Functional host-specific adaptation of the intestinal microbiome in hominids.

Fine-scale knowledge of the changes in composition and function of the human gut microbiome compared that of our closest relatives is critical for understanding the evolutionary processes underlying its developmental trajectory. To infer taxonomic and functional changes in the gut microbiome across hominids at different timescales, we perform high-resolution metagenomic-based analyzes of the fecal microbiome from over two hundred samples including diverse human populations, as well as wild-living chimpanzees, bonobos, and gorillas. We find human-associated taxa depleted within non-human apes and patterns of host-specific gut microbiota, suggesting the widespread acquisition of novel microbial clades along the evolutionary divergence of hosts. In contrast, we reveal multiple lines of evidence for a pervasive loss of diversity in human populations in correlation with a high Human Development Index, including evolutionarily conserved clades. Similarly, patterns of co-phylogeny between microbes and hosts are found to be disrupted in humans. Together with identifying individual microbial taxa and functional adaptations that correlate to host phylogeny, these findings offer insights into specific candidates playing a role in the diverging trajectories of the gut microbiome of hominids. We find that repeated horizontal gene transfer and gene loss, as well as the adaptation to transient microaerobic conditions appear to have played a role in the evolution of the human gut microbiome.

High-resolution entry and exit surface dosimetry in a 1.5 T MR-linac.

The magnetic field of a transverse MR-linac alters electron trajectories as the photon beam transits through materials, causing lower doses at flat entry surfaces and increased doses at flat beam-exiting surfaces. This study investigated the response of a MOSFET detector, known as the MOSkin™, for high-resolution surface and near-surface percentage depth dose measurements on an Elekta Unity. Simulations with Geant4 and the Monaco treatment planning system (TPS), and EBT-3 film measurements, were also performed for comparison. Measured MOSkin™ entry surface doses, relative to Dmax, were (9.9 ± 0.2)%, (10.1 ± 0.3)%, (11.3 ± 0.6)%, (12.9 ± 1.0)%, and (13.4 ± 1.0)% for 1 × 1 cm2, 3 × 3 cm2, 5 × 5 cm2, 10 × 10 cm2, and 22 × 22 cm2 fields, respectively. For the investigated fields, the maximum percent differences of Geant4, TPS, and film doses extrapolated and interpolated to a depth suitable for skin dose assessment at the beam entry, relative to MOSkin™ measurements at an equivalent depth were 1.0%, 2.8%, and 14.3%, respectively, and at a WED of 199.67 mm at the beam exit, 3.2%, 3.7% and 5.7%, respectively. The largest measured increase in exit dose, due to the electron return effect, was 15.4% for the 10 × 10 cm2 field size using the MOSkin™ and 17.9% for the 22 × 22 cm2 field size, using Geant4 calculations. The results presented in the study validate the suitability of the MOSkin™ detector for transverse MR-linac surface dosimetry.

Combined culture and metagenomic analyses reveal significant shifts in the composition of the cutaneous microbiome in psoriasis.

BACKGROUND: The treatment of psoriasis has been revolutionized by the development of biologic therapies. However, the pathogenesis of psoriasis, in particular the role of the cutaneous microbiome, remains incompletely understood. Moreover, skin microbiome studies have relied heavily on 16S rRNA sequencing data in the absence of bacterial culture. OBJECTIVES: To characterize and compare the cutaneous microbiome in 20 healthy controls and 23 patients with psoriasis using metagenomic analyses and to determine changes in the microbiome during treatment. METHODS: Swabs from lesional and nonlesional skin from patients with psoriasis, and from controls matched for site and skin microenvironment, were analysed using both 16S rRNA sequencing and traditional culture combined with mass spectrometry (MALDI-TOF) in a prospective study. RESULTS: Psoriasis was associated with an increased abundance of Firmicutes and a corresponding reduction in Actinobacteria, most marked in lesional skin, and at least partially reversed during systemic treatment. Shifts in bacterial community composition in lesional sites were reflected in similar changes in culturable bacteria, although changes in the microbiota over repeated swabbing were detectable only with sequencing. The composition of the microbial communities varied by skin site and microenvironment. Prevotella and Staphylococcus were significantly associated with lesional skin, and Anaerococcus and Propionibacterium with nonlesional skin. There were no significant differences in the amount of bacteria cultured from the skin of healthy controls and patients with psoriasis. CONCLUSIONS: Shifts in the cutaneous microbiome in psoriasis, particularly during treatment, may shed new light on the pathogenesis of the disease and may be clinically exploited to predict treatment response. What's already known about this topic? Alterations in the composition of the cutaneous microbiome have been described in psoriasis, although methodological differences in study design prevent direct comparison of results. To date, most cutaneous microbiome studies have focused on 16S rRNA sequencing data, including both living and dead bacteria. What does this study add? This prospective observational study confirms that changes in the composition of the cutaneous microbiome, detected by 16S rRNA sequencing, are consistent with those identified by bacterial culture and mass spectrometry. The changes in the microbiome during antipsoriasis therapy should be further investigated to determine whether these represent potential novel biomarkers of treatment response. What is the translational message? Characterization of cutaneous microbiota may ultimately move into the clinic to help facilitate treatment selection, not only by optimizing currently available treatments, but also by identifying new therapeutic targets.

