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1.
J Urol ; 211(6): 765-774, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38573938

ABSTRACT

PURPOSE: Our purpose was to determine changes in patient-reported hematuria and urinary symptoms after hyperbaric oxygen (HBO2) treatment for radiation cystitis (RC). MATERIALS AND METHODS: We analyzed prospectively collected data from the Multicenter Registry for Hyperbaric Oxygen Therapy Consortium accumulated within a week of beginning and ending HBO2. Measures included the modified Radiation Therapy Oncology Group (RTOG) Hematuria Scale, Urinary Distress Inventory Short Form, and EuroQol Five Dimension Five Level instrument. RTOG hematuria and Urinary Distress Inventory Short Form scores were compared using the sign test. Logistic regression was used to evaluate characteristics associated with hematuria improvement. RESULTS: A total of 470 registry patients had RC. The median age, number of HBO2 sessions, and years after radiation were 73 (IQR 12) years, 39 (IQR 10) sessions, and 5 (IQR 8) years, respectively. Eighty-four percent of patients (393/470) had prostate cancer‒related radiation. EuroQol Five Dimension Five Level scores improved from 0.83 (IQR 0.14) to 0.85 (IQR 0.22; P < .001. Three hundred seventy patients had complete RTOG hematuria scores that improved from 2 (IQR 2) to 0 (IQR 2; P < .001. Two hundred forty-six patients had complete Urinary Distress Inventory Short Form ratings that decreased from 33.3 (IQR 44) to 22.2 (IQR 33; P < .001). Regression analysis of those with visible hematuria before HBO2 showed lower improvement odds associated with higher HBO2 hematuria scores (odds ratio [OR] 0.44, 95% CI 0.26-0.73; P < .01), a smoking history (OR 0.44, 95% CI 0.21-0.92; P = .03), or a nonprostate cancer history (OR 0.32, 95% CI 0.10-0.99; P = .05). CONCLUSIONS: HBO2 for RC improved reported hematuria, urinary function, and quality of life. Higher baseline hematuria scores, smoking, and nonprostate cancer history were associated with lower odds of hematuria improvement.


Subject(s)
Cystitis , Hematuria , Hyperbaric Oxygenation , Patient Reported Outcome Measures , Radiation Injuries , Registries , Humans , Cystitis/therapy , Cystitis/etiology , Male , Aged , Radiation Injuries/therapy , Hematuria/etiology , Hematuria/therapy , Female , Middle Aged , Prospective Studies , Prostatic Neoplasms/radiotherapy , Prostatic Neoplasms/therapy , Prostatic Neoplasms/complications , Quality of Life , Aged, 80 and over , Treatment Outcome
2.
Int J Audiol ; 63(3): 207-212, 2024 Mar.
Article in English | MEDLINE | ID: mdl-36662150

ABSTRACT

OBJECTIVE: This exploratory study examined whether central auditory tests show differences between people living with HIV (PLWH) treated with two predominant antiretroviral drug therapy (ART) regimens. DESIGN: Cross-sectional. STUDY SAMPLE: 253 PLWH (mean age 39.8 years) from the Shanghai Public Health Clinical Centre, China. METHODS: The Hearing in Noise Test speech reception threshold (SRT) assessed central auditory function and the Montreal Cognitive Assessment (MoCA) assessed cognition. The relationship between ART regimen and SRT was evaluated with multivariable linear regression incorporating age, HIV duration, and peripheral hearing ability. Multivariable logistic regression was used to ascertain if SRT and ART regimen predicted MoCA impairment. RESULTS: The two predominant ART regimens differed by one drug (zidovudine or tenofovir). Participants taking the zidovudine-containing regimen had poorer SRT performance (p=.012) independent of age and hearing thresholds. MoCA scores did not differ between drug regimens, but a negative relationship was found between SRT and MoCA impairment (p=.048). CONCLUSIONS: ART regimens differed in their association with central auditory test performance likely reflecting neurocognitive changes in PLWH taking the zidovudine-containing regimen. Central auditory test performance also marginally predicted cognitive impairment, supporting further assessment of central auditory tests to detect neurocognitive deficits in PLWH.


Subject(s)
HIV Infections , Speech Perception , Adult , Humans , Zidovudine/therapeutic use , Cross-Sectional Studies , China , Hearing Tests , HIV Infections/complications , HIV Infections/drug therapy , HIV Infections/psychology
3.
J Tissue Viability ; 33(3): 449-451, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38851917

ABSTRACT

INTRODUCTION: Pyoderma gangrenosum (PG) is a rare, difficult-to-treat neutrophilic ulcerative cutaneous condition that severely impacts those affected. Treatment options for PG are limited, and disease remission is not guaranteed. Hyperbaric oxygen treatment is a potential therapeutic option for treating various ulcerative conditions not frequently utilized for PG. CASE REPORT: We present a case of a patient with treatment-resistant PG who achieved remission with adjunctive HBOT, and then later had difficulty achieving remission without HBOT during a future flare. DISCUSSION: HBOT should be more readily considered as a treatment option for those with PG.


