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Biomedical subjects

D K Nelson

Publications and source records attributed to D K Nelson.

At least 19 recordsLinked to original sources
PubMed1998

Independent cycles of exocrine pancreatic secretion, hormones and gastroduodenal motility in healthy fasting humans: reassessment of a complex partnership.

BACKGROUND: Interdigestive pancreatic secretion cycles in close association with the phases of the migrating motor complex (MMC) and release of regulatory hormones. The extrinsically denervated pancreas exhibits an intrinsic cyclic rhythm. We hypothesized that this intrinsic rhythm is normally present in the intact human pancreas. METHODS: 19 healthy males (age range 26-35 years) were studied after 12 h fasting. A manometry catheter was positioned with four pressure ports in the antrum and three in the duodenum, and motility was recorded for a complete MMC cycle or 5 h. Duodenal aspirates were sampled at 15-min intervals, and immediately analysed for amylase, lipase and chymotrypsin activities; enzyme outputs were calculated by standard marker perfusion techniques. Plasma levels of pancreatic polypeptide (PP) and motilin were also determined (RIA) at 15-min intervals. RESULTS: Output of amylase, lipase and chymotrypsin occurred in parallel. All phase III motility fronts were accompanied by a pancreatic secretory peak. However, in 12 subjects at least one secretory peak was observed without the concomitant occurrence of phase III. A total of 16 out of 51 secretory peaks identified across all subjects were independent (31%). These phase III-independent peaks of pancreatic secretion occurred in subjects with a longer MMC cycle (160 +/- 19 min vs 102 +/- 13 min, P < 0.05). Phase III-associated and -independent peaks had a similar magnitude (amylase output: 21.6 +/- 3.9 kUh-1 vs 21.1 +/- 2.8 kUh-1, respectively). Irrespective of MMC phases, antral but not duodenal motor activity was closely correlated with fluctuations of pancreatic secretion (P < 0.05). Cycling of PP and motilin were also closely coordinated with pancreatic enzymes, with a particularly tight link between endocrine and exocrine secretion from the pancreas. CONCLUSIONS: Peaks of pancreatic secretion invariably occur when a phase III motor activity occurs, but additional secretory peaks occur without a concomitant phase III. Interdigestive phasic pancreatic secretion is tightly coordinated with PP and motilin release as well as with antral motor activity. An intrinsic rhythm of the pancreas distinct from other cyclic activity may be present in healthy humans, expressed as peaks of pancreatic secretion independent of a motor phase III.

Adult↗
PubMed1997

Prospective randomized comparison of stonetome combination catheter versus conventional endoscopic clearance of common bile duct.

OBJECTIVES: To assess the therapeutic efficacy and performance characteristics of a novel cannula that has recently become available for clearance of the common bile duct (CBD), combining a sphincterotome and retrieval balloon in a single instrument, and to compare it with the conventional approach. METHODS: Seventeen consecutive patients with signs of biliary obstruction were prospectively randomized to undergo evaluation and clearance of the CBD by combination catheter (Stonetome, Microvasive) or conventional sphincterotomy (Ultratome) with separate balloon sweep. In all cases, three sweeps of the CBD were made with an 11.5-mm retrieval balloon after sphincterotomy. Fluoroscopy time was measured, as was total time from initiation of sphincterotomy to removal of endoscope from the patient. The same endoscopist performed all procedures. RESULTS: Patient groups were matched with regard to age, gender, proportion with prior cholecystectomy, CBD diameter, and stone size. Patients were successfully treated by either approach. Use of the Stonetome combination catheter reduced mean fluoroscopy time by 52% (from 3.1 +/- 0.6 to 1.5 +/- 0.2 min), mean total time by 57% (from 11.3 +/- 2.2 to 4.9 +/- 1.1 min), and dosage of midazolam used for conscious sedation. CONCLUSIONS: The new combination catheter allows the elimination of one step in exchanging the sphincterotome for a retrieval balloon after sphincterotomy. Its efficacy in clearing the CBD is equal to that of our conventional approach. Use of the combined approach should minimize the risk of losing cannulation, reduce fluoroscopic exposure, and improve the overall efficiency of the procedure.

Adult↗
PubMed1996

M1-muscarinic mechanisms regulate interdigestive cycling of motor and secretory activity in human upper gut.

