Temporal and spatial dynamics of arthropod groups in terrestrial subsurface habitats in central Portugal.

The mesovoid shallow substratum (MSS) can act as a climatic refuge for invertebrates, as a biogeographic corridor to deeper substrates or as a permanent habitat for some species. This study characterizes the seasonal invertebrate diversity and abundance of MSS ecosystems in central Portugal focusing on Diplopoda, Diplura, Orthoptera and Coleoptera during one year. Sampling was performed with standard MSS pitfalls in scree slopes (colluvial MSS) of karst areas and environmental parameters (temperature, pH, conductivity, water content, organic carbon, nitrate, phosphate and ammonium) were quantified. Our results show that winter was the season with the highest arthropod abundance and that the MSS acts as a permanent habitat for chordeumatidan millipedes and as a climatic refuge for orthopterans and most beetles. All Diplura collected belong to a single species known previously from surface habitats in the Iberian Peninsula, which does not seem to use the Portuguese MSS as a refuge. MSS habitats in central Portugal, classified as western Mediterranean and thermophile deposits protected by the Natura 2000 network based on plant communities and geology, revealed an abundant and diverse invertebrate community that urges characterization and protection.

Efficacy and safety of risedronate 150-mg once a month in the treatment of postmenopausal osteoporosis: 2-year data.

UNLABELLED: This study showed that risedronate 150-mg once a month provides similar efficacy and safety at 2 years compared with risedronate 5-mg daily for the treatment of postmenopausal osteoporosis. This adds to the range of risedronate dosing options and provides an alternative for patients who prefer once-a-month dosing. INTRODUCTION: Risedronate is effective in the treatment of postmenopausal osteoporosis in oral daily, weekly, or on two consecutive days per month doses. This 2-year randomized, double-blind, multicenter study assesses the efficacy and safety of a single risedronate 150-mg once-a-month oral dose compared with the 5-mg daily regimen. METHODS: Women with postmenopausal osteoporosis were randomly assigned to receive risedronate 5-mg daily (n = 642) or 150-mg once a month (n = 650) for 2 years. Bone mineral density (BMD), bone turnover markers, new vertebral fractures, and adverse events were evaluated. The primary efficacy endpoint was the mean percent change from baseline in lumbar spine BMD after 1 year. RESULTS: Four hundred ninety-eight subjects in the daily group (77.6 %) and 513 subjects in the once-a-month group (78.9 %) completed the study. After 24 months, the mean percent change in lumbar spine BMD was 3.9 % (95 % confidence interval [CI], 3.43 to 4.42 %) and 4.2 % (95 % CI, 3.68 to 4.65 %) in the daily and once-a-month groups, respectively. The once-a-month regimen was determined to be non-inferior to the daily regimen. The mean percent changes in BMD at the hip were similar in both dose groups, as were changes in biochemical markers of bone turnover. The incidence of adverse events, adverse events leading to withdrawal, and upper gastrointestinal tract adverse events were similar in the two treatment groups. CONCLUSIONS: After 2 years, treatment with risedronate 150-mg once a month provided similar efficacy and tolerability to daily dosing and provides an alternative for patients who prefer once-a-month oral dosing.

[Biological monitoring of the PAH exposure in the hardening of metals]. / Monitoraggio biologico dell'esposizione ad IPA nella tempra dei metalli.

The hardening of metals involves the immersion of hot components in mineral oil with production of aerosols containing PAHs, to wich workers can be exposed. The determination of airborne PAHs and urinary 1-hydroxypyrene (1-OHPy) was performed for a group of workers and the latter resulted within the reference values. However, the average 1-OHPy concentration on metal workers (0.07 microg/g creatinine) was statistically different from the average value obtained for a group of employees (0.03 microg/g creatinine), highlighting the risk of exposure to PAHs. Therefore, being these potentially carcinogenic compounds, interventions were prescribed in order to reduce the risk of occupational exposure.

Monthly dosing of 75 mg risedronate on 2 consecutive days a month: efficacy and safety results.

