Early Onset Rapidly Progressive Osteoarthritis of the Hip in a Young Athlete.

We report and discuss a very rare case of early-stage rapidly progressive osteoarthritis (RPO) in a 33-year-old female athlete. The etiopathology of RPO remained unclear, although in this case mechanical overloading due to constant joint overuse appeared to be the only significant contributing factor to the very early development of RPO. Key words: rapidly progressive osteoarthritis, rapid destructive arthrosis, hip arthrosis, total hip arthroplasty, athlete, osteoarthritis.

The Trial-Ready Cohort for Preclinical/Prodromal Alzheimer's Disease (TRC-PAD) Project: An Overview.

The Trial-Ready Cohort for Preclinical/prodromal Alzheimer's Disease (TRC-PAD) project is a collaborative effort to establish an efficient mechanism for recruiting participants into very early stage Alzheimer's disease trials. Clinically normal and mildly symptomatic individuals are followed longitudinally in a web-based component called the Alzheimer's Prevention Trial Webstudy (APT Webstudy), with quarterly assessment of cognition and subjective concerns. The Webstudy data is used to predict the likelihood of brain amyloid elevation; individuals at relatively high risk are invited for in-person assessment in the TRC screeing phase, during which a cognitive battery is administered and Apolipoprotein E genotype is obtained followed by reassessment of risk of amyloid elevation. After an initial validation study, plasma amyloid peptide ratios will be included in this risk assessment. Based on this second risk calculation, individuals may have amyloid testing by PET scan or lumbar puncture, with those potentially eligible for trials followed in the TRC, while the rest are invited to remain in the APT Webstudy. To date, over 30,000 individuals have participated in the Webstudy; enrollment in the TRC is in its early stage.

Recruitment into the Alzheimer Prevention Trials (APT) Webstudy for a Trial-Ready Cohort for Preclinical and Prodromal Alzheimer's Disease (TRC-PAD).

BACKGROUND: The Alzheimer Prevention Trials (APT) Webstudy is the first stage in establishing a Trial-ready Cohort for Preclinical and Prodromal Alzheimer's disease (TRC-PAD). This paper describes recruitment approaches for the APT Webstudy. OBJECTIVES: To remotely enroll a cohort of individuals into a web-based longitudinal observational study. Participants are followed quarterly with brief cognitive and functional assessments, and referred to Sites for in-clinic testing and biomarker confirmation prior to enrolling in the Trial-ready Cohort (TRC). DESIGN: Participants are referred to the APT Webstudy from existing registries of individuals interested in brain health and Alzheimer's disease research, as well as through central and site recruitment efforts. The study team utilizes Urchin Tracking Modules (UTM) codes to better understand the impact of electronic recruitment methods. SETTING: A remotely enrolled online study. PARTICIPANTS: Volunteers who are at least 50 years old and interested in Alzheimer's research. MEASUREMENTS: Demographics and recruitment source of participant where measured by UTM. RESULTS: 30,650 participants consented to the APT Webstudy as of April 2020, with 69.7% resulting from referrals from online registries. Emails sent by the registry to participants were the most effective means of recruitment. Participants are distributed across the US, and the demographics of the APT Webstudy reflect the referral registries, with 73.1% female, 85.0% highly educated, and 92.5% Caucasian. CONCLUSIONS: We have demonstrated the feasibility of enrolling a remote web-based study utilizing existing registries as a primary referral source. The next priority of the study team is to engage in recruitment initiatives that will improve the diversity of the cohort, towards the goal of clinical trials that better represent the US population.

The Trial-Ready Cohort for Preclinical and Prodromal Alzheimer's Disease (TRC-PAD): Experience from the First 3 Years.

