Grading schemes for severity of suspected allergic reactions have been applied to the perioperative setting, but there is no scoring system that estimates the likelihood that the reaction is an ...immediate hypersensitivity reaction. Such a score would be useful in evaluating current and proposed tests for the diagnosis of suspected perioperative immediate hypersensitivity reactions and culprit agents.
We conducted a Delphi consensus process involving a panel of 25 international multidisciplinary experts in suspected perioperative allergy. Items were ranked according to appropriateness (on a scale of 1–9) and consensus, which informed development of a clinical scoring system. The scoring system was assessed by comparing scores generated for a series of clinical scenarios against ratings of panel members. Supplementary scores for mast cell tryptase were generated.
Two rounds of the Delphi process achieved stopping criteria for all statements. From an initial 60 statements, 43 were rated appropriate (median score 7 or more) and met agreement criteria (disagreement index <0.5); these were used in the clinical scoring system. The rating of clinical scenarios supported the validity of the scoring system. Although there was variability in the interpretation of changes in mast cell tryptase by the panel, we were able to include supplementary scores for mast cell tryptase.
We used a robust consensus development process to devise a clinical scoring system for suspected perioperative immediate hypersensitivity reactions. This will enable objectivity and uniformity in the assessment of the sensitivity of diagnostic tests.
Unsubstantiated penicillin-allergy labels are common in surgical patients, and can lead to significant harm through avoidance of best first-line prophylaxis of surgical site infections and increased ...infection with resistant bacterial strains. Up to 98% of penicillin-allergy labels are incorrect when tested. Because of the scarcity of trained allergists in all healthcare systems, only a minority of surgical patients have the opportunity to undergo testing and de-labelling before surgery. Testing pathways can be modified and shortened in selected patients. A variety of healthcare professionals can, with appropriate training and in collaboration with allergists, provide testing for selected patients. We review how patients might be assessed, the appropriate testing strategies that can be used, and the minimum standards of safe testing.
Peroxisome proliferator-activated receptors (PPARs) play a key regulating role in homeostasis. In this study, we investigated the effects of DSP-8658, a novel selective PPARa/γ modulator, on ...adipogenesis and glucose metabolism in diabetic obese mice and compared these effects to those of pioglitazone, a PPARγ full agonist.
DSP-8658 functional activity was assessed by PPARγ-target genes expression in adipose 3T3-L1 cells and its anti-diabetic efficacy evaluated in db/db mice. The effects of DSP-8658 on adipogenesis were investigated diet induced obese (DIO) KK-A(y) mice.
DSP-8658 reduced the expression of PPARγ-target gene 11 beta hydroxysteroid dehydrogenase type 1 with an EC50 value 2.1-fold that of pioglitazone and 28.4-fold that of rosiglitazone. On the other hand, DSP-8658 increased the expression of fatty acid binding protein 4 and glycerol kinase genes with EC50 values 33-fold and >15-fold those of pioglitazone and 163-fold and >38-fold those of rosiglitazone, respectively. In db/db mice, DSP-8658, like pioglitazone, decreased blood glucose, HbA1c, and plasma triglyceride levels and increased plasma insulin concentration and pancreatic insulin contents. In DIO KK-A(y) mice, DSP-8658, unlike pioglitazone, decreased subcutaneous adipose tissue weight and mean adipocyte size. However, both DSP-8658 and pioglitazone improved blood glucose and HbA1c levels with similar efficacy. Although DSP-8658 did not change the expression levels of fatty acid transport protein 1 and glycerol kinase genes in subcutaneous adipose tissue of KK-A(y) mice, pioglitazone increased these gene expression levels.
Unlike PPARγ full agonists, DSP-8658 ameliorates blood glucose without increasing adipogenesis in diabetic obesity mice.
In previous studies, neurons in the medial vestibular nucleus (MVN) were classified mainly into 2 types according to their intrinsic membrane properties in in vitro slice preparations. However, it ...has not been determined whether the classified neurons are excitatory or inhibitory ones. In the present study, to clarify the relationship between the chemical and electrophysiological properties of MVN neurons, we explored mRNAs of cellular markers for GABAergic (glutamic acid decarboxylase 65, 67, and neuronal GABA transporter), glutamatergic (vesicular glutamate transporter 1 and 2), glycinergic (glycine transporter 2), and cholinergic neurons (choline acetyltransferase and vesicular acetylcholine transporter) expressed in electrophysiologically characterized MVN neurons in rat brain stem slice preparations. For this purpose, we combined whole cell patch-clamp recording analysis with single-cell reverse transcription-polymerase chain reaction (RT-PCR) analysis. We examined the membrane properties such as afterhyperpolarization (AHP), firing pattern, and response to hyperpolarizing current pulse to classify MVN neurons. From the single-cell RT-PCR analysis, we found that GABAergic neurons consisted of heterogeneous populations with different membrane properties. Comparison of the membrane properties of GABAergic neurons with those of other neurons revealed that AHPs without slow components and a firing pattern with delayed spike generation (late spiking) were preferential properties of GABAergic neurons. On the other hand, most glutamatergic neurons formed a homogeneous subclass of neurons exhibiting AHPs with slow components, repetitive firings with constant interspike intervals (continuous spiking), and time-dependent inward rectification in response to hyperpolarizing current pulses. We also found a small number of cholinergic neurons with various membrane properties. These findings clarify the electrophysiological properties of excitatory and inhibitory neurons in the MVN, and the information about the preferential membrane properties may be useful for identifying GABAergic and glutamatergic MVN neurons electrophysiologically.
Perioperative anaphylaxis is a life-threatening clinical condition that is typically the result of drugs or substances used for anesthesia or surgery. The most common cause of anaphylaxis during ...anesthesia is reportedly neuromuscular blocking agents. Of the many muscle relaxants that are clinically available, rocuronium is becoming popular in many countries. Recent studies have demonstrated that succinylcholine (but also rocuronium use) is associated with a relatively high rate of IgE-mediated anaphylaxis compared with other muscle relaxant agents. Sugammadex is widely used for reversal of the effects of steroidal neuromuscular blocking agents, such as rocuronium and vecuronium. Confirmed cases of allergic reactions to clinical doses of sugammadex have also been recently reported. Given these circumstances, the number of cases of hypersensitivity to either sugammadex or rocuronium is likely to increase. Thus, anesthesiologists should be familiar with the epidemiology, mechanisms, and clinical presentations of anaphylaxis induced by these drugs. In this review, we focus on the diagnosis and treatment of anaphylaxis to sugammadex and neuromuscular blocking agents. Moreover, we discuss recent studies in this field, including the diagnostic utility of flow cytometry and improvement of rocuronium-induced anaphylaxis with the use of sugammadex.
Suspected perioperative hypersensitivity reactions are rare but contribute significantly to the morbidity and mortality of surgical procedures. Recent publications have highlighted the differences ...between countries concerning the respective risk of different drugs, and changes in patterns of causal agents and the emergence of new allergens. This review summarises recent information on the epidemiology of perioperative hypersensitivity reactions, with specific consideration of differences between geographic areas for the most frequently involved offending agents.
We describe a new method for radio-frequency mandibular nerve rhizotomy under CT fluoroscopy. A patient with cancer had severe intractable and drug-resistant pain in his left mandibular region. ...Because he had an anatomic deformity due to cancer invasion and radiation therapy, we planned a mandibular nerve rhizotomy under CT fluoroscopic imaging. The needle was advanced to the mandibular nerve just caudal to the foramen ovale under real-time CT fluoroscopy, avoiding the cancer region. Pain scores of the patient were reduced after the nerve rhizotomy, without any complications.
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