Subject(s)
Hyperbaric Oxygenation , Pyoderma Gangrenosum , Humans , Pyoderma Gangrenosum/therapy , Hyperbaric Oxygenation/methods , Female , Middle Aged , Male
4.
Curr Opin Nephrol Hypertens ; 32(2): 172-176, 2023 Mar 01.
Article in English | MEDLINE | ID: mdl-36683542

ABSTRACT

PURPOSE OF REVIEW: Weightlessness increases both bone loss and kidney stone formation risk. The large interior volume of the International Space Station (ISS) has allowed for a mix of exercise devices to help maintain the skeleton. But space exploration is changing. Long stays on the ISS will be replaced by journeys in smaller spacecraft both to and around the Moon. Small private space stations are under development. This will limit the ability to do exercise countermeasures, which can increase both bone loss and kidney stone risk. This review examines this risk and how it can be minimized in this new era of spaceflight. RECENT FINDINGS: Simple, low-mass, low-power ways to track bone loss and kidney stone risk in space are being researched. Tracking urinary calcium concentration in the first morning void and targeting additional countermeasures (e.g. bisphosphonates) to those who run consistently high levels is one promising approach. SUMMARY: New exploration spacecraft would not have the room and capability to replicate the current 2 h, daily exercise countermeasure programme on the ISS. A monitoring approach, perhaps using urinary calcium as a marker, is needed to find those at greatest risk. This would allow countermeasures to be targeted individually and used efficiently.


Subject(s)
Bone Diseases, Metabolic , Kidney Calculi , Space Flight , Weightlessness , Humans , Weightlessness/adverse effects , Calcium , Spacecraft , Kidney Calculi/etiology
5.
Int J Audiol ; 62(5): 383-392, 2023 05.
Article in English | MEDLINE | ID: mdl-35521916

ABSTRACT

OBJECTIVE: This study's objective was determining whether gap detection deficits are present in a longstanding cohort of people living with HIV (PLWH) compared to those living without HIV (PLWOH) using a new gap detection modelling technique (i.e. fitting gap responses using the Hill equation and analysing the individual gap detection resulting curves with non-linear statistics). This approach provides a measure of both gap threshold and the steepness of the gap length/correct detection relationship. DESIGN: The relationship between the correct identification rate at each gap length was modelled using the Hill equation. Results were analysed using a nonlinear mixed-effect regression model. STUDY SAMPLE: 45 PLWH (age range 41-78) and 39 PLWOH (age range 38-79) were enrolled and completed gap detection testing. RESULTS: The likelihood ratio statistic comparing the full regression model with the HIV effects to the null model, assuming one population curve for both groups, was highly significant (p < 0.001), suggesting a less precise relationship between gap length and correct detection in PLWH. CONCLUSIONS: PLWH showed degraded gap detection ability compared to PLWOH, likely due to central nervous system effects of HIV infection or treatment. The Hill equation provided a new approach for modelling gap detection ability.


Subject(s)
HIV Infections , Humans , Adult , Middle Aged , Aged , HIV Infections/epidemiology , Nonlinear Dynamics , Surveys and Questionnaires
6.
Int J Audiol ; 62(3): 209-216, 2023 03.
Article in English | MEDLINE | ID: mdl-35130458

ABSTRACT

OBJECTIVE: Automated threshold audiometry (ATA) could increase access to paediatric hearing assessment in low- and middle-income countries, but few studies have evaluated test-retest repeatability of ATA in children. This study aims to analyse test-retest repeatability of ATA and to identify factors that affect the reliability of this method. DESIGN: ATA was performed twice in a cohort of Nicaraguan schoolchildren. During testing, the proportion of responses occurring in the absence of a stimulus was measured by calculating a stimulus response false positive rate (SRFP). Absolute test-retest repeatability was determined between the two trials, as well as the impact of age, gender, ambient noise, head circumference, and SRFP on these results. STUDY SAMPLE: 807 children were randomly selected from 35 schools in northern Nicaragua. RESULTS: Across all frequencies, the absolute value of the difference between measurements was 5.5 ± 7.8 dB. 89.6% of test-retest differences were within 10 dB. Intra-class correlation coefficients between the two measurements showed that lower SRFP was associated with improved repeatability. No effect of age, gender, or ambient noise was found. CONCLUSIONS: ATA produced moderate test-retest repeatability in Nicaraguan schoolchildren. Participant testing behaviours, such as delayed or otherwise inappropriate response patterns, significantly impacts the repeatability of these measurements.