BACKGROUND: The Trial-Ready Cohort for Preclinical and Prodromal Alzheimer's disease (TRC-PAD) aims to accelerate enrollment for Alzheimer's disease (AD) clinical trials by remotely identifying and tracking individuals who are at high risk for developing symptoms of AD, and referring these individuals to in-person cognitive and biomarker evaluation with the purpose of engaging them in clinical trials. A risk algorithm using statistical modeling to predict brain amyloidosis will be refined as TRC-PAD advances with a maturing data set. OBJECTIVES: To provide a summary of the steps taken to build this Trial-Ready cohort (TRC) and share results of the first 3 years of enrollment into the program. DESIGN: Participants are remotely enrolled in the Alzheimer Prevention Trials (APT) Webstudy with quarterly assessments, and through an algorithm identified as potentially at high risk, referred to clinical sites for biomarker confirmation, and enrolled into the TRC. SETTING: Both an online study and in-clinic non-interventional cohort study. PARTICIPANTS: APT Webstudy participants are aged 50 or older, with an interest in participation in AD therapeutic trials. TRC participants must have a study partner, stable medical condition, and elevated brain amyloid, as measured by amyloid positron emission tomography or cerebrospinal fluid analysis. Additional risk assessments include apolipoprotein E genotyping. MEASUREMENTS: In the APT Webstudy, participants complete the Cognitive Function Index and Cogstate Brief Battery. The TRC includes the Preclinical Alzheimer's Cognitive Composite, comprised of the Free and Cued Selective Reminding Test, the Delayed Paragraph Recall score on the Logical Memory IIa test from the Wechsler Memory Scale, the Digit-Symbol Substitution test from the Wechsler Adult Intelligence Scale-Revised, and the Mini Mental State Examination total score (1). RESULTS: During the first 3 years of this program, the APT Webstudy has 30,650 consented participants, with 23 sites approved for in person screening, 112 participants have been referred for in-clinic screening visits with eighteen enrolled to the TRC. The majority of participants consented to APT Webstudy have a family history of AD (62%), identify as Caucasian (92.5%), have over twelve years of formal education (85%), and are women (73%). Follow up rates for the first quarterly assessment were 38.2% with 29.5% completing the follow up Cogstate Battery. CONCLUSIONS: After successfully designing and implementing this program, the study team's priority is to improve diversity of participants both in the APT Webstudy and TRC, to continue enrollment into the TRC to our target of 2,000, and to improve longitudinal retention, while beginning the process of referring TRC participants into clinical trials.

Regulation of cellular gas exchange, oxygen sensing, and metabolic control.

Cells must continuously monitor and couple their metabolic requirements for ATP utilization with their ability to take up O2 for mitochondrial respiration. When O2 uptake and delivery move out of homeostasis, cells have elaborate and diverse sensing and response systems to compensate. In this review, we explore the biophysics of O2 and gas diffusion in the cell, how intracellular O2 is regulated, how intracellular O2 levels are sensed and how sensing systems impact mitochondrial respiration and shifts in metabolic pathways. Particular attention is paid to how O2 affects the redox state of the cell, as well as the NO, H2S, and CO concentrations. We also explore how these agents can affect various aspects of gas exchange and activate acute signaling pathways that promote survival. Two kinds of challenges to gas exchange are also discussed in detail: when insufficient O2 is available for respiration (hypoxia) and when metabolic requirements test the limits of gas exchange (exercising skeletal muscle). This review also focuses on responses to acute hypoxia in the context of the original "unifying theory of hypoxia tolerance" as expressed by Hochachka and colleagues. It includes discourse on the regulation of mitochondrial electron transport, metabolic suppression, shifts in metabolic pathways, and recruitment of cell survival pathways preventing collapse of membrane potential and nuclear apoptosis. Regarding exercise, the issues discussed relate to the O2 sensitivity of metabolic rate, O2 kinetics in exercise, and influences of available O2 on glycolysis and lactate production.

Hyperthermia induces injury to the intestinal mucosa in the mouse: evidence for an oxidative stress mechanism.

