Conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium in liver transplant patients presenting gastrointestinal disorders: a pilot study.

Gastrointestinal (GI) disorders are one of the main adverse events in patients treated by mycophenolic acid (MPA). The aim of this prospective study was to evaluate the effect of conversion from mycophenolate mofetil (MMF) to enteric-coated mycophenolate sodium (EC-MPS) in liver transplant patients presenting GI side-effects Since January 2003, stable liver transplant patients receiving MMF and presenting GI disorders, without evidence of other origin than MMF were enrolled. Conversion was performed without a washout period at an equimolar daily dosage. Thirty-six patients were included after a median delay of 45 months after liver transplantation (LT) (16 women and 20 men, median age of 47 years). Diarrhoea was the main clinical symptom (n = 28, 77.7%). At the time of inclusion, patients were treated with MMF since 18 months (range 3-28) and GI disorders were known for 9 months (range 3-12). After a median follow-up of 12 months after conversion, GI disorders were resolved in 20 patients (55%), improved in 6 patients (17%) and not modified or worsened in 10 patients (28%). Our results strongly suggest that conversion from MMF to EC-MPS in liver transplant patients can improve gastrointestinal disorders in a majority of the patients, and therefore might be considered as the best therapeutic option.     

Body weight and comorbidity predict mortality in COPD patients treated with oxygen therapy.

The aim of this study was to investigate the association between clinical variables and all-cause and respiratory mortality in patients with chronic obstructive pulmonary disease (COPD) undergoing long-term oxygen therapy (LTOT). The authors retrospectively studied a historic cohort of 128 patients with COPD (126 males, mean age+/-SD 68.9+/-9.7 yrs, body mass index (BMI) 25.1+/-4.5 kg.m-2, and forced expiratory volume in one second 25.4+/-8.8% predicted), who were being treated with long-term oxygen therapy in a tertiary teaching hospital between 1992 and 1999. Comorbidity, assessed with the Charlson Index, was present in 38% of the patients. Vital status and cause of death were assessed through the population death registry. A total of 78 patients (61%) had died by the end of follow-up. Three-year survival was 55%. Death was due to respiratory causes in 77% of cases. On Cox analysis, BMI<25 kg.m-2, comorbid conditions, age>or=70 yrs and cor pulmonale were associated with all-cause mortality. The BMI and comorbidity were the only significant predictive factors when the analysis was restricted to respiratory mortality. In conclusion, body mass index<25 kg.m-2 and comorbidity were predictors of all-cause and respiratory mortality in a cohort of chronic obstructive pulmonary disease patients treated with long-term oxygen therapy. These factors should be taken into account when considering the management and prognosis of these patients.     

Tuberculosis trends in Madrid, 1994-2003: impact of immigration and HIV infection.

SETTING: Tuberculosis (TB) cases reported from nine districts of Madrid, where the percentage of immigrant population varied from 1.9% in 1996 to 12.2% in 2003. OBJECTIVE: To describe the trends in TB incidence from 1994 to 2003. DESIGN: Observational study. RESULTS: Between 1994-1995 and 2002-2003, the TB rate decreased from 48.5 (95% CI 45.8-51.1) to 23.3 per 100000 population (95% CI 21.5-25.1) (P < 0.001). The percentage of TB cases co-infected with HIV decreased from 55.9% in 1994 to 14.3% in 2003 (P < 0.001), whereas TB cases in foreigners increased from 2.6% in 1994 to 33.7% in 2003 (P < 0.001). CONCLUSION: Although the TB rates showed a marked decrease in the study period, the increasing impact of immigration contributed to slowing down the trend.     

Dentin enhances the effectiveness of bioactive glass S53P4 against a strain of Enterococcus faecalis.

