- Email: [email protected]
Neurobiology of relaxation training in gastroesophageal reflux disease
February 1995
We analyzed the medical records of all patients with colorectal cancers or adenomatous polyps seen between 1983 and 1992; in all patients serum gastrin concentration was determined after an overnight fast, before the coloscopic procedure. As a control group, all consecutive patients with normal results of colonoscopy seen in the period between 1989 and 1992 veere used. Patients excluded were those with a history of gastric surgery or small bowel resection, a history of ulcers, evidence of inflammatory bowel disease, treatment with an H2-blocker or proton-pump inhibitor during the month preceding the determination of the gastrin level, hypercalcemia, renal insufficiency, gastrinoma, atrophic gastritis, or pernicious anemia. Ninety-one patients with an adenocarcinoma (mean age, 66 years), 89 patients with polyps (mean age, 61 years), and 101 controls (mean age, 62 years) were included. Fasting serum gastrin levels were similar in patients with tumors (20 pg/L; interquartile range, 1 5 - 31), polyps (20 pg/L; 15-35), and controls (21 pg/L; 18-31; P = 0.37, KruskalWallis test). Our results are in complete agreement with those of Penman et al. and confirm the absence of elevated serum gastrin levels in patients with colorectal tumors and polyps. Further investigations should focus on the presence ofgastrin receptors or progastrin-derived peptides in human tumors. A. ELEWAUT E. VANDERSTRAETEN
Department of Gastroenterology University Hospital De Pintelaan 185 B-9000 Ghent, Belgium 1. Penman ID, El-Omar E, Ardill JE, McGregor JR, Galloway DJ, O'dwyer PJ, McColl KE. Plasma gastrin concentrations are normal in patients with colorectal neoplasia and unaltered following tumor resection. Gastroenterology 1994; 1 0 6 : 1 2 6 3 - 1 2 7 0 . 2. Smith JP, Wood JG, Solomon TE. Elevated gastrin levels in patients colon cancer or adenomatous polyps. Dig Dis Sci 1 9 8 9 ; 3 4 : 1 7 1 174.
Reply. We welcome Drs. Elewant and Vanderstraeten's results, which support our own findings. Their study, however, measured serum gastrin concentrations in people before colonoscopy, and it is unclear what form of bowel preparation was used. Furthermore, we have reservations about using people with normal results of colonoscopy as "normal" controls, because they must have had some gastrointestinal symptoms in order to warrant the procedure in the first place. It is also not clear whether the different groups were matched for Helicobacter pylori status, which can clearly influence gastrin levels. Our principal concern was to match patient and control groups as closely as possible and to control for these, and other, possible factors that may influence gastrin levels. Since our study was published, the results have been further supported by preliminary data from another group, 1 who found that only Helicobacter-positive colorectal cancer patients had significantly greater gastrin concentrations than control patients. It seems clear that once all possible causes of hypergastrinaemia have been controlled for, colorectal tumor patients do not have higher circulating gastrin levels than control patients. Several studies 2'3 published recently suggest that gastrin gene expression with incomplete posttranslational processing may occur in some colorectal carcinomas, and we agree with Drs. Elewant and Vanderstraeten that future studies should concentrate on the signifi-
CORRESPONDENCE 619
cance ofprogastrin-derived peptides as putative autocrine or paracrine trophic factors in this disease. IAN D. PENMAN EMAD EL-OMAR KENNETH E. L. McCOLL
Department of Medicine and Therapeutics Gardiner Institute Western Infirmary Glasgow G11 6NT, Scotland 1. Meier R, Pullwitt G, Gamboni G, Baselgia L, Beglinger C. Further evidence of gastrin as an aetiological factor in the colon cancer carcinogenesis (a pilot study). Gut 1994;35(Suppl):A194. 2. Kochman ML, DelValle J, Dickinson CJ, Boland CR. Post-translational processing of gastrin in neoplastic human colonic tissues. Biochem Biophys Res Commun 1 9 9 2 ; 1 8 9 : 1 1 6 5 - 1 1 6 9 . 3. Nemeth J, Taylor B, Pauwels S, Varro A, Dockray GJ. Identification of progastrin-derived peptides in colorectal carcinoma extracts. Gut 1 9 9 3 ; 3 4 : 9 0 - 9 5 .
