Off-label dermatologic therapies. Usage, risks, and mechanisms

Off-label refers to the prescribing of Food and Drug Administration-approved drugs for a use not indicated on the package insert. The prescribing of off-label drugs may benefit patients with many dermatologic diseases including angiogenesis-related conditions. We surveyed 55 dermatologists from a single large academic program to assess their use of particular drugs for specific skin conditions, their perception of such use as being for Food and Drug Administration-approved or for off-label indications, and their attitudes towards off-label therapies. The practice of prescribing off-label drugs was common among the respondents, many of whom had misperceptions about which conditions are Food and Drug Administration-approved indications and about the legal ramifications of off-label therapies. We suggest that understanding the principles of off-label prescribing in conjunction with the mechanisms of drug action in diseases may help clinicians exercise their judgment in finding innovative therapies for their patients.     

Augmentation of lung liquid clearance via adenovirus-mediated transfer of a Na,K-ATPase beta1 subunit gene

The gastrointestinal hormone, glucagon-like peptide-1(7-36)amide (GLP-1) is released after a meal. The potency of synthetic GLP-1 in stimulating insulin secretion and in inhibiting glucagon secretion indicates the putative physiological function of GLP-1. In vitro, the nonmammalian peptide, exendin(9-39)amide [ex(9-39)NH2], is a specific and competitive antagonist of GLP-1. This in vivo study examined the efficacy of ex(9-39)NH2 as an antagonist of exogenous GLP-1 and the physiological role of endogenous GLP-1. Six healthy volunteers underwent 10 experiments in random order. In each experiment, a 30-min period of euglycemia was followed by an intravenous infusion of glucose for 150 min that established a stable hyperglycemia of 8 mmol/liter. There was a concomitant intravenous infusion of one of the following: (1) saline, (2) GLP-1 (for 60 min at 0.3 pmol . kg-1 . min-1 that established physiological postprandial plasma levels, and for another 60 min at 0.9 pmol . kg-1 . min-1 to induce supraphysiological plasma levels), (3-5) ex(9-39)NH2 at 30, 60, or 300 pmol . kg-1 . min-1 + GLP-1, (6-8) ex(9-39)NH2 at 30, 60, or 300 pmol . kg-1 . min-1 + saline, (9 and 10) GIP (glucose-dependent insulinotropic peptide; for 60 min at 0.8 pmol . kg-1 . min-1, with saline or ex(9-39)NH2 at 300 pmol . kg-1 . min-1). Each volunteer received each of these concomitant infusions on separate days. ex(9-39)NH2 dose-dependently reduced the insulinotropic action of GLP-1 with the inhibitory effect declining with increasing doses of GLP-1. ex(9-39)NH2 at 300 pmol . kg-1 . min-1 blocked the insulinotropic effect of physiological doses of GLP-1 and completely antagonized the glucagonostatic effect at both doses of GLP-1. Given alone, this load of ex(9-39)NH2 increased plasma glucagon levels during euglycemia and hyperglycemia. It had no effect on plasma levels of insulin during euglycemia but decreased plasma insulin during hyperglycemia. ex(9-39)NH2 did not alter GIP-stimulated insulin secretion. These data indicate that in humans, ex(9-39)NH2 is a potent GLP-1 antagonist without any agonistic properties. The pancreatic A cell is under a tonic inhibitory control of GLP-1. At hyperglycemia, the B cell is under a tonic stimulatory control of GLP-1.     

A preliminary study of clinical interventions in custody & access disputes.

Reviewed, retrospectively, 30 custody and access dispute cases (8 assessments, 22 arbitrations, and 10 mediations) and analyzed factors associated with each procedure. The factors examined were based on parents' views of their dispute, as recorded in an initial intake questionnaire completed preintervention. Findings suggest that couples who resolve their dispute through mediation tend to be more child-focused, future-oriented, positive about themselves, and helpful in providing suggestions for dispute resolution than parents involved in an assessment process. (French abstract) (6 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Whatever happened to scholarly discourse? A reply to B. F. Skinner.

