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The neutralizing antibody response to influenza virus is dominated by antibodies that bind to the globular head of haemagglutinin, which undergoes a continuous antigenic drift, necessitating the re-formulation of influenza vaccines on an annual basis. Recently, several laboratories have described a new class of rare influenza-neutralizing antibodies that target a conserved site in the haemagglutinin stem. Most of these antibodies use the heavy-chain variable region VH1-69 gene, and structural data demonstrate that they bind to the haemagglutinin stem through conserved heavy-chain complementarity determining region (HCDR) residues. However, the VH1-69 antibodies are highly mutated and are produced by some but not all individuals, suggesting that several somatic mutations may be required for their development. To address this, here we characterize 197 anti-stem antibodies from a single donor, reconstruct the developmental pathways of several VH1-69 clones and identify two key elements that are required for the initial development of most VH1-69 antibodies: a polymorphic germline-encoded phenylalanine at position 54 and a conserved tyrosine at position 98 in HCDR3. Strikingly, in most cases a single proline to alanine mutation at position 52a in HCDR2 is sufficient to confer high affinity binding to the selecting H1 antigen, consistent with rapid affinity maturation. Surprisingly, additional favourable mutations continue to accumulate, increasing the breadth of reactivity and making both the initial mutations and phenylalanine at position 54 functionally redundant. These results define VH1-69 allele polymorphism, rearrangement of the VDJ gene segments and single somatic mutations as the three requirements for generating broadly neutralizing VH1-69 antibodies and reveal an unexpected redundancy in the affinity maturation process.

Background & Aims: Patients diagnosed with colorectal cancer (CRC) are at risk for synchronous and metachronous lesions at the time of diagnosis or during follow-up evaluation. We performed a population-based study to evaluate the rate, predictors, and familial risk for synchronous and metachronous CRC in Utah., Methods: All newly diagnosed cases of CRC between 1980 and 2010 were obtained from the Utah Cancer Registry and linked to pedigrees from the Utah Population Database., Results: Of the 18,782 patients diagnosed with CRC, 134 were diagnosed with synchronous CRC (0.71%) and 300 were diagnosed with metachronous CRC (1.60%). The risk for synchronous CRC was significantly higher in men (odds ratio [OR], 1.45; 95% confidence interval [CI], 1.02-2.06) and in patients aged 65 years or older (OR, 1.50; 95% CI, 1.02-2.21). Synchronous CRCs were located more often in the proximal colon (OR, 1.70; 95% CI, 1.20-2.41). First-degree relatives of cases with synchronous (OR, 1.86; 95% CI, 1.37-2.53), metachronous (OR, 2.34; 95% CI, 1.62-3.36), or solitary CRC (OR, 1.75; 95% CI, 1.63-1.88) were at increased risk for developing CRC, compared with relatives of CRC-free individuals. Four percent of first-degree relatives of patients with synchronous or metachronous cancer developed CRC at younger ages than the age recommended for initiating CRC screening (based on familial risk), and therefore would not have been screened., Conclusions: Of patients diagnosed with CRC, 2.3% are found to have synchronous lesions or develop metachronous CRC during follow-up evaluation. Relatives of these patients have a greater risk of CRC than those without a family history of CRC. These results highlight the importance of obtaining a thorough family history and adhering strictly to surveillance guidelines during management of high-risk patients., (Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Aim: Emerging evidence suggests a pathophysiological role of micronutrient dyshomeostasis in heart failure, including promotion of adverse remodeling and clinical deterioration. We sought to evaluate serum copper (Cu) and zinc (Zn) levels in acute (AHF) and chronic (CHF) heart failure., Methods: We studied 125 patients, 71 % male, aged 69 ± 11 years, 37 % with preserved left ventricular ejection fraction (LVEF ≥40 %) (HFPEF), including 81 with AHF and 44 with CHF; 21 healthy volunteers served as controls. Serum Cu and Zn levels were determined using air-acetylene flame atomic absorption spectrophotometry., Results: Serum Cu levels were significantly higher in AHF (p = 0.006) and CHF (p = 0.002) patients compared to controls after adjusting for age, gender and comorbidities, whereas they did not differ between AHF and CHF (p = 0.840). Additionally, serum Cu in patients with LVEF <40 % was significantly higher compared to both controls (p < 0.001) and HFPEF patients (p = 0.003). Serum Zn was significantly lower in AHF (p < 0.001) and CHF (p = 0.039) compared to control after adjusting for the above-mentioned variables. Moreover, serum Zn was significantly lower in AHF than in CHF (p = 0.015). In multiple linear regression, LVEF (p = 0.033) and E/e ratio (p = 0.006) were independent predictors of serum Cu in total heart failure population, while NYHA class (p < 0.001) and E/e ratio (p = 0.007) were independent predictors of serum Zn., Conclusion: Serum Cu was increased both in AHF and CHF and correlated with LV systolic and diastolic function. Serum Zn, in contrast, was decreased both in AHF and CHF and independently predicted by clinical status and LV diastolic function.

