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Biomedical subjects

Robert J Thomas

Publications and source records attributed to Robert J Thomas.

At least 19 recordsLinked to original sources
PubMed2006

Optical properties of ocular tissues in the near infrared region.

Near infrared characterization of optical properties of aqueous humor and vitreous humor of healthy human and bovine eyes has been performed. The indices of refraction (n) of these ocular tissues were determined using a Michelson interferometer. The total diffuse reflection (R (d)) and total transmission (T (t)) measurements had been taken for individual ocular tissue by using a double-integrating sphere setup and infrared laser diodes. The inverse adding doubling (IAD) computational method based on the diffusion approximation and radiative transport theory was applied to the measured values of n, R (d), and T (t) to calculate the optical absorption and scattering coefficients of the human and bovine ocular tissues. The scattering anisotropy value was determined by iteratively running the IAD method program and a Monte Carlo simulation of light-tissue interaction until the minimum difference in experimental and computed value for T (t) was realized. A comparison between the optical characterization of human and bovine ocular samples was also made.

Aged↗
PubMed2006

Damage Thresholds for Exposure to NIR and Blue Lasers in an In Vitro RPE Cell System.

PURPOSE: Until reliable nonanimal systems of analysis are available, animal models will be necessary for ocular laser hazard analysis and for evaluating clinical applications. The purpose of this work was to demonstrate the utility of an in vitro system for laser bioeffects by identifying photothermal and photochemical cytotoxicity thresholds for continuous-wave (cw) and mode-locked (ml) laser exposures. METHODS: Exogenous melanosomes were added to hTERT-RPE1 cells in exposure wells 1 day before laser exposure. Thermal or photochemical laser exposures were delivered to artificially pigmented retinal pigment epithelial (RPE) cultures, with subsequent assay for viability 1 hour after exposure. Beam delivery for the 1-hour photochemical exposures was via a modified culture incubator. The cytoprotective effect of pretreatment with two antioxidants was investigated. RESULTS: Phagocytosis of melanosomes by the RPE cells was efficient, yielding cultures of uniform pigmentation. The damage threshold for the thermal exposure was consistent with published in vivo results. Thresholds for both blue exposures (cw and ml) were identical. Overnight treatment of cells with ascorbic acid (AA) minimized cell death from both cw and ml blue laser exposure, whereas similar treatment with N-acetyl-L-cysteine (NAC) was less effective. CONCLUSIONS: The in vitro system described is suitable for measuring meaningful thermal and photochemical laser damage thresholds. The system is also useful in comparative laser bioeffects studies, such as comparisons between cw and ml laser exposures, cells with various degrees of pigmentation, and studies determining the efficacy and mechanisms of treatments altering the response of cells to lasers.

Acetylcysteine↗
PubMed2006

Adults with ADHD and sleep complaints: a pilot study identifying sleep-disordered breathing using polysomnography and sleep quality assessment.

OBJECTIVE: ADHD and sleep-disordered breathing are both prevalent in adulthood. Because both conditions may be responsible for similar symptoms of cognitive impairment, the authors investigate whether their presentation may overlap in adults diagnosed with ADHD. METHOD: Data are collected from six adults with sleep complaints who were diagnosed with ADHD using rigorous clinical criteria. All participants undergo overnight polysomnography and complete questionnaires about sleep quality, circadian sleep pattern, and daytime fatigue. RESULTS: On standardized measures, all participants report poor sleep quality, two report daytime fatigue, and none report distinct deviation from normal sleep and wake cycle pattern. Polysomnography reveals evidence of sleep-disordered breathing and sleep fragmentation in all participants. CONCLUSION: Objective evidence of breathing-related sleep disorders can be found in some adults with carefully diagnosed ADHD who report sleep complaints. This report highlights the importance of identifying treatable sleep disorder comorbidity in adults with ADHD.

Adult↗
PubMed2005

A preliminary study of sleep-disordered breathing in major depressive disorder.

