What covariance mechanisms underlie green/red equiluminance, luminance contrast sensitivity and chromatic (green/red) contrast sensitivity?

In order to investigate the mechanisms underlying green/red equiluminance matches in human observers and their relationship to mechanisms subserving luminance and/or chromatic (green/red) contrast sensitivity, we tested 21 human subjects along these dimensions at 16 different spatial and temporal frequencies (spatial frequency, 0.25-2 c/deg; temporal frequency, 2-16 Hz) and applied factor analysis to extract mechanisms underlying the data set. The results from our factor analysis revealed separate sources of variability for green/red equiluminance, luminance sensitivity and chromatic sensitivity, thus suggesting separate mechanisms underlying each of the three main conditions. When factor analysis was applied separately to green/red equiluminance data, two temporally-tuned factors were revealed (factor 1, 2-4 Hz; factor 2, 8-16 Hz), suggesting the existence of separate mechanisms underlying equiluminance settings at low versus high temporal frequencies. In addition, although the three main conditions remained separate in our factor analysis of the entire data set, our correlation matrix nonetheless revealed systematic correlations between equiluminance settings and luminance sensitivity at high temporal frequencies, and between equiluminance settings and chromatic sensitivity at low temporal frequencies. Taken together, these data suggest that the high temporal frequency factor underlying green/red equiluminance is governed predominantly by luminance mechanisms, while the low temporal frequency factor receives contribution from chromatic mechanisms.

Prevalence of digital clubbing in bronchogenic carcinoma by a new digital index.

OBJECTIVE: Clubbing can be a paraneoplastic manifestation of bronchogenic carcinoma. We assessed a new digital index of clubbing and used it to determine the prevalence of clubbing for different cell types of lung cancer. METHODS: Clubbing was assessed by measurement of the thickness of both the base of the nailbed (distal phalangeal depth--DPD) and the distal interphalangeal depth (IPD) of the index finger in a control group compared to patient groups with either chronic obstructive lung disease, or lung cancer. RESULTS: Of the 55 normal subjects, no patient had a DPD/IPD ratio of more than 1.05 on either hand, while 11% of the patients with COPD had a ratio of more than one. For the cancer patients, 33% had a ratio greater than one, with 30 of 109 (37%) having a ratio > 1.05 (chi(2) = 17.6, p < 0.0001). There was no difference in the prevalence of clubbing between the 33 squamous cell patients, the 43 adenocarcinoma patients, and the 33 small cell lung carcinoma patients included. CONCLUSIONS: Measurement of the interphalangeal and distal phalangeal distance demonstrated that one-third of patients with lung cancer had evidence of clubbing. The type of bronchogenic carcinoma did not appear to affect the proportion of patients with clubbing.

Structure-activity studies related to ABT-594, a potent nonopioid analgesic agent: effect of pyridine and azetidine ring substitutions on nicotinic acetylcholine receptor binding affinity and analgesic activity in mice.

Analogs of A-98593 (1) and its enantiomer ABT-594 (2) with diverse substituents on the pyridine ring were prepared and tested for affinity to nicotinic acetylcholine receptor binding sites in rat brain and for analgesic activity in the mouse hot plate assay. Numerous types of modifications were consistent with high affinity for [3H]cytisine binding sites. By contrast, only selected modifications resulted in retention of analgesic potency in the same range as 1 and 2. Analogs of 2 with one or two methyl substituents at the 3-position of the azetidine ring also were prepared and found to be substantially less active in both assays.

ABT-089 [2-methyl-3-(2-(S)-pyrrolidinylmethoxy)pyridine dihydrochloride]: II. A novel cholinergic channel modulator with effects on cognitive performance in rats and monkeys.

