Optimisation of antibiotic therapy in cystic fibrosis patients. Pharmacokinetic considerations

Antibiotic therapy plays a central role in the medical management of patients with cystic fibrosis. While totally convincing efficacy data are lacking, antibiotics probably have a pronounced beneficial effect on both morbidity and mortality. Much has been learned in the past 20 years about antibiotic use in this population. At the same time, new antimicrobial agents with the potential to treat this condition have become available for use. The pharmacokinetics of a number of antibiotic classes, including beta-lactams, aminoglycosides and quinolones, are altered in this patient population. Increased total body clearance is a common occurrence but is not always changed enough to warrant altered dosages. Nonetheless, in light of altered pharmacokinetics in the cystic fibrosis population, appropriate dosage and monitoring parameters for a number of antibiotics have been determined.     

MR monitoring of focused ultrasonic surgery of renal cortex: experimental and simulation studies

The aim of the study was to test the hypothesis that magnetic resonance (MR) imaging-guided and -monitored noninvasive ultrasonic surgery can be performed in highly perfused tissues from outside the body. A simulation study was performed to evaluate the optimal sonication parameters. An MR-compatible positioning device was then used to manipulate a focused ultrasound transducer in an MR imager, which was used to sonicate kidneys of five rabbits at various power levels and different durations. Temperature elevation during sonication was monitored with a T1-weighted spoiled gradient-echo sequence. The simulation study demonstrated that a sharply focused transducer and relatively short sonication times (30 seconds or less) are necessary to prevent damage to the overlying skin and muscle tissue, which have a much lower blood perfusion rate than kidney. The experiments showed that the imaging sequence was sensitive enough to show temperature elevation during sonication, thereby indicating the location of the beam focus. Histologic evaluations showed that kidney necrosis could be consistently induced without damage to overlying skin and muscle. The study demonstrated that highly perfused tissues such as the renal cortex can be coagulated from outside the body with focused ultrasound and that MR imaging can be used to guide and monitor this surgery.     

Adenoid cystic carcinoma of the lacrimal gland in a six-year-old girl

A 6-year-old white female was found to have an adenoid cystic carcinoma originating in a lacrimal gland. Eighteen months following diagnosis, the tumor recurred. Conservative surgery has been the sole mode of therapy. To date, after four operations and quadrimenstral imaging surveillance, there is no sign of disease progression. Our purpose is to record the unusual occurrence of an adenoid cystic carcinoma of the lacrimal gland in a child. An interim report, 32 months after diagnosis, is presented.     

Recurrence and death in non-small cell lung carcinomas: a prognostic model using pathological parameters, microvessel count, and gene protein products

Optimized stent expansion by high-pressure inflations of oversized balloons has initially been derived from experience obtained with the Palmaz-Schatz stent, whereas there is little experience with this strategy in the Wallstent. By using this approach with quantitative coronary angiographic guidance, 20 Wallstents and 20 Palmaz-Schatz stents were implanted in 34 patients and consecutively examined by conventional two-dimensional (2D) intracoronary ultrasound (ICUS) and three-dimensional (3D) ICUS on the basis of the application of a pattern recognition algorithm. Ultrasound criteria of adequate stent expansion were defined as a complete apposition of the stent to the vessel wall, a stent symmetry index (SSI = minimum/maximum lumen diameter) > or = O.7, and a stent-reference lumen area ratio (SRR = Minimum intrastent lumen area/Average of proximal and distal reference lumen area) > or = O.8. In all cases a smooth angiographic lumen and a negative diameter stenosis, on the basis of a distal reference, was achieved. For the Wallstents ICUS showed a higher SSI (2D, 0.95 +/- 0.04 vs 0.85 +/- 0.09; p < 0.001; 3D, 0.90 +/- 0.09 vs 0.82 +/- 0.11, p < 0.05) and a lower SRR (2D, 0.66 +/- 0.12 vs 0.81 +/- 0.13, p < 0.005; 3D, 0.63 +/- 0.14 vs 0.74 +/- 0.15, p < 0.05) than for the Palmaz-Schatz stents. Ninety percent of failure in meeting these criteria resulted from a low SRR. The incidence of incomplete stent apposition (one in both stents) or SSI <0.7 was low and generally associated with an SRR <0.8. The Wallstents met the ICUS criteria less often (2D, 2(1O%) vs 10(50%), p < 0.01; 3D, 3(15%) vs 9(45%), p < 0.05), were significantly longer (35.1 +/- 7.7 mm and 14.3 +/- 3.3 mm, p < 0.0001), and generally demonstrated a larger vessel tapering, measured as proximal minus distal ICUS reference lumen area (1.33 +/- 2.91 mm2 vs 0.44 +/- 1.97 mm(2), not significant). Wallstents meeting the ICUS criteria, however, showed less vessel tapering (0.18 +/- 1.64 mm(2)). Thus optimized stent expansion was followed by excellent angiographic results for both Palmaz-Schatz and Wallstent. Although angiographic results and visual assessment of the ICUS examination suggested a good outcome, few Wallstents met the ICUS criteria in contrast to the Palmaz-Schatz stents. The low value of the SRR in the Wallstents is likely to be caused by vessel tapering, suggesting that this criterion may be unsuitable in assessing the adequacy of the expansion of relatively long stents such as the Wallstent.     

