Curative rectal cancer surgery in a low-volume hospital: a quality assessment.

AIMS: Hospital volume or caseload is often used as a surrogate measure for quality of care in rectal cancer treatment. The aim of this study was to assess outcome in a low-volume hospital and secondly to examine the impact of surgeon volume on the results. METHODS: A retrospective review of 131 patients' charts identified 102 patients receiving apparently curative resections for rectal cancer in the period 1993-2002. Our study population did not differ significantly from the national average except for shift towards more advanced Dukes stage (p=0.00) and a higher rate of node positive patients at time of diagnosis (p=0.00). RESULTS: There were no significant differences from the national outcome results, neither in perioperative mortality or complications, nor 5-year survival or local recurrences. Thirteen different on-staff surgeons performed rectal cancer surgery in our hospital in the decade, and median annual caseload was four. We detect a difference in 5-year survival when grouping the surgeons by annual caseload, but the significance is inconclusive. It is, however, interesting that in 85% of the resections, two or more certified gastrointestinal surgeons with specific training were involved. A relatively high number (9%) of discrepancies between the Norwegian Rectal Cancer Registry (NRCR) database and the local hospital database were identified. CONCLUSION: Adequate results for surgical outcome can be achieved in a low-volume hospital. Surgeon volume showed inconclusive impact for our results of outcome. A local quality initiative is justified in addition to national registries.

Phobic anxiety changes the function of brain-gut axis in irritable bowel syndrome.

OBJECTIVE: Disease severity in the irritable bowel syndrome (IBS) is highly influenced by psychiatric comorbidity. The mechanism of this influence is generally unknown, even if the brain-gut axis seems to be involved. Recent research has indicated that IBS patients have aberrant perception of visceral stimuli in the CNS. We compared IBS patients with and without comorbid phobic anxiety to see if the comorbid disorder influenced brain information processing of auditory stimuli, and looked for possible consequences with respect to visceral sensitivity thresholds and disease severity. METHODS: Eleven female patients with IBS with comorbid phobic anxiety disorder were compared with 22 age-matched female IBS patients without such comorbidity. The groups were compared with respect to event-related potentials (ERP), auditory-presented words with emotional contents, barostat-assessed visceral sensitivity thresholds, and symptom levels the last week before assessment. RESULTS: The comorbid group had a significantly enhanced first negative ERP wave (N1) to all stimuli, indicating increased use of brain attentional resources. It also had increased visceral threshold for the sensation of gas, and reduced gas-stool and gas-discomfort tolerances compared with the noncomorbid group. Enhanced N1 amplitude at the frontal electrode and reduced gas-stools tolerance significantly predicted subjective gas complaints, explaining 47% of the symptom variation. CONCLUSIONS: The study suggests an association between information processing in the frontal brain and visceral sensitivity characteristics in IBS patients, and indicates that subjective disease-related symptomatology is predicted by brain perceptual characteristics. The findings indicate that an interaction between IBS-related and anxiety-related hyperreactivity in the frontal brain may constitute a psychophysiological mechanism for the contribution of psychiatric comorbidity to severity and duration of the irritable bowel syndrome.

The Swedish Elbow Arthroplasty Register and the Swedish Shoulder Arthroplasty Register: two new Swedish arthroplasty registers.

Two new national orthopedic quality registers were started in Sweden in 1999, the Swedish Shoulder Arthroplasty Register and the Swedish Elbow Arthroplasty Register. Both are owned by the Swedish Shoulder and Elbow Section of the Swedish Orthopedic Association. The purpose of the registers is to improve surgical techniques and selection of implants and identify individual risk factors. Two of the main problems in starting a new national quality register involve inducing all centers in the country to participate and deciding on the data to register.

Relation between food provocation and systemic immune activation in patients with food intolerance.

We found that food provocation in food intolerant patients was characterised by a general and systemic immune activation accompanied by an increase in systemic symptoms. Our findings might be important for the understanding of the mechanisms involved in the pathogenesis of food intolerance.

Perceptual hyperreactivity to auditory stimuli in patients with irritable bowel syndrome.

