Ambulatory oesophageal pH-metry. Position paper of the Working Team on Oesophageal pH-metry by the GISMAD (Gruppo Italiano di Studio sulla Motilità dell'Apparato Digerente).

In the last three decades, oesophageal pH monitoring has progressed from a physiological research tool to a routine outpatient clinical investigation in patients with suspected gastro-oesophageal reflux disease, one of the most common gastrointestinal disorders. Technological progress has considerably simplified both the procedure and the interpretation of data obtained, and there is currently reasonable consensus as to the parameters that best discriminate between physiological and pathological reflux. There remains a need for internationally agreed definitions and standards with regard to indexes to quantitate the extent and the significance of the relationship between occurrence of symptoms and reflux episodes during the examination. It is felt that national or local normal values are to be used to circumvent different eating habits and other socio-cultural differences which may influence gastro-oesophageal reflux. The reproducibility of the test appears, at present, to be at least good enough to allow classification of the patient as a pathological or physiological refluxer, albeit wide day-to-day variations seem to exist as far as concerns the extent of gastro-oesophageal reflux. Clinical applications of the technique have increased with better knowledge of the protean clinical manifestations of gastro-oesophageal reflux disease, and include the evaluation of "typical" gastro-oesophageal reflux disease patients with negative endoscopy or refractory oesophagitis, the "atypical" manifestations of gastro-oesophageal reflux disease and the pre- and post-operative evaluation of patients undergoing antireflux surgery.

Acid exposure of proximal esophagus in healthy subjects.

BACKGROUND: An association between gastroesophageal reflux (GER) and pulmonary or laryngeal diseases has been recognized, and dual pH monitoring of both distal and proximal esophagus has been proposed to investigate chronic respiratory symptoms of unexplained etiology. However, the degree of acid reflux in the upper esophagus is still uncertain, making it difficult to discriminate between physiological and abnormal GER. AIM: To define normal values for proximal esophageal acid exposure. METHODS: Two-level esophageal pH monitoring was performed in 22 healthy subjects and 26 reflux patients. A dual pH sensor with electrodes spaced 15 cm that were positioned 5 and 20 cm above cardias was used. Two different thresholds of pH 4 and 5 were used to evaluate GER at proximal level. RESULTS: In healthy subjects, at proximal level, the acid exposure time (% time pH < 4) was 0.4%, 0.7% and 0.1% for 24-hrs, upright and recumbent periods, respectively. Using pH 5 as threshold, acid exposure time (% time pH < 5) was 1.5%, 2.3% and 0.3% for 24-hrs, upright and recumbent periods, respectively. Twenty cm above cardias, acid exposure was greater in reflux patients in comparison to controls; however, all reflux values were significantly different between the two groups only when pH 5 was used as threshold. The percentage of distal reflux reaching the proximal site (16.0%, 27.9% and 7.1% in controls for 24-hrs, upright and recumbent periods, respectively) was similar in the two groups. CONCLUSIONS: Acid reflux, to a limited extent, is physiologic in proximal esophagus. The technique of pH recording 20 cm above cardias might be useful in documenting the cephalic extend of GER, allowing to investigate patients with atypical presentations of GER disease. It may be best to use both thresholds 4 and 5 for evaluating proximal acid exposure.

[Esophageal motor disorders in patients with dysphagia]. / Disordini della motilità esofagea in pazienti con disfagia.

Endoscopy and radiology are usually suggested as the first line investigations in patients with dysphagia. Esophageal manometry is indicated if the above studies are unfruitful. Our aim was to evaluate the role of manometry in diagnosing motor disorders of the esophagus in patients with non-organic dysphagia. We retrospectively evaluated the results of seven years' experience with esophageal manometry performed in 114 patients with difficulty in swallowing not due to esophageal structural lesions or reflux esophagitis, both escluded by endoscopic and/or radiologic studies prior to manometric investigation. A variety of nonspecific esophageal motor disorders were the most common (32%) manometric abnormalities seen in patients with dysphagia. Achalasia was common (23%) too, whereas diffuse esophageal spasm (8%), nutcracker esophagus (6%) and hypertensive LES (1%) accounted for a few motility disorders associated with dysphagia. Low LES pressure was found in 3% of the patients, suggesting gastroesophageal reflux as the cause of their difficulty in swallowing. The study confirms the role of esophageal manometry in diagnosing the cause of a swallowing disorder, identified in 83 out of 114 patients (73%). Achalasia and nonspecific esophageal motor disorders accounted for more than 50% of the motility disorders in patients with dysphagia.

[Pharyngo-esophageal motility disorders in Steinert's myotonic dystrophy. Description of a case presenting with dysphagia]. / Disordini della motilità faringo-esofagea nella distrofia miotonica di Steinert. Descrizione di un caso esordito con disfagia.

