Attention-enhancing effects of propranolol and synergistic effects with nicotine.

Nicotine increases the output of every major neurotransmitter. In previous studies designed to identify the secondary neurotransmitter systems mediating nicotine's attention-enhancing effects in a rat model, the ß-adrenoceptor antagonist propranolol blocked these effects. The present study was designed to test whether this mechanism held true in humans, thus guiding development of novel nicotinic agonists for cognitive enhancement. Twenty-six nonsmokers completed a nicotine (7 mg/24 h transdermally) x propranolol (40 mg p.o., body weight-adjusted) interaction study. Over four test days, each participant received double-placebo, nicotine only, propranolol only, and nicotine plus propranolol in randomized sequence before cognitive testing. No drug effects were seen in a visuospatial attention task. In the Rapid Visual Information Processing Task, performed in two 15-min blocks, neither drug alone significantly affected hit rate, but both drugs combined acted synergistically to alleviate its decrement over time in the first block and displayed additive beneficial effects in the second. In a change detection task, propranolol enhanced accuracy and reduced reaction time independent of nicotine presence. Propranolol also enhanced subjective self-reports of vigor. Overall, the findings were contrary to those hypothesized. Propranolol displayed beneficial effects on cognition, especially on sustaining performance over time. ß-adrenoceptor activation by nicotine-induced noradrenaline release appeared to limit performance-enhancing effects of nicotine, because they were unmasked by ß-adrenoceptor antagonism. The results suggest that cognitive effects of changes in ß-adrenoceptor tone are context-dependent; contrary to rodent paradigms, human cognitive paradigms require no physical orienting in space but prolonged periods of remaining stationary while sustaining predictable processing demands.

Calcaneal Osteomyelitis: Current Treatment Concepts.

Calcaneal osteomyelitis can be a debilitating disease if proper treatment protocols are not initiated. This literature review details the epidemiology, clinical, diagnostic, and prognostic factors, and medical management in those who developed this disease.

Solid-Cystic Hidradenoma: A Dorsal Foot Presentation.

Solid-cystic hidradenoma is a benign cutaneous tumor with eccrine sweat gland origins that is most commonly found in the head, neck, trunk, and upper extremity regions of patients in the middle to older age groups. These lesions are generally asymptomatic, slow-growing, solitary, and nonulcerative in presentation. Degenerative malignant transformation of this tumor is very rare. In this case report, the authors describe the marginal surgical excision and subsequent microscopic pathologic diagnosis of a moderate sized solid-cystic hidradenoma of the dorsolateral forefoot in a middle-aged male patient.

Nicotine effects on cognitive remediation training outcome in people with schizophrenia: A pilot study.

Cognitive remediation training can alleviate cognitive impairment associated with schizophrenia, but the impact is limited by small effect sizes. The present study aimed at augmenting training effects by administering nicotine prior to training sessions. Twenty-five people with schizophrenia were enrolled in a 10-week, 5 days/week, computerized cognitive training regimen. Participants were randomized to two treatment groups: nicotine or placebo. Every Monday and Thursday, the nicotine group received a nicotine lozenge before the training, and the placebo group a placebo lozenge. Outcome measurements were conducted on a no-lozenge day in weeks 0, 4, 7, and 10, and at 4-week follow-up. The MATRICS Consensus Cognitive Battery composite score improved over time, but there was no group difference in this effect. A significant group difference emerged over time in the reasoning/problem solving sub-domain: the placebo group improved but not the nicotine group, suggesting that nicotine exposure negatively impacted training benefits on executive control processes. There were no effects on psychiatric symptoms. However, significant improvements were seen across groups on the Quality of Life Scale and the Cognitive Assessment Interview, measuring real-life functional outcome. In conclusion, the present study failed to find evidence that nicotine exposure during cognitive remediation training may potentiate training benefits.

Nicotine effects on associative learning in human non-smokers.

Tobacco smoking is the most common preventable cause of death in the US. Nicotine is considered the primary constituent responsible for tobacco addiction. Its paradoxically high abuse potential may reflect behavioral control by drug-associated stimuli, which appears to play a larger role for tobacco dependence than for other abused drugs. We tested a potential explanation, hypothesizing that nicotine enhances associative learning, the mechanism underlying the conditioning of drug-associated stimuli. Thirty-two non-smokers were exposed to transdermal nicotine (7 mg/24 h) and placebo in a double-blind cross-over study and tested with behavioral paradigms designed to isolate incidental stimulus-stimulus or stimulus-response learning. The stop signal task required speeded gender judgments of face stimuli. A tone signaled when to withhold the response. Unbeknownst to participants, some faces were always paired with stop trials. Nicotine enhanced the facilitation of stop-responses to these stimuli, and the slowing of go-responses when previously stop-associated stimuli were paired with go trials, indicating stronger associations between paired stimuli and the stop signal/stop response. Another task required feedback-based learning of associations between pairs of shape stimuli. Five pairs were made from either ten different stimuli, or from different combinations of two identical sets of five stimuli with correct associations depending on contextual information. Nicotine increased incorrect choices of stimuli that were associated in a different context, indicating stronger stimulus-stimulus associations at the expense of flexible context-adaptive behavior. The results indicate that nicotine can enhance incidental associative learning, a mechanism that may promote the formation of smoking-associated stimuli and cue-controlled drug-taking.

