ß-Defensin 1 plays a role in acute mucosal defense against Candida albicans.

Candida is an opportunistic fungal pathogen that colonizes the mucosal tract of humans. Pathogenic infection occurs in the presence of conditions causing perturbations to the commensal microbiota or host immunity. Early innate immune responses by the epithelium, including antimicrobial peptides (AMPs) and cytokines, are critical for protection against overgrowth. Reduced salivary AMP levels are associated with oral Candida infection, and certain AMPs, including human ß-defensins 1-3, have direct fungicidal activity. In this study, we demonstrate that murine ß-defensin 1 (mBD1) is important for control of early mucosal Candida infection and plays a critical role in the induction of innate inflammatory mediators. Mice deficient in mBD1, as compared with wild-type mice, exhibit elevated oral and systemic fungal burdens. Neutrophil infiltration to the sites of mucosal Candida invasion, an important step in limiting fungal infection, is significantly reduced in mBD1-deficient mice. These mice also exhibit defects in the expression of other AMPs, including mBD2 and mBD4, which may have direct anti-Candida activity. We also show that mBD1 deficiency impacts the production of important antifungal inflammatory mediators, including IL-1ß, IL-6, KC, and IL-17. Collectively, these studies demonstrate a role for the mBD1 peptide in early control of Candida infection in a murine model of mucosal candidiasis, as well as in the modulation of host immunity through augmentation of leukocyte infiltration and inflammatory gene regulation.

A novel role for the NLRC4 inflammasome in mucosal defenses against the fungal pathogen Candida albicans.

Candida sp. are opportunistic fungal pathogens that colonize the skin and oral cavity and, when overgrown under permissive conditions, cause inflammation and disease. Previously, we identified a central role for the NLRP3 inflammasome in regulating IL-1ß production and resistance to dissemination from oral infection with Candida albicans. Here we show that mucosal expression of NLRP3 and NLRC4 is induced by Candida infection, and up-regulation of these molecules is impaired in NLRP3 and NLRC4 deficient mice. Additionally, we reveal a role for the NLRC4 inflammasome in anti-fungal defenses. NLRC4 is important for control of mucosal Candida infection and impacts inflammatory cell recruitment to infected tissues, as well as protects against systemic dissemination of infection. Deficiency in either NLRC4 or NLRP3 results in severely attenuated pro-inflammatory and antimicrobial peptide responses in the oral cavity. Using bone marrow chimeric mouse models, we show that, in contrast to NLRP3 which limits the severity of infection when present in either the hematopoietic or stromal compartments, NLRC4 plays an important role in limiting mucosal candidiasis when functioning at the level of the mucosal stroma. Collectively, these studies reveal the tissue specific roles of the NLRP3 and NLRC4 inflammasome in innate immune responses against mucosal Candida infection.

An essential role for the NLRP3 inflammasome in host defense against the human fungal pathogen Candida albicans.

Candida albicans is an opportunistic fungal pathogen causing life-threatening mucosal and systemic infections in immunocompromised humans. Using a murine model of mucosal Candida infection, we investigated the role of the proinflammatory cytokine IL-1beta in host defense to Candida albicans. We find that the synthesis, processing, and release of IL-1beta in response to Candida are tightly controlled and first require transcriptional induction, followed by a second signal leading to caspase-1-mediated cleavage of the pro-IL-1beta cytokine. The known fungal pattern recognition receptors TLR2 and Dectin-1 regulate IL-1beta gene transcription, whereas the NLRP3-containing proinflammatory multiprotein complex, the NLRP3 inflammasome, controls caspase-1-mediated cleavage of pro-IL-1beta. Furthermore, we show that TLR2, Dectin-1, and NLRP3 are essential for defense against dissemination of mucosal infection and mortality in vivo. Therefore, in addition to sensing bacterial and viral pathogens, the NLRP3 inflammasome senses fungal pathogens and is critical in host defense against Candida.

