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Isoflurane has been characterized as a distressing agent for rodents, causing both physiologic and behavioral effects. Using a "darkened home cage" has been recommended during CO2 administration for rodent euthanasia; this is arguably a similar animal experience to anesthetic induction with isoflurane. Based on the premise that rodents perceive red light as darkness via the primary optic tract, we compared physiologic and behavioral markers of stress in 2 inbred strains of mice (C57BL/6J and BALB/cJ) anesthetized with isoflurane in either a red-tinted (dark) induction chamber or a traditional translucent induction chamber. Physiologic stress was assessed based on plasma levels of norepinephrine, epinephrine, and corticosterone. Stress-related behaviors (rearing, face wiping, and jumping) were recorded on video and scored from initiation of induction to loss of consciousness. No significant correlations were found between chamber type and physiologic stress hormones. As compared with the translucent chamber, stress-related behaviors were more frequent in the red-tinted chamber, including: 1) significantly higher rearing frequencies in BALB/cJ mice; 2) higher behavioral stress scores in BALB/cJ and male C57BL/6J mice; and 3) more face wiping behavior when considering all mice combined. These findings suggest that mice do not experience significant alleviation of physiologic indices of stress when anesthetized in a red-tinted induction chamber. Furthermore, isoflurane induction in the red-tinted chamber appeared to increase the expression of stress-related behaviors, particularly in BALB/cJ mice. Based on our findings and a growing body of literature on the unintended effects of red light, we do not recommend using red-tinted chambers for induction of anesthesia in mice.

Introduction CPAP adherence may drop substantially over a long time frame. Since minorities including Hispanics and low socioeconomic groups have lower short-term acceptance and adherence, long-term adherence may also be reduced. We adapted a brief motivational enhancement education program (BMEEP) (Lai, CHEST 2014) in a Los Angeles County safety-net sleep clinic and found improved CPAP adherence at 3 months. We now report longitudinal long-term adherence over >=2 years. Our hypothesis: Many patients would meet CMS adherence criteria over >= 2 years. Methods During 3/1/2016 - 4/1/17, 118 patients completed BMEEP during CPAP initiation and were scheduled for a reinforcement session and routine clinic visits at 1 and 3 months and every 6 months thereafter. Electronic adherence and efficacy data were accessed each visit. Multivariate regression analyses explored association of adherence variables with demographic, clinical and workflow features. Results Baseline characteristics (mean (SD) or percent): Age 57.2 (17.8); Women 44.9%; Hispanic 69.5%, Non-Hispanic-White 22.9%, Other 5%, Black 3%; BMI 37; Epworth score 10.4 (6.05). Home sleep testing (69 patients) respiratory event indices were >=15/hr in 67% and >=30/hr in 57%. Polysomnography (81 patients) apnea hypopnea indices were (AHI) >= 15 in 78% and >=30/hr in 43%. By 7/1/2019, 23 (19%) patients were lost with unknown CPAP use status, while 76 (70.5%) of remaining patients continued to use CPAP. At 2 years, CPAP adherence parameters included: Average nightly use, 75% (27.7); Average hours/night, 4.74 (2.5); Average nightly use >=4 hours, 65.2% (31.6); >=70% nightly use >= 4 hours, 35 (51.5%). Average residual AHI was 2.05 (1.69). Adherence parameters in individual patients remained similar throughout 2 years. Long-term adherence was not associated with the demographic, clinical or workflow variables tested. Conclusion Programs that educate, motivate and provide regular follow-up for predominantly Hispanic low income populations can achieve acceptable long-term CPAP adherence rates. Support None

STUDY OBJECTIVES: Sleep is increasingly recognized to influence a growing array of physiological processes. The relationship between sleep duration and testis size, a marker of male reproductive potential, has not been studied. METHODS: This was a preliminary cross-sectional analysis of the baseline data from 92 healthy men (mean ± standard deviation, age 33 ± 6 years, body mass index [BMI] 24.7 ± 6.1 kg/m(2)), of whom 66 underwent at-home actigraphy and 47 underwent in-laboratory polysomnography. Sleep duration and architecture were measured by actigraphy and polysomnography, testicular volume by Prader orchidometer, total testosterone by liquid chromatography tandem mass spectrometry, free testosterone by equilibrium dialysis, and luteinizing hormone and follicle-stimulating hormone (FSH) by immunochemiluminometric assay. RESULTS: Sleep duration was correlated with testicular volume (r = .31, P = .046) and with FSH (r = −.30, P = .035), and rapid eye movement sleep was correlated with FSH (r = .44, P = .006). The significance of these findings did not change after adjustment for age and BMI, and were confirmed nonparametrically by resampling. A putative inverse U-shaped relationship between testicular volume and sleep duration was observed by polynomial regression (P = .049), but not with resampling (P = .068). CONCLUSIONS: There is a positive linear and a possible inverse U-shaped relationship between sleep duration and testis volume. Longitudinal or interventional studies manipulating sleep are required to better define causality, and ultimately to establish how much sleep is needed to maximize male reproductive potential. CLINICAL TRIAL REGISTRATION: Title: Hormonal Mechanisms of Sleep Restriction, Registry: ClinicalTrials.gov, Identifier: NCT02256865, URL: https://clinicaltrials.gov/ct2/show/NCT02256865 CITATION: Zhang W, Piotrowska K, Chavoshan B, Wallace J, Liu PY. Sleep duration is associated with testis size in healthy young men. J Clin Sleep Med. 2018;14(10):1757–1764.

