clinical diagnosis of SSc. Methods: We enrolled 169 patients with diagnosis of Systemic Sclerosis. Results: 72.2 percent met the 1980 ACR criteria, and 99.4 percent met the ACR/EULAR 2013 criteria. The absolute agreement of the entire sample was 72.7 percent, 35.2 percent for the limited subtype, and 100 percent for the diffuse. Those patients with limited subtype who only met the ACR/EULAR 2013 criteria were compared with the rest of limited patients. The first group had statistically significantly lower sclerodactyly distal to MCF, lower presence of digital ulcers and pitting scars, less interstitial lung involvement, and greater abnormal nail fold capillaries. Conclusion: The new classification criteria for systemic sclerosis seem to be more suitable for detecting limited scleroderma. In the present study, statistically significant discrepancy was found in the limited subtype.

Frecuencia de úlceras digitales en esclerodermia / Digital ulcers frequency in scleroderma

Nuestro objetivo fue describir la frecuencia de úlceras digitales en una población de pacientes con Esclerosis Sistémica y comparar las características clínicas de los que desarrollaron úlceras de los que no lo hicieron. Se incluyeron en forma retrospectiva pacientes que cumplían criterios ACR para Esclerosis Sistémica. Se recolectaron datos demográficos, clínicos y serológicos de las historias clínicas. Se clasificó a los pacientes en dos grupos: un Grupo A con úlceras digitales y Grupo B aquellos pacientes sin antecedentes de úlceras digitales. Se compararon ambos grupos. Se estudiaron 60 pacientes con diagnóstico de Esclerosis Sistémica, 33% subtipo difuso, edad promedio al diagnóstico de 50,75 ± 14,75 años, el 15% (9 pacientes) eran de sexo masculino. La frecuencia de úlceras digitales fue de 33,33% (n=20). Los pacientes del grupo A eran más jóvenes al momento del diagnóstico (p=0,03) y tenían más tiempo de evolución de la enfermedad (pNS). En este grupo, fue más frecuente la forma difusa (p=0,002) y el fenómeno de Raynaud se inició a edades más precoces (p=0,006). Los pacientes del grupo A presentaron menor capacidad funcional, medida por HAQ score, y mayor frecuencia de patente tardía en la capilaroscopia, aunque no fue estadísticamente significativo. La totalidad de los pacientes de género masculino (n=9) tuvieron úlceras digitales (p <0,0001).Conclusión: El desarrollo de úlceras digitales en nuestro estudio se asoció a inicio más precoz de la enfermedad, a sexo masculino, a la forma difusa y a inicio más temprano de fenómeno de Raynaud.

The aim of this study was to describe digital ulcer frequency ina patient population with Systemic Sclerosis and to compare theclinical features of those who developed ulcers with those who didnot. Retrospectively, patients meeting ACR criteria for SystemicSclerosis were included. Demographic, clinical, and serologicalinformation was obtained from medical records. Patients wereclassified into two groups: Group A comprised patients with digitalulcers, while Group B included patients with no digital ulcers ontheir records. Findings for both groups were compared. We studied60 patients diagnosed with Systemic Sclerosis, 33% with diffusecutaneous subset, the mean age at the time of diagnosis was 50.75± 14.75 years, 15% (9 patients) were males. The frequency of digitalulcers was 33.33% (n=20). Group A patients were younger at thetime of diagnosis (p=0.03) and had longer time of evolution (pNS).The diffuse variant was more frequent in this group (p=0.002) andRaynaud’s phenomenon onset occurred at earlier ages (p=0.006).All male patients (n=9) entered into the study had digital ulcers (p<0.0001).Conclusions: In our study, development of digital ulcers wasassociated with an earlier onset of disease, males, diffuse subsetand an earlier onset of Raynaud’s phenomenon.

How gamma-rays and electron-beam irradiation would affect the antimicrobial activity of differently processed wild mushroom extracts?

AIMS: The effects of irradiation (gamma-rays and electron-beams), up to 10 kGy, in the antimicrobial activity of mushroom species (Boletus edulis, Hydnum repandum, Macrolepiota procera and Russula delica) differently processed (fresh, dried, freeze) were evaluated. METHODS AND RESULTS: Clinical isolates with different resistance profiles from hospitalized patients in Local Health Unit of Mirandela, Northeast of Portugal, were used as target micro-organisms. The mushrooms antimicrobial activity did not suffer significant changes that might compromise applying irradiation as a possible mushroom conservation technology. CONCLUSIONS: Two kGy dose (independently of using gamma-rays or electron-beams) seemed to be the most suitable choice to irradiate mushrooms. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides important results in antimicrobial activity of extracts prepared from irradiated mushroom species.