BACKGROUND AND PURPOSE: Individuals with obstructive sleep-disordered breathing (OSDB) commonly report symptoms of depression; however, the percentage of individuals with major depressive disorder (MDD) who experience OSDB is less clear. This study aimed to examine OSDB in a sample of individuals with MDD, unselected for sleep-related complaints, along a continuum of ventilatory and hypoxic abnormalities. PATIENTS AND METHODS: The overnight sleep-related breathing of 19 individuals with MDD and 15 non-depressed controls was recorded using an unattended nasal pressure-based home sleep monitoring device. The device recorded nasal airflow, breathing effort, heart rate, oxygen saturation, and body position. RESULTS: The two groups varied significantly on three sleep-related breathing variables: major flow-limitation events, major flow-limitation events accompanied by a desaturation, and average saturation throughout the evening; and these groups approached significance on minor flow-limitation events accompanied by a desaturation and average number of desaturations throughout the evening. Sleep-related breathing variables predicted accurate grouping in 81.3% of those with MDD and 80.6% of the non-depressed participants. CONCLUSIONS: These results suggest that OSDB may play a more important role in MDD than previously recognized. OSDB may contribute to or exacerbate the condition of someone predisposed to MDD, and the treatment of OSDB may ameliorate or possibly prevent depressive symptoms.

Adult↗
PubMed2005

Functional imaging of working memory in obstructive sleep-disordered breathing.

Functional magnetic resonance imaging was used to map cerebral activation in 16 patients with obstructive sleep-disordered breathing (OSDB) and 16 healthy subjects, during the performance of a 2-back verbal working memory task. Six patients with OSDB were reimaged after a minimum period of 8 wk of treatment with positive airway pressure. Working memory speed in OSDB was significantly slower than in healthy subjects, and a group average map showed absence of dorsolateral prefrontal activation, regardless of nocturnal hypoxia. After treatment, resolution of subjective sleepiness contrasted with no significant change in behavioral performance, persistent lack of prefrontal activation, and partial recovery of posterior parietal activation. These findings suggest that working memory may be impaired in OSDB and that this impairment is associated with disproportionate impairment of function in the dorsolateral prefrontal cortex. Nocturnal hypoxia may not be a necessary determinant of cognitive dysfunction, and sleep fragmentation may be sufficient. There may be dissociations between respiratory vs. cortical recovery and objective vs. subjective recovery. Hypofrontality may provide a plausible biological mechanism for a clinical overlap with disorders of mood and attention.

Adult↗
PubMed2005

Reorganization of sleep patterns in severe OSAS under prolonged CPAP treatment.

OBJECTIVE: To evaluate the immediate and long-term recovery processes of sleep and daytime vigilance in patients with sleep apnea syndrome (OSAS) after continuous CPAP treatment. METHODS: Five consecutive polysomnographic (PSG) studies were carried out on 10 male patients with severe OSAS. The first recording (baseline) was accomplished without ventilatory support (N0). The other 4 recordings were carried out during the CPAP titration night (N1), during the second night of treatment (N2), during the third night of treatment (N3), and after 30 days of regular CPAP use (N30). Ten age-balanced healthy male subjects were selected from the Parma Sleep Center database as controls. Respiratory variables, conventional PSG variables, arousals, CAP (cyclic alternating pattern) variables, and daytime function (including MSLT) were quantified. ANOVA followed by post-hoc tests explored the differences between controls and OSAS patients in the different recording conditions (N0, N1, N2, N3, N30). The PSG measures that showed significant ANOVA values were correlated with the MSLT scores. RESULTS: Values of control subjects were recovered by REM sleep, REM latency, subtypes A3 and arousal index during N1, by CAP rate and total arousals during N2, by deep sleep (stages 3 + 4) during N3, by light sleep (stages 1 + 2) during N30. The only measures which remained below control values even after 1 month of sustained treatment were the amount of CAP cycles and A1 subtypes. MSLT scores correlated significantly with CAP rate, deep sleep and arousals. CONCLUSIONS: The changes induced by CPAP treatment do not restore immediately a normal sleep structure, which is re-established with different time scales SIGNIFICANCE: The modifications of sleep patterns and the different adjustments of phase A subtypes allow us to monitor the reorganization of sleep in OSAS patients treated with CPAP and the hierarchy of the mechanisms involved in sleep regulation.