Comments that B. F. Skinner (see record 1988-00027-001) has presented an egregiously inaccurate characterization of humanistic psychology. The authors note that Skinnerian radical behaviorism emphasizes behavior, science, and technology, while humanistic psychologies emphasize human beings. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Frequency-Dependent Attenuation Effects in Pulsed Doppler Ultrasound: Experimental Results

The quantitative capability of pulsed Doppler ultrasound in clinical practice is limited by the effects of frequency-dependent attenuation of ultrasound in tissue, as well as several other spectral-broadening mechanisms which distort the Doppler spectrum of an ultrasonic echo. In this communication, we present results of in vitro experiments which demonstrate the magnitude of the errors expected in clinical measurements of blood flow parameters when frequency-dependent attenuation Of ultrasound in biological tissue is ignored. It is shown that errors as large as 15 percent may occur in Doppler measurements of blood flow velocity through 7 cm of intervening tissue. A comparison is also made between experimental results and a theoretical model which includes the effects of scattering and attenuation.     

Vocal interruptions in dyadic communication as a function of speech and social anxiety.

The relation between a speaker's personality and his/her propensity to interrupt was examined in 30-min unstructured conversations for 36 dyads of undergraduates (12 male, 12 female, and 12 mixed sex). Two predictions were tested: (a) interruptive behavior is inversely related to speech anxiety and positively related to confidence as a speaker, and (b) interruptive behavior is inversely related to social anxiety (avoidance–distress; fear of negative evaluation). A stepwise multiple regression analysis was performed, controlling for the systematic effects of sex, the conversational partner's personality and amount of speech, and the speaker's use of back-channel responses. These hypotheses were confirmed for rate of total interruptions and rate of successful interruptions, for percentage of successful interruptions, and for mean duration of interruptions; the results withstood cross-validation analysis. (37 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Flow cytometry and Zollinger-Ellison syndrome: relationship to clinical course

BACKGROUND: With successful means of controlling gastric acid secretion in patients with Zollinger-Ellison syndrome, the gastrinoma itself is becoming the major determinant of long-term survival. No methods have yet been described to predict which tumors will have more malignant courses thereby indicating which patients should undergo aggressive surgery or antitumor therapy. Because DNA analysis, using flow cytometry, has proved helpful in this regard in other tumors, the current study was designed to evaluate its utility in gastrinoma patients. METHODS: Flow cytometry was performed on 81 paraffin-embedded gastrinoma specimens from 59 patients. Results were compared with preoperative patient characteristics, findings at surgery, and postoperative follow up. RESULTS: Tumors were diploid in 54% of patients, near diploid in 15%, pure tetraploid in 0%, nontetraploid aneuploid in 25%, and multiple stem line aneuploid in 5%. All patients with multiple stem line aneuploid tumors had wide-spread metastases whereas all patients with nontetraploid aneuploid tumors had localized or regional disease. Median S phase percentage was 3.6. S phase percentages were higher in patients with widespread metastatic disease than in patients with localized or regional disease. Disease extent also correlated closely with fasting serum gastrin level. After removing this variable with logistic regression analysis, the significant correlation between disease extent and DNA analysis persisted. CONCLUSIONS: DNA analysis of gastrinoma tissue specimens correlates independently with the extent of disease and may be useful in planning therapeutic strategies for patients with Zollinger-Ellison syndrome.     

Serine 167 is the major estradiol-induced phosphorylation site on the human estrogen receptor

Serine 167 has been identified by radiolabel and amino acid sequencing as the major estrogen-induced phosphorylation site on the human estrogen receptor (hER) from human MCF-7 mammary carcinoma cells. The phosphorylation of the hER on serine 167 was estrogen-dependent, increasing 4-fold upon estradiol treatment of MCF-7 cells and accounted for almost half of the total [32P]phosphate incorporated into the recombinant hER from Sf9 insect cells and the native hER from MCF-7 cells. Casein kinase II was found to phosphorylate the purified recombinant hER on serine 167 in vitro. In addition, estradiol binding enhanced by 2-fold the phosphorylation of the purified recombinant hER by casein kinase II in vitro. Western blot analysis and [32P]phosphate incorporation confirmed the presence of casein kinase II in Sf9 cells. These results demonstrate that the hER is phosphorylated on serine 167 by casein kinase II in a hormone-dependent manner.     

Carcinosarcoma of the adrenal cortex presenting with mineralocorticoid excess

An adrenal carcinosarcoma is reported in a 79-year-old woman presenting with clinical signs of hyperaldosteronism. The tumor weighed 199 g and consisted of areas typical of adrenal carcinoma and areas of sarcoma. The sarcomatous component of the tumor showed osteogenic and chondroid differentiation. Vimentin stained both the carcinomatous and sarcomatous regions. Four months after resection, the patient developed metastases. This is the third reported case of adrenal carcinosarcoma and the only case in which hyperaldosteronism or bony differentiation was observed.