Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a devastating inherited disorder characterized by episodic syncope and/or sudden cardiac arrest during exercise or acute emotion in individuals without structural cardiac abnormalities. Although rare, CPVT is suspected to cause a substantial part of sudden cardiac deaths in young individuals. Mutations in RYR2, encoding the cardiac sarcoplasmic calcium channel, have been identified as causative in approximately half of all dominantly inherited CPVT cases. Applying a genome-wide linkage analysis in a large Swedish family with a severe dominantly inherited form of CPVT-like arrhythmias, we mapped the disease locus to chromosome 14q31-32. Sequencing CALM1 encoding calmodulin revealed a heterozygous missense mutation (c.161A>T [p.Asn53Ile]) segregating with the disease. A second, de novo, missense mutation (c.293A>G [p.Asn97Ser]) was subsequently identified in an individual of Iraqi origin; this individual was diagnosed with CPVT from a screening of 61 arrhythmia samples with no identified RYR2 mutations. Both CALM1 substitutions demonstrated compromised calcium binding, and p.Asn97Ser displayed an aberrant interaction with the RYR2 calmodulin-binding-domain peptide at low calcium concentrations. We conclude that calmodulin mutations can cause severe cardiac arrhythmia and that the calmodulin genes are candidates for genetic screening of individual cases and families with idiopathic ventricular tachycardia and unexplained sudden cardiac death.
The adductor-canal-blockade significantly reduced morphine consumption and pain during 45 degrees flexion of the knee compared with placebo. In addition, the adductor-canal-blockade significantly enhanced ambulation ability assessed by the TUG test.
Because both the saphenous nerve and in part the obturator nerve are traversing the adductor canal of the thigh, we hypothesised that repeated administration of a local anaesthetic (LA) into this aponeurotic space could be a useful option for post-operative analgesia after knee replacement surgery. A systematic search of the literature pertinent to the blockade of the saphenous and/or obturator nerves for pain relief after knee surgery was conducted. Further, pain and opioid requirements were evaluated in eight patients receiving a continuous blockade of the saphenous and obturator nerve (adductor-canal-blockade) after total knee arthroplasty (TKA). Finally, we performed cross-sectional MR scans of the adductor canal after injection of ropivacaine 30ml in one patient. The systematic literature search revealed only one controlled study, where selective blockade of the saphenous nerve was investigated for the purpose of clinical pain relief after knee arthroscopy. We located no studies reporting on saphenous and/or obturator nerve block for pain relief after TKA. Preliminary findings in eight patients demonstrated that a continuous adductor-canal-blockade for 48h after TKA was associated with low mean pain scores at rest and low mean requirements for supplemental morphine. MR scans in one patient demonstrated that 30ml of LA filled the adductor canal, including the distal part, where the posterior branch of the obturator nerve joins the vessels and the saphenous nerve. Continuous adductor-canal-blockade may be a valuable adjunct for post-operative analgesia after major knee surgery. These preliminary results should be confirmed in randomised, controlled trials.
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