Jack P. Freer

Inhibition of theophylline clearance by coadministered ofloxacin without alteration of theophylline effects.

The influence of multiple doses of ofloxacin (ORF 18489) on the disposition of theophylline was studied in 15 male volunteers. Subjects were confined in the Clinical Research Unit for 13 days and given a xanthine-free diet. A single dose (3 mg/kg) of theophylline was given orally, and blood samples were collected at fixed time intervals for 36 h. The concentrations of theophylline were measured with TDX (Abbott Diagnostics, Irving, Tex.), and clearance was calculated. Theophylline clearance was used to individualize subsequent doses to achieve average steady-state theophylline concentrations in plasma of 10 mg/liter. Individualized theophylline doses were administered every 8 h until steady-state conditions were reached. Theophylline clearance was determined again at steady state and on days 7 and 8. On day 8, ofloxacin (400 mg every 12 h) was given concomitantly with theophylline. Theophylline clearance was measured again on day 12, after the last theophylline dose. Administration of ofloxacin for 1 day did not change theophylline clearance, but coadministration for 4 days significantly decreased theophylline clearance by 12.1% (P less than 0.05). The area under the concentration-time curve for theophylline increased 9.9% (P less than 0.05), and average steady-state concentrations in plasma increased 10.3% (P less than 0.05). Despite changes in clearance, adverse effects of theophylline did not increase during coadministration of ofloxacin. Although statistically significant, the interaction between ofloxacin and theophylline is unlikely to be of major clinical importance.

The palliative medicine extended standardized patient scenario: a preliminary report.

An extended standardized patient scenario (ESPS) is described that utilizes standardized patients (SPs) in palliative care education of medical students and residents. The goals of the ESPS will be to: (1) improve physician communications skills in regard to breaking bad news and end-of-life care; (2) integrate evidence-based medicine into patient recommendations; and (3) enhance clinical skills in the practice of palliative medicine, particularly the evaluation and management of total suffering. The main features of the ESPS include a single SP scenario that is presented over several sessions, portraying an extended period in the patients life. The ESPS requires little in the way of equipment, but is labor intensive. The ESPS is a promising modality that deserves further scrutiny and outcomes research.

The safety of halobetasol 0.05% ointment in the treatment of psoriasis.

The effects on the hypothalamic‐pituitary‐adrenal axis of the ultra‐high potency corticosteroid halobetasol in the treatment of psoriasis were evaluated in seven patients with extensive, long‐standing plaque psoriasis. Each patient applied 3.5 g halobetasol 0.05% ointment in the morning and evening for 7 days. Morning plasma Cortisol levels and 24‐hour urinary excretion of 17‐hydroxycorticosteroid were determined before and on the last 2 days of treatment; plasma Cortisol levels were also determined 4 and 5 days after completion of therapy. Morning plasma Cortisol concentrations did not decrease significantly during treatment, and no values were below the normal range. Mean 24‐hour urinary 17‐hydroxycorticosteroid excretion fell from 6.6 ± 1.4 mg to 5.1 ± 1.4 mg. Two patients had mild, localized pruritus and stinging with the initial ointment application. No other adverse cutaneous effects were observed. Halobetasol was also clinically efficacious over the 7 days of treatment, based on evaluation of pruritus, erythema, scaling, and plaque elevation. These results demonstrate no adverse effects of the drug on the hypothalamic‐pituitary‐adrenal axis at doses that are clinically effective in the management of plaque psoriasis.

Physician Service to the Underserved

Many physicians find it difficult to accept uninsured or Medicaid patients due to low level or lack of reimbursement. Virtual Mentor is a monthly bioethics journal published by the American Medical Association.

Kidney function during naproxen therapy in patients at risk for renal insufficiency

The effects of naproxen on renal function in 34 patients with minimally elevated serum creatinine (Scr) or subnormal creatinine clearance (Ccr) were evaluated in a parallel-design study. All patients received open-label naproxen 375 mg twice daily for 2 weeks (phase I); patients were then randomly assigned to receive naproxen 750 mg twice daily (n = 26) or to continue naproxen 375 mg twice daily (n = 8) double-blind for an additional 2 weeks (phase II). Renal function was assessed by Scr, Ccr, and BUN measurements at baseline and at the end of each treatment phase. Neither treatment group had a clinically meaningful change in median laboratory values between baseline and the end of phase I, or between baseline and the end of phase II. During the first 2 weeks of treatment with naproxen 375 mg twice daily, there was no change in Scr. At the time of the first Scr measurement following the increase in naproxen dose to 750 mg twice daily, 13 of 26 patients had Scr levels of 1.1 mg/dL or higher, but four days later, only three patients had Scr levels of 1.1 mg/dL or higher, suggesting that a transient increase in Scr may accompany dosage increase. Chronic administration of naproxen 375 mg twice daily in patients at risk for renal insufficiency based on laboratory evidence of renal impairment was not associated with further deterioration in renal function. An increase in dosage to 750 mg twice daily in such patients appeared to be associated with only small, transient changes in laboratory measures of renal function.

Depression and Decision Making

a confidant, functional deficits, and one or more chronic conditions conferred excess risk of a positive screening score for depression. Of these factors, only less education and lack of a confidant demonstrated a very modest effect on a positive change score. Thus, the greatest proportion of risk of falling into the combined group was driven by risk of screening high. Reporting more symptoms 3 years after baseline added little additional power. We concluded that use of a cutpoint to designate a threshold of significant symptomatology provided a more valid method for identifying antecedent risk of depression than use of a pattern-of-change variable. Variability in scores beneath the threshold-even a rise of five points or morewas not as useful.

Sulfate Homeostasis. III. Effect of Chronic Naproxen or Sulindac Treatment on Inorganic Sulfate Disposition in Arthritic Patients with Renal Impairment

The purpose of the present investigation was to examine the influence of chronic naproxen (500 mg twice daily) or sulindac (200 mg twice daily) therapy on the disposition of inorganic sulfate in arthritic subjects with impaired renal function. Subjects were studied during a control period (after a 7-day NSAID washout) and after 14 days of treatment with either naproxen or sulindac. During the control period subjects in this investigation exhibited higher serum sulfate concentrations and lower sulfate renal clearance values than reported for younger subjects with normal renal function. Treatment with either sulindac or naproxen significantly decreased creatinine clearance. Sulindac therapy also increased the serum sulfate concentration and decreased the clearance of sulfate; a similar trend was observed after naproxen therapy but the average change was smaller and not statistically significant. There were significant correlations between the creatinine and the sulfate clearances or serum concentrations. The glomerular filtration rate of inorganic sulfate was not altered by drug treatment and there was no impairment of reabsorption. The serum concentrations and renal clearance of other electrolytes (sodium, potassium, magnesium, calcium, phosphorus) were largely unaffected. Therefore, chronic treatment with naproxen or sulindac decreases the renal clearance of endogenous sulfate in humans: this appears to be a consequence of the decrement in renal function observed in subjects with preexisting mild renal impairment.

Political discussions in the exam room.

Educating patients is an important part of practicing medicine, and, especially when health care-related legislation is changing, doctors may receive political questions from patients. They may want to have brief, prepared answers to such questions, but they should protect the clinical relationship by limiting discussions that are too long or too heated.