Dandruff: a condition characterized by decreased levels of intercellular lipids in scalp stratum corneum and impaired barrier function.

Dandruff is a major problem, yet little is known about the underlying mechanism and subsequent biochemical changes occurring in the scalp skin that lead to its manifestation. The characteristic flaking and scaling of the scalp experienced by dandruff sufferers suggests, similar to the changes classically seen in xerosis, that the desquamation process is impaired. We initiated studies to quantify the biochemical nature of the stratum corneum in the scalp of healthy individuals and dandruff sufferers. Total amounts and relative ratios of stratum corneum lipids species were analysed in scalp stratum corneum samples collected during studies conducted in the UK and Thailand in order to examine ethnic differences. In both populations, dandruff was associated with a dramatic decrease in free lipid levels, with significant decreases in ceramides, fatty acids, and cholesterol. Detailed sub-analysis of the major ceramide species within the total ceramide fraction revealed a decrease in ceramide 1 and increased proportions of ceramide 6i and 6ii. In a separate study, we demonstrated that dandruff sufferers show both an elevated blood flow and an increased reported incidence of itch in response to histamine topically applied to the scalp compared with no-dandruff controls. Taken together these two studies indicate that the quality and resilience of the epidermal water barrier is impaired in the scalp of dandruff sufferers. We propose that the perturbed barrier leaves dandruff sufferers more prone to the adverse effects of microbial and fungal toxins, and environmental pollutants, thus perpetuating their impaired barrier.

A phase II trial of 6-hydroxymethylacylfulvene (MGI-114, irofulven) in patients with advanced non-small cell cancer previously treated with chemotherapy.

PURPOSE: To test the efficacy and safety of the novel antitumor agent MGI-114 (NSC 683863) in patients with advanced non-small cell lung cancer (NSCLC) previously treated with chemotherapy. METHODS: A two-stage accrual design was used to ensure detection of a true response rate of at least 20% with a type I error of .04. Eligible patients received 11 mg/m2 daily for five consecutive days. Cycles were repeated every 28 days. RESULTS: Fifteen patients received a total of 34 cycles of MGI-114. All patients had a performance status of 0 or 1. Eleven patients had previously received carboplatin and paclitaxel +/- radiation. Two patients had received cisplatin and CPT-11, one patient had received weekly paclitaxel, and one patient had received carboplatin and docetaxel. None of the first 15 patients enrolled experienced objective tumor response, and the study was closed. Forty percent of patients developed > or = grade 2 thrombocytopenia. Grade 3 nausea and > or = grade 2 vomiting were observed in 40% and 47% of patients respectively. Thirty-three percent of patients experienced > or = grade 2 fatigue. CONCLUSIONS: MGI-114, at this dose and schedule, does not have significant activity as second line therapy for patients with advanced NSCLC.

Clinical utility of PET-FDG imaging in differentiation of benign from malignant adrenal masses in lung cancer.

This study was designed to evaluate the sensitivity, specificity, and predictive accuracy of PET-FDG imaging in detecting metastatic disease involvement of adrenal glands in patients with lung cancer. We wanted to compare efficacy of positron emission tomography (PET)-fluorodeoxyglucose (FDG) imaging to computed tomography (CT) scanning in differentiating benign from malignant involvement of adrenal glands in patients with lung cancer. Thirty patients with biopsy-proven lung cancer and abnormal findings on PET and/or CT scanning were studied for presence of adrenal abnormality suggestive of metastatic disease involvement (n = 26) or benign adrenal enlargement (n = 4). The results of PET and CT scanning were compared to histological findings and/or clinical follow-up for at least 1 year for presence or absence of adrenal metastases. PET-FDG imaging correctly detected the presence of metastatic involvement in 17 of 18 patients and excluded metastatic involvement in 11 of 12 patients for sensitivity, specificity, and accuracy of 94.4%, 91.6%, and 93.3%, respectively. CT scanning showed enlarged adrenals without metastases in 8 of 30 patients and normal-sized adrenals in the presence of metastases in 5 of 30 patients. There was a false-positive PET finding in 1 patient and a false-negative PET finding in another patient. PET-FDG imaging is a highly sensitive, specific, and accurate test to differentiate benign from malignant involvement of adrenal glands in patients with lung cancer and often ambiguous findings on CT scanning.

Maximum likelihood estimation of phylogenetic trees is consistent when substitution rates vary according to the invariable sites plus gamma distribution.

