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Persons with amnestic Mild Cognitive Impairment (aMCI) are at risk for experiencing changes in their daily functioning due to their memory impairment. The Memory Support System (MSS), a compensatory calendaring system, was developed to support functional independence in persons with aMCI (pwaMCI). This cross-sectional study examined procedural learning, declarative learning, and working memory as predictors of MSS learning efficiency in pwaMCI. Sixty pwaMCI participated in MSS training. The Serial Reaction Time Test and Mirror Tracing Test were used to assess procedural learning. The Rey Auditory Verbal Learning Test and CogState One Card Learning were used to assess declarative learning and the CogState One Back task was used to assess working memory. Multiple regression analyses were conducted to assess if procedural learning, declarative learning, and working memory predicted MSS learning efficiency. This study showed that declarative learning predicted MSS learning efficiency in pwaMCI, with less consistent results for procedural learning and non-significant results for working memory. Findings suggest that success in teaching compensatory tools is greater when training is offered in early aMCI before declarative learning skill is fully lost. Future studies should assess additional strategies to facilitate MSS learning in advanced aMCI.

Crucial to the fight against sex trafficking 1 is understanding the experiences of victims and survivors. Survivor surveys have illuminated key areas to address, but a clear gap in the research is in the reproductive, gynecological, and procreative health issues of victims and survivors. This article opens the door to research and dialogue by publishing the findings of a pilot survivor survey focused on survivors' sexual and reproductive health. The retrospective survey offers preliminary findings for a larger national study underway in 2023 that will enable healthcare providers, service providers and other first responders to identify and better meet the unique needs of victims and survivors of human trafficking in this area., (Copyright © 2023 by the National Legal Center for the Medically Dependent & Disabled, Inc.)

Objective: While declarative learning is dependent on the hippocampus, procedural learning and repetition priming can operate independently from the hippocampus, making them potential targets for behavioral interventions that utilize non-declarative memory systems to compensate for the declarative learning deficits associated with hippocampal insult. Few studies have assessed procedural learning and repetition priming in individuals with amnestic mild cognitive impairment (aMCI)., Method: This study offers an overview across declarative, conceptual repetition priming, and procedural learning tasks by providing between-group effect sizes and Bayes Factors (BFs) comparing individuals with aMCI and controls. Seventy-six individuals with aMCI and 83 cognitively unimpaired controls were assessed. We hypothesized to see the largest differences between individuals with aMCI and controls on declarative learning, followed by conceptual repetition priming, with the smallest differences on procedural learning., Results: Consistent with our hypotheses, we found large differences between groups with supporting BFs on declarative learning. For conceptual repetition priming, we found a small-to-moderate between-group effect size and a non-conclusive BF somewhat in favor of a difference between groups. We found more variable but overall trivial differences on procedural learning tasks, with inconclusive BFs, in line with expectations., Conclusions: The current results suggest that conceptual repetition priming does not remain intact in individuals with aMCI while procedural learning may remain intact. While additional studies are needed, our results contribute to the evidence-base that suggests that procedural learning may remain spared in aMCI and helps inform behavioral interventions that aim to utilize procedural learning in this population.

The Memory Support System (MSS) is the memory compensation tool used in the HABIT Healthy Action to Benefit Independence and Thinking ® Program. People diagnosed with mild cognitive impairment (pwMCI; n  = 153) participated in this cognitive rehabilitative programme with a partner. We first aimed to determine if prior research on the positive impact of higher baseline cognitive status on successful MSS learning would be replicated in a new sample. We further evaluated the impact of the pwMCI's and partner's personality traits, as measured by the Ten Item Personality Inventory, on successful learning. Better global cognitive status was again shown to increase the odds for MSS learning success. In terms of personality, the highest odds of learning success occurred when the pwMCI was high in Openness to Experience (OR = 5.43), followed by high partner Openness (OR = 2.53) or high Openness in both the pwMCI and partner (OR = 2.31). In sum, when the pwMCI possessed both better cognitive status and openness to new experience they were better able to master a cognitive rehabilitation tool for MCI.

Limited access to mental health and behavioral interventions is a public health issue that predated and is further worsened by coronavirus disease 2019 (COVID-19) social distancing restrictions. The Healthy Action to Benefit Independence and Thinking (HABIT) program is a cognitive rehabilitation and wellness program for patients with a diagnosis of mild cognitive impairment and their partners that involves groups of up to 32 people (16 dyads) at a time. Thus, the public health recommendation to avoid groups at the start of the COVID-19 pandemic immediately impacted our ability to offer this treatment protocol. This brief report provides patient and partner satisfaction data as well as clinical outcomes with a virtual adaptation of the HABIT program developed because of the COVID-19 pandemic. At the time of their participation, patients who attended in-person sessions had an average age of 74.4 years and those who attended virtual sessions had an average age of 75.4 years ( P =.60). Both groups had an average of 16.3 years of education ( P =.95). Approximately half of the patients in both groups were male (30 of 57 [53%]), most were White (54 of 57 [95%]) and were accompanied to the program by a spouse (50 of 57 [88%]). Overall, patient and partner satisfaction with the HABIT program remained high, ranging from a mean score of 5.8 to 6.6 on a rating scale of 1 to 7 for patients and partners, and clinical outcomes remained consistent with our face-to-face formatting when compared with pre-COVID pandemic sessions. The most notable changes across both formats were improvements in patient anxiety (Cohen's d =0.25 face-to-face; d =0.39 virtual), partner anxiety ( d =0.37 face-to-face; d =0.34 virtual), and partner depression ( d =0.37 face-to-face; d =0.35 virtual). This preliminary program evaluation suggests that transitioning the HABIT program to virtual formatting provides high-quality care similar to our in-person care models. Ongoing program evaluation is planned as we continue using virtual treatment for safety. Even after COVID-19 pandemic public health restrictions are lifted, these findings will have continued relevance to ongoing demand for telehealth., (© 2021 THE AUTHORS.)

Objectives: Lifestyle modifications for those with mild cognitive impairment (MCI) may promote functional stability, lesson disease severity, and improve well-being outcomes such as quality of life. The current analysis of our larger comparative effectiveness study evaluated which specific combinations of lifestyle modifications offered as part of the Mayo Clinic Healthy Action to Benefit Independence in Thinking (HABIT) program contributed to the least functional decline in people with MCI (pwMCI) over 18 months., Methods: We undertook to compare evidence-based interventions with one another rather than to a no-treatment control group. The interventions were five behavioral treatments: computerized cognitive training (CCT), yoga, Memory Support System (MSS) training, peer support group (SG), and wellness education (WE), each delivered to both pwMCI and care partners, in a group-based program. To compare interventions, we randomly withheld one of the five HABIT® interventions in each of the group sessions. We conducted 24 group sessions with between 8 and 20 pwMCI-partner dyads in a session., Results: Withholding yoga led to the greatest declines in functional ability as measured by the Functional Activities Questionnaire and Clinical Dementia Rating. In addition, memory compensation (calendar) training and cognitive exercise appeared to have associations (moderate effect sizes) with better functional outcomes. Withholding SG or WE appeared to have little effect on functioning at 18 months., Conclusions: Overall, these results add to the growing literature that physical exercise can play a significant and lasting role in modifying outcomes in a host of medical conditions, including neurodegenerative diseases.