Animal research pathology encompasses a wide array of procedures and may involve work with a variety of animal species and hazards. To protect laboratory personnel and ensure data integrity, pathologists must be familiar with the activities performed in their laboratories and the applicable regulatory and safety requirements. Failure to address issues proactively may result in exposure of personnel to hazardous materials and/or collection of data in a manner that does not conform to animal welfare or quality control standards. This manuscript provides a brief introduction to important animal research pathology regulatory and safety considerations. The importance of close communication between the principal investigator, pathologist, laboratory personnel, Institutional Animal Care and Use Committee, and institutional safety office/experts is emphasized and a mechanism for improving communication is discussed.

Background It would be clinically advantageous to develop a method of body temperature evaluation in cynomolgus macaques (Macaca fascicularis) that did not require sedation, restraint, surgical manipulation, or expensive equipment. Methods Body temperatures of 51 cynomolgus macaques were taken with rectal thermometry and non-contact infrared thermometry (NIFT) on the shoulder, face, abdomen, and axillary region. Results and conclusions Body temperature measurements from NIFT were statistically different (P

Study objectives Split-night polysomnography (PSG) and unattended home sleep studies have come into use as less-expensive tests for obstructive sleep apnea syndrome, but their impact on cost-effectiveness of the overall evaluation and treatment is unknown. We compared the cost-effectiveness of evaluations that employ these 2 procedures with a conventional approach using full-night PSG. Methods We used a decision-tree model that incorporated typical clinical algorithms for each of the 3 strategies to compare their cost-effectiveness from a third-party payer perspective over a 5-year period. Probabilities and test characteristics were derived from data from the published literature. Cost estimates were based on the 2004 Medicare Fee Schedule. Survival rates were taken from National Center for Health Statistics data and published studies. Effectiveness was measured as quality-adjusted life years. Results Trade-offs of overall costs versus effectiveness were identified. The home-studies strategy was less costly and less effective than split-night PSG and full-night PSG, as was split-night PSG compared with full-night PSG. Costs to attain additional quality-adjusted life years were below commonly accepted thresholds. A probabilistic analysis suggested that the home-studies approach was most cost-effective at the lowest amounts of third-party willingness to pay, whereas split-night PSG or full-night PSG was most cost-effective at higher amounts. Conclusions Home studies and split-night PSG are cost-effective alternatives to full-night PSG. Willingness-to-pay is an important consideration in choosing the most cost-effective approach. This study points out the importance of considering the complexities within the entire process of obstructive sleep apnea syndrome evaluation when comparing costs among different procedures.

The objective of this study was to demonstrate the efficacy of a novel peroxisome proliferator-activated receptor (PPAR) agonist and known PPARalpha and PPARdelta agonists to increase HDL-cholesterol (HDL-C) in the St. Kitts vervet, a nonhuman primate model of atherosclerosis. Four groups (n = 6) were studied and each group was assigned one of the following "treatments": a) vehicle only (vehicle); b) the PPARdelta selective agonist GW501516 (GW); c) the PPARalpha/delta agonist T913659 (T659); and d) the PPARalpha agonist TriCor (fenofibrate). No statistically significant changes were seen in body weight, total plasma cholesterol, plasma triglycerides, VLDL-C, LDL-C, or apolipoprotein B (apoB) concentrations. Each of the PPARalpha and PPARdelta agonists investigated in this study increased plasma HDL-C, apoA-I, and apoA-II concentrations and increased HDL particle size in St. Kitts vervets. The maximum percentage increase in HDL-C from baseline for each group was as follows: vehicle, 5%; GW, 43%; T659, 43%; and fenofibrate, 20%. Treatment with GW and T659 resulted in an increase in medium-sized HDL particles, whereas fenofibrate showed increases in large HDL particles. These data provide additional evidence that PPARalpha and PPARdelta agonists (both mixed and selective) have beneficial effects on HDL-C in these experimental primates.

Emerging on the horizon in cancer therapy is an expansion of the scope of treatment beyond cytotoxic approaches to in clude molecular management of cancer physiopathology. The goal in these integrative approaches, which extends beyond eradicating the affected cells, is to control the cancer phenotype. One key new approach appears to be modulation of the inflammatory cascade, as research is expanding that links cancer initiation, promotion, progression, angiogenesis, and metastasis to inflammatory events. This article presents a literature review of the emerging relation ship between neoplasia and inflammatory eicosanoids (PGE2 and related prostaglandins), with a focus on how inhibition of their synthesizing oxidases, particularly cyclooxygenase (COX), offers anticancer actions in vitro and in vivo. Although a majority of this research emphasizes the pharmaceutical applications of nonsteroidal anti-inflammatory drugs and selective COX-2 inhibitors, these agents fail to address alternate pathways available for the synthesis of proinflammatory eicosanoids. Evidence is presented that sug gests the inhibition of lipoxygenase and its by-products— LTB4, 5-HETE, and 12—HETE—represents an overlooked but crucial component in complementary cancer therapies. Based on the hypothesis that natural agents capable of modulating both lipoxygenase and COX may advance the efficacy of cancer therapy, an overview and discussion is presented of dietary modifications and selected nutritional and botanical agents (notably, omega-3 fatty acids, andoxi dants, boswellia, bromelain, curcumin, and quercetin) that favorably influence eicosanoid production.

U.S. federal regulations and standards governing the care and use of research animals enacted in the mid- to late 1980s, while having positive effects on the welfare and quality of the animals, have resulted in dramatic increases in overall research costs. In addition to the expenses of housing and caring for animals according to the standards, establishing the requisite internal compliance bureaucracies has markedly driven up costs, in both institutional monetary expenditures and lost research effort. However, many institutions are increasing these costs even further through additional self-imposed regulatory burden, typically characterized by overly complex compliance organizations and unnecessary policies and procedures. We discuss the sources of this self-imposed burden and recommend strategies for avoiding it while preserving an appropriate focus on animal well-being and research success.—Thulin, J. D., Bradfield, J. F., Bergdall, V. K., Conour, L. A., Grady, A. W., Hickman, D. L., Norton, J. N., Wal...

