Critical study of hair growth analysis with computer-assisted methods

BACKGROUND: Computer-assisted image analysis has been proposed for human hair growth studies. METHODS: The performances of Trichoscan, a commercially available automated system combining epiluminiscence microscopy with digital image analysis, developed for office-based hair growth measurements, have been evaluated comparatively on the same skin sites using standardized photographic equipment and calibrated processing for contrast-enhanced phototrichogram (CE-PTG) analysis. This reference method has been validated with scalp biopsies and histological examination of serial sectioning. RESULTS: Besides edge effects, hair fibres escaped the Trichoscan analysis for various reasons including, but not limited to, thickness, pigmentation, closeness and crossing. CONCLUSION: Most of these problems have been identified in the late 1980s and remain largely unsolved by the processing software that was evaluated in 2004. Therefore claims promoting the Trichoscan method for accurate hair measurements in clinical trials on scalp and body hair are not supported by the present investigation. The speed at which the analysis is performed is outweighed by the errors in signal detection. Therefore we suggest that improvements must be clearly documented before Trichoscan is established for quantified diagnostic purposes and detailed hair cycle monitoring during hair trials.     

双波长紫外分光光度法测定贝母中腺苷和胸苷的含量

将4种贝母的甲醇提取物经薄层色谱法粗分离后,直接用双波长紫外分光光度法测定其含量。结果表明,该方法线性关系好,腺苷和胸苷标准曲线的相关系数均为0.9999,同时也发现平贝、炉贝和伊贝中腺苷都占核苷总量60%以上,而浙贝中仅占约40%,提示贝母生药的抗凝血活性可能与贝母中核苷类化合物的种类和含量的差别有关。     

Effects of cytokines and R-837, a cytokine inducer, on UV-irradiation augmented recurrent genital herpes in guinea pigs.

We have recently reported that latently HSV-2-infected guinea pigs exhibit a three- to four-fold increase in recurrent lesions after exposure to ultraviolet radiation (UV), allowing rapid evaluation of antiviral drugs in treating recurrent HSV disease. In this report we examine the effect of alpha interferon (IFN-alpha), interleukin-2 (IL-2), and a cytokine inducer (R-837) on UV-induced recurrent genital herpes. We have previously shown that topical R-837 is a biologic response modifier with no in vitro anti-HSV activity, but with potent anti-HSV activity in vivo due to cytokine induction and enhancement of cell-mediated immune responses. Three-day regimens of intravaginal R-837, or five-day intraperitoneal (i.p.) administration of IFN-alpha or of IL-2 each significantly reduced recurrent genital HSV-2 disease that occurred within 7 days of UV exposure, suggesting that cytokines or cytokine inducers may be useful in the treatment of recurrent HSV disease. This model using ultraviolet radiation to induce recurrent herpes simplex virus infection proved useful in the evaluation of immunoactive agents as putative antiviral drugs.     

Phase I and pharmacokinetic study of gefitinib in children with refractory solid tumors: a Children's Oncology Group Study.

PURPOSE: Epidermal growth factor receptor is expressed in pediatric malignant solid tumors. We conducted a phase I trial of gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, in children with refractory solid tumors. PATIENTS AND METHODS: Gefitinib (150, 300, 400, or 500 mg/m2) was administered orally to cohorts of three to six patients once daily continuously until disease progression or significant toxicity. Pharmacokinetic studies were performed during course one (day 1 through 28). RESULTS: Of the 25 enrolled patients, 19 (median age, 15 years) were fully evaluable for toxicity and received 54 courses. Dose-limiting toxicity was rash in two patients treated with 500 mg/m2 and elevated ALT and AST in one patient treated with 400 mg/m2. The maximum-tolerated dose was 400 mg/m2/d. The most frequent non-dose-limiting toxicities were grade 1 or 2 dry skin, anemia, diarrhea, nausea, and vomiting. One patient with Ewing's sarcoma had a partial response. Disease stabilized for 8 to > or = 60 weeks in two patients with Wilms' tumor and two with brainstem glioma (one exophytic). At 400 mg/m2, the median peak gefitinib plasma concentration was 2.2 microg/mL (range, 1.2 to 3.6 microg/mL) and occurred at a median of 2.3 hours (range, 2.0 to 8.3 hours) after drug administration. The median apparent clearance and median half-life were 14.8 L/h/m2 (range, 3.8 to 24.8 L/h/m2) and 11.7 hours (range, 5.6 to 22.8 hours), respectively. Gefitinib systemic exposures were comparable with those associated with antitumor activity in adults. CONCLUSION: Oral gefitinib is well tolerated in children. Development of the drug in combination with cytotoxic chemotherapy will be pursued.     