There is currently limited and mixed evidence for the cognitive benefits of Computerized Cognitive Training (CCT) and yoga in persons with Mild Cognitive Impairment (pwMCI). The objective of this study was to investigate the benefit of computerized cognitive training (CCT) vs. physical (yoga) intervention on cognitive abilities. Participants in this study were part of the larger Mayo Clinic's Healthy Action to Benefit Independence and Thinking (HABIT) program comparative effectiveness trial. The HABIT program is designed for pwMCI and their care partner and consists of five behavioral interventions: CCT, Memory Support System-Calendar (MSS-Calendar), wellness education, support groups, and yoga. The subtractive study design randomly withheld one of the interventions for a total of five study arms. Longitudinal mixed-effects regression models were used to investigate the hypothesis that CCT and yoga has a greater positive impact on psychomotor and basic attention abilities at 12 months post-intervention as compared to the other HABIT interventions. Findings showed CCT had a positive impact compared to yoga on the Cogstate psychomotor/attention composite at 12 months post-intervention (ES = 0.54; unadjusted p value = 0.007, adjusted p value = 0.021). The impact of yoga or combining CCT with yoga did not show statistically significant improvement. Continued CCT practice at home showed further benefit on psychomotor/attention at 12 months post-intervention. There was no significant benefit of CCT or yoga on Cogstate learning/working memory composite.

Importance: Recommendations to engage in behavioral strategies to combat clinically significant cognitive and behavioral symptoms are routinely given to persons with mild cognitive impairment (MCI). The comparative effectiveness of these behavioral interventions is not well understood., Objective: To compare the incremental effects of combinations of 5 behavioral interventions on outcomes of highest importance to patients with MCI., Design, Setting, and Participants: In this multisite, cluster randomized, multicomponent comparative effectiveness trial, 272 patients from 4 academic medical outpatient centers (Mayo Clinic, Rochester, Minnesota; Mayo Clinic, Scottsdale, Arizona; Mayo Clinic, Jacksonville, Florida; and University of Washington, Seattle) were recruited from September 1, 2014, to August 31, 2016, with last follow-up March 31, 2019. All participants met the National Institute on Aging-Alzheimer's Association criteria for MCI., Interventions: The intervention program was modeled on the Mayo Clinic Healthy Action to Benefit Independence and Thinking (HABIT) program, a 50-hour group intervention conducted during 2 weeks, including memory compensation training, computerized cognitive training, yoga, patient and partner support groups, and wellness education. In our study, 1 of 5 interventions was randomly selected to be withheld for each intervention group. Participants and their partners had 1-day booster sessions at 6 and 12 months after intervention., Main Outcomes and Measures: Quality-of-life measurement of participants with MCI at 12 months was the primary outcome, selected based on the preference rankings of previous program participants. Mood, self-efficacy, and memory-based activities of daily living were also highly ranked., Results: A total of 272 participants (mean [SD] age, 75 [8] years; 160 [58.8%] male and 112 [41.2%] female) were enrolled in this study, with 56 randomized to the no yoga group, 54 to no computerized cognitive training, 52 to no wellness, 53 to no support, and 57 to no memory support system. The greatest effect size for quality of life was between the no computerized cognitive training and no wellness education groups at 0.34 (95% CI, 0.05-0.64). In secondary analyses, wellness education had a greater effect on mood than computerized cognitive training (effect size, 0.53; 95% CI, 0.21-0.86), and yoga had a greater effect on memory-related activities of daily living than support groups (effect size, 0.43; 95% CI, 0.13-0.72)., Conclusions and Relevance: These results provide further support for behavioral interventions for persons with MCI. Different outcomes were optimized by different combinations of interventions. These findings provide an initial exploration of the effect of behavioral interventions on patient-advocated outcomes in persons with MCI., Trial Registration: ClinicalTrials.gov identifier: NCT02265757.

This pilot study examined the functional impact of computerized versus compensatory calendar training in cognitive rehabilitation participants with mild cognitive impairment (MCI). Fifty-seven participants with amnestic MCI completed randomly assigned calendar or computer training. A standard care control group was used for comparison. Measures of adherence, memory-based activities of daily living (mADLs), and self-efficacy were completed. The calendar training group demonstrated significant improvement in mADLs compared to controls, while the computer training group did not. Calendar training may be more effective in improving mADLs than computerized intervention. However, this study highlights how behavioral trials with fewer than 30-50 participants per arm are likely underpowered, resulting in seemingly null findings., Competing Interests: The authors declare no conflict of interest. The funding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Cognitive interventions in Mild Cognitive Impairment (MCI) seek to ameliorate cognitive symptoms in the condition. Cognitive interventions may or may not generalize beyond cognitive outcomes to everyday life. This systematic review and meta-analysis sought to assess the effect of cognitive interventions compared to a control group in MCI on generalizability outcome measures [activities of daily living (ADLs), mood, quality of life (QOL), and metacognition] rather than cognitive outcomes alone. PRISMA guidelines were followed. MEDLINE and PsychInfo were utilized as data sources to locate references related to cognitive interventions in individuals with MCI. The cognitive intervention study was required to have a control or alternative treatment comparison group to be included. Thirty articles met criteria, including six computerized cognitive interventions, 14 therapist-based interventions, and 10 multimodal (i.e., cognitive intervention plus an additional intervention) studies. Small, but significant overall median effects were seen for ADLs (d = 0.23), mood (d = 0.16), and metacognitive outcomes (d = 0.30), but not for QOL (d = 0.10). Computerized studies appeared to benefit mood (depression, anxiety, and apathy) compared to controls, while therapist-based interventions and multimodal interventions had more impact on ADLs and metacognitive outcomes than control conditions. The results are encouraging that cognitive interventions in MCI may impact everyday life, but considerably more research is needed. The current review and meta-analysis is limited by our use of only PsychInfo and MEDLINE databases, our inability to read full text non-English articles, and our reliance on only published data to complete effect sizes.

Objective: To determine the effects of IM administration of acepromazine, hydromorphone, or the acepromazine-hydromorphone combination on degree of sedation in clinically normal dogs and to compare 2 sedation scoring techniques., Design: Prospective, randomized, blinded, controlled trial. Animals-46 random-source dogs., Procedures: Dogs were assigned to receive IM administrations of acepromazine (0.05 mg/kg [0.023 mg/lb]; [DOSAGE ERROR CORRECTED] n = 12), hydromorphone (0.1 mg/kg [0.045 mg/lb]; 11), acepromazine-hydromorphone (0.5 mg/kg and 0.1 mg/kg, respectively; 12), or saline (0.9% NaCI) solution (0.05 mL/kg [0.023 mL/lb]; 11). Sedation scores were determined at 0 (time of administration), 15, 30, 45, and 60 minutes by use of a subjective scoring system (SSS) and a simple numeric rating scale (NRS)., Results: Acepromazine caused significantly greater sedation than did saline solution at 15, 30, 45, and 60 minutes. Acepromazine-hydromorphone caused significantly greater sedation than did saline solution at 15, 30, 45, and 60 minutes and than did hydromorphone alone at 30 minutes. Hydromorphone alone did not cause significantly greater sedation than did saline solution. All treatments, including saline solution, caused significantly greater sedation at 45 and 60 minutes, compared with sedation at time 0. There was a significant correlation (r(2) = 0.72) between scores obtained with the SSS and NRS, but the NRS was less sensitive for detecting clinically important sedation., Conclusions and Clinical Relevance: Administration of acepromazine or acepromazine-hydromorphone caused sedation in clinically normal dogs, whereas administration of hydromorphone alone did not. The NRS was a less-reliable measure of sedation.

