Effect of goldenseal (Hydrastis canadensis) and kava kava (Piper methysticum) supplementation on digoxin pharmacokinetics in humans.

Phytochemical-mediated modulation of P-glycoprotein (P-gp) and other drug transporters may give rise to many herb-drug interactions. Serial plasma concentration-time profiles of the P-gp substrate, digoxin, were used to determine whether supplementation with goldenseal or kava kava modified P-gp activity in vivo. Twenty healthy volunteers were randomly assigned to receive a standardized goldenseal (3210 mg daily) or kava kava (1227 mg daily) supplement for 14 days, followed by a 30-day washout period. Subjects were also randomized to receive rifampin (600 mg daily, 7 days) and clarithromycin (1000 mg daily, 7 days) as positive controls for P-gp induction and inhibition, respectively. Digoxin (Lanoxin, 0.5 mg) was administered p.o. before and at the end of each supplementation and control period. Serial digoxin plasma concentrations were obtained over 24 h and analyzed by chemiluminescent immunoassay. Comparisons of area under the curve (AUC)((0-3)), AUC((0-24)), C(max,) CL/F, and elimination half-life were used to assess the effects of goldenseal, kava kava, rifampin, and clarithromycin on digoxin pharmacokinetics. Rifampin produced significant reductions (p < 0.01) in AUC((0-3)), AUC((0-24)), CL/F, t(1/2), and C(max), whereas clarithromycin increased these parameters significantly (p < 0.01). With the exception of goldenseal's effect on C(max) (14% increase), no statistically significant effects on digoxin pharmacokinetics were observed following supplementation with either goldenseal or kava kava. When compared with rifampin and clarithromycin, supplementation with these specific formulations of goldenseal or kava kava did not appear to affect digoxin pharmacokinetics, suggesting that these supplements are not potent modulators of P-gp in vivo.     

Practical management of patients with non-small-cell lung cancer treated with gefitinib.

PURPOSE: The use of gefitinib, the first drug approved to inhibit the epidermal growth factor receptor tyrosine kinase, is indicated in patients with non-small-cell lung cancer with tumors progressive after chemotherapy. The unique mechanism of action of this agent leads to distinctive patterns of response and toxicity in persons with lung cancer. Many of the principles of management relevant to gefitinib are distinct from those with conventional cytotoxic drugs. To meet this need, we present practical guidelines on the use of gefitinib in patients with non-small-cell lung cancer. METHODS: This article reviews gefitinib's indications, dosing, response phenomena, and patterns of relapse in individuals with radiographic response. RESULTS: We present our recommendations for the management of rash and diarrhea caused by this agent. CONCLUSION: This information can guide practitioners and help them inform their patients about what to expect when they receive gefitinib.     

The role of the le fort I maxillotomy in the management of incompletely resected pituitary macroadenomas.

Objective: The options available for the treatment of a nonsecreting pituitary macroadenoma that has been incompletely resected include reoperation, fractionated radiation therapy, and radiosurgery. Reoperation in this setting may be hindered by the same obstacles that prevented a complete resection during the initial surgical procedure, and should prompt consideration of an alternate approach or exposure. Methods: Between January 1998 and December 2003, 10 consecutive patients were referred to the Department of Neurosurgery at the University of Texas Southwestern Medical Center for the evaluation of a nonsecreting pituitary macroadenoma that measured 3 cm or greater in diameter despite having undergone an attempt at a complete resection elsewhere. Each of these patients was reoperated using a Le Fort I maxillotomy to enhance the exposure provided by a traditional transsphenoidal approach. Results: A total or near total (> 95%) resection was achieved in each case. One patient required reoperation for the repositioning of a fat graft to treat a cerebrospinal fluid fistula and one patient experienced a worsening of anterior pituitary function postoperatively. Five patients noted improved vision and no patient experienced further visual loss. Three patients have required subsequent treatment of small foci of recurrent or progressing tumor with stereotactic radiation therapy. No patient has received fractionated radiation therapy. Conclusion: The added exposure provided by a Le Fort I maxillotomy facilitates the resection of pituitary macroadenomas that have been incompletely resected by a traditional transnasal, trans-sphenoidal approach.     