Adult↗
PubMed2005

Fatigue in the executive cortical network demonstrated in narcoleptics using functional magnetic resonance imaging--a preliminary study.

BACKGROUND AND PURPOSE: To demonstrate dynamic changes in cerebral functional activation during a working memory task in a state of severe excessive daytime sleepiness. PATIENTS AND METHODS: Omitting the usual morning dose of stimulants in three narcoleptics induced sleepiness. Functional magnetic resonance imaging (fMRI) was used to map cerebral activation during the performance of a 2-back verbal working memory task. Repeated 9.5 min scans were performed, until the subjects felt they could not continue. This was the functional imaging equivalent of the maintenance of wakefulness test. RESULTS: Bilateral and widespread activation in known nodes of the executive network were seen during the first scan in all subjects, including the lateral prefrontal, posterior parietal and anterior cingulate cortex. There was a reduction in cerebral activation, especially but not exclusively in the prefrontal cortex, associated with slowing of performance from the first to the last tolerated scan. On stimulants, subjective alertness, activation and objective performance were readily maintained. CONCLUSION: This preliminary study suggests that fatigue in the executive cortical network may be demonstrated by a progressive reduction in regional cerebral activation across scans, which may be prevented by stimulant use. Averaging multiple scan runs, a typical practice in fMRI, could blur important dynamic components of activation.

Adult↗
PubMed2005

Recognition and management of complex sleep-disordered breathing.

PURPOSE OF REVIEW: The recent rapid evolution of our understanding of the mechanisms involved in control of respiration during sleep has yielded new insights to guide our care of difficult-to-treat sleep apnea patients with complex sleep-disordered breathing. This review will describe these recent advances in the literature and suggest a model for their incorporation into clinical practice. RECENT FINDINGS: Control of respiration during sleep shows amplified instability relative to that seen during wake in these difficult patients. Baseline (eupneic) carbon dioxide levels as well as the responsiveness of the ventilatory system to changes in carbon dioxide are all-important in this relative instability. Furthermore, the instability seen during sleep varies widely across sleep states. A further refinement of our definition of stable and unstable sleep has been developed that directly informs our understanding of the control of respiration across a night of sleep. SUMMARY: Complex sleep-disordered breathing is a distinct form of sleep apnea. It has recognizable characteristics that are present without, and often worsened during, positive airway pressure treatment. Both sleep state stability and the behavior of the respiratory control system contribute to this complexity. It is only with a clear understanding of the factors contributing to complex sleep-disordered breathing that implementation of truly effective clinical therapy can be achieved for this disorder, which to date is poorly controlled.

Acetazolamide↗
PubMed2005

The effect of three-dimensional co-culture of hepatocytes and hepatic stellate cells on key hepatocyte functions in vitro.

In this study, we demonstrate the ability of a three-dimensional co-culture model to preserve some key aspects of differentiated hepatocyte function in vitro. Freshly isolated rat hepatocytes in co-culture with activated stellate cells rapidly aggregate to form well-defined viable spheroids. After 5 days in culture, the spheroids have a complex extracellular matrix support and hepatic ultrastructure including bile canaliculi, tight junctions, desmosomes and lipid storage. Co-culture spheroids have superior cytochrome P450 (CYP450) 3A and 2B function, and increased inducibility of 2B function, relative to a range of hepatocyte monoculture techniques (high-performance liquid chromatography of testosterone metabolites). Increased function in co-culture is supported by greater expression of CYP450 3A23, 1A2, and 2E1 mRNA relative to monoculture (reverse transcriptase quantitative polymerase chain reaction). Also, high hepatocyte growth factor mRNA expression in co-culture suggests a post-traumatic, or possibly regenerative, environment. A preliminary study of human hepatocytes co-cultured with rat stellate cells demonstrated prolonged function of CYP450 3A4, 2C19 and 2C9. This study shows that stellate cells facilitate spheroid formation, influence spheroid architecture, and are an effective method of preserving some aspects of hepatocyte function in the early stage of culture.

Animals↗
PubMed2005

Perspective: the evolution of warning coloration is not paradoxical.