Objective: To evaluate the effect of topical 2% dorzolamide alone, and in combination with topical 0.5% timolol, on intraocular pressure (IOP) in normal cats., Animals: Twenty-four healthy Domestic Short-haired cats., Procedure: Baseline values of IOP were established at 7 am, 10 am, 1 pm, 5 pm and 9 pm during pretreatment phase (days 1-2). During treatment phase (days 3-10) cats received 2% dorzolamide HCl q 12 h in group A (n = 6), q 8 h in group B (n = 6), and combined with 0.5% timolol maleate q 12 h in group C (n = 6). Cats in control group D (n = 6) received artificial tears q 8 h. During treatment phase IOP measurements were continued at the same time-points as in the pretreatment phase., Results: Mean pretreatment IOP in all cats was 18.46 +/- 2.99 mmHg. Mean IOP decreased significantly (P < 0.0086) in all treatment groups compared to pretreatment values (group A: 16.40 +/- 0.49 mmHg, group B: 16.04 +/- 0.49 mmHg, group C: 17.76 +/- 0.49 mmHg). IOP did not decrease in control group D (18.55 +/- 0.49 mmHg). The difference in IOP between treatment groups (A, B, C) was not statistically significant, but comparison of IOP between each treatment group and the control group was statistically significant (A-D; P = 0.0057; B-D, P = 0.0012; C-D, P = 0.0212)., Conclusion: Topical 2% dorzolamide significantly lowers IOP in normal cats but the effect is mild. Concomitant application of 2% dorzolamide and 0.5% timolol does significantly decrease IOP, but the effect is not significantly greater than q 8 h administration of dorzolamide alone.

Background: Topical treatment with tacrolimus may be complicated by ingestion-related flushing caused by consuming small amounts of alcohol, a reaction that can be mistaken for food allergy., Objective: To increase awareness of a drug interaction with alcohol that can mimic food allergy., Methods: We describe 3 patients who used topical tacrolimus, 2 with an atopic history and 1 without, who presented with a flushing reaction after ingesting alcohol., Results: Cessation of topical tacrolimus use resolves the alcohol-related skin reaction., Conclusions: A careful history, including consideration of alcohol use, should be obtained in patients who use topical tacrolimus and present with new skin complaints, because these factors may be evidence of an avoidable drug interaction and not worsening of atopic disease or a food allergy.

Objective: To determine the effects of treatment with and without adjuvant radiation therapy on recurrence of ocular and adnexal squamous cell carcinoma (SCC) at specific anatomic locations in horses., Design: Retrospective study., Animals: 91 horses., Procedures: Medical records of horses with histologically confirmed ocular and adnexal SCC evaluated from 1985 to 2002 were reviewed. Sex, breed, age, type of treatment, location, and recurrence of SCC were recorded. Two treatment groups determined by recurrence of SCCs treated with and without adjuvant radiation therapy were established., Results: The anatomic site with the highest recurrence rate was the limbus (junction of the cornea and sclera) or bulbar conjunctiva (477%), independent of treatment group. There was a significant difference in recurrence rates of ocular and adnexal SCCs between the 2 treatment groups, independent of anatomic location. Recurrence rates of SCCs treated with and without adjuvant radiation therapy were 11.9% and 44.1%, respectively. Recurrence rates for SCCs of the eyelid, limbus or bulbar conjunctiva, and cornea treated with adjuvant radiation therapy were significantly different from those for SCCs treated without adjuvant radiation therapy. The most frequently represented anatomic site for ocular and adnexal SCCs was the eyelid (28.7%). Coat color, breed, and the interaction of age and breed had a significant effect on tumor recurrence regardless of treatment type and anatomic location., Conclusions and Clinical Relevance: Results indicated that ocular and adnexal SCCs treated with adjuvant radiation therapy had a significantly lower recurrence rate, compared with SCCs treated without adjuvant radiation therapy, independent of anatomic location.

Three-word recall tasks are widely used as brief measures of verbal memory function, although interpretation of performance is complicated by variations in test instructions and procedures. The purpose of this study was to examine 3-word recall performance in samples of healthy subjects aged 5275 (M age = 70) and age 7692 (M age = 82) compared to patients with Alzheimer's Disease (AD) when explicit prompts to remember the words were given. Those in the younger aging group remembered significantly more words than those in the older sample after a brief delay (M= 2.8 and 2.3, respectively). However, the majority of control subjects recalled 2 or 3 words after the delay, with only 3% of the 5075 year old group and 17% of the 76+ year old group recalling 0 or 1 word on delayed recall. This is in stark contrast to the 87% of individuals with AD who recalled 0 or 1 word. Even though 3-word recall performance decreases with age, good recall (2 or 3 words) can be expected in most cases of normal aging.

This study was performed to investigate whether spinal cord stimulation (SCS) at intensities below motor threshold prolongs cutaneous vasodilation and whether sustained vasodilation by SCS is mediated through sympathetic inhibition and/or antidromic activation of sensory fibers. SCS was applied to the dorsal surface of the L2-L3 spinal cord of anesthesized rats with stimulus parameters used clinically (i.e., 50 Hz, 0.2 ms duration, and stimulus intensity at 30%, 60%, or 90% of motor threshold). Peripheral vasodilation induced by 5-min SCS was not attenuated by hexamethonium, an autonomic ganglion-blocking agent, but was abolished by dorsal rhizotomy. SCS at < or = 60% of motor threshold increased cutaneous blood flow to the level similar to that obtained at 90% of motor threshold, but the vasodilation did not last for 5 min. SCS-induced vasodilation at 90% of motor threshold persisted for the entire stimulation period up to 30 min, and the vasodilation was not attenuated by hexamethonium. It is concluded that sustained vasodilation, which is induced by SCS at only 90% of motor threshold, in this study was mediated via antidromic activation of sensory fibers.

The aim of this study was to characterize thoracic spinal neurons receiving convergent inputs from the esophagus, heart and somatic receptive fields. Extracellular potentials of single T3-T4 spinal neurons were recorded in pentobarbital anesthetized male rats. Thoracic and cervical esophageal distensions (TED, CED) were produced by water inflation of a latex balloon. A catheter was placed in the pericardial sac to administer bradykinin or a mixture of algogenic chemicals. 96/311 (31%) neurons responded to both TED and intrapericardial chemicals (IC) and 48/177 (27%) neurons responded to both CED and IC. Long-lasting excitatory responses were more frequently encountered (P<0.05) in esophagocardiac spinal neurons responding to TED (T-ECSNs, 62/91) than in neurons responding to CED (C-ECSNs, 23/47). Ninety-one percent of T-ECSNs and 98% of C-ECSNs had somatic fields on chest, axilla and upper back areas. Esophagocardiac convergence on thoracic spinal neurons provided a spinal mechanism that might mediate viscerovisceral nociception and reflexes., (Copyright 2004 Elsevier B.V.)