Loss of the intestinal barrier is critical to the clinical course of heat illness, but the underlying mechanisms are still poorly understood. We tested the hypothesis that conditions characteristic of mild heatstroke in mice are associated with injury to the epithelial lining of the intestinal tract and comprise a critical component of barrier dysfunction. Anesthetized mice were gavaged with 4 kDa FITC-dextran (FD-4) and exposed to increasing core temperatures, briefly reaching 42.4°C, followed by 30 min recovery. Arterial samples were collected to measure FD-4 concentration in plasma (in vivo gastrointestinal permeability). The small intestines were then removed to measure histological evidence of injury. Hyperthermia resulted in a ≈2.5-fold elevation in plasma FD-4 and was always associated with significant histological evidence of injury to the epithelial lining compared with matched controls, particularly in the duodenum. When isolated intestinal segments from control animals were exposed to ≥41.5°C, marked increases in permeability were observed within 60 min. These changes were associated with release of lactate dehydrogenase, evidence of protein oxidation via carbonyl formation and histological damage. Coincubation with N-acetylcysteine protected in vitro permeability during hyperthermia and reduced histological damage and protein oxidation. Chelation of intracellular Ca(2+) to block tight junction opening during 41.5°C exposure failed to reduce the permeability of in vitro segments. The results demonstrate that hyperthermia exposure in mouse intestine, at temperatures at or below those necessary to induce mild heatstroke, cause rapid and substantial injury to the intestinal lining that may be attributed, in part, to oxidative stress.

Superoxide scavengers augment contractile but not energetic responses to hypoxia in rat diaphragm.

Acute exposure to severe hypoxia depresses contractile function and induces adaptations in skeletal muscle that are only partially understood. Previous studies have demonstrated that antioxidants (AOXs) given during hypoxia partially protect contractile function, but this has not been a universal finding. This study confirms that specific AOXs, known to act primarily as superoxide scavengers, protect contractile function in severe hypoxia. Furthermore, the hypothesis is tested that the mechanism of protection involves preservation of high-energy phosphates (ATP, creatine phosphate) and reductions of P(i). Rat diaphragm muscle strips were treated with AOXs and subjected to 30 min of hypoxia. Contractile function was examined by using twitch and tetanic stimulations and the degree of elevation in passive force occurring during hypoxia (contracture). High-energy phosphates were measured at the end of 30-min hypoxia exposure. Treatment with the superoxide scavengers 4,5-dihydroxy-1,3-benzenedisulfonic acid (Tiron, 10 mM) or Mn(III)tetrakis(1-methyl-4-pyridyl) porphyrin pentachloride (50 microM) suppressed contracture during hypoxia and protected maximum tetanic force. N-acetylcysteine (10 or 18 mM) had no influence on tetanic force production. Contracture during hypoxia without AOXs was also shown to be dependent on the extracellular Ca(2+) concentration. Although hypoxia resulted in only small reductions in ATP concentration, creatine phosphate concentration was decreased to approximately 10% of control. There were no consistent influences of the AOX treatments on high-energy phosphates during hypoxia. The results demonstrate that superoxide scavengers can protect contractile function and reduce contracture in hypoxia through a mechanism that does not involve preservation of high-energy phosphates.

Intraspecies and interspecies comparison of the compressive properties of the medial meniscus.

Quantification of the compressive material properties of the meniscus is of paramount importance, creating a "gold-standard" reference for future research. The purpose of this study was to determine compressive properties in six animal models (baboon, bovine, canine, human, lapine, and porcine) at six topographical locations. It was hypothesized that topographical variation of the compressive properties would be found in each animal model and that interspecies variations would also be exhibited. To test these hypotheses, creep and recovery indentation experiments were performed on the meniscus using a creep indentation apparatus and analyzed via a finite element optimization method to determine the material properties. Results show significant intraspecies and interspecies variation in the compressive properties among the six topographical locations, with the moduli exhibiting the highest values in the anterior portion. For example, the anterior location of the human meniscus has an aggregate modulus of 160 +/- 40 kPa, whereas the central and posterior portions exhibit aggregate moduli of 100 +/- 30 kPa. Interspecies comparison of the aggregate moduli identifies the lapine anterior location having the highest value (450 +/- 120 kPa) and the human posterior location having the lowest (100 +/- 30 kPa). These baseline values of compressive properties will be of help in future meniscal repair efforts.