Objectives: We sought to test the hypothesis that virtual histology characteristics of the culprit lesion in patients with ST-elevation myocardial infarction are associated with blood flow restoration after thrombolysis., Methods: Consecutive patients referred for coronary angiography after successful thrombolysis were included in this correlational cross-sectional study. Evaluation with intravascular ultrasound (IVUS) and virtual histology of the culprit arterial segment was performed in all cases., Results: Forty-eight patients (60.5 ± 10.7 years) were included. TIMI flow grade 3 was found in 24 (50%). Diabetes was strongly associated with lower TIMI flow 3 rate (26.7% vs 60.6%; p = 0.029) and there was a significant difference in the time to thrombolysis (2.0 ± 0.8 hours in those with TIMI flow 3 vs 3.0 ± 0.7 hours in TIMI flow grades 1-2; p < 0.001). Patients with TIMI flow grades 3 and 1-2 had similar absolute total plaque volume (152.8 ± 59.3mm(3) vs 147.5 ± 92.3mm(3); p = 0.817) and absolute necrotic core (NC) volume (31.2 ± 13.9 mm(3) vs 33.6 ± 23.2mm(3); p = 0.671). However, there were significant differences in the relative NC content, both in proportion to the whole plaque volume (26.3% vs 29.9%; p = 0.016) and as an area fraction at the largest NC site (31.5% vs 40.3%; p < 0.001)., Conclusion: The NC content of atherosclerotic plaques is meaningful for flow restoration after the occurrence of a coronary event. This finding highlights the importance of plaque composition, as studied with virtual histology, not only for the sequence of processes leading to an acute plaque-related event, but also for thrombus formation and lysis, following the occurrence of such an event., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background & Aims: Colorectal cancers (CRCs) diagnosed within a few years after an index colonoscopy can arise from missed lesions or the development of a new tumor. We investigated the proportion, characteristics, and factors that predict interval CRCs that develop within 6-60 months of colonoscopy., Methods: We performed a population-based cohort study of Utah residents who underwent colonoscopy examinations from 1995 through 2009 at Intermountain Healthcare or the University of Utah Health System, which provide care to more than 85% of state residents. Colonoscopy results were linked with cancer histories from the Utah Population Database to identify patients who underwent colonoscopy 6-60 months before a diagnosis of CRC (interval cancer). Logistic regression was performed to identify risk factors associated with interval cancers., Results: Of 126,851 patients who underwent colonoscopies, 2659 were diagnosed with CRC; 6% of these CRCs (159 of 2659) developed within 6 to 60 months of a colonoscopy. Sex and age were not associated with interval CRCs. A higher percentage of patients with interval CRC were found to have adenomas at their index colonoscopy (57.2%), compared with patients found to have CRC detected at colonoscopy (36%) or patients who did not develop cancer (26%) (P < .001). Interval CRCs tended to be earlier-stage tumors than those detected at index colonoscopy, and to be proximally located (odds ratio, 2.24; P < .001). Patients with interval CRC were more likely to have a family history of CRC (odds ratio, 2.27; P = .008) and had a lower risk of death than patients found to have CRC at their index colonoscopy (hazard ratio, 0.63; P < .001)., Conclusions: In a population-based study in Utah, 6% of all patients with CRC had interval cancers (cancer that developed within 6 to 60 months of a colonoscopy). Interval CRCs were associated with the proximal colon, earlier-stage cancer, lower risk of death, higher rate of adenoma, and family history of CRC. These findings indicate that interval colorectal tumors may arise as the result of distinct biologic features and/or suboptimal management of polyps at colonoscopy., (Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Clinically significant serum parathyroid hormone (PTH) variations have been reported in multiple myeloma (MM) patients treated with proteasome inhibitors. To elucidate the association between serum PTH variations and proteasome inhibition in MM, the effect of PTH and PTHR1 ligands on the proteasome inhibitors bortezomib and carfilzomib in vitro and in vivo was determined. The MM cell lines ARP1, OC1 and 5TGM1 expressed mRNA and protein encoding PTH receptor 1 (PTHR1). Treatment of 5TGM1 cells with either PTH(1-34), bortezomib or carfilzomib alone dose-dependently inhibited 5TGM1 cell proliferation. However, treatment with the potent PTHR1 antagonist [TYR34]PTH(7-34) (PTH(7-34)) had no significant effect on myeloma cell proliferation and cell viability. In contrast, when used in combination with bortezomib or carfilzomib, PTH(7-34) treatment significantly reduced the bortezomib or carfilzomib-associated decrease in cell proliferation. Treatment of the C57BL/KaLwRij mouse myeloma model with either bortezomib or carfilzomib provided a significantly prolonged survival benefit compared to controls (p=0.04; p=0.01 respectfully). This potent anti-myeloma effect was completely abrogated by concomitant treatment with PTH(7-34). These results suggest an important role of the PTHR1 in the anti-myeloma effect of proteosome inhibition., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Importance: To our knowledge, there are no recent studies that directly compare survival after breast conservation therapy (BCT) vs mastectomy., Objective: To compare the breast cancer-specific survival rates of patients undergoing BCT, mastectomy alone, or mastectomy with radiation using a contemporary cohort of patients., Design, Setting, and Participants: We performed univariate, multivariate logistic regression, and propensity analyses to compare the hazard of death for female patients with early-stage invasive ductal carcinoma treated with BCT, mastectomy alone, or mastectomy with radiation during the period from 1998 to 2008. The data were extracted from the Surveillance, Epidemiology, and End Results database. Early-stage breast cancer was defined as having a tumor size of 4 cm or smaller with 3 or less positive lymph nodes., Exposure: Breast conservation therapy, mastectomy alone, or mastectomy with radiation., Main Outcomes and Measures: Hazard of death due to breast cancer for patients undergoing BCT, mastectomy alone, or mastectomy with radiation., Results: A total of 132,149 patients were included in this analysis. Breast conservation therapy was used to treat 70% of patients, mastectomy alone was used to treat 27% of patients, and mastectomy with radiation was used to treat 3% of patients. The 5-year breast cancer-specific survival rates of patients who underwent BCT, a mastectomy alone, or a mastectomy with radiation were 97%, 94%, and 90%, respectively (P < .001); the 10-year breast cancer-specific survival rates were 94%, 90%, and 83%, respectively (P < .001). Multivariate analysis showed that women undergoing BCT had a higher survival rate than those undergoing mastectomy alone (hazard ratio, 1.31; P < .001) or mastectomy with radiation (hazard ratio, 1.47; P < .001). When propensity score stratification was used, the effect of treatment method on survival was similar., Conclusions and Relevance: Patients who underwent BCT have a higher breast cancer-specific survival rate compared with those treated with mastectomy alone or mastectomy with radiation for early-stage invasive ductal carcinoma. Further investigation is warranted to understand what may be contributing to this effect.

Purpose: Fatigue is a commonly reported symptom by prostate cancer survivors and is associated with significant distress and declines in quality of life. Qigong is a mind-body activity that consists of both physical activity and meditative aspects. This 12-week randomized controlled trial examined the feasibility and efficacy of a Qigong intervention for improving older prostate cancer survivors' levels of fatigue and distress., Methods: Forty older (median age = 72, range = 58-93), fatigued (cut-off value of ≥ 1 on the CTCAEv4.0, >20 on a fatigue grading scale), and sedentary (<150 min of moderate exercise/week) prostate cancer survivors were randomized to 12 weeks of Qigong or stretching classes. Primary outcomes were feasibility (i.e., retention and class attendance rates) and fatigue [Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue)], and secondary outcome was distress [Brief Symptom Inventory-18 (BSI-18)]., Results: Study retention rates did not significantly differ between study groups (Qigong = 80 %, stretching = 65 %, p = 0.48). The Qigong group had significantly higher class attendance than the stretching group (p = 0.04). The Qigong group had significantly greater improvements in the FACIT-Fatigue (p = 0.02) and distress (i.e., BSI-18 Somatization, Anxiety, & Global Severity Index, p's < 0.05), than the Stretching group., Conclusions: This 12-week Qigong intervention was feasible and potentially efficacious in improving senior prostate cancer survivors' levels of fatigue and distress levels. Future, larger definitive randomized controlled trials are needed to confirm these benefits in older prostate cancer survivors and in racially and ethnically diverse populations., Implications for Cancer Survivors: Qigong may be an effective nonpharmacological intervention for the management of senior prostate cancer survivors' fatigue and distress.

