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.     

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.     

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.     

Further study on the vascular basis for the reimplantation of the hand amputated through the palm

Summary Based on the anatomic data obtained from earlier studies on the vascular anatomy of the hand, the vascular architecture in the palm of the hand was studied on 60 sides of unembalmed adult upper extremities. Each palm was divided into 64 squares by 8 sagittal and 8 transverse sections. The vascular architecture in these squares and the arterial relations between them were observed and measured by angiography, operative microscopic dissection and computerised three-dimensional reconstruction. According to the pattern of the blood-vessels, the amputated palms can be classified into 4 types. The anatomic basis for the vascular anastomosis in each type is defined. There are three key-areas for the blood-supply of the palm and their significance is discussed. Apart from the 4 types of transversely amputated palms, the repair programe of the blood-vessles in 4 types of common obliquely amputated palms are also discussed.

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Etude complémentaire de l'anatomie vasculaire de la main pour la réimplantation des amputations transpalmaires

Résumé Sur la base de données anatomiques obtenues lors de précédents travaux sur l'anatomie vasculaire de la main, l'architecture vasculaire palmaire a été étudiée sur 60 extrémités supérieures de cadavres d'adultes, non embaumés. Chaque paume a été divisée en 64 carrés par 8 sections sagittales et 8 sections transversales. L'architecture vasculaire à l'intérieur des carrés et les relations artérielles entre eux ont été étudiées et mesurées par angiographie, dissection au microscope opérateur et reconstruction computérisée en 3D. Les paumes amputées ont été regroupées en 4 types d'après la distribution des vaisseaux sanguins. Les données anatomiques concernant les anastomoses vasculaires sont précisées. Il existe trois zones clés pour l'irrigation de la paume. Leur importance quant à l'irrigation de la main est exposée. Outre la division des paumes amputées transversalement en 4 types, le programme de réparation de vaisseaux dans les 4 types d'amputations obliques communes de la paume et aussi discuté.

     

Adenocarcinomain Situof the Uterine Cervix: Management and Outcome

Objective: To retrospectively review the management of adenocarcinomain situof the uterine cervix, to determine the outcome of conization versus hysterectomy, and to compare the results achieved by different methods of conization. Methods: We performed a retrospective pathology and chart review of 46 patients with cervical adenocarcinomain situfrom January 1980 to October 1994. Results: Nine patients were managed during the first half of the study period and 37 were managed in the second half. The mean age of patients was 38.4 years (range 25–72). Forty-five of 46 patients were diagnosed as a result of an abnormal Pap smear, although only 19 smears indicated adenocarcinomain situor other glandular abnormalities. Cold knife conization resulted in a 33% rate of positive margins for adenocarcinomain situcompared to 50% for large loop excision of the transformation zone (LLETZ). Among 24 conservatively managed patients with negative conization margins, there have been 2 (8.3%) recurrences of adenocarcinomain situ.Among patients not undergoing hysterectomy as definitive treatment, 1 of 18 (6%) patients undergoing cold knife conization recurred, compared to 4 of 14 (29%) managed with LLETZ, despite a 63.4-month shorter mean follow-up interval for the LLETZ patients. Conclusions: Cold knife conization is associated with a lower rate of recurrence of cervical adenocarcinomain situcompared to LLETZ. We recommend cold knife conization for patients who are not treated with hysterectomy.     

Melatonin responses to clonidine and yohimbine challenges.

Melatonin (MT) release from the pineal gland has been used as a marker for central noradrenergic function in major depression. Norepinephrine acts at both alpha and beta adrenergic receptors on the pinealocyte membrane to mediate nocturnal MT release, but in humans the contribution of each receptor class is unclear. In order to explore the effect of alpha 2 receptors on MT release, 10 female subjects were given oral challenges, in separate placebo-controlled trials, of either 10.8 mg of yohimbine, an alpha 2 adrenergic antagonist, or clonidine, a partial alpha 2 adrenergic agonist, at doses of either 200 micrograms or 300 micrograms. Post-challenge serum melatonin was measured from 18:00 h to 22:00 h in both studies as was urinary 6-sulphatoxy-melatonin (aMT6s), the major metabolite of MT (from 18:00 h to 22:00 h, and from 22:00 h to 10:00 h). Growth hormone (GH) was also assayed following the clonidine challenge, and blood pressure, pulse rate, and side effects were monitored after both challenges. Neither yohimbine nor clonidine significantly altered nocturnal serum MT levels compared to placebo. However, there was a significant increase in urinary aMT6s between 18:00 h and 22:00 h following yohimbine ingestion. Yohimbine ingestion produced significant rises in pulse rate and the urge to urinate compared to placebo. Both doses of clonidine resulted in a significant reduction in pulse rate, systolic and diastolic blood pressure, and significant increases in drowsiness and other measures of sedation following ingestion. Only clonidine 300 micrograms produced a significant elevation in GH release. This study highlights the limitations of oral neuroendocrine challenge studies.