Neurobiology of Relaxation Training in Gastroesophageal Reflux Disease Dear Sir: In their report of relaxation training (RT) in patients with gastroesophageal reflux disease (GERD), McDonald-Haile et al. find that subjective anxiety and mean heart rate were significantly lower for the RT group relative to the attention placebo (AP) group, but there were no significant differences in mean systolic blood pressure and diastolic blood pressure between the RT group and the AP group. They propose future research comparing a group undergoing RT with another group trained only in diaphragmatic breathing to determine if the deep-breathing component of this intervention could produce the same result as the complete muscle relaxation intervention) The neurobiology is suggested by profound effects on angina pectoris by attention to pauses during breathing induced by dopamine (DA) subserving the brain-gut axis, brainstem cardiovascular control, cardiovascular reactivity in challenging tasks, coping behavior, mood, and vasospasm. 2'3 This hypothesis is supported by optimal response organization at intermediate DA tone in a medial-frontal-striatal activation system, by the concept of cellular tone, and by operant conditioning of hippocampal CA1 pyramidal cell bursting at different concentrations of DA showing a sharp peak at 1 mmol/L and decreasing abruptly when this optimal concentration of DA was either halved or doubled. 4 It is also supported by unilateral naris closure leading to a reduction of DA 5 and by a neurochemical model underlying differences in reaction times between introverts and extroverts. ~ The fact that delay-dependent speeding of reaction time, indicating motor readiness, is abolished by depletion of DA, prompts the tailoring of interventions in GERD by monitoring speech hesitation and switching pauses. This method is supported by the correlation of the frequency and duration of hesitation pauses to sixfold coronary risk and mood, respectively, by the blood pressure-lowering effect of longer, less recurrent pauses, 2 and by adaptation to stress manifested by slower, deeper breathing contributing to a 6.5-fold reduction of mortality. 6 It is also supported by the construct validity of response latencies, easily obtainable through microcomputer testing of spontaneous speech in emotionally charged dialogues. These findings tend to confirm powerful isomorphisms between mind and body, physical and psychological nature, and the material and immaterial worlds.
620
CORRESPONDENCE
GASTROENTEROLOGY VoI. IO8, No. 2
They also point to the existence of deep and lawful mental structures governing human cognitive and emotional functioning, reflecting properties of neuronal activity and firing.2'4 ERNEST H. FRIEDMAN, M.D. 1831 ForestHills Boulevard East Cleveland, Ohio 44112-4313 1. McDonald-Haile J, Bradley LA, Bailey MA, Schan CA, Richter JE. Relaxation training reduces symptom reports and acid exposure in patients with gastroesophageal reflux disease. Gastroenterology 1994; 107:61-69.
2. Friedman EH, Owens JF, Matthews, KA, Stoney CM, Berga SL. Menopause and blood pressure (letter and reply). Circulation 1994;89:2947. 3. Friedman EH. Life-events stress: a significant precursor to subarachnoid hemorrhage (letter). Neuropsychiatry Neuropsychol Behav Neurol 1994;7:136-137. 4. Friedman EH, Karasawa Y. Neurobiology of passive avoidance impairment after ischemia (letter and reply). Stroke 1994;25:1526. 5. Brunjes PC. Unilateral naris closure and olfactory system development. Brain Res Rev 1994; 19:146-160. 6. Meerson F, Pozharov V, Minyailenko T. Superresistance against hypoxia after preliminary adaptation to repeated stress. J Appl Physiol 1994;76:1656-1861.
Notice of Duplicate Publication A version of the following notice appeared in Immunology (1994;82:505) at the request of Drs. L. Eckmann, M. F. Kagnoff, and M. T. Falco. An article entitled "Colonic Epithelial Cell Lines as a Source of Interleukin-8: Stimulation by Inflammatory Cytokines and Bacterial Lipopolysaccharide" by C.-C. Schuerer-Maly, L. Eckmann, M. F. Kagnoff, M. T. Falco, and F.-E. Maly, which was published in Immunology (1994;81:85-91), was submitted without the knowledge or approval of the coauthors L. Eckmann, M. F. Kagnoff, or M. T. Falco. Many of the data included in this paper duplicate a prior publication, "Differential Cytokine Expression by Human Intestinal Epithelial Cell Lines: Regulated Expression of Interleukin 8" (Gastroenterology 1993;105:1689-1697) by L. Eckmann, H. C. Jung, C. Schtirer-Maly, A. Panja, E. Morzycka-Wroblewska, and M. F. Kagnoff. Although Drs. Eckmann, Kagnoff, and Falco do not question the validity of the data in the paper in Immunology, they take no responsibility for the accuracy, interpretation, or duplicate publication of the data.
Correction Lunel F, Musset L, Cacoub P, Frangeul L, Cresta P, Perrin M, Grippon P, Hoang C, Piette JC, Huraux J.-M., Opolon P. Cryoglobulinemia in chronic liver diseases: role of hepatitis C virus and liver damage. Gastroenterology 1994;106:1291-1300.
