Space-time Bayesian analysis of the environmental impact of a dismissing nuclear power plant.

The assessment of the radiological impact of decommissioning activities at a nuclear power plant requires a detailed analysis of the distribution of radionuclides in the environment surrounding it. The present work concerns data of three campaigns carried out during the last twenty years in the plain of the Garigliano river surrounding the Garigliano Nuclear Power Plant (GNPP), which is located in Southern Italy and shut down in 1979. Moreover, some data from surveys held in the eighties, across the Chernobyl accident, have been taken in account. The results for the soil samples, in particular for 137Cs and 236U specific activity, were analyzed for their extension in space and in time. Some of the problems related to the classical analysis of environmental radiological data (non-normal distribution of the values, small number of sample points, multiple comparison and presence of values lesser than the minimum detectable activity) have been overcome with the use of Bayesian methods. The scope of the paper is threefold: (1) to introduce the data of the last campaign held in the Garigliano plain; (2) to insert these data in a larger spatio-temporal frame; (3) to show how the Bayesian approach can be applied to radiological environmental surveys, stressing out its advantages over other approaches, using the data of the campaigns. The results show that radionuclides specific activity in soil is dominated by the natural sources with the contribution of the atmospheric fallout. A detailed study was performed on the 137Cs data to evaluate both their statistical distribution and the trend over the space and the time. It results that (i) no new contribution there was in the last decades, (ii) specific activity values of the area surrounding the GNPP are consistent with those obtained in other farther areas, (iii) the effective depletion half-life factor for 137Cs is much lower than the half-life of the radionuclide.

Reproductive and genetic consequences of extreme isolation in Salix herbacea L. at the rear edge of its distribution.

BACKGROUND AND AIMS: At the rear edge of the distribution of species, extreme isolation and small population size influence the genetic diversity and differentiation of plant populations. This may be particularly true for Arctic-alpine species in mid-latitude mountains, but exactly how peripherality has shaped their genetic and reproductive characteristics is poorly investigated. The present study, focused on Salix herbacea, aims at providing new insights into the causes behind ongoing demographic dynamics and their consequences for peripheral populations of Arctic-alpine species. METHODS: We performed a whole-population, highly detailed sampling of the only two S. herbacea populations in the northern Apennines, comparing their clonal and genetic diversity, sex ratio and spatial genetic structure with a reference population from the Alps. After inspecting ~1800 grid intersections in the three populations, 563 ramets were genotyped at 11 nuclear microsatellite markers (nSSRs). Past demography and mating patterns of Apennine populations were investigated to elucidate the possible causes of altered reproductive dynamics. KEY RESULTS: Apennine populations, which experienced a Holocene bottleneck and are highly differentiated (FST = 0.15), had lower clonal and genetic diversity compared with the alpine population (RMLG = 1 and HE = 0.71), with the smaller population exhibiting the lowest diversity (RMLG = 0.03 and HE = 0.24). An unbalanced sex ratio was found in the larger (63 F:37 M) and the smaller (99 F:1 M) Apennine population. Both were characterized by the presence of extremely large clones (up to 2500 m2), which, however, did not play a dominant role in local reproductive dynamics. CONCLUSIONS: Under conditions of extreme isolation and progressive size reduction, S. herbacea has experienced an alteration of genetic characteristics produced by the prevalence of clonal growth over sexual reproduction. However, our results showed that the larger Apennine population has maintained levels of sexual reproduction enough to counteract a dramatic loss of genetic and clonal diversity.

AMS assessment of U-contamination of structural materials of the Garigliano NPP under decommissioning.

