Identification and characterization of cerebral cortical response to esophageal mucosal acid exposure and distention

BACKGROUND & AIMS: Esophageal acid exposure is a common occurrence in healthy individuals and patients with esophagitis. Clinically, perception of this exposure ranges from no perception to severe heartburn and chest pain. Cerebral cortical response to esophageal mucosal contact to acid has not been systematically studied. The aim of this study was to elucidate cerebral cortical response to esophageal acid exposure in normal individuals by functional magnetic resonance imaging (FMRI). METHODS: We studied 10 normal healthy volunteers. Cortical FMRI response to 10 minutes of intraesophageal perfusion of 0.1N HCl (1 mL/min) was determined, and the results were compared with those of saline infusion and balloon distention. RESULTS: Acid perfusion did not induce heartburn or chest pain but increased FMRI signal intensity by 6.7% +/- 2.0% over the preperfusion values. No increase was detected for saline infusion. FMRI signal intensity to balloon distention was similar to that of acid perfusion. Activation latency, activation to peak, and the deactivation periods for response to acid perfusion were significantly longer than those of balloon distention (P < 0.05). CONCLUSIONS: Contact of esophageal mucosa with acid, before inducing heartburn, evokes a cerebral cortical response detectable by FMRI. Temporal characteristics of this response are significantly different from those induced by esophageal balloon distention.     

Intraesophageal balloon distension test in Chagas' disease patients with noncardiac chest pain

Patients with Chagas' disease often have chest pain as a prominent symptom. The objective of this study was to compare the results of intraesophageal balloon distension in chagasic and nonchagasic patients with chest pain not caused by coronary obstruction. We studied 40 patients with chest pain and angiographically normal coronary arteries, 25 with a positive serologic test for Chagas' disease (Chagas group, 16 women, mean age 53+/-10 years), and 15 with a negative serologic test (control group, 11 women, mean age 46+/-10 years). All patients had radiologic and endoscopic examinations of esophagus, stomach, and duodenum, esophageal manometry with the acid infusion test in the distal esophagus, and intraesophageal balloon distension. None of them had esophageal dilation or any signs of cardiovascular disease. A 25-mm-long latex balloon located 10 cm above the lower esophageal sphincter was inflated and deflated over a period of 10 sec at 1-ml increments of air until the subjects reported chest pain or to a maximum volume of 20 mi. The test caused chest pain in 14 subjects in the control group (93%) and in 12 in the Chagas' disease group (48%, P < 0.05). The mean volume of air that caused chest pain was 10+/-3 ml in the control group and 15+/-4 ml in the Chagas' disease group (mean+/-SD, P < 0.05). The maximum intraesophageal pressure during the examination was higher in Chagas' disease patients with chest pain during balloon distension (60 +/- 21 mm Hg) than in patients who did not have chest pain (37 +/-18 mm Hg, P < 0.05) and did not differ from the control group (48+/-16 mm Hg, P > 0.05). With the other examinations there was no difference between groups or between patients with or without chest pain during the balloon distension test. Although esophagitis was observed in 47% of patients in the control group and in 40% of the Chagas' disease group, the acid infusion test was positive in 27% of patients in the control group and in 4% of patients in the Chagas' disease group. We conclude that, as compared to a group of patients with similar chest pain, chagasic patients are less sensitive to esophageal distension. Thus, it is unlikely that their chest pain is related to esophageal mechanisms.     

Chemokine receptor CXCR4 expression in endothelium

The aim of the present study was to study the sensibility in the area of saline-induced muscle pain. In three experiments, ten subjects were exposed to computer-controlled infusion of 0.5 ml isotonic (0.9%) or hypertonic (9%) saline into the anterior tibial muscle. The pain intensity was assessed on a visual analogue scale (VAS). The pain threshold (PT) to pressure and electrical stimulation in muscle and subcutaneous tissues was determined. Three experiments were performed in which infusion of hypertonic saline produced significantly higher VAS scores than isotonic saline. In all three experiments, there was no significant difference in PT obtained after infusion of isotonic saline compared with infusion of hypertonic saline. In experiment 1, the PT was determined at the infusion site and 4 cm from the infusion site. At the infusion site, the pressure PT decreased (-19 +/- 2%) 1, 3, 5, 7 and 9 min after infusion of isotonic and hypertonic saline, but remained unchanged 4 cm from the infusion site. The intramuscular electrical PT at the infusion site and 4 cm from the infusion site increased significantly (29 +/- 6%) 5, 7 and 9 min after saline infusion. In experiment 2, the pressure PT and the intramuscular electrical PT were recorded after two infusions of saline separated by 1 day. The day after the first infusion, the pressure PT was decreased compared with the PT before the first infusion, but the electrical PT was not affected. Moreover, the hypertonic saline infusion given on the second day produced significantly higher (130 +/- 50%) VAS scores than the infusion given on the first day. In experiment 3, the PT was determined in the subcutaneous tissue, but no significant effects of saline infusion were found. The present placebo-controlled experiments failed to show muscular or subcutaneous hyperalgesia after saline-induced muscle pain per se.     