Gut Dysbiosis With Bacilli Dominance and Accumulation of Fermentation Products Precedes Late-onset Sepsis in Preterm Infants.

BACKGROUND: Gut dysbiosis has been suggested as a major risk factor for the development of late-onset sepsis (LOS), a main cause of mortality and morbidity in preterm infants. We aimed to assess specific signatures of the gut microbiome, including metabolic profiles, in preterm infants <34 weeks of gestation preceding LOS. METHODS: In a single-center cohort, fecal samples from preterm infants were prospectively collected during the period of highest vulnerability for LOS (days 7, 14, and 21 of life). Following 16S rRNA gene profiling, we assessed microbial community function using microbial metabolic network modeling. Data were adjusted for gestational age and use of probiotics. RESULTS: We studied stool samples from 71 preterm infants with LOS and 164 unaffected controls (no LOS/necrotizing enterocolitis). In most cases, the bacteria isolated in diagnostic blood culture corresponded to the genera in the gut microbiome. LOS cases had a decelerated development of microbial diversity. Before onset of disease, LOS cases had specific gut microbiome signatures with higher abundance of Bacilli (specifically coagulase-negative Staphylococci) and a lack of anaerobic bacteria. In silico modeling of bacterial community metabolism suggested accumulation of the fermentation products ethanol and formic acid in LOS cases before the onset of disease. CONCLUSIONS: Intestinal dysbiosis preceding LOS is characterized by an accumulation of Bacilli and their fermentation products and a paucity of anaerobic bacteria. Early microbiome and metabolic patterns may become a valuable biomarker to guide individualized prevention strategies of LOS in highly vulnerable populations.

An absolute sodium abundance for a cloud-free 'hot Saturn' exoplanet.

Broad absorption signatures from alkali metals, such as the sodium (Na I) and potassium (K I) resonance doublets, have long been predicted in the optical atmospheric spectra of cloud-free irradiated gas giant exoplanets1-3. However, observations have revealed only the narrow cores of these features rather than the full pressure-broadened profiles4-6. Cloud and haze opacity at the day-night planetary terminator are considered to be responsible for obscuring the absorption-line wings, which hinders constraints on absolute atmospheric abundances7-9. Here we report an optical transmission spectrum for the 'hot Saturn' exoplanet WASP-96b obtained with the Very Large Telescope, which exhibits the complete pressure-broadened profile of the sodium absorption feature. The spectrum is in excellent agreement with cloud-free, solar-abundance models assuming chemical equilibrium. We are able to measure a precise, absolute sodium abundance of logεNa = [Formula: see text], and use it as a proxy for the planet's atmospheric metallicity relative to the solar value (Zp/Zʘ = [Formula: see text]). This result is consistent with the mass-metallicity trend observed for Solar System planets and exoplanets10-12.

Understanding Optimum Fluoride Intake from Population-Level Evidence.

Policy on fluoride intake involves balancing caries against dental fluorosis in populations. The origin of this balance lies with Dean's research on fluoride concentration in water supplies, caries, and fluorosis. Dean identified cut points in the Index of Dental Fluorosis of 0.4 and 0.6 as critical. These equate to 1.3 and 1.6 mg fluoride (F)/L. However, 1.0 mg F/L, initially called a permissible level, was adopted for fluoridation programs. McClure, in 1943, derived an "optimum" fluoride intake based on this permissible concentration. It was not until 1944 that Dean referred to this concentration as the "optimal" concentration. These were critical steps that have informed health authorities through to today. Several countries have derived toxicological estimates of an adequate and an upper level of intake of fluoride as an important nutrient. The US Institute of Medicine (IOM) in 1997 estimated an Adequate Intake (AI) of 0.05 mg F/kg bodyweight (bw)/d and a Tolerable Upper Intake Level (UL) of 0.10 mg F/kg bw/d. These have been widely promulgated. However, a conundrum has existed with estimates of actual fluoride intake that exceed the UL without the expected adverse fluorosis effects being observed. Both the AI and UL need review. Fluoride intake at an individual level should be interpreted to inform more nuanced guidelines for individual behavior. An "optimum" intake should be based on community perceptions of caries and fluorosis, while the ultimate test for fluoride intake is monitoring caries and fluorosis in populations.

