Autoradiographic evidence that quinuclidinyl 4-(bromophenyl)-2-thienylglycolate (QBPTG) displays in vivo selectivity for the muscarinic m2 subtype

OBJECTIVE: To assess the effect of expanding the vital signs to include smoking status. DESIGN: We prospectively conducted exit interviews with patients at a general internal medicine clinic in Madison, Wisconsin, during a 16-month period from 1991 to 1993. METHODS: Patients were surveyed briefly before (N = 870) and after (N = 994) the implementation of a simple institutional change in clinical practice. This change involved training the staff in how to use progress notepaper with a vital sign stamp that included smoking status (current, former, or never) along with the traditional vital signs. Included in the survey were questions about whether the patient smoked, whether the patient was asked that day about smoking status (by a clinician or other staff), and, for smokers, whether they were urged to quit smoking and given specific advice on how to do so. RESULTS: After expansion of the vital signs, patients were much more likely to report inquiries about their smoking status on the day of a clinic visit (an increase from approximately 58% at baseline to 81% at intervention; P < 0.0001). The vital sign intervention was associated with significant increases in the percentage of smokers who reported that their clinician advised them that day to quit smoking (from approximately 49% at baseline to 70% during the intervention; P < 0.01) and in the percentage who reported that their clinician gave them specific advice that day on how to stop smoking (from approximately 24% at baseline to 43% during the intervention; P < 0.01). CONCLUSION: Expanding the vital signs to include smoking status was associated with a dramatic increase in the rate of identifying patients who smoke and of intervening to encourage and assist with smoking cessation. This simple, low-cost intervention may effectively prompt clinicians to inquire about use of tobacco and offer recommendations to smokers.     

Esthetic overdenture for a patient with possible Seckel syndrome

This is a case report of a 21-year-old with possible Seckel syndrome (bird-headed dwarfism), micrognathia, microdontia, severe bony undercuts, and periodontal disease who sought treatment at a university dental clinic. Treatment included extractions, periodontal therapy, retention of premolars with sealants, and overdentures with resilient soft liners. A limited review of Seckel syndrome literature is included. The modification of existing dental materials and procedures required for successful functional and esthetic results are discussed.     

Measurement of DNA adducts in humans after complex mixture exposure

In contrast to acute or chronic dosing experiments with a single chemical in animals, man is exposed to thousands of chemicals during a lifetime. Each of these may act alone, additively, synergistically or antagonistically in terms of biological effects, but most current risk assessment procedures fail to recognize such interactions. In carcinogenesis, a mutational process that is thought to occur through DNA damage by endogenous and/or exogenous agents, a wide variety of host factors is involved in disease outcome. These include absorption of chemicals, their distribution, metabolism and excretion. In addition, once metabolic activation has occurred, there is an array of protective mechanisms that cells have evolved to maintain DNA integrity, such as DNA repair, genetic redundancy and programmed cell death. One approach to risk assessment is to regard all DNA-damaging events as potentially leading to cancer and to measure DNA damage as the biologically relevant endpoint. The main method, if not the only method, presently available to assay a wide range of DNA adducts is 32P-postlabelling. This method has high sensitivity (limit of detection > 1 adduct per 10(10) nucleotides) and is capable of visualizing many different DNA adducts in a single analysis. Postlabelling is best suited for detecting hydrophobic adducts--low molecular weight adducts usually need a preliminary separation procedure prior to being postlabelled. This chromatographic procedure has been used to study DNA samples from human tissues of cigarette smokers, occupationally exposed groups and individuals living in polluted environments. Correlations have been found between the severity of exposure and the level of DNA adducts detected for human samples. However, most studies are single-time point studies, whereas for risk assessment purposes it may be better to use more quantitative and representative measures of long-term exposure, for example the number of adducts formed per annum. This article reviews methods of DNA adduct measurement, with particular reference to the 32P-postlabelling technique, which has been used to determine DNA adduct levels in populations exposed to complex mixtures.     

A centering balloon for photodynamic therapy of esophageal cancer tested in a canine model

Delivery of uniform circumferential light is desirable during photodynamic therapy of early or advanced esophageal cancer in human beings. Studies were performed in the canine esophagus to investigate whether use of a centering balloon would improve circumferential illumination of esophageal mucosa for photodynamic therapy of esophageal cancer. When the centering balloon was used, photodynamic therapy produced uniform and circumferential injury. With the cylindrical diffuser used in human studies, non-uniform and focal esophageal injury occurred. Placement of isotropic probes on the balloon wall allowed measurement and verification of relatively uniform light doses delivered to esophageal mucosa during balloon photodynamic therapy. The centering balloon has a potential role in improving light dosimetry during esophageal photodynamic therapy.     

Interpersonal aggression and the Type A coronary-prone behavior pattern: A theoretical distinction and practical implications.

In Study 1, 85 male undergraduates were classified as Type A (coronary prone) or Type B (noncoronary prone) on the basis of scores on the Jenkins Activity Survey. Ss participated in a version of A. H. Buss's (1961) teacher–learner procedure that allowed the isolation of hostile from instrumental acts. Results indicate that a prior task frustration produced greater aggression by Type A's than Type B's, but only under conditions where the aggressive act could not affect a confederate's immediate performance (i.e., hostile aggression). Study 2 examined the representation of Type A's and Type B's among 20 women in treatment for child abuse, 20 women who were victims of spouse abuse, and 20 control women. Findings show that Type A's were more likely than Type B's to exhibit the extreme hostility found in child abuse. Both studies suggest that a lack of control may underlie the greater aggression displayed by Type A's and Type B's. (39 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Itraconazole resistance in Aspergillus fumigatus

Invasive aspergillosis is an increasingly frequent opportunistic infection in immunocompromised patients. Only two agents, amphotericin B and itraconazole, are licensed for therapy. Itraconazole acts through inhibition of a P-450 enzyme undertaking sterol 14alpha demethylation. In vitro resistance in Aspergillus fumigatus to itraconazole correlated with in vivo outcome has not been previously described. For three isolates (AF72, AF90, and AF91) of A. fumigatus from two patients with invasive aspergillosis itraconazole MICs were elevated. A neutropenic murine model was used to establish the validity of the MICs. The isolates were typed by random amplification of polymorphic DNA. Analysis of sterols, inhibition of cell-free sterol biosynthesis from [14C] mevalonate, quantitation of P-450 content, and [3H]itraconazole concentration in mycelial pellets were used to determine the mechanisms of resistance. The MICs for the three resistant isolates were >16 microg/ml. In vitro resistance was confirmed in vivo for all three isolates. Molecular typing showed the isolates from the two patients to be genetically distinct. Compared to the susceptible isolate from patient 1, AF72 had a reduced ergosterol content, greater quantities of sterol intermediates, a similar susceptibility to itraconazole in cell-free ergosterol biosynthesis, and a reduced intracellular [3H]itraconazole concentration. In contrast, AF91 and AF92 had slightly higher ergosterol and lower intermediate sterol concentrations, fivefold increased resistance in cell-free systems to the effect of itraconazole on sterol 14alpha demethylation, and intracellular [3H] itraconazole concentrations found in susceptible isolates. Resistance to itraconazole in A. fumigatus is detectable in vitro and is present in wild-type isolates, and at least two mechanisms of resistance are responsible.