We determined the influence of M1-muscarinic pathways in modulating temporal cycling of motor and secretory activity in the fasting upper gut. Eight healthy subjects were studied on two separate days, following a double-blind, randomized protocol. Antroduodenal motility (migrating motor complex, MMC), pancreatic exocrine secretion (amylase, lipase, trypsin, chymotrypsin), and plasma levels of associated hormones [motilin, pancreatic polypeptide (PP)] were monitored for two consecutive cycles during background infusion of placebo or telenzepine, a selective M1-muscarinic receptor antagonist. On placebo days, pancreatic enzymes and hormones cycled in synchrony with motor activity, as expected. During M1 blockade, duodenal output of each enzyme was decreased by 85-90% in phase I and by > 90% in phase III. Similarly, plasma concentrations of hormones were decreased during all phases and cycling was absent. Despite the loss of these putative influences, intestinal motility continued to cycle, albeit in an altered fashion. Intermittent phase II activity was replaced by phase I quiescence, while phase III-like fronts were diminished (contraction frequency, amplitude, propagation velocity reduced 30-60%, duration not altered) but recurred at expected intervals (cycle length 105 +/- 14 min vs 109 +/- 12 in placebo). Gastric motor activity was virtually abolished. These data suggest or extend several working hypotheses: (1) Motilin is released and/or acts via cholinergic (M1-muscarinic) pathways to initiate antral, but not duodenal, phase III activity. (2) M1 receptors mediate all components of the gastric MMC and phase II activity throughout the gut, but intestinal phase III activity arises via alternate pathways. (3) M1-muscarinic mechanisms regulate interdigestive cycling of pancreatic enzymes and PP. (4) Secretions from the endocrine/exocrine pancreas are not primary mediators of intestinal motility.

Adult↗
PubMed1996

Nasogastric enteral feeding in the management of hyperemesis gravidarum.

OBJECTIVE: To report our experience in treating hyperemesis gravidarum with nasogastric enteral feeding. METHODS: Seven women (ages 17-36 years, mean 27 years) presented with intractable nausea, vomiting, dehydration, and weight loss (mean 13 lb) and were hospitalized for management of symptoms and nutritional support. An 8-Fr Dobbhoff nasogastric feeding tube was placed and nutritional supplement was administered as a continuous infusion, starting at a rate of 25 mL/hour. The rate of infusion was increased in an incremental fashion until daily caloric requirements were met. RESULTS: Nausea and vomiting improved within 24 hours after nasogastric tube placement. Enteral feedings were well tolerated, and all patients were discharged from the hospital within 8 days. Enteral feedings were continued, in an outpatient setting, for a mean of 43 days (range 5-174). Ultimately, all patients resumed oral feeding and discontinued enteral feeding. Subsequently, all patients gave birth to full-term, normal-weight babies. CONCLUSION: Enteral feeding via nasogastric tube seems to be effective in relieving intractable nausea and vomiting and in providing adequate nutritional support. Enteral nutrition should be considered as an alternative to total parenteral nutrition in the management of hyperemesis gravidarum.

Adult↗
PubMed1996

M1 muscarinic mechanisms regulate intestinal-phase gallbladder physiology in humans.

The contribution of muscarinic receptor subtypes to biliary control mechanisms is unclear. We investigated stimulated gallbladder function and release of associated hormones during M1-receptor blockade. Following a double-blind, randomized, crossover protocol, healthy volunteers each received placebo and telenzepine, a selective M1-receptor antagonist, as 2-h background infusion. Gallbladder contraction (by ultrasonography), bilirubin output, and release of cholecystokinin (CCK) and pancreatic polypeptide (PP) were assessed during increasing doses of endogenous (intraduodenal nutrient) and exogenous (hormonal) stimulation. All parameters were stimulated in a dose-dependent manner on placebo days. Contractile and secretory responses to low-dose caerulein (CCK analogue) were inhibited by 60-80% under telezepine, whereas high-dose (supraphysiological) stimulation overrode this effect. Similar inhibition was achieved during nutrient stimulation. CCK plasma levels rose during endogenous and exogenous stimulation but were unaffected by M1 blockade, whereas stimulated PP release was completely inhibited (> 100% decrease), reflecting suppressed vagal tone. Selective M1-receptor blockade inhibits the physiological response of the gallbladder in humans; this effect cannot be attributed to suppressed CCK release. Our findings support the hypothesis that CCK acts at the gallbladder via cholinergic nerves under physiological conditions. Viewed with our previous observations, nonselective antagonism of biliary function by atropine is primarily mediated through M1 muscarinic pathways.

Adult↗
PubMed1995

The irritable bowel syndrome: long-term prognosis and the physician-patient interaction.

