ADAM17 is a survival factor for microglial cells in vitro and in vivo after spinal cord injury in mice.

A disintegrin and metalloprotease 17 (ADAM17) is a sheddase with important substrates including tumor necrosis factor-α (TNF-α) and its receptors, the p75 neurotrophin receptor (p75NTR), and members of the epidermal growth factor family. The rationale of this study was to inhibit ADAM17-induced shedding of soluble TNF-α in order to reduce detrimental inflammation after spinal cord injury (SCI). However, using the specific ADAM17 blocker BMS-561392 in neuronal and glial cell cultures, we show that proper functioning of ADAM17 is vital for oligodendrocyte and microglia survival in a p44 MAPK-dependent manner. In contrast, genetic ablation of ADAM17 specifically increases microglial death. Surprisingly, although blocking ADAM17 in vivo does not substantially change the ratio between membrane-bound and soluble TNF-α, it increases expression of the pro-apoptotic marker Bax and microglial apoptosis while impairing functional recovery after SCI. These data suggest that ADAM17 is a key survival factor for microglial cells after SCI.

[Summary of the practice guideline 'Otitis externa' (first revision) from the Dutch College of General Practitioners]. / Samenvatting van de standaard 'Otitis externa' (eerste herziening) van het Nederlands Huisartsen Genootschap.

* The practice guideline 'Otitis externa', first developed by the Dutch College of General Practitioners in 1995, has been revised and updated. * It is no longer recommended to perform a KOH test on material collected from the auditory canal in patients with otitis externa. * Eardrops that contain both acid and corticosteroids are preferred over eardrops that contain acid only. * Suitable options include acidic eardrops with hydrocortisone 1% FNA and acidic eardrops with triamcinolone acetonide 0.1% FNA at a dose of 3 drops thrice daily. * The guideline contains a detailed discussion of the ototoxicity of eardrops in patients with tympanic membrane perforation. * Management of these patients, however, remains unchanged: the preferred approach is aluminium acetotartrate eardrops 1.2% FNA.

Surgery for temporal lobe epilepsy after cerebral malaria.

The most common indication for epilepsy surgery is temporal lobe epilepsy (TLE) which usually is divided into two categories, mesial and lateral TLE. The commonest pathology underlying mesial temporal lobe epilepsy (MTLE) is mesial temporal sclerosis (MTS); we report on a 50-year-old male patient, who contracted cerebral malaria and developed MTLE shortly thereafter. Magnetic resonance imaging (MRI) showed MTS. Surgical treatment was an anteromedial temporal lobe resection with amygdalohippocampectomy. The patient is seizure free, 36 months after surgical treatment. This is the first report describing MTLE-onset subsequent to cerebral malaria and discussing the potential pathophysiological relationship between cerebral malaria and MTS.

Naïve CTLs require a single brief period of antigenic stimulation for clonal expansion and differentiation.

In defense of the host, the immune system must often raise an effective cytotoxic T lymphocyte (CTL) response from a small number of clonal precursors. The degree to which activation stimuli regulate the expansion and differentiation of naïve CTLs, however, remains unknown. Using an engineered antigen-presenting cell (APC) system that allows control over antigenic stimulation, we studied the signaling duration requirements for priming and clonal expansion of naïve CTLs. We found that naïve CTLs become committed after as little as 2 h of exposure to APCs and that their subsequent division and differentiation can occur without the need for further antigenic stimulation of the daughter cells, whether priming is in vitro or in vivo. These data show that after a brief interaction with stimulatory APCs, naïve CTLs initiate a program for their autonomous clonal expansion and development into functional effectors.

Comparison of the addition of three different doses of sufentanil to 0.125% bupivacaine given epidurally during labour.

In a double-blind, randomised, prospective study 150 women in labour received intermittent epidural injections of 10 ml 0.125% bupivacaine with adrenaline (1:800,000) with 5, 7.5 or 10 micrograms of sufentanil added. The onset, duration, and quality of analgesia were compared. Motor block, type of delivery and neonatal Apgar scores were noted. The onset, duration, and quality of analgesia were generally similar in the three groups, except following the second injection when the quality of analgesia was significantly superior in the sufentanil 7.5 and 10 micrograms groups. Motor blockade and type of delivery did not differ between the groups and there were no differences in neonatal Apgar scores. No patient required more than three injections. We conclude that 7.5 micrograms sufentanil is the optimal dose to add to intermittent epidural injections of 10 ml 0.125% bupivacaine with adrenaline (1:800,000) for pain relief in labour.