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Biomedical subjects

Michael J Farrell

Publications and source records attributed to Michael J Farrell.

9 recordsLinked to original sources

Pain sensitivity and fMRI pain-related brain activity in Alzheimer's disease.

People with Alzheimer's disease are administered fewer analgesics and report less clinical pain than cognitively intact peers with similar painful diseases or injuries, prompting speculation about the likely impact of neurodegeneration on central pain processing. The present study measured pain ratings and functional MRI (fMRI) brain responses following mechanical pressure simulation in 14 patients with Alzheimer's disease and 15 age-matched controls. Contrary to the prevailing hypothesis that this disease is likely to differentially reduce emotional responses to pain, we show that activity in both medial and lateral pain pathways is preserved. Moderate pain was evoked with similar stimuli in both groups, and was associated with a common network of pain-related activity incorporating cingulate, insula and somatosensory cortices. Between-group analyses showed no evidence of diminished pain-related activity in Alzheimer's disease patients compared with controls. In fact, compared with controls, patients showed greater amplitude and duration of pain-related activity in sensory, affective and cognitive processing regions consistent with sustained attention to the noxious stimulus. The results of this study show that pain perception and processing are not diminished in Alzheimer's disease, thereby raising concerns about the current inadequate treatment of pain in this highly dependent and vulnerable patient group.

Aged↗

Unique, common, and interacting cortical correlates of thirst and pain.

This study used positron-emission tomography to establish the patterns of brain activity involved in the isolated and concurrent experiences of thirst and pain. Ten subjects were scanned while experiencing pain evoked with noxious pressure, while experiencing thirst after the infusion of hypertonic saline, and while experiencing pain when thirsty. After the onset of thirst, noxious pressure evoked more intense sensations of pain. Noxious pressure did not change subjective ratings of thirst. Thirst caused activation in the anterior cingulate (Brodmann area 32) and the insula. Enhanced pain responses were associated with increased activity in cortical regions that are known to correlate with pain intensity, and also with unique activity in the pregenual anterior cingulate and ventral orbitofrontal cortex. These findings suggest a role for limbic and prefrontal cortices in the modulation of pain during the experience of thirst.

Adult↗

Role of penicillin-binding protein 1b in competitive stationary-phase survival of Escherichia coli.

The penicillin-binding proteins (PBPs) catalyze the synthesis and modification of bacterial cell wall peptidoglycan. Although the biochemical activities of these proteins have been determined in Escherichia coli, the physiological roles of many PBPs remain enigmatic. Previous studies have cast doubt on the individual importance of the majority of PBPs during log phase growth. We show here that PBP1b is vital for competitive survival of E. coli during extended stationary phase, but the other nine PBPs studied are dispensable. Loss of PBP1b leads to the stationary phase-specific competition defective phenotype and causes cells to become more sensitive to osmotic stress. Additionally, we present evidence that this protein, as well as AmpC, may assist in cellular resistance to beta-lactam antibiotics.

Bacterial Proteins↗

Sonographically guided percutaneous muscle biopsy in diagnosis of neuromuscular disease: a useful alternative to open surgical biopsy.

OBJECTIVE: The purpose of this study was to evaluate the feasibility of sonographically guided percutaneous muscle biopsy in the investigation of neuromuscular disorders. METHODS: Sonographically guided percutaneous needle biopsy of skeletal muscle was performed with a 14-gauge core biopsy system in 40 patients over a 24-month period. Patients were referred from the Department of Neurology under investigation for neuromuscular disorders. Sonography was used to find suitable tissue and to avoid major vascular structures. A local anesthetic was applied below skin only. A 3- to 4-mm incision was made. Three 14-gauge samples were obtained from each patient. All samples were placed on saline-dampened gauze and sent for neuropathologic analysis. As a control, we retrospectively assessed results of the 40 most recent muscle samples acquired via open surgical biopsy. RESULTS: With the use of sonography, 32 (80%) of 40 patients had a histologic diagnosis made via percutaneous needle biopsy. This included 26 (93%) of 28 patients with acute muscular disease and 6 (50%) of 12 patients with chronic disease. In the surgical group (all acute disease), 38 (95%) of 40 patients had diagnostic tissue attained. CONCLUSIONS: Sonographically guided percutaneous 14-gauge core skeletal muscle biopsy is a useful procedure, facilitating diagnosis in acute muscular disease. It provides results comparable with those of open surgical biopsy in acute muscular disease. It may also be used in chronic muscular disease but repeated or open biopsy may be needed.

