A large-scale assessment of lakes reveals a pervasive signal of land use on bacterial communities.

Lakes play a pivotal role in ecological and biogeochemical processes and have been described as "sentinels" of environmental change. Assessing "lake health" across large geographic scales is critical to predict the stability of their ecosystem services and their vulnerability to anthropogenic disturbances. The LakePulse research network is tasked with the assessment of lake health across gradients of land use on a continental scale. Bacterial communities are an integral and rapidly responding component of lake ecosystems, yet large-scale responses to anthropogenic activity remain elusive. Here, we assess the ecological impact of land use on bacterial communities from over 200 lakes covering more than 660,000 km2 across Eastern Canada. In addition to community variation between ecozones, land use across Eastern Canada also appeared to alter diversity, community composition, and network structure. Specifically, increasing anthropogenic impact within the watershed lowered diversity. Likewise, community composition was significantly correlated with agriculture and urban development within a watershed. Interaction networks showed decreasing complexity and fewer keystone taxa in impacted lakes. Moreover, we identified potential indicator taxa of high or low lake water quality. Together, these findings point to detectable bacterial community changes of largely unknown consequences induced by human activity within lake watersheds.

An experimental test of the causes of small-scale phenotypic differentiation in a population of great tits.

Phenotypic differentiation between populations is thought to occur mainly at spatial scales where gene-flow is restricted and selection regimes differ. However, if gene flow is nonrandom, dispersal may reinforce, rather than counteract, evolutionary differentiation, meaning that differences occurring over small scales might have a genetic basis. The purpose of this study was to determine the cause of differences in mean phenotype between two parts of a population of great tits Parus major, separated by <3 km. We conducted a partial cross-fostering experiment between two contrasting parts of this population to separate genetic and environmental sources of variation, and to test for gene-environment interaction. We found strong environmental effects on nestling size, mass and condition index, with nestlings reared in a low density part of the population being larger, heavier and in better condition, than those in a high density part, irrespective of their origin. In addition, we found smaller, but significant, differences in nestling condition and shape associated with the areas that birds originated from, suggesting the presence of genetic differences between parts of this population. There was no evidence of gene-environment interaction for any character. This experiment is thus consistent with previous analyses suggesting that differences between parts of this population had evolved recently, apparently due to phenotype-dependent dispersal, and indicates that population differentiation can be maintained over small spatial scales despite extensive dispersal.

Distribution and elimination of tobramycin administered in single or multiple daily doses in adult patients with cystic fibrosis.

Aminoglycosides are often prescribed as part of the treatment regimen for acute pulmonary exacerbations due to their potent activity and low potential for development of resistance. Preliminary evidence from randomized controlled trials in patients with cystic fibrosis (CF) suggests that once-daily administration of aminoglycosides results in similar efficacy and a low risk for toxicity compared with traditional dosing. The pharmacokinetics of aminoglycosides administered once daily in CF patients are currently not well described. In this study we compare the distribution and elimination patterns of traditional dosing (3.3 mg/kg q8h) versus once-daily dosing (10 mg/kg q24h) of tobramycin in six adult patients with CF. The pharmacokinetics of tobramycin administered either once daily or every 8 h were best described by a two-compartment model. No statistically significant differences in any of the pharmacokinetic parameter values between regimens were noted. The distribution phase half-lives of 32 and 24 min following the q8h and q24h regimens were longer than expected. The use of a one-compartment model requires clinical peak levels to be drawn 2 h after initiation of either a 30 min infusion for multiple daily dosing or a 60 min infusion with once-daily dosing, to ensure completion of the distribution phase. Our data indicate that a dose of 10 mg/kg/day provides post-distributional phase peak concentrations that achieve the desired goal for susceptible organisms (>20 mg/L) and AUC(24) values at the upper end of the desired range (70-100 mg.h/L).

Population pharmacokinetics and use of Monte Carlo simulation to evaluate currently recommended dosing regimens of ciprofloxacin in adult patients with cystic fibrosis.

