Pharmaceutical and biotechnological aerosols for cystic fibrosis therapy

This review addresses different aerosol therapies used to treat the underlying cause and symptoms of cystic fibrosis (CF) during the past two decades. A summary of the current methods of aerosol delivery and suggestions that may improve the efficacy of the current treatments are provided.     

Factors affecting the deposition of inhaled porous drug particles

Recent findings indicate that the inhalation of large manufactured porous particles may be particularly effective for drug delivery. In this study, a mathematical model was employed to systematically investigate the effects of particle size, particle density, aerosol polydispersity, and patient ventilatory parameters on deposition patterns of inhaled drugs in healthy human lungs. Aerodynamically similar particles with densities of 0.1, 1.0, and 2.0 g/cm(3) were considered. Particle size distributions were defined with mass median aerodynamic diameters (MMADs) ranging from 1 to 3 microm and geometric standard deviations ranging from 1.5 to 2.5, representing particles in the respirable size range. Breathing rates of 30 and 60 L/min with tidal volumes of 500 to 3000 mL were assumed, simulating shallow to deep breaths from a dry powder inhaler. Particles with a high density and a small geometric diameter had slightly greater deposition fractions than particles that were aerodynamically similar, but had lower density and larger geometric size (typical of manufactured porous particles). This can be explained by the fact that particles with a small geometric diameter deposit primarily by diffusion, which is a function of geometric size but is independent of density. As MMAD increased, the effect of density on deposition was less pronounced because of the decreased efficiency of diffusion for large particles. These data suggest that polydisperse aerosols containing a significant proportion of submicron particles will deposit in the pulmonary airways with greater efficiency than aerodynamically similar aerosols comprised of geometrically larger porous particles.     

Hypertension control: how well are we doing?

BACKGROUND: We compared blood pressure (BP) control in a recent cohort of hypertensive military veterans with BP control in a previous cohort and examined whether hypertension treatment practices, as defined by the frequency of antihypertensive medication dosage increases, have changed over time. METHODS: We abstracted 1999 outpatient chart data including visit type, BP measurements, comorbidities, and medication use for 981 randomly selected hypertensive veterans. We examined overall BP control and control in subgroups with diabetes mellitus and renal disease, and compared results with those of a sample of 800 veterans studied from 1990 to 1995. We also compared the frequency of antihypertensive medication dosage increases in the 2 samples. RESULTS: Mean BPs were significantly lower in 1999. The mean systolic drop was 3.1 mm Hg and reached 13.7 mm Hg for the subgroups with diabetes and renal disease. Even larger decreases were seen in mean diastolic BPs. In 1999, 57% of patients had BP measurements of 140/90 mm Hg or higher, vs 69% of patients in the 1990-1995 study (P<.001). In 1999, the BP control of patients with diabetes was similar to that of patients without diabetes, as 60% of the former had BP measurements of 140/90 mm Hg or higher. Patients with renal disease had better control than those without, however, as only 43% had BP measurements of 140/90 mm Hg or higher. When comparing samples, patients with diabetes, renal disease, or both had better BP control in 1999 than their counterparts in the 1990-1995 study (P<.003 in all cases). In 1999, more medical visits were associated with medication dosage increases than in the 1990-1995 study. CONCLUSIONS: Although overall BP control has improved, BP measurements still exceeded recommended levels in most patients. For patients with diabetes and renal disease BP was much better controlled in the more recent sample. However, BP control of patients with diabetes was similar to that of patients without diabetes, and not in agreement with the guideline-recommended tighter control. Thus, room for improvement remains, especially in this subgroup.     

Lesion response of long-term and recently immigrated resident endoneurial macrophages in peripheral nerve explant cultures from bone marrow chimeric mice

