Letter to the editors: does cockroach sensitivity to odors vary ten fold with circadian rhythm?
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Animals↗
Biomedical subjects
James R Miller
Publications and source records attributed to James R Miller.
Effects of phospholemman expression on swelling-activated ion currents and volume regulation in embryonic kidney cells.
Phospholemman (PLM) is a 72-amino-acid phosphoprotein that is a major substrate for cAMP-dependent protein kinase, protein kinase C, and NIMA kinase. In lipid bilayers, PLM forms ion channels selective for Cl-, K+, and taurine. Effluxes of these abundant intracellular osmolytes play an important role in the control of dynamic cell volume changes in many cell types. We measured swelling-activated ion currents and regulatory volume decrease (RVD) in human embryonic kidney cells stably overexpressing canine cardiac PLM. In response to swelling, two clonal cell lines overexpressing PLM had increased swelling-activated ion current densities and faster and more extensive RVD. A third clonal cell line overexpressing mutant PLM showed reduced ion current densities and a diminished RVD response. These results suggest a role for PLM in the regulation of cell volume, perhaps as a modulator of an endogenous swelling-activated signal transduction pathway or possibly by participating directly in swelling-induced osmolyte efflux.
Animals↗
Association between mandibular retrognathia and TMJ disorders in adult females.
OBJECTIVE: This study assesses the association between temporomandibular joint (TMJ) disorders and mandibular retrognathia. METHODS: We conducted a case-control study among women, aged 18-70 years, recruited from Kaiser Permanente Northwest Division (KPNW, Portland, OR) and Group Health Cooperative of Puget Sound (GHC, Seattle, WA). Cases (N= 160) were women seeking treatment for TMJ disorders at KPNW and GHC clinics. Controls (N=151) were women without TMJ disorders, selected from among adult female dental hygiene patients at KPNW or GHC enrollees. Case status was determined by questionnaire; mandibular sagittal position (orthognathic, mildly retrognathic, severely retrognathic, or prognathic) was measured using digitized facial photographs. Odds ratios (OR) and associated 95 percent confidence intervals (CI) estimated the magnitude of the association between TMJ disorders and mandibular sagittal position. RESULTS: Women with TMJ disorders were 4.0 times (95% CI=1.5, 10.8) more likely than controls to have severe retrognathia; no association with mild retrognathia or prognathia was seen. Results were similar when cases were restricted to those with recent onset of TMJ pain (OR=6.3; 95% CI=1.8, 21.8). CONCLUSIONS: We found a strong association between TMJ disorders and severe mandibular retrognathia in adult females. In some women this likely resulted from TMJ disorders influencing mandibular development over time. However, among a subset of women, our data support the reverse hypothesis--that severe mandibular retrognathia may influence the development of TMJ disorders. Despite this strong association, abnormal mandibular position contributed only a small portion to the overall rate at which women sought treatment for TMJ disorders.
Adolescent↗
Laboratory confirmation of generalized vaccinia following smallpox vaccination.
The reinitiation of smallpox vaccination has renewed interest in implementing modern diagnostic methods to assess orthopoxvirus infection and adverse events following vaccination. We report here the laboratory confirmation of vaccinia virus in pustular lesions of a healthy adult vaccinee by use of a two-tier algorithm incorporating TaqMan PCR and electron microscopy.
Adult↗
Stepped-care approach to treating MS: a managed care treatment algorithm.
OBJECTIVE: To introduce a model treatment algorithm for use in the managed care setting as a strategy to provide ongoing disease management and long-term care for patients with multiple sclerosis (MS), with the goal of delaying disease progression and the associated disability and cognitive dysfunction. SUMMARY: MS is a chronic inflammatory disorder of the central nervous system that is associated with progressive disability and cognitive dysfunction. Currently, management of MS involves planning an effective long-term treatment strategy that can delay the progression of the disease. This article reviews a typical stepped-care approach to treating MS that is based on the concept of a platform drug, which is an agent that provides baseline immunomodulatory action throughout the course of the disease. Considerations for selecting a platform therapy include the effect on the full spectrum of MS (disability, relapses, lesion load, and atrophy as well as patient compliance and the potential impact of neutralizing antibodies [NAbs]). Currently, 4 first-line therapies are approved for relapsing MS: the 3 interferon beta (IFNbeta) products and glatiramer acetate. Of these, the IFNbetas are generally recommended as platform therapy because all have shown significant effects on relapses, magnetic resonance imaging parameters of the disease, and because intramuscular (i.m.) IFNbeta-1a (Avonex) and subcutaneous (s.c.) IFNbeta-1a (Rebif) have been shown to slow the progression of sustained disability. Patients being treated with IFNbetas can develop NAbs to the drug, which can lead to a loss of efficacy and subsequent occurrence of breakthrough disease. The 3 different formulations of IFNbeta are associated with a varying incidence of NAbs (i.m. IFNbeta-1a, 5%; s.c. IFNbeta-1a, 24%; IFNbeta-1b [Betaseron], 45%). Antibodies also form against glatiramer acetate, although their clinical significance needs to be elucidated. As the disease progresses or has periods of aggressive activity, the stepped-care approach is to add other agents onto the platform therapy to improve control of the disease. CONCLUSION: Stepped care, as outlined in this model treatment algorithm for the managed care setting, is an effective method to achieve the fundamental goal of MS treatment, that is, to delay disease progression and the associated disability and cognitive impairment.