Repeated episodes of difficulty with arousal following general anesthesia in a patient with ulnar neuropathy.

Delayed emergence following general anesthesia may be due to serious life-threatening disorders and deserves prompt evaluation. Rarely, delayed emergence has been attributed to a psychiatric or psychological cause. This report describes an otherwise healthy and mentally sound 52-year-old woman who experienced repeated dissociative episodes following general anesthesia for minor surgical procedures. These episodes lasted for 5 h and resulted in admission to the intensive care unit. The current literature is reviewed to identify commonalities among previously reported cases and to discuss different psychiatric and psychological mechanisms that can play a role in the development of this disorder.

Periorbital ecchymoses during general anesthesia in a patient with primary amyloidosis: a harbinger for bleeding?

Primary amyloidosis is a result of proliferation of a population of plasma cells that leads to an increased secretion of monoclonal immunoglobulins (amyloid). Amyloid protein infiltrates increase capillary fragility. Such capillaries can burst, even after minor stress, resulting in periorbital hemorrhage. We describe a 64-yr-old man with primary amyloidosis who underwent general anesthesia. His eyes were gently closed with tape. Upon removal of the tape bilateral periorbital purpura was noted. All coagulation studies were normal. The periorbital hemorrhage was attributed to amyloidosis-induced capillary fragility.

Predictors of mortality following symptomatic pulmonary embolism in patients undergoing noncardiac surgery.

PURPOSE: To determine 30-day mortality and predictors of mortality following perioperative pulmonary embolism (PE). METHODS: We searched both the Mayo Clinic electronic medical records and Autopsy Registry, between January 1, 1998 and December 31, 2001, for patients who developed PE within 30 days after noncardiac surgery performed under general or neuraxial anesthesia. Medical records of all identified patients were reviewed using standardized data collection forms. The association between risk factors for PE and 30-day post-PE mortality was assessed using t tests, exact binomial tests, and logistic regression. RESULTS: We identified 158 patients with probable or definite perioperative PE. The overall 30-day mortality from the day of PE was 25.3%, i.e., 40 patients died. Hypotension requiring treatment, need for mechanical ventilation, and intensive care unit admission were the prominent univariate predictors of 30-day mortality (all P

Case report: intraoperative anaphylactoid reaction and hydroxyethyl starch in balanced electrolyte solution (Hextend).

PURPOSE: To report a first case of probable anaphylactoid reaction to 6% hydroxyethyl starch reconstituted in balanced electrolyte and glucose solution (Hextend). CLINICAL FEATURES: A 22-yr-old man was admitted for a partial nephrectomy. Near the end of the four-hour operation, an infusion of Hextend was initiated. Shortly thereafter, mechanical ventilation became difficult, peak inspiratory pressure increased to 55 cm H2O with audible wheezing over the patient's lungs. Blood pressure suddenly decreased to 68/46 mmHg. Multiple doses of phenylephrine, ephedrine and epinephrine were required to restore the patient's blood pressure. Postoperatively, a diffuse urticarial rash was apparent on his upper torso. The patient recovered uneventfully. His postoperative serum tryptase was 26.3 ng x mL(-1) (reference range, < 11.5 ng x mL(-1)) and the urine N-methyl-histamine was 2448 microg x g(-1) creatinine (reference range, 30-200 microg x g(-1) creatinine). Two months after the event, skin testing was conducted to test for possible allergy to latex, lidocaine, propofol, cisatracurium, succinylcholine, vecuronium, midazolam, fentanyl, ondansetron, neostigmine, and cephazolin, and all were negative. Hextend was also tested, starting with a 1:100,000 dilution and the results were negative. CONCLUSIONS: The temporal relationship of severe hypotension, bronchospasm and skin rash within ten minutes from administration of Hextend in this patient suggests an immediate hypersensitivity reaction to hetastarch. The elevated levels of serum tryptase and urinary N-methyl-histamine suggest that this hypersensitivity was mediated from mast cell degranulation. Negative skin testing suggests that the reaction was anaphylactoid.