OBJECTIVE: To evaluate the long-term course and prognosis associated with the irritable bowel syndrome (IBS) and to determine the influence of an effective physician-patient relationship on subsequent health care use. DESIGN: Prospective review of medical records. SETTING: Tertiary referral center. PATIENTS: 112 consecutive Olmsted County, Minnesota, residents who were first diagnosed with IBS at the Mayo Clinic during the period 1961-1963. RESULTS: The median follow-up was 29 years (range, 1 to 32 years) and patients made a median of 2 return visits for IBS-related symptoms (range, 0 to 12 visits). In addition to abdominal pain, diarrhea (reported by 50% of patients) was the predominant bowel symptom at diagnosis. Organic gastrointestinal disease occurred in 10 patients a median of 15 years after diagnosis of IBS. Survival in patients with IBS did not differ from expected survival (27 deaths; median survival > 30 years after initial diagnosis). A positive physician-patient interaction, defined a priori using objective criteria in the written record, was associated with fewer return visits for IBS. Of the eight variables examined, notations in the medical record about psychosocial history, precipitating factors, and discussion of diagnosis and treatment with patients were associated with fewer return visits for IBS-related symptoms. CONCLUSIONS: When diagnosed according to current criteria, IBS is associated with a good prognosis and the diagnosis is unlikely to be changed to that of an organic disease during follow-up. A positive physician-patient interaction may be related to reduced use of ambulatory health services by patients with IBS.

Adult↗
PubMed1995

Interdigestive cycling in chronic pancreatitis: altered coordination among pancreatic secretion, motility, and hormones.

BACKGROUND & AIMS: Secretions from the exocrine and endocrine pancreas may modulate interdigestive motility. To test this hypothesis in humans, we investigated interdigestive cycling in patients with chronic pancreatitis (CP) as a model of impaired pancreatic function. METHODS: Antroduodenal motility, pancreatic enzyme output, and pancreatic polypeptide release were monitored for two consecutive interdigestive cycles in 13 controls and 9 patients with CP. RESULTS: Interdigestive enzyme output was severely impaired in patients with CP (> 80% decrease); however, secretory cycling was still evident in most patients. All parameters describing interdigestive motility were similar in controls and patients with CP (duration of the migrating motor complex [MMC] was 107 +/- 19 minutes in patients with CP vs. 114 +/- 15 minutes in controls). The time between cyclic peaks of enzyme secretion (76 +/- 4 minutes vs. 101 +/- 4 minutes in controls) and pancreatic polypeptide (63 +/- 4 minutes vs. 106 +/- 7 minutes in controls) was shortened in patients with CP, and peaks were no longer temporally related to the MMC. Only 56% of phase III activity fronts were associated with a concomitant secretory peak in patients with CP compared with 92% in healthy subjects. CONCLUSIONS: CP not only decreases pancreatic secretion but interrupts the coordination among interdigestive cyclic phenomena. Our findings in several animal and human models refute the concept that pancreatic mechanisms exert a major regulatory influence on interdigestive motor activity.

Adult↗
PubMed1994

Relationship between postprandial release of CCK and PP in health and in chronic pancreatitis.

The aim of this study was to investigate the relationship between postprandial release of cholecystokinin (CCK) and pancreatic polypeptide (PP) in healthy subjects and patients with chronic pancreatitis (CP). 14 patients with CP and 14 age-matched healthy subjects were studied. Diagnosis of CP was confirmed by standardized imaging modalities (ERCP and CT). Exocrine pancreatic function was assessed in all 28 subjects using the pancreolauryl serum test (PLT). An oral test meal was administered to stimulate endogenous hormone release. Plasma samples were taken before and at several time points after the test meal. CCK and PP plasma levels were measured by specific radioimmunoassays. Basal CCK and PP plasma levels were not different between patients with CP and controls, and were not correlated in either group. However, a direct linear correlation between integrated postprandial release of CCK and PP was found in healthy subjects (r = 0.74, P < 0.005). This postprandial coupling was not evident in patients with CP (r = 0.16; n.s.). Peak fluorescein serum concentration in patients with CP and steatorrhea (SCP) (n = 6) was < 2.5 micrograms/ml, and CCK and PP responses to the meal were significantly impaired (CCK response = 61 +/- 14 pmol/l/120 min in SCP vs. 110 +/- 14 in controls, P < 0.05; PP response = 3920 +/- 1773 pg/ml/120 min in SCP vs. 13418 +/- 3299 in controls, P < 0.05). In patients with mild/moderate exocrine insufficiency, CCK and PP responses varied greatly and were not different from controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Impaired interdigestive pancreatic polypeptide release. Early hormonal disorder in chronic pancreatitis?

