Unraveling the mysteries of serum theophylline levels: a patient care report in the light of pharmacokinetics

One of our patients had trouble maintaining therapeutic and safe levels of theophylline, even though we were careful in planning and monitoring her drug regimen. This case report shows how we were able to use principles of pharmacokinetics to distinguish among plausible explanations for her experience. We discovered that she was not taking the drug consistently as prescribed and that supervised administration resolved apparent contradictions between doses and serum levels. We believe that physicians can use the same information and methods that we used to get better and safer results from theophylline therapy.     

The Framingham Disability Study: physical disability among community-dwelling survivors of stroke

The relationship between stroke and physical disability was examined in a cohort of adult, Framingham, Massachusetts, residents who, between 1948 and 1951, were assembled for a longitudinal examination of cardiovascular disease. Multivariate analyses examined the amount of residual disability attributable to stroke among 2540 community-dwelling survivors, 27 years after their initial examination, after controlling for age, cardiovascular risk factors, other cardiovascular diseases, and eight general health conditions related to physical disability. Among men living in the community, a history of stroke explained 12% of the variance in physical disability. Suffering a stroke, however, was not as strongly related to physical disability among women living in the community, accounting for only 3% of the variance. Results suggest that although older men and women die from the same major causes, they may not be disabled by the same conditions.     

Theoretical and practical considerations in the doubly-labelled water (2H2(18)O) method for the measurement of carbon dioxide production rate in man

In the doubly-labelled water (2H2(18)O) method for the measurement of carbon dioxide production rate in man, single exponential disappearance curves for 2H2O and H2(18)O in body water are used; the precision with which the slopes and intercepts of the curves are estimated determines the precision of the estimate of carbon dioxide production rate. In studies with infants, and in computer simulations, the effect of different experimental regimes on the overall precision of the carbon dioxide production estimate was investigated. When the number of data points used was progressively reduced by shortening the total observation period from 7 d (about 3 biological half-lives for the isotopes) to 1 d there was a deleterious effect on precision and in the infants there was an upward bias in the values for carbon dioxide production. When the number of data points was reduced by removing points from the middle of the exponential curves with the maintenance of the 7-d experimental period, precision was also reduced but by less than in the former procedure and there were no consistent trends in the average values for carbon dioxide production.     

The rotating contact glass holder

A rotating contact lens holder for the three-mirror Goldmann lens permits circular examination of the fundus or chamber angle without having to change the position of the fingers on the edge of the lens. The contact lens holder consists of an outer polygonal ring hold by the thumber and index finger. An inner rotating ring holds the contact lens. Continuous rotation of the contact lens is performed with the free middle Finger. This device permits circular examination of the retina without interruption of fixation. The instrument improves not only the speed but also the reliability of the examination.     

Eledoisin and lacrimal secretion in the rabbit

Eledoisin has been tried as a possible treatment for dry eye based on the hypothesis that it pharmacologically stimulates tear secretion when topically applied to the eye. To determine if topically applied eledoisin pharmacologically stimulates orbital lacrimal secretion, the orbital lacrimal gland excretory duct of normal rabbits was cannulated, and eledoisin was applied topically with and without prior administration of proparacaine. To determine if topically applied eledoisin stimulated accessory lacrimal gland secretion, isotonic buffer with and without eledoisin was tested in a rabbit model with only accessory lacrimal tissue remaining after the administration of proparacaine. Topically applied eledoisin did not pharmacologically stimulate lacrimal secretion but rather increased lacrimal gland secretion only in non-anesthetized eyes through a sensory reflex mechanism that is blocked by proparacaine.     

Phase I evaluation of diaziquone in childhood cancer

Summary We conducted a phase I clinical study of aziridinylbenzoquinone (Diaziquone, AZQ) given as a 4 hour infusion weekly × 4. Forty-five children with recurrent acute leukemia and 33 children with various advanced solid tumors participated. Severe myelosuppression was the dose limiting toxic effect, occurring in all patients at the upper dose levels. Gastrointestinal and hepatic toxicities were infrequent and not severe. No allergic reactions occurred. Objective tumor regression was noted in 3 of 25 patients with a CNS tumor and in 6 of 45 patients with acute leukemia. For phase II trials the recommended dosage of Diaziquone given by this schedule is 18 mg/M²×4 for patients with a solid tumor, and is 30 mg/M²/week × 4 for children with acute leukemia.