Dual Effects of Hexanol and Halothane on the Regulation of Calcium Sensitivity in Airway Smooth Muscle

Background: Contraction of airway smooth muscle is regulated by receptor-coupled mechanisms that control the force developed for a given cytosolic calcium concentration (i.e., calcium sensitivity). Halothane antagonizes acetylcholine-induced increases in calcium sensitivity by inhibiting GTP-binding (G)-protein pathways. The authors tested the hypothesis that hexanol, like halothane, inhibits agonist-induced increases in calcium sensitivity in airway smooth muscle by inhibiting G-protein pathways.

Methods: Calcium sensitivity was assessed using [alpha]-toxin-permeabilized canine tracheal smooth muscle. In selected experiments, regulatory myosin light chain phosphorylation was also determined by Western blotting in the presence and absence of 10 mm hexanol and/or 100 [mu]m acetylcholine.

Results: Hexanol (10 mm) and halothane (0.76 mm) attenuated acetylcholine-induced calcium sensitization by decreasing regulatory myosin light chain phosphorylation during receptor stimulation. Hexanol also inhibited increases in calcium sensitivity due to direct stimulation of heterotrimeric G-proteins with tetrafluoroaluminate but not with 3 [mu]m GTP[gamma]S, consistent with prior results obtained with halothane. In contrast, in the absence of receptor stimulation, both compounds produced a small increase in calcium sensitivity by a G-protein-mediated increase in regulatory myosin light chain phosphorylation that was not affected by pertussis toxin treatment.     

Anesthetics Inhibit Membrane Receptor Coupling to the Gq/11 Heterotrimeric G Protein in Airway Smooth Muscle

Background: Some anesthetics relax airway smooth muscle in part by inhibiting acetylcholine-induced increases in Ca2+ sensitivity, an effect associated with inhibition of guanosine nucleotide exchange at the [alpha] subunit of the Gq/11 (G[alpha]q/11) heterotrimeric G protein. This study tested the hypothesis that these anesthetic effects are not unique to the muscarinic receptor but are a general property of the heptahelical receptors that increase Ca2+ sensitivity in airway smooth muscle.

Methods: Anesthetic effects on agonist-induced increases in Ca2+ sensitivity were measured in porcine airway smooth muscle strips permeabilized with S. aureus [alpha]-toxin. Anesthetic effects on basal (without agonist stimulation) and agonist-promoted G[alpha]q/11 guanosine nucleotide exchange were determined in crude membranes prepared from porcine airway smooth muscle. The nonhydrolyzable, radioactive form of guanosine 5'-triphosphate was used as the reporter for nucleotide exchange at G[alpha]q/11.

Results: Acetylcholine, endothelin-1, and histamine caused a concentration-dependent increase in Ca2+ sensitivity. Halothane (0.67 +/- 0.07 mm) and hexanol (10 mm) significantly inhibited the increase in Ca2+ sensitivity induced by each agonist. Each agonist also caused a time- and concentration-dependent increase in G[alpha]q/11 nucleotide exchange. Neither anesthetic had an effect on basal G[alpha]q/11 nucleotide exchange, whereas halothane and hexanol significantly inhibited the increase in G[alpha]q/11 nucleotide exchange promoted by each agonist.     

Evaluating the responsiveness of the endometriosis health profile questionnaire: The EHP-30

OBJECTIVES: To evaluate the sensitivity to change of the Endometriosis Health Profile-30 (EHP-30) questionnaire. SETTING: The Women's Center, John Radcliffe Hospital, Oxford. DESIGN: Postal survey to 66 women undergoing conservative surgery for the treatment of endometriosis-associated pain. The EHP-30 and the Short Form-36 (SF-36) were administered 2 weeks before the operation, and 4 months post-operatively. At T2 a transition question was included to evaluate changes in patients health status. To evaluate responsiveness effect sizes, standardised response means, the index of responsiveness and the minimally and clinically important differences were calculated. RESULTS: Forty (66.6%) patients returned the questionnaires at time 1 and 2. Overall less responsive effect size scores were found for the SF-36 (0.1-0.5) compared to the EHP-30 (-0.1-1.1) for all patients who had undergone treatment. Minimally important differences and the index of responsiveness were overall higher for the EHP-30 (0.4-2.0) compared to the SF-36 (0.1-1.0). Change scores for four of the five scales were significantly correlated with women's responses to the transition question. CONCLUSIONS: Results suggest that the EHP-30 is sensitive to change. Its application in clinical trials should prove beneficial in assessing the impact of medical and surgical interventions upon quality of life for women with endometriosis.     

Evaluating risk factors associated with severe hypoglycaemia in epidemiology studies—what method should we use?