Because vagal and sympathetic inputs activate upper cervical spinal neurons, we hypothesized that stimulation of the esophagus would activate C(1)-C(2) neurons. This study examined responses of C(1)-C(2) spinal neurons to cervical and thoracic esophageal distension (CED, TED) and afferent pathways for CED and TED inputs to C(1)-C(2) spinal neurons. Extracellular potentials of single C(1)-C(2) spinal neurons were recorded in pentobarbital-anesthetized male rats. Graded CED or TED was produced by water inflation (0.1-0.5 ml) of a latex balloon. CED changed activity of 48/219 (22%) neurons; 34 were excited (E), 12 were inhibited (I), and 2 were E-I. CED elicited responses for 18/18 neurons tested after ipsilateral cervical vagotomy, for 12/14 neurons tested after bilateral vagotomy and for 9/11 neurons tested after bilateral vagotomy and C(6)-C(7) spinal cord transection. TED changed activity of 31/190 (16%) neurons (28E, 3 I). Ipsilateral cervical vagotomy abolished TED-evoked responses of 5/12 neurons. Bilateral vagotomy eliminated responses of 2/4 neurons tested, and C(6)-C(7) spinal transection plus bilateral vagotomy eliminated responses of 2/2 neurons. Thus inputs from CED to C(1)-C(2) neurons most likely entered upper cervical dorsal roots, whereas inputs from TED were dependent on vagal pathways and/or sympathetic afferent pathways that entered the thoracic dorsal roots. These results supported a concept that C(1)-C(2) spinal neurons play a role in integrating visceral information from cervical and thoracic esophagus.

The purposes of this study were to (1) compare responses of T(3)-T(4) spinal neurons to thoracic and cervical esophageal distension (TED, CED) and (2) determine afferent pathways for esophageal input to these neurons. Extracellular potentials of single superficial and deeper T(3)-T(4) neurons were recorded in pentobarbital anesthetized male rats. Graded TED or CED was produced by water inflation (0.1-0.5 ml) of a latex balloon. TED changed activity of 121/432 (28%) neurons (114 were excited); CED activated 69/269 (26%) neurons (56 were excited). Of 151 neurons that were tested for responses to both TED and CED, 40 (26%) neurons responded to both TED and CED. Mean duration of excitatory responses in convergent neurons to TED was significantly longer than the duration of responses to CED (31.4+/-2.8 vs. 25.4+/-1.0 s, n=34, P<0.05). A total of 105 out of 121 (87%) and 66 out of 69 (96%) neurons responsive to TED and CED had somatic fields. Spinal transection at rostral C(1) and at C(7)-C(8) indicated that excitatory responses to TED resulted from activation of afferent input that entered thoracic spinal segments; whereas, excitatory responses to CED resulted from afferent inputs entering cervical or thoracic spinal segments. These data showed that the upper thoracic spinal cord received sensory information from the esophagus through cervical and/or thoracic spinal visceral afferent pathways.

Objective: To investigate the potential damage to the canine corneal endothelium following transcorneal iridal laser photocoagulation using a semiconductor diode laser., Animals Studied: Sixteen young mongrel dogs., Procedures: Baseline corneal endothelial cell counts and corneal thickness were measured in the central and temporal quadrants using a noncontact specular microscope under general anesthesia. Transcorneal iridal photocoagulation was applied using a semiconductor diode laser in a continuous mode with the use of an operating microscope. Fifteen dogs were treated, and the sixteenth dog served as a control. Fifteen different treatment combinations were randomly assigned to the 30 eyes; the fellow eye was treated differently. Three treatment factors were investigated: (1) laser energy intensity, (2) target tissue to endothelial distance, and (3) laser application duration. After 3 weeks the dogs were euthanized, specular microscopy was repeated, and the cornea was examined by scanning electron microscopy., Results: Dyscoria and focal iris darkening were noted in all eyes immediately following laser treatment. Focal corneal edema (n = 2) and an incipient anterior capsular cataract (n = 1) were also noted. Baseline mean corneal endothelial cell densities were 2530 cells/mm2 centrally and 2607 cells/mm2 temporally. Postlaser corneal endothelial cell densities were 2499 cells/mm2 centrally and 2523 cells/mm2 temporally. Mean prelaser corneal thickness measurements were 0.555 mm centrally and 0.549 mm temporally. Postlaser corneal thickness measurements were 0.580 mm centrally and 0.554 mm temporally. Statistical analyzes revealed no significant changes in endothelial cell densities (P > 0.05) or corneal thickness (P > 0.05) induced by any treatment combination. Aside from tissue handling and processing artifacts, scanning electron microscopy revealed no endothelial cell damage., Conclusions: Our study demonstrated by specular and scanning electron microscopy that diode laser iridal photocoagulation had no significant effect on the canine corneal endothelium within the parameters described. However, one must take into consideration the young age of the dogs and the potential for corneal endothelial cell regeneration in young dogs, and the relatively short period of postoperative study.

The aims of this study were to examine effects of urinary bladder distension (UBD) on T(3)-T(4) spinal neurons receiving cardiac and somatic noxious inputs and to determine the pathway involved in transmitting urinary bladder inputs to thoracic spinal segments. Extracellular potentials of single T(3)-T(4) neurons were recorded in pentobarbital anesthetized male rats. Either bradykinin solution (10(-5) M) or an allogenic mixture (adenosine 10(-3) M, bradykinin, histamine, serotonin, prostaglandin E2 10(-5) M each) was administered intrapericardially. UBD was produced by saline inflation (0.5-2.0 ml, 20 s). Of 487 neurons tested for responses to UBD, 70 were inhibited and 37 were excited. Seventy-six out of 336 neurons received convergent input from UBD and heart; 69/76 viscerovisceral convergent neurons had somatic fields. Spinal transection at rostral C(1) abolished UBD inhibition in 5/9 neurons; whereas transections at L(1)-L(2) abolished UBD inhibition in 3/3 cells tested. Results showed that T(3)-T(4) spinal neurons processing cardiac and somatic nociceptive information were primarily inhibited by input from the urinary bladder through either supraspinal structures or direct intraspinal pathways.

The Dementia Rating Scale (DRS; Mattis, 1976, 1988) is commonly used in the assessment of dementia, although little is known about the relationship of performance on this test to specific cognitive deficits in Alzheimer's disease (AD). Additionally, cognitive profiles have not been investigated across different levels of dementia as determined by the DRS. A sample of 133 individuals diagnosed with possible or probable AD was administered the DRS as part of a comprehensive neuropsychological evaluation. Composite scores for the cognitive domains of attention, executive functioning, visuospatial skills, language abilities, immediate recall, and delayed memory were derived by averaging demographically corrected T scores of key measures. Individual domain scores were also averaged to develop a global index score. Pearson correlations between composite and total DRS scores were highly significant (p<.001) for all domains and the global index score, with the exception of delayed memory, which showed a floor effect. When the sample was divided into mild and moderate-to-severe groups to examine the effects of disease severity on the relationship between the DRS and standard neurocognitive domain scores, the resulting mean neuropsychological profile scores were significantly different while maintaining a parallel pattern of impairment across domains. Results demonstrate the relationship between the DRS and standard cognitive domain functions, which appears to underscore the validity and robustness of the DRS in characterizing patterns of cognitive impairment across the AD spectrum.