Olfactory stimuli provoke diffuse esophageal spasm: reversal by ipratropium bromide

Diffuse esophageal spasm (DES) is a motor disorder of the esophageal smooth muscle characterized by multiple spontaneous contractions and by swallow-induced contractions that are of simultaneous onset, large amplitude, long duration, and repetitive occurrence. Although the pathogenesis of DES is unknown, provocative studies with cholinergic stimulation, esophageal balloon distention, or acid instillation have suggested involvement of both sensory and motor mechanisms. This report describes a patient with DES who would predictably become symptomatic with dysphagia and chest pain upon inhalation of perfume or other strong odors. Using esophageal scintigraphy to quantitate and analyze esophageal transit in this patient, we report for the first time that olfactory stimulation triggers episodes of DES and that such phenomena are mediated through the vagus nerve, because they can be ameliorated by the administration of ipratropium bromide. These observations suggest a new (sensory) pathway for the induction of DES and raise the intriguing possibility that inhaled anticholinergics may have a therapeutic role in the management of spastic esophageal motility disorders.     

Esophageal dysfunction in syndrome X

Syndrome X is defined as anginal chest pain accompanied by objective signs of ischemia on exercise testing or myocardial scintigraphy, but with angiographically "normal" coronary arteries. The etiology of this enticing syndrome is still not known. Besides myocardial ischemia, esophageal dysfunction and visceral hypersensitivity may play a role in the development of pain. The purpose of this study was to study esophageal function and visceral sensitivity in patients with syndrome X. Twenty consecutive patients with the diagnosis of syndrome X were investigated with esophageal manometry and a 24-hour pH recording. Visceral esophageal sensitivity was explored by balloon distention of the distal esophagus, as well as by instillation of acid. Twelve patients (67% of the 18 evaluated) had some abnormality on 24-hour pH monitoring; 2 had abnormal global acid exposure time (pH <4) and 7 had symptoms coincidental with episodes of pH <4. Seven patients (35%) had esophageal dysmotility including 5 with the "nutcracker" esophagus. Esophageal hypersensitivity to acid (n = 9) or distention (n = 13) was seen in 14 of the 20 patients. Eleven patients received acid suppressive therapy that resulted in amelioration of chest pain in 8 (73%). Thus, results suggest that esophageal hypersensitivity rather than gross functional abnormality is an important factor for the development of chest pain in patients with syndrome X, and that acid in the context of a hypersensitive esophagus is the main culprit. Acid suppression may ameliorate pain in a substantial proportion of patients.     

Is rectal pain sensitivity a biological marker for irritable bowel syndrome: psychological influences on pain perception

BACKGROUND & AIMS: Rectal pain sensitivity has been called a biological marker for irritable bowel syndrome, but this conclusion may be premature. This article is a critical review of the evidence for psychological influences on perception. METHODS: The world literature accessible through Index Medicus from 1973 to 1997 was systematically reviewed. RESULTS: Evidence favoring a biological basis for pain sensitivity is that two thirds of patients report pain at abnormally low thresholds of rectal distention despite normal somatic pain thresholds. Pain thresholds are not correlated with anxiety or depression. Evidence favoring psychological influences on perception is that patients with the irritable bowel syndrome rate even sham distentions as more painful, and when perception tests that minimize psychological influences are used, they have normal sensory thresholds. Also, stress alters sensory thresholds. Sensitization by repeated distention has been cited as evidence of a biological basis for hyperalgesia, but it is not unique to patients with irritable bowel. Brain imaging shows that different regions are activated by painful distention in patients with irritable bowel syndrome, but this is consistent with psychological influences on perception. CONCLUSIONS: Psychological factors influence pain thresholds in patients with the irritable bowel syndrome. Two cognitive traits, selective attention to gastrointestinal sensations and disease attribution, may account for increased pain sensitivity.     