OBJECTIVE: The aim of the current study was to test the impact of dentin powder on the antimicrobial efficacy of bioactive glass S53P4 (BAG). STUDY DESIGN: BAG was suspended (preincubated) in saline at 37 degrees C for different time periods with or without human dentin powder, hydroxylapatite, or decalcified dentin. Subsequently, Enterococcus faecalis ATCC 29212 cells were added to these suspensions and bacterial recovery measured with and without the use of gentle sonication. Furthermore, survival of bacteria in test and control suspensions was assessed over time. Supernatants of suspensions were analyzed for their element contents using atomic absorption spectrophotometry. The effects of pH, silica, and osmolarity on E faecalis viability were assessed using specifically prepared solutions. RESULTS: BAG preincubated with dentin powder caused a significant (P < .05) decrease in viability compared to pure BAG suspensions. This was not based on adherence of bacteria to solid particles or agglutination of the cells, because sonication did not increase bacterial yields. Hydroxylapatite and decalcified dentin did not increase BAG killing efficacy. The additive effect of BAG + dentin powder was dose dependent, occurred only with solids in suspension, and increased with suspension time. An augmented dissolution of glass components, especially silicon, was measured in BAG + dentin powder compared to pure BAG suspensions or counterparts containing hydroxylapatite or decalcified dentin. High osmolarity per se did not affect E faecalis viability, whereas high pH and silica levels did. CONCLUSION: The observed phenomenon was related to an increased BAG dissolution triggered by dentin powder, causing elevated local pH and silica levels.     

Spinocerebellar ataxia types 2 and 3 segregating simultaneously in a single family.

Spinocerebellar ataxia (SCA) types 2 and 3 are autosomal-dominant neurodegenerative disorders caused by mutations in two different genes. We identified mutations for SCA2 and SCA3 segregating simultaneously in a single Brazilian family. The index patient had SCA2, whereas her two second-degree cousins had SCA3. Disease was more rapidly progressive in the SCA2 patient, who presented severe brainstem and pancerebellar atrophy, as opposed to the two SCA3 patients, who had only mild cerebellar vermian atrophy. In such situations, molecular confirmation of all patients may avoid misdiagnosis of SCA subtypes and eventual errors in predictive testing of unaffected family members.     

Cognitive function after on or off pump coronary artery bypass grafting.

OBJECTIVE: To investigate cognitive outcome after on and off pump coronary artery bypass grafting. METHODS: Seventy patients between 50 and 80 years with stable angina pectoris, ejection fraction >30%, serum creatinine <150 micromol/l, and lack of tight main stem stenosis were randomized to on or off pump coronary artery bypass grafting. Standardized neuropsychological tests evaluated attention, verbal and visuo-spatial short-term and working memory, verbal learning, delayed recall, visuo-motor speed, and aspects of executive functions. Levels of anxiety and depression were also investigated. Testing was performed before and at 1 week, 1 and 6 months after surgery. RESULTS: There was no difference in cognitive impairment (defined as a 20% reduction in at least 20% of the tests) between groups. The incidence at 1 week post-operatively was 57% in the on pump group and 58% in the off pump group, after 1 month 30% and 12% and after 6 months 19% and 15%, respectively (p for interaction=0.19). There was no difference between groups in anxiety (p=0.18) or depression (p=0.48). CONCLUSIONS: This prospective, randomized study showed no differences in post-operative cognitive function after on pump compared to off pump coronary artery bypass grafting in low risk patients.     

Spray coated pellets as carrier system for mucoadhesive drug nanocrystals.

High pressure homogenization can be employed to produce drug nanocrystals with a number of advantages, like improved solubility behaviors, better drug targeting or even increased mucoadhesiveness. To obtain a controlled drug delivery system it is necessary to transform the resulting nanosuspension into a solid dosage form. The present study shows the feasibility to use a mucoadhesive nanosuspension of poorly soluble hydrocortisone acetate produced by high pressure homogenization as layering dispersion in a fluidized bed process, followed by the application of an enteric coating to achieve a controlled drug release. To point out the advantages of drug nanocrystals the new fomulation was compared with a formulation containing micronized drug. Both formulations were characterized with regard to their particle size and crystallinity by using laser diffractometry, photon correlation spectroscopy and X-ray diffraction. The pellet morphology was characterized by using the environmental scanning electron microscopy (ESEM). In the in vitro dissolution tests an accelerated dissolution velocity and an increased drug release could be shown for the pellets containing drug nanocrystals.     

Blunted renal dopaminergic system activity in puromycin aminonucleoside-induced nephrotic syndrome.