Dominique Valla should have been listed after Catherine Hoang as an author of this paper.
We analyzed the medical records of all patients with colorectal cancers or adenomatous polyps seen between 1983 and 1992; in all patients serum gastrin concentration was determined after an overnight fast, before the coloscopic procedure. As a control group, all consecutive patients with normal results of colonoscopy seen in the period between 1989 and 1992 veere used. Patients excluded were those with a history of gastric surgery or small bowel resection, a history of ulcers, evidence of inflammatory bowel disease, treatment with an H2-blocker or proton-pump inhibitor during the month preceding the determination of the gastrin level, hypercalcemia, renal insufficiency, gastrinoma, atrophic gastritis, or pernicious anemia. Ninety-one patients with an adenocarcinoma (mean age, 66 years), 89 patients with polyps (mean age, 61 years), and 101 controls (mean age, 62 years) were included. Fasting serum gastrin levels were similar in patients with tumors (20 pg/L; interquartile range, 1 5 - 31), polyps (20 pg/L; 15-35), and controls (21 pg/L; 18-31; P = 0.37, KruskalWallis test). Our results are in complete agreement with those of Penman et al. and confirm the absence of elevated serum gastrin levels in patients with colorectal tumors and polyps. Further investigations should focus on the presence ofgastrin receptors or progastrin-derived peptides in human tumors. A. ELEWAUT E. VANDERSTRAETEN
Department of Gastroenterology University Hospital De Pintelaan 185 B-9000 Ghent, Belgium 1. Penman ID, El-Omar E, Ardill JE, McGregor JR, Galloway DJ, O'dwyer PJ, McColl KE. Plasma gastrin concentrations are normal in patients with colorectal neoplasia and unaltered following tumor resection. Gastroenterology 1994; 1 0 6 : 1 2 6 3 - 1 2 7 0 . 2. Smith JP, Wood JG, Solomon TE. Elevated gastrin levels in patients colon cancer or adenomatous polyps. Dig Dis Sci 1 9 8 9 ; 3 4 : 1 7 1 174.
Reply. We welcome Drs. Elewant and Vanderstraeten's results, which support our own findings. Their study, however, measured serum gastrin concentrations in people before colonoscopy, and it is unclear what form of bowel preparation was used. Furthermore, we have reservations about using people with normal results of colonoscopy as "normal" controls, because they must have had some gastrointestinal symptoms in order to warrant the procedure in the first place. It is also not clear whether the different groups were matched for Helicobacter pylori status, which can clearly influence gastrin levels. Our principal concern was to match patient and control groups as closely as possible and to control for these, and other, possible factors that may influence gastrin levels. Since our study was published, the results have been further supported by preliminary data from another group, 1 who found that only Helicobacter-positive colorectal cancer patients had significantly greater gastrin concentrations than control patients. It seems clear that once all possible causes of hypergastrinaemia have been controlled for, colorectal tumor patients do not have higher circulating gastrin levels than control patients. Several studies 2'3 published recently suggest that gastrin gene expression with incomplete posttranslational processing may occur in some colorectal carcinomas, and we agree with Drs. Elewant and Vanderstraeten that future studies should concentrate on the signifi-
CORRESPONDENCE 619
cance ofprogastrin-derived peptides as putative autocrine or paracrine trophic factors in this disease. IAN D. PENMAN EMAD EL-OMAR KENNETH E. L. McCOLL
Department of Medicine and Therapeutics Gardiner Institute Western Infirmary Glasgow G11 6NT, Scotland 1. Meier R, Pullwitt G, Gamboni G, Baselgia L, Beglinger C. Further evidence of gastrin as an aetiological factor in the colon cancer carcinogenesis (a pilot study). Gut 1994;35(Suppl):A194. 2. Kochman ML, DelValle J, Dickinson CJ, Boland CR. Post-translational processing of gastrin in neoplastic human colonic tissues. Biochem Biophys Res Commun 1 9 9 2 ; 1 8 9 : 1 1 6 5 - 1 1 6 9 . 3. Nemeth J, Taylor B, Pauwels S, Varro A, Dockray GJ. Identification of progastrin-derived peptides in colorectal carcinoma extracts. Gut 1 9 9 3 ; 3 4 : 9 0 - 9 5 .