Cystoscopic findings consistent with interstitial cystitis in normal women undergoing tubal ligation

PURPOSE: We test the hypothesis that women without chronic pelvic pain or irritative voiding symptoms do not demonstrate petechial hemorrhages known as glomerulations that are characteristic of patients with interstitial cystitis. MATERIALS AND METHODS: A prospective cohort design was used for examination with cystoscopy and bladder distention of 20 asymptomatic women undergoing tubal ligation. Cystoscopy with the patient under general anesthesia was performed to inspect the bladder mucosa before and after distention at 70 cm. of water pressure for 2 or 6 minutes. Photographs of the right, posterior and left of the bladder surfaces taken before and after the distention were scored on a scale of 1 to 5 using a panel of standards. Five urologists blinded to the source of individual photographs independently evaluated 120 research images interspersed with 46 other pictures from a library containing images from 19 symptomatic patients with and without interstitial cystitis. RESULTS: A total of 20 normal women with a mean age plus or minus standard deviation of 29+/-6 years consented to participate in this trial during laparoscopic tubal ligation. Photographs of bladder sites before and after distention with 890+/-140 ml. were scored as 1.4+/-0.3 (before distention) and 3.1+/-1.1 (after distention) on the scale of 1 to 5. The increase in scores following distention in normal subjects was seen to the same degree and in the same proportion as in patients with symptoms of interstitial cystitis (8 of 19 symptomatic patients in this series met current diagnostic criteria for interstitial cystitis). Slight but significant differences were seen among sites in the bladder but not between 2 and 6-minute distention durations. CONCLUSIONS: Bladder mucosal lesions characteristically associated with irritative voiding symptoms and pelvic pain in patients diagnosed with interstitial cystitis were observed in asymptomatic women.     

A conservation principle and its effect on the formulation of Na-Ca exchanger current in cardiac cells

In the rat the exact role of vagal fibers and the interaction between the extrinsic and intrinsic neural system in distention-induced gastrin release are still a matter of debate. Accordingly, the aim of the present study was to examine the contribution of afferent and efferent vagal fibers as well as intrinsic neurons on gastrin response to gastric distention. In anesthetized rats graded gastric distention by 5, 10 and 15 ml saline for 20 min caused a significant volume-dependent increase of plasma gastrin levels by 12+/-6 pg/ml (5 ml saline, n = 8, P =0.05), 26+/-7 pg/ml (10 ml saline, n = 10, P < 0.05) and 37+/-7 pg/ml (15 ml saline, n = 8, P < 0.01 ), respectively. To examine the role of the extrinsic vagal innervation, gastrin response to distention was studied in anesthetized rats after bilateral truncal vagotomy (n = 9) or selective afferent vagotomy following pretreatment with capsaicin (n = 6). Stimulation of gastrin release by 10 ml distention in sham-operated control rats was reversed to an inhibition after truncal vagotomy (26+/-7 vs. -11+/-4 pg/ml; P<0.05) and capsaicin-treatment (37+/-18 vs. -34+/-11 pg/ml; P<0.05). A contribution of cholinergic mechanisms to this vagovagal-mediated stimulation of distention-induced gastrin release was excluded, since atropine (100 microg/kg/h; n = 8) further augmented distention-stimulated gastrin release. Since bombesin/gastrin-releasing peptide (GRP)-neurons contribute to vagally stimulated gastrin secretion, we have examined gastrin response to distention in the presence of the specific bombesin-receptor antagonist D-Phe6-BN(6-13)OMe (400 microg/kg/h: n = 10). This bombesin-antagonist completely reduced distention-stimulated gastrin release in vivo. In contrast, distention of the isolated, extrinsically denervated stomach significantly decreased gastrin release by 13+/-5 pg/min (5 ml saline, n = 8, P < 0.05), 28+/-8 pg/min (10 ml saline, n = 11, P < 0.05) and 35+/-10 pg/min (15 ml saline, n = 8, P < 0.01), respectively, without changing the activity of bombesin/GRP-neurons. Distention-induced decrease of gastrin release was attenuated to 50 percent by atropine (10(-7) M: n = 10) or tetrodotoxin (TTX) (10(-6) M; n = 10), respectively. These data demonstrate, that in anesthetized rats distention-stimulated gastrin secretion depends on the activation of a vagovagal reflex and intrinsic bombesin/GRP-neurons. In contrast distention of the isolated rat stomach inhibits gastrin release in part via intrinsic cholinergic pathways and other as yet unknown mechanisms.     