The purpose of this study in anesthetized rats was to determine the effects of stimulating cardiopulmonary sympathetic afferents (CPSA) and vagal afferents on C1-C2 descending propriospinal neurons. We hypothesized that inhibition of spinal sensory neurons produced by CPSA or vagus activation might relay in C1-C2 spinal segments. Extracellular action potentials were recorded from 73 C1-C2 neurons whose axons were antidromically activated in lumbar segments. CPSA input excited 22 cells, inhibited two cells and excited/inhibited one cell, whereas vagal input excited eight cells and inhibited two cells. Results are consistent with the hypothesis that CPSA input can be processed in C1-C2 segments to produce neural modulation in distant spinal segments.

Some evidence shows that the upper cervical spinal cord might play an important role in propriospinal processing as a sensory filter and modulator for visceral afferents. The aims of this study were to determine (1). the responses of C(1)-C(2) spinal neurons to gastric distension and (2). the relative contribution of vagal and spinal visceral afferent pathways for transmission of gastric input to the upper cervical spinal cord. Extracellular potentials of single C(1)-C(2) spinal neurons were recorded in pentobarbital anesthetized male rats. Graded gastric distension (20-80 mm Hg) was produced by air inflation of a latex balloon surgically placed in the stomach. Sixteen percent of the neurons (32/198) responded to gastric distension; 17 neurons were excited and 15 neurons were inhibited by gastric distension. Spontaneous activity of neurons with inhibitory responses was higher than those neurons with excitatory responses (18.1+/-2.7 vs. 3.8+/-1.7 impulses s(-1), p<0.001). Twenty-eight of thirty-two (87.5%) neurons responded to mechanical stimulation of somatic fields on head, neck, ears or shoulder. Most lesion sites of neurons with excitatory responses were found in laminae V, VII; however, neurons with inhibitory responses were in laminae III, IV. Bilateral cervical vagotomy abolished responses of 4/8 neurons tested. Spinal transection at C(6)-C(7) abolished responses of the other four neurons that still responded to gastric distension after bilateral vagotomy. Results of these data supported the concept that a group of C(1)-C(2) spinal neurons might play a role in processing sensory information from the stomach that travels in vagal and spinal visceral afferent fibers.

This study was performed to investigate the respective role of sensory afferent and sympathetic fibers in peripheral vasodilatation induced by spinal cord stimulation at different hindpaw skin temperatures. Cooling the skin was used as a strategy to enhance sympathetic activity [Am. J. Physiol.: Heart Circ. Physiol. 263 (1992) H1197]. Cutaneous blood flow in the footpad of anesthetized rats was recorded using laser Doppler flowmetry. Local cooling (<25 degrees C) or moderate local cooling (25-28 degrees C) of the hindpaw was produced with a cooling copper coil. Spinal cord stimulation delivered at clinically relevant parameters and with 30%, 60%, and 90% of motor threshold induced the early phase of vasodilatation in the cooled and the moderately cooled hindpaw. In addition, spinal cord stimulation at 90% of motor threshold produced the late phase of vasodilatation only in the cooled hindpaw, which was possible to block by the autonomic ganglion-blocking agent, hexamethonium. The early responses to spinal cord stimulation in the moderately cooled hindpaw were not affected by hexamethonium. In contrast, both the early and the late phase responses were eliminated by CGRP (8-37), an antagonist of the calcitonin gene-related peptide receptor. After dorsal rhizotomy, spinal cord stimulation at 90% of motor threshold elicited hexamethonium-sensitive vasodilatation in the cooled hindpaw (late phase). These results suggest that spinal cord stimulation-induced vasodilatation in the cooled hindpaw (<25 degrees C) is mediated via both the sensory afferent (early phase of vasodilatation) and via suppression of the sympathetic efferent activity (late phase) although the threshold for vasodilatation via the sympathetic efferent fibers is higher than that via sensory nerves. In contrast, vasodilatation via sensory afferent fibers may predominate with moderate temperatures (25-28 degrees C). Thus, two complementary mechanisms for spinal cord stimulation-induced vasodilatation may exist depending on the basal sympathetic tone.

Selected patients with peripheral vascular disease can be treated with spinal cord stimulation (SCS) to improve blood flow in the limbs. However, the mechanisms producing these effects remain unclear. The present study was designed to investigate if SCS produces cutaneous vasodilation via antidromic activation of the unmyelinated C-fibers and/or the small myelinated fibers. SCS was applied to anesthetized rats with a ball electrode at the L2-L3 spinal level. In Protocol 1, effects of capsaicin were examined. Blood flow changes in the hindpaw induced by SCS were measured in the footpad with laser Doppler flowmeters. Topical application of capsaicin (1%) on the tibial nerve did not affect SCS-induced vasodilation at 30 and 60% of motor threshold (MT). However, the duration of vasodilation induced by SCS at 90% MT and at 10 times MT was significantly reduced after capsaicin application on the tibial nerve. In Protocol 2, antidromic compound action potentials (CAPs) of the tibial nerve were recorded in response to SCS. CAPs of the large and the small myelinated afferent fibers were observed in response to SCS at all intensities. However, even with SCS at ten times MT, CAPs of C-fibers could not be detected in the tibial nerve. In Protocol 3, antidromic CAPs of the dorsal root were measured in response to SCS. Antidromic CAPs of C-fibers in dorsal roots were evoked by SCS at >or=90% of MT. It is concluded that SCS-induced vasodilation at or=90% of MT may also involve antidromic activation of some unmyelinated C-fibers.

The purposes of this study were to examine responses of superficial (depth <300 microm) and deeper thoracic spinal neurons to chemical stimulation of cardiac afferents and effects of descending influences on these neurons. Extracellular potentials of single T(3)-T(4) neurons were recorded in pentobarbital anesthetized, paralyzed and ventilated male rats. A catheter was placed in the pericardial sac to administer 0.2 ml of a mixture of algogenic chemicals that contained adenosine (10(-3) M), bradykinin, histamine, serotonin, prostaglandin E(2) (10(-5) M). Fifteen of 55 (27%) superficial neurons responsive to intrapericardial chemicals were compared to 80/169 (47%) deeper neurons. All 15 superficial neurons that responded to cardiac afferents were excited (E), whereas 66 deeper neurons were excited, ten were inhibited and four showed excitation-inhibition. Spontaneous activity of superficial neurons with short-lasting excitatory responses was significantly lower than that of deeper neurons (P<0.05). Somatic receptive fields on chest, axilla, arm and upper back areas were found for 77/95 (81%) neurons that responded to intrapericardial chemicals. The proportion of somatic field properties and their sizes in superficial neurons were similar to deeper neurons. After cervical spinal transection, both spontaneous activity and responses to chemical stimulation of cardiac afferents significantly increased in six out of six neurons excited by intrapericardial injections. Results showed that chemical stimulation of cardiac afferents excited superficial T(3)-T(4) spinal neurons, whereas deeper neurons exhibited multiple patterns of responses. Some characteristics of subgroups of superficial neurons were quantitatively different from deeper neurons. Thoracic spinal neurons processing cardiac nociceptive information were under tonic descending inhibition.