Bronchoscopy is generally a useful procedure in patients with suspected pulmonary mycoses because specific treatment is required, and bronchoscopy specimens often provide diagnostic information not available from less invasive techniques. This article addresses the role of bronchoscopy for

Bronchoscopists are frequency called on to obtain lower respiratory tract specimens in patients for whom pulmonary fungal infection is considered a diagnostic possibility. Fungal pathogens that infect the lung can be classified as T-cell pathogens or neutrophil pathogens. This review discus

Human immunodeficiency virus (HIV)-associated respiratory infections, most notably Pneumocystis carinii pneumonia (PCP), but also bacterial pneumonia (BP), result in reductions in lung function that have been studied mainly during the course of acute infection. Whether HIV-associated pneumonias also cause permanent changes in pulmonary function is unknown. In this study we investigated the long-term effects of PCP and BP on pulmonary function in a cohort of HIV-infected persons. One thousand, one hundred forty-nine HIV-infected persons were followed in a prospective, observational cohort study at six centers in the United States. Study participants had pulmonary function testing performed at regular preset intervals. PCP and BP diagnoses were verified with defined criteria. Longitudinal multivariate analysis was used to model pulmonary function in terms of demographic data and occurrence of PCP or BP. We found that PCP or BP was associated with permanent decreases in FEV(1), FVC, FEV(1)/FVC, and the diffusing capacity of carbon monoxide. Neither infection resulted in statistically significant changes in TLC. We conclude that PCP and BP result in expiratory airflow reductions that persist after the acute infection resolves. The clinical implications of these changes are unknown, but they may contribute to prolonged respiratory complaints in HIV-infected patients who have had pneumonia.

The course of pneumonia caused by pyogenic bacteria and Pneumocystis carinii was examined in a multicity cohort study of HIV infection. The median duration of survival among 150 individuals following initial bacterial pneumonia was 24 months, compared with 37 months among 299 human immunodeficiency virus (HIV)-infected control subjects matched by study site and CD4 lymphocyte count (P 200 suggest that measures to prevent bacterial pneumonia should be emphasized.

OBJECTIVE: To investigate the effects of hormone replacement therapy (HRT) and social stress on body fat distribution in an animal model of women’s health, the female cynomolgus macaque (Macaca fascicularis). DESIGN/SUBJECTS: Adult female cynomolgus monkeys were ovariectomized and fed an atherogenic diet for two years while housed in social groups of 3–8 monkeys each. Animals were then fed a lipid-lowering diet and randomized into four experimental groups: a baseline group which was necropsied immediately and not included in the study reported here, 26 females fed diet only (CONTROL), 22 females fed diet plus conjugated equine estrogens (CEE), and 21 females fed the diet plus CEE and medroxyprogesterone acetate (CEE+MPA). Treatment lasted 30 months. MEASUREMENTS: During the last nine months of treatment, social status was determined three times at three month intervals. At the end of the study, whole body obesity and fat distribution patterns were determined using anthropometry and computerized tomography (CT). RESULTS: The addition of a progestin to the estrogen replacement regimen administered to surgically postmenopausal monkeys, increased all anthropometric and CT measures of obesity except intra-abdominal fat. HRT had no effect on patterns of fat distribution. Socially-dominant, ovariectomized females were more obese than subordinates using both anthropometric and CT measurements of whole body obesity. Dominant females were more likely to have their fat deposited centrally as measured anthropometrically. However, CT measures revealed a trend for dominants to preferentially deposit fat in the subcutaneous abdominal depot in contrast to subordinates who deposited fat in the intra-abdominal depot. CONCLUSIONS: The results of this study suggest that progestins, when administered in combination with estrogens, may increase fat deposition, particularly in subcutaneous depots. In addition, the social stress experienced by subordinate monkeys, may have mild effects on fat deposition patterns, even after removal of ovarian function as a factor. These observations may have implications for treatment recommendations in postmenopausal women. Lastly, CT may measure different characteristics of fat distribution than skinfolds and circumferences.

Study objectives To determine whether an algorithm consisting of a chest radiograph and the diffusing capacity of the lung for carbon monoxide (D lco ) is effective in detecting Pneumocystis carinii pneumonia (PCP) in symptomatic HIV-infected persons; and to establish a benchmark for future comparisons of alternative algorithms. Design Prospective, 64-month study. Setting Multicenter, ambulatory care. Patients 306 HIV-infected subjects enrolled in the Pulmonary Complications of HIV Infection Study who developed 467 episodes of new or worsening respiratory symptoms. Measurements Chest radiography followed by D lco measurement, if the radiograph was normal or unchanged. Results An algorithm combining a chest radiograph followed by a D lco measurement, if the radiograph was normal or unchanged, was effective and detected abnormalities that led to a diagnosis of PCP in 78 of 80 evaluable episodes (97.5%). The radiograph (specific parenchymal abnormality, number of lung zones involved) and the D lco (degree of decrease, degree of decrease from baseline) also provided additional information on the probability of PCP. Conclusions In symptomatic HIV-infected patients suspected of having PCP, the diagnostic evaluation should begin with a chest radiograph, followed by a D lco measurement, if the radiograph is normal or unchanged. If both of these tests are normal, it may be reasonable to conclude the evaluation rather than to proceed on to additional testing. This algorithm can serve as a benchmark for future comparisons.