The assessment of the radiological impact of decommissioning activities at a Nuclear Power Plant requires a detailed mapping of the distribution of radionuclides both in the environment surrounding the NPP and in its structural material. The detection of long-lived actinide isotopes and possibly the identification of their origin is particularly interesting and valuable if ultrasensitive measurement of the relative abundance of U isotopes is performed via Accelerator Mass Spectrometry (AMS). In this paper we present an investigation carried out on the structural materials of the Garigliano NPP aiming to determine the abundance of 235,236,238U in the various compartments of the plant buildings under decommissioning. Since the expected values both for isotopic ratios and total U concentrations range over different orders of magnitude, we have developed a novel methodology for the measurement of 234,235U/238U isotopic ratios in low U concentration samples. This allowed a systematic investigation of the distribution of all U isotopes in concrete and metal matrices of the NPP. The behavior of 235,236U/238U isotopic ratios in the different compartments of the NPP is discussed. The correlation of these ratios with 60Co and 137Cs specific activities is also studied to show a different behavior for concrete and metal samples. These data represent a very valuable information to direct the decommissioning procedures under course.

Environmentally induced transgenerational changes in seed longevity: maternal and genetic influence.

BACKGROUND AND AIMS: Seed longevity, a fundamental plant trait for ex situ conservation and persistence in the soil of many species, varies across populations and generations that experience different climates. This study investigates the extent to which differences in seed longevity are due to genetic differences and/or modified by adaptive responses to environmental changes. METHODS: Seeds of two wild populations of Silene vulgaris from alpine (wA) and lowland (wL) locations and seeds originating from their cultivation in a lowland common garden for two generations (cA1, cL1, cA2 and cL2) were exposed to controlled ageing at 45 °C, 60 % relative humidity and regularly sampled for germination and relative mRNA quantification (SvHSP17.4 and SvNRPD12). KEY RESULTS: The parental plant growth environment affected the longevity of seeds with high plasticity. Seeds of wL were significantly longer lived than those of wA. However, when alpine plants were grown in the common garden, longevity doubled for the first generation of seeds produced (cA1). Conversely, longevity was similar in all lowland seed lots and did not increase in the second generation of seeds produced from alpine plants grown in the common garden (cA2). Analysis of parental effects on mRNA seed provisioning indicated that the accumulation of gene transcripts involved in tolerance to heat stress was highest in wL, cL1 and cL2, followed by cA1, cA2 and wA. CONCLUSIONS: Seed longevity has a genetic basis, but may show strong adaptive responses, which are associated with differential accumulation of mRNA via parental effects. Adaptive adjustments of seed longevity due to transgenerational plasticity may play a fundamental role in the survival and persistence of the species in the face of future environmental challenges. The results suggest that regeneration location may have important implications for the conservation of alpine plants held in seed banks.

Intraosseous hemangioma of the clivus: a case report and review of the literature.

Intraosseous hemangiomas are benign vascular tumors that are encountered most commonly in vertebrae and rarely in the skull. When presenting in the skull, they are commonly found in the calvarium in frontal and parietal bones and seldom in the skull base. We encountered a patient with an incidental finding on magnetic resonance imaging (MRI) of an enhancing lesion in the clivus. Here we report an unusual location of a clival intraosseous hemangioma. A 62 year old man worked up for carpal tunnel syndrome had imaging of his cervical spine that revealed an enhancing clival lesion, which extended into the left occipital condyle. Endoscopic endonasal biopsy was performed on the abnormality revealing a capillary hemangioma. Patient tolerated the biopsy well and no further surgical intervention is indicated at this time. Patient will be followed at six month intervals. Primary intraosseus hemangiomas of the skull are extremely rare and usually occur in the calvarium. This is one of the few reported case of an intraosseus hemangioma in the clivus. We present this case in part because it is unusual, but more importantly, with the wider use of MRI, it is likely that these lesions will be discovered more frequently, and conceivably confused for more dangerous lesions.

The first use of (236)U in the general environment and near a shutdown nuclear power plant.

We present a first effort to investigate (236)U in the environment near a shutdown nuclear power plant far away from highly contaminated sites, by using accelerator mass spectrometry. The detection limit of about 1pg (236)U allowed us to identify a minimal increase of the (236)U/(238)U isotopic ratio correlated to a peak of (137)Cs in river sediments downstream of the nuclear power plant, and to detect anthropogenic (236)U also upstream, where it is probably not related to the power plant but to global fallout. The (236)U content shoved variations of the (236)U/(238)U isotopic ratio in relation to the chemical-physical characteristics of the sediments. This demonstrates the potential of (236)U as an environmental tracer, and as an indicator for releases from nuclear facilities.

