Phototherapy and photochemotherapy of skin diseases

One important aspect of photomedicine is the use of nonionizing electromagnetic radiation with and without exogenous photosensitizers to treat diseases. Phototoxicity (cell injury by photons) is a likely mechanism for phototherapy and photochemotherapy of several skin diseases. The mechanism of action for phototherapy of hyperbilirubinemia and of uremic pruritus appears to be photochemical alteration of extracellular metabolites. Psoriasis is an example of a disease benefitted by several forms of phototherapy and photochemotherapy with varying relative effectiveness and safety. Two successful forms of treatment are oral psoralen photochemotherapy and UVB plus topical adjunctive agents. New information about UVB therapy of psoriasis includes data about the therapeutic action spectrum and about the relative roles of various topical agents such as coal tar, mineral oil, "lubricants" and steroids. Although there are many surface similarities, phototherapy and psoralen photochemotherapy have fundamental differences which may alter longterm risks in quantitative and qualitative ways.     

Effects of water temperature on photosensitization in bath-PUVA therapy with 8-methoxypsoralen

The pharmacokinetic aspects of bath-PUVA are not completely clarified. Therefore, we determined the phototoxic response of human skin following psoralen baths at temperatures ranging from 32 degrees C to 42 degrees C (71.6-107.6 degrees F) and UVA doses ranging from 0.5 to 5.5 J/cm2. The highest therapeutical photosensitization (i.e., lowest minimal phototoxic dose) was assessed at temperatures of 37 degrees C (98.6 degrees F) and above. Photosensitization was significantly decreased at lower temperatures. These data indicate that a bath temperature of 37 degrees C (98.6 degrees F) should be used to gain optimal therapeutic efficiency in a clinical setting. Furthermore, in order to minimize the risk of adverse phototoxic effects in bath-PUVA, it is important to use a constant temperature during the psoralen bath.     

Time course of comparison.

Presents similarity as interactive activation and mapping (SIAM), a model of the dynamic course of similarity comparisons. According to SIAM, when structured scenes are compared, the parts of one scene must be aligned, or placed in correspondence, with the parts from the other scene. Emerging correspondences influence each other in a manner such that, with sufficient time, the strongest correspondences are those that are globally consistent with other correspondences. Relative to globally inconsistent feature matches, globally consistent feature matches influence similarity more when greater amounts of time are given for a comparison. A common underlying process model of scene alignment accounts for commonalities between different task conditions. Differences between task conditions are accounted for by principled parametric variation within the model. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Time course of apoptosis in collagen-induced arthritis

A heterodox model of healing incorporating the basic dualism of Western philosophy--the world of concrete material substance versus that of thought, ideals, and spirit--is proposed. Such dualism is reflected in Western constructions of healing. An explanatory paradigm model with a horizontal axis representing paradigms of healing from positivism to metaphysics and a vertical axis representing activities of healing from the material to the spiritual was derived from ethnographic work with healers. A health practice model following the same philosophical patterns illustrates reflected American cultural values in the relative positioning of healing modalities from the orthodox biomedical to the most metaphysical or alternative. Examples of specific modalities of healing, many of which are resurfacing with increasing public interest in alternative therapies, are illustrated. This model places biomedicine in the same context as other philosophical approaches to healing as a standard for comparison. Implications for practice and research are discussed.     

Time course of cocaine in rabbit hair

The accurate interpretation of analytical results from hair testing for drugs of abuse continues to be a complex and difficult problem since many questions still remain unanswered. In this paper an animal model was developed to ascertain the time course for the appearance and disappearance of cocaine and its metabolite benzoylecgonine (BE) in hair. Female Fauve Bourgogne red-haired rabbits (n = 6) were intraperitoneally administered a single dose of cocaine at 5 mg/kg. Animal hair was shaved just before drug administration and the newly grown back hair was subsequently shaved and collected daily over a period of two weeks. Samples were analyzed for cocaine and BE by gas chromatography-mass spectrometry (GC-MS). The profiles were quite similar for parent drug and metabolite. Cocaine and BE appeared in the first sampling (day 1), with peak concentration appearing that same day. 1.01 ng/mg and 0.51 ng/mg for cocaine and BE, respectively. Levels declined rapidly on day 2, remaining detectable for ten days after drug administration. This study demonstrates that the initial incorporation of cocaine compounds in rabbit hair is very rapid (24 h). A small fraction of the drug is detected ten days after exposure, at a time when concentrations in other biological specimens (blood or urine) are not detectable.     