BACKGROUND: A primary tubular sodium handling abnormality has been implicated in the edema formation of nephrotic syndrome. Dopamine synthesized by renal proximal tubules behaves as an endogenous natriuretic hormone by activating D(1)-like receptors as a paracrine/autocrine substance. METHODS: We examined the time courses of the urinary excretion of sodium, protein and dopamine in puromycin aminonucleoside (PAN)-treated and control rats. The rats were sacrificed during greatest sodium retention (day 7) as well as during negative sodium balance (day 14) for the evaluation of renal aromatic l-amino acid decarboxylase (AADC) activity, the enzyme responsible for the synthesis of renal dopamine. Also, the influence of volume expansion (VE) and the effects of the D(1)-like agonist fenoldopam (10 microg/kg bw/min) on natriuresis and on proximal tubular Na(+),K(+)-ATPase activity were examined on day 7. RESULTS: The daily urinary excretion of dopamine was decreased in PAN-treated rats, from day 5 and beyond. This was accompanied by a marked decrease in the renal AADC activity, on days 7 and 14. During VE, the fenoldopam-induced decrease in proximal tubular Na(+),K(+)-ATPase activity was more pronounced in PAN-treated rats than in controls. However, the urinary sodium excretion during fenoldopam infusion was markedly increased in control rats but was not altered in PAN-treated animals. CONCLUSION: PAN nephrosis is associated with a blunted renal dopaminergic system activity which may contribute to enhance the proximal tubular Na(+),K(+)-ATPase activity. However, the lack of renal dopamine appears not to be related with the overall renal sodium retention in a state of proteinuria.     

Analyzing and shaping human attentional networks.

In this paper we outline a conception of attentional networks arising from imaging studies as connections between activated brain areas carrying out localized mental operations. We consider both the areas of functional activation (nodes) and the structural (DTI) and functional connections (DCM) between them in real time (EEG, frequency analysis) as important tools in analyzing the network. The efficiency of network function involves the time course of activation of nodes and their connectivity to other areas of the network. We outline landmarks in the development of brain networks underlying executive attention from infancy and childhood. We use individual differences in network efficiency to examine genetic alleles that are related to performance. We consider how animal studies might be used to determine the genes that influence network development. Finally we indicate how training may aid in enhancing attentional networks. Our goal is to show the wide range of methods that can be used to suggest and analyze models of network function in the study of attention.     

Effects of long-term treatment with resveratrol and subcutaneous and oral estradiol administration on the pituitary-thyroid-axis.

The lack of estrogen during menopause is associated with various symptoms including osteoporosis, cardiovascular diseases, and menopausal symptoms. For many years, conventional hormone replacement therapy has been successfully used to treat these conditions. However, in light of recent studies that draw attention to potential hazards of conventional HRT, various attempts were undertaken to search for alternatives of classical HRT. Phytoestrogens are supposed to ameliorate various discomforts associated with menopause. Resveratrol (RES) is present in red wine, grapes and peanuts and has been implicated in cardioprotection and prevention of adverse side effects observed after regular HRT. As the pituitary-thyroid axis is a target of estrogen action, we first assessed the effects of E2 administration on thyroid hormone stimulating hormone releasing hormone (TRH)-induced thyroid stimulating hormone (TSH) secretion from pituitary cell cultures in vitro. Our data reveal that E2 treatment augments the TRH-induced TSH secretion. We furthermore designed a long-term study of three months to assess the effects of subcutaneous and oral administration of 17beta-estradiol (E2), as well as the actions of RES on the pituitary-thyroid axis in ovariectomized (OVX) female rats. Our results demonstrate that serum levels of 1.0 and 8.1 microM RES lead to a significant increase in total serum triiodthyronine (T3) levels. OVX induces TSHbeta mRNA in the adenohypohysis and E2 treatment attenuates this effect. Treatment of rats with subcutaneous implants of E2 does not affect the pituitary-thyroid axis, whereas orally applied E2 benzoate (E2B) increases plasma TSH and total thyroxine (T4) in OVX rats. In all animals, we could not detect changes in thyroid morphology as assessed by hematoxylin-eosin (HE) and Perjod-Acid Schiff's (PAS) staining.