Citations

Cigarette smoke, which serves as a nicotine delivery vehicle in humans, produces profound changes in physiology. Experimental studies suggest that nicotine has analgesic properties. However, epidemiologic evidence shows that smoking is a risk factor for chronic pain. The complex relationship between smoking and pain not only is of scientific interest, but also has clinical relevance in the practice of anesthesiology and pain medicine. This review will examine current knowledge regarding how acute and chronic exposure to nicotine and cigarette smoke affects acute and chronic painful conditions. It will cover the relevant pharmacology of nicotine and other ligands at the nicotinic acetylcholine receptor as related to pain, explore the association of cigarette smoking with chronic painful conditions and potential mechanisms to explain this association, and examine clinical implications for the care of smokers with pain.

ABSTRACTThe goal of this study was to evaluate the BioPlex 2200Toxoplasma, rubella, and cytomegalovirus (CMV) (ToRC) IgG and IgM multiplex immunoassays (Bio-Rad Laboratories, Hercules, CA) and compare the results to those of conventional testing by enzyme immunoassay (EIA) and enzyme-linked fluorescent assay (ELFA). Serum specimens (n= 600) submitted for routine ToRC IgG and IgM testing by EIA (SeraQuest, Doral, FL; Diamedix, Miami, FL) or ELFA (Vidas; bioMérieux, Durham, NC) were also tested by the BioPlex ToRC multiplex immunoassays. Samples showing discordant results were retested by both methods, with further discrepancies being arbitrated by a third assay. Following repeat testing, the BioPlexToxoplasma, rubella, and CMV IgG assays demonstrated agreements of 98.7 (592/600 specimens), 93.3 (560/600 specimens), and 98.3% (590/600 specimens), respectively, while the ToRC IgM assays yielded agreements of 91.2 (547/600 specimens), 87.3 (524/600 specimens), and 95.2% (571/600 specimens), respectively. The BioPlex ToRC IgG assays provided results comparable to EIA/ELFA results, with kappa coefficients showing near-perfect agreement for theToxoplasma(κ = 0.94) and CMV (κ = 0.97) IgG assays and substantial agreement for the rubella IgG assay (κ = 0.66). The BioPlex ToRC IgM assays showed lower specificity with only slight agreement forToxoplasmaIgM (κ = 0.07), poor agreement for rubella IgM (κ = −0.03), and moderate agreement for CMV IgM (κ = 0.55). Both the BioPlex IgG and IgM assays reduced turnaround time (1.7 h versus 5.5 h by EIA/ELFA for 100 specimens) and eliminated the necessity to manually pipette or aliquot specimens prior to testing.

Background: Medically intractable chronic migraine (CM) is a disabling illness characterized by headache ≥15 days per month. Methods: A multicenter, randomized, blinded, controlled feasibility study was conducted to obtain preliminary safety and efficacy data on occipital nerve stimulation (ONS) in CM. Eligible subjects received an occipital nerve block, and responders were randomized to adjustable stimulation (AS), preset stimulation (PS) or medical management (MM) groups. Results: Seventy-five of 110 subjects were assigned to a treatment group; complete diary data were available for 66. A responder was defined as a subject who achieved a 50% or greater reduction in number of headache days per month or a three-point or greater reduction in average overall pain intensity compared with baseline. Three-month responder rates were 39% for AS, 6% for PS and 0% for MM. No unanticipated adverse device events occurred. Lead migration occurred in 12 of 51 (24%) subjects. Conclusion: The results of this feasibility study offer promise and should prompt further controlled studies of ONS in CM.

Background Safe and efficient endoscopic frontal sinus surgery requires a thorough knowledge of the location of the frontal sinus outflow tract. This study was designed to describe the prevalence of the different frontal recess cells and 3D analysis by virtual endoscopy of their ostial orientation in relation to the frontal ostium. Methods Fifty high-resolution CT scans (100 sides) of disease-free paranasal sinuses were reviewed using triplanar and virtual 3D analysis. The prevalence and ostial locations of the frontal recess cells and the relationship of the various ostia to the frontal sinus ostium were mapped and analyzed. Results The cell type, prevalence, and most common relationship of the cell's ostium to the frontal ostium were intersinus septal cells, 7% medial and anterior; Kuhn type 1 cells, 28%, lateral and anterior; Kuhn type 2 cells, 6%, anterior and lateral; Kuhn type 3 cells, 11%, medial or lateral; supraorbital ethmoid cells, 11%, posterior; suprabullar cells, 68%, posterior; and frontal bullar cells, 16%, posterior or lateral. In 35% of the sides, none of the aforementioned cell types were found. There were many blind recesses that were seen in all locations except anterolateral to the frontal ostium. Openings of adjacent pneumatized middle turbinates were often posteromedial to the frontal ostium. Agger nasi cells were present in at least 86%, opening lateral to frontal ostium. Conclusion Frontal outflow tract mapping by virtual endoscopy and knowledge of the ostial configurations will help surgeons perform more efficient and accurate surgery particularly for minimally invasive approaches including balloon dilation.

