The effects of dietary supplementation with n-3 polyunsaturated fatty acids in patients with rheumatoid arthritis: a randomized, double blind trial

STUDY OBJECTIVE: To determine the effect of dietary supplementation with n-3 polyunsaturated fatty acids (n-3 PUFA) on disease variables in patients with rheumatoid arthritis. DESIGN: Multicenter, randomized, placebo controlled, double blind. SETTING: Three Danish hospital Departments of Rheumatology. PATIENTS: Fifty-one patients with active rheumatoid arthritis. INTERVENTION: Random allocation to 12 weeks of treatment with either six n-3 PUFA capsules (3.6 g) or six capsules with fat composition as the average Danish diet. MAIN RESULTS: Significant improvement of morning stiffness and joint tenderness. No significant effect on the four other assessed clinical parameters. No serious side effects. CONCLUSIONS: Dietary supplementation with n-3 PUFA in patients with rheumatoid arthritis improved two out of six patient reported disease parameters. Further studies are needed to clarify the more precise role of n-3 PUFA in the treatment of rheumatoid arthritis.     

Antinociceptive effects of trazodone and m-chlorophenylpiperazine (mCPP) in mice: interaction with morphine

1. The antidepressant trazodone and its main metabolite m-chlorophenylpiperazine (mCPP) were investigated for their analgesic properties and their sensitivity to a threshold dose of morphine in acetic acid abdominal constriction and hot plate tests. 2. The drugs elicited hypoalgesic effects at about the same doses in the two analgesic assays. 3. Naloxone (2 mg/kg i.p.) prevented the hypoalgesia of trazodone but not of mCPP in the hot plate test. The opiate antagonist did not affect the responses of both drugs to the writhing test. 4. Subanalgesic doses of the two drugs increased the sensitivity to morphine in both assays. The results further support the suggested role played by opioid and 5-HT systems on depression.     

Optimizing acitretin use in patients with plaque psoriasis

Acitretin is one of the systemic agents used for the treatment of psoriasis. Because different acitretin dosages resulted therapeutically successful, there is no general agreement on the optimal dose regimen. To report acitretin efficacy and safety in a real‐life setting, wherein patient‐tailored dose regimen is usually prescribed, a retrospective analysis evaluating charts of all plaque‐type psoriasis patients treated with acitretin from the clinic database was performed. PASI score improvement, as well as PASI 50, 75, 90, and 100 responses were assessed throughout the observational period. Overall, 52% PASI score reduction and a satisfactory safety profile were detected. PASI 50, 75, 90, and 100 response was achieved by 53%, 48%, 28%, and 14%, respectively. Treatment consisted on a mean daily acitretin dose of 25.01 mg. The initial dose was increased (51.2% of cases) or decreased (48.8%) prescribing a mean daily dose of 29.8 mg and 20.02 mg, respectively. This study proposed a dose regimen customized on clinical response and patient's needs, to optimized acitretin benefit.     

Perfil Clínico e Desfechos em 30 Dias de Pacientes Portadores de Valva Aórtica Bicúspide Submetidos à Cirurgia em Valva Aórtica e/ou Aorta

BackgroundThe bicuspid aortic valve (BAV) affects 0.5 to 2% of the population and is associated with valve and aortic alterations. There is a lack of studies on the profile of these patients in the Brazilian population.ObjectiveTo describe the profile of patients with BAV undergoing valve and/or aortic surgery in a tertiary cardiology center, in addition to the outcomes related to the intervention.MethodsRetrospective cohort including 195 patients (mean age 54±14 years, 73.8% male) diagnosed with BAV who underwent surgical approach (valvular and/or aorta) from 2014 to 2019. Clinical data, echocardiographic and tomographic studies were evaluated, as well as characteristics of the intervention and events in 30 days. A value of p<0.05 was considered statistically significant.ResultsWe found a high prevalence of aortic aneurysm (56.5%), with a mean diameter of 46.9±10.2 mm. Major aortic regurgitation was found in 25.1% and major aortic stenosis in 54.9%. Isolated aortic valve surgery was performed in 48.2%, isolated aortic surgery in 6.7% and combined surgery in 45.1%. The 30-day mortality was 8.2%. In the multivariate analysis, the predictors of the combined outcome at 30 days (death, atrial fibrillation and reoperation) were age (OR 1.044, 95% CI 1.009-1.081, p=0.014) and left ventricular mass index (OR 1.009, 95% CI 1.000-1.018, p=0.044).ConclusionPatients with BAV approached in our service have a higher incidence of aortopathy, with the additional need to evaluate the aorta with computed tomography or magnetic resonance imaging.     

