Immunomodulatory Metabolites Released by the Frog-Killing Fungus Batrachochytrium dendrobatidis

Batrachochytrium dendrobatidis is a fungal pathogen in the phylum Chytridiomycota that causes the skin disease chytridiomycosis. Chytridiomycosis is considered an emerging infectious disease linked to worldwide amphibian declines and extinctions. Although amphibians have well-developed immune defenses, clearance of this pathogen from the skin is often impaired. Previously, we showed that the adaptive immune system is involved in the control of the pathogen, but B. dendrobatidis releases factors that inhibit in vitro and in vivo lymphocyte responses and induce lymphocyte apoptosis. Little is known about the nature of the inhibitory factors released by this fungus. Here, we describe the isolation and characterization of three fungal metabolites produced by B. dendrobatidis but not by the closely related nonpathogenic chytrid Homolaphlyctis polyrhiza. These metabolites are methylthioadenosine (MTA), tryptophan, and an oxidized product of tryptophan, kynurenine (Kyn). Independently, both MTA and Kyn inhibit the survival and proliferation of amphibian lymphocytes and the Jurkat human T cell leukemia cell line. However, working together, they become effective at much lower concentrations. We hypothesize that B. dendrobatidis can adapt its metabolism to release products that alter the local environment in the skin to inhibit immunity and enhance the survival of the pathogen.     

Brief review: Angiotensin converting enzyme inhibitors and angioedema: anesthetic implications

PURPOSE: Angiotensin converting enzyme inhibitors (ACEIs) are a group of drugs used to treat hypertension and heart failure, with additional benefits, such as cardiovascular and renal protection, in patients with diabetes. However, angioedema as a complication of ACEI therapy is under-recognized. As there are important implications for anesthesiologists and emergency medicine physicians, a review was undertaken to document the scope of the problem of ACEI-induced angioedema.. METHODS: A review of the published literature (identified by searching Medline, EMBASE and CINAHL) was undertaken, addressing the clinical uses of ACEIs and the incidence, risk factors, pathophysiology, clinical presentation and management of angioedema associated with the use of these drugs. PRINCIPAL FINDINGS: The incidence of ACEI related angioedema has increased from 0.1-0.2% to 1% over the last decade. Patients who are receiving ACEIs are predisposed to developing angioedema which may be triggered by trauma, airway instrumentation, infection, and irritant fumes, particularly in those who are at increased risk. Cases of acute facial and airway oedema, due to ACEI drug administration, may be misdiagnosed as an anaphylactic reaction, and the association with ACEIs may be ignored. Some cases of intraoperative and postoperative airway edema may be precipitated by airway instrumentation in patients receiving ACEI drugs. The severity of airway compromise ranges from mild facial edema to severe laryngeal or subglottic edema which may prove life-threatening. CONCLUSION: In view of the widespread clinical indications and ever-increasing use of ACEI drugs, the potentially life-threatening adverse reaction of ACEI-associated angioedema, and its treatment, must be recognized by anesthesiologists and all clinicians involved in airway management.     

Comparison of asthma treatment given in addition to inhaled corticosteroids on airway inflammation and responsiveness.

There is increasing evidence that the assessment of eosinophilic airway inflammation using induced sputum and measurement of airway hyperresponsiveness provides additional, clinically important information concerning asthma control. The aim of this study was to directly compare the effects of different treatments on these markers in patients with asthma and persistent symptoms, despite the use of low-dose inhaled corticosteroids. A double-blind four-way crossover study was performed, which compared a 1-month treatment with budesonide 400 mug b.i.d., additional formoterol, additional montelukast and placebo in 49 patients with uncontrolled asthma despite budesonide 100 mug b.i.d., with each treatment separated by a 4-week washout period. The change in sputum eosinophil count with formoterol (2.4 to 3.8% change, 0.6-fold reduction, 95% confidence interval (CI) 0.5-0.9) differed significantly from placebo (2.8 to 2.5% change, 1.1-fold reduction, 95% CI 0.7-1.6) and high-dose budesonide (2.7 to 1.6% change, 1.6-fold reduction, 95% CI 1.2-2.2). The effects of montelukast did not differ from placebo. The changes in methacholine airway responsiveness were small and did not differ between treatments. High-dose budesonide had the broadest range of beneficial effects on other outcomes, including symptom scores, morning peak expiratory flow and forced expiratory volume in one second. In conclusion, treatment given in addition to low-dose inhaled corticosteroids results in modest benefits. Formoterol and high-dose budesonide have contrasting effects on eosinophilic airway inflammation.     

The expression of emotion through nonverbal behavior in medical visits

Relationship-centered care reflects both knowing and feeling: the knowledge that physician and patient bring from their respective domains of expertise, and the physician’s and patient’s experience, expression, and perception of emotions during the medical encounter. These processes are conveyed and reciprocated in the care process through verbal and nonverbal communication. We suggest that the emotional context of care is especially related to nonverbal communication and that emotion-related communication skills, including sending and receiving nonverbal messages and emotional self-awareness, are critical elements of high-quality care. Although nonverbal behavior has received far less study than other care processes, the current review argues that it holds significance for the therapeutic relationship and influences important outcomes including satisfaction, adherence, and clinical outcomes of care.     

