High-dose Amrinone Is Required to Accelerate Rewarming from Deliberate Mild Intraoperative Hypothermia for Neurosurgical Procedures

Background: Since the time available to provide the cooling and rewarming is limited during deliberate mild hypothermia, the technique to accelerate the cooling and rewarming rate of core temperature has been studied. Amrinone has been reported to accelerate the cooling rate but not the rewarming rate of core temperature during deliberate mild hypothermia. The failure of amrinone effect on the rewarming rate might be due to an insufficient dose of amrinone during hypothermic conditions. The authors therefore tested whether higher doses of amrinone can accelerate the rewarming rate of core temperature during deliberate mild hypothermia for neurosurgery.

Methods: After institutional approval and informed consent, 30 patients were randomly assigned to one of three groups. Patients in the control group (n = 10) did not receive amrinone; patients in the AMR 15 group (n = 10) received 15 [mu]g [middle dot] kg-1 [middle dot] min-1 amrinone with a 1.0-mg/kg loading dose of amrinone at the beginning of cooling; and patients in the ReAMR group (n = 10) received 5 [mu]g [middle dot] kg-1 [middle dot] min-1 amrinone with 1.0-mg/kg loading and reloading doses of amrinone at the beginning of cooling and rewarming, respectively. Administration of amrinone was started just after the induction of cooling and continued until the end of anesthesia. Anesthesia was maintained with nitrous oxide in oxygen, propofol, and fentanyl. After induction of anesthesia, patients were cooled, and tympanic membrane temperature was maintained at 34.5[degrees]C. After completion of the main surgical procedures, patients were actively rewarmed and extubated in the operating room.

Results: The cooling and rewarming rates of core temperature were both significantly faster in both amrinone groups than in the control group. During the cooling and rewarming periods, forearm minus fingertip temperature gradient was significantly smaller in both amrinone groups than in the control group. During the rewarming period, heart rate and mean arterial pressure in the AMR 15 group were significantly faster and lower, respectively, than in the control group. Systemic vascular resistance in the AMR 15 group was smaller than in the control group throughout the study; on the other hand, only the value after the start of rewarming in the ReAMR group was smaller than in the control group.     

Effect of L-phenylalanine supplementation and a high-protein diet on pharmacokinetics of cefdinir in healthy volunteers: an exploratory study

BACKGROUND: Upregulation of oligopeptide transport activity by dietary protein, certain dipeptides and amino acids has been reported in the rat intestine and a human intestinal cell line. OBJECTIVE: In this study, the pharmacokinetics of cefdinir were investigated after L-phenylalanine supplementation and a high-protein diet (HPD) in humans to explore changes in the activities of intestinal and renal oligopeptide transporters. METHODS: A normal-protein diet (NPD, 73.2 +/- 2.6 g/day), NPD + l-phenylalanine (7.5 g/day), or HPD (141.3 +/- 3.7 g/day) was given to six male healthy volunteers for 12 days followed by a single dose of cefdinir after an overnight fast in a randomized three-way crossover study with a 22-day washout. Blood and urine were collected over a 12-h period after administration of cefdinir. Concentrations of cefdinir in plasma and/or urine were measured by high-performance liquid chromatography. RESULTS: Plasma concentrations and urinary excretion of the drug did not change throughout the study. Physiological variables and laboratory values did not reveal any differences between the three periods except for serum and urinary nitrogen levels and serum triglyceride. DISCUSSION: A reason for the unchanged pharmacokinetics of cefdinir may be due to lower doses of L-phenylalanine and protein in humans than in animals when converting animal effective doses to humans. CONCLUSION: In humans, L-phenylalanine supplementation and HPD do not seem to upregulate intestinal and renal oligopeptide transport in the ranges of duration and dose examined.     

A patient with LQTS in whom verapamil administration and permanent pacemaker implantation were useful for preventing torsade de pointes

A 21-year-old woman with long QT syndrome and missense mutation in HERG (T613M), suffered from repeated attacks of pause dependent torsade de pointes, even though she was given beta-blockers and underwent stellate ganglion block twice at the age of eight. After she received permanent pacemaker implantation and administration of verapamil, no premature beats or pause dependent torsade de pointes was observed.     

The effects of intensive care environment on postoperative nightmare

Purpose

We retrospectively investigated the incidence of postoperative nightmares and evaluated the impact of postoperative intensive care on the incidence of during subsequent hospital stay. To reduce the effect of selection bias, we compared the incidence of nightmares in propensity-matched pairs with postoperative management in ICUs or in surgical wards.