Schizophrenia and the dopamine-beta-hydroxylase gene: results of a linkage and association study

PURPOSE: A dose-finding study to investigate the use of epidural infusions of ropivacaine for postoperative analgesia following orthopaedic surgery. METHODS: This was a randomized, double-blind study. Surgery was performed using a combination of a lumbar epidural block utilizing ropivacaine 0.5% and a standardized general anaesthetic. Postoperatively, an epidural infusion of the study solution (saline, ropivacaine 0.1%, 0.2% or 0.3%) was started at the rate of 10 ml.hr-1 and continued for 21 hr after arrival in the PACU. Analgesia was supplemented with PCA morphine (dose = 1.0 mg, lock-out = 5 min). RESULTS: Forty-four patients completed the study. The ropivacaine 0.1%, 0.2%, 0.3% groups required less morphine over the 21 hr than the saline group (P < 0.01). The VAS pain scores were also lower in the three ropivacaine groups (P < 0.001). The ropivacaine groups maintained sensory anaesthesia to pinprick when compared with saline (P < 0.05). The motor block in the 0.3% group was significantly higher than the saline group at all times (P < 0.05), and higher than the 0.1% group at eight hours (P < 0.01), while the 0.2% group had higher Bromage scores than saline at 4 and 21 hr (P < 0.05). CONCLUSIONS: The use of continuous epidural infusions of ropivacaine 0.1%, 0.2% and 0.3% at 10 ml.hr-1 improved postoperative pain relief and decreased PCA morphine requirements in patients undergoing major orthopaedic surgery. The 0.1% and 0.2% concentrations produced similar sensory anaesthesia with less motor blockade than the 0.3% concentration.     

Citric acid-induced cough thresholds in normal subjects, patients with bronchial asthma, and smokers

Several challenge procedures have been developed to characterize the cough reflex in patients with airway diseases. This study was performed to compare the interindividual range of cough sensitivity in asthmatic and normal subjects as well as smokers using an identical method. Sixteen normal subjects, 20 patients with mild bronchial asthma, 6 patients with moderate to severe bronchial asthma, 9 current smokers, and 7 occasional smokers were included. In all subjects, methacholine challenges and standardized citric acid challenges were performed. Sensitivity of the cough reflex was expressed as cough threshold, i.e., as concentration at which coughing occurred. Reproducibility was assessed in 23 subjects. Within a concentration range of 0.625-320.0 mg/ml, inhaled citric acid caused cough in all subjects. Geometric mean (range) cough threshold was 13 (2.5-160) in normal subjects, 14 (5-40) in patients with mild, and 32 (20-40) mg/ml in patients with moderate to severe asthma, 40 (20-80) in current smokers, and 119 (80-160) in occasional smokers. Cough thresholds were reproducible within one doubling concentration. In normal subjects and patients with mild bronchial asthma, thresholds were not significantly different from each other but lower than those of the other groups (p<0.05 each). Cough thresholds in smokers and patients with moderate to severe asthma did also not differ significantly and were lower than in occasional smokers (p<0.05). There was no significant correlation between cough threshold, baseline FEV subset1 , and methacholine responsiveness. Our data indicate that (1) subjects with mild asthma showed on average similar cough thresholds as normal subjects, (2) there was a large variation in cough thresholds within groups, (3) the reproducibility of cough thresholds was within one doubling concentration, (4) cough thresholds did not correlate with methacholine responsiveness or baseline airway tone. In view of the prevalence of cough as a symptom of bronchial asthma, it appears that the determination of citric acid-induced cough thresholds does not yield additional diagnostic information in these subjects.     