Bone Mineral Density Determinations by Dual-Energy x-ray Absorptiometry in the Management of Patients with Marfan Syndrome—Some Factors Which Affect the Measurement

Reduced bone mineral density (BMD) was sporadically reported in patients with Marfan syndrome. This may or may not place the Marfan patient at increased risk for bone fracture. In comparing the BMDs of our patients with those reported in the literature, it seemed that agreement between values, and hence the degree of osteoporosis or osteopenia reported, was dependent on the instrumentation used. The objective of this study was to statistically assess this impression. Bone mineral density measurements from our previously published study of 30 adults with Marfan syndrome performed on a Lunar DPXL machine were compared with studies published between 1993–2000 measured using either Lunar or Hologic bone densitometry instruments. The differences of our measurements compared with those made on other Lunar machines were not statistically significant, but did differ significantly with published results from Hologic machines (P < 0.001). Before progress can be made in the assessment of BMD and fracture risk in Marfan patients and in the evidence-based orthopedic management of these patients, standardization of instrumental bone density determinations will be required along with considerations of height, obesity, age, and sex.     

Assessment of extraocular muscles position and anatomy by 3-dimensional ultrasonography: a trial in craniosynostosis patients.

PURPOSE: To determine whether 3-dimensional ultrasonography (3D US) provides information about anatomy and position of extraocular muscles to better guide surgeons approaching strabismus in patients with craniosynostosis who often have anomalous or absent eye muscles. METHODS: The 4 rectus eye muscles were imaged using 3D US for 7 children with craniosynostosis before or after strabismus surgery. Reconstructed 3D images were interpreted as having normal or abnormal anatomy and position, based on comparison with images acquired from 6 normal eyes. Interpretation was validated against the intraoperative findings from strabismus surgery. RESULTS: A total of 34 scans from the study group were used for comparison and validation purposes. Accuracy of anatomical assessments was 85% +/- 12% (percentage +/- confidence interval) and of positional assessments was 62% +/- 16%. Sensitivity and specificity of anatomical assessments was 80% +/- 14% and 88% +/- 10%, respectively. Anatomic anomalies detected by 3D US included excessively thick, thin, scarred and fibrotic, and absent muscles. Sensitivity and specificity of positional assessments was 48% +/- 17% and 85% +/- 12%, respectively. Positional anomalies such as muscle displacement off the normal clock hour axis or posteriorly displaced insertion were also detected. CONCLUSIONS: The 3D US may have an adjunctive role in determining anatomy and position of rectus muscles in patients with craniosynostosis, although it was more accurate in assessing anatomic features rather than positional features of rectus muscles.     

Dreaming during Anesthesia and Anesthetic Depth in Elective Surgery Patients: A Prospective Cohort Study

Background: Dreaming reported after anesthesia remains a poorly understood phenomenon. Dreaming may be related to light anesthesia and represent near-miss awareness. However, few studies have assessed the relation between dreaming and depth of anesthesia, and their results were inconclusive. Therefore, the authors tested the hypothesis that dreaming during anesthesia is associated with light anesthesia, as evidenced by higher Bispectral Index values during maintenance of anesthesia.

Methods: With approval, 300 consenting healthy patients, aged 18-50 yr, presenting for elective surgery requiring relaxant general anesthesia with a broad range of agents were studied. Patients were interviewed on emergence and 2-4 h postoperatively. The Bispectral Index was recorded from induction until the first interview. Dream content and form were also assessed.

Results: Dreaming was reported by 22% of patients on emergence. There was no difference between dreamers and nondreamers in median Bispectral Index values during maintenance (37 [23-55] vs. 38 [20-59]; P = 0.68) or the time at Bispectral Index values greater than 60 (0 [0-7] vs. 0 [0-31] min; P = 0.38). Dreamers tended to be younger and male, to have high home dream recall, to receive propofol maintenance or regional anesthesia, and to open their eyes sooner after surgery. Most dreams were similar to dreams of sleep and were pleasant, and the content was unrelated to surgery.