Adult↗

Brain activity associated with painfully hot stimuli applied to the upper limb: a meta-analysis.

The capacity of pain to alert against potential injury or focus attention on damaged tissue is enhanced by the intrinsically aversive nature of the experience. Finding methods to relieve pain will ultimately be facilitated by deeper understanding of the processes that contribute to the experience, and functional brain imaging has contributed substantially toward that end. An impressive body of literature has identified a distributed network of pain-related activity in the brain that is subject to considerable modulation by different stimulus parameters, contextual factors, and clinical conditions. The fundamental substrates of the pain network are yet to be distilled from the highly variable results of studies published thus far. Qualitative reviews of the pain-imaging literature have been contributory, but lack the greater surety of quantitative methods. We employ the activation likelihood estimation (ALE) meta-analytic technique to establish the most consistent activations among studies reporting brain responses subsequent to the application of noxious heat. A network of pain-related activity was replicated for stimuli to either upper limb that included two discernible regions of the mid-anterior cingulate cortex, bilateral thalami, insula, and opercula cortices, posterior parietal cortex, premotor cortex, supplementary motor area, and cerebellum. The findings of the meta-analysis resonate with other streams of information that continue to enhance our understanding of pain in the brain. The results also point toward new areas of research that may be fruitful for the exploration of central pain processing.

Brain↗

Knee pain and radiographic osteoarthritis interact in the prediction of levels of self-reported disability.

OBJECTIVE: To determine predictors of disability depending on whether joint deformity and pain reporting exist independently or concurrently. METHODS: Subjects were 154 volunteers for an osteoarthritis screening examination. Eligible subjects completed questionnaires for physical function, pain, and depressive symptoms; underwent evoked pain testing for tenderness assessment; and had anteroposterior and lateral radiographs taken of both knees. Two blinded rheumatologists scored the images using Kellgren-Lawrence criteria to determine presence of deformity. RESULTS: Subjects were divided into 3 subgroups based on radiographic evidence of deformity and self-reported pain. Disability was greatest when pain and deformity occurred together (F[2,151] = 18.8, P < 0.0001). Self-reported disability in the absence of deformity was predicted by body mass index, pain threshold, and anxiety symptoms; disability was predicted by the number of osteophytes and depressive symptoms when pain and deformity occurred together. CONCLUSION: Self-reported disability in osteoarthritis of the knee is greatest with concurrent pain and joint deformity. When pain and deformity do not cooccur, disability appears to be related to separate factors, including anxiety and pain threshold (e.g., tenderness).

Aged↗

The growth advantage in stationary-phase phenotype conferred by rpoS mutations is dependent on the pH and nutrient environment.

Escherichia coli cells that are aged in batch culture display an increased fitness referred to as the growth advantage in stationary phase, or GASP, phenotype. A common early adaptation to this culture environment is a mutant rpoS allele, such as rpoS819, that results in attenuated RpoS activity. However, it is important to note that during long-term batch culture, environmental conditions are in flux. To date, most studies of the GASP phenotype have focused on identifying alleles that render an advantage in a specific environment, Luria-Bertani broth (LB) batch culture. To determine what role environmental conditions play in rendering relative fitness advantages to E. coli cells carrying either the wild-type or rpoS819 alleles, we performed competitions under a variety of culture conditions in which either the available nutrients, the pH, or both were manipulated. In LB medium, we found that while the rpoS819 allele confers a strong competitive fitness advantage at basic pH, it confers a reduced advantage under neutral conditions, and it is disadvantageous under acidic conditions. Similar results were found using other media. rpoS819 conferred its greatest advantage in basic minimal medium in which either glucose or Casamino Acids were the sole source of carbon and energy. In acidic medium supplemented with either Casamino Acids or glucose, the wild-type allele conferred a slight advantage. In addition, populations were dynamic under all pH conditions tested, with neither the wild-type nor mutant rpoS alleles sweeping a culture. We also found that the strength of the fitness advantage gained during a 10-day incubation is pH dependent.

Acids↗

The impact of dementia on the pain experience.

Advancing age is associated with an increased risk of illness. Investigating the influence of ageing on the experience of pain must take account of this association, as well as the impact of past experience of life. Dementia, which is almost exclusively restricted to older people, is an illness where the effects of past experience and future life anticipation are severely curtailed. The influence of dementia on the experience of pain has received little attention and many questions remain unanswered. This review draws upon this literature to describe current knowledge of the area. Suggestions for further research are made.

Aging↗