Introduction: The treatment for a majority of solid organ tumors is surgical resection; 10-20 % of patients suffer a perioperative complication. Perioperative complications may contribute to cancer recurrence. This study examined the relationship between postoperative complications and risk-adjusted patient overall survival., Methods: Data from 2003 to 2009 were linked from our clinical cancer registry, the National Surgery Quality Improvement Project (NSQIP), and medical records. Patients who had tumor extirpation for cure were included. The NSQIP was used to identify complications. Patients with a complication were matched to patients without a complication. χ (2) tests and Cox proportional hazard regression models were used., Results: A total of 415 patients were included for survival analysis. The hazard ratio (HR) for mortality associated with having a complication was 2.17. The HR for mortality after 200 days postoperatively was 2.47. Infectious complications were associated with the highest association with increased mortality (HR = 3.56). Noninfectious complications were not associated with an increased risk of mortality., Conclusions: This study investigated the relationship of surgical infectious complications in cancer patients with long-term survival for patients who had a number of different types of cancer. After taking into account the site, histology, and stage of the cancer, we found that patients with infectious complications had earlier death.

Objective: The purpose of this randomized controlled trial (RCT) was to examine the feasibility and acceptability of a Tai Chi Chih (TCC) intervention in senior female cancer survivors with physical functioning limitations, and its effects on health-related quality of life (QOL)., Design: This was a two-armed, parallel group, RCT with 12-weeks of Tai Chi Chih or Health Education Control., Methods: Sixty-three senior (M age = 67 years, SD = 7.15) female cancer survivors (83% breast cancer, stages I-III) with physical functioning limitations (SF-12 Health Survey role-physical & physical functioning subscales) were randomized to 12-weeks of TCC or Health Education control (HEC). Primary outcomes were feasibility and acceptability. Secondary outcomes included health-related QOL (SF-36 Health Survey), and participants' qualitative feedback on the intervention., Results: Retention (TCC = 91%; HEC = 81%) and class attendance (TCC = 79%; HEC = 83%) rates, and satisfaction levels for both study arms were high, but did not significantly differ from one another. At one-week post-intervention, none of the SF-36 scores differed between the TCC and HEC groups. Within-group analyses revealed significant improvements in the mental component summary score in TCC (p = 0.01), but not in HEC. Qualitative analyses indicated that the TCC group felt they received mental and physical benefits, whereas HEC group reported on social support benefits and information received., Conclusion: The TCC intervention was found to be a feasible and acceptable modality for senior female cancer survivors. Future, larger definitive trials are needed to clarify TCC dosage effects on QOL in this vulnerable population.

Purpose: Distress is prevalent in breast cancer patients and can be detrimental to quality of life, performance status, treatment adherence, and satisfaction with medical care. The National Comprehensive Cancer Network developed the distress thermometer (DT) as a self-assessment tool for screening distress in cancer patients. Given time and financial constraints, it is important to refine screening criteria to identify patients with elevated risk for distress. In this study, we identify clinical and epidemiological factors that are associated with an increased likelihood of elevated DT scores (≥ 4 and ≥ 7)., Methods: We assessed 229 female patients with the DT at their initial consultation for breast cancer at the Huntsman Cancer Hospital between September 2007 and December 2008. Descriptive statistics and logistic regression models were used to analyze DT and patient data., Results: Patients undergoing their initial distress thermometer screening within 30 days of receiving a diagnosis of breast cancer had the highest likelihood of scoring ≥ 4 and ≥ 7 on the DT screening tool. Emotional and physical concerns were associated with scores ≥ 4 and scores ≥ 7. Spiritual concerns became significant in patients reporting scores ≥ 7. Patients who were non-Caucasian, unemployed, had a prior history of depression, presented for recurrent disease, or who had been recently diagnosed had a higher likelihood of scores ≥ 4 and scores ≥ 7., Conclusions: Four groups of patients should be targeted for aggressive screening; patients with a prior diagnosis of depression, patients presenting with recurrent disease, unemployed patients, and non-Caucasian patients. Interventions should address physical, emotional, and spiritual concerns.