The cross-cultural program of research presented here is about matters of temporal persistence--personal persistence and cultural persistence--and about solution strategies for solving the paradox of "sameness-in-change." The crux of this paradox resides in the fact that, on threat of otherwise ceasing to be recognizable as a self, all of us must satisfy at least two constitutive conditions. The first of these is that selves are obliged to keep moving or die, and, so, must continually change. The second is that selves must also somehow remain the same, lest all notions of moral responsibility and any commitment to an as yet unrealized future become nonsensical. Although long understood as a problem demanding the attention of philosophers, we argue that this same paradox arises in the ordinary course of identity development and dictates the different developmental routes taken by culturally mainstream and Aboriginal youth in coming to the identity-preserving conclusion that they and others are somehow continuous through time. Findings from a set of five studies are presented. The first and second studies document the development and refinement of a method for parsing and coding what young people say on the topic of personal persistence or self-continuity. Both studies demonstrate that it is not only possible to seriously engage children as young as age 9 or 10 years in detailed and codable discussions about personal persistence, but that their reasoning concerning such matters typically proceeds in an orderly and increasingly sophisticated manner over the course of their early identity development. Our third study underscores the high personal costs of failing to sustain a workable sense of personal persistence by showing that failures to warrant self-continuity are strongly associated with increased suicide risk in adolescence. Study four documents this same relation between continuity and suicide, this time at the macrolevel of whole cultures, and shows that efforts by Aboriginal groups to preserve and promote their culture are associated with dramatic reductions in rates of youth suicide. In the final study we show that different default strategies for resolving the paradox of personal persistence and change--Narrative and Essentialist strategies--distinctly characterize Aboriginal and non-Aboriginal youth.

The aim of this study was to determine if thoracic respiratory interneurons (TRINs) might receive peripheral noxious somatic and visceral inputs. Extracellular potentials of 78 respiration-related T(3) neurons, whose activity was driven by central respiratory output, were recorded from the intermediate zone in pentobarbital anesthetized, paralyzed, and ventilated male rats. These neurons were identified as interneurons by their locations and by the absence of antidromic activation from the cervical sympathetic trunk and cerebellum. Thoracic esophageal distension (ED) was produced by water inflation of a latex balloon (0.1-0.5 ml, 20 s). A catheter was placed in the pericardial sac to administer 0.2 ml bradykinin (10(-5) M) for noxious cardiac stimulation. Of 78 TRINs examined for ED, activity of 24 TRINs increased and activity of 8 TRINs decreased. Intrapericardial bradykinin increased activity in 26/65 TRINs tested and decreased activity in 5 TRINs. Seventy-four TRINs were tested for effects of brush, pressure, and pinch of the chest and upper back areas. No TRINs responded to brushing hair. Low-threshold responses to pressure were observed in 27 TRINs. Fourteen TRINs were wide dynamic range and 4 TRINs had high-threshold responses. Peripheral stimuli affected all types of TRINs, including inspiratory, expiratory, and biphasic neurons. Simultaneous phrenic recordings showed that effects of various somatic and visceral stimuli on TRINs were independent of central respiratory drive. Various somatovisceral and viscerovisceral patterns of input were observed in TRINs. The results suggested that TRINs participate in intraspinal processing and integration of nociceptive information from somatic fields and visceral organs.

Discharge patterns of thoracic dorsal horn neurons are influenced by chemical activation of cell bodies in cervical spinal segments C(1)-C(2). The present aim was to examine whether such activation would specifically affect thoracic respiratory interneurons (TRINs) of the deep dorsal horn and intermediate zone in pentobarbital sodium-anesthetized, paralyzed, artificially ventilated rats. We also characterized discharge patterns and pathways of TRIN activation in rats. A total of 77 cells were classified as TRINs by location, continued burst activity related to phrenic discharge when the respirator was stopped, and lack of antidromic response from selected pathways. A variety of respiration-phased discharge patterns was documented whose pathways were interrupted by ipsilateral C(1) transection. Glutamate pledgets (1 M, 1 min) on the dorsal surface of the spinal cord inhibited 22/49, excited 15/49, or excited/inhibited 3/49 tested cells. Incidence of responses did not depend on whether the phase of TRIN discharge was inspiratory, expiratory, or biphasic. Phrenic nerve activity was unaffected by chemical activation of C(1)-C(2) in this preparation. Besides supraspinal input, TRIN activity may be influenced by upper cervical modulatory pathways.

Projection neurons located in high cervical segments of primates are generally excited instead of inhibited by cardiopulmonary spinal inputs, which enter thoracic dorsal roots. Thus, high cervical neurons with axons that either ascend to the thalamus or descend to thoracolumbar spinal segments can process and transmit excitatory cardiac information. The purpose of this study was to determine whether the excitatory effects observed to cardiopulmonary afferent stimulation are a universal response in high cervical projection neurons to spinal visceral inputs. Urinary bladder distension (UBD) was used to stimulate visceral afferent inputs that enter lumbosacral dorsal roots. Effects were determined on extracellular activity of either spinothalamic tract (STT) neurons or descending propriospinal neurons that were recorded in high cervical segments of anesthetized monkeys. Results showed that 17/34 STT neurons were inhibited by UBD and 3/34 STT neurons were excited. Widespread visceral inputs, therefore, can excite high cervical STT neurons but the majority of responsive STT neurons were inhibited by UBD. Effects of UBD on high cervical descending propriospinal neurons were significantly different from responses in STT neurons. Extracellular activity of fewer propriospinal neurons was affected by UBD and responses were more variable; 3/26 neurons were inhibited, 5/26 neurons were excited and one neuron was excited/inhibited by UBD. These results showed that the generally excitatory responses of high cervical projection neurons to cardiopulmonary inputs were not duplicated by stimulation of sensory input from the urinary bladder. Furthermore, results of this study indicated that effects of sensory inputs on spinal neurons might vary depending on axonal projections of the neurons examined., (Copyright 2002 Elsevier Science B.V.)

Background: Individuals with allergies or asthma have had a long-standing bias against the use of chicken, goose, and duck feather pillows, comforters, quilts, and mattresses., Objective: We show that raw, unprocessed feathers contain dust-mite allergen that is removed by washing, and that feather pillows, whether covered or not, do not internally accumulate dust-mite allergen when used in mite-infested bedrooms over a 3-month period., Methods: Feathers obtained from six companies as unprocessed feathers (n = 8 batches) and processed feathers (n = 16 batches) were analyzed for dust-mite (Der p 1 and Der f 1) using monoclonal antibody-based immunoenzyametric assays with appropriate internal controls. Five pairs of new feather pillows (one covered and one uncovered) were placed in five bedrooms with known dust-mite contamination for 90 days. The pillows were then assayed for mite content., Results: Dust-mite allergen was detected in 7 of 8 unprocessed feather samples; combined Der p 1 and Der f 1 mean = 524 ng/g, range 152 to 1,850 ng/g, whereas all 17 manufacturer-processed feather samples contained no detectable dust-mite. Although 4 of 5 bedrooms contained significant dust-mite allergen (>2,000 ng or Der p 1 and f 1, range 2,500 to 10,300 ng/g), none of the 90-day feather pillows became contaminated by dust-mite allergen even in the absence of a pillow cover., Conclusions: Feathers washed using industrial methods do not contain detectable dust-mite allergen. Pillows manufactured with processed feathers, whether encased in a dust cover or not, do not become contaminated by dust-mite allergen after 90 days of use in environments containing significant dust-mite allergen contamination.