[New evidences on spa therapy in fibromyalgia]. / Nuove acquisizioni sulla terapia termale nella fibromialgia.

Spa therapy is one of the most commonly used non-pharmacological approaches for many rheumatic diseases. In Fibromyalgia Syndrome (FS) it may be useful for the chronic widespread musculoskeletal pain. Because of the unknown aetiology and the not clear understood pathogenesis, there is no standard therapy regimen for FS. Also the mechanisms of action of spa therapy are not completely known, but most probably the benefits could be derived from mechanical, physical and chemical factors. Muscle tone and pain intensity can be positively influenced by mud packs and thermal baths. The review of international data from 2000 to 2007 confirms that spa therapy should be a valid tool in the multidisciplinary approach of the Primary FS.

[Frequency of diagnosis and clinic presentation of glomerulopathies in Uruguay]. / Frecuencia de diagnóstico y de presentación clínica de las glomerulopatías en el Uruguay.

UNLABELLED: The Uruguayan Registry of Glomerulopathies began its activity in 1974 and since 1985 is a national registry. The aim of this report is to analyze the incidence and the variations in frequencies of the histological diagnosis and clinical presentation during the 1980-2003 period. PATIENTS AND METHODS: From the 2,058 patients with renal biopsy in the whole period, we analyzed the histological diagnosis and the following data has been collected when the patients were registered: age, gender, clinical syndrome, proteinuria, hematuria, serum creatinine, blood pressure and time from the first symptom. Four periods of registry entry were considered: 1980-1989, 1990-1994, 1995-1999 and 2000-2003. Chi-square and Student test for independent samples were used to evaluate the differences among the variables frequencies in the four periods. RESULTS: The incidence of registered glomerulopathies per million population (pmp) increased from 13 (1980-1989) to 43 (2000-2003). In the 2000-2003 period, the incidences pmp were: primary glomerulopathy (PG), 25.3 and secondary glomerulopathy, 14.2. The highest incidences pmp were: focal and segmental glomeruloesclerosis (FSGS) 6.4; vasculitis 5.4; lupus nephritis 4.6; minimal change disease (MCD) 4.6; IgA nephropathy (IgAN) 4.5; and membranous nephropathy (MN) 4.0. The most frequent PG were the FSGS (29.3%) and the MCID (19.6%). The FSGS frequency decreased from 36.3% in 1995-1999 to 19.1% in 2000-2003. The IgAN frequency increased from 5.2% in 1980-1989 to 17.5% in 2000-2003. Nephrotic syndrome was the most frequent clinical presentation; its frequency was over 30% in the four periods. Asymptomatic urinary abnormality frequency increased from 14.0% in 1980-1989 to 22.7% in 2000-2003. The frequency of serum creatinine under 1.5 mg/dl, increased from 42.2% in 1980-1989 to 67.2% in 2000-2003 (p = 0.001). The frequency of serum creatinine over 6.0 mg/dl, decreased from 19.3% in 1990-1994 to 7.2% in 2000-2003. The percentage of patients referred since the first month of the apparent onset of the disease increased from 24.0% in 1980-1989 to 40.1% in 2000-2003 (p < 0.001). CONCLUSIONS: In Uruguay, the incidence of glomerulopathies with histological diagnosis has increased and the frequency of the different types has changed. Several indicators seem to show that the reference of patients to the nephrologist tended to be earlier in the last years.

Frecuencia de diagnóstico y de presentación clínica de las glomerulopatías en el Uruguay / Frequency of diagnosis and clinic presentation of glomerulopathies in Uruguay