Subject(s)
Audiometry , Noise , Humans , Child , Reproducibility of Results , Audiometry, Pure-Tone/methods , Auditory Threshold/physiology
7.
Ear Hear ; 43(4): 1222-1227, 2022.
Article in English | MEDLINE | ID: mdl-35044995

ABSTRACT

OBJECTIVE: HIV positive (HIV+) individuals with otherwise normal hearing ability show central auditory processing deficits as evidenced by worse performance in speech-in-noise perception compared with HIV negative (HIV-) controls. HIV infection and treatment are also associated with lower neurocognitive screening test scores, suggesting underlying central nervous system damage. To determine how central auditory processing deficits in HIV+ individuals relate to brain alterations in the cortex involved with auditory processing, we compared auditory network (AN) functional connectivity between HIV+ adults with or without speech-in-noise perception difficulties and age-matched HIV- controls using resting-state fMRI. DESIGN: Based on the speech recognition threshold of the hearing-in-noise test, twenty-seven HIV+ individuals were divided into a group with speech-in-noise perception abnormalities (HIV+SPabnl, 38.2 ± 6.8 years; 11 males and 2 females) and one without (HIV+SPnl 34.4 ± 8.8 years; 14 males). An HIV- group with normal speech-in-noise perception (HIV-, 31.3 ± 5.2 years; 9 males and 3 females) was also enrolled. All of these younger and middle-aged adults had normal peripheral hearing determined by audiometry. Participants were studied using resting-state fMRI. Independent component analysis was applied to identify the AN. Group differences in the AN were identified using statistical parametric mapping. RESULTS: Both HIV+ groups had increased functional connectivity (FC) in parts of the AN including the superior temporal gyrus, middle temporal gyrus, supramarginal gyrus, and Rolandic operculum compared to the HIV- group. Compared with the HIV+SPnl group, the HIV+SPabnl group showed greater FC in parts of the AN including the middle frontal and inferior frontal gyri. CONCLUSIONS: The classical auditory areas in the temporal lobe are affected by HIV regardless of speech perception ability. Increased temporal FC in HIV+ individuals might reflect functional compensation to achieve normal primary auditory perception. Furthermore, increased frontal FC in the HIV+SPabnl group compared with the HIV+SPnl group suggest that speech-in-noise perception difficulties in HIV-infected adults also affect areas involved in higher-level cognition, providing imaging evidence consistent with the hypothesis that HIV-related neurocognitive deficits can include central auditory processing deficits.


Subject(s)
Auditory Cortex , HIV Infections , Speech Perception , Adult , Audiometry , Auditory Threshold/physiology , Female , HIV Infections/complications , Humans , Male , Middle Aged , Noise , Speech Perception/physiology
8.
J Oral Maxillofac Surg ; 80(4): 728-735.e2, 2022 04.
Article in English | MEDLINE | ID: mdl-34953770

ABSTRACT

We describe a rare case of intraosseous sarcoidosis initially presenting as peri-implantitis, perform a review and analysis of 27 cases of intraosseous sarcoidosis, and provide a clinical review of this condition. We searched the literature for patients presenting with intraosseous sarcoidosis of the jaw through June 2020 using key phrases. Additional papers were included via a search of references and citing papers. Data including patient demographic characteristics and diagnostic tests were manually extracted from the cases and then qualitatively coded by the authors. Descriptive statistical analysis was performed to elucidate general themes and characteristics. A total of 27 cases, dating as early as 1943 and as recent as this case, were identified in the literature, including our case. The average age of these patients was 39 years old, with a range of 16 to 75 years. Eighteen (67%) cases were identified as female and nine (33%) as male. Fourteen cases were reported with localized mandibular involvement. Ten had maxillary disease; 3 cases were generalized to both regions. Nine cases presented anteriorly, 12 posteriorly, and 6 extended across both regions. Eight patients received surgical interventions, such as tooth extractions or lesion removal. Five patients received nonsurgical interventions, such as steroids. Ten patients received combination therapy, often involving surgical intervention and steroid therapy. Our patient had an unusual presentation of intraosseous sarcoidosis mimicking peri-implantitis. To our knowledge, no case in the English literature describes a patient with sarcoidosis presenting with peri-implantitis. Based on the literature review and analysis of our patient's experience, sarcoidosis should be considered on the differential diagnosis for patients with persistent, nonhealing bony lesions in the maxillofacial region, particularly when patients have not been exposed to osteoclast inhibitory therapy or radiation. Pathologic analysis of bone and surrounding tissue in these scenarios is essential.