AIMS: To determine the most appropriate regression models to use when assessing risk factors for severe hypoglycaemia and to investigate the impact of model misspecification and its clinical implications. METHODS: A total of 1229 children with Type 1 diabetes (mean age 11.7 years sd 4.1), of which 605 (49.2%) were males, were studied. Prospective assessment of severe hypoglycaemia (an event leading to loss of consciousness or seizure) was made over the 9-year period, 1992-2001. Patients were seen every 3 months and episodes of hypoglycaemia along with clinical data were recorded. Over 70% of children never experienced a severe hypoglycaemic event. Data were analysed using the Poisson regression, negative binomial, zero-inflated Poisson (ZIP) and zero-inflated negative binomial (ZINB) models. The over-dispersion and likelihood ratio statistics were calculated and the analytical methods compared. RESULTS: The Poisson regression model did not fit the data well. The negative binomial and the zero inflated Poisson and negative binomial models fitted the data better than Poisson. CONCLUSIONS: The commonly used Poisson regression models to analyse hypoglycaemia epidemiology may lead to biased parameter estimates and incorrect determination of risk factors for hypoglycaemia. We recommend the use of the negative binomial or zero inflated models to examine any risk factors associated with severe hypoglycaemia. Careful consideration must be given to the interpretation of hypoglycaemia surveys and their analysis.     

Use of somatosensory evoked potentials to detect peripheral ischemia and potential injury resulting from positioning of the surgical patient: case reports and discussion.

BACKGROUND: Somatosensory evoked potentials (SSEPs) have long been recognized as an excellent tool for detecting neural and vascular compromise during vascular, neurosurgical and orthopedic procedures. SSEPs have the ability to localize, central versus peripheral, the area of compromise. Many surgeons use only lower-limb SSEP monitoring when performing lumbar spinal surgery. The upper extremities are usually not monitored during such procedures, and monitoring oxygen saturation does not detect neural compromise. PURPOSE: To report that the expanded use of SSEP monitoring during surgery can be beneficial in detecting peripheral ischemia or neural compromise resulting from positioning. STUDY DESIGN: Three case reviews of orthopedic spine surgeries where SSEP monitoring provided early warnings of vascular and neural compression. METHODS: The cases review three different lumbar procedures in which evidence of peripheral ischemia and nerve compression were detected by SSEP monitoring. RESULTS: By the use of upper- and lower-extremity monitoring during lumbar procedures, early detection of ischemia and nerve compression were noted intraoperatively. These changes prompted examination of the patient and repositioning to correct the ischemia or compression. The repositioning in these cases corrected the problem, and no lasting effects were found. CONCLUSIONS: Including SSEP monitoring of the bilateral upper extremities should be considered during lumbar spinal procedures. Such monitoring can be offered for a slightly increased expense and only minimal time delay to place the additional required electrodes by the technician. As a direct result of the early warning of the SSEP monitoring, we were able to avoid potential ischemic injuries and improve patient outcomes.     

Endorectal surface coil MR imaging of prostatic carcinoma with the inversion-recovery sequence

The value of inversion-recovery (IR) sequences in the diagnosis and staging of prostatic carcinoma with magnetic resonance (MR) imaging was studied. Twenty-six patients with carcinoma of the prostate were imaged at 1.5 T with an endorectal surface coil and with a variety of IR sequences and a set of spin-echo (SE) sequences for comparison. Ex vivo prostate specimens were imaged again at the same field strength. The two images were correlated with histologic sections. Cancer was identified with MR imaging in 96% of patients. Of the tumors more than 4 mm in diameter, 87% were identified on T2-weighted SE images, whereas only 26% were identified on IR images. However, IR images may be more useful in local staging of carcinoma. Gross capsular infiltration was present in only two patients; however, it was detectable (and excluded in five other patients) by means of IR images. It was not detectable on SE images. The high quality of images obtained with the endorectal coil was confirmed. The authors conclude that addition of the IR sequence to MR imaging with the endorectal coil may improve the usefulness of this examination.     

Upper and midureteral calculi: percutaneous extraction with an occlusion balloon catheter

In 44 patients with one or more calculi in the upper two-thirds of the ureter, single-stage percutaneous nephrolithotomy was performed through a middle or upper calyceal nephrostomy after cystoscopic placement of an occlusion balloon catheter distal to the calculus; in 42, the procedure was successful. The occlusion balloon catheter permitted retrograde opacification of all systems for enhanced renal puncture. In the last 30 patients an attempt was made either to push the calculus upward mechanically or to flush it upward into the renal pelvis with carbon dioxide or dilute contrast material. This was successful in 24 of these patients. Prior overnight occlusion of the ureter by means of ureteral dilatation further facilitates dislodgment of the calculus, which was successful in 12 of 13 patients.