In Myotonic Dystrophy symptoms of gastrointestinal dysfunction may dominate the clinical picture or they may be manifested long before the musculoskeletal disturbances become apparent. A case of Myotonic Dystrophy in a 26-year-old woman with dysphagia as the symptom of clinical presentation is reported. Manometric investigations demonstrated motor dysfunctions in pharynx and in proximal, middle and distal portions of the esophageal body, indicating both striated and smooth muscle involvement. The pathophysiology of the esophageal motility disorders in Myotonic Dystrophy and the related therapeutic problems are briefly discussed.

Cisapride stimulates propulsive motility patterns in human jejunum.

The effects of cisapride on upper gut motility were studied in seven healthy volunteers by means of a novel intraluminal electromyographic technique in a placebo-controlled study. In the interdigestive state, cisapride (10 mg intravenous bolus injection) markedly increased the number of spike bursts. The most obvious effect was observed during the first 5-min period when a nonmigrating phase-3-like activity (stationary phase 3) occurred, which lasted for 2.6 +/- 0.4 min. This initial pattern was followed by an intense phase 2 activity, characterized by a 10-fold increase in the number of groups of repetitive spike bursts and a sixfold increase in the number of ultrarapid single propagated spike bursts (ultrarapid peristaltic rushes). Cisapride induces in the human upper gut a remarkable pattern of aborally propagated (peristaltic) contractions, which are very likely responsible for the active propulsion of intestinal contents in the interdigestive state.

Cisapride restores the decreased lower oesophageal sphincter pressure in reflux patients.

The effect of the new prokinetic drug cisapride on the resting lower oesophageal sphincter pressure and on the strength of peristaltic contractions was studied in 10 healthy controls and in 10 reflux patients with abnormally low (less than 10 mm Hg) basal lower oesophageal sphincter pressure. A slow intravenous injection of cisapride 10 mg significantly increased the sphincter pressure in the controls but even more in the patients in whom it almost doubled the resting lower oesophageal sphincter pressure of 8.7 (0.5) mm Hg to between 15 and 20 mm Hg for at least 90 min. Results are expressed as mean (SE). Cisapride also significantly increased the amplitude of peristaltic contractions in controls and reflux patients. Therefore, cisapride might be useful in the treatment of reflux.

Migrating action potential complexes in a patient with secretory diarrhea.

A 70-year-old woman with secretory diarrhea was studied with a novel technique of recording small intestinal myoelectrical activity which allowed us to obtain long, uninterrupted records of slow waves and spikes at eight or more different intestinal levels simultaneously. Typical migrating action potential complexes (MAPCs) were observed, consisting of spike bursts that extended over more than one slow wave and migrated distally at the same propagation velocity as the slow waves. This motility pattern occurred frequently during the period the patient presented with secretory diarrhea and disappeared with the disappearance of the diarrhea. It was observed only once in a series of 10 normal control subjects. This is the first report on MAPC activity in man and on the association of this myoelectrical pattern with secretory diarrhea in man.

Influence of metenkephalin analogue on motor activity of the gastrointestinal tract.

The effect of the metenkephalin analogue Hoe 825 on esophageal motility, fundic accommodation to distention, and migrating myoelectric complex was studied in 17 healthy volunteers. The metenkephalin analogue (40 micrograms i.v.) significantly increased the duration, amplitude, and propagation velocity of the postdeglutitive esophageal peristaltic contraction waves. It had no effect on the basal lower esophageal sphincter pressure but significantly decreased the completeness of the sphincteric relaxation from 85% +/- 5% on placebo to 70% +/- 7% (p less than 0.01). The metenkephalin analogue (40 micrograms i.v.) significantly decreased the fundic accommodation to distention. In doses ranging from 20 to 60 micrograms i.v. it induced a premature phase III of the migrating motor complex that started ectopically in the duodenum (without a gastric component) and migrated distally at a significantly higher velocity than a spontaneous phase III. It is hypothesized that the metenkephalin analogue induces these effects via an inhibition of the inhibitory nervous system.

Is determination of serum N-terminal procollagen type III peptide (sPIIIP) a marker of hepatic fibrosis?

Serum N-terminal procollagen type III peptide (sPIIIP) levels were evaluated in 58 patients affected by chronic liver disease, in order to assess the usefulness of sPIIIP as a marker of hepatic fibrosis. In 45 patients sPIIIP was also correlated to liver histology; biopsies were scored by two of the authors, without knowledge of diagnosis. Compared to normal controls, sPIIIP concentration was found to be significantly elevated in chronic active hepatitis (CAH) and in cirrhosis, but not in fatty liver. Patients affected by chronic persistent hepatitis (CPH) had values of sPIIIP higher than normal in four of 11 cases considered. A close correlation was found between sPIIIP values and histological parameters of inflammation, necrosis, and degeneration, while the relationship between sPIIIP levels and fibrosis was weaker. These data suggest that sPIIIP determination may reflect the extent of inflammatory changes in the liver; but it cannot be considered a reliable index of hepatic fibrosis.

