1,9-Dimethylhypoxanthine from a southern Australian marine sponge spongosorites species

A Spongosorites sp. collected off southern Australia has yielded 1, 9-dimethylhypoxanthine (4). The structure for 4 was solved by spectroscopic analysis.     

Cancer statistics, 2000

The Surveillance Research Program of the American Cancer Society's Department of Epidemiology and Surveillance Research reports its annual compilation of estimated cancer incidence, mortality, and survival data for the United States in the year 2000. After 70 years of increases, the recorded number of total cancer deaths among men in the US declined for the first time from 1996 to 1997. This decrease in overall male mortality is the result of recent down-turns in lung and bronchus cancer deaths, prostate cancer deaths, and colon and rectum cancer deaths. Despite decreasing numbers of deaths from female breast cancer and colon and rectum cancer, mortality associated with lung and bronchus cancer among women continues to increase. Lung cancer is expected to account for 25% of all female cancer deaths in 2000. This report also includes a summary of global cancer mortality rates using data from the World Health Organization.     

A Population Analysis of Nebulized (R)-albuterol in Dogs Using a Novel Mixed Gut-Lung Absorption PK-PD Model

Purpose. The objectives of this study were to 1) construct a pharmacokinetic-pharmacodynamic (PK-PD) model, and 2) determine the PKs and PDs of (R)-albuterol when given by nebulization to 8 dogs for 7 consecutive days. Methods. Four doses were evaluated (0.002, 0.02, 0.1, and 0.4 mg/kg/day). Blood samples were obtained after drug administration on days 1 and 7. Heart rates (HR) were obtained during treatment days 1, 4 and 7. All (R)-albuterol plasma concentrations were fitted using a mixed gut-lung absorption 2-compartment PK model. Day-1, 4, and 7 HR data were co-modeled using a direct response model with Hill-type equations, including a necessary tolerance phenomenon. The population PK-PD analysis was performed with an iterative 2-stage methodology (IT2S). Results. No chiral inversion was seen, and double absorption peaks on the plasma concentration versus time curves were observed in the majority of dogs. These were hypothesized to be the result of combined gut and lung absorption of (R)-Albuterol. Results indicated that 67% (range: 57-89%) of (R)-albuterol systemic exposure after nebulized administration is due to gut absorption. Mean population PK parameters were KaGI (10±5.7 h^–1), KaLUNG (21±9.5 h^–1), CLc/F (0.6±0.2 L/h/kg), CLd/F (1.4±0.5 L/h/kg), Vc/F (1.4±0.9 L/kg), and Vp/F (4.8±2.4 L/kg). (R)-albuterol administration was associated with an increase in the dogs heart rates. A tolerance effect related to the cumulative dose was observed and modeled. Conclusions. The presented PK-PD model appears to differentiate gut from lung absorption when (R)-albuterol is given by 15-minute nebulization to dogs. These results agree with the accepted hypothesis that most of the systemic exposure of (R)-albuterol after nebulized administration is due to gut absorption.     

Uterine phlebography

Hysterophlebographic studies were performed in 50 outpatients who had a long history of pelvic pain. The contrast medium was injected into the interstitial tissue of the fundus uteri and x-rays were taken at 10, 20, and 40 seconds. The rapidity of diffusion of the contrast medium is remarkable because 20 seconds after completion of the injection no traces of the radiopaque substance can normally be observed. Uterine phlebography is a useful method for the diagnosis of pelvic varicocele, and pelvic congestion is characterized by a delay in the elimination of the contrast medium. In 30 patients (60 per cent) the picture of pelvic congestion was found; in 6 patients (12 per cent) a diffuse pelvic varicocele was seen; and in 16 cases (32 per cent) the phlebographic study was normal.     

Functional evaluation of the patient with cholesteatoma

Aural cholesteatoma presents a challenging management problem. The literature abounds in excellent reports concerning surgical management, but emphasis should also be placed on the pre-operative evaluation of the patient in a systematic and complete manner. Relative to the patient's evaluation, the surgeon must decide whether or not surgery is necessary, the anticipated prognosis, and the effects of the management upon the patient in his socioeconomic environment. A series of seven questions are presented. Their answers should assist the otologist in systematically approaching the management of the patient with aural cholesteatoma.