Defective aeroallergen surveillance by airway mucosal dendritic cells as a determinant of risk for persistent airways hyper-responsiveness in experimental asthma.

A hallmark of atopic asthma is development of chronic airways hyper-responsiveness (AHR) that persists in the face of ongoing exposure to perennial aeroallergens. We investigated underlying mechanisms in sensitized rats focusing on a strain expressing the high-allergen-responder phenotype characteristic of human atopic asthmatics, and find that their high susceptibility to aeroallergen-induced persistent AHR is associated with deficiencies in the immunoregulatory and mucosal trafficking properties of inducible T-regulatory cells (iTregs). Counterintuitively, AHR susceptibility was inversely related to aeroallergen exposure level, high exposures conferring protection. We demonstrate that underlying this AHR-susceptible phenotype is reduced capacity of airway mucosal dendritic cells (AMDCs) for allergen sampling in vivo; this defect is microenvironmentally acquired, as allergen uptake by these cells in vitro is normal. Moreover, intranasal transfer of in vitro aeroallergen-loaded AMDC from naïve animals into AHR-susceptible animals during prolonged aerosol challenge markedly boosts subsequent accumulation of iTregs in the airway mucosa and rapidly resolves their chronic AHR, suggesting that compromised antigen surveillance by AMDC resulting in defective functional programming of iTreg may be causally related to AHR susceptibility.

Lack of an exaggerated inflammatory response on virus infection in cystic fibrosis.

Respiratory virus infections play an important role in cystic fibrosis (CF) exacerbations, but underlying pathophysiological mechanisms are poorly understood. We aimed to assess whether an exaggerated inflammatory response of the airway epithelium on virus infection could explain the increased susceptibility of CF patients towards respiratory viruses. We used primary bronchial and nasal epithelial cells obtained from 24 healthy control subjects and 18 CF patients. IL-6, IL-8/CXCL8, IP-10/CXCL10, MCP-1/CCL2, RANTES/CCL5 and GRO-α/CXCL1 levels in supernatants and mRNA expression in cell lysates were measured before and after infection with rhinoviruses (RV-16 and RV-1B) and RSV. Cytotoxicity was assessed by lactate dehydrogenate assay and flow cytometry. All viruses induced strong cytokine release in both control and CF cells. The inflammatory response on virus infection was heterogeneous and depended on cell type and virus used, but was not increased in CF compared with control cells. On the contrary, there was a marked trend towards lower cytokine production associated with increased cell death in CF cells. An exaggerated inflammatory response to virus infection in bronchial epithelial cells does not explain the increased respiratory morbidity after virus infection in CF patients.

Recent advances into understanding some aspects of the structure and function of mammalian and avian lungs.

Recent findings are reported about certain aspects of the structure and function of the mammalian and avian lungs that include (a) the architecture of the air capillaries (ACs) and the blood capillaries (BCs); (b) the pulmonary blood capillary circulatory dynamics; (c) the adaptive molecular, cellular, biochemical, compositional, and developmental characteristics of the surfactant system; (d) the mechanisms of the translocation of fine and ultrafine particles across the airway epithelial barrier; and (e) the particle-cell interactions in the pulmonary airways. In the lung of the Muscovy duck Cairina moschata, at least, the ACs are rotund structures that are interconnected by narrow cylindrical sections, while the BCs comprise segments that are almost as long as they are wide. In contrast to the mammalian pulmonary BCs, which are highly compliant, those of birds practically behave like rigid tubes. Diving pressure has been a very powerful directional selection force that has influenced phenotypic changes in surfactant composition and function in lungs of marine mammals. After nanosized particulates are deposited on the respiratory tract of healthy human subjects, some reach organs such as the brain with potentially serious health implications. Finally, in the mammalian lung, dendritic cells of the pulmonary airways are powerful agents in engulfing deposited particles, and in birds, macrophages and erythrocytes are ardent phagocytizing cellular agents. The morphology of the lung that allows it to perform different functions-including gas exchange, ventilation of the lung by being compliant, defense, and secretion of important pharmacological factors-is reflected in its "compromise design."