UNLABELLED: Postmenopausal women with osteoporosis received 75 mg risedronate on two consecutive days each month or 5 mg daily for 12 months. Changes in bone mineral density and bone turnover markers were similar between treatments. Risedronate 75 mg twice monthly was effective and safe suggesting a new, convenient dosing schedule. INTRODUCTION: Patients perceive less frequent dosing as being more convenient. This 2-year trial evaluates the efficacy and safety of a new monthly oral regimen of risedronate; 1 year results are presented here. METHODS: Postmenopausal women with osteoporosis (n = 1229) were randomly assigned to double-blind treatment with 75 mg risedronate on two consecutive days each month (2CDM), or 5 mg daily. The primary endpoint was the percent change from baseline in lumbar spine (LS) bone mineral density (BMD) at month 12. Secondary efficacy was evaluated by mean percent changes from baseline in BMD in LS, total hip, trochanter, and femoral neck, and bone turnover markers (BTMs). RESULTS: Risedronate 75 mg 2CDM was non-inferior to 5 mg daily (treatment difference 0.21; 95% CI -0.19 to 0.62). Mean percent change in LS-BMD was 3.4% +/- 0.16 and 3.6% +/- 0.15 respectively. Mean percent changes in BMD and BTMs were significant and similar for both treatment groups. New vertebral fractures occurred in 1% of subjects with either treatment. Both treatments were generally well tolerated and safe. CONCLUSIONS: Risedronate 75 mg 2CDM was non-inferior in efficacy and did not show a difference in safety vs. 5 mg daily after 12 months, leading to a similar benefit.

El traumatizado grave en la unidad de cuidados intensivos: comportamiento en el HMC Dr Carlos J. Finlay enero a junio 2006 / The it traumatized serious in the unit of intensive cares: behavior in the H M C: Dr Carlos J Finlay January to June 2006

La presente investigación se realizó con el objetivo de caracterizar e identificar las particularidades de los traumatizados graves en el Hospital Militar Central Dr Carlos J Finlay, mediante el análisis de múltiples variables entre los pacientes que ingresaron con dicho diagnóstico en el período comprendido entre el 1º de enero y el 30 de junio de 2006. El estudio demostró que las causas más frecuentes de ingreso estuvieron constituidas por los accidentes del tránsito, caídas y heridas por arma blanca que resultaron el 88,1% del total. Predominaron los pacientes del sexo masculino y con edades menores de 45 años. Los factores de riesgo identificados con resultados estadísticamente significativos fueron la edad, p = 0,007; estado de conciencia, p = 0,003; Escala de Trauma Revisada, p = 0,016; y la asociación de las complicaciones con la ventilación mecánica, p = 0,006

Risedronate pharmacokinetics and intra- and inter-subject variability upon single-dose intravenous and oral administration.

PURPOSE: To determine the pharmacokinetics and absolute bioavailability of risedronate after single-dose oral administration of 30 mg risedronate as a tablet and an aqueous solution, and 0.3 mg risedronate as an intravenous infusion. METHODS: This study was a randomized, three-treatment, four-period, partial replicate crossover study involving 33 healthy volunteers. Treatments were administered 7 weeks apart, and the third treatment was repeated during the fourth period. Serum and urine were collected over 72 hours and 672 hours, respectively. RESULTS: Following intravenous administration, renal clearance accounted for 87% of total clearance, with 65% of the dose excreted within 24 hours and 85% of the dose excreted within four weeks. The absolute bioavailability was approximately 0.62% after both oral formulations, and the relative bioavailability of the tablet compared with the oral solution was 104%. The rate and extent of absorption from the two formulations were bioequivalent based on the range proposed for highly variable drugs. Intrasubject variability following oral administration was 50-80%, and was primarily associated with absorption. CONCLUSION: The majority of the total clearance after intravenous administration of risedronate was renal clearance, indicating that only a small percentage of a systemic dose is potentially incorporated, or "cleared," into bone. The absolute bioavailability of orally administered risedronate is approximately 0.6%, and is independent of formulation. Variability in the pharmacokinetics following oral administration is primarily associated with intrasubject variability in absorption.

Efficacy and safety of daily risedronate in the treatment of corticosteroid-induced osteoporosis in men and women: a randomized trial. European Corticosteroid-Induced Osteoporosis Treatment Study.

