Pulmonary nontuberculous mycobacterial disease prevalence and clinical features: an emerging public health disease.

RATIONALE: Respiratory specimens with nontuberculous mycobacteria (NTM) are increasingly common; however, pulmonary disease prevalence is unknown. OBJECTIVES: To determine the disease prevalence, clinical features, and risk factors for NTM disease, and to examine the predictive value of the microbiologic criteria of the American Thoracic Society (ATS)/Infectious Diseases Society of America (IDSA) pulmonary NTM case definition for true NTM disease. METHODS: We identified all Oregon residents during 2005-2006 with at least one respiratory mycobacterial isolate. From a population-based subset of these patients, we collected clinical and radiologic information and used the ATS/IDSA pulmonary NTM disease criteria to define disease. MEASUREMENTS AND MAIN RESULTS: In the 2-year time period, 807 Oregonians had one or more respiratory NTM isolates. Four hundred and seven (50%) resided within the Portland metropolitan region, among which 283 (70%) had evaluable clinical records. For those with records, 134 (47%) met ATS/IDSA pulmonary NTM disease criteria for a minimum overall 2-year period prevalence of 8.6/100,000 persons, and 20.4/100,000 in those at least 50 years of age within the Portland region. Case subjects were 66 years of age (median; range, 12-92 yr), frequently female (59%), and most with disease caused by Mycobacterium avium complex (88%). Cavitation (24.5%), bronchiectasis (16%), chronic obstructive pulmonary disease (28%), and immunosuppressive therapy (25.5%) were common. Eighty-six percent of patients meeting the ATS/IDSA microbiologic criteria for disease also met the full ATS/IDSA disease criteria. CONCLUSIONS: Respiratory NTM isolates frequently represent disease. Pulmonary NTM disease is not uncommon, particularly among elderly females. The ATS/IDSA microbiologic criteria are highly predictive of disease and could be useful for laboratory-based NTM disease surveillance.

Prostaglandin FP receptors do not contribute to 24-hour intraocular pressure variation in mice.

PURPOSE: It is not known whether the prostaglandin FP receptor plays an important role in endogenous 24-hour regulation of intraocular pressure. The purpose of this study was to compare 24-hour intraocular pressure (IOP) in FP receptor-knockout mice with that of wild-type mice that have normal FP receptor expression. METHODS: The 24-hour IOP profile was determined by rebound tonometry in FP-knockout and wild-type mice. Peak and trough IOP was then measured by microneedle cannulation of the anterior chamber in homozygous (FP(-/-); n = 8), heterozygous (FP(+/-); n = 14), and C57BL/6 background strain mice (FP(+/+); n = 11). To confirm any differences in baseline IOP between genotypes, midafternoon IOP was also measured in a larger, separate group of FP(-/-) mice (n = 20), FP(+/-) mice (n = 49), and FP(+/+) (n = 23) wild-type littermates. RESULTS: Trough IOPs were measured between 10 AM and 12 PM, peak IOPs were measured between 8 and 10 PM. For FP(+/+), FP(+/-), and FP(-/-) mice trough IOP was 16.2, 15.3, and 15.1 mm Hg and peak IOPs were 18.2, 18.4, and 17.7 mm Hg, respectively. There was no significant difference among genotypes for mean peak or mean trough IOP or for peak-trough difference in IOP among genotypes (P > 0.05, ANOVA). In addition, there was no significant difference in midafternoon IOP between genotypes in a larger population (n = 92) of FP-knockout and wild-type mice. CONCLUSIONS: An intact FP receptor does not appear to be critical for normal 24-hour IOP regulation in the mouse eye.

Effect of bimatoprost on intraocular pressure in prostaglandin FP receptor knockout mice.

PURPOSE: To determine the effect of bimatoprost on intraocular pressure in the prostaglandin FP receptor knockout mouse. METHODS: The IOP response to a single 1.2-microg (4 microL) dose of bimatoprost was measured in the treated and untreated fellow eyes of homozygote (FP+/+, n = 9) and heterozygote (FP+/-, n = 10) FP-knockout mice, as well as in wild-type C57BL/6 mice (FP+/+, n = 20). Serial IOP measurements were also performed after topical bimatoprost in a separate generation of homozygous FP-knockout mice and wild-type littermate control animals (n = 4 per group). Aqueous humor protein concentrations were measured to establish the state of the blood-aqueous barrier. Tissue, aqueous humor and vitreous concentrations of bimatoprost, latanoprost, and their C-1 free acids were determined by liquid chromatography and tandem mass spectrometry. RESULTS: A significant reduction in IOP was observed in the bimatoprost-treated eye of wild-type mice at 2 hours, with a mean difference and 95% confidence interval (CI) of the difference in means of -1.33 mm Hg (-0.81 to -1.84). Bimatoprost did not lead to a significant reduction in IOP in either the heterozygous knockout -0.36 mm Hg (-0.82 to +0.09) or homozygous FP-knockout mice 0.25 mm Hg (-0.38 to +0.89). The lack of an IOP response in the FP-knockout mice was not a consequence of blood-aqueous barrier breakdown, as there was no significant difference in aqueous humor protein concentration between treated and fellow eyes. Tissue and aqueous humor concentrations of bimatoprost, latanoprost, and their C-1 free acids indicate that latanoprost, but not bimatoprost, is hydrolyzed in the mouse eye after topical administration. CONCLUSIONS: An intact FP receptor gene is critical to the IOP response to bimatoprost in the mouse eye.

Comparison of invasive and non-invasive tonometry in the mouse.

Assessment of the accuracy of non-invasive rebound tonometry, and comparison with invasive cannulation tonometry. An in vivo calibration technique was devised to improve the accuracy of the rebound tonometer. IOP was then measured in SW mice using both rebound and cannulation tonometry. The ability of the rebound tonometer to accurately measure small IOP reductions after instillation of a topical prostaglandin was also determined. With the rebound method, mid-afternoon IOP in two groups of similar aged SW mice was 15.9+/-3.9 mmHg (mean+/-s.d., n=25) compared to 16.3+/-1.2 mmHg (n=32) using the cannulation technique. This difference was not statistically significant (p=0.6). For serial measurements using both techniques in the same eyes of a third group of SW mice (n=14), mean IOP was 15.0+/-3.9 mmHg for rebound tonometry but only 13.4+/-2.3 mmHg for subsequent cannulation tonometry. This effect was subsequently shown to be a consequence of the rebound tonometry, as multiple rebound measurements induced a statistically significant reduction in IOP. The average IOP reduction observed 2 hr after a single application of topical latanoprost (200 ng) was 2.8+/-1.3 mmHg (p<0.001) and 2.4+/-4.7 mmHg (p=0.03) with cannulation and rebound tonometers, respectively. These differences were not significantly different (p=0.8). In vivo calibration of the rebound tonometer increased measurement accuracy and provided IOP values within the physiological range that agreed closely with the IOP measured by cannulation tonometry. However, IOP measurement with the rebound tonometer had larger variability compared with the cannulation method. Repeat IOP measurements with the rebound tonometer led to a reduction in IOP. The rebound tonometer was sufficiently sensitive to detect a 2-3 mmHg reduction in IOP following application of topical latanoprost. Despite these limitations, the rebound tonometer has a significant advantage over cannulation tonometry in that it permits longitudinal IOP measurement in conscious mice.