Objective: A change has recently been made to the Federation of Gynecology and Obstetrics (FIGO) staging system for cervical cancer to account for size within stage IIA cancers. This study was designed to investigate the impact of size within stage I-IIIB cervical carcinoma, and to validate these changes., Methods: The Surveillance, Epidemiology, and End Results Program database was used to extract data on patients from 1988 to 2008. Patients were included who had information recorded regarding stage, size, and type of treatment received. They were then stratified by stage and size, and analyzed for cause-specific survival (CSS) using Kaplan Meier estimates, as well as hazard ratios using Cox proportional hazards regression modeling., Results: A total of 18,649 cases were evaluated. All stages evaluated demonstrated improved CSS on Kaplan Meier estimates for smaller tumor sizes (largest p=0.0003). Hazard ratios were significantly worse for larger tumor sizes on both univariate and multivariate modeling. Specifically, stage IIA cancers demonstrated a hazard ratio of 2.0 on univariate, and 1.69 on multivariate analysis (C.I. 1.46-2.75, p<0.0001 and C.I. 1.20-2.38, p=0.0025, respectively). Further size subdivisions of 2 and 4cm for stage I, 4cm for stage IIB, and 4 and 6cm for stage IIIB also maintained prognostic significance. On multivariate analysis within each stage, size was the only variable to maintain independent significance in all stages evaluated., Conclusions: Size is independently prognostic within each stage in cervical cancer, validating the recent changes to the FIGO staging system., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to test the hypothesis that moderate procedural sedation can reduce the incidence of radial artery spasm., Background: Transradial access for left heart catheterization and percutaneous coronary intervention is increasingly used for emergent and elective procedures, in lieu of the femoral approach. However, increased rates of access site crossover have been reported, with radial artery spasm being a major contributor to this effect., Methods: Patients undergoing elective transradial percutaneous coronary intervention were prospectively randomized to receive fentanyl and midazolam during the procedure or no treatment (control subjects). The primary endpoint was angiographically confirmed radial artery spasm. Patient discomfort was quantified with a visual analogue scale., Results: Two thousand thirteen patients (age 64.5 ± 8.4 years) were randomized. Spasm occurred in 2.6% of the treatment group versus 8.3% of control subjects (p < 0.001; odds ratio [OR]: 0.29). The number needed to treat to avoid 1 case of spasm was 18 (95% confidence interval [CI]: 12.9 to 26.6). The access site crossover rate was 34% lower in the treatment group: 9.9% versus 15.0% (OR: 0.62; 95% CI: 0.48 to 0.82). Patient discomfort visual analogue scale score was 18.8 ± 12.5 in the treatment group versus 27.4 ± 17.4 in control subjects (p < 0.001). No significant differences were observed in the 30-day rate of death or repeat hospital stay for any cause: 4.6% versus 4.5% (OR: 1.02; 95% CI: 0.67 to 1.56)., Conclusions: Routine administration of relatively low doses of an opioid/benzodiazepine combination during transradial interventional procedures is associated with a substantial reduction in the rate of spasm, the need for access site crossover, and the procedure-related level of patient discomfort., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: In 2009, the International Federation of Gynecology and Obstetrics (FIGO) staging system was revised for endometrial cancers. Different histologies were examined in a large population database. The FIGO 1988 and 2009 staging systems were compared for stage at presentation, differences in patient populations, and disease-specific survival (DSS)., Methods/materials: A total of 10,839 cases from 1998 to 2006 were analyzed from the Surveillance, Epidemiology, and End Results (SEER) Program. Examined histologies included 1377 cases of clear cell carcinoma (CC), 2304 cases of uterine papillary serous carcinoma (PS), 755 cases of carcinosarcoma (CS), and 6403 cases of grade 3 endometrial adenocarcinoma (G3A). The median follow-up was 26 months. For each stage and histology, DSS for patient characteristics was examined., Results: Of the 10,839 women with CC, PS, CS, and G3A had a median age of 67 years. White, black, and other ethnicities composed 87.5%, 12%, and 7% of this group, respectively.A higher percentage of non-G3A histology (CS, PS, and CC) was found in 58% of black women versus 39% of white women. The best to worst 5-year DSS was G3A (76.2%), CC (68.8%), PS (59%), and CS (53.4%). Patients with FIGO IIIC2 disease had inferior survival outcomes in CC (P = 0.0079) and G3A (P = 0.047) compared with FIGO IIIC1 disease, whereas DSS was not significantly different for CS and PS between stages IIIC1 and IIIC2., Conclusions: These findings describe differences in the DSS of various aggressive histologies of EC, with poorer DSS in PS, CC, or CS histologies. Analysis demonstrated the usefulness of the new FIGO staging for DSS prediction between stages IIIC1 and IIIC2 for CC and G3A, and 2 divisions for stage I rather than three.

Immediate breast reconstruction allows for improved patient psychosocial outcomes after mastectomy. We used the Surveillance, Epidemiology, and End Results (SEER) database to study the breast cancer-specific survival of patients treated with immediate or early-delayed breast reconstruction after mastectomy. Population-level de-identified data was abstracted from the SEER database. All female patients treated with mastectomy for a diagnosis of ductal and/or lobular breast cancer between 1998 and 2002 were included. Breast cancer-specific survival was reported as hazard ratios using multivariate analysis to control for patient demographic and oncologic covariates. Demographic covariates included age, race, marital status, income, education, and county metropolitan status; oncologic covariates included tumor stage, histology, grade, lymph node status, hormone receptor status, receipt of radiation therapy, and unilateral or bilateral mastectomy. A total of 52,249 patients were included in the study. Patients treated with mastectomy and reconstruction had a significantly lower hazard of death (HR 0.73, p < 0.0001) compared with patients treated with mastectomy only. Black patients had a significantly increased hazard of death (HR 1.42, p < 0.0001) compared with white patients. Receipt of radiotherapy did not significantly associate with hazard of death (HR 1.03, p = 0.3494). Additionally, bilateral mastectomy did not significantly associate with hazard of death (HR 0.98, p = 0.763). Our analysis shows that patients who undergo breast reconstruction after mastectomy have a higher breast cancer-specific survival than those undergoing mastectomy alone, when controlling for demographic and oncologic covariates. Further research is required to understand the nature of this relationship., (© 2012 Wiley Periodicals, Inc.)

Current liver allocation policy in the United States grants liver transplant candidates with stage T2 hepatocellular carcinoma (HCC) a priority Model for End-Stage Liver Disease (MELD) score of 22, regardless of age. Because advanced age may portend an increase in all-cause mortality after transplantation for any diagnosis, the aim of this study was to examine overall posttransplant survival in elderly patients with HCC versus younger cohorts. Based on Organ Procurement and Transplantation Network data, Kaplan-Meier 5-year survival rates were compared. Recipients undergoing primary liver transplantation were stratified into cohorts based on age (<70 or ≥ 70 years) and the receipt of MELD exception points for HCC. Log-rank and Wilcoxon tests were used for statistical comparisons. In 2009, 143 transplants were performed for patients who were 70 years old or older. Forty-two percent of these patients received a MELD exception for HCC. Regardless of the diagnosis, the overall survival rate was significantly attenuated for the septuagenarians versus the younger cohort. After 5 years of follow-up, this disparity exceeded 10% to 15% depending on the populations being compared. The 1-, 2-, 3-, 4-, and 5-year actuarial survival rates were 88.4%, 83.2%, 79.6%, 76.1%, and 72.7%, respectively, for the patients who were younger than 70 years and 81.1%, 73.8%, 67.1%, 61.9%, and 55.2%, respectively, for the patients who were 70 years old or older. Five-year survival was negatively affected for patients with HCC who were younger than 70 years; this disparity was not observed for patients with HCC who were 70 years old or older. In conclusion, although patients who are 70 years old or older compose a small fraction of transplant recipients in the United States, patients in this group undergoing transplantation for HCC form an even smaller subset. Overall, transplantation in this age group yields outcomes inferior to those for younger cohorts. However, unlike patients who are less than 70 years old and receive MELD exception points, overall liver transplant survival is not affected by HCC at an advanced age., (Copyright © 2012 American Association for the Study of Liver Diseases.)