Protective role of gamma interferon during the recall response to influenza virus

During secondary immune responses to influenza virus, virus-specific T memory cells are a major source of gamma interferon (IFN-gamma). We assessed the contribution of IFN-gamma to heterologous protection against the A/WSN/33 (H1N1) virus of wild-type and IFN-gamma-/- mice previously immunized with the A/HK/68 (H3N2) virus. The IFN-gamma-/- mice displayed significantly reduced survival rates subsequent to a challenge with various doses of the A/WSN/33 virus. This was associated with an impaired ability of the IFN-gamma-/- mice to completely clear the pulmonary virus by day 7 after the challenge, although significant reduction of the virus titers was noted. However, the IFN-gamma-/- mice developed type A influenza virus cross-reactive cytotoxic T lymphocytes (CTLs) similar to the wild-type mice, as demonstrated by both cytotoxicity and a limiting-dilution assay for the estimation of CTL precursor frequency. The pulmonary recruitment of T cells in IFN-gamma-/- mice was not dramatically affected, and the percentage of CD4(+) and CD8(+) T cells was similar to that of wild-type mice. The T cells from IFN-gamma-/- mice did not display a significant switch toward a Th2 profile. Furthermore, the IFN-gamma-/- mice retained the ability to mount significant titers of WSN and HK virus-specific hemagglutination-inhibiting antibodies. Together, these results are consistent with a protective role of IFN-gamma during the heterologous response against influenza virus independently of the generation and local recruitment of cross-reactive CTLs.     

Physical fitness, physical activity, and functional limitation in adults aged 40 and older

PURPOSE: A cohort of middle-aged and older men and women were followed for an average of 5.5 yr to examine the association between physical fitness, physical activity, and the prevalence of functional limitation. METHODS: The participants received medical assessments between 1980 and 1988 and responded to a mail-back survey regarding functional status in 1990. RESULTS: Among 3495 men and 1175 women over 40 yr of age at baseline, 350 (7.5%) reported at least one functional limitation in daily or household activities at follow-up. The prevalence of functional limitation was higher among women than men. Physically fit and physically active participants reported less functional limitation than unfit or sedentary participants. After controlling for age and other risk factors, the prevalence of functional limitation was lower for both moderately fit (odds ratio = 0.4, 95% CI = 0.2-0.6) and high fit men (odds ratio = 0.3, 95% CI = 0.2-0.4), compared with low fit men. Corresponding figures for women were 0.5 (0.3-0.7) and 0.3 (0.2-0.5) for moderately fit and high fit women. The association between physical activity and functional limitation was similar to the data for physical fitness. CONCLUSIONS: These data support a protective effect of physical fitness and physical activity on functional limitation among older adults and extend this protective effect to middle-aged men and women.