Invited review: Adaptive responses of skeletal muscle to intermittent hypoxia: the known and the unknown.

Intermittent hypoxia (IH) describes conditions of repeated, transient reductions in O2 that may trigger unique adaptations. Rest periods during IH may avoid potentially detrimental effects of long-term O2 deprivation. For skeletal muscle, IH can occur in conditions of obstructive sleep apnea, transient altitude exposures (with or without exercise), intermittent claudication, cardiopulmonary resuscitation, neonatal blood flow obstruction, and diving responses of marine animals. Although it is likely that adaptations in these conditions vary, some patterns emerge. Low levels of hypoxia shift metabolic enzyme activity toward greater aerobic poise; extreme hypoxia shifts metabolism toward greater anaerobic potential. Some conditions of IH may also inhibit lactate release during exercise. Many related cellular phenomena could be involved in the response, including activation of specific O2 sensors, reactive oxygen and nitrogen species, preconditioning, hypoxia-induced transcription factors, regulation of ion channels, and influences of paracrine/hormonal stimuli. The net effect of a variety of adaptive programs to IH may be to preserve contractile function and cell integrity in hypoxia or anoxia, a response that does not always translate into improvements in exercise performance.

Selected Contribution: Improved anoxic tolerance in rat diaphragm following intermittent hypoxia.

Intermittent hypoxia (IH), associated with obstructive sleep apnea, initiates adaptive physiological responses in a variety of organs. Little is known about its influence on diaphragm. IH was simulated by exposing rats to alternating 15-s cycles of 5% O2 and 21% O2 for 5 min, 9 sets/h, 8 h/day, for 10 days. Controls did not experience IH. Diaphragms were excised 20-36 h after IH. Diaphragm bundles were studied in vitro or analyzed for myosin heavy chain isoform composition. No differences in maximum tetanic stress were observed between groups. However, peak twitch stress (P < 0.005), twitch half-relaxation time (P < 0.02), and tetanic stress at 20 or 30 Hz (P < 0.05) were elevated in IH. No differences in expression of myosin heavy chain isoforms or susceptibility to fatigue were seen. Contractile function after 30 min of anoxia (95% N2-5% CO2) was markedly preserved at all stimulation frequencies during IH and at low frequencies after 15 min of reoxygenation. Anoxia-induced increases in passive muscle force were eliminated in the IH animals (P < 0.01). These results demonstrate that IH induces adaptive responses in the diaphragm that preserve its function in anoxia.

NMR spin trapping: detection of free radical reactions with a new fluorinated DMPO analog.

Electron spin resonance (ESR) and nuclear magnetic resonance (NMR) spin trapping were used for detection of free radical reactions utilizing a new fluorinated analog of DMPO, 4-hydroxy-5,5-dimethyl-2-trifluoromethylpyrroline-1-oxide (FDMPO). The parent FDMPO spin trap exhibits a single 19F-NMR resonance at -66.0 ppm. The signal to noise ratio improved 10.4-fold compared to 31P-NMR sensitivity of the phosphorus-containing spin trap, DEPMPO. The spin adducts of FDMPO with .OH, .CH3, and .CH2OH were characterized. Competitive spin trapping of FDMPO with DMPO showed that both have similar rates of addition of .OH and C-centered radicals. The corresponding paramagnetic spin adducts of FDMPO were extremely stable to degradation. In the presence of ascorbate, reaction products from C-centered radicals resulted in the appearance of two additional 19F-NMR signals at -78.6 and -80 ppm for FDMPO/ .CH(3) and at -74.6 and -76.75 ppm for FDMPO/ .CH(2)OH. In each case, these peaks were assigned to the two stereoisomers of their respective, reduced hydroxylamines. The identification of the hydroxylamines for FDMPO/ .CH3 was confirmed by EPR and 19F-NMR spectra of independently synthesized samples. In summary, spin adducts of FDMPO were highly stable for ESR. For NMR spin trapping, FDMPO showed improved signal to noise and similar spin trapping efficiency compared to DEPMPO.