Caring, patient autonomy and the stigma of paternalism

BACKGROUND: Epinephrine increases the metabolic rate and contributes to the hypermetabolic state in severe illness. OBJECTIVE: We sought to determine the effect of prolonged elevation of epinephrine on resting energy expenditure (REE). DESIGN: Thirteen healthy men were placed on a well-defined diet for 5 d. Beginning on the morning of the second diet day, the subjects were infused for 24 h with saline, then for 23 h with epinephrine (0.18 nmol x kg(-1) x min(-1)) to increase plasma epinephrine concentrations into the high physiologic range (4720 +/- 340 pmol/L). REE and the respiratory quotient (RQ) were measured by indirect calorimetry in the postabsorptive state at the same time every morning. RESULTS: Infusion of epinephrine significantly increased heart rate and systolic blood pressure, but the response was transient (values after 23 h of epinephrine infusion were not significantly different from those on the day saline was infused). Infusion of epinephrine significantly increased REE by 12% and increased the RQ. These changes were apparent at the end of the 23-h infusion (REE: 97.5 +/- 2.3 kJ x kg(-1) x d(-1) with saline infusion and 108.9 +/- 2.3 kJ x kg(-1) x d(-1) with epinephrine infusion; RQ: 0.832 +/- 0.012 with saline infusion and 0.879 +/- 0.013 with epinephrine infusion). REE returned to baseline by 24 h after the epinephrine infusion ended, but the postabsorptive RQ remained modestly elevated. Infusion of epinephrine also produced a transient increase in urine flow and in urinary nitrogen excretion. This diuresis was compensated for by a drop in urine volume and nitrogen excretion after the epinephrine infusion was stopped. CONCLUSIONS: Epinephrine produced a prolonged increase in REE in healthy subjects. The fuel for this increase in REE, determined by the RQ, was from increased carbohydrate oxidation, not from that of fat or protein.     

Pneumatic balloon dilation in achalasia: a prospective comparison of balloon distention time

OBJECTIVE: Duration of Inflation in pneumatic balloon dilatation as treatment of achalasia has been variable ranging from 15 s to 6 min. A 60 s duration appears to be most often used. We compared the efficacy of dilation of achalasia with either 6- or 60-s inflation duration using a Rigiflex dilator of 3.0 cm diameter. METHODS: Eighty-one consecutive patients were prospectively studied in a randomized fashion, 41 in the 60-s group (A) and 40 patients in the 6-s group (B). Mean age of group A was 43 +/- 16.2 yr and of group B was 40 +/- 16.4 yr. Symptoms of dysphagia, chest pain, heartburn, regurgitation, and night cough were evaluated at basal (before dilation), 1- and 6-month intervals after dilation in both groups. Barium swallow was done to assess esophageal emptying 1 wk before dilation and 5 min postdilation in both groups. RESULTS: Significant and sustained improvement was seen for all symptoms in both groups. In addition, the degree of improvement in symptom scores between the two groups was similar. Barium esophagram in both groups at basal and immediately postdilation showed significant improvement in barium emptying but there was no significant difference between the two groups, indicative of equal efficacy in both distention times. Two patients needed repeat dilatation in group A and one in group B, with one drop out from group A, who was lost to follow-up, and was excluded from the analysis. No perforation occurred. CONCLUSION: Short duration of pneumatic balloon dilatation (6-s) is as effective as longer duration (60-s) in treatment of achalasia.     

Epidural epinephrine and clonidine: segmental analgesia and effects on different pain modalities

BACKGROUND: It is not known whether epidural epinephrine has an analgesic effect per se. The segmental distribution of clonidine epidural analgesia and its effects on temporal summation and different types of noxious stimuli are unknown. The aim of this study was to clarify these issues. METHODS: Fifteen healthy volunteers received epidurally (L2-L3 or L3-L4) 20 ml of either epinephrine, 100 microg, in saline; clonidine, 8 microg/kg, in saline; or saline, 0.9%, alone, on three different days in a randomized, double-blind, cross-over fashion. Pain rating after electrical stimulation, pinprick, and cold perception were recorded on the dermatomes S1, L4, L1, T9, T6, T1, and forehead. Pressure pain tolerance threshold was recorded at S1, T6, and ear. Pain thresholds to single and repeated (temporal summation) electrical stimulation of the sural nerve were determined. RESULTS: Epinephrine significantly reduced sensitivity to pinprick at L1-L4-S1. Clonidine significantly decreased pain rating after electrical stimulation at L1-L4 and sensitivity to pinprick and cold at L1-L4-S1, increased pressure pain tolerance threshold at S1, and increased thresholds after single and repeated stimulation of the sural nerve. CONCLUSIONS: Epidural epinephrine and clonidine produce segmental hypoalgesia. Clonidine bolus should be administered at a spinal level corresponding to the painful area. Clonidine inhibits temporal summation elicited by repeated electrical stimulation and may therefore attenuate spinal cord hyperexcitability.     