Time course of simultaneous masking in the starling's auditory forebrain

Simultaneous masking of pure tones was studied in the primary auditory forebrain of a songbird species, the European starling (Sturnus vulgaris). The responses of 32 multi-unit clusters in the input layer of the auditory neostriatum (field L2a) were recorded via radiotelemetry from freely moving birds. The probe was a 10-ms tone burst at the units' characteristic-frequency (CF) presented 20 dB above the threshold. The masker was an 80-ms tone burst presented either at the units' CF (excitatory masker) or at a frequency located in inhibitory side-bands (inhibitory masker) of the units' tuning curves. The probe was presented either 3 ms or 63 ms after masker onset. Probes presented at a 3-ms delay were influenced at significantly lower levels of an excitatory masker than probes presented at a 63-ms delay. The mean difference in masker level at the detection thresholds for both probe delays was 8 dB. No difference in masker level was observed for inhibitory-frequency maskers. The observed neural masking effects may be explained by at least four mechanisms: (1) swamping of the probe response by the response to the masker, (2) a reduction of the probe response during neural adaptation of the response to the masker, (3) a reduction of the probe response during side-band inhibition in the central nervous system, and (4) suppression originating in the cochlea.     

Time course of nerve-fiber regeneration in the noise-damaged mammalian cochlea

The time course of events which are essential for nerve-fiber regeneration in the mammalian cochlea was determined using a group of chinchillas that had been exposed for 3.5 hr to an octave band of noise with a center frequency of 4 kHz and a sound pressure level of 108 dB. The animals recovered from 40 min (0 days) to 100 days at which times their inner ears were fixed and the organs of Corti prepared for phase-contrast and bright-field microscopy as plastic-embedded flat preparations. Selected areas identified in the flat preparations were semi-thick and thin sectioned at radial or tangential angles for examination by bright-field and transmission electron microscopy. The following time-ordered events appeared critical for nerve-fiber regeneration: (1) The area of the basilar membrane in which regeneration had a possibility of occurring showed signs of severe injury. Outer hair cells degenerated first followed by outer pillars, inner pillars, inner hair cells and other supporting cells; (2) Myelinated nerve fibers in the osseous spiral lamina became fragmented, starting at the distal ends of the fibers. This degeneration gradually extended back to Rosenthal's canal; (3) Fibrous processes, originating from Schwann-like cells in the osseous spiral lamina, extended laterally on the basilar membrane; (4) Schwann cells lined up medial to the habenulae perforata in the areas of severest damage, apparently ready to migrate through the habenulae onto the basilar membrane; (5) Schwann-cell nuclei appeared on the basilar membrane beneath the developing layer of squamous epithelium which was in the process of replacing the degenerated portion of the organ of Corti; (6) Regenerated nerve fibers with thin myelin sheaths or a simple investment of Schwann cell cytoplasm appeared in areas of total loss of the organ of Corti; and (7) The myelin sheaths on the regenerated nerve fibers gradually became thicker.     

Time course of symptom resolution in patients with community-acquired pneumonia

The majority of patients with community-acquired pneumonia are at low risk for short-term mortality or serious morbidity and are increasingly managed in the outpatient setting. Efforts to improve the quality of care for these patients will need to measure patient outcomes such as disease-specific symptom resolution. The aims of this study were to (1) develop a self-administered daily version of a symptom questionnaire for patients with pneumonia, (2) measure the reliability of this instrument, and (3) provide estimates for recovery rates based on symptom resolution in a cohort of low-risk patients with community-acquired pneumonia. This study was conducted as part of a prospective study of a new emergency department protocol for pneumonia at the Massachusetts General Hospital. Eligible study subjects included all adult patients with pneumonia presenting to the emergency department with a predicted low risk of short-term mortality. The main outcome measures were based on a new five item symptom questionnaire which rates the severity of cough, fatigue, dyspnea, myalgia, and fever. The questionnaires were self-administered on days 0-7, 14, 21 and 28 from the time of diagnosis of pneumonia. The symptom questions were also administered during patient interviews on days 0, 7, 14 and 28 in order to assess the questionnaire's reliability. Of the 166 eligible patients, 134 (81%) consented to participate in this study. The mean intra-class reliability coefficient of the symptom questionnaire was 0.75. The median times to resolution of individual symptoms ranged from 3 days for fever to 14 days for cough and fatigue. Thirty-five percent of patients had at least one symptom still present at the end of the 28-day study period. We found that a daily self-report questionnaire is a reliable measure of symptom resolution for patients with pneumonia. Full resolution of symptoms takes more than 28 days for a significant proportion of patients with pneumonia.     

Laser photosensitization of cells by hypericin

Administering a light dose of 90 J/cm2 at 599 nm during incubation with hypericin to a highly differentiated normal epithelial cell line (FRTL-5), derived from Fisher rat thyroid, and to a neoplastic cell line (MPTK-6), derived from the lung metastases of a thyroid carcinoma induced in Fisher rats, produces cell kill at drug doses 1000 times lower than those necessary to cause the same mortality in the dark. The photocytocidal activity of this polycyclic quinone drug on neoplastic cells is superior to that of antitumor anthraquinone drugs, such as daunomycin and mitoxanthrone, and to the photosensitized antiviral activity previously reported for hypericin.     