Exploring the Balance between DNA Pressure and Capsid Stability in Herpesviruses and Phages.

UNLABELLED: We have recently shown in both herpesviruses and phages that packaged viral DNA creates a pressure of tens of atmospheres pushing against the interior capsid wall. For the first time, using differential scanning microcalorimetry, we directly measured the energy powering the release of pressurized DNA from the capsid. Furthermore, using a new calorimetric assay to accurately determine the temperature inducing DNA release, we found a direct influence of internal DNA pressure on the stability of the viral particle. We show that the balance of forces between the DNA pressure and capsid strength, required for DNA retention between rounds of infection, is conserved between evolutionarily diverse bacterial viruses (phages λ and P22), as well as a eukaryotic virus, human herpes simplex 1 (HSV-1). Our data also suggest that the portal vertex in these viruses is the weakest point in the overall capsid structure and presents the Achilles heel of the virus's stability. Comparison between these viral systems shows that viruses with higher DNA packing density (resulting in higher capsid pressure) have inherently stronger capsid structures, preventing spontaneous genome release prior to infection. This force balance is of key importance for viral survival and replication. Investigating the ways to disrupt this balance can lead to development of new mutation-resistant antivirals. IMPORTANCE: A virus can generally be described as a nucleic acid genome contained within a protective protein shell, called the capsid. For many double-stranded DNA viruses, confinement of the large DNA molecule within the small protein capsid results in an energetically stressed DNA state exerting tens of atmospheres of pressures on the inner capsid wall. We show that stability of viral particles (which directly relates to infectivity) is strongly influenced by the state of the packaged genome. Using scanning calorimetry on a bacterial virus (phage λ) as an experimental model system, we investigated the thermodynamics of genome release associated with destabilizing the viral particle. Furthermore, we compare the influence of tight genome confinement on the relative stability for diverse bacterial and eukaryotic viruses. These comparisons reveal an evolutionarily conserved force balance between the capsid stability and the density of the packaged genome.

Assessing a therapeutic exchange protocol for second-generation antidepressants: clinical results.

OBJECTIVE: To design a therapeutic exchange protocol for antidepressants and clinically assess variables, such as: compliance level, frequency of cases with clinically significant increase on the Udvalg-für-Kliniske-Undersogelser (UKU) psychopharmacological scale, adverse effects analysis, overall analysis of UKU rating development and patients' level of acceptance. Secondary objectives were to correlate psychopharmacological treatment aspects with the pharmacological morbidity level, and evaluate the clinical impact of pharmacotherapeutic optimisation measures. METHOD: The protocol is designed in accordance with a bibliographical review, which was approved by the Pharmacy and Therapeutics Commission. Sequential study was carried out with a sample of 30 patients. Three measurements were taken (base line, at 48-72 hours and at 1-3 weeks) to calculate the pharmacotherapeutic morbidity with the UKU rating scale and the Global Clinical Impression. Pharmacotherapeutic optimisation measures were used for those patients with high pharmacotherapeutic morbidity levels. RESULTS: The compliance level was 73.3%. One patient experienced ≥25% increase on the UKU rating scale and another patient suffered from an adverse effect. The final UKU rating reached statistical significance compared with the measurements taken at 48-72 hours (P=.032) and with the base line measurement (P=.007). Patient acceptance was 90%. The impact of optimisation measurements on the pharmacotherapeutic morbidity level was clinically and statistically significant (P<.001). CONCLUSIONS: The proposed protocol has been widely accepted and it is quite certain that it is to be introduced in at a general hospital level.

[Assessment of a pharmaceutical interventional programme in patients on medications with renal risk]. / Evaluación de un programa de intervención farmacéutica en pacientes con medicamentos de riesgo renal.