Noxious stimulation of spinal afferents inhibits primate spinothalamic tract (STT) neurons in segments distant from the region of afferent entry. Inhibitory effects of cardiopulmonary sympathetic afferent (CPSA) stimulation remain after C(1) transection but disappear with spinal transection between C(3) and C(7). We hypothesized that spinal inhibitory effects produced by CPSA stimulation are processed by neurons in C(1)-C(3) segments. One purpose of this study in anesthetized monkeys was to determine whether chemical activation of high cervical neurons reduced sacral STT cell responses to colorectal distension (CRD) and urinary bladder distension (UBD). First, effects and interactions of pelvic and cardiopulmonary visceral afferent inputs were determined in 10 monkeys on extracellular activity of sacral STT neurons recorded in deep dorsal horn. CRD and UBD increased activity in 95 and 91% of sacral STT neurons, respectively. CPSA and cardiopulmonary vagal stimulation decreased activity in 84 and 56% of STT neurons, respectively. CPSA stimulation decreased CRD-evoked activity in six of eight sacral STT neurons and decreased UBD-evoked activity in five of eight STT neurons tested. Excitatory amino acid application at C2 segment decreased CRD-evoked responses in 7 of 10 sacral STT neurons and decreased UBD-evoked responses in 9 of 12 STT neurons. The second purpose of this study was to examine responses of C(1)-C(3) descending propriospinal neurons to stimulation of cardiopulmonary afferent fibers. If C(1)-C(3) neurons process CPSA input to suppress STT transmission, then CPSA stimulation should excite C(1)-C(3) neurons with descending projections. Effects of thoracic vagus nerve stimulation also were examined. Vagal stimulation inhibits STT neurons in segments below C(3) but excites C(1)-C(3) STT neurons; we theorized that vagal inhibition of sensory transmission might relay in high cervical segments and, therefore, excite C(1)-C(3) descending propriospinal neurons. Extracellular discharge rate was recorded for C(1)-C(3) neurons antidromically activated from thoracic or lumbar spinal cord in 24 monkeys. CPSA stimulation increased activity of 16 of 45 neurons and inhibited one cell. Thoracic vagus stimulation increased activity of 20 of 43 neurons and inhibited one cell; stimulation of abdominal vagus fibers did not affect activity of six of six cells that were excited by thoracic vagal input. Mechanical stimulation of somatic fields excited 30 of 41 neurons tested. All neurons activated by visceral input received convergent somatic input from noxious pinch of somatic receptive fields that generally included the neck and upper body; 11 C(1)-C(3) propriospinal neurons did not respond to any afferent input examined. Results of these studies were consistent with the idea that modulation of spinal nociceptive transmission might involve neuronal connections in high cervical segments.

Electrical stimulation of vagal afferents or cardiopulmonary sympathetic afferent fibers excites C(1)--C(2) spinal neurons. The purposes of this study were to compare the responses of superficial (depth <0.35 mm) and deeper C(1)--C(2) spinal neurons to noxious chemical stimulation of cardiac afferents and determine the relative contribution of vagal and sympathetic afferent pathways for transmission of noxious cardiac afferent input to C(1)--C(2) neurons. Extracellular potentials of single C(1)--C(2) neurons were recorded in pentobarbital anesthetized and paralyzed male rats. A catheter was placed in the pericardial sac to administer a mixture of algogenic chemicals (0.2 ml) that contained adenosine (10(-3) M), bradykinin, histamine, serotonin, and prostaglandin E(2) (10(-5) M each). Intrapericardial chemicals changed the activity of 20/106 (19%) C(1)--C(2) spinal neurons in the superficial laminae, whereas 76/147 (52%) deeper neurons responded to cardiac noxious input (P < 0.01). Of 96 neurons responsive to cardiac inputs, 48 (50%) were excited (E), 41 (43%) were inhibited (I), and 7 were excited/inhibited (E-I) by intrapericardial chemicals. E or I neurons responsive to intrapericardial chemicals were subdivided into two groups: short-lasting (SL) and long-lasting (LL) response patterns. In superficial gray matter, excitatory responses to cardiac inputs were more likely to be LL-E than SL-E neurons. Mechanical stimulation of the somatic field from the head, neck, and shoulder areas excited 85 of 95 (89%) C(1)--C(2) spinal neurons that responded to intrapericardial chemicals; 31 neurons were classified as wide dynamic range, 49 were high threshold, 5 responded only to joint movement, and no neuron was classified as low threshold. For superficial neurons, 53% had small somatic fields and 21% had bilateral fields. In contrast, 31% of the deeper neurons had small somatic fields and 46% had bilateral fields. Ipsilateral cervical vagotomy interrupted cardiac noxious input to 8/30 (6 E, 2 I) neurons; sequential transection of the contralateral cervical vagus nerve (bilateral vagotomy) eliminated the responses to intrapericardial chemicals in 4/22 (3 E, 1 I) neurons. Spinal transection at C(6)--C(7) segments to interrupt effects of sympathetic afferent input abolished responses to cardiac input in 10/10 (7 E, 3 I) neurons that still responded after bilateral vagotomy. Results of this study support the concept that C(1)-C(2) superficial and deeper spinal neurons play a role in integrating cardiac noxious inputs that travel in both the cervical vagal and/or thoracic sympathetic afferent nerves.

This study examined whether spinal cord stimulation (SCS) at intensities below motor threshold (MT) produces cutaneous vasodilation through sympathetic inhibition and/or antidromic activation of sensory fibers. SCS was applied to anesthetized rats with stimulus parameters used clinically, i.e. 50 Hz, 0.2 ms and stimulus intensities at 30, 60 or 90% of MT. SCS-induced vasodilation was not attenuated by hexamethonium, an autonomic ganglion blocking agent, but was abolished by CGRP-(8-37), an antagonist of the calcitonin gene-related peptide (CGRP) receptor. We concluded that SCS-induced vasodilation under the conditions of this study was mediated by peripheral release of CGRP via antidromic activation of sensory fibers.

Extracellular potentials of 38 C1-C2 spinothalamic tract (STT) neurons in anesthetized monkeys (Macaca fascicularis) were examined for responses to intrapericardiac injections of an algogenic chemical mixture (adenosine, 10(-3) M; bradykinin, prostaglandin E(2), serotonin, histamine, each 10(-5) M). Chemical stimulation of cardiac/pericardiac receptors increased activity of 21 cells, decreased activity of 5 cells, and did not change activity of 12 cells. Cells excited by chemical stimuli received input from noxious mechanical stimulation of somatic fields; most receptive fields included the neck, inferior jaw, or head areas. Nerve ablations in 11 cells excited by intrapericardiac chemicals showed that cardiac input activated by algogenic chemicals traveled primarily in vagal afferent fibers to C1-C2 segments; phrenic or cardiopulmonary sympathetic inputs were predominant in 2 of 11 cells. These results supported the concept that activation of cardiac vagal afferents might lead to the production of referred pain sensation in somatic fields innervated from high cervical segments.