Long-term use of high-dose corticosteroids often results in bone loss, which may lead to osteoporosis-related fractures. This was a multicenter, double-blind study in which 290 ambulatory men and women receiving high-dose oral corticosteroid therapy (prednisone > or = 7.5 mg/day or equivalent) for 6 or more months were randomized to receive placebo, risedronate 2.5 mg/day, or risedronate 5 mg/day for 12 months. All patients received calcium 1 g and vitamin D 400 IU daily. The primary endpoint was lumbar spine bone mineral density (BMD) at month 12. Additional measurements included BMD at the femoral neck and trochanter and the incidence of vertebral fractures. Overall, there were statistically significant treatment effects on BMD at 12 months at the lumbar spine (p < 0.001), femoral neck (p = 0.004), and trochanter (p = 0.010). Risedronate 5 mg increased BMD at 12 months by a mean (SEM) of 2.9% (0.49%) at the lumbar spine, 1.8% (0.46%) at the femoral neck, and 2.4% (0.54%) at the trochanter, whereas BMD was maintained only in the control group. Although not powered to show fracture efficacy, we observed a reduction in the incidence of vertebral fractures of 70% in the combined risedronate treatment groups, relative to placebo (p = 0.042). Risedronate was well tolerated, had a good safety profile, and was not associated with gastrointestinal adverse events. We conclude that risedronate increases BMD and potentially reduces the incidence of vertebral fractures in patients with corticosteroid-induced osteoporosis.

Improvement of pagetic bone lesions with risedronate treatment: a radiologic study.

Risedronate is a potent pyridinyl bisphosphonate in clinical development for treatment and prevention of osteoporosis, and has been recently approved for treatment of Paget's disease in the United States. An open-label study was conducted to determine the effect of risedronate treatment on pagetic bone lesions in patients with moderate to severe Paget's disease (mean serum alkaline phosphatase levels [ALP] approximately seven times the upper limit of normal). Patients were treated with 30 mg/day oral risedronate for 84 days followed by a 112-day nontreatment period. This 196-day cycle was repeated once in patients whose ALP did not normalize or who experienced relapse, defined as a > or =25% increase in ALP from the lowest value measured. Radiographs of affected anatomical sites in 26 patients were collected at baseline, 6 months, and/or 12 months. Eleven patients received one course and 15 patients received two courses of treatment. Radiographs were examined by a skeletal radiologist who was blinded to their time sequence. Changes in pagetic lesions were categorized as "improved," "deteriorated," or "no change." Between baseline and 6 months, 16 patients improved and 3 deteriorated; at 12 months, 11 patients improved and 2 deteriorated. Most lesions remained unchanged between 6 and 12 months. Improvements were noted in all skeletal sites (tibia, femur, humerus, forearm, pelvis, spine, and skull), but were most pronounced in weight-bearing long bones. In weight-bearing bones, nine lesions had osteolytic fronts. Of these, seven improved and two remained unchanged at 6 months; at 12 months, all but one lesion (which improved) remained unchanged. This radiographic assessment demonstrates that oral risedronate, 30 mg/day in one or two 3-month courses, is highly effective for improving bone lesions in patients with Paget's disease. Risedronate treatment had no deleterious effect on osteolytic lesions in weight-bearing bones; indeed, the majority of lesions with osteolytic fronts were improved after 6 months of risedronate treatment.

Effect of renal function on risedronate pharmacokinetics after a single oral dose.

AIMS: To determine the relationship between risedronate pharmacokinetics and renal function. METHODS: Risedronate was administered to adult men and women (n=21) with various degrees of renal function (creatinine clearance 15-126 ml min-1 ) as a single oral dose of 30 mg. Serum samples were obtained for 72 h after dosing, and urine samples were collected for 72 h after dosing and then periodically for 6 weeks. Risedronate concentrations were determined using an enzyme-linked immunosorbent assay (ELISA). Risedronate serum concentration-time and urinary excretion rate-time profiles were analysed simultaneously using nonlinear regression. RESULTS: Renal clearance and volume of distribution were linearly related to creatinine clearance (r2=0.854, P<0.001; and r2=0.317, P<0.01, respectively). Decreases in predicted renal clearance and volume of distribution of 82 and 69%, respectively, were observed when creatinine clearance decreased from 120 to 20 ml min-1. A 64% decrease in predicted oral clearance was observed when creatinine clearance decreased from 120 to 20 ml min-1 (P=0.064). Iohexol clearance, a predictor of renal function, produced similar results to those observed with creatinine clearance. Risedronate was well tolerated by the study population. CONCLUSIONS: Risedronate renal clearance was significantly related to a decrease in renal function. There was a consistent reduction in oral clearance with a decrease in creatinine clearance. However, based on the regression analysis, generally no dosage adjustment appears to be necessary for most patients with mild or moderate renal impairment (creatinine clearance >20 ml min-1 ).