Estudio multicéntrico de deterioro cognitivo en lupus eritematoso sistémico: ECLES / Multicenter study of cognitive decline in systemic lupus erythematousus: ECLES

Introducción: los pacientes lúpicos presentan un riesgo incrementado de deterioro cognitivo (DC) comparado con individuos sanos, el cual puede ser debido a múltiples causas. Objetivo: Describir la frecuencia y características del deterioro cognitivo en pacientes con lupus sin manifestaciones neuropsiquiátricas conocidas. Materiales y método: Se incluyeron pacientes de 16 a 55 años con diagnóstico de LES según criterios del Colegio Americano de Reumatología (ACR) de 1997. Se incluyeron test neuropsicológicos acordes a la propuesta del ACR y el cuestionario de Beck para evaluar depresión. Se definió DC a valores de <2 o más desvíos estándar comparada con la media de población normal en al menos un test. Se consideró focal cuando afectó una o más medidas de un dominio y multifocal en 2 o más dominios. Para comparar proporciones se utilizó prueba exacta de Fisher y para comparar variables numéricas se usó prueba de Kruskal-Wallis. Se consideró significativo un valor de p <0,05. Resultados: Se estudiaron 86 pacientes con lupus, el 90% de origen caucásico, 8% mestizos y 1% amerindio. El 82% alcanzó nivel secundario. La frecuencia de DC fue del 65% (56/86). Los dominios afectados: memoria 45%, funciones ejecutivas 30%, atención 29%, lenguaje 4,6%. Se detectó depresión en un 48% de los pacientes. Se analizaron diferentes factores de riesgo, sin hallar diferencias estadísticamente significativas a excepción de la etnia (p=0,02). Conclusión: Se halló una frecuencia elevada de deterioro cognitivo en pacientes con LES, los pacientes no caucásicos tuvieron mayor DC con diferencias significativas en comparación con los pacientes caucásicos.

Background: patients with systemic lupus erythematosus (SLE)have an increased risk of cognitive impairment (CI) compared tohealthy individuals and it may be due to multiple causes. Objective: To determine the frequency and characteristics of CI inlupus patients without known previous neuropsychiatric events. Methods: Patients aged 16 to 55 fulfilling the 1997 ACR criteria forSLE were included. The neuropsychological test battery proposedby the ACR was used to determine CI and Beck depression werealso assessed. CI was defined as values of ≤2 standard deviationscompared to the mean of the general population in at least one test. It was considered focal involvement if it affected one or more measuresof a single domain and multifocal if 2 or more domains wasaffected. To compare proportions, Fisher’s exact test was used andto compare numerical variables, Kruskal-Wallis. A value of p <0.05was considered significant. Results: 86 patients were evaluated, 90% were Caucasian, 8%mestizos and 1% Amerindian. 82% had high school. CI was foundin 65% of patients (56/86). The affected domains were: memory45%, executive functions 30%, attention 29% and language 4.6%. Depression was detected in 48% of patients. Different risk factorswere analyzed and found no statistically significant differences exceptfor ethnicity (p=0.02). Conclusion: A high frequency of CI was found in patients with SLE,non-Caucasian had higher CI with significant differences in comparisonwith Caucasian patients.

Calciphylaxis in a patient with systemic lupus erythematosus without renal insufficiency or hyperparathyroidism.

Calciphylaxis is a frequent entity in patients with chronic renal failure of diverse etiology. The main pathogenic mechanism of calciphylaxis is impairment of either calcium and phosphate metabolism or plasma levels of parathyroid hormone. There are communications of patients with normal renal function, and in some cases with chronic inflammatory diseases such as rheumatoid arthritis, systemic lupus erythematosus (SLE) and antiphospholipid syndrome. We report a patient with SLE and no renal failure or hyperparathyroidism who developed severe calciphylaxis.