El Registro Uruguayo de Glomerulopatías ha registrado en el período 1980-2003,datos de 2.058 pacientes con biopsia renal. El objetivo del presente informe es analizarla incidencia y las variaciones de la frecuencia de los diagnósticos y de la presentaciónclínica en dichos pacientes.Pacientes y métodos: En los 2.058 pacientes registrados se analizaron el diagnósticoy los siguientes datos correspondientes a la fecha de la primera biopsia renal(BR): edad, sexo, síndrome clínico, proteinuria, hematuria, creatinininemia, presiónarterial y tiempo de evolución desde el primer síntoma. Se consideraron cuatro períodos:1980-1989, 1990-1994, 1995-1999 y 2000-2003 y las diferencias de frecuenciasde las distintas variables se valoraron con chi-cuadrado y con test de Studentpara muestras independientes.Resultados: La incidencia de las glomerulopatías registradas por millón de población(pmp) aumentó de 13 (1980-1989) a 43 (2000-2003). En el período 2000-2003 las incidencias pmp fueron: glomerulopatía primaria (GP) 25,3 y glomerulopatíasecundaria (GS) 14,2. Las mayores incidencias pmp fueron: esclero-hialinosisfocal y segmentaria (EHFS) 6,4, vasculitis 5,4, lupus eritematoso sistémico 4,6,lesión glomerular mínima 4,6, nefropatía a IgA (NIgA) 4,5 y glomerulopatía membranosa4,0.Las GP más frecuentes fueron la EHFS (29,3%) y la LGM (19,6%). La frecuenciade la EHFS descendió de 36,3% en 1995-1999 a 27,1% en 2000-2003 y la de laNIgA aumentó de 5,2% en 1980-1989 a 17,5% en 2000-2003.La presentación clínica más frecuente fue el síndrome nefrótico, mayor de 30%en todos los períodos. La frecuencia de la alteración urinaria asintomática aumentóde 14,0% en 1980-1989 a 22,7% en 2000-2003. La frecuencia de creatinina séricamenor de 1,5 mg/dl aumentó de 42,2% en 1980-1989 a 67,2% en 2000-2003 (p =0,001). El porcentaje de pacientes referidos dentro del primer mes de evoluciónaumentó de 24,0% en 1980-1989 a 40,1% en 2000-2003.Conclusiones: La incidencia de glomerulopatías con BR en el Uruguay ha aumentadomodificándose algunas frecuencias. Algunos indicadores muestran que lospacientes son referidos más tempranamente al nefrólogo en los últimos años

The Uruguayan Registry of Glomerulopathies began its activity in 1974 and since1985 is a national registry. The aim of this report is to analyze the incidence and thevariations in frequencies of the histological diagnosis and clinical presentation duringthe 1980-2003 period.Patients and methods: From the 2,058 patients with renal biopsy in the wholeperiod, we analyzed the histological diagnosis and the following data has been collectedwhen the patients were registered: age, gender, clinical syndrome, proteinuria,hematuria, serum creatinine, blood pressure and time from the first symptom. Fourperiods of registry entry were considered: 1980-1989, 1990-1994, 1995-1999 and2000-2003. Chi-square and Student test for independent samples were used to evaluatethe differences among the variables frequencies in the four periods.Results: The incidence of registered glomerulopathies per million population (pmp)increased from 13 (1980-1989) to 43 (2000-2003). In the 2000-2003 period, the incidencespmp were: primary glomerulopathy (PG), 25.3 and secondary glomerulopathy,14.2. The highest incidences pmp were: focal and segmental glomeruloesclerosis(FSGS) 6.4; vasculitis 5.4; lupus nephritis 4.6; minimal change disease (MCD) 4.6;IgA nephropathy (lgAN) 4.5; and membranous nephropathy (MN) 4.0.The most frequent PG were the FSGS (29.3%) and the MCID (19.6%). The FSGSfrequency decreased from 36.3% in 1995-1999 to 19.1% in 2000-2003. The lgANfrequency increased from 5.2% in 1980-1989 to 17.5% in 2000-2003.Nephrotic syndrome was the most frequent clinical presentation; its frequency wasover 30% in the four periods.Asymptomatic urinary abnormality frequency increasedfrom 14.0% in 1980-1989 to 22.7% in 2000-2003. The frequency of serum creatinineunder 1.5 mgldi, increased from 42.2% in 1980-1989 to 67.2% in 2000-2003 (p =0.001). The frequency of serum creatinine over 6.0 mgldl, decreased from 19.3% in1990-1994 to 7.2% in 2000-2003.The percentage of patients referred since the first month of the apparent onset ofthe disease increased from 24.0% in 1980-1989 to 40.1% in 2000-2003 (p < 0.001).Conclusions: In Uruguay, the incidence of glomerulopathies with histological diagnosishas increased and the frequency of the different types has changed. Several indicatorsseem to show that the reference of patients to the nephrologist tended to beearlier in the last years

[Ischemic cadiopathy in patients undergoing chronic hemodialysis]. / Cardiopatía isquémica en pacientes en hemodiálisis crónica.

