Treatment with intermittent calcitriol and calcium reduces bone loss after renal transplantation

BACKGROUND: Bone loss occurs during the first 6 months after renal transplantation (RT), and corticosteroid therapy plays an important role. Although calcium plus vitamin D administration prevents corticosteroid-induced osteoporosis, its use in RT recipients is limited by the risk of hypercalcemia. METHODS: This double-blind, randomized, and controlled prospective intervention trial examined the effect of intermittent calcitriol (0.5 microg/48 h) during the first 3 months after RT, plus oral calcium supplementation (0.5 g/day) during 1 year with calcium supplementation alone. The primary outcome measure was the change in bone mineral density (BMD) at 3 and 12 months after RT; we also explored whether the effect of calcitriol on BMD was different among vitamin D receptor (VDR) genotypes (BsmI). Forty-five recipients were randomized to calcitriol therapy (CT) and 41 were randomized to placebo (PL). RESULTS: Both groups had a similar degree of pre-existing hyperparathyroidism (197 +/- 229 vs. 191 +/- 183 pg/mL), but a more pronounced decrease of parathyroid hormone (PTH) levels after RT was observed in CT patients (at 3 months: 61.4 +/- 42.2 vs. 85.7 +/- 53.1 pg/mL, P= 0.02; at 12 months: 67.3 +/- 33.7 vs. 82.6 +/- 37 pg/mL; P= 0.08). CT patients preserved their BMD at the total hip significantly better than those on PL (3 months: 0.04 +/- 3.3 vs. -1.93 +/- 3.2%, P= 0.01; 12 months: 0.32 +/- 4.8 vs. -2.17 +/- 4.4%, P= 0.03); significant differences were noted at the intertrochanter, trochanter, and Ward's triangle. Differences did not reach significance at the femoral neck. Two CT patients (4.4%) and 4 PL patients (9.8%) developed a hypercalcemic episode during the first 3 months after RT. The effect of CT on BMD at 3 months was more prominent in recipients with the at-risk allele of the VDR gene (P= 0.03). CONCLUSION: Therapy with low-dose calcium supplements during 1 year, plus intermittent calcitriol for 3 months after RT, is safe, decreases PTH levels more rapidly, and prevents bone loss at the proximal femur; a more pronounced effect is seen in recipients with at least one at-risk allele of the VDR genotype.     

Complicated acute pediatric bacterial sinusitis: Imaging updated approach

Acute bacterial sinusitis is usually a clinical diagnosis. Orbital complications require emergent evaluation with computed tomography. Using the orbital septum as an anatomic landmark, such infections can be classified as pre- or postseptal and treated with the most adequate therapy, ie, oral or intravenous antibiotics or surgical endonasal drainage. Intracranial complications can be seen in 3.7% to 11% of these patients, often with subtle clinical symptoms and signs. Radiologists play a decisive role in the final management of these patients and should be familiar with the most relevant complications. In this article, we present a retrospective review of all pediatric patients referred to our department for paranasal sinuses and orbital computed tomography because of acute complicated bacterial sinusitis. They were studied with an emergent enhanced facial and cranial computed tomography within 24 hours of admission, followed by magnetic resonance imaging when intracranial complications were suspected. Particular emphasis is placed on the imaging algorithm and the most relevant complications; we correlate imaging findings with clinical and bacteriological data.     

Quantitative age-related changes in dorsal lateral geniculate nucleus relay neurons of the rat

An ultrastructural and quantitative study of the age-related changes occurring in the relay neurons of the dorsal lateral geniculate nucleus (dLGN) was carried out using male Wistar rats aged 3, 18, 24, and 28 months. Morphometric techniques were used to obtain data regarding cellular activity including soma, nuclear, and nucleolar size. Volume fractions for rough endoplasmic reticulum (RER), mitochondria, and lipofuscin, as well as numbers and sizes of mitochondria and dense bodies (DB) was also calculated. Among the few alterations found in the perikaryon, we can highlight the redistribution and fragmentation of RER and an increase and progressive aggregation of lipofuscin. Quantitative data show a significant decrease in the volume of the soma (-42.77%) and the nucleus (-33.66%), and in the volume fraction of the RER (-18.81%) and mitochondria (-10.16%). A significant increase in lipofuscin (+213.29%), and variations in size and number of mitochondria and dense bodies were also found. Some histophysiological considerations about the findings are discussed. The findings lead to the conclusion that a relative degree of morphological stability is exhibited by relay neurons, although the quantitative data show evident intracellular changes, especially from 24 to 28 months. These changes suggest that accompanying physiological alterations may occur, with putative effects on visual function during ageing.     

