Anterior insular volume decrease is associated with dysfunction of the reward system in patients with chronic pain.

BACKGROUND: Chronification of pain is associated with both anatomical and functional alterations of the brain. Alteration in regional grey matter volume might potentially be associated with modified activity of specific brain networks. In this cross-sectional, observational study, we sought to identify brain regions with grey matter volume changes in patients with chronic pain and to reveal its significance by analysing alteration in functional connectivity from those regions. We further explored relevance of such alterations with psychometrics of chronic pain. METHODS: We recruited 23 patients with chronic pain and 17 age-, gender-matched healthy control subjects. After completing multiple psychophysical questionnaires, each subject underwent resting-state functional magnetic resonance imaging and three-dimensional anatomical imaging on a 3 Tesla magnetic resonance imaging scanner. RESULTS: Patients with chronic pain showed significant volume decrease at the right anterior insular cortex (p < 0.001) and the left middle cingulate cortex (p < 0.001) compared with healthy controls. They also showed decreased connectivity between the right anterior insular cortex and the left nucleus accumbens in negative association with the Pain Catastrophizing Scale (R2  = 0.20, p = 0.046) and the Beck's Depression Inventory scores (R2  = 0.24, p = 0.017). CONCLUSIONS: Decreased grey matter volumes of those core regions for affective processing of pain might be a common cerebral feature shared by, at least some of, different aetiologies of chronic pain. Dysfunctional network between the anterior insular cortex and the nucleus accumbens might reflect affective and motivational disability involved in chronic pain. Such anatomical and functional profiles could potentially be part of a cerebral signature for chronification of pain. SIGNIFICANCE: This article illustrates decreased network activity of the reward system in association with insular cortical volume decrease in patients with chronic pain, and its close relationships with affective and cognitive morbidity of pain. Attenuation of brain's reward system involving cortical plastic changes might have a key role in chronification of pain.

Comparative impact of hearing and vision impairment on subsequent functioning.

OBJECTIVES: The purpose of this study was to compare independent impacts of two levels of self-reported hearing and vision impairment on subsequent disability, physical functioning, mental health, and social functioning. DESIGN: A 1-year prospective cohort study. SETTING: San Francisco Bay Area, California. PARTICIPANTS: Two thousand four hundred forty-two community-dwelling men and women age 50 to 102 from the Alameda County Study (California). MEASUREMENTS: Hearing and vision impairment were assessed in 1994. Outcomes, measured in 1995, included physical disability (activities of daily living, instrumental activities of daily living, physical performance, mobility, and lack of participation in activities), mental health (self-assessed, major depressive episode), and social functioning (feeling left out, feeling lonely, hard to feel close to others, inability to pay attention). All 1995 outcomes were adjusted for baseline 1994 values. RESULTS: Both impairments had strong independent impacts on subsequent functioning. Vision impairment exerted a more wide-ranging impact on functional status, ranging from physical disability to social functioning. However, the results also highlighted the importance of hearing impairment, even when mild. CONCLUSIONS: These impairments can be partially ameliorated through prevention, assessment, and treatment strategies. Greater attention to sensory impairments by clinicians, patients, public health advocates, and researchers is needed to enhance functioning in older adults.

Dexmedetomidine reduces seizure threshold during enflurane anaesthesia in cats.

Dexmedetomidine is an alpha 2 agonist and has been reported to have proconvulsant actions. To investigate the interaction of dexmedetomidine with convulsant anaesthetics, we studied effects on seizure threshold in cats during enflurane anaesthesia. Cats were prepared with chronic implantation of electrodes for recording of the cortical electroencephalogram (EEG) and midbrain reticular formation multi-unit activity (R-MUA). Seizure threshold, the reciprocal of the number of electrical stimuli required to induce generalized EEG seizure activity x 1000 (seizure induction index (SII)), was assessed. The effects of dexmedetomidine 1, 10 and 100 micrograms kg-1 i.v. and yohimbine 500 micrograms kg-1, an alpha 2 antagonist, on SII during 3.5% enflurane anaesthesia were investigated. Dexmedetomidine significantly increased SII at 10 and 100 micrograms kg-1, and this effect was reversed by yohimbine. We found that high-dose dexmedetomidine reduced seizure threshold during enflurane anaesthesia.