Objective: Electrical stimulation of the dorsal aspect of the upper thoracic spinal cord is used increasingly to treat patients with severe angina pectoris refractory to conventional therapeutic strategies. Clinical studies show that spinal cord stimulation (SCS) is a safe adjunct therapy for cardiac patients, producing anti-anginal as well as anti-ischemic effects. However, little information is yet available about the underlying mechanisms involved., Methods: In order to determine its mechanism of action, the effects of SCS on the final common integrator of cardiac function, the intrinsic cardiac nervous system, was studied during basal states as well as during transient (2 min) myocardial ischemia. Activity generated by intrinsic cardiac neurons was recorded in 9 anesthetized dogs in the absence and presence of myocardial ischemia before, during and after stimulating the dorsal T1-T2 segments of the spinal cord at 66 and 90% of motor threshold using epidural bipolar electrodes (50 Hz; 0.2 ms; parameters within the therapeutic range used in humans)., Results: The SCS suppressed activity generated by intrinsic cardiac neurons. No concomitant change in monitored cardiovascular indices was detected. Neuronal activity increased during transient ventricular ischemia (46%), as well as during the early reperfusion period (68% compared to control). Despite that, activity was suppressed during both states by SCS., Conclusions: SCS modifies the capacity of intrinsic cardiac neurons to generate activity. SCS also acts to suppress the excitatory effects that local myocardial ischemia exerts on such neurons. Since no significant changes in monitored cardiovascular indices were observed during SCS, it is concluded that modulation of the intrinsic cardiac nervous system might contribute to the therapeutic effects of SCS in patients with angina pectoris.

Responses of upper cervical inspiratory neurons (UCINs) to abdominal visceral or cardiopulmonary sympathetic stimulation were studied using extracellular recordings from 213 UCINs in 54 pentobarbital sodium-anesthetized and paralyzed rats. Phrenic nerve activity was used to assess inspiration. The UCINs discharging during inspiration only were mainly in the C(1) segment, whereas phase-spanning UCINs were mostly in the C(2) segment. Phase-spanning activity was typically retained after overventilation or vagotomy. When greater splanchnic nerve (GSN) or cardiopulmonary sympathetic afferent (CPSA) fibers were electrically stimulated, augmented UCIN activity was observed in 65% of cells responding to CPSA stimulation but in only 17% of cells responding to GSN. Response latencies were 10.7 +/- 0.5 and 20.6 +/- 1.5 (SE) ms, respectively. Many augmented responses to CPSA stimulation (64%) and all augmented responses to GSN stimulation were followed by suppression of UCIN discharge (biphasic response). Phrenic nerve activity was suppressed by both GSN and CPSA stimulation, but with shorter latency for the latter (29 +/- 0.7 vs. 14.0 +/- 0.7 ms). Excitation of UCINs using CPSA stimulation occurs more often and by a more direct pathway than for GSN input.

Children's developing conceptions of what is right or proper are commonly studied without reference to concomitant changes in their understanding of beliefs, just as studies of young people's maturing grasp of the belief entitlement process ordinarily proceed separately from any examination of the value considerations that invest beliefs with meaning. In an effort to reverse these isolationist practices, a case is made for rereading the fact-value dichotomy that currently works to divide the contemporaneous literatures dealing with children's moral reasoning development and their evolving theories of mind. Findings from two research programs, in which children's beliefs about truth and rightness are combined, serve to illustrate the natural interdependence of these moral and epistemic matters.

We have shown that stimulation of cardiopulmonary sympathetic afferent fibers activates relays in upper cervical segments to suppress activity of lumbosacral spinal cells. The purpose of this study was to determine if chemical excitation (glutamate) of upper cervical cell bodies changes the spontaneous activity and evoked responses of lumbosacral spinal cells to colorectal distension (CRD). Extracellular potentials were recorded in pentobarbital-anesthetized male rats. CRD (80 mmHg) was produced by inflating a balloon inserted in the descending colon and rectum. A total of 135 cells in the lumbosacral segments (L(6)-S(2)) were activated by CRD. Seventy-five percent (95/126) of tested cells received convergent somatic input from the scrotum, perianal region, hindlimb, and tail; 99/135 (73%) cells were excited or excited/inhibited by CRD; and 36 (27%) cells were inhibited or inhibited/excited by CRD. A glutamate (1 M) pledget placed on the surface of C(1)-C(2) segments decreased spontaneous activity and excitatory CRD responses of 33/56 cells and increased spontaneous activity of 13/19 cells inhibited by CRD. Glutamate applied to C(6)-C(7) segments decreased activity of 10/18 cells excited by CRD, and 9 of these also were inhibited by glutamate at C(1)-C(2) segments. Glutamate at C(6)-C(7) increased activity of 4/6 cells inhibited by CRD and excited by glutamate at C(1)-C(2) segments. After transection at rostral C(1) segment, glutamate at C(1)-C(2) still reduced excitatory responses of 7/10 cells. Further, inhibitory effects of C(6)-C(7) glutamate on excitatory responses to CRD still occurred after rostral C(1) transection but were abolished after a rostral C(6) transection in 4/4 cells. These data showed that C(1)-C(2) cells activated with glutamate primarily produced inhibition of evoked responses to visceral stimulation of lumbosacral spinal cells. Inhibition resulting from activation of cells in C(6)-C(7) segments required connections in the upper cervical segments. These results provide evidence that upper cervical cells integrate information that modulates activity of distant spinal neurons responding to visceral input.

Trigeminal, spinal and vagal afferent fibers overlap in C1-C2 segments. We hypothesized that trigeminal input from the superior sagittal sinus (SSS) can excite C1-C2 spinothalamic tract (STT) neurons receiving thoracic visceral or phrenic inputs. Effects of SSS stimulation were evenly divided among cells responding to each nerve stimulus; magnitude of responses to ipsilateral vagal input was greater in neurons excited by SSS input. Somatic fields of 80% of neurons responding to SSS stimulation included face areas innervated by the trigeminal nerve, whereas somatic fields of 89% of neurons unaffected by SSS stimulation were located only on areas innervated by cervical spinal nerves. Results are consistent with the idea that pain referred to trigeminal areas could originate in thoracic organs., (Copyright 1999 Elsevier Science B.V.)

The purpose of this study was to determine the involvement of supraspinal centers and spinal synaptic integration in cutaneous vasodilation mediated by dorsal spinal cord stimulation (DCS). Laser Doppler flowmetry was used to assess cutaneous blood flow changes in the rat hindpaw during DCS with a unipolar ball electrode placed at the L2-L3 spinal level. Results demonstrated that transecting the spinal cord at the T10 spinal segment did not alter the DCS response while T13 spinal transection abolished the DCS-induced vasodilation. Inhibition of synaptic activity with topical application of muscimol (0.2 mM) on the dorsal surface of the spinal cord markedly attenuated the DCS response. In conclusion DCS-induced vasodilation involved synaptic integration but did not require input from rostral spinal sites or supraspinal areas.

The spatial distribution and densities of photoreceptors in seven whole-mounted porcine retinas were studied and maps illustrating photoreceptor topography were constructed. Total photoreceptor densities ranged from to 83 000 to 200 000 cells/mm2, with a mean of 138 500 cells/mm2. Cone densities ranged from 39 000 (area centralis) to 8500 cones/mm2 (peripherally), with a mean of 16 400 cones/mm2. Rod:cone ratios ranged from 3:1 centrally to 16:1 peripherally, with a mean ratio of 8:1. Averaged photoreceptor densities are greatest (166 000 cells/mm2) within the central inferior retina, and regional differences in rod:cone ratios were found. Cone densities are increased in a broad region dorsal to the optic disk, extending both nasally and temporally. This region is believed to represent the area centralis. Cone densities gradually decrease and taper towards the periphery and inferior retina as rod:cone ratios increase. In addition to the many anatomic and ultrastructural similarities to the human eye, this study illustrates similarities within the photoreceptor mosaic of these two species and supports the use of the pig retina as a model for human/animal research.