BACKGROUND: Patients with irritable bowel syndrome (IBS) have abnormal perception of visceral stimuli; however, no study has so far investigated the perception of non-visceral stimuli in IBS. In the present study we used event-related potentials (ERP) to study whether IBS patients differed from healthy controls in processing of auditory stimuli and, if so, how this was influenced by emotions. METHODS: We compared ERPs to auditory stimuli in 40 female diarrhoea-predominant IBS patients without current psychiatric illness with those in 20 healthy controls. Tones were used as standard and target stimuli, and words with emotional content as distractors. Characteristics of the first negative wave (N100) and mean amplitudes in 50-msec time intervals between 150 and 600 msec were assessed. RESULTS: At the frontal midline electrode IBS patients had significantly enhanced N100 amplitude to all stimuli, persisting after adjustment for age, current emotions, and personality traits. They additionally had enhanced waves 200-300 msec and 400-500 msec after stimulus. The latter differences disappeared after adjustment for emotions and personality traits. CONCLUSIONS: In the frontal brain region, IBS patients seem to have a hyperreactivity to auditory stimuli compared with controls. Later elements (P300, N400) of stimulus processing were influenced by emotions and personality traits. These may possibly contribute to changes in intestinal motility caused by stress. The study indicates that aberrant brain functioning may be an element of the irritable bowel syndrome. It may elucidate a mechanism for brain-gut interaction by which psychosocial stress may influence visceral pain perception in non-psychiatric subjects with an intestinal motility disorder and also the efficacy of psychiatric treatment on IBS symptoms.

Rectal tone and brain information processing in irritable bowel syndrome.

We studied differences in rectal tone between healthy controls, nonpsychiatric irritable bowel syndrome (IBS) patients, and IBS patients with comorbid phobic anxiety disorders to assess the impact of psychiatric comorbidity on rectal tone. The groups were additionally compared with respect to brain information processing of everyday words with emotional content to see if we could identify an association between perception of emotional material in the brain and rectal tone. We found that both nonpsychiatric IBS patients and IBS patients with phobic anxiety disorder had increased baseline rectal tone compared with healthy controls (F = 9.81, P < 0.001). The phobic anxiety patients tended to have increased tone compared with nonpsychiatric IBS patients, but the difference did not reach statistical significance. Similar differences were found in the attentional elements of brain information processing activity assessed by event-related potentials. Rectal tone significantly predicted brain reactivity to emotional words, suggesting that changes in intestinal motor function may influence brain perception.

Intestinal reactivity to words with emotional content and brain information processing in irritable bowel syndrome.

The intestinal reactivity to emotional experiences is poorly understood. We therefore compared healthy controls with nonpsychiatric irritable bowel syndrome (IBS) patients and IBS patients with comorbid phobic anxiety disorders with respect to rectal wall reactivity during exposure to everyday words with emotional content. We found that 70.3% of the subjects responded either with increased or decreased rectal tone during exposure to anger words, 75.0% when exposed to sadness words, and 76.6% when exposed to anxiety words. We also investigated event-related potentials in the brain to the same stimuli. We observed significant group differences in the frontal brain to sadness (P < 0.001) and anxiety (P = 0.013) distracter words, and threshold significant group difference to anger (P = 0.053) distracter words. Rectal wall reactivity during the word series significantly predicted frontal amplitude to the same word series, indicating a close interaction among mind, brain, and gut.

Efficacy and safety of prolonged-release lanreotide in patients with gastrointestinal neuroendocrine tumors and hormone-related symptoms.

PURPOSE: To evaluate the prolonged release (PR) of the long-acting somatostatin analog lanreotide in patients with gastrointestinal neuroendocrine tumors and its effect on hormone-related symptomatology, tumor markers, tumor size, tolerability, and quality of life (QOL). PATIENTS AND METHODS: Eligible patients had the following substantial daily symptoms: for patients with carcinoid tumors, three or more stools and/or 1.5 or more flushing episodes; for patients with gastrinoma, greater than 50% elevated basic acid output; and for patients with vasoactive intestinal peptide-secreting tumors (VIPomas), four or more stools and/or a stool volume of >/= 800 mL, a measurable tumor, and an elevated biochemical tumor marker (>/= two times the upper limit of the normal reference range). Lanreotide PR was administered intramuscularly every 14 days at 30 mg for 6 months. We measured efficacy by studying symptoms, tumor markers, tumor size, and QOL. Side effects were scored according to the National Cancer Institute's toxicity grading system and ultrasound examination of the gallbladder. RESULTS: Fifty-five patients were included in the study (48 patients with carcinoid tumors, six patients with gastrinoma, and one patient with VIPoma). Symptomatic improvement (> 50% reduction) occurred in 38% of the assessable patients with carcinoid tumors, in 67% of the gastrinoma patients, and in the VIPoma patient. Tumor markers normalized in two of 45 assessable patients, 19 patients exhibited a reduction (> 50%), 19 patients exhibited no change, and tumor markers rose by more than 50% in five patients. Tumor size was reduced in two of 31 assessable patients and remained stable in 25 patients; four patients experienced progression. QOL assessments after 1 month showed improvements in emotional and cognitive function, and diminished fatigue, sleeping disorders, and diarrhea. Eight of 30 assessable patients developed gallstones. CONCLUSION: Lanreotide PR is a well-tolerated somatostatin analog with significant clinical, biochemical, and antitumor effects that bring about a significant improvement in QOL for patients with neuroendocrine tumors.