Neurobiology of Relaxation Training in Gastroesophageal Reflux Disease Dear Sir: In their report of relaxation training (RT) in patients with gastroesophageal reflux disease (GERD), McDonald-Haile et al. find that subjective anxiety and mean heart rate were significantly lower for the RT group relative to the attention placebo (AP) group, but there were no significant differences in mean systolic blood pressure and diastolic blood pressure between the RT group and the AP group. They propose future research comparing a group undergoing RT with another group trained only in diaphragmatic breathing to determine if the deep-breathing component of this intervention could produce the same result as the complete muscle relaxation intervention) The neurobiology is suggested by profound effects on angina pectoris by attention to pauses during breathing induced by dopamine (DA) subserving the brain-gut axis, brainstem cardiovascular control, cardiovascular reactivity in challenging tasks, coping behavior, mood, and vasospasm. 2'3 This hypothesis is supported by optimal response organization at intermediate DA tone in a medial-frontal-striatal activation system, by the concept of cellular tone, and by operant conditioning of hippocampal CA1 pyramidal cell bursting at different concentrations of DA showing a sharp peak at 1 mmol/L and decreasing abruptly when this optimal concentration of DA was either halved or doubled. 4 It is also supported by unilateral naris closure leading to a reduction of DA 5 and by a neurochemical model underlying differences in reaction times between introverts and extroverts. ~ The fact that delay-dependent speeding of reaction time, indicating motor readiness, is abolished by depletion of DA, prompts the tailoring of interventions in GERD by monitoring speech hesitation and switching pauses. This method is supported by the correlation of the frequency and duration of hesitation pauses to sixfold coronary risk and mood, respectively, by the blood pressure-lowering effect of longer, less recurrent pauses, 2 and by adaptation to stress manifested by slower, deeper breathing contributing to a 6.5-fold reduction of mortality. 6 It is also supported by the construct validity of response latencies, easily obtainable through microcomputer testing of spontaneous speech in emotionally charged dialogues. These findings tend to confirm powerful isomorphisms between mind and body, physical and psychological nature, and the material and immaterial worlds.
620
CORRESPONDENCE
GASTROENTEROLOGY VoI. IO8, No. 2
They also point to the existence of deep and lawful mental structures governing human cognitive and emotional functioning, reflecting properties of neuronal activity and firing.2'4 ERNEST H. FRIEDMAN, M.D. 1831 ForestHills Boulevard East Cleveland, Ohio 44112-4313 1. McDonald-Haile J, Bradley LA, Bailey MA, Schan CA, Richter JE. Relaxation training reduces symptom reports and acid exposure in patients with gastroesophageal reflux disease. Gastroenterology 1994; 107:61-69.
2. Friedman EH, Owens JF, Matthews, KA, Stoney CM, Berga SL. Menopause and blood pressure (letter and reply). Circulation 1994;89:2947. 3. Friedman EH. Life-events stress: a significant precursor to subarachnoid hemorrhage (letter). Neuropsychiatry Neuropsychol Behav Neurol 1994;7:136-137. 4. Friedman EH, Karasawa Y. Neurobiology of passive avoidance impairment after ischemia (letter and reply). Stroke 1994;25:1526. 5. Brunjes PC. Unilateral naris closure and olfactory system development. Brain Res Rev 1994; 19:146-160. 6. Meerson F, Pozharov V, Minyailenko T. Superresistance against hypoxia after preliminary adaptation to repeated stress. J Appl Physiol 1994;76:1656-1861.
Notice of Duplicate Publication A version of the following notice appeared in Immunology (1994;82:505) at the request of Drs. L. Eckmann, M. F. Kagnoff, and M. T. Falco. An article entitled "Colonic Epithelial Cell Lines as a Source of Interleukin-8: Stimulation by Inflammatory Cytokines and Bacterial Lipopolysaccharide" by C.-C. Schuerer-Maly, L. Eckmann, M. F. Kagnoff, M. T. Falco, and F.-E. Maly, which was published in Immunology (1994;81:85-91), was submitted without the knowledge or approval of the coauthors L. Eckmann, M. F. Kagnoff, or M. T. Falco. Many of the data included in this paper duplicate a prior publication, "Differential Cytokine Expression by Human Intestinal Epithelial Cell Lines: Regulated Expression of Interleukin 8" (Gastroenterology 1993;105:1689-1697) by L. Eckmann, H. C. Jung, C. Schtirer-Maly, A. Panja, E. Morzycka-Wroblewska, and M. F. Kagnoff. Although Drs. Eckmann, Kagnoff, and Falco do not question the validity of the data in the paper in Immunology, they take no responsibility for the accuracy, interpretation, or duplicate publication of the data.
Correction Lunel F, Musset L, Cacoub P, Frangeul L, Cresta P, Perrin M, Grippon P, Hoang C, Piette JC, Huraux J.-M., Opolon P. Cryoglobulinemia in chronic liver diseases: role of hepatitis C virus and liver damage. Gastroenterology 1994;106:1291-1300.
Dominique Valla should have been listed after Catherine Hoang as an author of this paper.