Background: Recent changes were made to the International Federation of Gynecology and Obstetrics (FIGO) staging system for endometrial cancer. The objective of this study was to compare survival outcomes for patients who were staged according to the 1988 FIGO staging system versus the 2009 FIGO staging system., Methods: Data were obtained from the Surveillance, Epidemiology, and End Results Program for the years 1998 to 2006. Patients who had a diagnosis of adenocarcinoma of the uterus with complete staging information were included. Patients were staged according to the 1988 and 2009 FIGO staging systems, and Kaplan-Meier estimates were derived for cause-specific survival (CSS). Univariate and multivariate analyses using Cox proportional hazards models were used to identify the factors associated with survival., Results: In total, 47,284 patients were included. The median follow-up was 37 months. The 5-year CSS rates for patients who had 2009 FIGO stage IA and IB disease were 96.6% and 89.9%, respectively (P < .0001). After accounting for age, grade, and race, this survival difference remained significant (hazard ratio [HR], 1.97; 95% confidence interval [CI], 1.74-2.24; P < .0001). Patients who had 1988 FIGO stage IIA disease had a 5-year CSS rate similar to that of patients who had 1988 FIGO stage IC disease (88.6% vs 89.9%, respectively; P = .09). Patients who had positive pelvic washings had a 5-year CSS rate similar to that of patients who had stage IIIA disease according to the 2009 FIGO system (74.2% vs 72.1%, respectively; P = .37). The 5-year CSS rate for patients who had stage IIIC1 disease was significantly improved compared with that for patients who had stage IIIC2 disease (68.2% vs 57.3%, respectively; P < .0001). In the multivariate model, the survival difference remained (HR, 1.49; 95% CI, 1.26-1.76; P < .0001)., Conclusions: The 2009 staging system for endometrial cancer produced better discrimination in CSS outcomes compared with the 1988 system., (Copyright © 2011 American Cancer Society.)

Mastectomy is used to treat one third of the nearly 180,000 women diagnosed with breast cancer in the United States annually. In this study, we use population-level data from multiple years of the Surveillance, Epidemiology, End Results (SEER) database to further define patient, tumor, and geographic characteristics associated with immediate and early-delayed breast reconstruction. Population level de-identified data for the years 1998 to 2002 were extracted from the National Cancer Institute's (NCI) SEER cancer database. All female patients who were treated with mastectomy for a diagnosis of ductal and/or lobular breast cancer (including Paget disease) were included. The primary end point of interest was odds of reconstruction. Multivariate analysis was performed to control for patient demographic and oncologic characteristics. A total of 52,249 patients met the inclusion criteria. Reconstruction was performed in 8,446 patients (16.2%). Odds of reconstruction varied by region from 0.60 (Seattle) to 2.81 (Atlanta). African Americans were noted to have a significantly lower likelihood of reconstruction when compared with Caucasian patients (OR 0.60 versus 1.00). Patients living in nonmetropolitan regions were also significantly less likely to undergo reconstruction. Receipt of radiation therapy was also negatively correlated with likelihood of reconstruction. In this multicenter, multiyear analysis of factors associated with immediate or early-delayed reconstruction after mastectomy, we demonstrate that younger age, white race, metropolitan locale, and lower stage disease were all independently associated with higher likelihood of reconstruction. This information provides insight into breast reconstruction utilization and will help guide future studies to understand how these factors affect patient and physician decision-making., (© 2011 Wiley Periodicals, Inc.)

This is a case report regarding the retrieval, by means of an improvised snare and guiding catheter, of a stent dislodged in the brachial artery during a transradial coronary intervention. A full-length guiding catheter could not be used to approach the lost stent, which was a mere 30 to 35 cm away from the sheath insertion site at the radial artery, and a commercial snare was not available at the time. Thus, we had to improvise a shortened guiding catheter and a snare, which was formed by folding an angioplasty Whisper guide wire (Abbott Laboratories, Abbott Park, IL) and was used successfully to snare the stent and retrieve it.

Introduction: The transfemoral approach (TFA) has been the mainstay for arterial access during percutaneous coronary intervention (PCI) in the setting of acute ST-segment elevation myocardial infarction (STEMI). However, the transradial approach (TRA) has been shown to be an equally effective and possibly safer way of performing primary PCI (pPCI)., Methods: The study population included 98 serially recruited patients who underwent pPCI in our institution. All patients were clinically followed during their hospital stay (6.4 ± 3.1 days)., Results: In the 98 patients included in the study, 65 procedures (66.3%) were completed via TRA, whereas the remaining 33 procedures (33.7%) used TFA. Door-to-balloon time was similar (57 ± 19 min vs. 54 ± 15 min, p=ns). Patients in the TRA group were mobilized sooner (28 ± 9 hours vs. 36 ± 13 hours, p<0.05). Hospital stay was significantly shorter in the TRA group (6.0 ± 3.2 days vs. 7.1 ± 2.8 days, p<0.05). TRA and TFA did not differ significantly as to the incidence of death, non-fatal myocardial infarction or subacute stent thrombosis, but major access-related vascular complications were significantly more frequent in the TFA group (2% vs. 15%, p<0.01). Cerebrovascular events did not differ between TRA and TFA., Conclusions: Compared to TFA, TRA seems to be associated with a lower incidence of bleeding complications, as well as earlier mobilization and discharge from hospital. It is conceivable that TRA could become the first choice in the treatment of STEMI patients in the near future, while TFA is kept as an alternative.

We prospectively evaluated the bone changes associated with proteasome inhibition using single agent bortezomib in relapsed or refractory myeloma patients. Ten patients received bortezomib 1.3 mg/m(2) per days 1, 4, 8 and 11 for three 21-day cycles, and 6 patients received 1 mg/m(2) per day with the same schedule. Bone architecture and metabolism changes were assessed by bone markers, micro-CT, bone histomorphometry, tetracycline labeling and serum parathormone levels. Bone parameter variations were compared by response to treatment. Microarchitectural changes were observed in all evaluable responsive patients. Bone alkaline phosphatase changes were associated with disease response (≥PR vs. others P=0.03 cycle 1, day 11) serum parathormone levels were also significantly increased (P=0.04 on days 11, 21, 33) in responding individuals. This study demonstrates that the myeloma control produced by proteasome inhibition is associated with bone changes and to a discrete pattern of hormonal variation.