Angioleiomyoma of the Lower Leg.

Angioleiomyomas are benign tumefactions that originate from smooth muscle in vascular structures and are difficult to definitively diagnose preoperatively. Although these lesions are rarely encountered in the foot, the lower extremity is the most common site of occurrence. An angioleiomyoma typically manifests as a small, painful, solitary, mobile lesion. This case report describes a lateral retromalleolar para-Achilles tendon insertional location for a moderately sized immobile solid tumefaction in the subcutaneous tissues. The lesion was nonpainful and progressively enlarged over 5 years. An excisional biopsy was performed, and the nodular lesion was subsequently diagnosed histopathologically as an angioleiomyoma. Owing to the ambiguous nature of the clinical findings, angioleiomyoma should be included in the differential diagnosis of lower-extremity soft-tissue manifestations.

A test of the cognitive-enhancing potential of low-dose mecamylamine in healthy non-smokers.

RATIONALE: The beneficial effects of nicotinic acetylcholine receptor (nAChR) agonists on cognitive performance have been widely shown. Paradoxically, recent preclinical studies employing extremely low doses of nAChR antagonists have also found cognitive enhancement, perhaps pointing to a novel treatment mechanism for cognitive deficits. OBJECTIVES: The aim was to test whether low doses of the nAChR antagonist mecamylamine would benefit performance in human volunteers. METHODS: The study employed a double-blind within-subject design. Over four separate days, healthy adult non-smokers (n = 23) were tested with placebo and three trace doses of mecamylamine (0.25-1 mg, p.o.), adjusted for body weight. Participants performed three computerized tasks: a task of spatial selective attention and stimulus detection, the rapid visual information processing task (RVIPT) taxing sustained attention and working memory, and a change detection short-term memory task. Subjective state and vital signs were assessed repeatedly. RESULTS: Mecamylamine did not improve performance in any of the tasks. Any trends that were observed instead pointed toward performance impairment. Mecamylamine also had no effects on subjective state or vital signs. CONCLUSIONS: The present results do not support the hypothesized cognitive-enhancing potential of low doses of mecamylamine. Contrary to preclinical reports, these findings speak against low-dose nAChR antagonism as a novel avenue for treating cognitive deficits.

Effects of repeated yohimbine administration on reinstatement of palatable food seeking: involvement of dopamine D1 -like receptors and food-associated cues.

Acute exposure to the pharmacological stressor yohimbine induces relapse to both food and drug seeking in a rat model. However, no systematic studies on the effects of chronic stress on relapse have been conducted. Because chronic stress causes changes in dopamine D1 -like receptor-mediated transmission in prefrontal cortex (a relapse node), we tested the hypothesis that chronic exposure to stress increases vulnerability to relapse via dopamine-mediated mechanisms. Additionally, to determine the role of food-conditioned cues in reinstatement of food seeking, we made discrete food-paired cues either available (CS Present) or not available (CS Absent) during extinction and reinstatement testing. Rats responded for palatable food reinforcers in daily 3-hour sessions, and the behavior was extinguished. To model chronic stress, rats were injected daily with yohimbine (0.0, 2.5, or 5.0 mg/kg; i.p.) during the first 7 days of extinction. Injections were combined with SCH-23390 (0.0, 5.0, or 10.0 µg/kg; i.p.), a D1 -like receptor antagonist. Rats were then tested for reinstatement of food seeking triggered by acute yohimbine (0.0, 1.0, or 2.0 mg/kg; i.p.) and pellet priming. Rats treated previously with chronic yohimbine displayed increased responding following acute yohimbine priming relative to non-chronically stressed rats, but in the CS Absent condition only. Conversely, the lower dose of chronic yohimbine caused an increase in pellet-primed reinstatement, but this effect was more pronounced in the CS Present condition. Importantly, SCH-23390 combined with repeated yohimbine injections attenuated these effects. Thus, chronic stress may increase vulnerability to relapse under specific circumstances via a dopamine D1 -like receptor-mediated mechanism.