Subject(s)
Dental Implants , Peri-Implantitis , Sarcoidosis , Adolescent , Adult , Aged , Dental Implants/adverse effects , Diagnosis, Differential , Female , Humans , Male , Mandible , Middle Aged , Peri-Implantitis/diagnostic imaging , Sarcoidosis/diagnostic imaging , Young Adult
9.
J Acoust Soc Am ; 152(4): 2257, 2022 10.
Article in English | MEDLINE | ID: mdl-36319232

ABSTRACT

Although a causal relationship exists between military occupational noise exposure and hearing loss, researchers have struggled to identify and/or characterize specific operational noise exposures that produce measurable changes in hearing function shortly following an exposure. Growing evidence suggests that current standards for noise-exposure limits are not good predictors of true hearing damage. In this study, the aim was to capture the dose-response relationship during military rifle training exercises for noise exposure and hearing threshold. To capture exposure, a wearable system capable of measuring impulse noise simultaneously on-body and in-ear, behind hearing protection was used. To characterize hearing threshold changes, portable audiometry was employed within 2 h before and after exposure. The median 8-h time-weighted, protected, free-field equivalent in-ear exposure was 87.5 dBA at one site and 80.7 dBA at a second site. A significant dose-response correlation between in-ear noise exposure and postexposure hearing threshold changes across our population ( R = 0.40 , p = 0.0281) was observed. The results demonstrate an approach for establishing damage risk criteria (DRC) for in-ear, protected measurements based on hearing threshold changes. While an in-ear DRC does not currently exist, it may be critical for predicting the risk of injury for noise environments where protection is mandatory and fit status can vary.


Subject(s)
Hearing Loss, Noise-Induced , Military Personnel , Noise, Occupational , Occupational Exposure , Humans , Noise, Occupational/prevention & control , Prospective Studies , Hearing , Auditory Threshold/physiology
10.
Int J Audiol ; 61(3): 187-196, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34107827

ABSTRACT

OBJECTIVE: Sampling distortion product otoacoustic emissions (DPOAEs) at multiple f2/f1 ratios and f2 frequency values produces a DPOAE "map." This study examined the efficacy of DPOAE mapping compared with pure tone audiometry and standard DPOAEs for detecting noise effects in subjects exposed to loud sound. DESIGN: A map significance score was developed as a single measure of map change. Significance scores were evaluated before and after exposure to: loud music (LM), controlled noise (CN), and firing range noise (FR) in three separate sets of subjects. Scores were compared to audiometry and standard DPOAE results in the LM study. STUDY SAMPLE: The LM and CN exposure studies involved 22, and 20 healthy young subjects respectively with normal hearing. Eight Marines were studied before and after FR exposure. RESULTS: After LM exposure, audiometry showed significant changes at 1, 2, 4, and 6 kHz. Standard DPOAE measures were also significantly different at several frequencies. Map significance scores detected changes more effectively and showed the distribution of DPOAE alterations. CONCLUSIONS: Map significance scores detected changes after noise exposure more reliably than audiometry and standard DPOAEs. Additionally, maps showed a diffuse response to sound exposure perhaps explaining why individual DP-grams appear less sensitive.


Subject(s)
Music , Otoacoustic Emissions, Spontaneous , Audiometry, Pure-Tone/methods , Auditory Threshold/physiology , Humans , Noise/adverse effects , Otoacoustic Emissions, Spontaneous/physiology
11.
Undersea Hyperb Med ; 49(3): 275-287, 2022.
Article in English | MEDLINE | ID: mdl-36001560

ABSTRACT

Introduction: The International Multicenter Registry for Hyperbaric Oxygen Therapy (International Report Registered Identifier DERR1-10.2196/18857) was established in 2011 to capture outcomes and complications data for both Undersea and Hyperbaric Medical Society (UHMS) approved and selected unapproved hyperbaric oxygen (HBO2) therapy indications. Methods: A Research Electronic Data Capture (REDCap) template was designed and distributed to all participating centers for prospective data collection. Centers contributed de-identified demographic, treatment, complications, and outcome data. This report provides summary data on sites and enrollment, as well as pre- and post-treatment data on quality of life (EQ-5D-5L questionnaire), head and neck radiationoutcomes, non-healing wounds (Strauss score), and idiopathic sudden sensorineural hearing loss. Data were analyzed mainly using the Wilcoxon signed-rank test. Results: Twenty-two centers contributed data for 2,880 patients. The most common UHMS-approved indication was delayed radiation injury, followed by enhancement of wound healing, and carbon monoxide poisoning. One hundred and twenty-five patients were treated for non-UHMS approved indications. Quality of life, head and neck radiation symptoms, Strauss wound scores, and hearing were significantly improved after HBO2. Complication rates were low and comparable to previous reports. The registry also offered the ability to analyze factors that affect outcomes, such as smoking and severity of hearing loss. Discussion: The registry accrues prospective data on defined outcomes from multiple centers and allows for analysis of factors affecting outcomes. This registry does not have a control group, which is a limitation. Nevertheless, the registry provides a unique, comprehensive dataset on HBO2 outcomes from multiple centers internationally.