Introduction: No prospective randomized trials exist to delineate the role of combined chemoradiotherapy (CRT) in the treatment of vaginal cancer (VC). We sought to describe the utilization rate of CRT and evaluate the potential survival benefit of CRT over radiotherapy alone in VC., Methods: A retrospective analysis of the SEER-Medicare-linked database was performed analyzing women with VC treated with external beam radiation and/or brachytherapy and diagnosed between 1991 and 2005., Results: Of the 1709 primary VC patients in the SEER-Medicare database, 326 met inclusion criteria. Most were white (80.1%) and in the 70- to 74-year age group (42.1%). Squamous cell carcinoma was the most predominant histologic diagnosis (80.4%). Brachytherapy was used in 34% of patients, whereas cisplatin was the chemotherapy of choice in 59% of CRT patients. Median follow-up was 21.5 months. Kaplan-Meier estimated that 5-year cause-specific survival (CSS) and overall survival (OS) was 67.6% and 27.1%, respectively. Before 1999, CRT was used in 7.5% of patients compared with 36.1% of patients thereafter (P < 0.001). Chemoradiotherapy was less likely to be used in patients older than 80 years (P < 0.001) but was otherwise balanced in race, stage, grade, histologic diagnosis, comorbidities, and brachytherapy use. Chemoradiotherapy did not correlate with CSS (hazard ratio [HR], 0.91; P = 0.84) or OS (HR, 1.34; P = 0.21) by multivariate analysis. Factors associated with worse CSS include stage IVA disease (HR, 4.2; P = 0.003) and 2 or more comorbidities (HR, 2.89; P = 0.03). Factors associated with worse OS include age older than 80 years (HR, 1.78; P = 0.04), stage IVA disease (HR, 3.35; P < 0.0001), and 2 or more comorbidities (HR, 2.58; P = 0.001)., Conclusions: Chemoradiotherapy utilization for VC has increased since 1999. We failed to delineate a CSS or OS benefit for CRT in this cohort.

The aim of this prospective, open-label, cohort study was to compare the effect of muscle functional electrical stimulation (FES) on endothelial function to that of conventional bicycle training. Eligible patients were those with New York Heart Association class II or III heart failure symptoms and ejection fractions ≤ 0.35. Two physical conditioning programs were delivered: FES of the muscles of the lower limbs and bicycle training, each lasting for 6 weeks, with a 6-week washout period between them. Brachial artery flow-mediated dilation (FMD) and other parameters were assessed before and after FES and the bicycle training program. FES resulted in a significant improvement in FMD, which increased from 5.9 ± 0.5% to 7.7 ± 0.5% (95% confidence interval for the difference 1.5% to 2.3%, p < 0.001). Bicycle training also resulted in a substantial improvement of endothelial function. FMD increased from 6.2 ± 0.4% to 9.2 ± 0.4% (95% confidence interval for the difference 2.5% to 3.5%, p < 0.001). FES was associated with a 41% relative increase in FMD, compared to 57% with bicycle exercise (95% confidence interval for the difference between the relative changes 1.2% to 30.5%, p = 0.034). This resulted in attaining a significantly higher FMD value after bicycle training compared to FES (9.2 ± 0.4% vs 7.7 ± 0.5%, p < 0.001). In conclusion, the effect of muscle FES in patients with heart failure on endothelial function, although not equivalent to that of conventional exercise, is substantial. Muscle FES protocols may prove very useful in the treatment of patients with heart failure who cannot or will not adhere to conventional exercise programs., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Background: An increasing number of dermatologists are using physician assistants (PAs) in their practices. A lack of information regarding the use of PAs in Mohs micrographic surgery (MMS) served as the driving force for this research., Objectives: To quantify the extent to which Mohs surgeons are using PAs in MMS., Methods: Five hundred seventy-six fellows of the American College of Mohs Surgery were sent surveys in the mail in January 2009. The survey was focused on what percentage of Mohs surgeons are using PAs and how those PAs are being used., Results: One hundred forty-three of the 576 surgeons surveyed (24.8%) responded; 43 of those (30.1%) currently employed one or more PAs; and of those 43, 15 (34.9%) reported that PAs in their practice perform preoperative consults, 25 (58.1%) reported that PAs perform postoperative follow-up, 18 (41.9%) reported that PAs were participating in some aspect of repairs, and 35 (81.4%) reported that PAs were seeing general dermatology patients., Conclusion: Mohs surgeons are using PAs for perioperative care, as well as seeing general dermatology patients. A smaller percentage of Mohs surgeons are using PAs to perform portions of MMS or the consequent repairs., (© 2010 by the American Society for Dermatologic Surgery, Inc.)

Social marketing involves applying marketing principles to promote social goods. In the context of health behavior, it has been used successfully to reduce alcohol-related car crashes, smoking among youths, and malaria transmission, among other goals. Features of social marketing, such as audience segmentation and repeated exposure to prevention messages, distinguish it from traditional health promotion programs. A recent review found 8 of 10 rigorously evaluated social marketing interventions responsible for changes in HIV-related behavior or behavioral intentions. We studied 479 injection drug users to evaluate a community-based social marketing campaign to reduce injection risk behavior among drug users in Sacramento, California. Injecting drugs is associated with HIV infection in more than 130 countries worldwide.

Neuroblastomas secreting large amounts of catecholamines may require preoperative antihypertensive treatment to avoid intraoperative hypertensive crises as do pheochromocytomas. This is typically achieved with alpha-adrenergic followed if necessary by beta-adrenergic receptor blockade. Because of its predominant beta-blockade, labetalol as a combined alpha-adrenergic and beta-adrenergic receptor antagonist is relatively contraindicated as sole and first agent in pheochromocytomas releasing epinephrine and norepinephrine. We report successful monotherapy with labetalol over 24 hours in a 2-year-old child with a giant thoracoabdominal neuroblastoma and predominant dopamine secretion.

Background: Tacrolimus is often coadministered with various topical corticosteroids in the treatment of steroid-responsive dermatoses; however, the stability of these products in combination has not been examined extensively., Objective: To assess the in vitro compatibility of three tacrolimus-corticosteroid ointment combinations compared with unmixed controls., Methods: Tacrolimus-clobetasol propionate, tacrolimus-desoximetasone, and tacrolimus-hydrocortisone-17-valerate ointment combinations were prepared, stored with unmixed ointments at three temperature/humidity conditions, and evaluated for stability at days 0, 1, 2, 7, 14, and 28 via reverse-phase high-performance liquid chromatography., Results: There was no significant difference in the rate of drug degradation in mixed and unmixed ointments over time or across temperatures for tacrolimus (time p = .94; temperature p = .44), clobetasol (time p = .98, temperature p = .30), desoximetasone (time p = .98; temperature p = .94), or hydrocortisone-17-valerate (time p = .87, temperature p = .36)., Limitations: This study did not examine the compatibility of tacrolimus with nonointment formulations., Conclusion: Tacrolimus-clobetasol propionate (superpotent), tacrolimus-desoximetasone (high potent), and tacrolimus-hydrocortisone-17-valerate (midpotent) ointment combinations are chemically compatible for at least 4 weeks.