Lupus eritematoso sistémico inducido por interferón-α pegilado en un paciente con infección por VHC / Pegylated interferon-α induced lupus in a patient with chronic hepatitis C

El Lupus inducido por drogas tiene una prevalencia estimada del 10%, debe sospecharse frente al antecedente de la exposición a un farmaco y están relacionado en forma temporal al uso del mismo. Generalmente, luego de suspender la droga el cuadro se resuelve. El Interferón-α puede ser responsable tanto de gatillar una respuesta inmune en pacientes predispuestos como de exacerbarla en aquellos con patologías autoinmunes previas. Comunicamos el caso de un varón de 54 años con infección por virus de hepatitis C que desarrolló LES inducido por IFN-α pegilado y realizamos una revisión de la literatura.(AU)

Lupus eritematoso sistémico inducido por interferón-α pegilado en un paciente con infección por VHC / Pegylated interferon-α induced lupus in a patient with chronic hepatitis C

El Lupus inducido por drogas tiene una prevalencia estimada del 10%, debe sospecharse frente al antecedente de la exposición a un farmaco y están relacionado en forma temporal al uso del mismo. Generalmente, luego de suspender la droga el cuadro se resuelve. El Interferón-α puede ser responsable tanto de gatillar una respuesta inmune en pacientes predispuestos como de exacerbarla en aquellos con patologías autoinmunes previas. Comunicamos el caso de un varón de 54 años con infección por virus de hepatitis C que desarrolló LES inducido por IFN-α pegilado y realizamos una revisión de la literatura.

Liver transplantation in systemic lupus erythematosus: case report and review of the literature.

Severe liver involvement requiring liver transplantation is a rare complication in systemic lupus erythematosus (SLE), but very few cases have been reported. We describe a 39-year-old woman with SLE who underwent successful liver transplantation due to acute liver failure. The patient persisted without reactivation of SLE and with good long-term survival. Management and diagnosis considerations are reviewed.

Antioxidant potential of chestnut (Castanea sativa L.) and almond (Prunus dulcis L.) by-products.

The antioxidant properties of almond green husks (Cvs. Duro Italiano, Ferraduel, Ferranhês, Ferrastar and Orelha de Mula), chestnut skins and chestnut leaves (Cvs. Aveleira, Boa Ventura, Judia and Longal) were evaluated through several chemical and biochemical assays in order to provide a novel strategy to stimulate the application of waste products as new suppliers of useful bioactive compounds, namely antioxidants. All the assayed by-products revealed good antioxidant properties, with very low EC(50) values (lower than 380 µg/mL), particularly for lipid peroxidation inhibition (lower than 140 µg/mL). The total phenols and flavonoids contents were also determined. The correlation between these bioactive compounds and DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging activity, reducing power, inhibition of ß-carotene bleaching and inhibition of lipid peroxidation in pig brain tissue through formation of thiobarbituric acid reactive substances, was also obtained. Although, all the assayed by-products proved to have a high potential of application in new antioxidants formulations, chestnut skins and leaves demonstrated better results.

Utilidad de la videocapilaroscopia de lecho ungueal en el síndromede Sjõgren con fenómeno de Raynaud / Utility of nailfold videocapillaroscopy in Sjõgren's syndrome with Raynaud's

La videocapilaroscopia de lecho ungueal (VCLU) es un método sencillo, no invasivo, de bajo costo y útil para la evaluación de las anormalidades microvasculares halladas en las enfermedades del tejido conectivo (ETC)1. Describimos una paciente con síndrome de Sjõgren (SS) primario que presentó alteraciones características en la VCLU y desarrolló una esclerosis sistémica (ES) limitada.

Influencia de factores sociodemográficos en actividad de enfermedad, estadofuncional y calidad de vida de pacientes con artritis psoriásica / Influence of sociodemographic features on clinical manifestations, disease activity, functional status and quality of life of patients with psoriatic artritis