The effect of dilute vasopressin solution on blood loss during operative hysteroscopy: a randomized controlled trial

OBJECTIVE: To assess the effect of intracervical injection of dilute (0.05 U/mL) vasopressin solution on blood loss during operative hysteroscopy. METHODS: In a randomized, double-blind study, dilute vasopressin solution or placebo (normal saline) was injected into the cervical stroma of 106 women before dilation of the cervix in preparation for operative hysteroscopy. Intraoperative bleeding was calculated by dividing the number of red blood cells per milliliter of outflow distention fluid by the number of red blood cells per milliliter of the woman's blood immediately before the procedure and multiplying this quotient by the total amount of outflow fluid collected. Pressures were kept constant with a hysteroscopic infusion pump. RESULTS: The mean (+/-standard error of the mean) intraoperative blood loss of the treated (vasopressin) and control (placebo) groups was 20.3 +/- 4.1 mL (range 0-135) and 33.4 +/- 5.4 mL (range 0-290), respectively. The volume of distention fluid intravasation in the treated and control groups was 448.5 +/- 47.0 mL (range 30-1410) and 819.1 +/- 79.7 mL (range 20-1977), respectively. The operating time in the treated and control groups was 31.1 +/- 1.2 minutes (range 18-52) and 34.1 +/- 1.3 minutes (range 19-65), respectively. For all three outcome measures, the differences between the two groups were statistically significant, but for visual clarity of the uterine cavity during surgery, the difference was not significant. CONCLUSION: Administration of dilute vasopressin solution (0.05 U/mL) to the cervical stroma significantly reduces blood loss, distention fluid intravasation, and operative time during hysteroscopy. Further evaluation is required to determine the optimum dosage.     

Esophageal dysmotility elicited by acid perfusion in children with esophagitis

OBJECTIVE: To determine the importance of acid reflux-induced dysmotility in the genesis of noncardiac chest pain in children. METHOD: We performed esophageal manometries during intraesophageal perfusion with 0.9% NaCl or 0.1 N HCl in 19 children (age, 14.5 +/- 0.5 yr) with gastroesophageal reflux, biopsy-proven esophagitis, and complaints of at least one episode of chest pain per day. RESULTS: Baseline esophageal motilities were normal in all patients. Eight of 19 children (42%) complained of chest pain during intraesophageal acid perfusion. In three of these eight patients, complaints of chest pain during acid perfusion were temporally associated with "conversion" of previously normal motility patterns to manometric tracings, indicating esophageal dysmotility. Compared with findings during saline perfusion, esophageal acid exposure in these three children resulted in significant increases in both the duration (13.6 +/- 4.0 vs 3.2 +/- 0.2 s, p < 0.05) and amplitude (105.2 +/- 7.8 vs 61.2 +/- 2.1 mm Hg, p < 0.05) of esophageal contractions during wet swallows. Symptoms of chest pain resolved in all patients after therapy with H2-receptor antagonists. CONCLUSIONS: These data represent the first demonstration of acid-induced esophageal dysmotility in children with chest pain and suggest that reflux-induced motor abnormalities contribute to the onset and/or exacerbation of chest pain in pediatric patients with gastroesophageal reflux and esophagitis.     

Plasma levels of atrial natriuretic peptide and brain natriuretic peptide following intravenous saline infusion in oedematous chronic obstructive pulmonary disease and non-oedematous chronic obstructive pulmonary disease

Some patients with chronic obstructive pulmonary disease (COPD) develop oedematous COPD (oCOPD) with peripheral oedema and have a poor prognosis. The cause of the fluid retention is poorly understood but could be due to defective release of a natriuretic factor. We investigated this hypothesis by measuring levels of brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) before and after a 0.1 ml/kg/min 2.7% saline infusion in 6 patients with hypoxemic COPD but no history of oedema and 7 COPD patients with oCOPD. Vasopressin, aldosterone, plasma and urinary urea and electrolytes and osmolality were measured. Arterial blood gases and spirometry were also recorded. The two groups were similar in terms of age, weight, PaO2, PaCO2 and FVC. FEV1 was significantly lower in the oCOPD group. The oCOPD group excreted less urine (202 +/- 23 vs. 364 +/- 48 ml; p < 0.05) and less sodium (32 +/- 3 vs. 68 +/- 9 mmol/l; p < 0.01) as a percentage of the saline load given (18 +/- 2 vs. 30 +/- 4%; p < 0.05). Pre-infusion BNP and ANP levels were similar in both groups. BNP and ANP had an exaggerated increase in the oCOPD group on saline loading. In the oCOPD group, ANP levels were significantly greater 1 h after the saline load compared to the pre-infusion values (30 +/- 7 vs. 11 +/- 2; p < 0.05). BNP did not reach significantly greater levels than baseline values until 3 h after the infusion had ended (45 +/- 6 vs. 27 +/- 2; p < 0.05). At 1 h after the saline load, BNP and ANP levels were significantly greater in the oCOPD group (BNP 32 +/- 2 vs. 24 +/- 1; p < 0.01 and ANP 30 +/- 7 vs. 7 +/- 2; p < 0.05) when compared to COPD controls. BNP levels remained significantly different from the COPD control group 3 h after the infusion ended (45 +/- 6 vs. 26 +/- 2; p < 0.05). Although aldosterone levels were greater in the oCOPD group before the saline infusion, the hormone level was suppressed appropriately by the infusion. In conclusion, the cause of oedema in oCOPD and the inability to excrete a saline load is not due to a failure of release of BNP or ANP.     