Time course of eye and head deviation in spatial neglect.

Spatial neglect is characterized by a deviation of the eyes and the head during active search, as well as at rest. Here the authors investigate the hitherto unknown relationship between these striking behaviors in the course of recovery. Gaze, eye-in-head, and head-on-trunk positions were recorded separately under two experimental conditions: (i) at rest (i.e., without any specific requirements, doing nothing) and (ii) during active exploratory search in a large visual array of 240° × 80° over a 10-month period. The authors observed a parallel decrease of eye and head (= gaze) deviation in both conditions, accompanied by a comparable decline in neglect severity. The results strengthen the view that the marked gaze deviation toward the ipsilesional side in patients with spatial neglect is due to a very elementary disturbance of human spatial information processing. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Time course evolution of ventilatory responses to inspiratory unloading in patients

Inspiratory muscle unloading decreases ventilatory drive. In this study, we examined the time course of this effect in patients with chronic obstructive pulmonary disease receiving two modes of ventilatory support: pressure support ventilation (PSV), during which each cycle was assisted, and biphasic positive airway pressure (BIPAP), set up in such a manner that one spontaneous breath took place between two consecutive pressure-assisted breaths. The first breath following the switch from spontaneous breathing to PSV was associated with an increase in tidal volume (VT) and a drop in mean transdiaphragmatic pressure (mean Pdi) and inspiratory work (WI) performed per liter but with unchanged values of esophageal occlusion pressure at 100 ms (Pes 0.1), diaphragmatic electrical activity (EMGdi), and WI performed by breath. The same phenomena were observed for the assisted breath of BIPAP as compared with the preceding spontaneous breath. During the subsequent breaths of PSV, Pes 0.1, EMGdi, and WI performed per breath decreased progressively up to the sixth to eighth breaths, and VT returned to pre-PSV values. We conclude that in patients with chronic obstructive pulmonary disease the decrease in ventilatory drive associated with PSV takes place from the first breath onwards but requires six to eight breaths to be fully achieved. During BIPAP, as a consequence of the kinetics of the PSV-induced downregulation of ventilatory drive, assisted breaths following spontaneous breaths are characterized by an enhanced inspiratory efficiency.     

Time course of the blindness to response-compatible stimuli.

This article examines the time course of a deficit in identifying a stimulus sharing a compatible feature with a response that is executed in parallel ("blindness to response-compatible stimuli," J. Müsseler & B. Hommel, 1997a). In 5 experiments, participants performed a timed response, and the presentation point of time of a to-be-identified stimulus was varied in respect to response execution. A blindness effect was observed when the stimulus was presented between response cue offset and response execution. In contrast, the identification of a stimulus presented before the response cue or after response execution was not affected by stimulus-response compatibility—a finding that rules out a retention-based explanation. These results support an explanation that states that the perceptual processing of a stimulus feature is impaired as long as the shared perception–action feature code is integrated into the representation of a to-be-executed response. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Time course of growth factor expression in mercuric chloride acute renal failure

BACKGROUND: Renal EGF expression decreases in varying models of acute renal failure (ARF). We found previously that the loss of distal tubular EGF during gentamicin ARF is strongest in the cortex, where proximal tubular injury was most severe. To gain more insight into the mechanism underlying this apparent anatomical association, renal growth factor expression was investigated during mercuric chloride ARF, in which proximal tubular injury is most severe in the outer stripe of the outer medulla (OSOM). METHODS: Endogenous renal growth factor expression was investigated by RNA hybridization and by immunohistochemistry in a rat model of mercuric chloride ARF. In addition we determined temporal and spatial profiles of tubular injury, cell proliferation, and mononuclear cell infiltration during the 3-week observation period. RESULTS: Serum creatinine values were maximal 2 days after treatment and were again normalized at day 6. Tubular injury was most severe in the PST and maximal at day 2. Cell proliferation was also higher in the PST and maximal at day 4. Three weeks after treatment, normal renal morphology was restored. Increased numbers of mononuclear cells appeared transiently in the renal interstitium from day 1 on. Most of these cells were macrophages and T lymphocytes; macrophages surrounded preferentially the severely injured PST in the OSOM. In analogy to gentamicin ARF, renal EGF and IGF-I gene expression were decreased early in the setting of mercuric chloride ARF. The decrease in distal tubular EGF staining was most pronounced in the OSOM, i.e. the anatomical area where mercuric-chloride-induced proximal tubular injury was most severe. CONCLUSIONS: Renal EGF and IGF-I gene expression decreases strongly during mercuric chloride ARF. The spatial association between the initial decrease of distal tubular EGF expression and the zone of major proximal tubular injury could originate from metabolic alterations secondary to oxygen starvation. A possible role of mononuclear cells remains to be determined.     