Study objectives To examine the significance of previously suggested risk factors and assess outcomes associated with Aspergillus identification in respiratory specimens from HIV-seropositive individuals. Design This was a nested case-control study. Patients who had Aspergillus species identified in respiratory specimens were matched at the time of study entry 1:2 with control subjects according to study center, age, gender, race, HIV transmission category, and CD4 count. Setting The multicenter Pulmonary Complications of HIV Infection Study. Participants HIV-seropositive study participants. Measurements and results Between November 1988 and March 1994, Aspergillus species were detected in respiratory specimens from 19 (1.6%) participants. The rate of Aspergillus identification among participants with CD4 counts Conclusions Although Aspergillus is infrequently isolated from HIV-infected persons, the associated high mortality would support serious consideration of its clinical significance in those with advanced disease and risk factors.

To examine intensive care unit (ICU) admission rates and diagnoses of patients with HIV infection, and to determine the outcomes of different critical illnesses, we analyzed data derived from the 63 patients who were admitted to an ICU from among the 1,130 adults with HIV infection who did not have AIDS at the time of enrollment in a multicenter prospective study. Patients were admitted and treated according to the judgment of their physicians. During 4,298 patient-years of follow-up for the entire cohort, there were 1,320 hospital admissions, of which 68 (5%) included admission to an ICU. Twenty-five (40%) of the patients admitted to the ICU died during that admission. Twenty-four patients (38%) were admitted with a principal diagnosis of lung disease; 11 had Pneumocystis carinii pneumonia (PCP), one of whom was coinfected with Aspergillus fumigatus and Legionella pneumophilia, and six of them (55%) died. Four had bacterial pneumonia, two had pulmonary edema caused by renal failure, and one each had pulmonary tuberculosis, pulmonary Kaposi's sarcoma, pneumothorax, adult respiratory distress syndrome, severe pulmonary fibrosis, cytomegalovirus pneumonitis, and metastatic adenocarcinoma to the lungs. Eleven of these 14 patients (79%) died. Thirty-nine patients had 44 admissions for nonpulmonary diagnoses, including gastrointestinal disorders (14 admissions), cardiovascular disorders (nine), sepsis syndrome (six), neurologic disorders (four), monitoring and ICU nursing care during or after a procedure (four), metabolic disorders (three), trauma (two), drug overdose (one), and unknown reasons (one). Nine (23%) of these patients died. Twenty-eight patients underwent mechanical ventilation, and 16 (57%) died. Seven (25%) had PCP (five died), seven had other primary pulmonary diseases (six died), and 14 were placed on mechanical ventilation for nonpulmonary disorders (five died). Survival did not correlate with CD4 count determined within 6 mo of admission to the ICU. In conclusion, the range of indications for critical care in patients with HIV infection is diverse. PCP accounted for only 16% of the ICU admissions, and mechanical ventilation for PCP and other pulmonary disorders was associated with a high mortality rate. In contrast, mechanical ventilation for nonpulmonary disorders, and admission to the ICU for nonpulmonary diagnoses was associated with a more favorable outcome.

OBJECTIVES HIV disease is frequently complicated by episodic acute bronchitis, suggesting the presence of chronic bronchial inflammation. To further examine this concept, we investigated the possible association of nonspecific airway hyperresponsiveness (AHR) and HIV disease. DESIGN Methacholine inhalation challenge studies were performed on 66 HIV-seropositive and 8 HIV-seronegative members of the Pulmonary Complications of HIV Infection Study Cohort. AHR was defined as 20% or more decline in FEV1 from the postdiluent value after inhalation of 125 or less cumulative breath units. The prevalence of AHR in HIV-seropositive cohort members was compared with that in matched control subjects who had undergone methacholine challenge testing for two unrelated studies. Demographic, behavioral, and clinical features in HIV cohort members with and without AHR were contrasted. The relationship between AHR and the occurrence of episodic airway disease or symptoms suggestive of airway disease was examined. RESULTS AHR was not more prevalent in HIV-seropositive cohort members than control subjects (19.3% vs 12.9%; p > 0.1). Within the cohort, AHR was detected more frequently in members with than without a history of asthma (60% vs 16%; p < 0.05). A greater proportion with than without AHR had 1 or more episode of pneumonia within 2 years (46% vs 9%; p < 0.01), 1 or more asthma episode during the study period (39% vs 1.9%; p < 0.001), or wheeze noted during clinic visits (62% vs 17%; p < 0.01). The proportion that experienced acute bronchitis did not differ in the two groups. CONCLUSIONS This study suggest that HIV-infected persons do not have increased prevalence of nonspecific AHR. In HIV disease, AHR is associated asthma, but not episodic acute bronchitis. Thus, the possibility that airway injury without demonstrable AHR might complicate HIV disease remains.