Subject(s)
Carbon Monoxide Poisoning , Hearing Loss, Sudden , Hyperbaric Oxygenation , Carbon Monoxide Poisoning/therapy , Hearing Loss, Sudden/therapy , Humans , Hyperbaric Oxygenation/methods , Oxygen/adverse effects , Quality of Life , Registries
12.
Ophthalmology ; 128(2): 309-316, 2021 02.
Article in English | MEDLINE | ID: mdl-32659310

ABSTRACT

PURPOSE: The spaceflight-associated neuro-ocular syndrome (SANS) affects astronauts on missions to the International Space Station (ISS). The SANS has blurred vision and ocular changes as typical features. The objective of this study was to investigate if microgravity can create deformations or movements of the eye or optic nerve, and if such changes could be linked to SANS. DESIGN: Cohort study. PARTICIPANTS: Twenty-two astronauts (age 48 ± 4 years). METHODS: The intervention consisted of time in microgravity at the ISS. We co-registered pre- and postspaceflight magnetic resonance imaging (MRI) scans and generated centerline representations of the optic nerve. The coordinates for the optic nerve head (ONH) and optic chiasm (OC) ends of the optic nerve were recorded along with the entire centerline path. MAIN OUTCOME MEASURES: Optic nerve length, ONH movement, and OC movement after time in microgravity. RESULTS: Optic nerve length increased (0.80 ± 0.74 mm, P < 0.001), primarily reflecting forward ONH displacement (0.63 ± 0.53 mm, P < 0.001). The forward displacement was positively related to mission duration, preflight body weight, and clinical manifestations of SANS. We also detected upward displacement of the OC (0.39 ± 0.50 mm, P = 0.002), indicative of brain movement, but this observation could not be linked to SANS. CONCLUSIONS: The spaceflight-induced optic nerve lengthening and anterior movement of the ONH support that SANS is caused by an altered pressure difference between the brain and the eye, leading to a forward push on the posterior of the eye. Body weight is a potential contributing risk factor. Direct assessment of intracranial pressure in space is required to verify the implicated mechanism behind the ocular findings in SANS.


Subject(s)
Optic Disk/pathology , Optic Nerve/pathology , Papilledema/etiology , Space Flight , Vision Disorders/etiology , Weightlessness/adverse effects , Astronauts , Cohort Studies , Extraterrestrial Environment , Female , Humans , Intracranial Pressure , Magnetic Resonance Imaging , Male , Middle Aged , Optic Disk/diagnostic imaging , Optic Nerve/diagnostic imaging , Papilledema/diagnostic imaging , Syndrome , Time Factors , Vision Disorders/diagnostic imaging
13.
Int J Audiol ; 60(7): 555-560, 2021 07.
Article in English | MEDLINE | ID: mdl-33043734

ABSTRACT

OBJECTIVE: Distortion product otoacoustic emission (DPOAE) mapping characterises cochlear function, can include both the 2f1-2f2 and 2f2-2f1 DPOAEs, and shows promise for tracking cochlear changes. DPOAE amplitude measurements are not as repeatable longitudinally as pure-tone audiometry, likely due in part to probe placement sensitivity. We hypothesised that DPOAE level map variation over multiple testing sessions could be minimised by replacing traditional rubber tips with custom-moulded probe tips. DESIGN: Traditional rubber tips (TRT) and custom-moulded probes tips (CMPT) were used to measure DPOAE level maps repeatedly over five sessions. Probe placement was assessed using a frequency sweep in the ear canal. Repeatability of the DPOAE level maps was assessed using a Bland-Altman analysis. Overall map repeatability was assessed by measuring differences in distortion product amplitude over sessions. STUDY SAMPLE: Crossover study with a convenience sample size of six adults. RESULTS: The CMPT frequency sweeps showed reduced variability in probe placement. The repeatability coefficient for individual DPOAEs measurements improved from 6.9 dB SPL with the TRT to 5.1 dB SPL with the CMPT. Map repeatability improved for most subjects with the CMPT.