Maximum likelihood estimation of phylogenetic trees from nucleotide sequences is completely consistent when nucleotide substitution is governed by the general time reversible (GTR) model with rates that vary over sites according to the invariable sites plus gamma (I + gamma) distribution.

Treatment outcome of lung cancer patients as optimized by preoperative whole-body positron emission tomography fluorodeoxyglucose imaging.

Positron emission tomography (PET) fluorodeoxyglucose (FDG) imaging may be more accurate than computed tomography (CT) scanning for staging of lung cancer disease. In the present study, we evaluate whether whole-body PET-FDG imaging can accurately stratify lung cancer patients by stage and thus predict patient outcome. Forty-one consecutive patients underwent whole-body PET and CT scanning for preoperative staging, which was then confirmed by mediastinoscopy, thoracotomy, and/or other tests revealing distant metastases. The effect of PET on patient management was determined. PET was significantly more accurate than CT for staging of lung cancer (97.6% vs. 70.7%). One-year follow-up for survival rate and treatment response was also compared in different patient groups. PET accurately identified patients with resectable disease (Group A). Group B patients, with medically inoperable disease, and Group C patients, with unresectable advanced disease, had 100% and 53% incidence of adverse events (defined as recurrence, evidence of new disease, or death), respectively. Group A patients with resectable disease who underwent surgery showed the best patient outcome, with only 7% incidence of adverse events. In conclusion, whole-body PET can be useful in identifying a group of lung cancer patients with resectable disease most likely to benefit from surgical resection. Further studies are needed to explore whether PET can predict patient outcome of various lung cancer patients receiving different treatment regimens.

Multiple local maxima for likelihoods of phylogenetic trees: a simulation study.

Steel demonstrated that the maximum-likelihood function for a phylogenetic tree may have multiple local maxima. If this phenomenon were general, it would compromise the applicability of maximum likelihood as an optimality criterion for phylogenetic trees. In several simulation studies reported on in this paper, the true tree, and other trees of very high likelihood, rarely had multiple maxima. Our results thus provide reassurance that the value of maximum likelihood as a tree selection criterion is not compromised by the presence of multiple local maxima--the best estimates of the true tree are not likely to have them. This result holds true even when an incorrect nucleotide substitution model is used for tree selection.

Comparative efficacy of positron emission tomography with FDG and computed tomographic scanning in preoperative staging of non-small cell lung cancer.

OBJECTIVE: To determine the sensitivity, specificity, and accuracy of positron emission tomography with 2-fluorine-18-fluorodeoxyglucose (PET-FDG) in the preoperative staging (N and M staging) of patients with lung cancer. The authors wanted to compare the efficacy of PET scanning with currently used computed tomography (CT) scanning. MATERIALS AND METHODS: Results of whole-body PET-FDG imaging and CT scans were compared with histologic findings for the presence or absence of lymph node disease or metastatic sites. Sampling of mediastinal lymph nodes was performed using mediastinoscopy or thoracotomy. RESULTS: PET-FDG imaging was significantly more sensitive, specific, and accurate for detecting N disease than CT. PET changed N staging in 35% and M staging in 11% of patients. CT scans helped in accurate anatomic localization of 6/57 PET lymph node abnormalities. CONCLUSION: PET-FDG is a reliable method for preoperative staging of patients with lung cancer and would help to optimize management of these patients. Accurate lymph node staging of lung cancer may be ideally performed by simultaneous review of PET and CT scans.

Comparison of two systems for tibial external fixation in rabbits.

BACKGROUND AND PURPOSE: Use of rabbits in orthopedic investigations is common. In this study, focus is on factors that influence bone healing and on distraction osteogenesis. Biomechanical characteristics of two external fixator systems (Orthofix device and Hoffmann device) for long bones were tested. METHODS: Twelve freshly dissected tibiae were obtained from six skeletally mature New Zealand White rabbits, and four-point bending stiffness in two planes (90 and 180 degrees to the fixator pins) and torsional stiffness and strength of the bone-fixator complex were evaluated by use of a material testing machine. RESULTS: In four-point bending, Orthofix device had higher stiffness and strength, compared with Hoffmann device. When the load was applied 180 degrees to the pins, both devices had higher stiffness, compared with that at 90 degrees. In torsional testing, Orthofix device had significantly higher stiffness and strength. CONCLUSIONS: Significant differences in structural properties between the two systems were evident. Loading direction and gap conditions were important factors in determining properties of the systems. Therefore, type of external fixation system and fixation technique should be considered when designing experiments, using the rabbit long bone model.