Molecular characterization of CTX‐M‐15‐producing clinical isolates of Escherichia coli reveals the spread of multidrug‐resistant ST131 (O25:H4) and ST964 (O102:H6) strains in Norway

Nationwide, CTX‐M‐producing clinical Escherichia coli isolates from the Norwegian ESBL study in 2003 (n=45) were characterized on strain and plasmid levels. Bla_CTX‐M allele typing, characterization of the genetic environment, phylogenetic groups, pulsed field gel electrophoresis (PFGE), serotyping and multilocus sequence typing were performed. Plasmid analysis included S1‐nuclease‐PFGE, polymerase chain reaction‐based replicon typing, plasmid transfer and multidrug resistance profiling. Bla_CTX‐M‐15 (n=23; 51%) and bla_CTX‐M‐14 (n=11; 24%) were the major alleles of which 18 (78%) and 6 (55%), respectively, were linked to ISEcp1. Thirty‐two isolates were of phylogenetic groups B2 and D. Isolates were of 29 different XbaI‐PFGE‐types including six regional clusters. Twenty‐three different O:H serotypes were found, dominated by O25:H4 (n=9, 20%) and O102:H6 (n=9, 20%). Nineteen different STs were identified, where ST131 (n=9, 20%) and ST964 (n=7, 16%) were dominant. Bla_CTX‐M was found on ≥100 kb plasmids (39/45) of 10 different replicons dominated by IncFII (n=39, 87%), FIB (n=20, 44%) and FIA (n=19, 42%). Thirty‐nine isolates (87%) displayed co‐resistance to other classes of antibiotics. A transferable CTX‐M phenotype was observed in 9/14 isolates. This study reveals that the majority of CTX‐M‐15‐expressing strains in Norway are part of the global spread of multidrug‐resistant ST131 and ST‐complex 405, associated with ISEcp1 on transferrable IncFII plasmids.     

A comparative study of pseudorabies virus (PRV) strains with defects in thymidine kinase and glycoprotein genes

In the course of two experiments, an examination was made of the virulence and neuroinvasiveness for pigs of two pseudorabies virus mutants (strain 6C2TK(-), with a defect in thymidine kinase (TK) function; and strain 6C2TK(-), gI(-)/gE(-), with defects in TK and glycoproteins I and E) and of the wild-type parent strain (86/27V). At various times after intranasal inoculation, pigs were killed and samples of tonsil, lung and different levels of the trigeminal and olfactory nervous pathways were examined by methods that included viral isolation, polymerase chain reaction assay and immunohistochemistry. Both mutant viruses were of reduced virulence, as indicated by no more than moderate clinical signs and lesions, and only sporadic isolation of virus; moreover, unlike the wild-type parent strain, the mutant viruses were not reactivated from the latent state by corticosteroid treatment. In addition, migration of the mutant strains to the central nervous system (olfactory and trigeminal nervous pathways) was reduced as compared with that of the wild-type strain. Thus, mutations in the genes encoding the TK enzyme and the gI/gE complex were associated with reduced virulence, reduced replication in peripheral target tissues, and reduced migration to the olfactory and trigeminal pathways.     