UNLABELLED: We report a retrospective study of patients on chronic hemodialysis in whom a diagnosis of ischemic heart disease had been established. We compared the findings on coronary cineangiography and the treatment (medical only, surgical revascularisation [CABG] and percutaneous transluminal coronary angioplasty [PTCA]) with the early and late evolution. From a population of 2,287 patients on chronic hemodialysis treatment during the 5 year period 1994-1999, 83 patients who underwent coronary cineangiography after starting dialysis were selected. Their mean age was 63 +/- 9.4 (39-80) and the mean time on hemodialysis was 6 years (6 months-19 years). RESULTS: 65 patients (78%) had severe coronary lesions, 40% of whom had three vessel disease. 14 patients had medical treatment only (group 1), 23 had CABG (group 2) and 28 PTCA (group 3). Mortality within 30 days of intervention was 13% in group 2 and 21.4% in group 3. Global survival at two years was 82% in group 2 and 69% in group 3. Survival without angina at 6 and 24 months were 69% and 46% in group 2 and 55% and 22% in group 3 respectively. Survival without acute myocardial infarction at 6 and 24 months was 95% and 95% in group 2 and 89% and 64% in group 3. Data analysis using Cox proportional risk model showed that PTCA posed a higher risk of angina and death than CABG. CONCLUSION: Surgery yielded better early and later results than angioplasty even in those patients with severe coronary artery disease.

Cardiopatía isquémica en pacientes en hemodiálisis crónica / Ischaemic heart disease in patients on chronic hemodialysis

El objetivo de este estudio es analizar en forma retrospectiva, en un grupo de pacientes en hemodiálisis crónica con diagnóstico presuntivo de cardiopatía isquémica, los hallazgos de la cineangiocoronariografía (CACG) y la evolución inmediata y alejada de acuerdo al tratamiento instituido: cirugía de revascularización coronaria (by-pass) y angiosplatia transluminal percutánea (APT). De un total de 2.287 pacientes en hemodiálisis en un período de 5 años (1994-1999) se analizaron 83 pacientes a los que se realizó cineangiocoronariografía por presentar sintomatología compatible con cardiopatía isquémica, después de comenzado el tratamiento dialítico. La edad media de los pacientes fue 63 ñ 9,4 (39-80) y el tiempo medio en hemodiálisis de 6 años (6 meses-19 años).Resultados: 65 pacientes (78 por ciento) tenían lesiones coronarias severas, 40 por ciento con lesión en 3 vasos. A 23 pacientes se les realizó by-pass aortocoronario con circulación extracorpórea (grupo 1) y a 28 APT (grupo 2). La mortalidad quirúrgica (30 días) fue de 13 por ciento para el grupo 1 y 21,4 por ciento para el grupo 2. La sobrevida global a los 2 años fue de 82 por ciento para el grupo 1 y de 69 por ciento para el grupo 2. La sobrevida libre de angor a 6 y 24 meses fue de 69 por ciento y 46 por ciento para el grupo 1 y 55 por ciento y 22 por ciento para grupo 2. La sobrevida libre de infarto agudo de miocardio fue 95 por ciento para el grupo 1 a los 6 y 24 meses y 89 por ciento y 64 por ciento respectivamente en el grupo 2. El análisis de sobrevida con el modelo de riesgo proporcional de Cox, mostró mayor riesgo de angor y muerte en los pacientes tratados con angioplastia que en los pacientes tratados con cirugía de revascularización coronaria. Conclusiones: En estos pacientes la cirugía tuvo mejor evolución inmediata y alejada que la angioplastia aún en pacientes con cardiopatía severa, por lo que lo consideramos el método terapéutico de elección. (AU)

The role of imaging techniques in the study of renal osteodystrophy.