Animals that are brightly colored have intrigued scientists since the time of Darwin, because it seems surprising that prey should have evolved to be clearly visible to predators. Often this self-advertisement is explained by the prey being unprofitable in some way, with the conspicuous warning coloration helping to protect the prey because it signals to potential predators that the prey is unprofitable. However, such signals only work in this way once predators have learned to associate the conspicuous color with the unprofitability of the prey. The evolution of warning coloration is still widely considered to be a paradox, because it has traditionally been assumed that the very first brightly colored individuals would be at an immediate selective disadvantage because of their greater conspicuousness to predators that are naive to the meaning of the signal. As a result, it has been difficult to understand how a novel conspicuous color morph could ever avoid extinction for long enough for predators to become educated about the signal. Thus, the traditional view that the evolution of warning coloration is difficult to explain rests entirely on assumptions about the foraging behavior of predators. However, we review recent evidence from a range of studies of predator foraging decisions, which refute these established assumptions. These studies show that: (1) Many predators are so conservative in their food preferences that even very conspicuous novel prey morphs are not necessarily at a selective disadvantage. (2) The survival and spread of novel color morphs can be simulated in field and aviary experiments using real predators (birds) foraging on successive generations of artificial prey populations. This work demonstrates that the foraging preferences of predators can regularly (though not always) result in the increase to fixation of a novel morph appearing in a population of familiar-colored prey. Such fixation events occur even if both novel and familiar prey are fully palatable and despite the novel food being much more conspicuous than the familiar prey. These studies therefore provide strong empirical evidence that conspicuous coloration can evolve readily, and repeatedly, as a result of the conservative foraging decisions of predators.

Adaptation, Physiological↗
PubMed2004

Sub-50-fs laser retinal damage thresholds in primate eyes with group velocity dispersion, self-focusing and low-density plasmas.

BACKGROUND: In vivo retinal injury studies using sub-50-femtosecond laser pulses in the near-infrared must consider nonlinear effects such as group velocity dispersion (GVD), self-focusing, laser-induced breakdown (LIB) and low-density plasmas (LDPs). In this paper we present the results of our theoretical calculations of nonlinear effects and our experimental measurements for the visible lesion thresholds in live eyes. We compare these values with the measured LIB and LDP thresholds in an artificial eye. All three thresholds were measured with and without pre-chirping the input pulse to compensate for GVD effects. METHODS: We recorded the minimum visible lesion (MVL) thresholds in vivo for sub-50-fs laser pulses, with and without pre-chirping the input pulses. In addition, we measured the LIB and LDP thresholds, with and without pre-chirping, within an artificial eye. Different degrees of pre-chirping were required to give optimal compensation for GVD in the live eye and the artificial eye. Probit analysis was used on all data, and comparisons among thresholds were made, to determine the effects on the three thresholds of chirp compensation for GVD. RESULTS: Results of our nonlinear modeling and calculations for GVD compensation, self-focusing, LIB, and low-density plasmas were compared with our experimental results using live eyes and the artificial eye. The damage threshold in live eyes dropped in energy from 0.25 microJ, for the flat-phase input, to 0.17 microJ when optimally chirped pulses were used, while the LIB threshold was reduced from 0.29 microJ to 0.19 microJ with optimally chirped pulses. The LDP threshold dropped from 0.21 microJ to 0.14 microJ with the pre-chirped pulse. At 44 fs, these energies produced peak powers at least twice the calculated critical power that produces nonlinear self-focusing and beam collapse, for propagation of non-aberrated gaussian beams in a uniform medium. CONCLUSIONS: Based on our measurements of the MVL thresholds, with and without GVD compensation, we conclude that the visible lesion thresholds produced by 44 fs pulses in rhesus eyes are increased in energy due to GVD. The MVL ED50 was reduced by one third when the pulse was pre-chirped to compensate for GVD in the eye. This reduction in amplitude also holds true in the artificial eye for the LIB ED50 bubble thresholds and the LDP ED50 plasma channels, when using pre-chirped pulses versus non-chirped pulses. We also conclude from the data presented that low-density plasmas, and not LIB cavitation bubbles, are the probable mediating factor at the visible lesion thresholds observed within live eyes, for pulse durations at and below 50 fs. Therefore, the plasma channel created by LDPs is the major damage mechanism, if not the only damage mechanism, at MVL threshold energies for these pulse durations.