Adjuvants, Immunologic↗
The importance of early diagnosis of multiple sclerosis.
OBJECTIVE: To describe the current understanding of the diagnosis and treatment of multiple sclerosis (MS) and to explore the use of magnetic resonance imaging (MRI) assessment as a prognostic tool and an indicator in the diagnosis of MS. SUMMARY: MS is a chronic, progressive, demyelinating disease of the central nervous system that is associated with a significant economic burden. At this time, immunomodulatory agents (interferon beta-1a (IFNbeta-1a) [Avonex], IFNbeta-1a [Rebif], IFNbeta-1b [Betaseron], and glatiramer acetate [Copaxone]) are first-line agents, which are reported to reduce relapse rates. The diagnostic criteria for MS have evolved over time to include MRI findings as an integral part of the diagnosis. However, the most recent criteria (McDonald) are focused on the diagnosis of definite MS and do not address the status of patients with a first demyelinating event (clinically isolated syndrome [CIS]). This is an important issue because a CIS is highly predictive of developing further inflammation and definite MS when the episode occurs in conjunction with lesions on the initial MRI. Many times, MRI findings do not correlate with clinical symptoms, and clinically silent lesions are identified. Therefore, the use of MRI is salient to the early diagnosis of high-risk patients. The evolution of thought concerning early treatment in MS is based on an increased understanding of the pathology of the disease. Axonal loss occurs early in the disease process, and both white matter and gray matter are affected. Studies that have analyzed early treatment in patients highly likely to have MS (clinically isolated events with evidence of lesions on MRI) report significant benefits in delaying further changes on MRI and further attacks. Patients who begin treatment later do not reap the same benefits as those who begin treatment earlier during the disease course. CONCLUSION: Patients with clinically isolated events should be referred promptly to a neurologist for assessment, including MRI scans. An early recognition of the inflammatory process enables patients to begin treatment with an immunomodulatory agent even before the technical diagnosis of definite MS so that the degenerative progression of MS can be retarded.
Adjuvants, Immunologic↗
Selective enhancement of multipotential hematopoietic progenitors in vitro and in vivo by IL-20.
In a search for novel growth factors, we discovered that human interleukin-20 (IL-20) enhanced colony formation by CD34+ multipotential progenitors. IL-20 had no effect on erythroid, granulocyte-macrophage, or megakaryocyte progenitors. IL-20 transgenic mice increased the numbers and cell cycling of multipotential but not other progenitors. IL-20 administration to normal mice significantly increased only multipotential progenitor cells, demonstrating that IL-20 significantly influences hematopoiesis, with specificity toward multipotential progenitors. This is the first cytokine with such specificity identified.
Animals↗
Increased EAG responses of tortricid moths after prolonged exposure to plant volatiles: evidence for octopamine-mediated sensitization.
