Long-term acceptance of continuous positive airway pressure in obstructive sleep apnea

We studied the long-term acceptability of nasal continuous positive airway pressure (CPAP) treatment in 168 consecutive patients, 147 with obstructive sleep apnea (OSA) and 21 with snoring. Follow-up was between 1.5 and 78 months. At latest follow-up 107 of 168 (64%) were still using CPAP. Acceptance of CPAP was least for patients with snoring alone (6 of 21 persisted) and best for patients with both excessive daytime somnolence and severe hypoxemia (minimum SaO2 less than 75%), of whom 40 of 45 (89%) persisted with treatment. Patients with excessive daytime somnolence but without severe hypoxemia were less tolerant of CPAP (39 of 71, 55%, persisted) than patients with no symptoms of excessive somnolence but with severe hypoxemia (21 of 30, 70%, persisted). The most common reasons for discontinuing CPAP were intolerance of the mask (26 of 61), the inconvenience of treatment (16 of 61), and the lack of symptomatic benefit from treatment (10 of 61). We concluded that long-term acceptance of CPAP was difficult to predict in advance but that it was most likely in patients with the most severe sleep apnea. Because intolerance of the mask and inconvenience were the most common reasons for ceasing treatment, improvements in the design of CPAP systems and careful patient training may improve the acceptability of CPAP substantially.     

Improved, computer-generated system for pyocin typing of Pseudomonas aeruginosa.

We applied numerical clustering algorithms to the selection of a new indicator strain set for the pyocin typing of Pseudomonas aeruginosa. The new indicator set is composed of selected indicator strains from the sets described in 1966 by Gillies and Govan (J. Pathol. Bacteriol. 91:339-345) and in 1974 by Jones, Zakanycz, Thomas, and Farmer (Appl. Microbiol. 27:400-406) and is designated the G-F set. This indicator set consists of 14 indicator strains which typed 99.5% of 114 test cultures, has a high degree of discrimination (10 patterns encompass 50% of the test strains), and provides 62.3% reproducibility of the same typing pattern in duplicate tests done on different days. The G-F set of indicator strains provides slightly higher percentages of typable cultures than either of the other two sets, has greater discriminatory capability, and is more reproducible than they are. We recommend that the G-F set of indicator strains be used instead of the two other sets for pyocin typing of P. aeruginosa. We also tested a recently described overlay procedure for pyocin testing of P. aeruginosa and found it to be superior to previous methods in that it is easier to perform, it provides answers in only 24 h instead of 48 h, and it can be used to type mucoid strains (which previous techniques could not readily do). Thus, the application of numerical clustering algorithms and use of a revised typing procedure have produced an improved system for pyocin typing of P. aeruginosa. Similar procedures may be applicable to other typing systems.     

Role of computed tomography in screening for hepatocellular carcinoma in patients with cirrhosis

One hundred patients with cirrhosis underwent abdominal computed tomography (CT) using a delayed contrast technique to determine liver and spleen volume. These scans were reviewed to screen this "at risk" population for hepatocellular carcinoma (HCC). Fifteen of the 100 screened patients had focal abnormalities suspicious for HCC. On biopsy, only 1 patient was shown to have HCC. The other 14 patients had either fatty infiltration or focal regeneration. In the same time interval, a total of 10 patients had histologically proven HCC. All presented with symptoms and died within 4 months of diagnosis. The results show that focal hepatic lesions can be detected by CT but in this population the lesions may not be due to HCC. The incidence of HCC was approximately 1%, probably reflecting a truly low incidence in this population.     

Relationship of oxidative damage to the hepatocarcinogenicity of the peroxisome proliferators di(2-ethylhexyl)phthalate and Wy-14,643

Quantitative comparisons of the time course of biochemical andmorphological changes induced by peroxisome proliferators resultingin low and high incidences of hepatic cancer have not been conductedpreviously under bioassay conditions. [4-Chloro-6-(2,3 xylidino)-2-pyrimidyl-thio]aceticacid (Wy-14,643) at 0.1% in the diet produced a much higherincidence of hepatic cancer in male rats than 1.2% di(2-ethylhexyl)phthalate(DEHP) in the diet. Both diets, however, caused similar degreesof peroxisome proliferation. To investigate this differencein carcinogenicity, H₂O₂-detoxification mechanisms and indicesof oxidative damage were evaluated in male F-344 rats fed 1.2%DEHP or 0.1% Wy-14,643 for up to one year. DEHP or Wy-14,643treatment increased hepatic catalase activity 25% from 8 to365 days. DEHP or Wy-14,643 treatment decreased hepatic glutathioneperoxidase activity by 50% from 8 to 365 days. Glutathione concentrationswere not affected by 151 days of DEHP or Wy-14,643 feeding.The similar effects of DEHP and Wy on H₂O₂ detoxification enzymesand glutathione concentrations suggests that these factors arenot responsible for the widely different carcinogenicities ofWy-14,643 and DEHP. Hepatic vitamin E concentrations were 50%lower in rats receiving Wy-14,643 for 151 days as compared torats fed DEHP or control diets. Lipofuscin, which was containedwithin lysosomes, was increased 3-fold after 39 days of DEHPand remained at this level up to 365 days of treatment. In comparison,lipofuscin was increased 4-fold after 18 days of Wy-14,643 andcontinued to accumulate in a linear manner reaching values 30-foldover controls after 365 days of treatment. DEHP treatment for39–365 days increased the activities of the lysosomalenzymes -fucosidase, ß-galactosidase and N-acetylglucosaminidase50–100%. The same enzyme activities were increased 4-foldafter 39–365 days of Wy-14,643. Lysosomal cathepsin Bactivity was unchanged by DEHP but doubled by 151 and 365 daysof Wy-14,643. Acid phosphatase activity was unchanged by DEHPbut increased by 50% after 151 and 365 days of Wy-14, 643. Inaddition, conjugated dienes were increased (45%) only in ratsreceiving Wy-14,643 for 151 and 365 days. These data show forthe first time that the magnitude and time course of lipofuscindeposition, induction of lysosomal enzymes and conjugated dieneaccumulation, is correlated closely with the degree of carcinogenicity.Wy-14,643-induced decreases in hepatic vitamin E concentrationscould contribute to the observed accumulation of conjugateddienes at later time points. The data suggest that lipofuscinaccumulation is an early biomarker that is quantitatively predictiveof the carcinogenicity of the peroxisome proliferators DEHPand Wy-14,643.