Agomelatine and its therapeutic potential in the depressed patient

Despite advances in understanding potential disease mechanisms and in developing novel therapeutic approaches to the treatment of major depressive disorder, the disease continues to carry an enormous personal, social, and economic burden. Agomelatine represents an important opportunity to advance the treatment of depression. It is a melatonergic (MT₁ and MT₂) agonist and serotonergic (5HT_2C) antagonist. Evidence from animal models of depression, complements emerging clinical data. In a dose range of 25–50 mg daily, agomelatine is an effective antidepressant with a very favorable side-effect profile. In particular, sleep restorative action in the absence of sedation and minimal effect on sexual function suggests that agomelatine represents a worthwhile treatment alternative for patients with major depressive disorder.     

Cyclophosphamide 'pulses' in chronic progressive multiple sclerosis. A preliminary clinical trial

To our knowledge, this is the first clinical trial in multiple sclerosis (MS) demonstrating the feasibility of directing immunomodulating therapy by monitoring immunologic results. Cyclophosphamide was administered at monthly intervals, escalating the dose until there was a significant reduction in both the number of blood B lymphocytes and helper/inducer (CD4) T cells of 14 patients with chronic progressive MS. The frequency and severity of adverse effects led us to conclude that the regimen is too toxic for the long-term treatment of patients with MS.     

Scapulothoracic motion in normal shoulders and shoulders with glenohumeral instability and impingement syndrome. A study using Moiré topographic analysis.

Qualitative visual inspection and manual muscle testing are traditional methods of evaluation that may overlook subtle weakness of the axioscapular musculature. A modification of the standard technique of Moiré topographic analysis of spinal deformity was applied to assess axioscapular muscle function in 51 subjects: 22 asymptomatic individuals, 22 with shoulder instability, and seven with impingement syndrome. Static Moiré evaluation demonstrated scapulothoracic asymmetry or increased topography in 14% of asymptomatic subjects, compared with 32% and 57% in the instability and impingement groups, respectively. The dynamic Moiré test demonstrated an abnormal Moiré pattern in 18% of asymptomatic individuals, compared with 64% and 100% in the instability and impingement groups, respectively. Axioscapular muscle dysfunction is common with both instability and impingement syndrome of the shoulder, although it remains to be determined whether this represents a primary or secondary phenomenon.     

Treatment of ischemic leg ulcers with pentoxifylline: a case report and theoretical considerations

Ischemic ulcers remain difficult to treat. We describe a patient with bilateral ischemic leg ulcers treated preoperatively with pentoxifylline. She had a successful skin graft with no rejection of the graft. The theoretical advantage of treatment with pentoxifylline is discussed, with emphasis not only on its hemorheological properties, but also on its actions on the prostaglandin pathway, platelet aggregation, and thrombosis. We suggest that preoperative pentoxifylline treatment may be a useful adjunct in the closure of ischemic ulcers.     

Epinephrine reduces the sedative side effects of epidural sufentanil for labour analgesia

PURPOSE: The use of opioids in labour analgesia has primarily been as an adjuvant to local anesthetics. For early labour, satisfactory analgesia with epidural sufentanil alone is possible. This study evaluates the impact of epinephrine on sedative side effects and analgesia related to the latter technique. METHODS: After Institutional Review Board approval and informed consent this prospective, randomized, double-blind study evaluated 43 nulliparous subjects requesting epidural analgesia. The study site, a tertiary care obstetric unit, accommodates 3500-4500 deliveries annually. Group selection was randomized and blinded by selection of a sealed envelope containing a number which corresponded to a premixed labelled syringe of saline or epinephrine (100 microg/mL). An epidural catheter was placed in a standardized fashion. All subjects received 40 microg of sufentanil and 0.5 mL from the premixed syringe, diluted to 10 mL with NaCl. A blinded observer collected data on maternal sedation, lightheadedness, hemodynamics, oxygenation, and fetal heart rate over a one-hour period following sufentanil injection. RESULTS: The addition of epinephrine significantly (P <0.05) reduced the incidence of sedation and lightheadedness after epidural sufentanil at all data collection points, except two. Analgesic duration was also significantly prolonged by this addition (120 +/- 56 vs 84 +/- 32 min). Maternal satisfaction was high regardless of solution. CONCLUSION: Forty micrograms of epidural sufentanil produces satisfactory analgesia in early labour. The addition of epinephrine improves the side effect profile of this technique while prolonging the duration of analgesia. Epidural sufentanil requires attention to maternal monitoring of oxygenation as maternal desaturation occurred in both groups.     

Non-isotopic hybridization assays for bacterial DNA samples

The background problem associated with the use of streptavidin in detecting biotin-labelled probes hybridized to DNA in crude bacterial extracts has been investigated. We have found that streptavidin binds specifically to a limited number of polypeptides which are difficult to remove by rapid extraction processes. Altering the hybridization and detection protocols results in a marked but not complete reduction of non-specific background in streptavidin-biotin assays. Complete elimination of non-specific background was achieved only when streptavidin was replaced with antibodies for the detection of biotinylated or sulphone-modified probes. The antibody-sulphone and streptavidin-biotin dot blot assays described here require 4.5-5 hours to perform and can detect DNA sequences in samples extracted from 2 x 10(7) cells or fewer.