Objetivo: Determinar la influencia de factores sociodemográficos en las manifestaciones clínicas, actividad de la enfermedad, estado funcional y calidad de vida de pacientes con artritis psoriásica (APs). Métodos: Se incluyeron 148 pacientes con APs reclutados de varios centros de reumatología de Argentina. Se determinaron factores sociodemográficos: edad, sexo, raza, nivel de educación, fuentes de ingreso personal, escala de Graffar y clases sociales. Al inicio de la enfermedad se evaluaron las siguientes variables: edad al inicio, duración de la enfermedad, manifestaciones clínicas y forma clínica de presentación. La actividad de la enfermedad fue evaluada mediante número de articulaciones activas, escala visual análoga (EVA) global del paciente y BASDAI. El estado funcional y la calidad de vida de los pacientes se determinó por medio de BASFI, ASQoL y SF-12 (Versión 1.0). Para el análisis estadístico de los datos obtenidos se utilizó test de Chi-cuadrado, test exacto de Fisher y test de Kruskal-Wallis. Resultados: De los 148 pacientes, 58,8% fueron mujeres con una edad media al inicio de la enfermedad de 53,2 ± 13,6 años y una duración media de enfermedad de 9,3 ± 8,9 años. La edad al inicio, el sexo, la raza y la escala de Graffar no estuvieron asociados con manifestaciones clínicas, actividad de la enfermedad, estado funcional y calidad de vida

Systemic lupus erythematosus: mortality and survival in Argentina. A multicenter study.

OBJECTIVE: To analyze the factors associated with mortality, survival and causes of death in patients with systemic lupus erythematosus (SLE) in Argentina. PATIENTS AND METHOD: A series of 366 patients with SLE (45 men and 321 women), mean age 29 y (range 11-70 y) and mean disease duration 6 y, was evaluated from 1990 to 1998. A total of 57 clinical, serological and therapeutic variables were studied. RESULTS: Five- and 10-year survival was 91% and 85% respectively. Forty four patients died (12%): 54% due to sepsis and 32% due to active SLE. Mortality risk factors included heart involvement CRR 3.82), hyperlipidemia (RR 2.72), renal damage (RR 2. 62), infections (RR 2.44), lung disease (RR 2.20) and myositis (RR 2. 07). High-dose prednisone (RR 3.4) or cyclophosphamide (RR 9.19) treatments increased the risk of sepsis (P=0.003) as a cause of death. However, corticosteroids, antimalarial agents and accumulated cyclophosphamide doses proved to be protective factors in overall mortality figures (RR <1). CONCLUSIONS: The main risk factors of death in SLE were heart involvement, hyperlipidemia and renal damage. Treatment with steroids, antimalarial agents and cyclophosphamide improved survival. High-dose corticosteroids and cyclophosphamide were associated with sepsis as a cause of death.

Site-dependent bone mineral density response to oral pamidronate and calcium in postmenopausal osteoporosis: a preliminary report.

Radiologically diagnosed postmenopausal osteoporotic patients with at least one nontraumatic vertebral flattening were treated for one year with either oral pamidronate (APD), 300 mg/day plus calcium 1 g/day (n=39) or with calcium alone (n=21). Bone mineral density (BMD) was assessed in lumbar spine, femoral neck, trochanter and Ward's triangle by dual X-ray absorptiometry in order to determine the number of responders at each site. As no densitometric inclusion criteria were stipulated, wide inter- and intra-individual variations in both regional basal BMD and response to therapy were found. However, the APD-treated group showed significant mean BMD increases in spine (+3.1%; p < 0.001) and femoral neck (+3.2%; p < 0.002) versus basal level, whereas the calcium only group failed to exhibit significant differences. The entire 60-strong population was then split into two groups, according to whether individual BMD content was greater or less than the mean basal value for each skeletal site evaluated. For either treatment, subpopulations with lower basal BMD tended to achieve greater bone gain, though statistically significant differences were only disclosed at trochanter (p < 0.004) with APD and at femoral neck (p < 0.002) in the calcium only group. Globally speaking, increases in BMD were observed in 60-80% of patients receiving either treatment - who were thus defined as responders - at each particular skeletal area assessed. However, when only skeletal areas with low basal BMD were considered, the number of responders reached 60-100%. Responsive sites varied among patients: out of 56 cases, 9 (24%) on APD and 6 (32%) on calcium alone responded in all 4 areas evaluated, while a single case on the latter treatment failed to show BMD response at any site. Overall, the mean number of responsive sites was 2.7. Odds ratios were calculated considering treatment modality and high or low basal BMD as parameters, but no significant differences were found in the number of responders. It may be concluded that APD induces moderate lumbar and femoral neck bone mass gain in severe postmenopausal osteoporosis, whereas calcium alone leads to non significant variations, both findings being in agreement with reported data. Therefore, evaluated APD doses enhance mineralization in responsive sites alone, but fail to increase the total number of responders. Interestingly, responsive sites seem to be those relitively spared by the course of the disease.