Embryonic chicken trachea as a new in vitro model for the investigation of mucociliary particle clearance in the airways.

Mucociliary clearance (MC) is an important defense mechanism of the respiratory system to eliminate inhaled and possibly noxious particles from the lung. Although the principal mechanics of MC seem to be relatively clear there are still open questions regarding the long-term clearance of particles. Therefore, we have developed a new set-up based on embryonic chicken trachea (ECT) to investigate mucociliary particle clearance in more detail. ECT was placed in an incubation chamber after carbon particles were applied and tracked using optical microscopy. The aim of the study was to validate this model by investigating the impact of temperature, humidity and drugs on particle transport rates. Particles were transported reproducibly along the trachea and clearance velocity (2.39 +/- 0.25) mm/min was found to be in accordance to data reported in literature. Variation in temperature resulted in significantly reduced MC: (0.40 +/- 0.12) mm/min (20 degrees C); (0.42 +/- 0.10) mm/min (45 degrees C). Decreasing humidity (99-60%) had no significant effect on MC, whereas reduction to 20% humidity showed a significant influence on particle clearance. The use of different cilio- and muco-active drugs (propranolol, terbutalin, N-acetylcysteine) resulted in altered MC according to the pharmacological effect of the substances: a concentration dependent decrease of MC was found for Propranolol. From our results we conclude that this model can be employed to investigate MC of particles in more detail. Hence, the model may help to understand and identify decisive physico-chemical parameters for MC and to answer open questions regarding the long-term clearance phenomenon.

Adequacy of pain assessment and pain relief and correlation of patient satisfaction in 68 ED fast-track patients.

INTRODUCTION: The new standards of the joint commission on accreditation of healthcare organizations specify the patient's right to appropriate assessment and management of pain. With this impetus, we looked at our own practice to see how well we assess and manage patients with pain. METHODS: Patients who presented with minor nonemergent pain were interviewed on arrival, and then again before discharge, with use of a structured questionnaire. A total of 68 completed pain surveys were analyzed. RESULTS: With use of a visual analog scale, patients rated their pain on arrival and at discharge; they also rated pain they were willing to accept when it was time for discharge. Sixty percent of the patients went home with more pain than they were willing to accept. Fifty-one percent of the patients were offered something for pain, and only half of them said the pain relief was adequate. The median time from arrival to administration of pain medication was 104 minutes. Surprisingly, the median patient satisfaction rating for overall care was "very good." DISCUSSION: This survey revealed that acute pain conditions are underevaluated and undertreated in one fast-track setting, suggesting that ED staff need more education about the management of acute pain. It also showed that relying on patient satisfaction surveys as surrogate markers for how well we manage pain is erroneous.

Follow-up of discrepancies in X-ray and electrocardiogram interpretations, and positive laboratory results.

This article describes the 1-year follow-up program implemented at Baystate Medical Center Emergency Department during 1999. Our previous system used staff who worked clinically, which led to prolonged delays in follow-up. Before initiating the program, 57% [95% confidence interval (CI): 55-59%] of all follow-up cases were done within 3 days. After program implementation, 69% (95% CI: 67-72%) of all follow-up cases were completed in the same time frame. We reduced our "delayed" follow-up cases from 20% (95% CI: 18-22%) to 4% (95% CI: 3-5%) of all cases. Critical to the new system is the assignment of nurse-physician pairing to do follow-up when they are not doing direct patient care.

Development of an ED teaching program aimed at reducing prehospital delays for patients with chest pain.