Subject(s)
Cochlea , Otoacoustic Emissions, Spontaneous , Acoustic Stimulation , Adult , Audiometry, Pure-Tone , Cross-Over Studies , Culture , Humans
14.
Undersea Hyperb Med ; 48(1): 1-12, 2021.
Article in English | MEDLINE | ID: mdl-33648028

ABSTRACT

The SARS-Cov-2 (COVID-19) pandemic remains a major worldwide public health issue. Initially, improved supportive and anti-inflammatory intervention, often employing known drugs or technologies, provided measurable improvement in management. We have recently seen advances in specific therapeutic interventions and in vaccines. Nevertheless, it will be months before most of the world's population can be vaccinated to achieve herd immunity. In the interim, hyperbaric oxygen (HBO2) treatment offers several potentially beneficial therapeutic effects. Three small published series, one with a propensity-score-matched control group, have demonstrated safety and initial efficacy. Additional anecdotal reports are consistent with these publications. HBO2 delivers oxygen in extreme conditions of hypoxemia and tissue hypoxia, even in the presence of lung pathology. It provides anti-inflammatory and anti-proinflammatory effects likely to ameliorate the overexuberant immune response common to COVID-19. Unlike steroids, it exerts these effects without immune suppression. One study suggests HBO2 may reduce the hypercoagulability seen in COVID patients. Also, hyperbaric oxygen offers a likely successful intervention to address the oxygen debt expected to arise from a prolonged period of hypoxemia and tissue hypoxia. To date, 11 studies designed to investigate the impact of HBO2 on patients infected with SARS-Cov-2 have been posted on clinicaltrials.gov. This paper describes the promising physiologic and biochemical effects of hyperbaric oxygen in COVID-19 and potentially in other disorders with similar pathologic mechanisms.


Subject(s)
COVID-19/therapy , Hyperbaric Oxygenation/methods , COVID-19/blood , COVID-19/complications , COVID-19/immunology , Cell Hypoxia , Cytokine Release Syndrome/immunology , Cytokines/blood , Humans , Hypoxia/therapy , Inflammation/therapy , Mesenchymal Stem Cells , Oxygen/poisoning , Oxygen Consumption , Thrombophilia/etiology , Thrombophilia/therapy
15.
Magn Reson Med ; 81(2): 781-794, 2019 02.
Article in English | MEDLINE | ID: mdl-30277275

ABSTRACT

PURPOSE: Transcutaneous oxygen tension (TcpO2 ) provides information about blood perfusion in the tissue immediately below the skin. These data are valuable in assessing wound healing problems, diagnosing peripheral vascular/arterial insufficiency, and predicting disease progression or the response to therapy. Currently, TcpO2 is primarily measured using electrochemical skin sensors, which consume oxygen and are prone to calibration errors. The goal of the present study was to develop a reliable method for TcpO2 measurement in human subjects. METHODS: We have developed a novel TcpO2 oximetry method based on electron paramagnetic resonance (EPR) principles with an oxygen-sensing skin adhesive film, named the superficial perfusion oxygen tension (SPOT) chip. The SPOT chip is a 3-mm diameter, 60-µm thick circular film composed of a stable paramagnetic oxygen sensor. The chip is covered with an oxygen-barrier material on one side and secured on the skin by a medical adhesive transfer tape to ensure that only the oxygen that diffuses through the skin surface is measured. The method quantifies TcpO2 through the linewidth of the EPR spectrum. RESULTS: Repeated measurements using a cohort of 10 healthy human subjects showed that the TcpO2 measurements were robust, reliable, and reproducible. The TcpO2 values ranged from 7.8 ± 0.8 to 22.0 ± 1.0 mmHg in the volar forearm skin (N = 29) and 8.1 ± 0.3 to 23.4 ± 1.3 mmHg in the foot (N = 86). CONCLUSIONS: The results demonstrated that the SPOT chip can measure TcpO2 reliably and repeatedly under ambient conditions. The SPOT chip method could potentially be used to monitor TcpO2 in the clinic.


Subject(s)
Oxygen/analysis , Skin/blood supply , Adhesives , Adolescent , Adult , Arterial Occlusive Diseases/physiopathology , Calibration , Cohort Studies , Electron Spin Resonance Spectroscopy , Female , Foot , Forearm , Healthy Volunteers , Humans , Male , Middle Aged , Oxygen/blood , Peripheral Vascular Diseases/physiopathology , Reproducibility of Results , Skin Physiological Phenomena , Temperature , Wound Healing , Young Adult
17.
Article in English | MEDLINE | ID: mdl-29229641