Expression of p68 protein kinase and its prognostic significance during IFN-alpha therapy in patients with carcinoid tumours.

The aim of this study was to evaluate the antiproliferative effects of interferon alpha (IFN-alpha) on neuroendocrine differentiated cell lines and, retrospectively, to assess the prognostic significance of p68 protein kinase (PKR) induction in neuroendocrine gut and pancreatic tumour patients. Archive specimens from 56 patients were studied, 43 before IFN-alpha and 56 during therapy. The tissues were immunostained for p68 protein kinase (PKR) using the monoclonal antibody (MAb) TJ4C4. A significant increase in immunostaining after treatment with IFN-alpha compared with before treatment (3.47 +/- 0.12 versus 2.72 +/- 0.15, P < 0.001) was noted. The p68 score was significantly increased after treatment only in patients with stable disease before = 2.71 +/- 0.19, after = 3.40 +/- 0.14 (P < 0.001) or an objective response before 3.13 +/- 0.22, after = 4.00 +/- 0.24 (P < 0.05) but not in those with progressive disease (before = 2.32 +/- 0.24, after 2.86 +/- 0.26, NS). A low p68 score (< 3.0) during treatment was a predictor of shorter duration of response and overall survival (P = 0.0062 and P < 0.0001, respectively). Furthermore, IFN-alpha showed a significant antiproliferative effect (by [3H]thymidine incorporation) on two carcinoid tumour cell lines in a dose-dependent manner which correlated with a dose-dependent induction of p68 mRNA and protein expression (by Northern and Western blot analysis). We conclude that IFN-alpha can effectively inhibit the in vitro growth of carcinoid tumor cell lines and upregulates the expression of p68 at both mRNA and protein levels in carcinoid tumours. The induction of p68 could be a prognostic indicator of response in patients with carcinoid tumours during IFN-alpha treatment.

[Gastrointestinal amyloidosis. Differential diagnosis or a complication of inflammatory bowel disease?]. / Gastrointestinal amyloidose. Differensialdiagnose eller komplikasjon til inflammatorisk tarmsykdom?

A 77 year-old man developed intermittent diarrhoea and malabsorption. Endoscopic findings and preliminary histological examination indicated ulcerative colitis. Special staining of biopsies from the duodenum and colon revealed amyloid deposits. Classification of the amyloid fibril protein verified AL-amyloidosis, and the diagnosis primary idiopathic amyloidosis was made. Amyloid deposit in the gastrointestinal tract are a common feature of primary and secondary amyloidosis. The symptoms and findings are nonspecific and resemble those of chronic inflammatory bowel disease and ischemic colitis. Secondary amyloidosis can be seen as a rare complication of Crohn's disease and ulcerative colitis. Special staining is necessary to show amyloid deposit, and the distinction between primary and secondary amyloidosis requires immunohistochemistry.

Regulation of insulin-like growth factor-binding protein-1 and progesterone secretion from human granulosa-luteal cells: effects of octreotide and insulin.