Time course of word identification and semantic integration in spoken language.

The minimum duration signal necessary to identify a set of spoken words was established by the gating technique; most words could be identified before their acoustic offset. Gated words were used as congruous and incongruous sentence completions, and isolation points established in the gating experiment were compared with the time course of semantic integration evident in event-related brain potentials. Differential N400 responses to contextually appropriate and inappropriate words were observed about 200 ms before the isolation point. Semantic processing was evident before the acoustic signal was sufficient to identify the words uniquely. Results indicate that semantic integration can begin to operate with only partial, incomplete information about word identity. Influences of semantic constraint, word frequency, and rate of presentation are described. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Time course of forward masking tuning curves in cat primary auditory cortex

Nonsimultaneous two-tone interactions were studied in the primary auditory cortex of anesthetized cats. Poststimulatory effects of pure tone bursts (masker) on the evoked activity of a fixed tone burst (probe) were investigated. The temporal interval from masker onset to probe onset (stimulus onset asynchrony), masker frequency, and intensity were parametrically varied. For all of the 53 single units and 58 multiple-unit clusters, the neural activity of the probe signal was either inhibited, facilitated, and/or delayed by a limited set of masker stimuli. The stimulus range from which forward inhibition of the probe was induced typically was centered at and had approximately the size of the neuron's excitatory receptive field. This "masking tuning curve" was usually V shaped, i.e., the frequency range of inhibiting masker stimuli increased with the masker intensity. Forward inhibition was induced at the shortest stimulus onset asynchrony between masker and probe. With longer stimulus onset asynchronies, the frequency range of inhibiting maskers gradually became smaller. Recovery from forward inhibition occurred first at the lower- and higher-frequency borders of the masking tuning curve and lasted the longest for frequencies close to the neuron's characteristic frequency. The maximal duration of forward inhibition was measured as the longest period over which reduction of probe responses was observed. It was in the range of 53-430 ms, with an average of 143 +/- 71 (SD) ms. Amount, duration and type of forward inhibition were weakly but significantly correlated with "static" neural receptive field properties like characteristic frequency, bandwidth, and latency. For the majority of neurons, the minimal inhibitory masker intensity increased when the stimulus onset asynchrony became longer. In most cases the highest masker intensities induced the longest forward inhibition. A significant number of neurons, however, exhibited longest periods of inhibition after maskers of intermediate intensity. The results show that the ability of cortical cells to respond with an excitatory activity depends on the temporal stimulus context. Neurons can follow higher repetition rates of stimulus sequences when successive stimuli differ in their spectral content. The differential sensitivity to temporal sound sequences within the receptive field of cortical cells as well as across different cells could contribute to the neural processing of temporally structured stimuli like speech and animal vocalizations.     

Time course of the tilorone-induced lysosomal accumulation of sulphated glycosaminoglycans in cultured fibroblasts

Dicationic amphiphilic drugs such as the immunomodulator tilorone [2,7-bis-[2-(diethylamino)ethoxy]fluoren-9-one] are accumulated in lysosomes and disturb the degradation of sulphated glycosaminoglycans (GAGs) thus leading to generalized lysosomal GAG storage (mainly dermatan sulphate) in vivo and in cultured cells. In the present study, the time course of the tilorone-induced GAG storage was determined in cultured bovine corneal fibroblasts by a radiochemical approach and by morphological examination. In contrast to the rapid lysosomal accumulation of the drug as reported previously, it took approximately 42 h to reach 50% of the GAG storage obtained after 96 h. This is thought to be due to the fact that the temporal development of storage of undigested GAGs depends on the natural delivery of GAGs towards the lysosomal apparatus.     

Sensitization of ingestive responding in preweanling rats: Time course and specificity.

Two experiments measured the response-enhancing effects of oral stimulation in young rats with no feeding experience. In Experiment 1, pups were implanted with oral cannulas and deprived for 0, 6, or 24 hr. In nondeprived rats, sucrose exposure transiently sensitized oral responding to subsequent stimuli for several minutes. Among 24-hr-deprived rats, baseline oral responding had increased to where sucrose exposure was no longer sensitizing. Unlike oral responding, sensitization of activity by sucrose exposure increased with deprivation. Sensitization was also evident in the microstructure of responses to infusions. In Experiment 2, the specificity of sensitization was examined by varying stimulus palatability. Sucrose exposure sensitized oral responding to both sucrose and quinine-adulterated sucrose, but quinine-adulterated sucrose was not sensitizing. The results suggest that in inexperienced rats, oral stimulation initiates changes in responding that may mimic the endogenous sequelae of deprivation, perhaps representing early substrates for learned controls of intake. (PsycINFO Database Record (c) 2010 APA, all rights reserved)