Animals↗
PubMed2004

Obstructive sleep-disordered breathing with a dominant cyclic alternating pattern--a recognizable polysomnographic variant with practical clinical implications.

OBJECTIVES: To define the clinical and polysomnographic features of a distinct variant of obstructive sleep-disordered breathing that is remarkably mild during rapid eye movement (REM) sleep. DESIGN: Observational study and evaluation of polysomnographic and clinical records. SETTING: American Academy of Sleep Medicine-accredited multidisciplinary sleep disorders center and laboratory. PATIENTS: 35 medication-free subjects with clinical and polysomnographic severe obstructive sleep-disordered breathing selected for dominance of 1 of 2 disordered breathing patterns. INTERVENTIONS: Positive airway pressure titration. MEASUREMENTS AND RESULTS: Nasal pressure was used to score respiratory events. Sleep was scored by both the standard criteria and cyclic alternating pattern (CAP), and the distribution of respiratory events was tabulated and analyzed. A distinct clinical and polysomnographic syndrome emerged, CAP-dominant sleep-disordered breathing, characterized by severe relatively short cycle obstructive events during non-REM sleep that were mild in REM sleep. Characteristics include lower body mass index, fewer apneas, and a lower hypoxic burden as reflected by frequency and severity of nocturnal oxygen saturation. During positive pressure titration, a remarkable respiratory instability emerged selectively during CAP, in contrast to stability during REM sleep. This partial treatment failure was associated with persistent clinical symptoms. CONCLUSIONS: This variant of sleep apnea may reflect a dominant component of respiratory instability and periodic breathing coupled with upper-airway obstruction. Its existence questions the conventional practice of calculating global respiratory indexes. Besides positive airway pressure, measures to treat periodic breathing may be required.

Electroencephalography↗
PubMed2004

Mechanisms of arousal from sleep and their consequences.

PURPOSE OF REVIEW: In recent years, understanding of the mechanisms by which sleep is maintained and the consequences of abnormal arousal from sleep has improved rapidly. This review describes the recent insights into the nature of sleep and arousal and the particular insights gained in common disease states such as sleep-disordered breathing. RECENT FINDINGS: Expansion of the definitions of the classic stages of non-REM and REM sleep to include consideration of the role of cyclic alternating pattern sleep as a gating mechanism for arousal and maintenance of stable sleep has led to a significant advancement in understanding the nature of normal and pathologic arousals from sleep. In addition, the effect of arousals from sleep on cerebral cortical electrophysiology and autonomic activation has been further defined, with a potential effect on clinical practice. SUMMARY: Arousal from sleep is dependent on wake-promoting influences overwhelming forces promoting sleep. Autonomic activation and cortical arousal can significantly affect and destabilize sleep homeostasis. The understanding of sleep-respiration interactions continues to evolve. The definition of the minimal arousal event is an important research goal. It will be important in clinical practice and research to consider sleep stability domains as a complement to sleep depth staging to allow better understanding of the relative stability and instability of the system and to consider all components of the consequences of arousal.

Arousal↗
PubMed2002

Eye size in birds and the timing of song at dawn.

Why do different species of birds start their dawn choruses at different times? We test the hypothesis that the times at which different species start singing at dawn are related to their visual capability at low light intensities. Birds with large eyes can achieve greater pupil diameters and hence, all other things being equal, greater visual sensitivity and resolution than birds with small eyes. We estimated the maximum pupil diameter of passerine birds by measuring the diameter of the exposed eye surface, and measured the times of the first songs at dawn of songbirds present in different bird communities, and the light intensities at these times. Using phylogenetic comparative analyses, we found that songbirds with large eyes started to sing at lower light intensities (and therefore earlier) than species with smaller eyes. These relationships were stronger when differences in body size were controlled for statistically, and were consistent between two phylogenies and when species were treated as independent data points. Our results therefore provide robust support for the hypothesis that visual capability at low light levels influences the times at which birds start to sing at dawn.

Animals↗
PubMed2002

A comparative study of retinal effects from continuous wave and femtosecond mode-locked lasers.