Dose-proportional pharmacokinetics of risedronate on single-dose oral administration to healthy volunteers.

Risedronate is a pyridinyl bisphosphonate approved for the treatment of Paget's disease (US-FDA) and in development for the treatment and prevention of osteoporosis. This study examined risedronate pharmacokinetics and tolerability after oral administration using a randomized, double-blind, parallel-group design. Healthy male and female volunteers (n = 22-23 subjects per dose) received a single oral dose of 2.5, 5, or 30 mg risedronate. Serum and urine samples were collected for 72 and 672 hours, respectively, and risedronate concentrations were determined by ELISA. Safety was evaluated by monitoring adverse events, clinical laboratory measurements, vital signs, and electrocardiograms. Mean Cmax (0.41, 0.94, and 5.1 ng/mL for 2.5, 5, and 30 mg, respectively), AUC (1.8, 3.9, and 21 ng.h/mL for 2.5, 5, and 30 mg, respectively), and urinary excretion (22, 63, and 260 micrograms for 2.5, 5, and 30 mg, respectively) were dose proportional, and there were no significant differences in tmax or CLR among the three doses. All doses were well tolerated; no serious adverse events occurred, and all but one of the adverse events were mild or moderate in severity. There was no evidence of an acute phase reaction occurring after oral administration of risedronate.

Neurocisticercosis en fase granulomatosa: presentación de un caso / A case report of glanulomatous-phase neurocysticercosis

El 13 de diciembre de 1997 acudió al servicio de urgencias del Hospital Mocel una paciente femenina de 27 años de edad con historia de cefalea de seis meses de evolución. Había sido diagnosticada en otro hospital con neurocisticercosis y tratada médicamente en forma muy irregular. Dos días antes de su ingreso presentó síndrome cráneo-hipertensivo con deterioro del estado de conciencia, hemiparesia derecha y síndrome de babinski bilateral de predominio derecho. Se le practicó una tomografía de cráneo urgente que demostró lesión anular con centro hipodenso, punto pericentral y bordes de hiperdensidad mayor, localizado en la porción anterior del lóbulo frontal izquierdo, hasta la convexidad, compresión del cuerno frontal, gran edema perilesional e importante efecto de masa, motivo por el cual fue sometida a una operación quirúrgica de urgencia

Risedronate, a highly effective oral agent in the treatment of patients with severe Paget's disease.

Thirteen patients with severe Paget's disease of bone [mean serum alkaline phosphatase (SAP) level 17 times the upper limit of normal] were treated with 30 mg oral risedronate daily for 8 weeks. Patients were followed for 16 weeks without treatment. The change from baseline SAP was the primary end point. Those patients whose SAP levels did not reach the normal range were retreated with 30 mg for another 8 weeks. There was a mean percent decrease in SAP of 77% after the first course of risedronate treatment and 87% after the second course of treatment. All patients who completed the study had a decrease in SAP of at least 77% from the baseline. The urinary hydroxyproline/creatinine level was decreased by 64% and 79%, respectively, during the first and second treatment courses. There were transient asymptomatic decreases in serum calcium and phosphorus levels. The urinary calcium/creatinine ratio also decreased in these patients. Serum intact PTH and 1,25-dihydroxyvitamin D levels increased transiently during risedronate treatment. Oral risedronate was well tolerated by the patients. Only one patient discontinued treatment because of an adverse event (diarrhea) thought to be related to risedronate therapy.

Risedronate in the treatment of Paget's disease of bone: an open label, multicenter study.