Pharmacodynamic data on ciprofloxacin indicate that a target area under the concentration-time curve from 0 to 24 h (AUC(0-24))/MIC ratio of >or=125 is necessary to achieve optimal bactericidal activity for the treatment of gram-negative pneumonia. The purpose of this prospective study was to (i) develop a pharmacokinetic (PK) model to be utilized for therapeutic drug monitoring (TDM) of ciprofloxacin and (ii) evaluate current ciprofloxacin dosing regimens for pneumonias in cystic fibrosis (CF) patients. Twelve adult CF patients received a single 400-mg dose of IV ciprofloxacin. Six blood samples were obtained over a 12-h interval. Serum drug concentrations were determined by high-pressure liquid chromotography and were fitted to one- and two-compartment models by using NPEM2. Ciprofloxacin MIC data for Pseudomonas aeruginosa were obtained from 1,213 CF patients enrolled in a large clinical trial. A Monte Carlo simulation was performed to estimate the fractional attainment of an AUC(0-24)/MIC ratio of >or=125. A two-compartment model best describes the serum drug concentration data. The mean fitted PK parameter values are volume of distribution in the central compartment, 0.29 liter/kg; volume of distribution at steady state, 1.1 liters/kg; total clearance, 0.34 liter/h/kg; distributional clearance, 0.89 liter/h/kg; half-life at alpha phase, 0.16 h; and half-life at beta phase, 2.9 h. The overall fractional attainment of achieving an AUC(0-24)/MIC ratio of >or=125 against P. aeruginosa isolates with ciprofloxacin (400 mg every 12 h [q12h] and 8 qh) were 10 and 30%, respectively. A clinical breakpoint MIC of <0.5 microg/ml for susceptibility is suggested, based on an examination of the fractional attainment of the AUC(0-24)/MIC target at each MIC. The recommended doses of 400 mg q8h or q12h may be inadequate to treat an acute pulmonary exacerbation when given alone. The poor and variable AUC(0-24)/MIC ratios support the use of TDM to monitor and adjust the dosage to optimize the efficacy of ciprofloxacin therapy in these patients.

Pharmacokinetics of tobramycin in adults with cystic fibrosis: implications for once-daily administration.

Once-daily administration of aminoglycosides is routinely used in many institutions. However, comparative efficacy data for patients with cystic fibrosis (CF) are lacking. The purpose of the present study was to compare the predicted pharmacodynamic activity of tobramycin at 10 mg/kg of body weight/day administered every 24 h (q24h), q12h, and q8h. Pharmacokinetic (PK) data were derived from analysis of data on the drug concentration in sera from 60 adult CF patients. Individual maximum a posteriori probability Bayesian PK parameter values were used to construct serum concentration-versus-time curves and to determine various indices (peak concentration/MIC ratio [peak/MIC], area under the concentration-time curve/MIC ratio [AUC/MIC], and time that the concentration was less than the MIC [T

Lung transplantation for cystic fibrosis: an update and practical considerations for referring candidates.

In this article, the authors provide an update to Maurer and Chaparro's 1995 review in this journal of lung transplantation for cystic fibrosis. Bilateral (sequential) cadaver donor transplantation is the usual procedure of choice. The four-year survival rate for adult, all-disease, double-bilateral lung transplantation has improved to 53%. Because of lower [corrected] survival rate among adults, living-donor lobar transplantation should be performed only when cadaver lungs are unlikely to become available. The International Society for Heart and Lung Transplantation and the Cystic Fibrosis Foundation have promulgated uniform guidelines for transplantation candidate selection. Issues of diabetes mellitus, mechanical ventilation, osteoporosis, malnutrition, fungi and drug-resistant bacteria, pleural fibrosis, and sinusitis in relation to transplantation candidacy are discussed. Some practical points regarding transplantation center referral are presented, and a list of cystic fibrosis transplantation centers in the United States is supplied.

Mediastinal masses: magnetic resonance imaging in comparison with computed tomography.