As measured by electroantennograms (EAG), both male and female obliquebanded leafrollers, Choristoneura rosaceana (Harris), and redbanded leafrollers, Argyrotaeniavelutinana (Walker), were similarly sensitive to host-related plant volatiles: trans-2-hexenal, benzaldehyde, 1-hexenol, cis-3-hexen-1-ol, geraniol, linalool, (+)-limonene, hexenal and trans-2-hexenol. Females of both species were similarly sensitive to the shared major component of their sex-attractant pheromone ((Z)11-14:Ac). Continuous 60 min pre-exposure of male and female C. rosaceana and A. velutinana to successively higher concentrations of a mixture of the nine plant volatiles in Teflon chambers with continuous air exchange caused a dosage-dependent increase in subsequent responsiveness (sensitization) to green leaf volatiles, as measured by EAGs. In addition, 60 min of pre-exposure of male C. rosaceana to certain individual volatiles ((+)-limonene, geraniol, benzaldehyde) increased EAGs nearly as much as did the mixture of nine volatiles. Pre-exposures to the nine plant-volatile mixture at concentrations achieved by 100 microg and 1 mg loading dosages in 100 microl of mineral oil significantly increased EAG depolarization to pheromone (cross-sensitization) in males but not females of both moth species. Antennae of male C. rosaceana pre-injected with 100 microg of octopamine (OA) without volatile pre-exposure exhibited sensitization nearly identical to that induced by pre-exposing moths to sensitizing concentrations of the plant-volatile mixture. Moreover, injection of the OA antagonist chlorpromazine (CP) blocked sensitization by the plant-volatile pre-exposure. Collectively, these findings suggest that exposures of tortricid moths to certain host-plant related volatiles may modulate subsequent olfactory sensitivity to behaviorally relevant chemical cues and that plant-volatile induced sensitization may be octopamine mediated.
Adrenergic alpha-Agonists↗
World Trade Center rescue worker injury and illness surveillance, New York, 2001.
BACKGROUND: The September 11, 2001, terrorist attacks on the World Trade Center in New York City, New York, prompted an unprecedented rescue and recovery response. Operations were conducted around the clock, involved over 5000 workers per day, and extended into months following the attacks. The City of New York Department of Health and Mental Hygiene and the Centers for Disease Control and Prevention implemented prospective surveillance to characterize rescue worker-related injury and illness and to help guide public health interventions. METHODS: From September 11 to October 11, 2001, personnel reviewed medical records at four Manhattan hospital emergency departments (EDs), and healthcare providers completed data collection forms at five temporary Disaster Medical Assistance Team (DMAT) facilities located at the site. Rescue workers included construction workers, police officers, firefighters, emergency medical service technicians, or Urban Search and Rescue workers. Data collected included demographic characteristics, injury type, illness, and disposition. RESULTS: Of 5222 rescue worker visits, 89% were to DMAT facilities and 12% to EDs. Musculoskeletal conditions were the leading cause of visits (19%), followed by respiratory (16%) and eye (13%) disorders. Incidence rates were estimated based on total injuries and/or illnesses reported times 200,000 (100 equivalent full-time workers in 1 year at 40 hours per week x 50 weeks per year), then divided by the total number of hours worked. Eye disorders (59.7) accounted for the highest estimated injury and illness rate, followed by headache (46.8). One death, 52 hospital admissions, and 55 transports were reported. Findings underscored the need to coordinate distribution and enforcement of personal protective equipment use, purchase of diagnostic equipment to diagnose corneal abrasions, and distribution of health advisories. CONCLUSIONS: This system provided objective, timely information that helped guide public health interventions in the immediate aftermath of the attacks and during the prolonged rescue and recovery operations. Lessons learned can be used to guide future surveillance efforts.
Adolescent↗
Presence of long-lasting peripheral adaptation in oblique-banded leafroller, Choristoneura rosaceana and absence of such adaptation in redbanded leafroller, Argyrotaenia velutinana.
Pre-exposure of male oblique-banded leafrollers, Choristoneura rosaceana (Harris), to the main component of their pheromone blend and traces of its geometric isomer (Z11-14:Ac and E11-14:Ac, respectively) at 36 +/- 12 ng/ml air for durations of 15 and 60 min in sealed Teflon chambers with continuous air exchange significantly reduced peripheral sensory responses to these compounds as measured by electroantennograms (EAGs). The EAG responses of C. rosaceana to all tested dosages of pheromonal stimuli and blank controls were lowered by 55-58% and made a linear recovery to 70-100% of the pre-exposure amplitude within 12.5 min at a rate of 3-4 %/min. Exposures of 5 min were insufficient to maximally adapt C. rosaceana; however, exposures of 15 and 60 min reduced sensory responsiveness to the same minimum. In contrast, EAG responses of redbanded leafroller, Argyrotaenia velutinana (Walker), after identical pheromone exposure for 5 and 60 min yielded no long-lasting peripheral sensory adaptation as measured by EAGs, even though this species shares the same main pheromone components with C. rosaceana. We postulate that the long-lasting peripheral adaptation observed for C. rosaceana is a mechanism that impedes central nervous system habituation in this species. In contrast, A. velutinana may be more susceptible to central nervous system habituation because it lacks the capacity for minutes-long adaptation. We propose that long-lasting adaptation may be a mechanism explaining some of the variation in efficacy of pheromone-based mating disruption across taxa.