We examined trends in the incidence of specific respiratory disorders in a multicenter cohort with progressive human immunodeficiency virus (HIV) disease during a 5-yr period. Individuals with a wide range of HIV disease severity belonging to three transmission categories were evaluated at regular intervals and for episodic respiratory symptoms using standard diagnostic algorithms. Yearly incidence rates of respiratory diagnoses were assessed in the cohort as a whole and according to CD4 count or HIV transmission category. The most frequent respiratory disorders were upper respiratory tract infections, but the incidence of lower respiratory tract infections increased as CD4 counts declined. Specific lower respiratory infections followed distinctive patterns according to study-entry CD4 count and transmission category. Acute bronchitis was the predominant lower respiratory infection of cohort members with entry CD4 counts > or = 200 cells/mm3. In cohort members with entry CD4 counts of 200 to 499 cells/mm3, the incidence of bacterial and Pneumocystis carinii pneumonia each increased an average of 40% per year. In members with entry CD4 counts < 200 cells/mm3, acute bronchitis, bacterial pneumonia, and P. carinii pneumonia occurred at high rates without discernible time trends, despite chemoprophylaxis in more than 80% after Year 1, and the rate of other pulmonary opportunistic infections increased over time. Each year, injecting drug users had a higher incidence of bacterial pneumonia than did homosexual men. The yearly rate of tuberculosis was < 3 episodes/100 person-yr in each entry CD4 and HIV-transmission group. We conclude that the time trends of HIV-associated respiratory disorders are determined by HIV disease stage and influenced by transmission category. Whereas acute bronchitis is prevalent during all stages of HIV infection, incidence rates of bacterial pneumonia and P. carinii pneumonia rise continuously during progression to advanced disease. In advanced disease, the incidence of acute bronchitis, bacterial pneumonia and P. carinii pneumonia is high despite widespread chemoprophylaxis.

Pulmonary infections caused by several types of viruses and other miscellaneous organisms may cause disease in HIV infection. Evidence suggests that pulmonary conditions may result from infections of the lung by HIV itself. Other viruses, most commonly cytomegalovirus, may be primary perpetrators of pneumonitis or may contribute to diseases caused by coexisting infections. Although diagnosis and assessment of the clinical significance of these infections may be difficult, their recognition is of practical importance because potentially effective therapeutic agents are available for several of them. Miscellaneous infections such as pulmonary toxoplasmosis and pertussis are other uncommon but potentially treatable complications of HIV disease.

Objective : To study the overall and cause-specific HIV-related mortality in a cohort of HIV-seropositive subjects according to transmission category, race/ethnicity, sex and severity of immunosuppression. Design : A cohort of 1129 HIV-seropositive homo-/bisexual men, injecting drug users, and female partners of HIV-infected men were enrolled at six centers in San Francisco, Los Angeles, Chicago, Newark, Detroit and New York between 1 November 1988 and 1 November 1989. Subjects were evaluated every 6 months at least until 31 March 1994. Methods : The analyses of overall mortality for the subgroups of interest were performed with Kaplan-Meier plots and Cox proportional hazards models. Cause-specific analyses were performed on the primary cause of death using rates per 100 person-years of exposure. Results and Conclusions : Baseline severity of immunosuppression is the strongest predictor of mortality. There were no statistically significant differences in overall HIV-related mortality among transmission categories, race/ethnicity groups or sexes. There were differences, however, in cause-specific mortality among the different risk groups.

Background Patients with human immunodeficiency virus (HIV) infection are at increased risk for bacterial pneumonia in addition to opportunistic infection. However, the risk factors for bacterial pneumonia and its incidence in this population are not well defined. Methods In a multicenter, prospective, observational study, we monitored 1130 HIV-positive and 167 HIV-negative participating adults for up to 64 months for pulmonary disease. The HIV-positive group comprised 814 homosexual or bisexual men, 261 injection-drug users, and 55 female partners of HIV-infected men. Results There were 237 episodes of bacterial pneumonia among the HIV-positive participants (rate, 5.5 per 100 person-years), as compared with 6 episodes among the HIV-negative participants (rate, 0.9 per 100 person-years; P

To determine the prevalence, incidence, and types of lung diseases that occur in association with HIV infection, 1,353 subjects, including HIV-seropositive homosexual men, injection drug users, female sexual partners of HIV-positive men, and HIV-seronegative control subjects from the first two transmission categories were evaluated prospectively in a multicenter study. Patients with AIDS at the time of initial evaluation were excluded. One thousand two-hundred ninety-four subjects who had no AIDS-defining diagnosis within 3 mo of enrollment had measurements of FVC, FEV1 and DLCO at the time of enrollment. As a group, all subjects had mean values of FVC and FEV1 close to 100% predicted. Those with CD4 counts below 200/mm3 had slightly reduced DLCO compared with the others. Subjects with a history of HIV-associated symptoms (thrush, weight loss, herpes zoster) also had a reduced DLCO compared with those without symptoms. Injection drug users had reduced FVC, FEV1 and DLCO compared with homosexual men and female sexual partners of HIV-infected men, with DLCO more substantially reduced. Part of the reduction in DLCO in drug users was attributable to factors other than HIV infection, especially cigarette smoking and race. Using predicted values that take cigarette smoking into account, the prevalence of abnormality in DLCO was higher among injection drug users (33.3%) than among homosexual men (11.2%) and female sexual partners (12.7%). These results show that advanced HIV infection, characterized by CD4 count200/mm3 or HIV-associated symptoms, and factors unrelated to HIV infection, including race, cigarette smoking, and injection drug use, are all associated with reductions in DLCO measurements.

A prospective multicenter cohort study comprising 1,171 individuals who were seropositive for human immunodeficiency virus (HIV) but did not have AIDS at the time of enrollment and 182 HIV-seronegative controls, was studied by means of routine induced-sputum analysis in an attempt to detect occult tuberculosis or Pneumocystis carinii pneumonia. One occult case of tuberculosis was discovered upon the patient's enrollment (at baseline); none were discovered during follow-up. Two additional Mycobacterium tuberculosis isolates were recovered (one at baseline, one during follow-up) from subjects with symptoms or abnormalities evident on chest roentgenograms. Three specimens were false-positive (one for M. tuberculosis, two for P. carinii). Five pathogenic nontuberculous mycobacteria isolates were recovered during follow-up. Nonpathogenic, nontuberculous mycobacteria were recovered from 51 (4.6%) of 1,113 baseline specimens and 56 (3.7%) of 1,518 follow-up specimens, primarily at a center where the water supply was contaminated. We conclude that routine induced-sputum analysis is not an effective strategy for screening HIV-infected asymptomatic subjects for tuberculosis or P. carinii pneumonia before the onset of clinically recognizable disease activity.