Synthesis, conformational analysis, and cytotoxicity of conformationally constrained aplidine and tamandarin A analogues incorporating a spirolactam beta-turn mimetic

With the aim of studying the contribution of the beta II turn conformation at the side chain of didemnins to the bioactive conformation responsible for their antitumoral activity, conformationally restricted analogues of aplidine and tamandarin A, where the side chain dipeptide Pro8-N-Me-d-Leu7 is replaced with the spirolactam beta II turn mimetic (5R)-7-[(1R)-1-carbonyl-3-methylbutyl]-6-oxo-1,7-diazaspiro[4.4]nonane, were prepared. Additionally, restricted analogues, where the aplidine (pyruvyl9) or tamandarin A [(S)-Lac9] acyl groups are replaced with the isobutyryl, Boc, and 2-methylacryloyl groups, were also prepared. These structural modifications were detrimental to cytotoxic activity, leading to a decrease of 1-2 orders of magnitude with respect to that exhibited by aplidine and tamandarin A. The conformational analysis of one of these spirolactam aplidine analogues, by NMR and molecular modeling methods, showed that the conformational restriction caused by the spirolactam does not produce significant changes in the overall conformation of aplidine, apart from preferentially stabilizing the trans rotamer at the pyruvyl9-spirolactam amide bond, whereas in aplidine both cis and trans rotamers at the pyruvyl9-Pro8 amide bond are more or less equally stabilized. These results seem to indicate a preference for the cis form at that amide bond in the bioactive conformation of aplidine. The significant influence of this cis/trans isomerism upon the cytotoxicity suggests a possible participation of a peptidylprolyl cis/trans isomerase in the mechanism of action of aplidine.     

Lack of association between the serotonin transporter promoter gene polymorphism and impulsivity or aggressive behavior among suicide attempters and healthy volunteers

The association between a polymorphism in the promoter area of the serotonin transporter (17q11.1-q12) with impulsivity and history of aggressive behavior was studied in a Spanish general hospital. Subjects comprised 216 suicide attempters (152 women and 64 men) and 223 control blood donors (124 women and 99 men). They were classified as S individuals (s/s or s/l) with low expression of the serotonin transporter, and L individuals (l/l) with high expression. The genotype was not associated with high levels of impulsivity (measured with the Barratt Impulsiveness Scale) or history of aggressive behavior (measured with the Brown-Goodwin scale). This lack of association did not appear to be explained by lack of statistical power. High scores on the Barratt Impulsiveness Scale (BIS) and the Brown-Goodwin Aggressive Behavior Scale were associated with being an attempter, male gender and borderline personality disorder. While our Spanish suicide attempters and published US suicide attempters have similar BIS scores, our Spanish suicide attempters have significantly lower aggressive behavior scores. If cross-cultural differences in aggressive behavior scores are definitively established, country norms for aggressive behavior scales will need to be developed to compare genetic studies in different countries.     

Lack of association between polymorphic variations in the alpha 3 subunit GABA receptor gene (GABRA3) and suicide attempts

This is the first case-control study exploring the association between suicide attempts and the polymorphic variations of the alpha 3 subunit gamma-aminobutyric acid (GABA) receptor gene (GABRA3) located in chromosome X. In a Spanish general hospital, 184 suicide attempters (127 women and 57 men) and 275 control blood donors (109 women and 166 men) were recruited. The four frequent variants (A1, A2, A3 and A4) of GABRA3 were studied. There were no significant differences in the total or by-gender frequencies of the four alleles. In females, there were no significant differences in the genotypes. This study can rule out even small size effects in the total sample and suggests a lack of association between GABRA3 polymorphism and suicide attempt, in the Spanish population.     

Antioxidant effects of taurine, vitamin C, and vitamin E on oxidative damage in hippocampus caused by the administration of 3-nitropropionic acid in rats

The administration of 3-nitropropionic acid increases reactive oxygen species (ROS). Antioxidant defense mechanisms buffer these ROS converting them into non-damaging compounds. Taurine and vitamins C and E are antioxidants that play a role in the defense against cellular damage. This study examines the antioxidant effect of taurine, vitamin C, and vitamin E on acute hippocampal damage caused by 3-NP. Animals treated with 3-NP increased lipid peroxidation levels and astrocytic damage in the hippocampus. Administration of taurine, vitamin C, and vitamin E partially protected from oxidative damage, indicate that while all substances had antioxidant effects, only taurine showed morphological protection in surviving cells.     

Solitary fibrous tumor of the thyroid with capsular invasion

This report describes the clinical and pathologic findings of a peculiar case of solitary fibrous tumor of the thyroid gland that showed capsular invasion. After four and a half years of follow-up, neither local recurrence nor metastasis has developed.     

Prevalence of anti-human respiratory syncytial virus antibodies over three consecutive years in a healthy adult population

The titers of anti-human respiratory syncytial virus (HRSV) antibodies have been measured by enzyme-linked immunosorbent assay (ELISA) in a cohort of healthy adult volunteers over 3 consecutive years. Significant increases in the level of these antibodies were detected in a small percentage of individuals (3-3.3%), when paired serum samples taken from two consecutive seasons were compared. In these cases, a significant increase was generally noted in the level of antibodies directed against either the F or the G glycoproteins, and in the level of neutralizing antibodies. However, no correlation was found between the level of binding and neutralizing antibodies, when samples representative of the population under study were analyzed. These results indicate some level of infection by HRSV in the adult population. The implications of these results for the epidemiology of HRSV are discussed.