[General anesthesia with propofol and fentanyl for adult cardiac surgery].

We employed propofol anesthesia with a restricted dose of fentanyl in adult cardiac surgery with the aim of early tracheal extubation and evaluated its effects on the intraoperative factors and postoperative recovery compared with those of a previous benzodiazepine-fentanyl regimen. During surgery, control group patients (n = 17) received intermittent bolus of benzodiazepines and fentanyl without restriction, whereas propofol group patients (n = 17) received continuous administration of propofol and the restricted dose of fentanyl (20 micrograms.kg-1). There were no significant differences in the times to eye opening (average 2.4 hr vs 1.6 hr, respectively, P = 0.30) and tracheal extubation (average 5.4 hr vs 4.0 hr, P = 0.25) between the groups. Both groups had similar postanesthetic circulatory status: cardiac index (average 3.6 l.min-1.m-2 vs 3.4 l.min-1.m-2, P = 0.46). The propofol group patients required smaller doses of vasodilators during cardiopulmonary bypass (average PGE1: 0.096 microgram.kg-1.min-1 vs 0.047 microgram.kg-1.min-1, P = 0.046, NTG: 0.69 microgram.kg-1.min-1 vs 0.31 microgram.kg-1.min-1, P = 0.009). It is suggested that propofol-based anesthesia could replace the previous regimen with no adverse hemodynamic effects and might have a potential to provide faster recovery and improve peripheral circulatory status in adult cardiac surgery.

Helicobacter pylori infection and atrophic gastritis: a nested case-control study in a rural town in Japan.

A seroepidemiologic, nested case-control study was conducted to evaluate the risk for atrophic gastritis associated with Helicobacter pylori infection. Atrophic gastritis was diagnosed on the basis of serum pepsinogen levels: pepsinogen I level < or = 70 ng/ml and pepsinogen I/pepsinogen II ratio < or = 3.0. Cases were 23 men and 39 women who were not diagnosed with atrophic gastritis in 1987, but who were diagnosed with the condition in 1992. Controls were the 120 men and 282 women who did not meet the serologic criteria for atrophic gastritis in either time period. Neither cases nor controls had a history of upper gastrointestinal operations. Helicobacter pylori infection at the initial survey was associated with a significantly increased risk of atrophic gastritis incidence for both sexes combined (odds ratio = 3.72; 95% confidence interval, 1.78-7.79; P = 0.0005). Cigarette smoking and consumption of alcohol and green-yellow vegetables were not associated with incidence of atrophic gastritis.

Use of Positron Emission Tomography to Measure Brain Activity Responses to Fentanyl Analgesia.

This review illustrates the potential of positron emission tomography (PET) in elucidating the supraspinal analgesic mechanisms of opioids in humans. First, a range of PET methodologies, available for functional brain mapping both on the receptor and neuronal network level in humans, is examined briefly. Subsequently, studies that have taken advantage of only a small portion of these PET techniques are reviewed. In light of the limitations of these experiments, a series of strategies is discussed that, by exploiting the full arsenal of PET techniques, could provide unique insights into the supraspinal mechanisms of opioid analgesia under the clinically most relevant circumstances--in the living human brain.

Effect of xenon on central nervous system electrical activity during sevoflurane anaesthesia in cats: comparison with nitrous oxide.

We have compared the effects of xenon and nitrous oxide on central nervous system (CNS) electrical activity during sevoflurane anaesthesia in cats by recording the electroencephalogram (EEG), multi-unit activity of the midbrain reticular formation (R-MUA) and somatosensory evoked potentials (SEP). Basal anaesthesia with 2% and 5% sevoflurane was used. With 2% sevoflurane, 70% xenon initially produced rhythmic slow waves which were followed by bursts of high-amplitude sharp waves interrupted by low amplitude slow waves on the EEG. Xenon induced an initial increase, followed by a decrease in R-MUA. Nitrous oxide 70% decreased the amplitude of the EEG activity which was associated with an increase in R-MUA. Xenon suppressed the amplitude of both the initial positive and negative deflections of the SEP to a greater extent than nitrous oxide. With 5% sevoflurane anaesthesia, both anaesthetics increased the frequency of spikes on the EEG and facilitated R-MUA. These findings indicate that xenon has a stimulatory action on CNS background activity and a suppressive action on CNS reactive capability which is more potent than that of nitrous oxide.

