Methotrexate: its use in the rheumatic diseases

Methotrexate in a low dose intermittent regimen has become popular as a therapeutic choice for refractory psoriatic arthritis, polymyositis, Reiter's disease and more recently rheumatoid arthritis. As a folate analogue, it inhibits the formation of reduced folate cofactors which participate in a host of important reactions including DNA synthesis. It has been shown to have both immunosuppressive and anti-inflammatory properties although its precise mechanism of action in these diseases is not known. It may be variably absorbed especially in psoriatics and its action may be antagonized by folate supplements. Its major route of metabolism appears to be via the enterohepatic circulation. Numerous drugs, including salicylates, may increase serum levels by displacing the drug from protein binding sites and by competing for renal excretion. It has fewer short term side effects than the other immunosuppressives used in rheumatic disease. Its major long term toxicity is liver fibrosis or cirrhosis which appears to increase with greater cumulative dosage and treatment duration. Several recent reports of hypersensitivity pneumonitis reinforce the previous literature on this topic. Pulmonary toxicity may be more common than suggested as more patients are treated with methotrexate for rheumatic diseases. Clinical studies in general have been uncontrolled and lacking in scope and size. Nevertheless, the literature to date appears to show this to be an excellent drug for use in the diseases mentioned. Prospective double blind controlled studies on psoriatic arthritis and rheumatoid arthritis should help establish this drug as the immunosuppressive of choice in these diseases.     

A brief sleep scale for Posttraumatic Stress Disorder: Pittsburgh Sleep Quality Index Addendum for PTSD

Sleep disturbances reflect a core dysfunction underlying Posttraumatic Stress Disorder (PTSD). Specifically, disruptive nocturnal behaviors (DNB) may represent PTSD-specific sleep disturbances. The Pittsburgh Sleep Quality Index Addendum for PTSD (PSQI-A) is self-report instrument designed to assess the frequency of seven DNB. The goal of this study was to examine the psychometric properties of the PSQI-A to characterize DNB in a group of participants with and without PTSD. Results indicate that the PSQI-A has satisfactory internal consistency and good convergent validity with two standard PTSD measures even when excluding their sleep-related items. A global PSQI score of 4 yielded a sensitivity of 94%, a specificity of 82%, and a positive predictive value of 93% for discriminating participants with PTSD from those without PTSD. The PSQI-A is a valid instrument for PTSD applicable to both clinical and research settings.     

Alterations in regional cerebral glucose metabolism across waking and non-rapid eye movement sleep in depression

BACKGROUND: Depression is associated with sleep disturbances, including alterations in non-rapid eye movement (NREM) sleep. Non-rapid eye movement sleep is associated with decreases in frontal, parietal, and temporal cortex metabolic activity compared with wakefulness. OBJECTIVE: To show that depressed patients would have less of a decrease than controls in frontal metabolism between waking and NREM sleep and to show that during NREM sleep, they would have increased activity in structures that promote arousal. DESIGN: Subjects completed electroencephalographic sleep and regional cerebral glucose metabolism assessments during both waking and NREM sleep using [(18)F]fluoro-2-deoxy-D-glucose positron emission tomography. SETTING: General clinical research center. PATIENTS: The study included 29 unmedicated patients who met the Structured Clinical Interview for DSM-IV criteria for current major depression and who had a score of 15 or greater on a 17-item Hamilton Rating Scale for Depression and 28 medically healthy subjects of comparable age and sex who were free of mental disorders. MAIN OUTCOME MEASURES: Electroencephalographic sleep and regional cerebral metabolism during waking and NREM sleep. RESULTS: Depressed patients showed smaller decreases than healthy subjects in relative metabolism in broad regions of the frontal, parietal, and temporal cortex from waking to NREM sleep. Depressed patients showed larger decreases than healthy subjects in relative metabolism in the left amygdala, anterior cingulate cortex, cerebellum, parahippocampal cortex, fusiform gyrus, and occipital cortex. However, in post hoc analyses, depressed patients showed hypermetabolism in these areas during both waking and NREM sleep. CONCLUSIONS: The smaller decrease in frontal metabolism from waking to NREM sleep in depressed patients is further evidence for a dynamic sleep-wake alteration in prefrontal cortex function in depression. Hypermetabolism in a ventral emotional neural system during waking in depressed patients persists into NREM sleep.     

Disposable material for tracheal intubation: pilot study using Penlon Crystal blades and Penlon Lary Gard sheaths

OBJECTIVE: The risk of cross infection due to non-conventional infectious agents has led to the development of single-use disposable medical material. For laryngoscopy, two attitudes have been proposed: the use of disposable blades or disposable translucide cover sheaths with steel blades. Practice studies assessing the quality of these devices are scarce, leaving the physician to his own experience. STUDY DESIGN: Open pilot study assessing satisfaction of the users during tracheal intubation. PATIENTS AND METHODS: Hundred patients of general surgery requiring tracheal intubation underwent laryngoscopy in routine condition with disposable blades (Penlon Crystal) or disposable cover sheaths (Penlon Lary Gard) with steel blades. The users gave a general appreciation of the device and specific comments on the easiness of insertion of the blade, intensity of light and its focus, quality of glottic exposure, easiness of tracheal tube insertion, and solidity of the device. RESULTS: With both devices, intubation was impossible in 6% of the patients. The users considered that intubation was performed in comfortable conditions with both devices. Dim light was noticed with Crystal blade. CONCLUSION: In case of use of disposable material, both devices seem to be close in terms of quality of intubation.     

Update on psychotropic medication use in renal disease

Renal failure is a common medical condition, and many patients have comorbid psychiatric disorders. In this review, which is intended as a resource for consultation psychiatrists, the authors discuss pharmacokinetic considerations and provide information about the use of individual psychotropic medications in patients with renal disease. Most psychotropic medications are fat soluble, easily pass the blood-brain barrier, are not dialyzable, are metabolized primarily by the liver, and are excreted mainly in bile. Consequently, the majority of these drugs can be safely used with the end-stage renal disease population.     

In vivo antigen presentation

Monoclonal antibodies specific for defined peptide-MHC complexes are now being used to physically detect T-cell receptor ligands. These reagents have resulted in the identification of the cells that present antigen in lymphoid and non-lymphoid tissues after various forms of antigen administration. In addition, recent advances in real-time imaging technology have begun to measure the rate and directionality of T-cell movement relative to antigen-presenting cells in lymph nodes, shedding light on the earliest events in T-cell activation in a physiological setting.