Seventy-eight patients with mediastinal abnormalities were imaged with magnetic resonance imaging (MRI) to evaluate mediastinal masses and associated lung, pleural, or chest wall disease. Magnetic resonance images were compared with computed tomography (CT) scans, which were available in 45 patients. While MRI and CT were equally effective in demonstrating mediastinal lesions, CT was superior for displaying calcification within a mass in eight patients and for demonstrating associated lung abnormality in four patients. Computed tomography should remain the imaging procedure of choice after chest radiography to evaluate mediastinal masses, although MRI may be indicated in selected patients.

Sensitivity and specificity of first screen mammography in the Canadian National Breast Screening Study: a preliminary report from five centers.

Sensitivity and specificity of first screen mammography in a randomized screening trial at five centers are reported. A total of 23,101 women underwent mammography; in 139, breast cancer was detected at first screening; in 20, less than 12 months after first screening; and in 47, at second screening. All 206 cancer cases were histologically confirmed, and 174 were defined as being detectable at first screening. Average length of follow-up for all women was 3.2 years. Interpretations of first screen mammograms by the center radiologists were matched to known outcomes. Simultaneous blind review was performed by a single reference radiologist with mammograms from all 206 cancer cases and those of a random sample of 739 women not known to have breast cancer at 15 months or more after initial screening. Overall, the five screening centers achieved a sensitivity of 69% (range, 60%-78%), a specificity of 94% (range, 93%-96%), a positive predictive value of 8.6% (range, 3%-16%), and a negative predictive value of 99.7% (range, 99.6%-99.9%).

Conservation of oxygen supply using a reservoir nasal cannula in hypoxemic patients at rest and during exercise.

A reservoir nasal cannula which stores oxygen during exhalation and delivers it as a bolus during inhalation has been reported to conserve oxygen delivery in patients with chronic obstructive pulmonary disease (COPD) at rest. We compared the effects upon arterial oxygen saturation (SaO2) of the reservoir cannula and a standard nasal cannula in hypoxemic obstructed and restricted patients at rest and during exercise. The SaO2 was monitored by ear oximeter. While at rest, 13 obstructed and four restricted patients breathed oxygen from the reservoir cannula at 0.5, 1.0, 1.5, and 2.0 L/min and from a standard cannula at 0.5, 1.0, 2.0, 3.0, and 4.0 L/min. Mean SaO2 was significantly higher with the reservoir cannula compared to the standard cannula at 1.0 and 2.0 L/min (p less than 0.0006) and tended to be higher at 0.5 L/min (p less than 0.1). Seven obstructed patients walked on a level treadmill at 0.75 mph while breathing oxygen at 0.5 and 1.5 L/min from the reservoir cannula and at 1.0 and 3.0 L/min from the standard cannula. The SaO2 during exercise with the reservoir cannula was comparable to that with the standard cannula at approximately half of the oxygen flow rate. The ratio of the oxygen flow rate of the standard to the reservoir cannula to produce 90 percent saturation was estimated and found to be 2.5 +/- 0.8 (mean +/- SD) for patients at rest and 2.9 +/- 1.8 during exercise. We conclude that in hypoxemic patients at rest and during exercise, the reservoir cannula uses less than half the oxygen of a standard cannula to produce similar improvement in SaO2 and thus has advantages of a reduced cost of ambulatory therapy with low-flow oxygen and a longer time permitted away from a stationary source of oxygen.

Acute and subacute bronchial effects of oral cannabinoids.