Unique in vivo applications of spin traps.

The ultimate goal of in vivo electron spin resonance (ESR) spin trapping is to provide a window to the characterization and quantification of free radicals with time within living organisms. However, the practical application of in vivo ESR to systems involving reactive oxygen radicals has proven challenging. Some of these limitations relate to instrument sensitivity and particularly to the relative stability of these radicals and their nitrone adducts, as well as toxicity limitations with dosing. Our aim here is to review the strengths and weaknesses of both traditional and in vivo ESR spin trapping and to describe new approaches that couple the strengths of spin trapping with methodologies that promise to overcome some of the problems, in particular that of radical adduct decomposition. The new, complementary techniques include: (i) NMR spin trapping, which monitors new NMR lines resulting from diamagnetic products of radical spin adduct degradation and reduction, (ii) detection of *NO by ESR with dithiocarbamate: Fe(II) "spin trap-like" complexes, (iii) MRI spin trapping, which images the dithiocarbamate: Fe(II)-NO complexes by proton relaxation contrast enhancement, and (iv) the use of ESR to follow the reactions of sulfhydryl groups with dithiol biradical spin labels to form "thiol spin label adducts," for monitoring intracellular redox states of glutathione and other thiols. Although some of these approaches are in their infancy, they show promise of adding to the arsenal of techniques to measure and possibly "image" oxidative stress in living organisms in real time.

Tibiotalocalcaneal arthrodesis.

The purpose of this multicenter retrospective study of 55 patients (56 ankles) who underwent simultaneous tibiotalocalcaneal arthrodesis with severe disease involving the ankle and subtalar joints was to determine improvement of pain and function. The surgical indications included osteoarthritis, posttraumatic injury, failed previous surgery, talar avascular necrosis, osteoarthritis, and rheumatoid arthritis involving the ankle and subtalar joints. The average age at the time of the operation was 53 years. The average time of follow-up was 26 months after the operation. Fusion was achieved in 48 ankles, with an average time of fusion of 19 weeks. Forty-eight of the 55 patients were satisfied with the procedure. The average leg length discrepancy was 1.4 cm. The average amount of dorsiflexion was 2 degrees and plantar flexion was 5 degrees. Following surgery, 42 patients complained of pain, 40 patients required shoe modification or an orthotic device, and 34 patients had a limp. Fourteen patients described their activity as unlimited. Based on the AOFAS evaluation, the patients scored an average of 66 on the ankle-hind foot scale following surgery. The most common complications were nonunion (8 ankles) and wound infection (6 ankles). This study demonstrates that tibiotalocalcaneal arthrodesis is an effective salvage procedure for patients with disease both involving the ankle and subtalar joints.

Intra- and extracellular measurement of reactive oxygen species produced during heat stress in diaphragm muscle.

Skeletal muscles are exposed to increased temperatures during intense exercise, particularly in high environmental temperatures. We hypothesized that heat may directly stimulate the reactive oxygen species (ROS) formation in diaphragm (one kind of skeletal muscle) and thus potentially play a role in contractile and metabolic activity. Laser scan confocal microscopy was used to study the conversion of hydroethidine (a probe for intracellular ROS) to ethidium (ET) in mouse diaphragm. During a 30-min period, heat (42 degrees C) increased ET fluorescence by 24 +/- 4%, whereas in control (37 degrees C), fluorescence decreased by 8 +/- 1% compared with baseline (P < 0.001). The superoxide scavenger Tiron (10 mM) abolished the rise in intracellular fluorescence, whereas extracellular superoxide dismutase (SOD; 5,000 U/ml) had no significant effect. Reduction of oxidized cytochrome c was used to detect extracellular ROS in rat diaphragm. After 45 min, 53 +/- 7 nmol cytochrome c. g dry wt(-1). ml(-1) were reduced in heat compared with 22 +/- 13 nmol. g(-1). ml(-1) in controls (P < 0.001). SOD decreased cytochrome c reduction in heat to control levels. The results suggest that heat stress stimulates intracellular and extracellular superoxide production, which may contribute to the physiological responses to severe exercise or the pathology of heat shock.