OBJECTIVE: Delays in providing thrombolytic agents to patients with chest pain occur mainly in the prehospital arena. To reduce prehospital delay in treating patients with chest pain, we created a discharge teaching video that emphasized calling 911 in the event of a possible heart attack and a written action plan to be posted near the telephone. We also gave patients their EKG readings to bring with them on their next visit to the emergency department. SETTING AND SAMPLE: All patients with chest pain admitted to the Chest Pain Observation Unit at Baystate Medical Center, Springfield, Mass, were eligible for this teaching effort. We tracked 127 nonconsecutive patients from January 1997 to May 1997. Of these patients, 108 were included in the study. RESULTS: We interviewed 102 patients (94%) 3 days after they were discharged from the Chest Pain Observation Unit. Within this group, 92% were able to describe what a heart attack might feel like, and 81.4% said they would call 911 or go to the hospital if they had symptoms of a heart attack. If they thought that their symptoms might be indigestion, 69% said they would take an antacid, then go to the hospital if they did not feel better. Fifty-one percent remembered what to do with their EKG readings, and 60.7% knew how to take their nitroglycerin correctly. CONCLUSION: We concluded that patients understood the message they were given and retained some of the material 3 days after discharge from the Chest Pain Observation Unit. The follow-up telephone calls revealed areas for improvement in the discharge teaching tools.

Enigmatic relationship of two Microsporum species.

Unusual cultures of a Microsporum species were isolated from eleven patients who had either tinea capitis or tinea corporis or both. Although the macroconidia produced in the primary cultures resembled those of M. canis, hyphal morphology and colony characteristics were different from any of the more commonly occurring Microsporum species. Careful examination of subcultures showed that the isolates were composed of two species; M. canis and M. distortum, whose relationship remains enigmatic.

Peptido polysaccharide antigens from Trichophyton mentagrophytes var. granulosum.

Two highly purified peptido polysaccharide antigens have been isolated from surface-grown cultures of Trichophyton mentagrophytes var. granulosum. Trichloroacetic acid extraction and ethanol precipitation yielded a mixture containing high-molecular-weight components which were first separated on Sephadex G-200. Subsequent fractionation by ion-exchange chromatography on DE-52-cellulose (borate form) yielded the two peptido polysaccharides. Both of the peptido polysaccharides reacted with rabbit antiserum to T. mentagrophytes var. granulosum. The two peptido polysaccharides contain 73.2% hexoses (mannose-galactose-glucose, 7.5:0.7:1), 8.6% amino acids and 1.8% amino sugars and 77.4% hexoses (mannose-galactose-glucose, 9:0.3:1), 6.2% amino acids, and 0.4% amino sugars, respectively. Each contains 16 different amino acids, threonine, proline, and serine predominating.

Caffeic acid-containing medium for identification of Cryptococcus neoformans.

A new growth medium containing caffeic acid and ferric citrate is described. The pigment produced on this medium is specific for the identification of Cryptococcus neoformans and differentiates it from other cryptococci. The medium is more easily compounded and requires less time for pigment formation than the conventional Guizotia extract media. The medium is stable in the dry form as well as in the prepared form.

Systemic amyloidosis in mice inoculated with lyophilized Candida cells.

Injection of lyophilized Candida albicans or C. parapsilosis cells induced amyloidosis in outbred CFW mice. The disease process was irreversible, and a significant number of animals died of systemic amyloidosis within 400 days after the last treatment. The techniques described may represent a model system for the study of systemic amyloidosis.

Trichophyton rubrum infections according to age, anatomical distribution and sex.

Trichophyton rubrum caused 72.9% of the cases of dermatophytosis observed in a sample of caucasoids from Philadelphia. Tinea pedis was found in 84% of the female and male patients with dermatophytosis. Tinea manuum occurred with equal frequency in both sexes whereas tinea unguium was more prevalent in females. Tinea cruris occurred almost exclusively in males. Infections of two or more anatomical sites were observed more frequently in males. The data are compared with those reported by Rosman (1966) from a similar study done in Copenhagen.

Antibodies with affinity for epithelial tissue in chronic dermatophytosis.

Antibodies to dermatophytes which also had affinity for intercellular material of epithelial tissue, were detected in sera from 80% of patients with chronic dermatophytosis using an indirect fluorescent antibody test. The class of immunoglobulins reactive with both the dermatophyte and the epithelial tissue was identified as IgM. IgM antibodies with affinity for arthrospores of Trichophyton mentagrophytes and intercellular substance of epithelial tissue could be removed from sera with mycelium of Trichophyton rubrum.