ABT-089 [2-methyl-3-(2-(S)-pyrrolidinylmethoxy)pyridine dihydrochloride], a novel ligand at neuronal nicotinic acetylcholine receptors with reduced adverse effects and improved oral bioavailability relative to (-)-nicotine, was tested in a variety of cognitive tests in rats and monkeys. Administered acutely, ABT-089 only marginally improved the spatial discrimination water maze performance of septal-lesioned rats. However, more robust improvement (45% error reduction on the last training day) was observed when ABT-089 was administered continuously via subcutaneous osmotic pumps (minimum effective dose: 1.3 micromol/kg/day). Continuous infusion of (-)-nicotine produced comparable improvement in the spatial discrimination water maze performance of septal-lesioned rats, but a 40-fold higher dose of (-)-nicotine was required (62 micromol/kg/day). Continuous infusion of ABT-089 to aged rats enhanced spatial learning in a standard Morris water maze, as indexed by spatial bias exhibited during a probe trial conducted after 4 days of training, but not when they were subsequently trained in a two-platform spatial discrimination water maze. The compound induced a small impairment in young rats on the standard water maze, but not on the two-platform task. A probe trial conducted after additional training in the standard water maze revealed no age or drug effects. ABT-089 did not affect performance of either the aged or young rats during inhibitory (passive) avoidance training. Also, continuous infusion of ABT-089 did not affect responses to acoustic startle or prepulse inhibition of acoustic startle in young, aged or septal-lesioned rats and did not affect locomotor activity in either sham-lesioned or septal-lesioned rats. In monkeys, acute administration of ABT-089 modestly improved the delayed matching-to-sample performance of mature, adult monkeys and more robustly improved performance in aged monkeys. Improved performance in the aged monkeys was restricted to the longest delay intervals and was not accompanied by changes in response latencies.

Comparison of site specific injections into the basal forebrain on water maze and radial arm maze performance in the male rat after immunolesioning with 192 IgG saporin.

In this study we investigated the effects of 192 IgG saporin injections into the medial septal area (MSA), or nucleus basalis magnocellularis (NBM), and combined injections into the MSA and NBM, on the water maze and radial arm maze performance in the male rat. The results of the present study reveal a dissociation between the effects of 192 IgG saporin injections into the basal forebrain on the performance of two tasks of spatial learning in the rat. Bilateral injections of 192 IgG saporin into the NBM, MSA or combined MSA/NBM failed to disrupt water maze performance when compared to controls. In contrast, injections of 192 IgG saporin into the MSA, NBM or MSA/NBM induced mild impairments on a radial arm maze task. Overall, the disruption of spatial learning observed in this study however was relatively mild compared to deficits in spatial learning reported using less selective lesions of the cholinergic basal forebrain. Consequently, the results of this study suggest that a selective reduction in cholinergic transmission in the basal forebrain is by itself, insufficient to account for the functional impairments observed in spatial learning in the rat. Although our data does support the use of 192 IgG saporin as a selective cholinergic toxin in the basal forebrain, it further suggests that assessment of spatial learning in the rat following 192 IgG saporin lesions of the basal forebrain in combination with lesions to other neurotransmitter systems, may be a more viable approach to the elucidation of the neuropathological mechanisms that are associated with the cognitive deficits seen in Alzheimer's Disease.

Sleep apnea in sarcoidosis.

BACKGROUND AND AIM OF WORK: Sleep apnea is reported to occur in 2-4% of the general population. Patients with sarcoidosis are at increased risk for sleep apnea, possibly due to factors such as steroid use, neurosarcoid, or upper airway obstruction. METHODS: In order to determine the prevalence and risk factors for sleep apnea in sarcoidosis patients, we studied 83 consecutive patients with sarcoidosis seen over a six-week time period. Patients were screened using the Epworth Sleepiness Scale questionnaire and the age, sex, race, weight, and medications were recorded. The presence of previously diagnosed sleep apnea, neurosarcoid, lupus pernio, and sinus disease were also noted. A control group of 91 patients seen in general pulmonary clinics were similarly screened. Patients with a positive sleep questionnaire were referred for sleep studies. RESULTS: A total of 14 sarcoid patients (17%) were found to have sleep apnea, which was significantly higher than our control group with 3/91 (3%, p < 0.001). The presence of lupus pernio was significantly more frequent in the sleep apnea group. Although 5/51 (10%) female sarcoid patients had sleep apnea, overall it was more frequent in male sarcoid patients. CONCLUSIONS: Sleep apnea was frequent in sarcoid patients and was associated with lupus pernio.