Diagnostic significance of anti-HBc IgM (RIA) in healthy HBsAg carriers and in chronic hepatitis B.

The diagnostic significance of IgM antibody against hepatitis B core antigen (anti-HBc) in healthy hepatitis B surface antigen (HBsAg) carriers and in subjects affected by chronic hepatitis B was evaluated. IgM anti-HBc was sought and found in all nine patients examined who were affected by acute HBsAg-positive hepatitis. It was also detected in 2 out of 18 patients with HBsAg-positive chronic persistent hepatitis and in 12 out of 42 patients affected by HBsAg-positive chronic active hepatitis. The absence of this marker was noted in all 26 HBsAg healthy carriers and in the subjects with HBsAg-positive cirrhosis. No relationship was found between the presence of IgM anti-HBc and the degree of inflammatory activity in the patients with HBsAg-positive chronic active hepatitis. A correlation was not found between the presence of IgM anti-HBc and the presence of hepatitis B e antigen (HBeAg) in the same patients. These data show that the absence of IgM anti-HBc may be useful in identifying healthy carriers of HBsAg. The presence of this antibody may be a suitable indication of acute HBsAg-positive hepatitis. In patients with chronic active hepatitis B the presence of IgM anti-HBc cannot be used as diagnostic tool in predicting the severity of liver disease.

Diagnostic approach to hepatic hemangiomas detected by ultrasound.

Eighty cases of hepatic hemangioma were studied using ultrasound. In one group consisting of 28 subjects a final diagnosis of hepatic hemangioma was supported by arteriography (21 cases) or surgery (7 cases). In the remaining 52 cases, the diagnosis was uncertain and the normal clinical and biochemical findings with the ultrasound follow-up studies at intervals of 3, 6 and 12 months, made a diagnosis of hemangioma highly probable. Twenty-nine cases (9 cases of the first group and 20 of the second) were also evaluated by Tc-99m colloid and in vivo Tc-99m-labelled red blood cell scintigraphy. On the basis of ultrasound appearance and internal structure, hemangiomas may be divided into three groups: hyperechoic pattern (of which there were 16 cases in our study), cystic or anechoic pattern (5 cases), and complex pattern (7 cases). Fifty-two cases of uncertain diagnosis showed hyperechoic focal lesions with rounded, well-defined margins and no clinical or biological abnormalities. Differentiation from malignant forms must be approached according to the specific ultrasound pattern observed and the presence or absence of symptoms. Only in cases of hyperechoic, well-defined lesions detected in asymptomatic patients may a reliable diagnosis of hemangioma be made. The use of in vivo Tc-99m-labeled red blood cell scintigraphy (Tc-99m RBC scintigraphy) is useful in hyperechoic and cystic forms having a diameter greater than 3 cm. Complex forms invariably require additional studies, using complementary procedures (angiography, angio-CT) to confirm diagnosis.

Long term follow-up of mild chronic active hepatitis.

A group of 41 patients (25 males and 16 females) with mild chronic active hepatitis was studied for a mean follow-up period of 6.5 years. All patients had liver biopsy on admission and a second biopsy during the follow-up period. All but 7 patients were treated with prednisolone. Most of the patients were asymptomatic. There was no history of alcohol abuse or chronic administration of drugs. Fourteen patients were HBsAg positive and 27 HBsAg negative. Circulating autoantibodies were absent. Thirty-three patients did not demonstrate any change in disease activity. Four developed liver cirrhosis and four were apparently cured.

Calcitonin increases peripheral plasma somatostatin-like immunoreactivity levels in humans.

Even though the inhibitory effects of CT on both hormone secretion and gastrointestinal functions have been well established, the exact mechanism of action still remains unclear. Since the effects of CT can be reproduced by somatostatin, we studied in man the effect of SCT on peripheral plasma SLI levels. Immediately after the onset of CT infusion SLI rose from its mean basal value of 45 +/- 5.5 pg/ml to a peak value of 91 +/- 11 pg/ml (p less than 0.005). SLI levels were still significantly elevated at 30 (p less than 0.05), 45 (p less than 0.05), 90 (p less than 0.005) and 120 min (p less than 0.02). Our results, in good agreement with the previous report by Chiba et al. on isolated perfused rat stomach, suggest that CT effects may, at least in part, be mediated by endogenous somatostatin release.