Secondary hyperparathyroidism is the most common form of this condition found in renal osteodystrophy. Enlarged parathyroid glands are the rule in severe secondary hyperparathyroidism because of a marked parathyroid cell hyperplasia. For several years, ultrasonography, computed tomography, and scintigraphy with thallium201-technetium99 have been useful techniques to identify enlarged parathyroid glands. More recently, ultrasonography with color Doppler and parathyroid scintigraphy with 99mTc-sestamibi have proved to be useful as well. Computed tomography and magnetic resonance imaging can be used, but their sensitivity is similar to ultrasonography and they cost more. Ultrasonography with color Doppler signals has made it possible to evaluate tissue blood supply, an aid in differentiating thyroid nodules. The degree of blood supply may be an indirect index of cell proliferation when there is neither necrosis nor calcification, because an enriched blood supply suggests vigorous cell growth and nodule formation. Scintigraphy with 99mTc-sestamibi allows identification of ectopic glands, including those located in the mediastinum, and also provides functional information. Sestamibi uptake is closely related to both parathyroid hormone levels and to the histological type of parathyroid proliferation. In our experience, when hyperparathyroidism is not too severe, 2 weeks after 2 g of calcitriol is administered intravenously, these scintigraphic images can disappear (inhibition test). This suggests a possibility for a medical treatment. By contrast, when parathyroid hormone levels are higher, parathyroid sestamibi uptake remained unchanged. In such patients, parathyroidectomy or ethanol injection should be the best treatment. These glands would correspond to the most actively functioning glands; they would have a lesser expression of vitamin D receptors, rendering them refractory to medical treatment with calcitriol.

[(99m)Tc]-sestamibi parathyroid scintigraphy in chronic haemodialysis patients: static and dynamic explorations.

BACKGROUND: The place of parathyroid gland imaging by [(99m)Tc](technetium)-sestamibi scintigraphy in uraemic patients with secondary hyperparathyroidism remains a matter of debate. The purpose of the present study was (i) to assess its value with respect to plasma intact parathyroid hormone (iPTH) levels and to surgical parathyroidectomy (PTx), and (ii) to explore the possibility of suppressing parathyroid [(99m)Tc]-sestamibi uptake by calcitriol. METHODS: In a first cross-sectional, static study 52 chronic haemodialysis (HD) patients with plasma iPTH levels between 14 and 2791 pg/ml (normal, 10-65 pg/ml) had a [(99m)Tc]-sestamibi scan, and 21 of them underwent surgical PTx. In a second longitudinal, dynamic study 14 chronic HD patients with advanced secondary hyperparathyroidism received short-term calcitriol treatment in an attempt to suppress [(99m)Tc]-sestamibi imaging of parathyroid glands. Calcitriol was given intravenously for 2 weeks, 2 microg after each haemodialysis session. Scintigraphy was carried out before and at the end of this inhibition test. RESULTS: [(99m)Tc]-Sestamibi scan led to imaging of one or more (maximum three) parathyroid glands in most, but not all, HD patients with plasma iPTH values >600 pg/ml. Based on surgical findings, overall sensitivity of [(99m)Tc]-sestamibi scan in correctly locating parathyroid glands was only 50%, whereas specificity was 100%. In contrast, its sensitivity was 100% in locating single glands in the subgroup of five patients with recurrent hyperparathyroidism. The calcitriol inhibition test showed suppression of [(99m)Tc]-sestamibi uptake by at least one parathyroid gland in eight patients (57%), with complete suppression in five of them (36%). Basal plasma iPTH or decrease of plasma iPTH in response to calcitriol was not predictive of suppressible [(99m)Tc]-sestamibi uptake in the individual case, although mean iPTH was markedly higher in patients with non-suppressible parathyroid glands. CONCLUSION: Because of its relatively low sensitivity the [(99m)Tc]-sestamibi scan is of limited help in the exploration of uraemic patients with severe secondary hyperparathyroidism before a first surgical PTx. However, it is very useful in locating the remaining parathyroid gland(s) in case of reoperation. The novel calcitriol inhibition test of [(99m)Tc]-sestamibi uptake could help to better distinguish parathyroid glands with non-suppressible, autonomous activity from glands whose activity might be amenable to long-term suppression.