Trigeminal neuropathic pain: pathophysiological mechanisms examined by quantitative assessment of abnormal pain and sensory perception

OBJECTIVE: This study was undertaken to examine the pathophysiological characteristics of trigeminal neuropathic pain. METHODS: The study included 23 consecutive patients with trigeminal neuropathic pain (15 patients with pain after nerve injury and 8 patients with pain of spontaneous origin). For each patient, quantitative examination of sensory and pain perception was performed in the painful facial skin area, and results were compared with the findings for the contralateral nonpainful facial skin area. RESULTS: In the painful facial skin area of patients with neuropathic pain after nerve injury, we demonstrated increased temperature and tactile thresholds, as well as abnormal temporal summation of pain (i.e., repetitive nonpainful skin stimulation produced an abnormal progressive increase of pain intensity, with abnormal radiation of pain and aftersensation). In the painful skin area of patients with pain of spontaneous origin, temperature and tactile thresholds were not increased, but heat pain and cold pain thresholds were significantly reduced, indicating heat and cold hyperalgesia. The characteristics of temporal summation of pain were not significantly altered in the painful facial skin area in this group of patients. CONCLUSION: This clinical study provides evidence that the pathophysiological mechanisms of trigeminal neuropathic pain after nerve injury involve impaired function of both small unmyelinated fibers and large myelinated fibers. An explanation for the finding of abnormal temporal summation of pain may involve hyperexcitability of central wide-dynamic range neurons. The results suggest that other mechanisms are involved in trigeminal neuropathic pain of spontaneous origin. Reduced heat and cold pain thresholds indicate heat and cold hyperalgesia, which possibly may be explained by sensitization of peripheral C nociceptors.     

Coronary flow analysis during autoperfusion angioplasty

BACKGROUND: Autoperfusion balloons are available for the protection of the myocardium during balloon angioplasty. The aortic pressure is the driving force that delivers blood to the distal vessel during balloon inflation. Autoperfusion balloons can achieve sufficient flow rates in vitro. The use of these devices is recommended in high-risk patients in danger of haemodynamic collapse during balloon inflation. The quantity of the distal blood flow during balloon inflation in vivo is still unknown. OBJECTIVES: To measure distal coronary perfusion using Doppler guidewires during percutaneous transluminal coronary angioplasty (PTCA) with autoperfusion balloons. METHODS: Coronary flow velocity was measured with 0.014-inch Doppler guidewires bypassing the autoperfusion balloon in eight patients undergoing elective PTCA (degree of stenosis 74 +/- 7.2%). We used balloons with diameters of 3.0 and 3.5 mm. The coronary diameter at the location of the flow measurements was obtained by quantitative angiography in two planes. Coronary blood flow was calculated as the luminal area multiplied by the average peak flow velocity of the Doppler wire divided by 2. Coronary flow velocity reserve was measured before and after angioplasty by intracoronary injection of adenosine. RESULTS: Coronary blood flow was 35 +/- 11.6 ml/min before PTCA. During average inflation times of 4.6 +/- 0.9 min, coronary blood flow was 19 +/- 3.8 ml/min (P = 0.002) after withdrawing the guidewire in the autoperfusion balloon. Five minutes after angioplasty it increased to 42 +/- 13.5 ml/min (P < 0.001). Four patients had electrocardiographic changes during balloon inflation; three patients reported chest pain. One patient required a stent because of a local dissection. To achieve satisfactory angiographic results (residual stenosis 11 +/- 8.5%), we performed 2.1 +/- 0.78 inflations on average with a cumulative inflation time of 8.8 +/- 3.35 min. Coronary flow velocity reserve increased from 1.3 +/- 0.20 to 2.2 +/- 0.22 (P < 0.001). CONCLUSIONS: Using the autoperfusion balloon we measured a coronary blood flow during angioplasty of 56 +/- 10.3% of the distal perfusion before PTCA. In high-risk patients dependent on adequate coronary perfusion, autoperfusion balloons are not able to provide sufficient distal coronary blood flow during balloon inflation. In these patients active coronary or circulatory support devices are recommended.     