Adaptation, Physiological↗
Reassessment of the role and utility of wind in suppression of mosquito (Diptera: Culicidae) host finding: stimulus dilution supported over flight limitation.
In a Central Michigan wetland setting, with abundant Aedes vexans (Meigen), Anopheles walkeri (Theobald), and Coquillettidea perturbans (Walker), electric fan-generated wind strongly reduced mosquito catches in Centers for Disease Control and Prevention light traps releasing carbon dioxide at 650 or 1,950 ml/min. This relationship was negatively logarithmic over the range of velocities tested (0 m/s to 3.7 m/s; 0-8.3 mph) and closely matched the theoretical dilution function predicted to occur with increasing wind flows over a constantly releasing point source of volatile chemical. Tripling the carbon dioxide release rate consistently doubled the number of mosquitoes caught across the range of wind velocities tested. Neither applied wind velocity nor carbon dioxide release rate was correlated with mosquito body mass across the range of wind velocities tested. Collectively, these data support the conceptual model that applied wind diminishes mosquito catches primarily by diluting attractants rather than by exceeding mosquito flight capability. Previously published estimates of maximum air speeds of which mosquitoes are capable may now need to be reassessed if they were based upon shut-down of catches in traps baited with chemical attractants. Addition of DEET vapor significantly reduced the number of mosquitoes caught relative to equivalently moving air without repellent. We recommend that fan-generated wind should be pursued as a practical means of protecting humans or pets from mosquitoes in the backyard setting.
Aedes↗
Dead bird clusters as an early warning system for West Nile virus activity.
An early warning system for West Nile virus (WNV) outbreaks could provide a basis for targeted public education and surveillance activities as well as more timely larval and adult mosquito control. We adapted the spatial scan statistic for prospective detection of infectious disease outbreaks, applied the results to data on dead birds reported from New York City in 2000, and reviewed its utility in providing an early warning of WNV activity in 2001. Prospective geographic cluster analysis of dead bird reports may provide early warning of increasing viral activity in birds and mosquitoes, allowing jurisdictions to triage limited mosquito-collection and laboratory resources and more effectively prevent human disease caused by the virus. This adaptation of the scan statistic could also be useful in other infectious disease surveillance systems, including those for bioterrorism.
Animals↗
Generalized vaccinia 2 days after smallpox revaccination.
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Adult↗
Tumor vascularity in the prognostic assessment of primary cutaneous melanoma.
PURPOSE: The vascular supply of the primary tumor is recognized to play an important role in the progression of a number of solid tumors. However, the role of tumor vascularity in the prognostic assessment of melanoma remains unclear. The purpose of this study was to determine the prognostic impact of patterns of vascularity on the outcome associated with cutaneous melanoma. PATIENTS AND METHODS: Tumor vascularity was documented prospectively using routine histopathologic analysis of 417 primary cutaneous melanomas from the University of California at San Francisco Melanoma Center database. Four patterns of tumor vascularity were recorded: absent, sparse, moderate, and prominent. RESULTS: Increasing tumor vascularity significantly increased the risk of relapse and death associated with melanoma, corresponding to reduced relapse-free and overall survival. By multivariate analysis, tumor vascularity was the most important determinant of overall survival, surpassing tumor thickness. Increasing tumor vascularity was associated with increased incidence of ulceration in the primary tumor. CONCLUSION: Tumor vascularity is an important prognostic factor in melanoma, rivaling tumor thickness. Increasing tumor vascularity is highly correlated with ulceration, possibly helping to explain the biologic basis of this known prognostic factor.
Adolescent↗
Prognostic factors in patients with thick cutaneous melanoma (> 4 mm).
