Nightly sleep duration in the 2-week period preceding multiple sleep latency testing.

STUDY OBJECTIVE: To assess usual nightly sleep duration of patients referred for a Multiple Sleep Latency Test (MSLT). DESIGN: Retrospective chart review. SETTING: Military, hospital-based, sleep center. PATIENTS: Fifty-four patients with excessive daytime sleepiness referred for an MSLT. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Self-reported average nightly sleep duration (6.13 +/- 1.23 hours), sleep log-recorded average nightly sleep duration (6.99 +/- 0.85 hours), and actigraphy-measured average nightly sleep duration (5.56 +/- 1.50 hours) were compared for the 2-week period immediately preceding an MSLT One-way analysis of variance revealed a significant difference in the 3 estimates of nightly sleep duration (p < 0.0001), and only actigraphy-measured average nightly sleep duration correlated with mean sleep latency on the MSLT (r = 0.4258, p = 0.0016). Subgroup analysis showed that patients with a mean sleep latency shorter than 8 minutes slept an average of 1.57 hours less per night than did those patients with a mean sleep latency of 8 minutes or longer (4.53 +/- 1.37 vs 6.10 +/- 1.37 hours per night, p < 0.001) as measured by actigraphy. There was no difference in either self-reported average nightly sleep duration or sleep log-recorded average nightly sleep duration between the 2 subgroups. CONCLUSIONS: Prolonged actigraphy monitoring may provide useful clinical information about pre-MSLT sleep not always obtainable from patient self-reporting or sleep logs.

Assessing success after cerebral revascularization for ischemia.

Cerebral revascularization continues to evolve as an option in the setting of ischemia. The potential to favorably influence stroke risk and the natural history of cerebrovascular occlusive disease is being evaluated by the ongoing Carotid Occlusion Surgery Study and the Japanese Extracranial-Intracranial Bypass Trial. For those patients who undergo bypass in the setting of ischemia, four key areas of follow-up include functional neurological status, neurocognitive status, bypass patency, and status of cerebral blood flow and perfusion. Several stroke scales that can be used to assess functional status include the National Institutes of Health Stroke Scale, Bathel Index, Modified Rankin Scale, and Stroke Specific Quality of Life. Neurocognition can be checked using the Repeatable Battery for the Assessment of Neuropsychological Status, among other tests. Bypass patency is checked intraoperatively using various flow probes and postoperatively using magnetic resonance angiography (MRA) or computed tomographic angiography (CTA). Cerebral blood flow and perfusion can be assessed using a host of modalities that include positron emission tomography (PET), xenon CT, single photon emission computed tomography (SPECT), transcranial Doppler (TCD), CT, and MR. Paired blood flow studies after a cerebral vasodilatory stimulus using one of these modalities can determine the state of autoregulatory vasodilation (Stage 1 hemodynamic compromise). However, only PET with oxygen extraction fraction measurements can reliably assess for Stage 2 compromise (misery perfusion). This article discusses the various clinical, neuropsychological, and radiographic techniques available to assess a patient's clinical state and cerebral blood flow before and after cerebral revascularization.

Phase II trial of gefitinib in recurrent glioblastoma.

PURPOSE: To evaluate the efficacy and tolerability of gefitinib (ZD1839, Iressa; AstraZeneca, Wilmington, DE), a novel epidermal growth factor receptor tyrosine kinase inhibitor, in patients with recurrent glioblastoma. PATIENTS AND METHODS: This was an open-label, single-center phase II trial. Fifty-seven patients with first recurrence of a glioblastoma who were previously treated with surgical resection, radiation, and usually chemotherapy underwent an open biopsy or resection at evaluation for confirmation of tumor recurrence. Each patient initially received 500 mg of gefitinib orally once daily; dose escalation to 750 mg then 1,000 mg, if a patient received enzyme-inducing antiepileptic drugs or dexamethasone, was allowed within each patient. RESULTS: Although no objective tumor responses were seen among the 53 assessable patients, only 21% of patients (11 of 53 patients) had measurable disease at treatment initiation. Seventeen percent of patients (nine of 53 patients) underwent at least six 4-week cycles, and the 6-month event-free survival (EFS) was 13% (seven of 53 patients). The median EFS time was 8.1 weeks, and the median overall survival (OS) time from treatment initiation was 39.4 weeks. Adverse events were generally mild (grade 1 or 2) and consisted mainly of skin reactions and diarrhea. Drug-related toxicities were more frequent at higher doses. Withdrawal caused by drug-related adverse events occurred in 6% of patients (three of 53 patients). Although the presence of diarrhea positively predicted favorable OS from treatment initiation, epidermal growth factor receptor expression did not correlate with either EFS or OS. CONCLUSION: Gefitinib is well tolerated and has activity in patients with recurrent glioblastoma. Further study of this agent at higher doses is warranted.

Interleukin-8 stimulation of osteoclastogenesis and bone resorption is a mechanism for the increased osteolysis of metastatic bone disease.

Interleukin 8 (IL-8) is a member of the alpha chemokine family of cytokines originally identified as a neutrophil chemoattractant. Recently, we reported that elevated levels of IL-8, but not parathyroid hormone-related protein (PTHrP), correlated with increased bone metastasis in a population of human breast cancer cells. We hypothesized that IL-8 expression by breast cancer cells would either indirectly influence osteoclastogenesis via nearby stromal cells or directly influence osteoclast differentiation and activity. In the present study, we investigated the role of IL-8 in the process of osteoclast formation and bone resorption, which is associated with metastatic breast cancer. The addition of recombinant human (rh) IL-8 (10 ng/ml) to cultures of stromal osteoblastic cells stimulated both RANKL mRNA expression and protein production, with no effect on the expression of osteoprotegerin. In addition, rhIL-8 also directly stimulated the differentiation of human peripheral blood mononuclear cells into bone-resorbing osteoclasts. In these cultures, IL-8 was able to stimulate human osteoclast formation even in the presence of excess (200 ng/ml) RANK-Fc. The effect of IL-8 on osteoclasts and their progenitors was associated with the cell surface expression of the IL-8-specific receptor (CXCR1) on the cells. These results demonstrate a direct effect of IL-8 on osteoclast differentiation and activity. Together, these data implicate IL-8 in the osteolysis associated with metastatic breast cancer.