BACKGROUND AND OBJECTIVES: In order to provide a direct comparison of the effects of mode-locked systems to those with continuous-wave (CW) or nonpulsed output, we have performed an experiment with lasers possessing otherwise identical output characteristics. This in vivo minimum visible lesion study compares retinal effects of mode-locked and CW lasers complete with histopathology of the treated areas. STUDY DESIGN/MATERIALS AND METHODS: Titanium:Sapphire lasers produced 800-nm output for either mode-locked (76 MHz repetition rate, 120 femtoseconds) or CW exposures. Alternating CW and mode-locked laser exposures were delivered to the paramacular retinal region of rhesus subjects. Laser exposure duration was set to one-quarter second for both types of exposures. Through ophthalmoscopic examination of the fundus, a minimal visible lesion (MVL) threshold for damage was established. RESULTS: Approximately 75 test sites for each type of exposure were examined. The laser dosage thresholds and 95% confidence intervals for minimal visible damage at 24 hours postexposure were found to be 5.9 mJ (5.23-6.6 mJ) and 5.84 mJ (5.23-6.58 mJ) for mode-locked and CW exposures, respectively. CONCLUSIONS: Results are compared with published studies conducted at similar exposures. These nearly identical damage thresholds indicate a primarily thermal tissue damage mechanism. Comparative histopathology of acute and chronic lesions of both exposure types is also presented.

Animals↗
PubMed2002

Thresholds for retinal injury from multiple near-infrared ultrashort laser pulses.

Multiple-pulse lasers are routinely used in the laboratory for research, manufacturing, medical procedures, and in military applications. In order to provide a safe work environment for personnel using these lasers, safety standards have been established and have been in use for many years. These safety standards have addressed laser pulses of nanosecond duration and longer. Recently, safety standards have been updated to address laser pulses as short as 100 femtoseconds in duration. In order to tie these "ultrashort" laser pulses to hazard trends in currently established standards for multiple-pulse exposures with repetition rates less than several kilohertz, this experiment was conducted. Reported herein are minimum visible lesion thresholds in the paramacula of the primate retina using an 800-nm wavelength laser with 1,000 pulses per second, at 130 femtoseconds (fs) pulse duration. The minimum visible lesion (MVL) thresholds were determined at 1 h and 24 h post exposure for 1, 10, 100, 1,000, and 10,000 pulses and are compared with thresholds reported by other researchers. These new data are evaluated relative to the current safety standards for retinal exposure limits as a function of the number of pulses for femtosecond-pulse duration. Data from this study show that the retinal ED50 thresholds/pulse in the paramacula decrease by almost a factor of four as the number of pulses goes from one to ten and then decrease very little for an increase of three decades more in the number of pulses. The MVL-ED50 at the threshold decreased from 0.55 microJ for a single pulse to 0.15 microJ/pulse for 10 pulses and then only to 0.11 microJ/pulse for 10,000 pulses.

Animals↗
PubMed2002

Crucibles of leadership.

What makes a great leader? Why do some people appear to know instinctively how to inspire employees--bringing out their confidence, loyalty, and dedication--while others flounder again and again? No simple formula can explain how great leaders come to be, but Bennis and Thomas believe it has something to do with the ways people handle adversity. The authors' recent research suggests that one of the most reliable indicators and predictors of true leadership is the ability to learn from even the most negative experiences. An extraordinary leader is a kind of phoenix rising from the ashes of adversity stronger and more committed than ever. In interviewing more than 40 leaders in business and the public sector over the past three years, the authors discovered that all of them--young and old alike--had endured intense, often traumatic, experiences that transformed them and became the source of their distinctive leadership abilities. Bennis and Thomas call these shaping experiences "crucibles," after the vessels medieval alchemists used in their attempts to turn base metals into gold. For the interviewees, their crucibles were the points at which they were forced to question who they were and what was important to them. These experiences made them stronger and more confident and changed their sense of purpose in some fundamental way. Through a variety of examples, the authors explore the idea of the crucible in detail. They also reveal that great leaders possess four essential skills, the most critical of which is "adaptive capacity"--an almost magical ability to transcend adversity and emerge stronger than before.

Cultural Diversity↗