Minimum Alveolar Concentration of Volatile Anesthetics in Rats during Postnatal Maturation

Background: Although neonatal rats have become widely used as experimental laboratory animals, minimum alveolar concentration (MAC) values of volatile anesthetics in rats during postnatal maturation remain unknown.

Methods: We determined MAC values of volatile anesthetics in spontaneously breathing neonatal (2-, 9-, and 30-day-old) and adult Wistar rats exposed to increasing (in 0.1-0.2% steps) concentrations of halothane, isoflurane, or sevoflurane (n = 12-20 in each group), using the tail-clamp technique. MAC and its 95% confidence intervals were calculated using logistic regression and corrected for body temperature (37[degrees]C).

Results: In adult rats, inspired MAC values corrected at 37[degrees]C were as follows: halothane, 0.88% (confidence interval, 0.82-0.93%); isoflurane, 1.12% (1.07-1.18%); and sevoflurane, 1.97% (1.84-2.10%). In 30-day-old rats, the values were as follows: halothane, 1.14% (1.07-1.20%); isoflurane, 1.67% (1.58-1.76%); and sevoflurane, 2.95% (2.75-3.15%). In 9-day-old rats, inspired MAC values were as follows: halothane, 1.68% (1.58-1.78%); isoflurane, 2.34% (2.21-2.47%); and sevoflurane, 3.74% (3.64-3.86%). In 2-day-old rats, inspired MAC values were as follows: halothane, 1.54% (1.44-1.64%); isoflurane, 1.86% (1.72-2.01%); and sevoflurane, 3.28% (3.09-3.47%).     

The discard of deceased donor kidneys in the UK

It is essential to minimize the unnecessary discard of procured deceased donor kidneys, but information on discard rates and the extent to which discard can be avoided are limited. Analysis of the UK Transplant Registry revealed that the discard rate of procured deceased donor kidneys has increased from 5% in 2002‐3 to 12% in 2011‐12. A national offering system for hard‐to‐place kidneys was introduced in the UK in 2006 (the Declined Kidney Scheme), but just 13% of kidneys that were subsequently discarded until 2012 were offered through the scheme. In order to examine the appropriateness of discard, 20 consecutive discarded kidneys from 13 deceased donors were assessed to determine if surgeons agreed with the decision that they were not implantable. Donors had a median (range) age of 67 (31–80) yr. Kidneys had been offered to a median of 3 (1–12) centers before discard. Four (20%) of the discarded kidneys were thought to be usable, and nine (45%) were possibly usable. As a result of these findings, major changes to the UK deceased donor kidney offering system have been implemented, including simultaneous offering and broader entry criteria for hard‐to‐place kidneys. Organizational changes are necessary to improve utilization of deceased donor kidneys.     

Antigen‐specific CD4+CD25+ T cells induced by locally expressed ICOS‐Ig: the role of Foxp3, Perforin,Granzyme B and IL‐10 ‐ an experimental study

We have previously reported that ICOS‐Ig expressed locally by a PIEC xenograft induces a perigraft cellular accumulation of CD4⁺CD25⁺Foxp3⁺ T cells and specific xenograft prolongation. In the present study we isolated and purified CD4⁺CD25⁺ T cells from ICOS‐Ig secreting PIEC grafts to examine their phenotype and mechanism of xenograft survival using knockout and mutant mice. CD4⁺CD25⁺ T cells isolated from xenografts secreting ICOS‐Ig were analysed by flow cytometry and gene expression by real‐time PCR. Regulatory function was examined by suppression of xenogeneic or allogeneic primed CD4 T cells in vivo. Graft prolongation was shown to be dependent on a pre‐existing Foxp3⁺ Treg, IL‐10, perforin and granzyme B. CD4⁺CD25⁺Foxp3⁺ T cells isolated from xenografts secreting ICOS‐Ig demonstrated a phenotype consistent with nTreg but with a higher expression of CD275 (ICOSL), expression of CD278 (ICOS) and MHC II and loss of CD73. Moreover, these cells were functional and specifically suppressed xenogeinic but not allogeneic primed T cells in vivo.     

