The role of prolactin in the suppression of the response to restraint stress in the lactating mouse.

Suppression of the hypothalamic-pituitary-adrenal (HPA) axis is a well-characterised maternal adaptation that limits the exposure of the offspring to maternally-derived stress hormones. This current study has investigated the possible involvement of the lactogenic hormone, prolactin, in this physiologically important adaptation. As expected, circulating prolactin levels were higher in unstressed lactating mice compared to their virgin counterparts. Interestingly however, the ability of an acute period of restraint stress to further elevate prolactin levels was diminished in the former group. The stress-induced rise in prolactin levels in the virgin animals was concurrent with an increase in prolactin receptor activation within the adrenal cortical cells. This adrenal response was not seen in either the stressed or control lactation group, an observation that may be in part explained by the observed downregulation of prolactin receptor mRNA expression within this tissue. Further evidence of suppression of the HPA axis during lactation was revealed using in situ hybridisation to demonstrate that while acute restraint stress increased corticotrophin releasing hormone (CRH) mRNA expression in the hypothalamic paraventricular nucleus in both virgin and lactating mice, the magnitude of this response was reduced in the latter group. This potentially adaptive response did not, however, appear to result from the altered prolactin profile during lactation because it was not affected by the pharmacological suppression of prolactin secretion from the pituitary. This study therefore suggests that during lactation the response of the HPA axis to stress is suppressed at multiple physiological levels which are mediated by both prolactin-dependent and prolactin-independent mechanisms.

Central processing of rectal pain: a functional MR imaging study.

BACKGROUND AND PURPOSE: Although the central processing of somatic pain has been dealt with in numerous brain imaging studies, the neural correlates of visceral pain have received much more limited attention. Our goal was to assess the feasibility of detecting brain activation patterns induced by rectal pain by means of functional MR imaging. We hypothesized that the cerebral processing of rectal pain would exhibit strong similarities with the central processing of somatic pain. METHODS: Functional MR imaging data were obtained from eight healthy subjects. A block paradigm was applied. Rectal pain was induced by inflating a latex balloon catheter that had been inserted into the rectum. Functional responses were established by means of cross-correlation analysis. RESULTS: Activation was detected within the anterior cingulate gyrus, the prefrontal cortex, the insular cortex, the sensory-motor cortex, the inferior parietal lobule, the posterior cingulate gyrus, and the visual cortex. CONCLUSION: Functional MR imaging of visceral pain is feasible in healthy subjects. The activation patterns observed in this study support the hypothesis that the cerebral processing of visceral pain involves multiple components, similar to the central processing of somatic pain. Our results constitute a first step toward the identification of possible aberrations in the activation patterns of patients suffering from visceral hypersensitivity.

A malignant gastrointestinal stromal tumour in a patient with multiple endocrine neoplasia type 1.

Loss of heterozygosity for polymorphic markers flanking the multiple endocrine neoplasia type 1 (MEN-1) gene in parathyroid and pancreatic islet tumours from subjects with MEN-1 has been well documented and has led to the hypothesis that the MEN-1 gene functions as a recessive tumour suppressor gene. We report a case of MEN-1 with duodeno-pancreatic gastrinoma, parathyroid hyperplasia, pituitary adenoma, adrenal adenoma, and lipomas, whose rare association with a malignant gastrointestinal stromal tumour (GIST) represents an undescribed combination. MEN-1 mutation in this family was shown as a frameshift (1607delA) in exon 10. To assess the role of the MEN-1 gene in the pathogenesis of tumours less commonly associated with MEN-1, we studied GIST DNA for loss of the unaffected MEN-1 gene allele. Stromal tumour and peripheral leucocyte DNAs from our patient were examined for loss of heterozygosity using the PYGM microsatellite polymorphism and an intragenic polymorphism (D418D in exon 9) in the MEN-1 gene. We showed no evidence for loss of the wild-type MEN-1 allele in GIST. The MEN-1 germline inactivating mutation 1607delA-ter558 in exon 10 was detected in the stromal tumour DNA, but no somatic mutation in the wild-type MEN-1 allele in GIST DNA was detected. Occurrence of GIST could be consistent with the possibility that this MEN-1-related uncommon neoplasm arose independently by a mechanism unrelated to the MEN-1 gene.

[Is argon plasma coagulation an efficient treatment for digestive system vascular malformation and radiation proctitis?].