Identifying Risk Drinking in Expectant Fathers

Abstract: Background: Identification of risk drinking in expectant fathers may be helpful as an important part of efforts to minimize maternal alcohol use, and as an opportunity to inform them about a problematic practice during a critical developmental stage for the couple. The purpose of this study was to evaluate the T‐ACE screening questionnaire, which asks about t olerance to alcohol, being a nnoyed by other's comments about drinking, attempts to c ut down, and having a drink first thing in the morning (“ e ye‐opener”), in the male partners of pregnant women who themselves were T‐ACE positive. Methods: Two hundred fifty‐four male partners were asked to complete the T‐ACE embedded in a health survey, the Alcohol Use Disorders Identification Test (AUDIT), and other questions about their alcohol use in the past 30 days when their pregnant partners had a median gestation of 11.5 weeks (T₁). After delivery, male partners again completed the T‐ACE and quantity‐frequency questions (T₂). The predictive ability of the T‐ACE and AUDIT was compared, using risk drinking (>4 drinks/day or >14 drinks/week) as the criterion standard. Results: A substantial minority of male partners had risk drinking, 31 percent at T₁ and 25 percent at T₂. Although the AUDIT was better than the T‐ACE as an independent predictor of risk drinking, the latter was most accurate when the tolerance threshold exceeded 2 drinks, the same established for pregnant women. The sensitivity (T₁ = 84.6%, T₂ = 82.8%) and specificity (T₁ = 43.8%, T₂ = 51.1%) of the T‐ACE at this threshold compared favorably with those of the AUDIT at the standard cut point of 8. Conclusions: The T‐ACE may be a practical way for clinicians to identify risk drinking in both pregnant women and expectant fathers. (BIRTH 33:2 June 2006)     

Mild traumatic brain injury in an insured population: subjective complaints and return to employment

The great majority of traumatic brain injury (TBI) is of mild severity, with Glasgow Coma Scores (GCS) of 13-15, post-traumatic amnesia of less than 48 hours and brief, if any, hospitalization. All mild TBI admissions to hospital were provided with education in the form of a brief interview and a brochure on minor head trauma from the National Head Injury Foundation. Seventy-seven insured individuals with mild TBI were contacted by phone between 1 and 3 months post-injury to determine the frequency and severity of post-traumatic symptoms and the rate of return to work (RTW). Twenty-six per cent of those contacted had subjective complaints; 88% had returned to work or school; 16% of those returning did so with some symptoms. Only 45% of symptomatic individuals sought medical consultation for their condition when offered. Education about post-traumatic symptoms from the onset may provide sufficient reassurance to most individuals that future use of medical services is seen as unnecessary. Rate of RTW is relatively higher than reported in previous studies of mild TBI.     

Two Novel Pyrrolopyrimidine Lipid Peroxidation Inhibitors U-101033E and U-104067F Protect Facial Motor Neurons Following Neonatal Axotomy

Recent reports suggest that oxygen radical-induced lipid peroxidation plays a role in the retrograde degeneration of motor neurons following facial nerve axotomy in the neonatal rat. The purpose of the present study was to explore this notion further by testing the neuroprotective properties of two novel brain-penetrating, lipid peroxidation inhibitors, U-101033E and U-104067F, in this model of neuronal degeneration. In Experiment 1, 14-day-old rats were pretreated with 3, 10, or 30 mg/kg U-101033E (po) 10 min before right facial nerve axotomy (Day 0) and then posttreated once a day from Day 1 to Day 6, and once every other day from Day 8 to Day 21. Rats were sacrificed 21 days postaxotomy and surviving cholinergic cell bodies were identified using choline acetyltransferase immunocytochemistry. Both 10 and 30 mg/kg U-101033E significantly enhanced motor neuron survival, with survival rates of 65.9–88.9% being noted in comparison to 51.7–62% survival in vehicle controls (P ≤ 0.05). Experiment 2 demonstrated a significant neuroprotective effect of 10 and 30 mg/kg U-104067F using the same dosing schedule. Experiment 3 was designed to test whether shorter periods of drug exposure (e.g., 5 or 7 days) would be sufficient to preserve motor neurons in rats treated with 10 mg/kg U-101033E. The results suggested that as little as 5 days of drug treatment is sufficient to enhance motor neuron survival. Finally, Experiment 4 demonstrated an 18–19% increase in motor neuron survival in rats treated with 10 and 30 mg/kg U-104067F for 5 consecutive days postaxotomy. Taken together, the attenuation of motor neuron degeneration by the two pyrrolopyrimidine lipid peroxidation inhibitors, U-101033E and U-104067F, lends support to the notion that lipid peroxidation contributes to the pathogenesis of axotomy-induced neurodegeneration.