Monitoring systemic donor lymphocyte macrochimerism to aid the diagnosis of graft-versus-host disease after liver transplantation

BACKGROUND: The diagnosis of graft-versus-host disease (GvHD) after liver transplantation can be difficult because early symptoms are often nonspecific. In this study, the presence of donor lymphocyte macrochimerism in recipient peripheral blood was examined as a diagnostic aid for GvHD after cadaveric donor liver transplantation. METHODS: Between 1996 and 2002, 33 liver transplant recipients with a clinical suspicion of GvHD (skin rash, diarrhea, pyrexia, pancytopenia, or anemia, without an obvious alternative cause) were investigated for peripheral blood donor lymphocyte macrochimerism. Donor macrochimerism was determined at the time of first clinical presentation by a low-sensitivity polymerase chain reaction (PCR) to detect donor human leukocyte antigen (HLA) alleles using genomic DNA extracted from recipient peripheral blood. Where donor HLA alleles were detected, the percentage of donor T cells was quantified by two-color flow cytometric analysis using antibodies specific for mismatched donor and recipient HLA alleles. The relationship between the presence or absence of donor lymphocyte macrochimerism and final diagnoses based on clinical and histological criteria was examined. RESULTS: Seven of the 33 patients were PCR positive for donor HLA alleles. All had macrochimerism, with donor T lymphocyte levels ranging from 4% to 50% of circulating lymphocytes. All seven patients had normal liver function tests, skin rash, and diagnosis of GvHD histologically confirmed by skin or gut biopsies. Twenty-six patients were PCR negative, and, in 23, an alternative diagnosis was eventually established. The remaining three patients made a rapid and spontaneous recovery with no further symptoms suggestive of GvHD. CONCLUSIONS: Donor lymphocyte macrochimerism was present in all patients in whom the diagnosis of GvHD was confirmed. In patients with symptoms consistent with GvHD and a negative PCR for donor HLA, an alternative diagnosis was eventually established or the patients recovered spontaneously. Detection of donor HLA alleles in recipient peripheral blood by PCR is a useful diagnostic tool for GvHD after liver transplantation.     

No association between high-altitude tolerance and the ACE I/D gene polymorphism

PURPOSE: The absence (deletion allele [D]) of a 287 base-pair fragment in the ACE gene is associated with higher ACE tissue activity than its presence (insertion allele [I]) and, as such, may enhance vasoconstriction and fluid retention through increased levels of angiotensin II and aldosterone. Because fluid retention is found in acute mountain sickness (AMS) and exaggerated pulmonary hypertension is essential in the pathophysiology of high-altitude pulmonary edema (HAPE), we hypothesized that the DD genotype is associated with increased susceptibility to these illnesses. METHODS: ACE genotype was thus determined in 83 mountaineers staying over night at 4559 m and related to AMS symptoms. Genotype was similarly determined in 76 mountaineers who had participated in previous studies at 4559 m; 38 of the latter group had a history of HAPE, and 25 had developed HAPE again during these studies. RESULTS: The allele frequency was in Hardy-Weinberg equilibrium in both investigations. Neither the history nor the observed episodes of HAPE nor the prevalence of AMS defined as an AMS-C score >/= 0.70 (environmental symptom questionnaire) in the first study or in both studies taken together were significantly different between the genotypes DD, ID, and II. CONCLUSION: We conclude that I/D-ACE gene polymorphism has no important effect on susceptibility to AMS or HAPE.     

The 200- and 150-kDa neurofilament proteins react with IgG autoantibodies from patients with kuru, Creutzfeldt-Jakob disease, and other neurologic diseases.

Sera from 65 patients with spongiform virus encephalopathies (29 with kuru, 36 with Creutzfeldt-Jakob disease), 79 with other neurologic diseases, and 65 control subjects were examined for reactivity in immunoblots of preparations of myelinated axons and neurofilaments from mouse brain. The sera reacted most frequently with the 200-kDa and 150-kDa neurofilament proteins and less frequently with the 70-kDa neurofilament protein and a 62-kDa neurofilament-associated protein. The sera reacted with the same proteins as those which reacted with rabbit and mouse polyclonal antibodies and mouse monoclonal antibody to neurofilament proteins. Serum reactions were also seen with Trixon X-100 extracts of chimpanzee brain and bovine spinal cord but not with Triton extracts of liver, kidney, and muscle.     

The midterm experience of tapered stent grafts in the endovascular management of iliac artery aneurysms with unfavorable anatomy

We report our experience and the midterm results of a modern technique for endovascular management of isolated iliac artery aneurysms (IAAs) with unfavorable neck anatomy, which involves the inversion of an iliac leg of a Zenith stent graft. Patients who underwent endovascular IAA repair from 2002 to 2010 were reviewed. A total of 12 patients, with a mean age of 77.6 years, underwent endovascular repair of 13 IAAs. Mean size of the aneurysms was 54.6 mm (range 34-133 mm). Mean proximal neck diameter was 18 mm (range 15-22 mm). In 7 patients, the length of the proximal neck was <15 mm (10-14 mm). Only 1 patient developed thrombosis of the stent graft immediately after the operation. Patients were followed up for a mean of 31.5 months (range 18-72 months). Our midterm results demonstrate the durability of this technique in the management of iliac aneurysms with unfavorable anatomy.     