An open-label, multicenter study was conducted to determine the efficacy and safety of oral risedronate (a pyridinyl bisphosphonate) in 162 patients (102 men, 60 postmenopausal women; mean age, 68 years) with moderate to severe Paget's disease of bone (mean serum alkaline phosphatase [ALP] approximately seven times the upper limit of normal). Patients were treated with oral risedronate, 30 mg/day for 84 days, followed by 112 days without treatment. This 196-day cycle was repeated once if serum ALP did not normalize or increased from the nadir value by > or = 25%. At the end of the first and second cycles, the mean percentage decreases for serum ALP were 65.7% and 69.1%, and for urinary hydroxyproline/creatinine 50.4% and 66.9%, respectively. The decreases from baseline in ALP and urinary hydroxyproline/creatinine were significant (p < 0.001). Normalization of serum ALP was observed in 86 patients (53.8%): 53 during the first treatment cycle and 33 during the second. There was a significant proportion of patients reporting a decrease in the pagetic bone pain at days 84 and 196 (p < 0.001). Overall, risedronate was well tolerated. Five patients withdrew due to adverse events, none of which were considered to be drug related. In conclusion, 30 mg of oral risedronate administered daily for 84 days significantly reduced the biochemical indices of disease activity and was associated with pain reduction in patients with moderate to severe Paget's disease of bone. Normalization of ALP was observed in the majority of patients. Repeated administration of risedronate was shown to be beneficial. In general, risedronate was well tolerated and demonstrated a good safety profile.

Risedronate gastrointestinal absorption is independent of site and rate of administration.

PURPOSE: Two studies were conducted to compare the absorption of risedronate administered as a solution to three different gastrointestinal sites (study A) and to determine the extent of absorption of risedronate solution administered by rapid and slow infusion to the second part of the duodenum (study B). METHODS: Each study was designed as a single-dose, crossover (three periods, study A; two periods, study B) trial in healthy male subjects, with a 14-day washout period between dosing. Subjects fasted overnight before drug administration and for 4 hours after drug administration. In study A, a risedronate solution of 40 mg in 30 mL of water was administered directly into the stomach, the second part of the duodenum, or the terminal ileum over 1 minute via a nasoenteral tube in a three-period crossover design. In study B, a risedronate solution of 40 mg in 30 mL of water was administered directly into the second part of the duodenum over 1 minute and over 1 hour in a randomized, two-period crossover design. Serum and urine samples were obtained for 48 hours after dosing for risedronate analysis. RESULTS: Eight subjects completed each study. No statistically significant site-specific differences in any pharmacokinetic parameter were observed (study A). Based on the area under the serum concentration-time profile and the amount of drug excreted in the urine unchanged, the extent of risedronate absorption did not differ significantly following a rapid or a slow infusion (study B). Only minor symptomatic complaints were reported by subjects, such as headaches and body aches. CONCLUSIONS: These studies indicate that the rate and extent of risedronate absorption are independent of the site of administration along the gastrointestinal tract, and that the extent of absorption is not affected by the rate of administration.

Paget's disease of bone: reduction of disease activity with oral risedronate.

Risedronate monosodium [1-hydroxy-2-(3-pyridinyl)ethylidene bisphosphonic acid monosodium salt] is a pyridinyl bisphosphonate drug under development as a treatment for Paget's disease of bone and other metabolic bone disorders. An open-label, single-center study was conducted to determine the efficacy and safety of oral resedronate in patients with severe Paget's disease [mean baseline serum alkaline phosphatase (ALP) about six times the upper limit of normal]. 20 patients (12 men, 8 women; mean age 74 years) were treated with 30 mg/day of oral risedronate for 84 days, followed by 112 days without treatment. This 196 day period was repeated once in 19 patients in whom ALP did not reach the midpoint of the normal range or increased by > or = 25% from the nadir value by the end of the first 196 day period. At the end of the first 196 day period, the mean percentage decrease from baseline in excess ALP and excess urinary hydroxyproline/creatinine (OHP/Cr) was 79.5% and 85.5%, respectively (excess defined as difference between the patient's ALP or OHP/Cr and midpoint of the normal range). At the end of the second period, the decreases were 86.3% and 101.3%, respectively. The decreases in excess ALP and OHP/Cr were significant (p < 0.0001). In 13 patients (65%), ALP normalized: 8 during the first treatment period and 5 during the second. There was a progressive decline and elimination of pagetic bone pain: 70% (14 of 20) of patients reported pagetic bone pain at baseline, 25% (5 of 20) reported pain after the first 196 day period; and 0% at retreatment day 56 (p = 0.003). Thereafter, all patients remained pain-free until the end of the study. No patients withdrew from the study due to adverse events, and no adverse events were judged related to the study drug. In summary, 30 mg/day of oral risedronate given in 3 month course significantly reduced the biochemical indices of disease activity, showing normalization of ALP in the majority of patients with severe Paget's disease, and was associated with a significant reduction in pagetic bone pain. Risedronate was well-tolerated and demonstrated a good safety profile.

