Oral misoprostol before office endometrial biopsy

OBJECTIVE: To evaluate oral misoprostol use before office endometrial biopsy. METHODS: Forty-two nonpregnant women aged 35-77 years were randomized to a prospective, double-blind study to receive either 400 microg oral misoprostol or placebo 3 hours before office endometrial biopsy. Misoprostol effects were assessed by 1) cervical resistance, 2) ease of performing the endometrial biopsy, 3) success rate of obtaining an endometrial biopsy, 4) pain intensity associated with the endometrial biopsy, and 5) adverse clinical side effects. RESULTS: Patients in the misoprostol group experienced significantly (P <.01) more pain associated with the endometrial biopsy. The observed power to detect this difference in misoprostol-placebo comparison using the Wilcoxon rank sum test at 0.05 level of significance is 89%. In addition, significantly (P <.05) more patients had the adverse side effect of uterine cramping at 1.5 hours after medication ingestion in the misoprostol group. The observed power to detect this difference is 98%. There were no differences between the misoprostol and placebo groups in cervical resistance, ease of performing the biopsy, success rate for obtaining an endometrial biopsy, or adverse side effects at 3 hours post medication ingestion. CONCLUSION: Oral misoprostol 400 microg caused more uterine cramping and pain in nonpregnant women undergoing office endometrial biopsy when given 3 hours before biopsy attempt. No other cervical effects were noted.     

Maurotoxin: a potent inhibitor of intermediate conductance Ca2+-activated potassium channels

Maurotoxin, a 34-amino acid toxin from Scorpio maurus scorpion venom, was examined for its ability to inhibit cloned human SK (SK1, SK2, and SK3), IK1, and Slo1 calcium-activated potassium (K(Ca)) channels. Maurotoxin was found to produce a potent inhibition of Ca(2+)-activated (86)Rb efflux (IC(50), 1.4 nM) and inwardly rectifying potassium currents (IC(50), 1 nM) in CHO cells stably expressing IK1. In contrast, maurotoxin produced no inhibition of SK1, SK2, and SK3 small-conductance or Slo1 large-conductance K(Ca) channels at up to 1 microM in physiologically relevant ionic strength buffers. Maurotoxin did inhibit (86)Rb efflux (IC(50), 45 nM) through, and (125)I-apamin binding (K(i), 10 nM) to SK channels in low ionic strength buffers (i.e., 18 mM sodium, 250 mM sucrose), which is consistent with previous reports of inhibition of apamin binding to brain synaptosomes. Under similar low ionic strength conditions, the potency for maurotoxin inhibition of IK1 increased by approximately 100-fold (IC(50), 14 pM). In agreement with its ability to inhibit recombinant IK1 potassium channels, maurotoxin was found to potently inhibit the Gardos channel in human red blood cells and to inhibit the K(Ca) in activated human T lymphocytes without affecting the voltage-gated potassium current encoded by Kv1.3. Maurotoxin also did not inhibit Kv1.1 potassium channels but potently blocked Kv1.2 (IC(50), 0.1 nM). Mutation analysis indicates that similar amino acid residues contribute to the blocking activity of both IK1 and Kv1.2. The results from this study show that maurotoxin is a potent inhibitor of the IK1 subclass of K(Ca) potassium channels and may serve as a useful tool for further defining the physiological role of this channel subtype.     

Inhibition of LPS-induced splenocyte proliferation by ortho-substituted polychlorinated biphenyl congeners

Polychlorinated biphenyls (PCBs) are persistent environmental contaminants, and their ubiquitous nature has prompted studies of their potential health hazards. As a result of their lipophilic nature, PCBs accumulate in breast milk and subsequently affect the health of offspring of exposed individuals. Biological effects of PCBs in animals have mostly been attributed to coplanar congeners, although effects of ortho congeners also have been demonstrated. To investigate the relationship of immunotoxicity and chlorine substitution pattern, the effects of PCB congeners and mixtures of ortho and non-ortho-substituted constituents of Aroclor 1242 on splenocytes from C57B1/6 mice were examined. The immunotoxic endpoints investigated included splenocyte viability, lipopolysaccharide (LPS)-induced splenocyte proliferation, and LPS-induced antibody secretion. Congeners with multiple ortho chlorines preferentially inhibited splenocyte proliferation as compared with non- or mono-ortho-substituted congeners. However, mixtures of non- and mono-ortho-substituted congeners and multi-ortho-substituted congeners inhibited LPS-induced splenocyte proliferation and antibody secretion at similar concentrations. Exposure of splenocytes to these mixtures did not activate the aryl hydrocarbon receptor (AhR) signal transduction pathway. These results suggest individual multi-ortho-substituted congeners preferentially inhibit LPS-induced splenocyte proliferation, while congeners not exhibiting an effect individually may have additive effects in a mixture to produce an immunotoxic response through an AhR-independent pathway.     

Primary care residents self assessment skills in dementia

The ability to accurately self-assess is a critical component of professionalism and is included in the newly required Accreditation Council of Graduate Medical Education (ACGME) core competencies. To assess residents' ability to accurately self-assess their competencies related to a commonly presenting problem in geriatrics, a Standardized Patient, portraying an individual with early signs of dementia, was inserted into family medicine residents' clinic schedules. Immediately post the encounter, each resident self-assessed his/her performance using a four category (Communication, History of Present Illness, Social History, Functional Assessment), 17-item behavioral checklist. The items in each category highlighted items specific to a dementia-screening interview (e.g., HPI: Used a standardized exam which includes orientation, memory, recall and registration). Resident ratings were compared to ratings from two faculty assessors who independently viewed the videotape of each resident's SP interview. While statistically significant differences between the self-assessment and expert assessors appeared in only one of the four major check list categories (functional assessment), item specific analysis revealed significant differences on discrete items within the dementia screening interview. Implications for teaching and assessment consistent with the ACGME required competency assessment category of professionalism are discussed. This revised version was published online in September 2006 with corrections to the Cover Date.     

Preliminary study on reducing oral moist snuff use

BACKGROUND: Tobacco exposure reduction may be an alternative treatment approach for those tobacco users who are unwilling or unable to quit tobacco use. However, very little information is available on the feasibility of this type of intervention, especially in the area of oral moist snuff tobacco (ST). This pilot study examined whether reducing ST use using various methods can be achieved and whether this reduction results in lower exposure to carcinogens. METHODS: Moist snuff users (N=40 males) were randomly assigned to 4 mg nicotine gum, non-tobacco mint snuff, brand switching, or elimination of ST use in specific situations. These approaches were used to reduce ST use or nicotine exposure by at least 25% for the first 2 weeks and 50% the subsequent 6 weeks of treatment. Follow-up sessions occurred at 12 and 26 weeks. RESULTS: Significant reductions were observed in tins per week and cotinine levels across all conditions. Among the intent-to-treat population, the abstinence rate was 15% at 26 weeks. Reduction in nicotine exposure was associated with reduction in exposure to nitrosamines. CONCLUSION: Reduction in ST use may be a viable approach for those oral moist ST users with no immediate quit plans. Future research in this area is needed.