OBJECTIVE: To examine the effects of the synthetic somatostatin-analogue octreotide and human recombinant insulin on the release of insulin-like growth factor binding protein-1 (IGFBP-1) and P from human granulosa-luteal cells. DESIGN: Primary culture of human granulosa-luteal cells. SETTING: Academic research laboratory. PATIENT(S): Women undergoing oocyte retrieval for IVF-ET because of tubal infertility. INTERVENTION(S): Octreotide or insulin were added to the cultures; sampling of culture medium was performed after 48 hours. MAIN OUTCOME MEASURE(S): Insulin-like growth factor binding protein-1 and P. RESULT(S): Octreotide significantly inhibited IGFBP-1 (58.8% compared with controls) and P release (66.1% compared with controls). Insulin abolished IGFBP-1 release while stimulating P release (200.7% compared with controls). There was a significant and positive correlation between IGFBP-1 and P levels. CONCLUSION(S): Octreotide and insulin have a significant effect on human granulosa-luteal cell function in terms of IGFBP-1 and P release. Our results suggest a local ovarian mechanism for the recently observed effects of octreotide in the treatment of women with polycystic ovary syndrome.

A prospective, randomized study with an independent observer comparing open carpal tunnel release with endoscopic carpal tunnel release.

In order to define the role of two-portal endoscopic carpal tunnel release, a prospective randomised study with an independent observer was performed to compare endoscopic and open surgery. Thirty-two hands in 29 patients, with symptoms, clinical signs and EMG changes consistent with idiopathic carpal tunnel syndrome were randomised to either endoscopic carpal tunnel release or open release. No significant difference in sick leave between the two groups could be found, being a mean of 17 days (range 0-31 days) with endoscopic surgery, and 19 days (range 0-42 days) with open conventional surgery. No differences in surgical results were found, but three patients in the endoscopic group suffered transient numbness on the radial side of the ring finger.

[Sick of food? Knowledge and hypothesis on food intolerance]. / Syk av mat? Kunnskap og hypoteser om matvareintoleranse.

Food intolerance is frequently reported by patients and represent a diagnostic and therapeutic challenge. We review the nomenclature and report on symptoms, diagnostic tests and treatment. The nomenclature presented is based on the primary events such as toxic reactions, allergy or an undefined mechanism, including psychosomatic, although these subgroups may involve common pathogenetic mechanism. Double blind placebo controlled food challenge is the golden standard in the diagnostic workup and the importance of elimination diets--individually tailored to each patients requirements in cooperation with a nutritionist--is stressed. Through strict adherence to diagnostic and therapeutical guidelines, therapy may resolve food induced symptoms. Based on preliminary findings of signal transduction, we propose that symptoms in some patients may depend on an allergy type IV reaction. This working hypothesis forms the basis for further accumulation of knowledge of food intolerance reactions.

Proteinase inhibitors induce selective stimulation of human trypsin and chymotrypsin secretion.

Among the variety of signals stimulating pancreatic secretion, cholecystokinin (CCK) and related hormones are assumed to be responsible for modulating proteinase output. In some species, intraduodenal tryptic activity has to be abolished to demonstrate feedback-induced CCK release. The aim of this study was to investigate in vivo effects of modest inhibition of intraduodenal proteolytic enzymes on the secretion patterns of pancreatic enzymes and plasma CCK concentrations. Two inhibitors (Kunitz trypsin inhibitor and Bowman-Birk inhibitor) were applied. Intermittent sampling of plasma nd duodenal juice was performed during intraduodenal saline and inhibitor instillations in six healthy volunteers. Enzyme activities and concentrations were determined in the duodenal samples and expressed as percentage of basal values. Instillation of Kunitz trypsin inhibitor caused an increase in trypsin and the pancreatic secretory trypsin inhibitor (PSTI), without changes in plasma CCK. This result demonstrates, for the first time, that pancreatic exocrine secretion of trypsin and chymotrypsin is regulated by different mechanisms. Bowman-Birk inhibitor additionally stimulated the secretion of chymotrypsin and carboxypeptidase A and B and increased plasma CCK. Elastase 1 and amylase secretions were not increased by either instillations. Although the inhibitors have similar in vitro inhibition patterns, their in vivo effects are different. The nonparallel secretion of proteinases (trypsin, chymotrypsin and elastase 1) supports the view of a complex system involved in feedback regulation of human pancreatic exocrine secretion, including signals other than CCK.

Interferon-alpha 2b, with or without prior hepatic artery embolization: clinical response and survival in mid-gut carcinoid patients. The Norwegian carcinoid study.