Multicenter randomized trial comparing meropenem (1.5 g daily) and imipenem/cilastatin (2 g daily) in the hospital treatment of community-acquired pneumonia.

An open, multicenter study with 144 patients, aged between 18 and 94 years, was performed to compare the efficacy and safety of meropenem with imipenem/cilastatin in the hospital treatment of community-acquired pneumonia. Patients were randomized to receive either intravenous meropenem (500 mg every 8 h) or intravenous imipenem/cilastatin (1,000 mg every 12 h). The primary end point was considered to be clinical efficacy and the secondary end points were bacteriological response and safety assessment. At the end of therapy, cure or improvement in signs and symptoms as a satisfactory clinical response was observed in 57 of 64 (89.1%) meropenem-treated patients and in 60 of 66 (90.9%) imipenem/cilastatin patients. The mean duration of treatment was 10 days for meropenem and 9.7 days for imipenem/cilastatin. In patients who were followed up for weeks 2-4, the response was satisfactory (100%) for both treatments. A satisfactory bacteriological response, defined as either presumed or confirmed eradication of all pathogens, was found in eight patients who had received meropenem and in 14 patients who had received imipenem/cilastatin. Response was considered satisfactory in 100% of the meropenem group and in 92.9% of the imipenem/cilastatin group and at follow-up, it was 100% for both treatments. Drug-related adverse events were reported in three (4.2%) meropenem-treated patients and in eight (11.0%) imipenem/cilastatin-treated patients. None of these events was classified as serious. The results of this study show that the clinical and bacteriological efficacy and tolerability of meropenem (500 mg every 8 h) are similar to that of imipenem/cilastatin (1,000 mg every 12 h) in the hospital treatment of community-acquired pneumonia.

Are there any differences in the parathyroid response in the different types of renal osteodystrophy?

With the purpose of studying the curve of parathyroid response to variations of serum calcium during dialysis, we studied 20 patients on haemodialysis: 10 women and 10 men, with different forms of bone disease diagnosed by bone biopsy (adynamic bone disease, mild hyperparathyroidism, severe hyperparathyroidism). In all patients, we performed parathyroid stimulation by 4 h dialysis with 1 mEq/l of Ca2+ in the dialysate, and an inhibition test in another dialysis session with 4 mEq/l of Ca2+, with a 48 h interval. Ca2+ and intact parathyroid hormone (iPTH) were measured prior to dialysis and every hour subsequently, to obtain a Ca2+-iPTH for each patient. The analysis of the curves was made using Brown's four-parameter model. Stimulation and inhibition levels were similar in all groups, but basal iPTH and the response profiles obtained varied in the different histological groups. Basal, maximal and minimal iPTH were lower in adynamic forms than in the other two groups (P<0.04), and basal calcium was higher than basal calcium of severe hyperparathyroidism, expressing a basal inhibition status. In severe hyperparathyroidism, basal calcium was lower than the set-point, showing a permanent stimulation, and the slope was higher than in other groups, showing more sensitivity to serum calcium variations. The set-point of severe hyperparathyroidism was significantly higher than the set-point of mild and adynamic forms. In conclusion, the functional parathyroid study showed a different response in the different forms of renal osteodystrophy.

Can we use 99mTc-MIBI in functional studies of the parathyroid gland?