Comparison of site-specific injections into the basal forebrain on water maze and radial arm maze performance in the male rat after immunolesioning with 192 IgG saporin.

In this study, we investigated the effects of 192 IgG saporin injections into the medial septal area (MSA), or nucleus basalis magnocellularis (NBM), and combined injections into the MSA and NBM, on water maze and radial arm maze performance in the male rat. The results of the present study reveal a dissociation between the effects of 192 IgG saporin injections into the basal forebrain on the performance of two tasks of spatial learning in the rat. Bilateral injections of 192 IgG saporin into the NBM, MSA or combined MSA/NBM failed to disrupt water maze performance when compared to controls. In contrast, injections of 192 IgG saporin into the MSA, NBM or MSA/NBM induced mild impairments on a radial arm maze task. Overall, the disruption of spatial learning observed in this study was, however, relatively mild compared to deficits in spatial learning reported using less selective lesions of the cholinergic basal forebrain. Consequently, the results of this study suggest that a selective reduction in cholinergic transmission in the basal forebrain is, by itself, insufficient to account for the functional impairments observed in spatial learning in the rat. Although our data do support the use of 192 IgG saporin as a selective cholinergic toxin in the basal forebrain, they further suggests that assessment of spatial learning in the rat following 192 IgG saporin lesions of the basal forebrain in combination with lesions to other neurotransmitter systems, may be a more viable approach to the elucidation of the neuropathological mechanisms that are associated with the cognitive deficits seen in Alzheimer's disease.

Changes in the inflammatory response of the lung during acute respiratory distress syndrome: prognostic indicators.

We studied paired bronchoalveolar lavage (BAL) in patients with sepsis-associated acute respiratory distress syndrome (ARDS). Patients were evaluated at one institution and underwent bronchoscopy with BAL within 48 h of the onset of ARDS. Patients were restudied with bronchoscopy and BAL after 4 d of treatment. Fifty-eight patients were initially studied, with 44 patients having follow-up bronchoscopy after 4 d. The overall 30-d survival for the ARDS group was 60%. In the initial lavage, there was no difference in the neutrophils between the survivors and nonsurvivors (survivors: 59 [0-98]%; Median [Range]; nonsurvivors: 55 [0-92]%). The follow-up lavage demonstrated a significant drop in the neutrophils for the survivors (36 [4-89]%, p < 0.002) which was not seen for the nonsurvivors (70 [26-95]%). Initial IL-8 concentrations in the BAL fluid were not significantly different between the two groups. In the follow-up lavage, there was a significant fall for the IL-8 concentrations for the survivors but not the nonsurvivors. We conclude that neutrophil influx in ARDS may rapidly resolve within a week of the onset of ARDS. The resolution of neutrophils was associated with a good prognosis.

Effects of intraseptal injection of 192-IgG-saporin in mature and aged Long-Evans rats.

In this study, the effects intraseptal injections of the selective cholinergic immunotoxin, 192-IgG-saporin, were investigated in mature (6-month-old) and aged (24-26-month-old) male Long-Evans rats. Ten days following intraseptal injection of either 192-IgG-saporin or saline, testing began in a battery of behavioral tests modulated by the septohippocampal system including two versions of the Morris water maze (i.e. submerged platform task, and 2-platform spatial discrimination), inhibitory avoidance, and pre-pulse inhibition of acoustic startle. In both mature and aged rats, intraseptal injection of 192-IgG-saporin selectively reduced ChAT activity in the hippocampus and posterior cingulate cortex, without affecting ChAT activity of amygdala or parietal cortex. In general, in all of the behavioral tests analyzed, intraseptal 192-IgG-saporin treatment had no effect in mature animals. Age-related deficits were observed in the spatial memory tasks, however this impairment was largely a function of the poor performance of aged rats treated with the toxin. In addition, an increase in the response to an acoustic startle was found in aged rats treated with 192-IgG-saporin. Thus, although intraseptal injection of 192-IgG-saporin produced similar reductions of ChAT activity, performance of mature and aged rats in tasks believed to be modulated by the septohippocampal pathway tended to be differentially affected in mature and aged rats.