OBJECTIVE: To compare the adaptation of medical prescriptions according to the dosage guides in patients with renal disease, before and after applying a pharmaceutical intervention programme. The secondary objectives were to prepare a guide to dosing in renal disease and to measure the prevalence of prescription of drugs with renal risk. METHOD: Non-randomised, experimental interventional study (before/after) conducted in a general hospital with 800 beds, including hospitalised patients, over the age of 18, with kidney disease and drugs with renal risk prescribed in their pharmacotherapeutic profile. The study was designed to be carried out in two descriptive cross-cutting phases (control group) and a prospective interventional cohort study (intervention group). The primary variable was the percentage non-adaptation according to the stage of renal disease. RESULTS: The study included 185 patients, 88 in the control group and 97 in the intervention group. In the intervention group, the prevalence of non-compliance before and after the intervention was 18.7 % and 2.1 %, representing a statistically significant reduction in non-adaptation of the dose. The costs saved with the pharmaceutical intervention programme were 1,939.63 euro over two months, the average saving per medication intervened amounting to 62.57 euro (CI 95 %, 23.99-101.14 euro; p = 0.02). CONCLUSIONS: The results of the study indicate that the application of a pharmaceutical care model based on the prospective validation of drugs with renal risk, very significantly improved the adaptation of dosing regimens in kidney disease.

The effect of sesamoid position on outcome following scarf osteotomy for hallux abducto valgus.

BACKGROUND: Hallux valgus is a common forefoot condition, with numerous operations described to correct the deformity. Debate remains as to the relative importance of correcting the position of the sesamoid apparatus. METHODS: Forty-six cases were reviewed. Preoperative and post-operative X-rays were used to measure forefoot width, inter-metatarsal angle (IM), hallux valgus (HV) angle and sesamoid position (Reynolds stations). Satisfaction was assessed via questionnaire. RESULTS: Significant improvements were seen in all radiological parameters. 37/43 patients were satisfied with the result. Comparison between the satisfied and non-satisfied group revealed significant differences in the IM angle (p<0.05) and HV angle (p<0.05). However, patient satisfaction was not associated with post-op sesamoid position or change in sesamoid position (p>0.05). CONCLUSIONS: This study showed that scarf osteotomy, can successfully correct hallux valgus, with high levels of satisfaction. Satisfaction is associated with a greater correction of deformity. Improvement in sesamoid position was not associated with patient satisfaction.

[Use and cost of biological disease-modifying anti-rheumatic drugs in Spain (PRAXIS study)]. / Utilización y coste de los modificadores biológicos de la artritis reumatoide en España (estudio PRAXIS).

OBJECTIVE: To analyse the use of health care resources and the associated costs in patients with rheumatoid arthritis (RA) treated with three biological disease-modifying anti-rheumatic drugs (bDMARDs): etanercept, infliximab and adalimumab. DESIGN: observational, retrospective, multicentre study. Length of study: 6 months. TARGET POPULATION: patients with RA, who have been undergoing treatment for at least one year. SCOPE: Spanish National Health System hospitals. Use of resources: review of the patient records of all patients included in the study by the Hospital Pharmacy Departments. Health care costs: the unit costs were obtained from Spanish databases; disease costs per patient were estimated from the use of resources results (euro in July 2006). Sensitivity analysis: univariate of base case. Budget impact analysis: replacement of infliximab and adalimumab by etanercept for three hospital populations. RESULTS: 1,111 patient records from 41 Spanish hospitals were reviewed, 432 patients were treated with etanercept, 396 were treated with infliximab and 283 with adalimumab. Mean doses: etanercept: 48.90 mg per week; infliximab: 4.14 mg/kg every 8 weeks; adalimumab: 41.58 mg every two weeks (97.8, 138 and 104% respectively, of recommended doses). Treatment with etanercept led to fewer costs. Compared to infliximab, six-monthly costs per patient were reduced with etanercept as follows: bDMARD treatment (232.23 euro), treatment failure (163.42 euro), consultations (54.88 euro), tests (22.52 euro) and costs associated to bDMARD administration (euro 474.42). The saving per patient treated with etanercept compared to infliximab for six months was 577.94 euro. With respect to adalimumab, the savings with etanercept were mainly related to bDMARDs (1,111.74 euro) and test costs (10.16 euro), obtaining a six-monthly saving of euro 906.68 per patient treated with etanercept. Sensitivity analysis confirmed the robustness of the base case in the majority of cases, with six-monthly savings of 395.79-644.32 euro per patient compared to infliximab and of 672.09-1.159.46 euro compared to adalimumab. Infliximab treatment was less expensive than etanercept and adalimumab treatment when taking into consideration the minimum possible number of doses of infliximab (3 doses for six months). Hospital budget savings could be obtained as a consequence of a reduction in costs due to use of etanercept, ranging from 14,500-231,100 euro when replacing infliximab with etanercept and from 22,600-362,600 euro when replacing adalimumab with etanercept, according to the hospital population included (50 to 200 patients). CONCLUSIONS: Our results showed that in most cases, the treatment of rheumatoid arthritis with etanercept compared to infliximab and adalimumab reduced hospital costs.