BACKGROUND: The current study was conducted to examine the role of multiple clinical and histologic factors in the prognostic assessment of patients with thick primary melanoma (> 4 mm, classified as T4). METHODS: A retrospective analysis was performed in 329 patients with T4 cutaneous melanomas who were seen at the University of California at San Francisco Melanoma Center between 1978 and 2000. Fourteen histopathologic features were recorded prospectively by a single dermatopathologist. In addition, 9 clinical factors were analyzed. RESULTS: Several histologic factors were found to have a significant impact on the survival of patients with T4 melanoma. On univariate analysis, tumor thickness, ulceration, mitotic rate, microsatellites, vascular involvement, and histogenetic type of the primary tumor all were found to have a significant impact on the overall survival rate. Regional lymph node involvement reduced the overall survival of T4 patients dramatically. The 5-year overall survival of patients with lymph node-negative T4 disease was 61%, compared with 30% for those with lymph node-positive disease. When lymph node status was taken into account, tumor thickness, vascular involvement, and ulceration all remained independent predictors of overall survival on multivariate Cox regression analysis. Neither age, gender, nor anatomic location appeared to affect the recurrence-free or overall survival rates. CONCLUSIONS: Patients with thick primary cutaneous melanomas (> 4 mm) comprise a heterogeneous group. The presence or absence of lymph node involvement, vascular involvement, and ulceration appears to result in significantly divergent overall survival rates in this patient cohort. Consideration of these factors has important implications in the management of patients with T4 melanoma.
Adult↗
Altered clinical course of malignant melanoma in HIV-positive patients.
OBJECTIVE: To determine whether the natural history of melanoma is different in patients who test positive for human immunodeficiency virus (HIV) compared with matched control subjects. DESIGN: Retrospective cohort analysis. SETTING: Ambulatory care at 2 university-affiliated medical centers. PATIENTS: Each HIV-positive melanoma patient (n = 17) was randomly matched with 2 HIV-negative patients (HIV status unknown, but without risk factors for HIV) based on the melanoma subtype, tumor thickness, Clark level, tumor location, and sex and age of the patient. MAIN OUTCOME MEASURES: Disease-free survival and overall survival of HIV-positive and HIV-negative melanoma patients were compared using a matched-pairs analysis. CD4 cell counts were recorded at the time of melanoma diagnosis and disease recurrence. RESULTS: Melanoma patients who were HIV positive had a significantly shorter disease-free survival (P =.03) and overall survival (P =.045) compared with HIV-negative melanoma patients by matched-pairs analysis. There was an inverse relationship between CD4 cell counts and time to first melanoma recurrence. CONCLUSIONS: The natural history of malignant melanoma in HIV-positive patients is more aggressive compared with matched HIV-negative melanoma patients. Altered immune response and comorbid disease may play a role in the poor clinical outcome of HIV-positive patients. These findings have important implications in the management of melanoma in the setting of HIV disease.
Adult↗
Early season crow mortality as a sentinel for West Nile virus disease in humans, northeastern United States.
The 1999 New York epidemic of human West Nile virus (WN) encephalitis and meningitis was preceded by a crow die-off also caused by WN infection. As one component of the subsequently developed national surveillance system, crow mortality data were collected to detect WN activity before humans might become infected. However, predicting areas at risk for human WN disease likely requires assessment of multiple factors, including the intensity and timing of crow epizootics. To identify early season measures of WN activity in crows associated with subsequent WN disease in humans, county-level crow mortality data from seven northeastern states were analyzed. A predictive model was developed based on analysis of 2000 surveillance data and then assessed for 2001. To characterize the intensity of early season WN activity in crows, 15 variables were constructed from surveillance data of 52 counties that tested at least four crows during the early season (defined as June 17-July 28, 2000). County values for each variable were dichotomized at the 75th percentile into "high" and "low" activity. Multivariate analysis indicated that "high" early season activity of two variables-density of reported dead crow sightings (reported dead crows/area) and [(WN-infected crows/tested crows) x (human population)]--were associated with report of at least one human WN disease case (for each variable: adjusted odds ratio, 6.9; 95% confidence interval, 1.2-40.6). An assessment of this model using 2001 surveillance data from 61 counties yielded similar findings. With emphasis on early season WN activity, crow surveillance may allow timely targeting of interventions to protect the public health.
Animals↗
Spatial analysis of West Nile virus: rapid risk assessment of an introduced vector-borne zoonosis.
The distribution of human risk for West Nile virus was determined by spatial analysis of the initial case distribution for the New York City area in 1999 using remote sensing and geographic information system technologies. Cluster analysis revealed the presence of a statistically significant grouping of cases, which also indicates the area of probable virus introduction. Within the cluster, habitat suitability for potentially infective adult mosquitoes was measured by the amount of vegetation cover using satellite imagery. Logistic regression analysis revealed satellite-derived vegetation abundance to be significantly and positively associated with the presence of human cases. The logistic model was used to estimate the spatial distribution of human risk for West Nile virus throughout New York City. Accuracy of the resulting risk map was cross-validated using virus-positive mosquito sample sites. These new epidemiological methods aid in rapid entry point identification and spatial prediction of human risk of infection for introduced vector-borne pathogens.
Animals↗