The usefulness of technetium-99m-sestamibi (99mTc-MIBI) in patients with secondary hyperparathyroidism on haemodialysis was assessed. We studied 33 patients with parathyroid scintigraphy with i.v. (99mTc-MIBI). Static images in a scintillation camera were taken at 15 and 120 min after the injection. With P x Ca<80, we performed an inhibition test with calcitriol i.v. 2 microg, three times a week, for 2 weeks. The MIBI study and assessment of intact parathyroid hormone (iPTH) were performed before (baseline study) and after inhibition. A 'focal positive study' corresponded to one or more areas of abnormal hypercaptation in relation to surrounding thyroid tissue seen in early images and persisting in later images, and a 'negative study' did not correspond to the previous image. In the baseline study, iPTH in the positive MIBI group was significantly greater than in the negative group. Eight positive MIBI patients had a bone biopsy; six corresponded to severe osteitis fibrosa and two to mild osteitis fibrosa. In the negative MIBI group, four of the six patients who had bone biopsy had mild forms of osteitis fibrosa (Fisher=0.03); the other two had low turnover forms. A positive inhibition test was defined when the basal uptake disappeared after calcitriol administration. In these patients, we observed a significant decrease of iPTH, not observed in the negative inhibition test. In 10 patients who had been parathyroidectomized, those with alpha positive basal MIBI result had a nodular parathyroid hyperplasia. We conclude that a scintigraphic parathyroid study with 99mTc-MIBI showed a good correlation with functional parathyroid status. With the same inhibition test, only some glands were inhibited, suggesting that this could be the expression of different vitamin D receptor densities in inhibited glands and/or a different kind of proliferation in those glands. This test would be of value in functional studies when a therapeutic decision must be made.

Bronchodilation and beta 2-selectivity of broxaterol in asthmatics: a crossover, single-blind, terbutaline- and placebo-controlled study.

To investigate the beta 2-receptor selectivity of a new beta 2-adrenoceptor agonist, broxaterol, we compared the respiratory and cardiovascular effects of this compound with those of terbutaline and placebo. Twelve asthmatic patients were evaluated in a randomized, single blind, crossover study. A single dose of each study treatment (broxaterol 400 micrograms and terbutaline 500 micrograms was administered with metered dose inhalers. Measurements of lung function (vital capacity, forced expiratory volume in one second, airway resistance and specific airway conductance), heart rate and systolic/diastolic blood pressure were performed before and at 15, 30, 60, 120, 240 and 360 min after each study treatment. No significant difference was observed between broxaterol and terbutaline in VC, FEV1 and Raw changes, although a greater and significant increase in sGaw was found only with broxaterol. Significant increases in heart rate and systolic blood pressure were observed only with terbutaline. The results of this study suggest that broxaterol can promote a greater bronchodilator effect with less cardiovascular side effects than terbutaline, probably through a greater beta 2-receptor selectivity.

Negligible metabolic effects of long-term oral treatment with a new beta 2-agonist: broxaterol.

Drugs that stimulate adrenergic receptors are expected to affect glucose and lipid metabolism. Therefore, it was deemed to be of interest to assess whether the new selective beta 2-adrenoceptor agonist, broxaterol, exerts any metabolic effect. Broxaterol has been evaluated in 21 patients, 18 men and 3 women, aged 34 to 80 years, with a diagnosis of reversible obstructive airways disease. Broxaterol was administered orally at doses of 0.5 mg thrice daily for 1-12 months, according to an open design. In addition to metabolic parameters (plasma glucose, insulin, high and low density lipoprotein-cholesterol, triglycerides, free fatty acids, glycerol, sodium, potassium), arterial pH, partial arterial oxygen and carbon dioxide pressure, lung function tests--forced expiratory volume in one second (FEV1), maximum mid-expiratory flow (MMEF75-25) and specific airways conductance (SGaw)--heart rate and blood pressure were assessed at baseline and after 1, 2, 3, 4, 5, 6, 9, 12 months of treatment. No statistically significant change from baseline was observed in the levels of plasma glucose, cholesterol, triglycerides, or free fatty acids. Plasma levels of insulin, glycerol and sodium only increased in the first three months of treatment; a slight hypokalaemia was also observed during the same period. The bronchodilation (significant increase in FEV1, MMEF75-25, SGaw) was maintained throughout the study; no hospital admission was necessary. Tremor, palpitations and restlessness were reported in six patients; no significant changes in heart rate and blood pressure were observed. The data suggest that the metabolic effects of long-term treatment with oral broxaterol can be considered as very negligible.