BACKGROUND: Mid-gut carcinoid tumours often present with liver metastases, and survival has then been less than 2 years in earlier reports. We have evaluated the effects of interferon therapy on clinical response and survival, with or without hepatic artery embolization in these patients. METHODS: In a prospective study 30 female and 12 male patients, aged 23 to 75 years, with mid-gut carcinoid tumours and liver metastases underwent surgery with removal of as much as possible of their primary tumour. If technically feasible, embolization of hepatic arteries was performed in the absence of contraindications. Seventeen patients were embolized, and all patients received interferon-alpha 2b treatment for 1 year. Response factors were computer tomography (CT) measurement of the largest liver metastasis and the 24-h urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA). After 12 months patients with objective response or stable disease either continued or withdrew from interferon therapy. Survival was estimated when all patients had been observed for at least 36 months. RESULTS: Nine patients reduced the dose, and five withdrew from interferon treatment owing to side-effects the 1st year. Three patients died. Fifteen patients (39%) showed objective response 12 months after inclusion. Cumulative 5-year survival estimated from inclusion was 37.5% in all 42 patients but 71.4% in those who continued interferon therapy. The difference in survival between the interferon-treated and those who withdrew from interferon therapy at 12 months was significant when embolization was corrected for in a Cox model (p < 0.0125). The seemingly increased survival in embolized versus non-embolized patients did not reach statistical significance (p = 0.07). CONCLUSION: Interferon induced an objective response in mid-gut carcinoid patients as judged by the 24-h urinary 5-HIAA excretion. Patients receiving continuous interferon therapy showed improved response and survival compared with patients who stopped the treatment. Regardless of medical therapy, more survivors and more responders, as evaluated from CT measurements, were found among the embolized patients than among the non-embolized. Embolization could, however, not be shown to have a significant effect on survival.

Somatostatin in physiological concentrations inhibits basal and enhances luteinizing hormone-stimulated progesterone release from human granulosa-luteal cells.

To study the effect of somatostatin on ovarian function, we investigated the action of physiological concentrations of somatostatin (5.0 x 10(-12)-1.0 x 10(-10) M) on the basal and luteinizing hormone (LH)-stimulated progesterone release from cultured human granulosa-luteal cells obtained from in-vitro fertilization patients. Somatostatin exerted a significant and inhibitory effect on basal progesterone release from the granulosa-luteal cells, whereas it was unable to inhibit LH-stimulated progesterone release. Instead, a significant increase in progesterone release was observed after concomitant incubation with LH and somatostatin compared with the untreated controls. We suggest that somatostatin may serve as a regulator of ovarian functions under physiological conditions.

Clinical effects of octreotide compared to placebo in patients with gastrointestinal neuroendocrine tumours. Report on a double-blind, randomized trial.

OBJECTIVES: To compare the effect of octreotide with f placebo on symptoms, tumour marker and quality of life in patients with gastrointestinal neuroendocrine tumours and liver metastases. DESIGN: A blinded, placebo-controlled, cross-over study was performed. The number of flushing epidodes and diarrhoea episodes were registered for 1 week prior to the study and for the 8-week duration of the study. Quality of life and 24-h urinary 5-hydroxyindoleacetic acid (5-HIAA) excretion were measured before the start, and at 4 and 8 weeks. Quality of life was registered with the Psychosocial Adjustment to Illness Scale (PAIS) and 5-HIAA measured by high-performance chromatography with electrochemical detection. 5-HIAA values exceeding 45 mumol 24 h-1 were considered to be elevated. SETTING: The study was performed in a tertiary referral centre. SUBJECTS: Twelve patients were approached; eleven patients were included, with a mean age of 56.5 (range 30-72) years. The primary tumour originated from the small intestine in nine and from the pancreas in two patients. The main symptoms were diarrhoea, flushing and nausea. The 24-h excretion of 5-HIAA was increased in all patients. INTERVENTIONS: Patients were treated for 4 weeks with octreotide (100 micrograms) subcutaneously, twice daily, and for 4 weeks on placebo (octreotide vehicle) in random starting order. MAIN OUTCOME MEASURES: The main outcome measures were the number of episodes of the main clinical symptom(s) and 24-h 5-HIAA excretion. RESULTS: Octreotide lowered diarrhoea and flushing frequency significantly compared to placebo. 5-HIAA excretion was reduced during treatment with the active drug. Two domains of the PAIS were significantly improved, indicating that the reduction of tumour marker and symptoms were clinically important. CONCLUSIONS: The clinical effect of octreotide on symptoms in patients with neuroendocrine tumours was demonstrated in a controlled, prospective trial.

Cardiac manifestations in mid-gut carcinoid disease.