BACKGROUND AND AIMS: Argon beam coagulation is an innovative no-touch electrocoagulation technique in which high-frequency monopolar alternating current is delivered to the tissue through ionized argon gas. The aim of this prospective study was to evaluate the efficacy and safety of argon plasma coagulation (APC) for the treatment of hemorrhagic digestive vascular malformations and hemorrhagic radiation proctosigmoiditis. METHODS AND PATIENTS: From March 1998 through April 1999, we used endoscopic APC (ERBE, Lyon, France, argon gas source ICC 300, high-frequency electrosurgical generator ICC 200, gas flow 1 L/min, power setting 50 W) to treat 39 consecutive patients (mean age 70.3 +/- 10 years). The indications for treatment were anemia (n =10), active or oozing haemorrhage (n =15) from digestive angiodysplastic lesions (n =25), hemorrhagic antral telangiectatic vascular lesions (n =2), and hemorrhagic radiation proctosigmoiditis (n =12) after failure of medical treatments (5-aminosalicylic acid, corticosteroids, or sucralfate enemas). The efficacy of APC treatment was evaluated on symptoms, transfusion requirement, bleeding recurrence, hemoglobin value before and 6 months after APC therapy. RESULTS: On the average, 1 +/- 0.5 sessions per patient was required to treat digestive vascular malformations. Definitive haemostasis of digestive angiodysplastic lesions with active or oozing haemorrhage was achieved in one session in all patients. No bleeding recurrence was observed during the follow-up period of 6 months. Anemia recurrence was observed in 2 patients (7%). Average hemoglobin levels recorded before and 6 months after APC therapy were 78.8 +/- 21.2 g/L and 108 +/- 13.7 g/L, respectively (P<0.05). On the average, 2.8 +/- 0.8 sessions per patient were required to treat hemorrhagic radiation proctosigmoiditis. Ten patients (83%) reported improvement or cessation of rectal bleeding, most of them immediately after APC therapy. Endoscopic control was performed one month after APC therapy and showed complete disappearance of lesions in 8 patients (66%). Average hemoglobin levels recorded before and 6 months after APC therapy were of 102.7 +/- 21 g/L and 120 +/- 19.5 g/L, respectively (P <0.05). Complications were observed in 5 cases (13%): pneumoperitoneum in 2 cases, chronic rectal ulcerations in 2 cases, and nonsymptomatic rectal stenosis in 1 case. CONCLUSION: APC appears to be a simple, safe, and effective technique in the management of hemorrhagic radiation-induced proctosigmoiditis and hemorrhagic lesions.

[Are self-expanding metallic esophageal prostheses an effective treatment for malignant stenosis of the esophagus? A prospective study of 32 cases]. / Les prothèses oesophagiennes métalliques expansives sont-elles un traitement efficace des sténoses malignes de l'oesophage?. Etude prospective de 32 cas.

UNLABELLED: The treatment of esophageal carcinoma is frequently palliative. The aims of this prospective study were to evaluate the functional results of covered self expanding esophageal metal stents in patients with malignant obstruction of the esophagus and to compare two models of stent. PATIENTS AND METHODS: From April 1994 to August 1996, 32 patients were treated with 35 metal stents (Cook Z Stent Wilson Cook: n = 21; Ultraflex Boston Scientific: n = 14). Ten patients had a fistula. Previous treatment was effective in 30 patients. Initial score of dysphagia was 2.68 +/- 0.7. Initial score of Karnofsky was 60 +/- 10%. The metal stents could be placed in 100% of cases. The 30-day mortality was 0%. The morbidity of device placement of metal stents was 28%. The treatment of fistulas was effective without complication in 100% of cases. At month 3, we observed a significant decrease of dysphagia score (0.43 +/- 0.25) and a significant increase of Karnofsky score (75 +/- 10%) (P < 0.001). The mean duration of hospitalization was 5.4 +/- 1.3 days. During mean follow-up of 18 +/- 3.5 months, 14 patients (44%) died. Any difference concerning mortality and functional results was observed between 2 kinds of metal stents. We only observed a significant decrease of retrosternal pain in patients treated with Ultraflex prothesis. CONCLUSION: Self-expanding esophageal metal stents are a simple and effective palliative treatment of malignant obstruction of the esophagus. However, their high cost need other cost-efficacy studies to define their indications.

Relationship between acid reflux episodes and gastroesophageal reflux symptoms is very inconstant.

In this prospective study 244 consecutive patients presenting with typical and chronic signs of gastroesophageal reflux were included. Conventional 24-hr esophageal pH monitoring was carried out to establish the symptom association probability, the concordance index, and the symptom sensitivity index. The symptom association probability could be calculated in 110 patients (45%). Two groups were identified: group 1 had normal duration of esophageal acid exposure; subgroup la (nonsignificant symptom association probability) included 39 patients (35.5%) and subgroup lb (significant symptom association probability) included 24 patients (21.8%); group 2 had abnormal duration of esophageal acid exposure; subgroup 2a (nonsignificant symptom association probability) included 21 patients (19.1%) and subgroup 2b (significant symptom association probability) included 26 patients (23.6%). In all, 56.6% of the patients presented typical symptoms of reflux not directly determined by one or repeated acid reflux episodes. The correlation between symptom association probability and the symptom sensitivity index allows for more accurate determination of esophageal acid sensitivity (subgroups lb and 2b).

Central processing of rectal pain in patients with irritable bowel syndrome: an fMRI study.

OBJECTIVES: In healthy subjects, the neural correlates of visceral pain bear much similarity with the correlates of somatic pain. In patients with irritable bowel syndrome, the central nervous system is believed to play a strong modulatory or etiological role in the pathophysiology of the disease. We hypothesize that this role must be reflected in aberrations of central functional responses to noxious visceral stimulation in these patients. To verify this hypothesis, we have induced transient rectal pain in patients and assessed the functional responses of the brain by means of functional magnetic resonance imaging. METHODS: Twelve right-handed patients (11 female) were examined. Functional imaging (1.5 T) was performed following a block paradigm, alternating epochs with and without noxious stimulation of the rectum. Rectal pain was induced by inflating a latex balloon. Whole-brain coverage was achieved by means of echo-planar magnetic resonance acquisition. RESULTS: A strong variability of the individual responses to rectal pain was found in patients with irritable bowel syndrome. Significant activations were found in only two patients, and group analysis did not reveal significant activations. In contrast, all patients exhibited significant deactivations. Group analysis revealed significant deactivations within the right insula, the right amygdala, and the right striatum. CONCLUSIONS: This study reveals aberrant functional responses to noxious rectal stimulation in patients with irritable bowel syndrome. Those results add grounds to the hypothesis that the central nervous system plays a significant role in the pathophysiology of this syndrome.