Development, reliability, and validity of a dissociation scale

Dissociation is a lack of the normal integration of thoughts, feelings, and experiences into the stream of consciousness and memory. Dissociation occurs to some degree in normal individuals and is thought to be more prevalent in persons with major mental illnesses. The Dissociative Experiences Scale (DES) has been developed to offer a means of reliably measuring dissociation in normal and clinical populations. Scale items were developed using clinical data and interviews, scales involving memory loss, and consultations with experts in dissociation. Pilot testing was performed to refine the wording and format of the scale. The scale is a 28-item self-report questionnaire. Subjects were asked to make slashes on 100-mm lines to indicate where they fall on a continuum for each question. In addition, demographic information (age, sex, occupation, and level of education) was collected so that the connection between these variables and scale scores could be examined. The mean of all item scores ranges from 0 to 100 and is called the DES score. The scale was administered to between 10 and 39 subjects in each of the following populations: normal adults, late adolescent college students, and persons suffering from alcoholism, agoraphobia, phobic-anxious disorders, posttraumatic stress disorder, schizophrenia, and multiple personality disorder. Reliability testing of the scale showed that the scale had good test-retest and good split-half reliability. Item-scale score correlations were all significant, indicating good internal consistency and construct validity. A Kruskal-Wallis test and post hoc comparisons of the scores of the eight populations provided evidence of the scale's criterion-referenced validity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Is there a genetic susceptibility locus for Parkinson's disease on chromosome 22q13?

The cytochrome P450 mono-oxygenase gene, CYP2D6 on chromosome 22q13 (ch22q13), has been inconsistently associated with Parkinson's disease. Associations with CYP2D6 have either been absent altogether or have involved more than one polymorphism, many of which have the same metabolic effect on gene expression. We examined the association between CYP2D6 polymorphisms and Parkinson's disease in a case-control study and included 10 polymorphic dinucleotide repeat markers linked to CYP2D6 to determine whether the association was present or due to linkage disequilibrium. There was no association between any polymorphism of CYP2D6 and Parkinson's disease, but two of 10 dinucleotide repeat markers linked to CYP2D6 were associated with the disease. These results provide evidence to suggest that there may be an unidentified locus for susceptibility to Parkinson's disease that is in linkage disequilibrium with dinucleotide repeat markers mapping near CYP2D6 on ch22q13.     

Synthesis and in vitro LTD4 antagonist activity of bicyclic and monocyclic cyclopentylurethane and cyclopentylacetamide N-arylsulfonyl amides

The dissociation constants (KB) at the LTD4 receptor on guinea pig trachea of a series of monocyclic and bicyclic cyclopentylurethane and cyclopentylacetamide N-arylsulfonyl amides have been measured. The KB was found to be remarkably tolerant of changes in the electronic constitution and lipophilicity of the bicyclic ring system (template). Thus, N-[4[[6-[[(cyclopentyloxy)carbonyl]amino]benzimidazol-1- yl]methyl]-3-methoxybenzoyl]benzenesulfonamide (11a) and N-[4-[[5-[[(cyclopentyloxy)carbonyl]amino]benzo[b]thien-3- yl]methyl]-3-methoxybenzoyl]benzene-sulfonamide (25a) had closely similar affinities (pKB, 9.20 and 9.31, respectively; LTE4 as agonist). It has been shown that the hetero-ring of the template need not be aromatic in order to achieve high affinity, since indoline 31 and 2,3-dihydrobenz-1,4-oxazines 37a-c had pKBs greater than 9. Further, it has been shown that an o-aminophenone (see 42 and Figure 3) can function as a template; the template in 42 [see iii] is bicyclic by virtue of the presence of an intramolecular hydrogen bond. In contrast, when the template is a phenyl ring (48), receptor affinity is markedly reduced. These findings support the notion that central bicyclic ring system in this family of peptidoleukotriene antagonists is a molecular feature which helps to preorganize the acylamino and acidic chains and thereby facilitate the molecular recognition event.