Surfactant treatment impairs gas exchange in a canine model of acute lung injury.

UNLABELLED: The effectiveness of surfactant (SURF) treatment in acute lung injury in the adult is controversial. In this study, we tested the effectiveness of early surfactant treatment in a commonly used animal model of acute lung injury, phorbol-myristate acetate (PMA), to see if it would attenuate the progression of lung injury. We measured the effect on lung compliance and whether positive end-expiratory pressure (PEEP) (10 cm H2O) during SURF administration had a synergistic effect. METHODS: Four groups of anesthetized dogs were studied: a) normals; b) PMA injury only; c) PMA injury + SURF; and d) PMA + SURF + PEEP. Lung injury was induced with 25-30 microg/kg of PMA. Responses were measured over 7 hrs. Surfactant was administered in the form of Survanta, 4 x 25 mg/kg doses via tracheal instillation 2.5 hrs after PMA. For the group receiving PEEP, 10 cm H2O PEEP was begun 1.5 hrs after PMA, 1 hr before SURF. Postmortem, the left lung was excised and inflated three times to total lung capacity (volume at 30 cm H2O) and expiratory compliance was measured with 25-100 mL volume increments. The trachea was then clamped and trapped volume was determined by water displacement. RESULTS: PMA-induced lung injury significantly reduced expiratory compliance and total lung capacity (p < .05 from normal). Wet/dry lung weights did not differ between groups. SURF without PEEP further decreased lung compliance as compared with PMA only. CONCLUSIONS: SURF administration after PMA injury causes marked reductions in lung compliance when no PEEP is coadministered. However, the loss of static expiratory lung compliance appears partly ameliorated by application of PEEP + SURF. Given that tracheal instillation of SURF is known to acutely elevate lung impedance in the first few hours after administration, coadministration of PEEP appears to be critically important in counteracting these early effects of surfactant instillation on the lung.

Increased susceptibility to pulmonary emphysema among HIV-seropositive smokers.

BACKGROUND: Previous uncontrolled reports have suggested that HIV-seropositive persons develop an accelerated form of emphysema. OBJECTIVE: To characterize the risk for emphysema in a stable HIV-seropositive outpatient population. DESIGN: Controlled, cross-sectional analysis. SETTING: Midwestern urban community. PARTICIPANTS: HIV-seropositive persons (n = 114) without AIDS-related pulmonary complications and HIV-seronegative controls (n = 44), matched for age and smoking history. MEASUREMENTS: Measurement of pulmonary function, bronchoalveolar lavage, and high-resolution computed tomography of the chest. RESULTS: The incidence of emphysema was 15% (17 of 114) in the HIV-seropositive group compared with 2% (1 of 44) in the HIV-seronegative group (P = 0.025). The incidence of emphysema in participants with a smoking history of 12 pack-years or greater was 37% (14 of 38 persons) in the HIV-seropositive group compared with 0% (0 of 14 persons) in the HIV-seronegative group (P = 0.011). The percentage of cytotoxic lymphocytes in lavage fluid was much higher in HIV-seropositive smokers with emphysema. CONCLUSIONS: Infection with HIV accelerates the onset of smoking-induced emphysema. The results of this study support the emerging concept that cytotoxic lymphocytes may have an important role in emphysema pathogenesis.

Oxidants and skeletal muscle function: physiologic and pathophysiologic implications.