Coordinated activity of the new "rectum" and anal sphincter after sphincter-saving resection of the rectum for colitis or carcinoma

PURPOSE: The aim of this study was to determine whether coordinated activity exists across a stapled enteroanal anastomosis. METHODS: Twenty-nine patients were studied for a median of one year after complete excision of the rectum and stapled enteroanal anastomosis; 12 patients underwent low anterior resection with coloanal anastomosis for carcinoma, and 17 patients underwent restorative proctocolectomy with ileoanal anastomosis. RESULTS: Maximum anal resting pressures were slightly lower after coloanal anastomosis than after ileoanal anastomosis [median range, 56 (11-60) cm H2O, cf 69 (40-107) cm H2O, P = NS]. During distention of the neorectum, anal sphincter pressures at 2.5, 1.5, and 0.5 cm from the anal verge were significantly lower after coloanal anastomosis compared with after ileoanal anastomosis (P < 0.01 at each station). The volume of neorectal distention required to produce maximal inhibition of the anal sphincter was significantly less after coloanal anastomosis at 50 (range, 20-60) ml of air than after ileoanal anastomosis at 240 (range, 100-420) ml of air (P < 0.01). Minor fecal leakage and urgency of bowel action were significantly more common after coloanal anastomosis (P < 0.01). CONCLUSION: Alterations in the dynamic response of the anal sphincter to distention of the neorectum may explain why the clinical results were better after ileal pouch-anal anastomosis than after coloanal anastomosis.     

Beneficial effects of atrial natriuretic peptide on exercise-induced myocardial ischemia in patients with stable effort angina pectoris

BACKGROUND: It has been shown that atrial natriuretic peptide (ANP), an endogenous vasodilator, dilates coronary arteries and decreases coronary vascular resistance. The purpose of this study was to determine whether an intravenous administration of ANP attenuated exercise-induced myocardial ischemia in 14 patients with stable effort angina pectoris. METHODS AND RESULTS: The first 12 patients (patients 1-12) who had exercise-induced ST segment depression underwent treadmill exercise testing and the last seven patients (patients 8-14) underwent the exercise 201Tl-single-photon emission computed tomography (SPECT) study while synthetic 28-amino acid alpha-human ANP (0.1 micrograms/kg per minute) or saline was intravenously infused in a double-blind, cross-over manner. The duration of exercise testing was the same during ANP and saline infusion, which was determined in preliminary exercise testings in each patient to cause a transient perfusion defect and/or ischemic ST segment depression. During saline infusion, all 12 patients developed exercise-induced ischemic ST segment depression, whereas no significant ST segment depression appeared during ANP infusion. Average ST segment depression during ANP infusion was significantly less (p < 0.01) than that during saline infusion (0.0 +/- 0.0 versus 0.2 +/- 0.1 mV, mean +/- SD). The averaged extent and severity scores assessed by 201Tl-SPECT were smaller (p < 0.05) during ANP infusion than during saline infusion (extent score: 0.22 +/- 0.20 versus 0.42 +/- 0.20; severity score: 18.77 +/- 23.45 versus 38.24 +/- 24.04, respectively). ANP decreased resting systolic blood pressure from 125 +/- 15 to 110 +/- 15 mm Hg (p < 0.01) but did not alter resting heart rate. At peak exercise, systolic blood pressure, heart rate, and the rate-pressure products did not differ during ANP and saline infusion. At peak exercise, plasma ANP increased from 98 +/- 45 to 4,383 +/- 2,782 pg/ml and cGMP increased from 3.6 +/- 1.7 to 34.5 +/- 16.1 pmol/ml during ANP infusion; values were significantly higher than those during saline infusion (from 96 +/- 42 to 133 +/- 66 pg/ml and from 3.4 +/- 1.8 to 4.6 +/- 1.8 pmol/ml, respectively). CONCLUSIONS: An intravenous administration of ANP attenuated exercise-induced myocardial ischemia in patients with stable effort angina pectoris. Although the mechanism by which ANP attenuated myocardial ischemia was not defined, increased myocardial perfusion to the ischemic region might be an important factor.