[ST segment elevation acute coronary syndrome during pregnancy: a case report and review of therapeutic options]. / Síndrome coronario agudo con elevación de ST durante el embarazo: descripción de un caso y revisión de las opciones terapéuticas.

ST segment elevation acute coronary syndrome is a clinical condition that is rarely observed in pregnant women. However, its manifestation is a situation of high maternal-fetal risk. Pharmacotherapeutical management of these patients is difficult and requires individualized care by a multidisciplinary team since many of the standard treatments are included within the categories of teratogencity C or D of the Food and Drug Administration and experience with techniques such as coronary angioplasty with stent placement is scarce. The case of a 32-year woman who was 11 weeks pregnant and diagnosed of acute coronary syndrome with ST segment and its therapeutic approach are described. Furthermore, the information available on epidemiology, etiology and pathophysiology of acute coronary syndrome with ST segment during pregnancy and the specific role of the currently available treatment options are reviewed.

Evaluation of certain food additives and contaminants.

This report represents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluate the safety of various food additives, including flavouring agents, with a view to recommending acceptable daily intakes (ADIs) and to preparing specifications for identity and purity. The Committee also evaluated the risk posed by two food contaminants, with the aim of advising on risk management options for the purpose of public health protection. The first part of the report contains a general discussion of the principles governing the toxicological evaluation and assessment of intake of food additives (in particular flavouring agents) and contaminants. A summary follows of the Committee's evaluations of technical, toxicological and intake data for certain food additives (acidified sodium chlorite, asparaginase from Aspergillus oryzae expressed in Aspergillus oryzae, carrageenan and processed Eucheuma seaweed, cyclotetraglucose and cyclotetraglucose syrup, isoamylase from Pseudomonas amyloderamosa, magnesium sulfate, phospholipase A1 from Fusarium venenatum expressed in Aspergillus oryzae, sodium iron(III) ethylenediaminetetraacetic acid (EDTA) and steviol glycosides); eight groups of related flavouring agents (linear and branched-chain aliphatic, unsaturated, unconjugated alcohols, aldehydes, acids and related esters; aliphatic acyclic and alicyclic terpenoid tertiary alcohols and structurally related substances; simple aliphatic and aromatic sulfides and thiols; aliphatic acyclic dials, trials and related substances; aliphatic acetals; sulfur-containing heterocyclic compounds; aliphatic and aromatic amines and amides; and aliphatic alicyclic linear alpha, beta -unsaturated di- and trienals and related alcohols, acids and esters); and two food contaminants (aflatoxin and ochratoxin A). Specifications for the following food additives were revised: maltol and ethyl maltol, nisin preparation, pectins, polyvinyl alcohol, and sucrose esters of fatty acids. Specifications for the following flavouring agents were revised: maltol and ethyl maltol, maltyl isobutyrate, 3-acetyl-2,5-dimethylfuran and 2,4,5-trimethyl-delta-oxazoline (Nos 1482, 1506 and 1559), and monomenthyl glutarate (No. 1414), as well as the method of assay for the sodium salts of certain flavouring agents. Annexed to the report are tables summarizing the Committee's recommendations for intakes and toxicological evaluations of the food additives and contaminants considered.

A change of expression in the conserved signaling gene MKK7 is associated with a selective sweep in the western house mouse Mus musculus domesticus.

Changes in gene expression are known to occur between closely related species, but it is not yet clear how many of these are due to random fixation of allelic variants or due to adaptive events. In a microarray survey between subspecies of the Mus musculus complex, we identified the mitogen-activated protein-kinase-kinase MKK7 as a candidate for change in gene expression. Quantitative PCR experiments with multiple individuals from each subspecies confirmed a specific and significant up-regulation in the testis of M. m. domesticus. Northern blot analysis shows that this is due to a new transcript that is not found in other tissues, nor in M. m. musculus. A cis-trans test via allele specific expression analysis of the MKK7 gene in F1 hybrids between domesticus and musculus shows that the expression change is mainly caused by a mutation located in cis. Nucleotide diversity was found to be significantly reduced in a window of at least 20 kb around the MKK7 locus in domesticus, indicative of a selective sweep. Because the MKK7 gene is involved in modulating a kinase signalling cascade in a stress response pathway, it seems a plausible target for adaptive differences between subspecies, although the functional role of the new testis-specific transcripts will need to be further studied.