The bronchodilating activity of oral cannabinoids was evaluated in three double-blind experiments that involved the study of dose-response and interactive relationships and the potential development of tolerance. Data indicated that delta 8-tetrahydrocannabinol (delta 8-THC), cannabinol (CBN), and cannabidiol (CBD) in maximal doses of 75 mg, 1200 mg, and 1200 mg, respectively, did not induce significant dose-related physiologic effects in experienced marijuana smokers. delta 8-THC (75 mg) was, however, associated with bronchodilation, tachycardia, and peak highs less than that after delta 9-tetrahydrocannabinol (delta 9-THC). The combinations of CBN and CBD with low-dose delta 9-THC (5 mg) did not induce significant bronchodilation but did exert interactive effects on heart rate and "high." A 20-day study of daily delta 9-THC (20 mg), CBN (600 mg), and CBD (1200 mg) did not indicate tolerance or reverse tolerance to any drug. We conclude that delta 9-THC and, to a lesser extent, delta 8-THC, have acute bronchodilator activity but that CBN, CBD, and their combinations do not provide effective bronchodilation. The daily use of delta 9-THC was not associated with clinical tolerance.

Respiratory status of seventy-four habitual marijuana smokers.

Previous studies of the long-term effects of habitual marijuana smoking on respiratory status and lung function have yielded conflicting results. In the present study, lung function tests obtained in 74 regular marijuana smokers (duration of smoking > two-five years; frequency of smoking three days/week to several times/day) who denied intravenous narcotic drug abuse were compared with similar tests performed in two groups of control subjects. One group consisted of individuals tested in a mobile laboratory who were computer-matched to the marijuana smokers for anthropometric characteristics and quantity and duration of tobacco smoking; the other group was comprised of 41 nonsmokers of marijuana who were tested in the same laboratory as the marijuana smokers. Paired and unpaired t analyses revealed lower values for specific airway conductance (-0.07 to -0.08 +/- 0.02; P < 0.001) in the marijuana smokers compared with either group of control subjects, but no differences in spirometric indices, closing volume or delta N2 750-1250. When non-tobacco smoking marijuana users (n = 50) were matched with either non-tobacco smoking or tobacco smoking control subjects, significant differences were again noted in specific airway conductance (P < 0.001) but not in spirometric tests, closing volume or delta N2 750-1250. These results suggest that habitual smoking of marijuana may cause mild, but significant, functional impairment predominantly involving large airways which is not detectable in individuals of the same age who regularly smoke tobacco. The clinical implications of these findings await further study.

Methods of intermittent positive pressure breathing.

Inspiratory capacity (IC) was evaluated in 60 patients during the following four respiratory maneuvers: (1) coached unassisted inspiration; (2) inspiratory positive-pressure breathing (IPPB) at 15 cm H2O with the patient passively inspiring; (3) IPPB at 15 cm H2O with the patient coached to actively inspire; and (4) IPPB at a peak pressure adjusted according to the judgment of the respiratory therapist, with the patient coached to actively inspire. The IC attained with these maneuvers were, respectively, as follows: (1) 1.29 +/- 0.75 L; (2) 1.13 +/- 0.52 L; (3) 1.77 +/- 0.11 L; and (4) 2.27 +/- 0.11 L (mean +/- SE). The peak ventilator pressure for maneuver 4 averaged 30 +/- 7 cm H2O (mean +/- SD), and no patient experienced harmful side effects from these peak pressures. These data indicate that the method of treatment with IPPB has profound effects upon the degree of pulmonary expansion. All research on therapy with IPPB should be carefully controlled for the method of administering IPPB, and the volumes obtained during the treatment should be carefully documented before general conclusions are drawn concerning the effects of IPPB on morbidity. For the present, we suggest that IPPB, when administered clinically, be given as described in method 4.

Familial Warthin's tumor. 1. Its synchronous occurrence in mother and son. 2. Its association with cystic oncocytic metaplasia of the larynx.

Warthin's tumor of the parotid gland is an unusual tumor for which a number of theories of pathogenesis have been advanced through the years, ranging from a branchiogenic origin to an embryonic lymph node origin to true neoplasia from parotid epithelial duct cells. Recently Allegra has suggested that Warthin's tumor may be a hypersensitivity disease. Presented here are two unique cases of Warthin's tumor, having both a familial relationship (synchronous occurrence in mother and son) and the association with cystic oncocytic metaplasia of the larynx. Observations lead to the conclusion that the lesion is primarily metaplastic, not neoplastic, with a secondary lymphoid reaction of the delayed hypersensitivity type.