Airway responsiveness to hyperosmolar saline challenge in cystic fibrosis: A pilot study

Hyperosmolar aerosols are used to assess airway responsiveness in subjects with asthma. Using a 10% NaCl aerosol, we investigated airway responsiveness in 23 cystic fibrosis (CF) subjects (12 females, 11 males; 19.1 ± 3.3 years) who had asthma-like symptoms. The pre-challenge predicted forced expiratory volume in 1 second (FEV₁) was 74.7 ± 21.5. The aerosol was generated by a MistO₂gen 143A ultrasonic nebulizer and inhaled for 0.5, 1, 2, 4, 8, 8, and 8 minutes or part thereof. Spirometry was performed before and 1 minute after each inhalation period. The challenge was stopped when a ≥20% fall from the baseline FEV₁ was recorded, after the last inhalation period, or when requested by the subject. We recorded different responses to 10% NaCl among subjects. In 7, the FEV₁ fell progressively throughout the challenge in a manner similar to asthmatics. By contrast, in 15 subjects the FEV₁ was higher at the completion of challenge compared to during challenge, i.e., the fall in FEV₁ was transient. In 7 of these subjects, the final FEV₁ at the end of the challenge was higher than the pre-challenge FEV₁. We conclude that inhaled 10% hyperosmolar saline causes either progressive and sustained or transient airway narrowing during challenge in the majority of CF subjects. The cause of the transient airway narrowing requires further investigation. Pediatr Pulmonol. 1996;21:282–289. © 1996 Wiley-Liss, Inc.     

Characterization of In100, a new integron carrying a metallo-{beta}-lactamase and a carbenicillinase, from Pseudomonas aeruginosa

In100, a new integron carrying a carbapenemase gene (bla(VIM-2)) associated with a carbenicillinase (blaP1b) and aminoglycoside resistance genes (aacA4 and aadA2), was detected in a Pseudomonas aeruginosa clinical isolate. The particular gene cassette organization of In100 seems to reflect the evolution of antibiotic usage in therapeutics.     

The photoneuroendocrine control of seasonal breeding in the ewe

The major environmental parameter controlling seasonal breeding in ewes is photoperiod. Short days stimulate, and long days inhibit breeding activity. One of the more intriguing enigmas of neuroendocrinology is the endocrine mechanism whereby a mere change in daylength initiates or prevents estrous cycles. Recent experiments have begun to solve this problem by demonstrating that in ewes, photoperiod governs response of the hypothalamo-pituitary axis to the negative feedback action of estradiol. In long days, estradiol is a potent inhibitor of gonadotropin secretion, whereas in short days it is relatively ineffective in this regard. These photoperiod-induced changes in estradiol feedback are proposed to permit or prevent estrous cycles by controlling the occurrence of a crucial step in the sequence of events leading to ovulation, namely a sustained, preovulatory rise in LH. Thus, estrous cycles cease in long days because an increase in estradiol negative feedback prevents the sustained rise in LH. In short days, estrous cycles resume because a decrease in estradiol feedback permits the sustained rise in LH required for ovulation. Even more puzzling, at present, than the mechanism of transduction of photoperiodic information into an endocrine event controlling seasonal breeding is the problem of transmission of photoperiodic information from the environment to the hypothalamo-pituitary axis. In sheep, early investigations of the transmission pathway have elicited provocative results, only some of which are similar to those obtained in other species. Among the questions which remain to be answered are: what is the location of the photoreceptors, and what, if any, are the roles of the suprachiasmatic nuclei and the pineal in photoperiodic control of seasonal breeding? These issues promise to provide a tantalizing challenge for future investigations into the photoneuroendocrine control of seasonal breeding.     

Medication errors during medical emergencies in a large, tertiary care, academic medical center

Purpose

Evaluate the rate, type and severity of medication errors occurring during Medical Emergency Team (MET) care at a large, tertiary-care, academic medical center.

Methods

A prospective, observational evaluation of 50 patients that required MET care was conducted. Data on medication use were collected using a direct-observation method whereby an observer documented drug information such as drug, dose, frequency, rate of administration and administration technique. Subsequently, a team of three clinicians assessed rate, type and severity of medication errors using definitions consistent with United States Pharmacopeia MEDMARX system. Severity was assessed on a scale of minor, moderate and severe.

Results

One hundred eighty six doses were observed for 36 different medications. A total of 296 errors were identified; of these 196 errors (66%) were inappropriate aseptic technique. Of the remaining 100 errors, 46% were prescribing errors, 28% administration technique errors, 14% mislabeling errors, 10% drug preparation errors and 2% improper dose prescribing. Examples included: (1) prescribing errors, (2) administering wrong doses, (3) mislabeling, and (4) wrong administration technique such as not flushing intravenous medication through intravenous access. The rate of medication administration errors was 1.6 errors/dose including aseptic technique and 0.5 errors/dose excluding aseptic technique. A notable portion (14%) of errors was considered at least moderate in severity.