ABSTRACT

Recent estimates suggest that more than 3 million people have chronic or invasive fungal infections, causing more than 600,000 deaths every year. Aspergillus fumigatus causes invasive pulmonary aspergillosis (IPA) in patients with compromised immune systems and is a primary contributor to increases in human fungal infections. Thus, the development of new clinical modalities as stand-alone or adjunctive therapy for improving IPA patient outcomes is critically needed. Here we tested the in vitro and in vivo impacts of hyperbaric oxygen (HBO) (100% oxygen, >1 atmosphere absolute [ATA]) on A. fumigatus proliferation and murine IPA outcomes. Our findings indicate that HBO reduces established fungal biofilm proliferation in vitro by over 50%. The effect of HBO under the treatment conditions was transient and fungistatic, with A. fumigatus metabolic activity rebounding within 6 h of HBO treatment being removed. In vivo, daily HBO provides a dose-dependent but modest improvement in murine IPA disease outcomes as measured by survival analysis. Intriguingly, no synergy was observed between subtherapeutic voriconazole or amphotericin B and HBO in vitro or in vivo with daily HBO dosing, though the loss of fungal superoxide dismutase genes enhanced HBO antifungal activity. Further studies are needed to optimize the HBO treatment regimen and better understand the effects of HBO on both the host and the pathogen during a pulmonary invasive fungal infection.


Subject(s)
Antifungal Agents/pharmacology , Aspergillus fumigatus/pathogenicity , Hyperbaric Oxygenation/methods , Animals , Antifungal Agents/therapeutic use , Aspergillosis/drug therapy , Aspergillosis/microbiology , Aspergillus fumigatus/drug effects , Biofilms/drug effects , Disease Models, Animal , Reactive Oxygen Species/metabolism
18.
Am J Gastroenterol ; 113(10): 1516-1523, 2018 10.
Article in English | MEDLINE | ID: mdl-29453383

ABSTRACT

BACKGROUND: Hyperbaric oxygen therapy (HBOT) markedly increases tissue oxygen delivery. Case series suggest it may have a potential therapeutic benefit in ulcerative colitis (UC). We investigated the therapeutic potential of HBOT as an adjunct to steroids for UC flares requiring hospitalization. METHODS: The study was terminated early due to poor recruitment with 18 of the planned 70 patients enrolled. UC patients hospitalized for moderate-severe flares (Mayo score ≥6, endoscopic sub-score ≥2) were block randomized to steroids + daily HBOT (n = 10) or steroids + daily sham hyperbaric air (n = 8). Patients were blinded to study assignment, and assessments were performed by a blinded gastroenterologist. Primary outcome was the clinical remission rate at study day 5 (partial Mayo score ≤2 with no sub-score >1). Key secondary outcomes were: clinical response (reduction in partial Mayo score ≥2, rectal bleeding sub-score of 0-1) and progression to second-line therapy (colectomy or biologic therapy) during the hospitalization. RESULTS: A significantly higher proportion of HBOT-treated patients achieved clinical remission at study day 5 and 10 (50 vs. 0%, p = 0.04). HBOT-treated patients less often required progression to second-line therapy during the hospitalization (10 vs. 63%, p = 0.04). The proportion requiring in-hospital colectomy specifically as second-line therapy for medically refractory UC was lower in the HBOT group compared to sham (0 vs. 38%, p = 0.07). There were no serious adverse events. CONCLUSION: In this small, proof-of-concept, phase 2A trial, the use of HBOT as an adjunctive therapy to steroids for UC patients hospitalized for moderate-severe flares resulted in higher rates of clinical remission, and a reduction in rates of progression to second-line therapy during the hospitalization. Larger well-powered trials are needed, however, to provided definitive evidence of therapeutic benefit.


Subject(s)
Biological Products/administration & dosage , Colectomy/statistics & numerical data , Colitis, Ulcerative/therapy , Glucocorticoids/administration & dosage , Hyperbaric Oxygenation/adverse effects , Adult , Colitis, Ulcerative/diagnosis , Combined Modality Therapy/adverse effects , Combined Modality Therapy/methods , Disease Progression , Double-Blind Method , Drug Resistance , Female , Gastrointestinal Hemorrhage , Glucocorticoids/adverse effects , Hospitalization , Humans , Male , Middle Aged , Pilot Projects , Proof of Concept Study , Remission Induction/methods , Severity of Illness Index , Symptom Flare Up , Treatment Outcome , Young Adult
19.
Am J Physiol Regul Integr Comp Physiol ; 315(3): R496-R499, 2018 09 01.
Article in English | MEDLINE | ID: mdl-29768035