The extent of heart disease and its relationship to the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA), was studied with M-mode, 2D and Doppler echocardiography in 42 consecutive patients, 30 females and 12 males, median age 63 (range 23-75) years with histologically verified mid-gut tumour, liver metastases and 24-h urinary 5-HIAA excretion above 47 mumol.24 h-1. All patients had normal left ventricular ejection fractions, median 65% (interquartile range (IQR) 54-74%). Moderate to severe tricuspid regurgitation (TR) was diagnosed in 22 patients (59%); mitral or aortic regurgitation was found in nine (24%) and six (16%) patients, respectively. The mitral flow peak early (E) on late (A) velocity ratio was significantly decreased compared to age-matched normal subjects. The group of patients with 5-HIAA excretion exceeding 1000 mumol.24h-1 contained significantly more patients with severe TR than those with a lower excretion. The decrease in the E/A ratio may indicate reduced left ventricular compliance, possibly secondary to fibrous changes similar to those seen intra-abdominally and in the right side of the heart. As serotonin is degraded in the lung circulation, other mediators such as tachykinins and cytokines (PDGF) may be involved.

Subcutaneous immunoglobulin replacement in patients with primary antibody deficiencies: safety and costs.

Immunoglobulins (IgG) as replacement therapy in primary antibody deficiencies can be given as intramuscular injections, or as intravenous or subcutaneous infusions. Our aims were to obtain information on the frequency of adverse systemic reactions during subcutaneous therapy, the occurrence and intensity of tissue reactions at the infusion sites, and serum IgG changes. Furthermore, we compared costs between the different replacement regimes. Our study included 165 patients (69 women, 96 men, aged 13-76 years) with primary hypogammaglobulinaemia or IgG-subclass deficiencies. Data were compiled from questionnaires filled in by the patients and from their medical records. 33,168 subcutaneous infusions (27,030 in home therapy) had been given. 106 (of which 16 were at home) adverse systemic reactions (100 mild, 6 moderate) were recorded in 28 patients (17%). No severe or anaphylactoid reactions occurred. Despite large immunoglobulin volumes given during 434 patient years (28,480 infusions), no signs have been found that indicate the transmission of hepatitis virus. Transient tissue reactions occurred at the infusion sites but were not troublesome to most patients and we found significant increases in mean serum IgG. The use of subcutaneous instead of intravenous infusions at home would reduce the yearly cost per patient for the health-care sector by US $10,100 in Sweden alone. We conclude that subcutaneous administration of IgG is a safe and convenient method of providing immunoglobulins. We were able to reach serum IgG concentrations similar to those by the intravenous therapy and we found that the method could also be used successfully in patients with previous severe or anaphylactoid reactions to intramuscular injections.

Inhibitor-stimulated non-parallel pancreatic secretion in man: hormonal and neural regulation?

BACKGROUND: We wanted to study whether a total inhibition of tryptic activity in the duodenum would induce a cholecystokinin (CCK)-dependent increase in pancreatic exocrine proteinase secretion. METHODS: Concentrations of CCK and activities and concentrations of pancreatic enzymes were measured in human plasma and duodenal juices, respectively, collected during continuous intraduodenal instillations of proteinase inhibitors, with and without intravenous atropine administration. RESULTS: Inhibitor instillation totally abolished tryptic activity and reduced the chymotryptic and elastase (1 and 2) activities by 95-100%. The inhibitors caused a rapid increase in the concentrations of trypsin, chymotrypsin, and pancreatic secretory trypsin inhibitor (PSTI) but had only a slight or no effect on amylase and elastase 1 secretion. An enhanced secretion of PSTI lends support to a possible connection between PSTI (resembling the monitor peptide causing CCK release in rats) and the enzyme secretion in man. CCK increased from 7 to 12-13 pmol/l. Intravenous atropine almost completely blocked the inhibitor-stimulated enzyme and PSTI secretion and reduced amylase activity by 50%. A further significant (P = 0.002) increase in the inhibitor-induced CCK output was found during atropine administration, as compared with the test situation without atropine. CONCLUSION: The inhibitor-induced pancreatic secretion during total inhibition of tryptic activity shows a non-parallel secretion requiring different signals for different enzymes. The increase in plasma CCK levels indicates that CCK is feedback-regulated by both an inhibitor-mediated decrease in duodenal enzyme activity and a further decrease in pancreatic enzyme secretion by atropine.