Seizures in HIV-seropositive individuals: epidemiology and treatment

Seizures are a relatively common occurrence in patients with HIV infection. They may be a result of HIV infection of the CNS or a manifestation of an opportunistic infection. Because seizures are likely to recur in patients infected with HIV and because they are a poor prognostic indicator, it is generally recommended that all HIV-seropositive patients experiencing a first seizure without a recognisable and reversible cause be treated. Clinicians faced with treating seizures in HIV-seropositive patients often encounter a therapeutic dilemma since few data exist in this area. In selecting appropriate anticonvulsant therapy, clinicians must consider both therapy-compromising drug-drug and drug-disease interactions. Ideal anticonvulsants for this setting are those that do not effect viral replication, have limited protein binding and have no effects on the cytochrome P450 system, such as gabapentin, topiramate and tiagabine. Unless the benefits outweigh the risks, valproic acid (sodium valproate) should be avoided as it has been shown to stimulate HIV replication. Since few data exist, controlled trials examining pharmacokinetic and pharmacodynamic interactions between anticonvulsants and antiretrovirals are needed. Until such time, clinicians caring for these patients should examine existing data carefully and employ vigilant monitoring.     

Use of club drugs by HIV-seropositive and HIV-seronegative gay and bisexual men

Club drugs such as methylenedioxymethamphetamine (MDMA, ecstasy), gamma hydroxybutyrate (GHB), and ketamine are among the fastest-growing drugs of abuse in the United States. Reports have shown that some gay and bisexual men are likely to engage in club-drug use in a myriad of venues. This is concerning given that the use of club drugs has been linked to high-risk sexual behaviors. Further, the use of club drugs by HIV-seropositive individuals may have detrimental outcomes on disease progression by either influencing adherence, resulting in drug-drug interactions with antiretrovirals, or potentially compounding immune suppression. Clinicians caring for HIV-seropositive and -seronegative individuals should be aware of the clinical effects and management guidelines associated with these chemicals. This article reviews the available literature with regard to the use of club drugs by HIV-seropositive and -seronegative gay and bisexual men. Although club-drug use may be associated with many risk behaviors for HIV infection, this review focuses on risk behavior among gay and bisexual men since this is the group for which the most data have been reported. The clinical effects and management guidelines associated with these agents are described, and the potential detrimental effects of these substances on HIV disease are discussed.     

Epilepsy surgery in tuberous sclerosis: multistage procedures with bilateral or multilobar foci

Refractory seizures are common in patients with tuberous sclerosis and can contribute to developmental delay and behavioral problems. Surgical intervention can reduce the seizure burden in selected patients with tuberous sclerosis and refractory epilepsy, thereby improving cognitive function, behavior, and quality of life. However, the risks of surgery are usually considered unacceptable when the epileptogenic focus lies over dominant hemisphere eloquent cortex or is multilobar. Multistage invasive monitoring can provide detailed data regarding the location and number of ictal foci and functional extraoperative mapping can precisely delineate the boundaries of eloquent areas of the brain. If independent ictal onsets are demonstrated, a staged surgical approach can allow a more aggressive yet safe procedure in selected patients. A combination of staged resection and multiple subpial transections may provide an opportunity to treat epileptogenic foci located over eloquent cortex. Bilateral staged resections can be used when independent bihemispheric foci are present in patients with tuberous sclerosis. This article presents two cases, one of which (case 2) was previously reported, on successful multistage surgical treatment of epileptogenic foci located over an eloquent cortex or in both hemispheres in children with tuberous sclerosis. This case is represented since there is additional follow-up available and the prior report was to a neurosurgical audience. This multistage approach permitted resection of epileptogenic foci that would traditionally have been considered inoperable.     

Peripheral blood abnormalities in Alzheimer disease: evidence for early endothelial dysfunction

Clinical and epidemiologic studies demonstrate that vascular risk factors may be involved in Alzheimer disease (AD). To evaluate whether vascular abnormalities are an early feature of AD, several parameters of coagulation and fibrinolysis were assessed. Thirty patients with mild AD and 30 age-matched control subjects entered the study. All subjects performed a standardized clinical and laboratory protocol. Persons with vascular risk factors and systemic diseases were excluded. AD patients present significant increased levels of thrombomodulin (p < 0.0001) and sE-selectin (p < 0.03). In contrast, no difference was found between the two diagnostic groups in the levels of beta-thromboglobulin, prothrombin fragment 1+2, fibrinogen, and von Willebrand factor. No other association but diagnosis was found with thrombomodulin and sE-selectin. These findings suggest that endothelial dysfunction is an early event in AD patients.