Treatment options for obstructive sleep apnea

Opinion statement  Sleep apnea is a major public health problem that afflicts 9% of women and 24% of men 30 to 60 years of age. It is highly treatable, but when untreated, it has been associated with (but not necessarily linked to) increased probability of cerebral and coronary vascular disease, congestive heart failure, metabolic dysfunction, cognitive dysfunction, excessive daytime sleepiness, motor vehicle accidents, reduced productivity, and decreased quality of life. The gold standard for treatment in adults is positive airway pressure (PAP) therapy: continuous PAP (CPAP), bilevel PAP, autotitrating CPAP, or autotitrating bilevel PAP. Measures to increase compliance with PAP therapy include medical or surgical treatment of any underlying nasal obstruction, setting appropriate pressure level and airflow, mask selection and fitting, heated humidification, desensitization for claustrophobia, patient and partner education, regular follow-up with monitoring of compliance software, and attendance of support groups (eg, AWAKE). Adjunctive treatment modalities include lifestyle or behavioral measures and pharmacologic therapy. Patients with significant upper airway obstruction who are unwilling or unable to tolerate PAP therapy may benefit from surgery. Multilevel surgery of the upper airway addresses obstruction of the nose, oropharynx, and hypopharynx. A systematic approach may combine surgery of the nose, pharynx, and hypopharynx in phase 1, whereas skeletal midface advancement or tracheotomy constitutes phase 2. Clinical outcomes are reassessed through attended diagnostic polysomnogram performed 3 to 6 months after surgery. Oral appliances can be used for patients with symptomatic mild or moderate sleep apnea who prefer them to PAP therapy or for whom PAP therapy has failed or cannot be tolerated. Oral appliances also may be used for patients with severe obstructive sleep apnea who are unable or unwilling to undertake PAP therapy or surgery. For children, the main treatment modality is tonsillectomy and adenoidectomy, with or without turbinate surgery. Children with craniofacial abnormalities resulting in maxillary or mandibular insufficiency may benefit from palatal expansion or maxillary/mandibular surgery. PAP therapy may be used for children who are not surgical candidates or if surgery fails.     

Transesophageal echocardiography-related gastrointestinal complications in cardiac surgical patients

OBJECTIVE: The aim of this audit was to determine the incidence of major gastrointestinal (GI) complications associated with intraoperative transesophageal echocardiography (TEE) in adult cardiac surgical patients in this institution. DESIGN: Retrospective database audit. SETTING: University-affiliated teaching hospital. PARTICIPANTS: Eight hundred fifty-nine consecutive cardiac surgical patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The records of all patients who developed a major upper GI complication within 30 days of cardiac surgery between January 2001 and May 2003 were examined. The patients were identified by cross-referencing cardiac surgery and endoscopy databases. A major GI complication was defined as a perforation of the esophagus or stomach or upper GI bleeding requiring transfusion, endoscopic, or surgical intervention. Early presentation was defined as <24 hours; late presentation was defined as >24 hours. During the audit period, 859 patients underwent cardiac surgery. Five hundred sixteen patients had cardiac surgery with TEE (group 1), and 343 patients had cardiac surgery without TEE (group 2). Six patients were identified, 1.2% (95% confidence interval [CI], CI, 0.5%-2.5%) in group 1 who had a major upper GI complication consistent with TEE injury. Two patients, 0.38% (95% CI, 0.05%-1.40%), presented early, and 4 patients, 0.76% (95% CI, 0.21%-1.98%), presented late. One patient in group 2 developed a major upper GI complication, 0.29% (95% CI, 0.01%-1.6%). CONCLUSION: The incidence of major GI complications attributed to TEE in this group of cardiac surgical patients was higher than previously reported. Late presentation was more common than early presentation. Previous studies that have not included late presentations may have underestimated the true incidence of major GI complications related to TEE.     

Photoimmunosuppression: a brief overview

Exposure to ultraviolet radiation can lead to suppression of many adaptive immune responses, both to antigens encountered within a short period of the irradiation (primary) and to antigens previously encountered (memory). The pathways involved are complex and not completely elucidated. This brief review summarizes the information available currently regarding the multiple steps involved, with the aim of providing a general overview of the main aspects of photoimmunosuppression and its clinical consequences.