Methods

This is a retrospective review of an institutional registry containing 21,606 anesthesia cases and was conducted with ethics board approval. Outcomes of surgical patients treated in ICUs and in postsurgical wards (ICU admission vs non ICU admission) were compared first for nightmares using the initial 12,508 patients. To avoid channeling bias, propensity score analysis was used to generate a set of matched cases (ICU admission) and controls (non ICU admission), yielding 642 matched patient pairs. The incidence rate of nightmares was compared as the primary outcome.

Results

Before adjusting patients’ characteristics, ICU environment exposure increased the incidence of nightmares compared with non-ICU environment during subsequent hospital stay [ICU vs non-ICU: 101/718 (12.3 %) vs 1147/10,542 (9.81 %)]. The odds ratio (95 % CIs) for ICU was 1.29 (1.03–1.61) for nightmares (p = 0.022). After propensity score matching, however, an equal rate of nightmares occurred in the ICU environment exposure compared to the non-ICU environment [ICU vs non-ICU: 81/561 (12.6 %) vs 73/569 (11.4 %)]. The odds ratio and 95 % CIs for ICU were 1.13 (0.80–1.58) for nightmares (p = 0.54).

Conclusions

The incidence of nightmares did not become more evident during subsequent hospital stay after ICU environment exposure.

     

Impact of TRPV3 on the development of allergic dermatitis as a dendritic cell modulator

The transient receptor potential channel vanilloid subfamily V member 3 (TRPV3), which functions as a thermosensor in keratinocytes, plays an important role in the development of allergic and itchy dermatitis in rodents. Although real‐time PCR analysis using lesional and non‐lesional skin samples from patients with atopic dermatitis showed that TRPV3 was expressed in lesional skin, the role that TRPV3 plays in patients with dermatitis is still relatively obscure. Here, we determined whether TRPV3 was a dendritic cell (DC) modulator using DS‐Nh mice with a gain‐of‐function mutation in TRPV3 (TRPV3Gly573Ser), because increasing skin temperature is associated with the modulation of dermal dendritic cells (DCs). Interestingly, increased responses to haptens by skin and DCs were observed in DS‐Nh mice compared with those from DS mice with wild‐type TRPV3. Increased thymic stromal lymphopoietin (TSLP) responses were also observed in keratinocytes from DS‐Nh mice compared with those from DS mice. Taken together, we propose that the DS‐Nh mouse is a good model to use in order to better understand the role of this orphan channel and that TRPV3 may represent a new therapeutic target in certain types of dermatitis through the control of DCs.     

A prostaglandin D2 receptor antagonist modifies experimental asthma in sheep

Background Prostaglandin (PG) D₂ is the major cylooxygenase metabolite released by mast cells upon allergen stimulation, and elicits responses through either the prostanoid DP1 receptor and/or the chemoattractant receptor homologous molecule expressed on T-helper type 2 (Th2) cells (CRTH2/DP2). Experimental evidence suggests that stimulation of one or both these receptors contributes to asthma pathophysiology.
Objective The aim of this study was to test the hypothesis that the prostanoid DP1 receptor contributes to asthma pathophysiology by determining the efficacy of an orally active antagonist for this receptor, S-5751, on allergen-induced bronchoconstriction, airway hyperresponsiveness (AHR) and cellular inflammation in the sheep model of asthma.
Methods PGD₂-induced cyclic adenosine monophosphate (cAMP) production in platelet-rich plasma was used to establish the in vitro efficacy of S-5751. In vivo , sheep naturally allergic to Ascaris suum were challenged with an aerosolized antigen with and without S-5751 treatment (given 4 days before and for 6 days after the challenge).
Results S-5751 inhibited PGD₂-induced cAMP production in platelet-rich plasma with an IC₅₀ value of 0.12 μ m . S-5751 at 30 mg/kg, but not at 3 mg/kg, reduced the early bronchoconstriction and inhibited the late bronchoconstriction. AHR and inflammatory cell infiltration in bronchoalveolar lavage fluid at days 1 and 7 were also inhibited with the 30 mg/kg dose. The responses observed with S-5751 at 30 mg/kg were comparable with those with montelukast treatment (0.15 mg/kg, twice a day, intravenous); however, S-5751 did not block inhaled leukotrieneD₄-induced broncoconstriction.
Conclusion Prostanoid DP1 receptor inhibition may represent an alternative target for asthma therapy.