ABSTRACT

On Earth, tissue weight generates compressive forces that press on body structures and act on the walls of vessels throughout the body. In microgravity, tissues no longer have weight, and tissue compressive forces are lost, suggesting that individuals who weigh more may show greater effects from microgravity exposure. One unique effect of long-duration microgravity exposure is spaceflight-associated neuroocular syndrome (SANS), which can present with globe flattening, choroidal folds, optic disk edema, and a hyperopic visual shift. To determine whether weight or other anthropometric measures are related to ocular changes in space, we analyzed data from 45 individual long-duration astronauts (mean age 47, 36 male, 9 female, mean mission duration 165 days) who had pre- and postflight measures of disk edema, choroidal folds, and manifest ocular refraction. The mean preflight weights of astronauts who developed new choroidal folds [78.6 kg with no new folds vs. 88.6 kg with new folds ( F = 6.2, P = 0.02)] and disk edema [79.1 kg with no edema vs. 95 kg with edema ( F = 9.6, P = 0.003)] were significantly greater than those who did not. Chest and waist circumferences were also significantly greater in those who developed folds or edema. The odds of developing disk edema or new choroidal folds were 55% in the highest- and 9% in the lowest-weight quartile. In this cohort, no women developed disk edema or choroidal folds, although women also weighed significantly less than men [62.9 vs. 85.2 kg ( F = 53.2, P < 0.0001)]. Preflight body weight and anthropometric factors may predict microgravity-induced ocular changes.


Subject(s)
Astronauts , Body Weight , Choroid Diseases/etiology , Eye/physiopathology , Papilledema/etiology , Space Flight , Vision Disorders/etiology , Vision, Ocular , Weightlessness/adverse effects , Choroid Diseases/diagnosis , Choroid Diseases/physiopathology , Female , Humans , Male , Papilledema/diagnosis , Papilledema/physiopathology , Risk Factors , Time Factors , Vision Disorders/diagnosis , Vision Disorders/physiopathology
20.
Ear Hear ; 39(3): 548-554, 2018.
Article in English | MEDLINE | ID: mdl-29112532

ABSTRACT

OBJECTIVES: Human immunodeficiency virus positive (HIV+) individuals report hearing difficulties, but standard audiological tests show no, or small, changes in peripheral hearing ability. The hearing complaints may reflect central nervous system (CNS) auditory processing deficits, rather than middle or inner ear problems, and may result from CNS damage due to HIV infection or treatment. If central auditory task performance and cognitive deficits in HIV+ individuals are shown to be related, then central auditory tests might serve as a "window" into CNS function in these patients. DESIGN: We measured cognitive performance (Mandarin Montreal Cognitive Assessment [MoCA]) and speech in noise perception (Mandarin hearing-in-noise test [HINT]) in 166 normal-hearing HIV+ individuals (158 men, 8 women, average age 36 years) at the Shanghai Public Health Clinical Center in Shanghai, China. Data collection included audiometry, tympanometry, and the Amsterdam Inventory of Auditory Handicap (AIAH), which assesses the subjective ability to understand speech and localize sound. RESULTS: Subjects had no middle ear disease and met criteria for normal-hearing sensitivity (all thresholds 20 dB HL or less). A significant negative relationship between speech reception thresholds (SRT) and MoCA scores (r = 0.15, F = 28.2, p < 0.001) existed. Stepwise linear regression showed that when the factors of age, MoCA scores, hearing thresholds, and education level were considered, only age and MoCA scores contributed independently to the SRT results (overall model r = 0.30, F = 38.8, p < 0.001). Subjective hearing complaints from the AIAH supported the HINT results. AIAH and MoCA scores were also related (r = 0.05, F = 8.5, p = 0.004), with those with worse MoCA scores having more problems on the AIAH. When the cohort was divided into those with normal and abnormal performance on the MoCA, those with abnormal performance on the MoCA had significantly higher average SRTs (p < 0.001). CONCLUSIONS: Understanding speech in noise measured both objectively with the HINT and subjectively with the AIAH was inversely related to cognitive abilities despite a normal ability to hear soft sounds determined by audiometry. Although age was also an important independent factor affecting speech perception, the age relationship within the speech findings in this study may represent more than just age-related declines in speech in noise understanding. Although reliable data on disease duration are not available, the older members of this cohort likely had HIV longer and probably had more severe symptoms at presentation than the younger members because early detection and treatment of HIV in Shanghai has improved over time. Therefore, the age relationship may also include elements of disease duration and severity. Speech perception, especially in challenging listening conditions, involves cortical and subcortical centers and is a demanding neurological task. The problems interpreting speech in noise HIV+ individuals have may reflect HIV-related or HIV treatment-related, central nervous damage, suggesting that CNS complications in HIV+ individuals could potentially be diagnosed and monitored using central auditory tests.


Subject(s)
Cognitive Dysfunction/diagnosis , HIV Infections/psychology , Hearing Loss/etiology , Noise , Speech Perception , Acoustic Impedance Tests , Adult , Age Factors , Audiometry , Cognitive Dysfunction/etiology , Female , HIV Infections/complications , Hearing Loss/diagnosis , Humans , Linear Models , Male , Middle Aged , Perceptual Masking , Surveys and Questionnaires , Young Adult
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