Comparison of on-demand vs planned relaparotomy for treatment of severe intra-abdominal infections.

AIM: To compare morbidity and mortality of patients with severe intra-abdominal infections after two types of surgical treatment, on-demand ("wait and see") relaparotomy and modified planned relaparotomy. METHODS: We prospectively analyzed the outcomes of 65 patients with severe peritonitis surgically treated in two Croatian hospitals. In one hospital, 34 patients were treated on-demand, and in another hospital 31 patients were treated by planned relaparotomy. We compared severe postoperative complications, mortality, and length of hospital stay in the two groups of patients. RESULTS: Severity of patient's disease, as measured from preoperative group-average Acute Physiology and Chronic Health Evaluation (APACHE) II scores, was comparable in both on-demand and planned relaparotomy groups. The mortality rate was higher in patients operated on-demand (59% vs 29%, P=0.024). In nonadjusted model, the relative risk of dying was 2.5-fold higher for patients treated by on-demand operation in comparison with planned relaparatomy (P=0.030). However, after the adjustment of the survival data for individual patient's sex and APACHE II scores, the difference in the relative risk became non-significant (P=0.178). The patients who died had higher APACHE II scores (26.1+/-8.9 vs 19.7+/-5.9, P=0.009). Relative risk of dying per 5-point increase in APACHE II score was 1.24 (95% confidence interval, 1.01-1.51; P=0.039), irrespective of the surgical technique. CONCLUSIONS: Patients with severe peritonitis treated with planned relaparotomy seemed to have lower mortality. However, the relative risk of dying was not statistically different between the on-demand and planned relaparotomy groups after adjustment for preoperative APACHE II scores. The severity of disease rather than surgical approach plays more important role in survival of these patients.

Neostigmine-induced prolonged neuromuscular blockade in a patient with atypical pseudocholinesterase.

A patient with unrecognized atypical pseudocholinesterase was given succinylcholine and then vecuronium before neuromuscular monitoring was instituted. Subsequently, when neostigmine and glycopyrrolate were given to reverse what was thought to be a nondepolarizing block, the patient became further relaxed, and his trachea could not be extubated for more than 10 hours. In this report, we discuss drug interactions, phase II block, and the importance of timely neuromuscular monitoring.

Fatal acute pulmonary embolism in a patient with pelvic lipomatosis after surgery performed after transatlantic airplane travel.

We describe a case of a 37-yr-old patient who traveled from Europe to the United States and succumbed to a massive pulmonary embolism 6 days after elective pelvic surgery despite routine postoperative thrombotic prophylaxis. In retrospect, he was likely to have developed a deep venous thrombosis during the transatlantic trip to our hospital. Anesthesiologists and other physicians involved in perioperative management need to be aware of the prevalence of venous thromboembolism in patients with a history of recent prolonged air travel. This is particularly true in tertiary referral centers, where patients with rare diseases may have a major surgical intervention within days of prolonged air travel.

Prolonged cardiovascular collapse due to unrecognized latex anaphylaxis.

UNLABELLED: We present a case of a prolonged anaphylactic reaction that occurred in temporal relationship to the administration of cefazolin. Subsequent allergy testing was positive for latex and negative for cefazolin-both unexpected results. Our case illustrates that medications administered before the onset of anaphylaxis should not be assumed to be the causative allergen and that a latex allergy should be considered in the differential diagnosis. Because the etiology of an anaphylactic reaction cannot be immediately determined, patients experiencing intraoperative cardiovascular collapse should be treated in a latex-free environment. IMPLICATIONS: We describe a patient who experienced latex-induced intraoperative anaphylaxis. The event coincided with antibiotic administration, which prompted us to erroneously assume that the causative allergen was medication related. Allergy to latex must always be considered as a potential culprit of perioperative cardiovascular collapse.

Extrapyramidal reactions to ondansetron: cross-reactivity between ondansetron and prochlorperazine?

