Sequence Variants in Myopathies: Expression and Functional Studies in Two Families.

The skeletal muscle ryanodine receptor (RyR1), i.e., the Ca channel of the sarco/endoplasmic reticulum (S/ER), and the voltage-dependent calcium channel Cav1.

Functional and genetic characterization of clinical malignant hyperthermia crises: a multi-centre study.

Background: Malignant hyperthermia (MH) is a rare pharmacogenetic disorder which is characterized by life-threatening metabolic crises during general anesthesia. Classical triggering substances are volatile anesthetics and succinylcholine (SCh). The molecular basis of MH is excessive release of Ca2+ in skeletal muscle principally by a mutated ryanodine receptor type 1 (RyR1).

Undiagnosed myopathy before surgery and safe anaesthesia table.

Patients with muscle pathology are a challenge for anaesthesiologists because of possible life-threatening general anaesthesia complications. A review of the current medical literature on the issue clearly indicates that increasing awareness by anaesthesiologists in recent years has led to a reduction in the occurrence of adverse events in patients with diagnostically well-defined muscle disease. On the other hand, the current emerging aspect is that the great majority of complications concern subjects with clinically non-overt (silent to mildly symptomatic) and thus undiagnosed myopathy.

Identification and functional characterization of malignant hyperthermia mutation T1354S in the outer pore of the Cavalpha1S-subunit.

To identify the genetic locus responsible for malignant hyperthermia susceptibility (MHS) in an Italian family, we performed linkage analysis to recognized MHS loci. All MHS individuals showed cosegregation of informative markers close to the voltage-dependent Ca(2+) channel (Ca(V)) α(1S)-subunit gene (CACNA1S) with logarithm of odds (LOD)-score values that matched or approached the maximal possible value for this family. This is particularly interesting, because so far MHS was mapped to >178 different positions on the ryanodine receptor (RYR1) gene but only to two on CACNA1S.

Functional characterization of ryanodine receptor (RYR1) sequence variants using a metabolic assay in immortalized B-lymphocytes.

Mutations in the RYR1 gene are linked to malignant hyperthermia (MH), central core disease and multi-minicore disease. We screened by DHPLC the RYR1 gene in 24 subjects for mutations, and characterized functional alterations caused by some RYR1 variants. Three novel sequence variants and twenty novel polymorphisms were identified.

Antithrombin reduces ischemic volume, ameliorates neurologic deficits, and prolongs animal survival in both transient and permanent focal ischemia.

Background And Purpose: Antithrombin (AT), a glycoprotein belonging to the serpin family, blocks thrombin formation and activity at several steps. Thrombin, beside its relevant role in the coagulation cascade, exerts neurodetrimental effects through the activation of a family of protease-activated receptors, which can be implicated in stroke pathophysiology. The aims of the present study were to evaluate whether AT could reduce brain damage, ameliorate neurologic deficits, and prolong animal survival.

Analgesia in PACU: indications, monitoring, complications.

The correct treatment of postoperative pain, in the early period immediately following surgery, is founded on the following four principles: 1-correct diagnosis of the source and magnitude of nociception; 2-understanding of the relationship of ongoing nociception and other components of pain including anxiety, ethnocultural components, meaning, prior experience; 3-treatment by establishment and maintenance of drug level at active sites to achieve and maintain analgesia and anxiolysis as appropriate; 4-continued re-evaluation of the therapy and refinement of the approach. The PACU standard of cure requires a strict accordance between intra and postoperative analgesia. It requires "proactive preoperative plan" that includes: preoperative patient evaluation; discussion with a single patient on different treatment options; patient and family education; pre-emptive measures as indicated; intra-operative multimodal analgesia; a correct triage of analgesia, just after initial evaluation of vital parameters in PACU; re-evaluation of analgesia plan, if analgesia is inadequate; a new titration, intravenous or epidural way, in order to achieve a stable VAS < 3; plan a new analgesia scheme or confirm a preoperative plan; control of adverse events, related to analgesia plan (gastric bleeding and/or bleeding of the surgical wound site, NSAIDs-induced renal damage, respiratory depression, delayed canalisation, nausea, vomiting, excessive sedation, difficulty in bladder emptying, itchiness); a transmission of analgesia plan to ward nurses; a control quality for verify at prefixed times patients satisfaction level, analgesia performed, adverse effects percent, analgesia related, plan variations percent.