[Replacement therapy with protein C for meningococcal sepsis and fulminant purpura in pediatric patients]. / Tratamiento sustitutivo con proteína C en sepsis meningocócica y púrpura fulminante en pacientes pediátricos.

Disseminated intravascular coagulation as associated to sepsis contributes to the development of clinical multiple organ failure by extensive thrombosis in microcirculation vessels. This condition commonly manifests itself in severe meningococcal sepsis. On the skin, its clinical manifestation is extensive purpura with necrotic lesions that usually progress to serious distal ischemia and may call for amputation. A common denominator in these events regarding hemostasis is a depletion of so-called natural anticoagulant proteins, particularly protein C. According to clinical observations replacement therapy with human plasma-derived protein C concentrates has been associated with significantly improved clinical outcome in patients with meningococcal sepsis and fulminant purpura. This paper reports a case of acquired protein C deficiency in a girl with meningococcal sepsis, fulminant purpura, disseminated intravascular coagulation, and septic shock. Fresh plasma therapy was intended to increase consumption coagulopathy-depleted coagulation factors and to provide small amounts of protein C. The inability to restore protein C concentrations above 30%, and the presence of severe thrombopenia in the setting of disseminated intravascular coagulation led to the onset of replacement therapy using a human protein C concentrate (Ceprotin), which increased plasma protein C concentrations and contributed to revert the existing hypercoagulability status. Finally, evidence available in the literature regarding fulminant meningococcal sepsis management using human protein C concentrates and recombinant activated protein C is discussed.

Monitoring trough plasma concentrations of mycophenolate mofetil in patients with uveitis.

BACKGROUND: Mycophenolate mofetil (MMF) has been used successfully in patients with various forms of uveitis not responsive to other immunosuppressants. Nevertheless, for these patients neither recommendations for optimal dosage of MMF nor data concerning drug exposure of MMF are available. OBJECTIVE: To describe the results of the therapeutic drug monitoring (TDM) of MMF trough concentrations in a cohort of patients with uveitis, with the aim of optimizing the dosage of this drug, by maintaining a target concentration to achieve adequate immunosuppression with a minimal risk of therapeutic failure or toxicity. PATIENTS AND METHODS: This study describes the results of monitoring trough plasma concentrations of MMF in 12 patients with uveitis during a mean period of 21.4 months. Patients included one with Stevens-Johnson syndrome, one with Graves-Basedow's disease, one with Behcet's disease, one with idiopathic thrombocytopenic purpura and the rest with idiopathic uveitis. All patients were treated with steroids and additional therapy prior to treatment with MMF. RESULTS: Pharmacokinetic monitoring of mycophenolic acid (MPA) was performed with 108 trough plasma samples using an EMIT assay. Mean daily MMF dose was 24.5 +/- 6.3 mg/kg and mean trough MPA concentration was 2.9 +/- 1.9 microg/mL. Therapy was effective in 10 patients (83%). There were few side-effects: diarrhoea, excitement, agitation and cough that disappeared with daily dose reduction of MMF. CONCLUSIONS: MMF was effective in the majority of patients with uveitis with an acceptable profile of side-effects. TDM of MMF in patients with uveitis is clinically practicable and may help to optimize individual immunosuppressive therapy. We estimated that MMF dosages in the range of 0.5-1.5 g/day might be sufficient for treating uveitis and we recommend an initial target range of 2-4 microg/mL, which included 50% of our results. Randomized controlled trials are essential to confirm the efficacy of MMF in uveitis.

[Pharmacokinetic interaction between valproic acid and carbapenem-like antibiotics: a discussion of three cases]. / Interacción farmacocinética entre ácido valproico y antibióticos carbapenémicos: descripción de tres casos.

A number of literature references suggest that carbapenem-like antibiotics decrease plasma concentrations of valproic acid in epileptic patients. This interaction may result in a recurrence of epileptic seizures in these patients. To clarify the possible mechanism of such carbapenem-valproic acid interaction several experimental studies have been carried out in animals. However, the mechanism of this drug-drug interaction is as yet uncertain. in this article we report three new cases that were observed in our hospital within three months. One of these patients developed seizures. We also review the different mechanisms proposed, as well as cases published to this day. All these data demonstrate that care should be taken in using these potent antibiotics in patients receiving valproic acid.