IMPLICATIONS: Ondansetron can rarely induce extrapyramidal reactions in susceptible individuals. Our patient had a history of drug-induced dystonic reaction; therefore, these patients may be susceptible to extrapyramidal adverse reactions after ondansetron.

Intrathecal fentanyl, sufentanil, or placebo combined with hyperbaric mepivacaine 2% for parturients undergoing elective cesarean delivery.

UNLABELLED: Worldwide, long-acting bupivacaine is the most popular local anesthetic for spinal anesthesia in parturients undergoing elective cesarean delivery. With advances in surgical techniques, e.g., the Misgav Ladach method, and shorter duration of surgery, the local anesthetic mepivacaine, with an intermediate duration of action, may be a reasonable alternative. Our aim in the present study was to evaluate the effects of 2% hyperbaric mepivacaine alone, or combined with either intrathecal fentanyl (5 and 10 microg), or sufentanil (2.5 and 5 microg), on sensory, motor, and analgesic block characteristics, hemodynamic variables, and neonatal outcome in a randomized, prospective, and double-blinded study (n = 100, 20 parturients per group, singleton pregnancy, >37 wk of gestation). No parturient experienced intraoperative pain. The average duration of motor block Bromage 3 in all groups was 68 min, and resolution time to Bromage 0 was 118 min. Maximal cephalad sensory block level was T3-6 and could be established within 6 min. Complete analgesia was significantly prolonged in all groups receiving intrathecal opioids, yet, with sufentanil 5 microg, even the duration of effective analgesia was significantly extended. Neonatal outcome was not affected by intrathecal opioid administration. In conclusion, 2% hyperbaric mepivacaine is a feasible local anesthetic for spinal anesthesia in parturients undergoing elective cesarean delivery, particularly with short duration of surgery. IMPLICATIONS: Sensory, motor, and analgesic block characteristics of the local anesthetic mepivacaine alone or combined with intrathecal opioids were studied in parturients undergoing elective cesarean delivery in a randomized, double-blinded clinical trial. Mepivacaine was found to be an acceptable local anesthetic for spinal anesthesia in parturients undergoing cesarean delivery. In combination with sufentanil 5 microg, complete and effective analgesia were significantly prolonged.

Fast track anesthesia for liver transplantation reduces postoperative ventilation time but not intensive care unit stay.

Fast tracking is an approach to health care delivery that emphasizes the efficient use of resources. This investigation was designed to determine whether shorter-acting drugs and different drug administration practices reduce the length of time for which patients require mechanical ventilation and intensive care after liver transplantation. After obtaining Institutional Review Board approval and informed consent, we randomized 80 consecutive patients (>17 years) undergoing liver transplantation to receive either our traditional anesthetic (thiopental, pancuronium, 50 microg/kg fentanyl), or fast track anesthetic (propofol, cisatracurium, 20 microg/kg fentanyl). The patients were weaned to extubation in the intensive care unit after an established clinical protocol. Measured data included the occurrence of intraoperative hypotension, intraoperative hypertension, intraoperative tachycardia, the length of postoperative mechanical ventilation, length of intensive care unit stay, and episodes of reintubation. Seventy-eight patients remained in the study through the investigation (two died intraoperatively). Operating time; amount of intraoperative red blood cells transfused; lowest body temperature achieved; and minutes of intraoperative hypotension, hypertension, and tachycardia were not different between the traditional and fast track patient groups. Postoperative ventilation time was greater in the patients who received the traditional anesthetic; mean. 1,081 minutes (median, 855) versus mean, 553.5 minutes (median, 390) (P <.001). However, there was no difference in length of intensive care unit stay. Five patients required reintubation (two patients given the traditional anesthetic, three given the fast track anesthetic). We conclude that a fast track approach to anesthetic care reduces the requirement for postoperative mechanical ventilation, but does not reduce intensive care unit stay after liver transplantation.