The effects of the Northridge earthquake on the pattern of emergency department care.

This study's objective was to describe the types of injuries that should be anticipated after a major earthquake. Data for the 6 days prior to the earthquake, the 6 days after the earthquake, and for the day of the earthquake the previous year were obtained from the Emergency Department of Northridge Hospital, Northridge, CA. Demographic data, including age and sex, as well as the reason for the visit, were obtained from patient logs. The average number of patients per day was 110 before the earthquake and 185 after the earthquake. On the day of the earthquake, 343 patients were seen. Lacerations increased from 7.1% of all visits before the earthquake to 22.4% after the earthquake (P < .01). Immediately after the Northridge earthquake, there was a threefold increase in emergency patient visits. The biggest increase occurred in the number of patients presenting with contusions and lacerations. The number of pregnant women presenting in labor and with vaginal bleeding also increased. Disaster managers should take these patterns into account when planning for major seismic events.

NSAIDs increase risk of gastrointestinal bleeding in primary care patients with dyspepsia.

BACKGROUND: A 1-year prospective study of 545 patients with dyspepsia examined the natural history of dyspepsia in a primary care population. Predictors of gastrointestinal bleeding and other related utilization-of-service indicators were identified. METHODS: Subjects were adult primary care patients seen at a southern California county medical center. Data were collected by means of a patient questionnaire as well as from medical charts and a computerized hospital billing system. Chi-square, t test, and stepwise multiple logistic regression analyses were used to analyze the data. Outcome events were follow-up visits for any gastrointestinal event and follow-up visits for gastrointestinal bleeding specifically. RESULTS: Prior exposure to nonsteroidal anti-inflammatory drugs doubled the odds for any follow-up gastrointestinal event (odds ratio = 1.9; 95% CI = 1.4 to 2.8). Nonsteroidal anti-inflammatory drugs increased the risk for gastrointestinal bleeding by a factor of 7 (odds ratio = 7.1; 95% CI = 1.3 to 50.0). CONCLUSIONS: In a cohort of primary care patients with dyspepsia, use of nonsteroidal anti-inflammatory drugs was the most important predictor of a follow-up gastrointestinal event, both for any gastrointestinal event and gastrointestinal bleeding specifically.

Helicobacter pylori infection and gastric cancer. A nested case-control study in a rural area of Japan.

We conducted a seroepidemiological nested case-control study to determine the association of gastric cancer with Helicobacter pylori infection and atrophic gastritis. A cohort of 2858 participants in an annual multiphasic health check-up were followed for eight years. Data for 45 gastric cancer cases and 225 sex-, age-, and address-matched control subjects were analyzed. Helicobacter pylori infection was determined by IgG antibodies, and atrophic gastritis was diagnosed by both serum pepsinogen I level (< or = 70 ng/ml) and the pepsinogen I/II ratio (< or = 3.0). Univariate analysis showed that Helicobacter pylori and atrophic gastritis were significantly associated with gastric cancer. In a multivariate analysis, atrophic gastritis was associated with significantly increased risk of cancer (odds ratio, 3.38; 95% confidence interval, 1.54-7.42); however, Helicobacter pylori was not associated with cancer (odds ratio, 1.84; 95% confidence interval, 0.59-5.72). These results suggest that Helicobacter pylori infection alone is not directly associated with gastric carcinogenesis but has an indirect relation to gastric cancer through the development of atrophic gastritis.

The effect of xenon on spinal dorsal horn neurons: a comparison with nitrous oxide.

We compared the effects of xenon (Xe) on the spinal cord dorsal horn neurons with those of nitrous oxide (N2O) in cats anesthetized with chrolarose and urethane. We assessed the potency of both anesthetics by the inhibition of wide dynamic range neuron responses evoked by cutaneous noxious (pinch) stimulation to a hindpaw. During 70% Xe inhalation, the responses of 7 of 11 neurons to pinch stimulation were suppressed. N2O, 70%, suppressed it in 8 of 11 neurons. The potency of Xe and N2O was compared in six neurons that were suppressed by both anesthetics. After 20 min of Xe inhalation, the response to pinch was suppressed to 49.5% +/- 8.2% (mean +/- SE), while N2O, 70% in oxygen, suppressed it to 45.9% +/- 7.9%. The difference between N2O and Xe was not significant. We conclude that Xe and N2O suppress the spinal cord dorsal horn neurons to a similar degree.