Is epibatidine really analgesic? Dissociation of the activity, temperature, and analgesic effects of (+/-)-epibatidine.

The experiments in the present study were designed to determine if the activity, temperature, and analgesic effects of (+/-)-epibatidine treatment could be dissociated. Initially (i.e., 15 min) (+/-)-epibatidine treatment (0.1 mumol/kg = 28 micrograms/kg, IP) impaired rotorod performance, decreased activity, decreased temperature, and increased jump latency (e.g., analgesic effect). For the remaining time points measured (i.e., 30, 60, and 120 min), activity and temperature remained significantly reduced. In contrast, by 120 min (+/-)-epibatidine's effects on rotorod performance and analgesia (jump latency) were not observed. When administered after (+/-)-epibatidine (0.05 mumol/kg, IP), mecamylamine treatment (5 mumol/kg = 1 mg/kg, IP) produced a potentiation of analgesia. This potentiation effect was not observed on activity and temperature measures. The effect of (+/-)-epibatidine treatment (0.1 mumol/kg, IP) was also determined in mice with central nicotinic receptor blockade induced by treatment with chlorisondamine (23 mumol/kg = 10 mg/kg, IP). An (+/-)-epibatidine-induced reduction in activity was not attenuated in chlorisondamine-treated mice and only a minimal effect was observed on (+/-)-epibatidine-induced hypothermia in chlorisondamine-treated mice. In contrast, in chlorisondamine-treated mice (+/-)-epibatidine's analgesic effect was attenuated. Taken together, these data suggest that various centrally mediated effects of (+/-)-epibatidine can be dissociated.

The influence of Bay K 8644 treatment on (+/-)-epibatidine-induced analgesia.

The purpose of this investigation was to determine if analogous to (-)-nicotine's analgesic effect, the analgesic effect of the recently characterized potent nicotinic acetylcholine receptor (nAChR) agonist (+/-)-epibatidine was altered in response to treatment with the calcium channel agonist (+/-)-Bay K 8644. In addition, the effects of the enantiomers, (+)-Bay K 8644, reported to be a calcium channel antagonist, and (-)-Bay K 8644, reported to be a calcium channel agonist were examined. (+/-)-Bay K 8644 (2.8 mumol/kg; i.p.) produced a large analgesic response in mice in the hot-plate paradigm that rapidly dissipated by 30 min after treatment. This analgesic effect of (+/-)-Bay K 8644 was not prevented by pre-treatment with the nicotinic antagonist mecamylamine (5 mumol/kg; i.p.). Treatment with non-analgesic doses of the calcium channel agonists (+/-)- and (-)-Bay K 8644 (1.4 mumol/kg; i.p.) significantly potentiated the analgesic effect of (+/-)-epibatidine (0.05 mumol/kg; i.p.). Potentiation of (+/-)-epibatidine's analgesic effect occurred when the agonists were administered prior to (+/-)-epibatidine or after (+/-)-epibatidine as long as analgesia testing was conducted 15 to 30 min after Bay K 8644 treatment. Pre-treatment with the calcium channel antagonist (+)-Bay K 8644 was found to attenuate (+/-)-epibatidine-induced analgesia. When given after (+/-)-epibatidine, (+)-Bay K 8644 had no effect on (+/-)-epibatidine's analgesic effect. These data provide additional in vivo evidence that altering calcium dynamics can modulate neuronal nAChR function.