Measures aimed at preventing complications and slowing progression of type-1 human immunodeficiency virus (HIV-1) can potentially reduce morbidity. Although little is known about the use of such measures, such data are critical for program planning. This study was performed to quantify the frequency and patterns of use for such interventions. We enrolled 1,171 persons infected with HIV, but without an acquired immunodeficiency syndrome (AIDS) defining diagnosis, in a multicenter prospective study of the pulmonary complications of HIV infection. Participants were homosexual/bisexual men, injection drug users (IDUs), or female sexual contacts of HIV-infected men. Centers were university-based and geographically dispersed across the United States. Standardized questionnaires were administered on entry and at three-month or six-month intervals; we correlated use of general and HIV-related preventive measures before entry and during the first three years in study with clinical/epidemiologic characteristics. Overall use of preventive interventions was low; only one third of study entrants had used such measures. Use was greatest among those with advanced HIV infection, but only half used preventive measures on entry; IDUs were less likely than homosexuals to use these services. Although use of interventions such as anti-Pneumocystis and antiretroviral agents increased during study participation, general measures such as pneumococcal vaccine and tuberculosis prophylaxis were used by less than 30% of those eligible for use. Among IDUs, cumulative use of these measures remained below 20% during the first three years of this study. We conclude that HIV-infected persons underuse preventive interventions, particularly general measures. Although IDUs are especially unlikely to receive preventive interventions, homosexual/bisexual men and female partners also appear to underuse preventive measures. Strategies for enhancing the use of preventive intervention are needed. [Am J Prev Med 1994:10:259–66]

To assess the effect of Xenopus husbandry on oocyte quality for membrane transport physiology experiments, we compared a recirculating-water housing system with a static-water system in a 23-mo study. Two groups of frogs (n = 8) were maintained separately for the entire study: one group was housed in a multiinvestigator centrally managed Xenopus facility, which consists of 33 tanks placed on a shared and recirculating water system; the other group was housed in a satellite facility used by a single investigator and consisting of static tanks placed in a dedicated cold-room. The activity of a heterologously expressed membrane transporter was assessed every 4 to 5 wk for a total of 23 mo. Activity of the mouse cotransporter NKCC1 was assessed through isotopic (86) Rb influx measurements under 2 experimental conditions: stimulation of cotransporter by coinjection of regulatory kinases and by exposure to a hypertonic solution. The results showed a significant difference in the level of ion fluxes under these 2 experimental conditions between the 2 groups of oocytes. During the entire period, oocytes isolated from frogs maintained in the static facility demonstrated consistently robust NKCC1 function, whereas oocytes isolated from frogs maintained in the recirculating facility showed inconsistent and weaker cotransporter function. Furthermore, the oocytes isolated from frogs maintained in the recirculating facility showed significant deterioration during the summer months (April to August), a seasonal variation that was muted in frog oocytes maintained in the static facility.

Although the pulmonary complications of advanced human immunodeficiency virus (HIV) infection have been well described, there is little information on respiratory manifestations of earlier disease. This report describes the respiratory disorders diagnosed over an 18-month period in a cohort of persons with or at risk for HIV infection with variable immunologic status. Cohort members were followed routinely and evaluated for respiratory disease by standard diagnostic algorithms. The 18-month incidence of each respiratory diagnosis was determined, and for frequent diagnoses, incidence by transmission category, location of residence, smoking status, CD4 count, and performance score at entry were compared. The most frequent respiratory diagnoses in HIV-seropositive cohort members were common to the general population: upper respiratory infection (33.4%), acute bronchitis (16.0%), acute sinusitis (5.3%), and bacterial pneumonia (4.8%). Pneumocystis carinii pneumonia occurred in 3.9%. Ambulatory respiratory illnesses were reported frequently regardless of immunologic status. The rates of P. carinii pneumonia and bacterial pneumonia were significantly greater in cohort members with entry CD4 counts < 250. Bacterial pneumonia occurred more frequently in injecting drug users and in cohort members with entry Karnofsky scores < 90. Disease stage and demographic and exposure factors are important variables affecting the respiratory manifestations of HIV infection.

We enrolled 1,353 subjects in a multicenter study to evaluate the spectrum of pulmonary complications associated with human immunodeficiency virus (HIV) infection and the feasibility of detecting pulmonary infections in asymptomatic members of this group. There were 1,171 who were HIV-seropositive; the remaining 182 were HIV-seronegative, but they belonged to high-risk transmission groups (homosexual/bisexual, or injection drug users). Single-breath carbon monoxide diffusing capacity (DlCO) was measured serially (at 3- to 12-month intervals) in a prospective fashion to determine whether a decline of ⩾ 20% predicted the presence of Pneumocystis carinii pneumonia or other pulmonary infections in the absence of new pulmonary symptoms and no new abnormalities on chest roentgenograms. In 64 subjects (6% of the group who had two or more measurements) DlCO declined ⩾ 20% from a prior value within 2 yr of entry, unassociated with fever, increased cough or dyspnea, or new chest roentgenogram abnormalities. Induced...