Isolated free fluid on abdominal computerized tomographic scan: an indication for surgery in blunt trauma patients?

A retrospective study of 792 patients who sustained blunt traumatic injury and underwent abdominopelvic computerized tomographic scan (CT) evaluation was performed. Patients who had free intraperitoneal fluid without evidence of solid visceral organ damage served as the study population. Sixty-six (8.3%) of patients were identified as having free fluid without evidence of solid organ injury. Pelvic fractures occurred in 14 of the 66 (21.2%) patients. Splenic injuries requiring laparotomy were not diagnosed initially on CT scan of the abdomen in four (6%) patients. Mesenteric or small bowel injuries occurred in six (9%) patients. Nine (13.6%) of the patients expired. Thirty-five patients (53%) had no sequelae of intra-abdominal injuries and required no surgical intervention. If patients with pelvic fractures are excluded, 10 (19.2%) of the patients required operative intervention for their injuries. It is our conclusion that free fluid as the only significant finding on CT scan in blunt trauma patients may be a harbinger of significant intra-abdominal injury, and that these patients need to be closely observed to decrease morbidity associated with these potential injuries.

Normal and abnormal function of the hypothalamic-pituitary-adrenocortical system in man.

The first half of this manuscript is devoted to a review of the methods used and the results obtained in the published measurements of the normal responses to tests of the three main types of hypothalamic-pituitary-adrenocortical (HPA) activity in man. These are, I, basal, unstressed activity leading to appropriate levels of total daily production of cortisol in the characteristic circadian pattern; II, responses to feedback stimulation of HPA activity by metyrapone administration; and III, responses to tests of the effects of stress on the HPA system including the effects of hypoglycemia, induced fever, vasopressin administration, and ACTH injections and infusions. The advantages and shortcomings of each type of procedure are discussed. The second half of this paper describes the authors' attempts to establish the limits of normality of standard and modified methods of evaluating the HPA system. The defined limits of normality have been used to assess the HPA function in 158 patients with known or suspected disorders of the HPA system. In normal controls, halfhourly plasma cortisol determinations established the normality of circadian and postprandial fluctuations and of mean plasma cortisol concentration, 6.2 +/- 0.3 (SEM) micrograms/dl, which were closely approximated by determinations every 6 h. Metyrapone, given in a dose of 500 mg every 2 h for 24 h increased urinary 17-OHCS excretion to 10.5-32.6 mg/day or to 1.7-7.8 times basal excretion rate. Increasing rates of insulin infusion disclosed significant relationships between resulting plasma glucose and cortisol concentrations. The slopes of the delta cortisol/delta glucose responses were similar after insulin infusions (0.46 +/- 0.05) and after insulin injections, 0.15 U/kg (0.43 +/- 0.09), and were always greater than 0.20 micrograms/mg. This index provides a useful objective measure of the normality of responses to hypoglycemic stress, 0.20-0.87 micrograms/mg. Adrenocortical responses to iv infusions of ACTH (cosyntropin 0.25 mg) may be equivocal at 2 h but are clear cut at 4, 6 and 8 h. Of 158 patients in whom hypopituitarism was known or suspected because of the presence of a pituitary tumor, acromegaly, hyperprolactinemia, or clinical features, HPA function was found to be entirely normal in 88 patients and partially or severely abnormal in the remaining 70 patients.(ABSTRACT TRUNCATED AT 400 WORDS)

No inhibition of corticotrophin (ACTH)-hypersecretion in adrenal insufficiency by somatostatin.

Somatostatin (250 micrograms as a bolus iv and 250 micrograms as a 1 h infusion) was administered to 6 patients with primary adrenal insufficiency (Addison's disease). The fall in plasma ACTH during the infusion period ranged between 0-30% with a mean reduction of 11.2 +/- 11.6%. These findings suggest that with the method employed, somatostatin is not an inhibitor of ACTH secretion in a condition in which glucocorticoids are lacking.