Serum kinetics, bioavailability and bone scanning of 99mTc-labelled sodium olpadronate in patients with different rates of bone turnover.

The activity of olpadronate labelled with technetium-99m(99mTc) was monitored in plasma and urine samples after single oral (925 MBq 99mTc/10 mg, coadministered with 50 mg cold drug) and intravenous (925 MBq 99mTc/5 mg) administrations to two groups of patients with different rates of bone turnover. The first group comprised high bone turnover (HBTO) patients suffering from Paget's bone disease; the second group comprised patients with normal to low bone turnover (NBTO) having the diagnosis of rheumatoid arthritis and secondary osteoporosis. Kinetic variables were correlated with anthropomorphometric variables, biological markers of bone metabolism and plasma proteins. Data were also obtained after repeatedly dosing the HBTO patients. Additionally, Paget's bone and healthy bone (PB/HB) uptake before and after low-dose oral treatment were assessed by means of scintigraphy. Results showed that most of the kinetic variables did not differ between the two groups of patients, except for a greater Vss and smaller blood area under the curve AUC in the patients with HBTO. After a repeated-dose administration period, the blood AUC activity and Whole Body Retention (WBR) of the HBTO patients tended to be similar to those of the NBTO patients. In both groups, after oral dosing, the Cmax was 20 times lower than the C0.5 after i.v. injection, and the oral bioavailability ranged from 3% to 4%. Finally, the plasma t1/2 beta ranged from 9 to 14 h. Correlation coefficients were obtained from multiple regression analysis; kinetic variables showed very low correlations with anthropomorphometric measurements. In contrast the Vss and WBR were significantly correlated with serum alkaline phosphatase levels and the Vss also with urine hydroxyproline levels. Plasma protein concentration was also correlated with excretion parameters such as CLP and plasma t1/2 beta after an oral dose. Scintigraphic studies in the HBTO group allowed bone selectivity to be seen through skeletal drug uptake. The 15 Pagetic lesions analysed in the HBTO group showed a decrease in PB/HB ratio from 3.8 in the basal study to 2.7 after olpadronate administration for 30 days at the rate of 50 mg/day. In conclusion, the kinetic profile of 99mTc-labelled olpadronate, mainly AUC and WBR, showed a dependence upon bone metabolism and seemed unrelated to body size variables. HBTO patients showed a lower blood AUC but a higher Vss. Both variables may have been reflecting the fact that the drug binds selectively with calcified tissues and, in turn, with the target compartment. Scintigraphy confirmed the labelled-compound bone selectivity as a desirable feature for a bone-scanning agent.

Effect of low doses of deflazacort vs prednisone on bone mineral content in premenopausal rheumatoid arthritis.

Longterm administration of steroid drugs, particularly prednisone, is known to induce osteoporosis, as well as bone growth inhibition and delayed fracture union. Recently deflazacort, an oxazoline prednisone derivative, has been developed to reduce such deleterious effects. We carried out a comparative study in premenopausal patients with rheumatoid arthritis (RA). Sixteen cases whose mean age was 36.5 years and mean disease duration 29 months, all fulfilling ARA criteria, were evaluated in a randomized, double blind trial. Visually identical deflazacort or prednisone capsules were given and patients were instructed to maintain an adequate calcium intake. Laboratory tests focussed on bone mineral density in lumbar spine, femoral neck and Ward's triangle and whole body mineral content. Differences between baseline and 12-month values were processed statistically. Persistent synovitis control proved similar for both drugs and features suggestive of Cushing's syndrome were only found in the prednisone group. The difference in whole body bone mineral content between the deflazacort and prednisone groups just failed to reach statistical significance. In the deflazacort group, the difference between the nonsignificant bone mineral density increase at the femoral neck and the significant decrease in the prednisone group proved statistically significant. Ward's triangle was the most sensitive area to bone mineral density changes in patients receiving prednisone, with a highly significant intergroup difference (p < 0.01). We believe this is the first study on corticosteroid induced osteoporosis, as evaluated by whole body mineral content measurements in premenopausal patients with short term RA, showing that deflazacort is a promising alternative in cases severe enough to require steroid therapy.