Animal models of movement disorders can present special challenges for the research institutions that use them. Such models often affect the animals’ ability to ambulate and perform normal body functions, and these potential effects on health and well-being mandate additional steps to ensure humane animal care and use. Indeed, the appropriate level of care for these models may call for actions that go beyond what is required or considered standard for other protocols. A proactive team approach to animal use protocol development and animal management is important. Through the commitment and involvement of the entire team—researchers, facility personnel, and institutional animal care and use committee members— institutions that use these valuable models can ensure both the fulfillment of research objectives and the implementation of the best practices for animal care. Among the most commonly used animal models of movement disorder are models of stroke, brain and spinal cord injury, dystonia, Parkinson’s disease, and Huntington’s disease. Despite their relatively wide use, there is very little in the literature that describes the specific needs of individual models and the challenges those needs may present in today’s regulatory environment. In this article, we discuss animal use considerations and provide the available animal care information on specific models. Interested readers are also referred to the additional information in the accompanying articles in this issue of ILAR Journal.

Split-night polysomnography (PSG) and unattended home sleep studies have come into use as less-expensive tests for obstructive sleep apnea syndrome, but their impact on cost-effectiveness of the overall evaluation and treatment is unknown. We compared the cost-effectiveness of evaluations that employ these 2 procedures with a conventional approach using full-night PSG.We used a decision-tree model that incorporated typical clinical algorithms for each of the 3 strategies to compare their cost-effectiveness from a third-party payer perspective over a 5-year period. Probabilities and test characteristics were derived from data from the published literature. Cost estimates were based on the 2004 Medicare Fee Schedule. Survival rates were taken from National Center for Health Statistics data and published studies. Effectiveness was measured as quality-adjusted life years.Trade-offs of overall costs versus effectiveness were identified. The home-studies strategy was less costly and less effective than split-night PSG and full-night PSG, as was split-night PSG compared with full-night PSG. Costs to attain additional quality-adjusted life years were below commonly accepted thresholds. A probabilistic analysis suggested that the home-studies approach was most cost-effective at the lowest amounts of third-party willingness to pay, whereas split-night PSG or full-night PSG was most cost-effective at higher amounts.Home studies and split-night PSG are cost-effective alternatives to full-night PSG. Willingness-to-pay is an important consideration in choosing the most cost-effective approach. This study points out the importance of considering the complexities within the entire process of obstructive sleep apnea syndrome evaluation when comparing costs among different procedures.

This Update describes recent advances in treating pulmonary hypertension and outlines the issues surrounding proposals to screen for lung cancer by using low-dose computed tomography.

The relationship between the stress associated with low social status and disease susceptibility is apparent in human and non-human primates. In human beings, low socioeconomic status is associated with increased mortality from all causes, increased coronary heart disease (CHD) morbidity and mortality, increased rates of depression, the prevalence of themetabolic syndrome, and central obesity (1). We have studied these relationships in female cynomolgus monkeys for many years. Like human beings, low social status (subordinate) female monkeys are more susceptible than their dominant counterparts to a number of pathological processes that result in disease, including depression and coronary artery atherosclerosis. This chapter will focus on the relationship between social status, fat distribution patterns, and two disease endpoints in adult female cynomolgus monkeys, coronary heart disease risk and depression.

Background Much care for non-emergency problems is provided at “episodic care” settings (e.g., urgent care and emergency room). Methods Ninety-four subjects, without known occupational disease, who were seeking care for a chronic or sub-acute problem in an episodic care location, were interviewed to assess the frequency and types of occupational health concerns. They were asked whether work probably “caused” or “made worse” their illness and whether their illness “made work difficult.” Results Categorized hierarchically, 20% reported causation, 15% worsening, and 15% interference of illness with work. (Each was categorized in one category only). Only 50% reported absence of a workplace-health interaction. One-third reported that workplace changes could improve their functional status. Nevertheless, workplace factors were discussed only 21% of the time in physician-patient encounters. Conclusions This study suggests that occupational health issues are frequent in episodic care settings and that the definition of occupational health issues should be broadened to include “made worse” and “illness makes work difficult” as well as the traditional workplace causation definition. Further, episodic care settings present unique opportunities for prevention. Am. J. Ind. Med. 43: 221–226, 2003. © 2003 Wiley-Liss, Inc.

The role of liver acyl-CoA:cholesterol acyltransferase 2 (ACAT2), earlier shown to be the principal ACAT enzyme within primate hepatocytes, as a regulator of the hypercholesterolemia induced by dietary cholesterol was studied. At the end of low and high cholesterol diet periods, liver biopsies were taken from cynomolgus monkeys, a species highly responsive to dietary cholesterol, and less responsive African green monkeys. Liver cholesterol and cholesteryl ester concentrations were highest in cynomolgus monkeys fed cholesterol, despite the fact that in order to induce equivalent hypercholesterolemia, dietary cholesterol levels were 50% lower than was fed to green monkeys. Hepatic cholesteryl oleate secretion rate, measured during liver perfusion as an indicator of ACAT activity, was significantly higher in cynomolgus monkeys. Liver microsomal ACAT activity was 2-3-fold higher in cynomolgus monkeys than in green monkeys. The responses of ACAT2 were compared with those of ACAT1 that is found primarily in Kupffer cells. ACAT2 protein mass was significantly correlated to microsomal total ACAT activity in both species; ACAT1 mass was less well correlated. Dietary cholesterol induced a significant 3-fold increase of ACAT2 protein mass in cynomolgus monkeys, a much greater increase than was found for mRNA abundance; neither ACAT2 mRNA nor protein was diet-responsive in green monkeys. In cynomolgus monkeys but not in green monkeys, liver free cholesterol concentrations were elevated when cholesterol was fed and were correlated with ACAT2 protein levels. The data suggest a mechanism whereby the elevation of hepatic free cholesterol concentrations by dietary cholesterol, seen only in cynomolgus monkeys, resulted in higher ACAT2 protein levels in hepatocytes, either through increased production or stabilization of the protein. Regulation of ACAT2 gene transcription was not a factor.

