Remifentanil in general anesthesia

Remifentanil is a potent mu-opioid receptor agonist and has some unique pharmacokinetic characteristics compared with fentanyl. Properties of remifentanil such as rapid onset of action, easy titration of concentration and quick emergence even after a long duration of anesthesia with high doses may produce analgesia strong enough to keep patients free from surgical stresses during general anesthesia. Understanding its pharmacological advantages and some experiences will provide better care for our patients. Analgesia-oriented opioid-based anesthesia with remifentanil will become a new trend that may significantly alter our anesthesia practice.     

Muscle Strength and Walking Ability After Laparoscopic Hernioplasty Versus Conventional Repair

Purpose: We examined muscle strength and walking ability after hernia repair to compare the effects of laparoscopic hernioplasty and conventional repair. Methods: Twenty-seven patients with primary inguinal hernias were randomly divided into two groups according to the surgical procedure: 15 patients were treated with laparoscopic hernioplasty and 12 with conventional repair. Two types of muscle testing around the inguinal region, one by manual examination and one using a musculator, were done preoperatively and 1 week postoperatively. Walking exercise tests were performed at the same time as muscle testing. Results: Manual examination showed that the postoperative muscle strength of the iliopsoas muscle was decreased in six patients from the conventional repair group, but not in any of those from the laparoscopic hernioplasty group. The musculator showed decreased strength of the iliopsoas muscle after conventional repair, but not after laparoscopic hernioplasty. The walking exercise test showed that conventional hernia repair influenced walking. Conclusion: A decline in muscle strength of the iliopsoas muscle and walking ability was evident after conventional repair, but not after laparoscopic hernioplasty. Thus, laparoscopic hernioplasty is superior to conventional repair from the perspective of muscle testing and walking ability. Received: March 29, 2002 / Accepted: July 2, 2002 Reprint requests to: N. Murata     

State-dependent blocking actions of azimilide dihydrochlo-ride (NE-10064) on human cardiac Na(+) channels.

BACKGROUND: Azimilide reportedly blocks Na(+) channels, although its mechanism remains unclear. METHODS AND RESULTS: The kinetic properties of the azimilide block of the wild-type human Na(+) channels (WT: hH1) and mutant DeltaKPQ Na(+) channels (DeltaKPQ) expressed in COS7 cells were investigated using the whole-cell patch clamp technique and a Markovian state model. Azimilide induced tonic block of WT currents by shifting the h infinity curve in the hyperpolarizing direction and caused phasic block of WT currents with intermediate recovery time constant. The peak and steady-state DeltaKPQ currents were blocked by azimilide, although with only a slight shift in the h infinity curve. The phasic block of peak and steady-state DeltaKPQ currents by azimilide was significantly larger than the blocking of the peak WT current. The affinity of azimilide predicted by a Markovian state model was higher for both the activated state (Kd(A) =1.4 micromol/L), and the inactivated state (Kd(I) =1.4 micromol/L), of WT Na(+) channels than that for the resting state (Kd(R) =102.6 micromol/L). CONCLUSIONS: These experimental and simulation studies suggest that azimilide blocks the human cardiac Na(+) channel in both the activated and inactivated states.     

Absence of a trafficking defect in R1232W/T1620M, a double SCN5A mutant responsible for Brugada syndrome.

BACKGROUND: A trafficking defect of mutant cardiac Na-channels (SCN5A) has been implicated in Brugada syndrome. Although R1232W polymorphism and T1620M mutation by themselves have little effect on Na-channel function, their combination has been reported to disrupt membrane trafficking, resulting in a non-functioning Na channel. METHODS AND RESULTS: Contrary to previous findings, patch-clamp recordings of heterologously expressed R1232W/T1620M showed robust Na currents and confocal microscopy exhibited predominant expression in the plasma membrane, similar to the wild-type channel. CONCLUSIONS: It is unlikely that an intragenic interaction between R1232W and T1620M of SCN5A causes a trafficking defect leading to a non-functioning Na channel.     

Transient lymphocytic panhypophysitis associated with SIADH leading to diabetes insipidus after glucocorticoid replacement

A 52-year-old man presented with vomiting, general fatigue and hyponatremia. His symptoms and signs were consistent with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Endocrine studies revealed hypopituitarism and administration of hydrocortisone resulted in a marked polyuria. The patient was diagnosed as masked diabetes insipidus. The lymphocytic hypophysitis was also diagnosed on the basis of MRI findings and anti-pituitary antibody. Six months later, these abnormalities disappeared. Diabetes insipidus may exist in a case of hyponatremia due to contrastive SIADH. Such patients may recover spontaneously and careful follow-up is required, avoiding a long-term treatment by monotonous continuation of hormonal replacement.     

Normal development of the gut-associated lymphoid tissue except Peyer's patch in MyD88-deficient mice

MyD88 is a key adaptor molecule for signalling via Toll-like receptors (TLRs) and the response to gut commensal microbes. To investigate the role of TLRs/MyD88 pathway in the development of the gut-associated lymphoid tissue (GALT), we examined the development of Peyer's patches (PPs) and cryptopatch (CP), and also one of effector compartment, intraepithelial lymphocyte (IEL) in MyD88-/-, TLR2-/- and TLR4-/- mice. In MyD88-/- mice, the organogenesis of PPs was not disturbed. However, PPs in 2-week-old MyD88-/- mice were significantly smaller than those in MyD88+/- mice. Also, in 2-week-old TLR4-/-, but not TLR2-/- mice, PPs did not develop rapidly. The development of PPs in MyD88-/- and TLR4-/- mice was completely recovered in 10 weeks. PP cells from MyD88-/- mice showed significant decrease in proliferation when stimulated with lipopolysaccharide. The development of CP and IEL was also normal in 10-week-old MyD88-/- mice. These results suggest that the TLRs/MyD88 pathway might be involved in the development of PPs only at early postnatal stage, and TLRs/MyD88-independent signalling is critically involved in the development of GALT in adult mice.     

Effect of prostaglandin E1 on inflammatory responses and gas exchange in patients undergoing surgery for oesophageal cancer

Background. Oesophageal surgery causes morbidity and mortalityfrom respiratory complications. We tested the possibility thatprostaglandin E₁ (PGE₁) could reduce inflammatory cytokine responsesand improve gas exchange after oesophagectomy. Methods. We randomized 14 patients into two groups. One groupreceived PGE₁ 20 ng kg^–1 min^–1 i.v. during anaesthesia(PGE₁ group) and the other group did not (control group). Anaesthesiawas maintained with sevoflurane and epidural anaesthesia. Duringoesophagectomy, ventilation of one lung was carried out witha double-lumen bronchial tube. The patients were extubated onor after the first postoperative day. Blood samples were takenat induction of anaesthesia, at the end of thoracotomy, at theend of the operation, 2 h after surgery and on the first dayafter surgery. Results. The groups were similar for ASA physical status, age,FEV₁%, operation time, duration of thoracotomy, intraoperativefluid volume and blood loss. The arterial blood gas and arterialpressure during surgery were also similar in the PGE₁ and controlgroups. However, the ratio on the first day after surgery was significantly greater in the PGE₁ groupcompared with the control group. Serum concentrations of IL-6and IL-8 increased after surgery in both groups. IL-6 was significantlyless in the PGE₁ group at the end of the operation and 2 h afterthe operation. Conclusions. Intraoperative PGE₁ reduced IL-6 production inpatients undergoing oesophagectomy and oxygenation was betterin the postoperative period.