Vagal reflexes can be induced by stimulation of select epicardial and endocardial areas of the left atrium. The present report describes the case of a 54-year-old woman with a history of recurrent symptomatic episodes of paroxysmal atrial fibrillation. During radiofrequency application around the left superior pulmonary vein, the patient exhibited an excessive vagal response with a sinus pause of 17 s.

Background: Local excision (LE) has been used in an attempt to preserve anal function in T1-2 rectal carcinoma. The current study compares LE to radical resection (RR), each with or without radiation therapy (RT)., Methods: Patients reported to the SEER registry of the National Cancer Institute from 1988 to 2003 who had T1-2N0M0 rectal carcinoma were identified. A retrospective analysis of survival was performed using the Kaplan-Meier method. Comparative risks of mortality were evaluated using multivariate adjusted Cox regression models., Results: Of 4,320 patients, 13% underwent LE alone, 7% underwent LE plus RT, 70% underwent RR alone, and 10% underwent RR plus RT. On multivariate analysis, patients who underwent LE without RT had inferior overall survival compared to patients who underwent RR (P < .05). Patients who underwent LE with or without RT had inferior cause-specific survival compared to patients who underwent RR (P < .05)., Conclusions: RR without RT was associated with superior overall survival compared to LE without RT, and RR without RT was associated with superior cause-specific survival compared to LE with or without RT. Randomized trials are necessary to determine if LE with or without RT can offer equivalent survival compared to RR in early stage rectal carcinoma.

Fibroblast growth factor receptor 1 (FGFR1) is frequently amplified and highly expressed in lobular carcinomas of the breast. In this report, we evaluated the biological activity of FGFR1 in a wide range of in vitro assays. Conditional activation of FGFR1 in the nontransformed MCF10A human mammary cell line, MCF10A, resulted in cellular transformation marked by epidermal growth factor-independent cell growth, anchorage-independent cell proliferation and survival, loss of cell polarity, and epithelial-to-mesenchymal transition. Interestingly, small-molecule or small interfering RNA inhibition of ribosomal S6 kinase (RSK) activity induced death of the FGFR1-transformed cells, but not of the parental MCF10A cell line. The dependence of FGFR1-transformed cells on RSK activity was further confirmed in cell lines derived from mouse and human lobular carcinomas that possess high FGFR1 activity. Taken together, these results show the transforming activity of FGFR1 in mammary epithelial cells and identify RSK as a critical component of FGFR1 signaling in lobular carcinomas, thus implicating RSK as a candidate therapeutic target in FGFR1-expressing tumors.

Background: There is a well-documented relationship and a complex interaction between atrial fibrillation (AF) and heart failure. The coexistence of these 2 clinical entities renders their management even more challenging., Methods and Results: We searched current literature to review the management of AF in patients with heart failure. The cornerstones of AF treatment are rate control, cardioversion, and maintenance of sinus rhythm (SR), and prevention of thromboembolism. The issue of rhythm versus rate control remains unresolved. Nonpharmacologic therapies such as radiofrequency catheter ablation of the atrioventricular node with permanent pacemaker implantation, curative catheter ablation of AF, and cardiac resynchronization therapy are emerging and may alter the management of these patients., Conclusion: Treatment of atrial fibrillation in the setting of heart failure encompasses a variety of approaches including drugs, devices, and ablation. Larger randomized trials are required to clarify the management of such patients.

Background: We reviewed the outcomes of oropharyngeal squamous cell carcinoma treated with external beam radiation and interstitial brachytherapy., Methods: Ninety patients with squamous cell carcinoma of the oropharynx were treated with interstitial brachytherapy at the University of Utah between 1984 and 2001. Seventy-two patients received external beam radiotherapy (EBRT) followed by brachytherapy boost, 11 had surgery followed by EBRT and brachytherapy, 4 had surgery and brachytherapy, and 3 were treated with brachytherapy alone. Median doses for EBRT and brachytherapy were 50 and 24 Gy, respectively., Results: Median follow-up after brachytherapy was 48.3 months for all patients. Five-year local control, disease-free survival, and overall survival were 76%, 61%, and 55%. For T1, T2, T3, and T4, 5-year local control rates were 83%, 79%, 79%, and 64%, respectively. Severe complications occurred in 13 patients, including 2 treatment-related deaths., Conclusions: EBRT combined with interstitial brachytherapy provide good local control rates for locally advanced oropharyngeal squamous cell carcinoma., ((c) 2006 Wiley Periodicals, Inc.)

Pre- and post-transplant predictive factors of graft survival for optimal and expanded criteria grafts have been studied in the past. The goal of our study was to evaluate the recent large set of United Network of Organ Sharing records (1990-1998) to generate a prediction algorithm of 3-yr graft survival based on pre-transplant variables alone. The dataset of patients with end-stage renal disease and cadaveric kidney or kidney-pancreas transplantation (1990-1998) used in the study consisted of 37,407 records. Logistic regression (LM) and a tree-based model (TBM) were used to identify predictors of 3-yr allograft survival and to generate prediction algorithm. Donor and recipient demographic characteristics (age, race, and gender) and body mass index showed non-linear, while human leukocyte antigen match showed strong linear relationships with 3-yr graft survival. Prediction of the probability of graft survival from the model, achieved a good match with the observed survival of the separate dataset, with a correlation of r = 0.998 for LM and r = 0.984 for TBM. The positive predictive value (PV) of allograft survival with LM and TBM was 76.0% and the negative PV was 63 and 53.8% for LM and TBM, respectively. Both LM and the TBM can potentially be used in clinical practice for long-term prediction of kidney allograft survival based on pre-transplant variables.