Two young adult Macaca fascicularis each had unilateral mydriasis and ptosis. Both animals were euthanatized, monkey No. 1 for progressive neurologic signs and monkey No. 2 because of a positive intradermal tuberculin test. At necropsy, each animal had a single intracranial mass on the ventral surface of the midbrain, surrounding the oculomotor nerve. Histologically, both masses were immunoblastic lymphomas. Immunohistochemical staining revealed the neoplasms to be of B-cell origin. Simian retrovirus (SRV) was isolated from both monkeys, but simian immunodeficiency virus was not found. Both animals lacked antibody to SRV. Both animals had antibodies to Epstein-Barr-like virus (EBV), but EBV antigens were not found by immunohistochemistry. Polymerase chain reaction analysis for integrated EBV DNA was unproductive. One of the animals (monkey No. 2) had a pulmonary infection with Mycobacterium avium, suggesting that immunosuppression was present. These cases represent a unique and previously undescribed type of solitary lymphoma in SRV-infected macaques.

An 8-year-old male rhesus monkey ( Macaca mulatta) died following a 6-day illness consisting of progressive depression, anorexia, labored abdominal breathing, coughing, and tachypnea. Gross necropsy findings included severe multifocal (miliary) granulomatous pneumonia, granulomatous splenitis, and multifocal cerebral abscesses. Histologic examination revealed 10–15-μm broad-based budding organisms within pyogranulomatous inflammatory lesions in the lung, tracheobronchial lymph node, brain, spleen, and liver. The distribution of extrapulmonary lesions was intermediate between that described for dogs and that described for humans. These findings were consistent with blastomycosis, which is previously unreported in nonhuman primates.

The Pulmonary Complications of HIV Infection Study is a prospective, multicenter, observational study evaluating pulmonary disease among HIV-infected persons. For approximately 52 mo, 1,182 HIV-infected subjects were followed. All participants were evaluated for pulmonary disease on a predetermined schedule. There were 145 episodes of Pneumocystis carinii pneumonia (PCP). Low CD4 count correlated with risk of PCP (p < 0.0001); 79% had CD4 counts less than 100/microl and 95% had CD4 counts less than 200/microl. Subtle changes in diffusing capacity for carbon monoxide (DLCO) were associated with PCP. Univariate analysis identified recurrent undiagnosed fevers, night sweats, oropharyngeal thrush, and unintentional weight loss to be associated with risk among persons with CD4 counts above 200/microl. Subjects in whom CD4 counts declined to below 200/microl and who were not receiving preventive therapy were nine times more likely to develop PCP within 6 mo compared with subjects who received such therapy. A strong trend toward differences between the sexes was detected. Black subjects had less than one third the risk of developing PCP as did white subjects (p < 0.0001). There was no significant difference in risk by HIV transmission category, study site, frequency of follow-up, age, education, smoking history, or use of antiretroviral therapy. Multivariable analysis revealed low CD4 lymphocyte count (p < 0.0001), use of prophylaxis (p < 0.0001), racial differences (p < 0.0001), and declining DLCO (p = 0.015) to influence risk. Constitutional signs and symptoms indicate increased risk for PCP among HIV-infected persons with CD4 counts above 200/microl.

Testing with antigens that elicit delayed-type cutaneous hypersensitivity reactions is commonly used to evaluate immune competence in persons infected with the human immunodeficiency virus; however, the reliability of such testing has not been determined. We performed serial testing with tuberculin, mumps, and Candida antigens in 491 HIV-infected persons and found that 30% of persons who initially had no reaction (0 mm) to any of the three antigens, and, thus, were considered to be anergic, had reaction to the mumps or Candida antigen when they were retested 12 months later. We also examined the results of mumps antigen tests in 50 subjects who had a negative tuberculin tests after an initial positive test. The mumps antigen test was positive in 39% of the subjects when the tuberculin test was falsely negative. We conclude that tests commonly used to define anergy cannot reliably identify the anergic state. Moreover, using the mumps antigen to aid in the interpretation of the tuberculin test will often lead to erroneous conclusions. These data indicate that the results of anergy testing should not be used to make individual patient decisions concerning preventive therapy for tuberculosis.

The effect of heavy, habitual marijuana use compared with tobacco smoking on the composition of bronchoalveolar and peripheral blood lymphocytic phenotypes was examined. Bronchoalveolar lavage (BAL) and peripheral blood (PB) samples were taken from 14 nonsmokers (NS), 14 tobacco smokers (TS), 19 heavy, habitual marijuana smokers (MS), and 9 marijuana and tobacco smokers (MTS). In BAL fluid, marijuana use was associated with significantly higher alveolar macrophage concentrations, whereas tobacco smoking was associated with significantly higher alveolar macrophage, as well as higher bronchoalveolar lymphocyte and neutrophil concentrations. The bronchoalveolar T-lymphocytic phenotypic profiles of marijuana users differed from those of tobacco smokers. Tobacco, not marijuana, was found to have a significant effect toward lower percentages of bronchoalveolar CD4 cells, toward higher concentrations of bronchoalveolar CD8 cells, and toward lower bronchoalveolar CD4:CD8 ratios. Marijuana use had a significant effect toward lower percentages of bronchoalveolar CD8 cells. In peripheral blood, marijuana, but not tobacco, use was associated with significantly higher percentages of CD4 cells, lower percentages of CD8 cells, and higher CD4:CD8 ratios. These findings suggest that tobacco and marijuana have effects on bronchoalveolar and peripheral blood immunoregulatory T-lymphocytic subpopulations that differ in type or magnitude.