Dyspepsia in primary care: perceived causes, reasons for improvement, and satisfaction with care.

BACKGROUND: While dyspepsia is a common problem in primary care populations, very little is known about patient perceptions of medical care for this disease. The present study of patients with dyspepsia treated by primary care physicians looks at causes, procedures, and reasons for improvement from the patient's viewpoint and relates these factors to patient satisfaction with family physicians' medical care. METHODS: Medical chart and billing data were collected for 545 adult patients who visited five family health centers for digestive complaints during a 6-month period in 1993. A questionnaire was completed by 288 patients 6 to 8 weeks after patient's index visit. Baseline findings are reported. RESULTS: The two most common causes of gastrointestinal problems were attributed to stress or anxiety (58%) and diet (46%). Between the time of the index visit and the baseline survey, 48% reported that they had recovered or improved. Of those who recovered or improved, most (75%) credited "taking GI medicine" followed by change in diet (44%). Patients who reported recovery or improvement of their gastrointestinal complaints (P < .001) and older patients (P = .032) were the most satisfied with overall medical care. Satisfaction with medical care was not associated with insurance coverage, procedures done, race, antiulcer medication treatment, diagnosis, general health status, or sex. CONCLUSIONS: Specific health status, ie, improvement of gastrointestinal (GI) problems, predicted patient satisfaction for 70% of cases in this study. Most patients who improved credited GI medicines for their improvement, and those who improved were more satisfied with their medical care.

Meta-analysis of risk factors for peptic ulcer. Nonsteroidal antiinflammatory drugs, Helicobacter pylori, and smoking.

Attributable risk models describe the role of three risk factors for peptic ulcer and related serious upper gastrointestinal (GI) events. The factors-nonsteroidal antiinflammatory drugs (NSAIDs), Helicobacter pylori, and cigarette smoking-have been identified as major risk factors for peptic ulcer in numerous clinical and epidemiologic studies. Overall risk ratios for each risk factor were based on meta-analyses of English-language studies of risk for peptic ulcer-related GI events. Exposure estimates for factors used data from North American populations. Summary risk and exposure values were computed for the general population, males and females separately, and the elderly. Hypothetical models of multiple factor attributable risks were developed using population attributable risk percent calculated from these summary values. General population attributable risk percent were as follows: 24%, NSAIDs; 48%, H. pylori; and 23%, cigarette smoking. Based on these numbers, the "no interaction" attributable risk model estimates that 95% of total peptic ulcer related risk is attributable to these factors in the general population. The "interaction" model attributes 89% of cases to these risk factors: 24%, NSAIDs alone; 31%, H. pylori alone; 34%, H. pylori/smoking combined. Between 89% and 95% of peptic ulcer-related serious upper GI events may be attributed to NSAID use, H. pylori infection, and cigarette smoking.

Effects of isoflurane on in vivo release of acetylcholine in the rat cerebral cortex and striatum.

BACKGROUND: Acetylcholine (ACh) is one of the major excitatory neurotransmitters in the central nervous system, and changes in neural activity induced by anesthesia alter the release of ACh. However, the effects of isoflurane, one of the most widely used volatile anesthetics, on ACh release are not known. The present study attempts to clarify the dose-effect relationship of isoflurane on the in vivo release of ACh in rat brains. METHODS: Changes in the extracellular concentration of ACh and choline in the cerebral cortex and striatum induced by 0.5, 1.0, and 1.5 minimum alveolar concentration (MAC) of isoflurane were determined using a brain microdialysis technique. RESULTS: In the cortex, the ACh release decreased to 30.8+/-10.1 (mean+/-SEM), 10.2+/-4.1, and 8.1+/-2.9% of basal value by increasing doses of isoflurane, and in the striatum, to 73.3+/-4.4, 49.2+/-4.2, and 40.7+/-4.5%. The ACh release rapidly recovered control levels with the discontinuance of isoflurane. Choline concentration was not changed significantly by isoflurane except for a decrease to 74.8+/-4.6% in the striatum by 0.5 MAC. In both the cortex and striatum, the choline concentration decreased with the discontinuance of isoflurane to 70.3+/-13.3, and 68.2+/-5.4%, respectively. CONCLUSION: The fact that all classic anesthetics reported previously, as well as isoflurane, reduce ACh release supports the hypothesis that the suppression of cholinergic cells is, at least in part one of the mechanisms of anesthesia.