Conclusions

One out of 2 doses was administered in error after errors of using inappropriate aseptic technique were excluded. There is a need for education and systematic changes to prevent medication errors during medical emergencies as an effort to avoid harm.     

Design of an inhalable dry powder formulation of DOTAP-modified PLGA nanoparticles loaded with siRNA

Matrix systems based on biocompatible and biodegradable polymers like the United States Food and Drug Administration (FDA)-approved polymer poly(DL-lactide-co-glycolide acid) (PLGA) are promising for the delivery of small interfering RNA (siRNA) due to favorable safety profiles, sustained release properties and improved colloidal stability, as compared to polyplexes. The purpose of this study was to design a dry powder formulation based on cationic lipid-modified PLGA nanoparticles intended for treatment of severe lung diseases by pulmonary delivery of siRNA. The cationic lipid dioleoyltrimethylammoniumpropane (DOTAP) was incorporated into the PLGA matrix to potentiate the gene silencing efficiency. The gene knock-down level in vitro was positively correlated to the weight ratio of DOTAP in the particles, and 73% silencing was achieved in the presence of 10% (v/v) serum at 25% (w/w) DOTAP. Optimal properties were found for nanoparticles modified with 15% (w/w) DOTAP, which reduced the gene expression with 54%. This formulation was spray-dried with mannitol into nanocomposite microparticles of an aerodynamic size appropriate for lung deposition. The spray-drying process did not affect the physicochemical properties of the readily re-dispersible nanoparticles, and most importantly, the in vitro gene silencing activity was preserved during spray-drying. The siRNA content in the powder was similar to the theoretical loading and the siRNA was intact, suggesting that the siRNA is preserved during the spray-drying process. Finally, X-ray powder diffraction analysis demonstrated that mannitol remained in a crystalline state upon spray-drying with PLGA nanoparticles suggesting that the sugar excipient might exert its stabilizing effect by sterical inhibition of the interactions between adjacent nanoparticles. This study demonstrates that spray-drying is an excellent technique for engineering dry powder formulations of siRNA nanoparticles, which might enable the local delivery of biologically active siRNA directly to the lung tissue.     

Identification of lead compounds targeting the cathepsin B-like enzyme of Eimeria tenella

Cysteine peptidases have been implicated in the development and pathogenesis of Eimeria. We have identified a single-copy cathepsin B-like cysteine peptidase gene in the genome database of Eimeria tenella (EtCatB). Molecular modeling of the predicted protein suggested that it differs significantly from host enzymes and could be a good drug target. EtCatB was expressed and secreted as a soluble, active, glycosylated mature enzyme from Pichia pastoris. Biochemical characterization of the recombinant enzyme confirmed that it is cathepsin B-like. Screening of a focused library against the enzyme identified three inhibitors (a nitrile, a thiosemicarbazone, and an oxazolone) that can be used as leads for novel drug discovery against Eimeria. The oxazolone scaffold is a novel cysteine peptidase inhibitor; it may thus find widespread use.     

Perceptions of crisis care in populations who self‐referred to a telephone‐based mental health triage service

Although psychiatric crises are very common in people with mental illness, little is known about consumer perceptions of mental health crisis care. Given the current emphasis on recovery‐oriented approaches, shared decision‐making, and partnering with consumers in planning and delivering care, this knowledge gap is significant. Since the late 1990s, access to Australian mental health services has been facilitated by 24/7 telephone‐based mental health triage systems, which provide initial psychiatric assessment, referral, support, and advice. A significant proportion of consumers access telephone‐based mental health triage services in a state of crisis, but to date, there has been no published studies that specifically report on consumer perceptions on the quality and effectiveness of the care provided by these services. This article reports on a study that investigated consumer perceptions of accessing telephone‐based mental health triage services. Seventy‐five mental health consumers participated in a telephone interview about their triage service use experience. An eight‐item survey designed to measure the responsiveness of mental health services was used for data collection. The findings reported here focus on the qualitative data produced in the study. Consumer participants shared a range of perspectives on telephone‐based mental health triage that provide invaluable insights into the needs, expectations, and service use experiences of consumers seeking assistance with a mental health problem. Consumer perceptions of crisis care have important implications for practice. Approaches and interventions identified as important to quality care can be used to inform educational and practice initiatives that promote person‐centred, collaborative crisis care.