Objective To provide information about the clinical use of acupuncture at an academic medical centre in the USA. Methods A retrospective review of 904 patients (receiving 6070 treatments) who were referred for acupuncture treatment at the Mayo Clinic (Rochester, Minnesota, USA) between 1 January 2004 and 31 December 2008. Data gathered included age, sex, primary diagnosis, number of treatments per diagnosis and health insurance carrier. Results The mean (SD) age of the patients was 53.4 (16.2) years; 73.8% were female and 26.2% were male. The three most common diagnostic categories for which acupuncture was used were spinal pain (33.4%), pain (other) (25.1%) and joint pain (12.3%). About 42% of visits were not covered by health insurance carriers and hence patients had to pay themselves. For the remaining 58% of visits, health insurance carriers picked up all or part of the cost of the acupuncture treatments. Conclusion The results indicate that pain is the most common reason for use of acupuncture in an academic medical centre and that women use acupuncture more than men. This is one of the few reports of clinical use of acupuncture at academic medical centres in the USA.

As part of the Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) Trial, a prospective multicenter cohort of 221 children and adolescents with systemic lupus erythematosus (SLE) (mean age 15.7 years, 83% female) underwent baseline measurement of markers of cardiovascular risk, including fasting levels of high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TG), lipoprotein A (Lpa), homocysteine and high-sensitivity C-reactive protein (hs-CRP). A cross-sectional analysis of the baseline laboratory values and clinical characteristics of this cohort was performed. Univariable relationships between the cardiovascular markers of interest and clinical variables were assessed, followed by multivariable linear regression modeling. Mean levels of LDL, HDL, Lpa, TG, hs-CRP and homocysteine were in the normal or borderline ranges. In multivariable analysis, increased Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), prednisone dose, and hypertension (HTN) were independently associated with higher LDL levels. Higher hs-CRP and creatinine clearance were independently related to lower HDL levels. Higher body mass index (BMI), prednisone dose, and homocysteine levels were independently associated with higher TG levels. Only Hispanic or non-White status predicted higher Lpa levels. Proteinuria, higher TG and lower creatinine clearance were independently associated with higher homocysteine levels, while use of multivitamin with folate predicted lower homocysteine levels. Higher BMI, lower HDL, and longer SLE disease duration, but not SLEDAI, were independently associated with higher hs-CRP levels. The R 2 for these models ranged from 7% to 23%. SLE disease activity as measured by the SLEDAI was associated only with higher LDL levels and not with hs-CRP. Markers of renal injury (HTN, proteinuria, and creatinine clearance) were independently associated with levels of LDL, HDL, and homocysteine, highlighting the importance of renal status in the cardiovascular health of children and adolescents with SLE. Future longitudinal analysis of the APPLE cohort is needed to further examine these relationships.

Abstract Few studies have examined the outcome of large numbers of patients with the microgranular variant (M3V) of acute promyelocytic leukemia (APL) in the all-trans retinoic acid era. Here, the outcome of 155 patients treated with all-trans retinoic acid–based therapy on 3 clinical trials, North American Intergroup protocol I0129 and Programa para el Estudio de la Terapéutica en Hemopatía Maligna protocols LPA96 and LPA99, are reported. The complete remission rate for all 155 patients was 82%, compared with 89% for 748 patients with classical M3 disease. The incidence of the APL differentiation syndrome was 26%, compared with 25% for classical M3 patients, and the early death rate was 13.6% compared with 8.4% for patients with classical M3 morphology. With a median follow-up time among survivors of 7.6 years (range 3.6-14.5), the 5-year overall survival, disease-free survival, and cumulative incidence of relapse for patients with M3V were 70%, 73%, and 24%, respectively. With a median follow-up time among survivors of 7.6 years (range 0.6-14.3), the 5-year overall survival, disease-free survival, and cumulative incidence of relapse among patients with classical M3 morphology were 80% (P = .006 compared with M3V), 81% (P = .07), and 15% (P = .005), respectively. When outcomes were adjusted for the white blood cell count or the relapse risk score, none of these outcomes were significantly different between patients with M3V and classical M3 APL.

Abstract Primary and secondary cancers of the liver are a significant health problem with limited treatment options. We sought here to develop an oncolytic measles virus (MV) preferentially activated in liver tumor tissue, thus reducing infection and destruction of healthy tissue. We documented that in primary tumor tissue, urokinase-type plasminogen activator and especially matrix metallproteinase-2 (MMP-2) are significantly more active than in adjacent nontumorous tissue. We then generated variants of the MV fusion protein by inserting different MMP substrate motifs at the protease cleavage site and identified the motif PQGLYA as the most efficient cleavage site as determined by syncytia formation on protease-positive tumor cells. The corresponding MMP-activatable oncolytic MV-MMPA1 virus was rescued and shown to be strongly restricted on primary human hepatocytes and healthy human liver tissue, while remaining as effective as the parental MV in the tumor tissue sections. Our findings underline the clinical potency of the MMP activation concept as a strategy to generate safer oncolytic viruses for the treatment of primary and secondary cancers of the liver. Cancer Res; 70(19); 7620–9. ©2010 AACR.