Resident macrophages of the peripheral nervous system have recently been shown to respond rapidly to Wallerian degeneration before the influx of blood-derived macrophages. Because resident endoneurial macrophages are slowly but incompletely exchanged from the blood within 3 months, they could potentially comprise a heterogenous cell population consisting of long-term resident cells and more mobile cells undergoing turnover. We used bone marrow chimeric mice created by transplanting bone marrow from green fluorescent protein-transgenic mice into irradiated wildtype recipients to selectively analyse the response of these two resident macrophage populations to Wallerian degeneration in sciatic nerve explant cultures. In such nerves, recently immigrated macrophages exhibit green fluorescence whereas long-term resident macrophages do not. Studies in cultures from wildtype controls revealed rapid morphological changes of resident macrophages towards a bloated phenotype, a proliferative response resulting in a 3.7-fold increase of macrophage numbers over 2 weeks, and phagocytosis of myelin basic protein-immunoreactive myelin debris. When chimeric mice were analysed, both populations of resident endoneurial macrophages participated in morphological transformation, proliferation and phagocytosis. Quantitative studies revealed a stronger proliferative and phagocytic response in long-term resident endoneurial macrophages compared with recently immigrated macrophages. Our results point towards subtle, but not principal, differences between the two macrophage populations, which might indicate different stages of macrophage differentiation rather than the existence of entirely distinct endoneurial macrophage populations. The results further underline the versatility of resident endoneurial macrophages following peripheral nerve injury, which is reminiscent of the lesion response of microglial cells within the brain.     

Response of macroinvertebrates to copper and zinc in a stream mesocosm

Metal pollution of streams and rivers is recognized as one of the major concerns for management of freshwaters. Macroinvertebrate communities were established within 12 artificial streams and exposed to three replicated concentrations of a metals mixture (copper and zinc) for 34 d. The cumulative criterion units (CCU = sigma[metals]/hardness-adjusted U.S. Environmental Protection Agency [U.S. EPA] 1996 chronic criterion value) of total metals in the low, medium, and high treatments were 2.4, 5.9, and 18 CCUs. Zinc comprised approximately 75% of the CCUs in each of the treatments. Effects on taxa richness and the number of taxa in the orders Ephemeroptera, Plecoptera, and Trichoptera (EPT) were moderate at the high exposure concentration (-23% and -26% respectively, p < 0.05). All of the five major mayfly species showed near extinction, whereas four of the seven caddisflies showed stimulation (up to +121%) and three were reduced (up to -76%). Redundancy analysis for this metal gradient indicated that 94% of the variance in community structure was explained by three quantitative variables: total mayfly abundance, a mollusk (Potamopyrgus antipodarum) abundance, and the number of EPT individuals, indicating that multiple indices do provide improved predictors of metal stress. Most species showed a threshold response relationship, whereas some community indicators showed apparent hormetic responses (e.g., number of mayfly taxa, total taxa, and number of EPT taxa). Model concentration-response relationships with generalized linear models were used to provide threshold of 20% effective concentration values for species and community metrics. Threshold effect values ranged upwards of 1.4 CCUs, indicating that U.S. EPA chronic criteria would be protective of species and community responses.     

Obstetric risk factors for postnatal depression in urban and rural community samples

OBJECTIVE: The objective of this study was to examine obstetric risk factors for postnatal depression in an urban and rural community sample, with concurrent consideration of personality, psychiatric history and recent life events. METHODS: This was a prospective study with women planning to give birth in one of the four participating hospitals recruited antenatally. Obstetric information was obtained from the New South Wales Midwives Data Collection, completed shortly after delivery. Personality, psychiatric history and life-events information were obtained from a questionnaire, administered within 1 week postpartum. Depression status was assessed at 8 weeks postpartum using the Edinburgh Postnatal Depression Scale. RESULTS: Complete data were obtained from 490 women. Several non-obstetric risk factors for the development of postnatal depression at 8 weeks postpartum were reported including: sociodemographic (up to technical college level education, rented housing, receiving a pension/benefit), personality (those who described themselves as either nervy, shy/selfconscious, obsessional, angry or a worrier), psychiatric history (familial history of mental illness, personal history of depression or anxiety or a history of depression in the participant's mother) and recent life-events (major health problem, arguments with partner and friends/relatives). None of the obstetric variables were significantly associated with increased risk for postnatal depression, but several showed marginally significant increases (multiparous women, antepartum haemorrhage, forceps and caesarean section deliveries). CONCLUSIONS: The results emphasize the importance of psychosocial risk factors for postnatal depression and suggest that most obstetric factors during pregnancy and birth do not significantly increase risk for this depression. Early identification of potential risk for postnatal depression should include assessment of sociodemography, personality, psychiatric history and recent life events, as well as past and present obstetric factors.     

Aspiration of an oropharyngeal airway during nasotracheal intubation

The oropharyngeal airway (OPA) has been a remarkably safe device since its invention by Guedel in 1933. This plastic device is easily placed in the mouth and used for aiding in mask ventilation. We report a case of the aspiration of an OPA causing near total upper airway obstruction.