Previous studies have demonstrated that skeletal muscles generate considerable reactive oxygen during intense muscle contraction. However, the significance of this phenomenon and whether it represents normal physiology or pathology are poorly understood. Treatment with exogenous antioxidants suggests that normal redox tone during contraction is influencing ongoing contractile function, both at rest and during intense exercise. This could represent the influence of redox-sensitive proteins responsible for excitation-contraction coupling or redox-sensitive metabolic enzymes. Some conditions associated with intense exercise, such as local tissue hypoxia or elevated tissue temperatures, could also contribute to reactive oxygen production. Evidence that muscle conditioning results in upregulation of antioxidant defenses also suggests a close relationship between reactive oxygen and contractile activity. Therefore, there appears to be a significant role for reactive oxygen in normal muscle physiology. However, a number of conditions may lead to an imbalance of oxidant production and antioxidant defense, and these, presumably, do create conditions of oxidant stress. Ischemia-reperfusion, severe hypoxia, severe heat stress, septic shock, and stretch-induced injury may all lead to oxidant-mediated injury to myocytes, resulting in mechanical dysfunction.

Focal air trapping in patients with HIV infection: CT evaluation and correlation with pulmonary function test results.

OBJECTIVE: HIV-positive individuals commonly have symptoms of airway disease. We evaluated thin-section CT scans of HIV-infected individuals during inspiration and expiration for evidence of focal air trapping. We also correlated imaging findings with pulmonary function test results. SUBJECTS AND METHODS: Fifty-nine subjects, 48 of whom were HIV-positive and 11 of whom were HIV-negative, underwent thin-section CT of the thorax during inspiration and expiration. All subjects also underwent pulmonary function tests. Two radiologists, who were unaware of the subjects' HIV status and smoking history and of the results of pulmonary function tests, evaluated the CT scans for the presence and severity of focal air trapping. RESULTS: Expiratory CT revealed focal air trapping in 33 subjects: 30 were HIV-positive and three were HIV-negative (p = .0338). The mean values of forced expiratory volume in 1 sec (FEV1), forced mid expiratory flow, and diffusion capacity (DL(CO)) were significantly lower for subjects with focal air trapping (mean = 88.85, 84.52, and 80.80, respectively) than for those with normal findings on CT (mean = 100.84, 99.24, and 95.82, respectively; p = .001, p = .021, and p = .003, respectively). We found no significant differences in smoking history between HIV-positive and HIV-negative subjects. Severe air trapping on expiratory CT scans was seen in three subjects: All three had HIV infection, low CD4 counts, and abnormally decreased FEV1 and DL(CO) values. CONCLUSION: Focal air trapping was a common finding on thoracic CT scans obtained during expiration in HIV-positive subjects. In addition, focal air trapping was associated with significantly lower FEV1, forced mid expiratory flow, and DL(CO) values than those found for subjects in whom CT revealed no focal air trapping. These results suggest that small airways disease may accompany a decline in pulmonary function in HIV-positive individuals.

NMR spin trapping: detection of free radical reactions using a phosphorus-containing nitrone spin trap.

This study employs (31)P-nuclear magnetic resonance (NMR) to probe for changes in molecular structure arising from reactions between free radicals and a phosphorus-containing nitrone spin trap, 5-diethoxyphosphoryl-5-methyl-1-pyrroline-N-oxide (DEPMPO). A number of biologically relevant free radical reactions were detected: a) reactions of DEPMPO with ( small middle dot)OH resulted in a new (31)P-NMR resonance at 27.05 ppm (shifted from the parent compound at 23.67 ppm); evidence suggests that this species is a diamagnetic hydroxy-pyrrolidone reduction product; b) (31)P-NMR spectra of DEPMPO/( small middle dot)CH(3) reactions resulted in peaks at 24.54, 30.83, and 32.31 ppm, while DEPMPO/( small middle dot)CH(2)OH produced peaks at 24.05, 30.80 and 32.52 ppm; in the presence of excess ascorbate, only resonances between 30 and 32 ppm were evident, which we have tentatively assigned to the hydroxylamine isomers of their respective adducts; and c) reaction of DEPMPO with O(2)( small middle dot-), produced by xanthine/xanthine oxidase or stimulated neutrophils, resulted in a single line, indistinguishable from DEPMPO/( small middle dot)OH reaction products. We conclude that NMR spin trapping is a useful approach for detecting free radical reaction pathways. It may have future applications for human free radical biology and imaging. Magn Reson Med 42:228-234, 1999.