Background: A high prevalence and early onset of type 2 diabetes in Pima Indians is well known. Our objective is to use several statistical models to identify predictors of glomerular filtration rate (GFR) deterioration and develop an algorithm to predict GFR 4 years after the initial evaluation., Methods: All records (n = 86) were randomly assigned to a training set (n = 60) and a testing set (n = 26). Linear regression, generalized additive, tree-based, and artificial neural network models were used to identify predictors of outcome and develop a prediction algorithm., Results: Proteinuria remained the single most important predictor of long-term renal function; other predictors included baseline GFR, blood pressure, plasma renin activity, lipid profile, age, weight/body mass index, and diabetes duration. All four models achieved a good correlation (r = 0.73 to 0.78) between observed and predicted 4-year GFRs on a separate (testing) data set. Best results in predicting the value of GFR were achieved using a tree-based model with six terminal nodes (r = 0.78; root mean squared prediction error = 38.9). The tree-based and generalized additive models achieved high positive (91%) and negative (100%) predictive values in identifying subjects, who developed depressed GFRs in 4 years. An artificial neural network achieved the highest area under the receiver operating characteristic curve (0.91)., Conclusion: GFR depression within 4 years can be predicted with a precision that suggests potential clinical utility. A tree-based model with six terminal nodes has shown the best results in predicting the actual value of GFR, whereas an artificial neural network is the model of choice to identify the group of patients that will develop renal insufficiency., (Copyright 2002 by the National Kidney Foundation, Inc.)

Three-hundred eleven tree holes were sampled for Culicoides at 27 localities in Colorado, Kansas, Nebraska, Oklahoma and South Dakota. Of the 311 samples taken, 170 produced specimens, and 2,899 Culicoides were collected including 12 species. The 5 most common species (number collected) were C. guttipennis (1,468), C. arboricola (355), C. paraensis (292), C. elemae (186) and C. footei (159). Other species collected were C. villosipennis, C. nanus, C. hinmani, C. oklahomensis, C. snowi, C. lahillei and C. byersi. New state records include C. byersi and C. arboricola for Colorado; C. arboricola for Wyoming; and C. lahillei, C. elemae, C. nanus and C. paraensis for Oklahoma. Culicoides byersi, whose larval habitat was previously unknown, was reared from a cottonwood tree hole.

The relationship between skin temperature and mosquito blood feeding behavior was examined in nine human subjects. A system implementing computer control of skin temperature was utilized during blood feeding sessions in which feeding behavior (preforaging, foraging, probing, feeding) was timed and compared at five successive skin temperatures (29.0 degrees C-36.2 degrees C). Preforaging, foraging, and probing times were not significantly different at the skin temperatures examined. Average blood meal size (3.3 microliters) also did not differ at these skin temperatures, but the time of engorgement decreased from 249.3 s at 30.8 degrees C to 100.7 s at 36.2 degrees C. The decreased feeding time resulted in an increase in feeding rate from 1.1 microliters/min (29.0 degrees C) to 2.2 microliters/min (36.2 degrees C).

Spring emergence patterns of tree hole Culicoides were examined at 11 geographic locations. Habitat selection was one mechanism of partitioning used by Culicoides. One group (3 species) occupied tree holes with standing water (wet), while the other (7 species) inhabited tree holes without standing water (dry). The wet tree hole species had sustained emergence patterns, emergence maintained over several consecutive weeks. The dry tree hole species had phasic or biphasic emergence lasting fewer days or occurring as 2 short periods. In both dry and wet habitats, species emerged in a temporal sequence. This temporal sequence was disrupted if a species occupied a type of tree hole (wet/dry) from which it did not normally occur.

Ten species of Culicoides were collected from 166 tree holes at 20 widely separated geographic locations to assess relationships with habitat pH. Wet tree holes (containing standing water) had a mean pH of 7.46 while dry tree holes (no standing water) had a mean pH of 8.60. Culicoides arboricola, C. guttipennis and C. villosipennis occurred in wet tree holes that had mean pH values of 7.66, 7.95 and 7.31, respectively. Dry tree holes, where C. hinmani, C. elemae, C. paraensis, C. nanus, C. snowi and C. footei occurred, had pH values ranging from 8.13 to 9.08. Culicoides lahillei, a dry tree hole species, was collected from habitats with a pH range similar to the wet tree hole species.

Chemical and electronic synapses are present in the ocellar synaptic region of the moth, Trichoplusia ni. The chemical synapses all appear to be of "conventional" type. Four different chemical synaptic contacts were observed: Receptor cell axons presynaptic to receptor cell axons, receptor cell axons presynaptic to 1st order interneurons, 1st order interneurons presynaptic to receptor cell axons, and 1st order interneurons presynaptic to 1st order interneurons. Two different types of contact made by electronic synapes were observed: Contacts between receptor cell axons and 1st order interneurons, and contacts between 1st order interneurons. The significance of this synaptic arrangement for the generation of "on" and "off" responses in the 1st order interneurons is discussed.

The prevalence of canine heartworm (Dirofilaria immitis) was examined in the domestic dog, coyote (Canis latrans), and red fox (Vulpes fulva) populations of southeastern Nebraska. Microfilariae were detected in 21.4% (22 of 103) of the domestic dogs. The average age of infection for dogs was 5.8 yr. Nine of the 22 infected dogs also were positive for Dipetalonema reconditum. Thirty-nine of 443 (8.9%) coyotes were found to have adult heartworms. The average number of male and female worms per heart was 3.7 and 3.9, respectively. The mean age of infected coyotes was 3.6 yr. Red foxes had an infection rate of 4.8% (1 of 21). This fox heart had only 1 immature female worm. A mail survey of 6 veterinary clinics was also conducted. Veterinarians reported infection rates of 0% to 18.8% in domestic dogs for their localities.

Gustatory hairs were investigated on the legs and mouthparts of Culiseta inornata (Williston) (Diptera: Culicidae). One type of hair, each innervated by four neurons, was found on the legs. Two of the neurons responded to NaCl stimulation, one neuron to water stimulation, and one neuron to sucrose stimulation. Three kinds of hairs designated Type I (T1), Type 2 (T2) and Type 3 (T3) were analyzed on the labella. The T1 hairs are innervated by one sugar neuron, one mechanoreceptor, two salt neurons and one water neuron. The T2 hairs are innervated by two salt neurons and one mechanoreceptor. The T3 hairs, located on the oral surface of the labella, are innervated by a variable number (2-5) of neurons. Precise identification of the T3 chemosensory neurons was not made because of the small size and inaccessibility of the T3 hairs. Chemosensory hairs on the tip of the labrum were tested electrophysiologically. the sequence of decreasing effeectiveness for the three salts tested was KCl greater than NaCl greater than LiCl. Labral chemoreceptors also responded positively to sucrose.