Subcutaneous and visceral fat distribution and daily physical activity: comparison between young and middle aged women.

OBJECTIVE: To examine the effects of aging and physical activity on distribution patterns in subcutaneous and visceral fat. METHODS: Distributions of subcutaneous rat mass at six segments (face and neck, forearm, upper arm, trunk, thigh, and lower leg) were determined by adipose tissue thickness measurements by B mode ultrasonogram and body surface areas. Visceral fat mass was calculated by subtracting subcutaneous fat mass from the total fat mass determined hydrodensitometrically. Measurements were made on young and middle aged, trained and sedentary women (four groups). RESULTS: Per cent body fat was lower in trained than in sedentary individuals, both in the young and the middle aged subjects. The distribution of subcutaneous fat mass differed between sedentary and trained women. Trained young women had a reduced subcutaneous fat mass compared to sedentary young subjects in all segments except face and neck; the disparity between middle aged sedentary and trained women was limited to upper arm and trunk (P < 0.01 each), with no significant difference in face and neck, forearm, and lower limb segments. Differences in visceral fat mass between sedentary and trained subjects were similar for young and middle aged women (young, 2.5 v 3.7 kg; middle aged, 4.0 v 6.5 kg). CONCLUSIONS: Women who exercise regularly appear to accumulate less adipose tissue, especially in upper arm and trunk segments as they get older, with visceral fat mass remaining lower than in sedentary individuals.

Halothane and diazepam inhibit ketamine-induced c-fos expression in the rat cingulate cortex.

BACKGROUND: Ketamine, a noncompetitive N-methyl-D-aspartate antagonist, has psychotomimetic side effects. Recent studies have shown that noncompetitive N-methyl-D-aspartate antagonists cause morphologic damage to the cingulate and retrosplenial cortices and induce c-fos protein (c-Fos) in the same regions. Although benzodiazepines are effective in preventing these side effects, the neural basis of the drug interactions has not been established. METHODS: The effects of diazepam and halothane on c-Fos expression induced by ketamine were studied. Diazepam (1 and 5 mg/kg) or vehicle were administered subcutaneously, followed 7 min later by 100 mg/kg ketamine given intraperitoneally. Halothane (1.0 and 1.8%), was administered continuously from 10 min before ketamine administration until brain fixation. Two hours after ketamine injection, rats were perfused and their brains fixed and extracted. Brain sections were prepared in a cryostat and c-Fos expression was detected using immunohistochemical methods. RESULTS: Ketamine induced c-Fos-like immunoreactivity in the cingulate and retrosplenial cortices, thalamus, and neocortex. Diazepam suppressed the ketamine-induced c-Fos-like immunoreactivity in the cingulate and retrosplenial cortices in a dose-dependent manner, leaving the thalamus and neocortex less affected. Halothane suppressed the ketamine-induced c-Fos-like immunoreactivity in the cingulate and retrosplenial cortices and the neocortex in a dose-dependent manner, leaving the thalamus relatively unaffected. CONCLUSION: Halothane and diazepam inhibited ketamine-induced c-Fos expression in the cingulate and retrosplenial cortices, leaving the thalamus relatively unaffected.

Nitrous oxide depresses somatocardiac sympathetic A- and C-reflexes in anesthetized rats.

Effect of nitrous oxide (N2O) on the somatosympathetic A- and C-reflexes was investigated using artificially ventilated rats anesthetized with alpha-chloralose and urethane. Somatocardiac sympathetic A- and C-reflexes were elicited in the inferior cardiac nerve by electrical stimulation of A and C afferent fibers of the tibial nerve, respectively. Both reflexes were depressed by inhalation of N2O for 20 min. The depression was greater in the C-reflex than in the A-reflex. The depressive effects of N2O on both reflexes were unchanged after pretreatment with intravenous naloxone (0.2 or 2.0 mg/kg) or by prolongation of the inhalation of N2O for 2 h. These results suggest that the opioid receptor is not involved and that acute tolerance is not developed in the depressive action of N2O on the somatosympathetic A- and C-reflexes.