The purpose of this study was to investigate interdigestive cycling and postprandial release of pancreatic polypeptide (PP) in relation to exocrine pancreatic function in chronic pancreatitis (CP). We investigated nine patients with mild-moderate CP (MCP), eight patients with severe CP and steathorrea (SCP), and 17 healthy subjects as controls. Interdigestive antroduodenal motility was monitored by means of manometry. Following two consecutive motility cycles, a standard test meal was administered. Plasma samples were drawn for PP determinations every 15 min throughout the entire study, which concluded 2 hr after ingestion of the meal. Mean interdigestive PP plasma concentrations during phase III motor activity were lower in MCP (146 +/- 46 pg/ml) than in controls (270 +/- 42 pg/ml) and lower still in SCP (55 +/- 8 pg/ml). Accordingly, the percent increase in PP concentrations during phase III over those in phase I was progressively decreased from controls (112%) to MCP (62%) to SCP (19%). Mean interdigestive PP concentrations were also lower during phase I and II in SCP than in controls or MCP. None of the postprandial parameters for PP release was affected in the early stage of disease, while mean, peak, and integrated postprandial values were significantly lower in SCP than in controls or MCP. Thus, we observed a progressive diminution of both interdigestive and postprandial PP release with increasing severity of disease. Interdigestive release parameters, in particular, were tightly correlated with exocrine function. CP appears to alter interdigestive PP release to a greater extent than postprandial PP release; this effect is already apparent in early stages of the disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Long-acting somatostatin analogue therapy and protein metabolism in patients with jejunostomies.

BACKGROUND/AIMS: Previous studies have shown that secretory losses in patients with end jejunostomy syndrome (EJS) on home parenteral nutrition (HPN) can be suppressed by the somatostatin analogue, octreotide, thus facilitating fluid balance. However, the hormone also has antianabolic actions that may interfere with the use of infused amino acids. METHODS: Amino acid metabolism, pancreatic enzyme synthesis and secretion, and mucosal protein turnover were measured by primed/continuous intravenous infusion of [1-14C] leucine tracer, duodenal aspiration, and endoscopic mucosal biopsy techniques during hormonal stimulation with pentagastrin and cholecystokinin 8. RESULTS: In comparison with normal healthy controls, baseline measurements of amino acid metabolism were normal in patients with EJS/HPN, but pancreatic enzyme synthesis and secretion were elevated. Octreotide therapy improved fluid balance but suppressed gut hormone (insulin, gastrin, glucagon, peptide YY) levels in blood and the uptake of amino acids into pancreatic enzyme and mucosal proteins, increasing oxidative losses. CONCLUSIONS: Octreotide improves fluid balance in patients who have undergone jejunostomy but reduces the use of amino acids for splanchnic protein synthesis. This may interfere with the physiological process of adaptation to intestinal resection.

Adult↗
PubMed1994

Is the plasma amino acid consumption test an accurate test of exocrine pancreatic insufficiency?

BACKGROUND/AIMS: The amino acid consumption test has been proposed as an accurate test of exocrine pancreatic function. The diagnostic accuracy of this test was determined by simultaneously measuring plasma amino acids and enzyme secretion during stimulation of the pancreas with cholecystokinin octapeptide (CCK-OP) in 60 consecutive patients suspected of having pancreatic insufficiency. METHODS: All patients underwent duodenal intubation and intravenous infusion of CCK-OP (40 ng.kg-1.h-1). Pancreatic enzyme (lipase and trypsin) outputs and plasma amino acids were measured for a period of 1 hour. Total and individual plasma amino acids were quantitated by ion-exchange chromatography. The severity of pancreatic insufficiency was graded on the basis of enzyme output during CCK-OP infusion. RESULTS: There was no relationship between pancreatic enzyme output and plasma concentrations of individual or total amino acids before or during CCK-OP stimulation. Using a total amino acid decrease of 12% as the cutoff, the amino acid consumption test was 91% sensitive, but very nonspecific (21% specificity) for detection of pancreatic insufficiency. CONCLUSIONS: The amino acid consumption test with CCK-OP stimulation does not discriminate between patients with normal and impaired exocrine pancreatic secretion.

Adult↗
PubMed1994

Role of the duodenum in postprandial release of pancreatic and gastrointestinal hormones.

In previous studies we found that duodenectomy abolished the interdigestive cycles of plasma motilin and pancreatic polypeptide (PP). In the current studies, we tested the hypothesis that an intact duodenopancreatic axis is necessary for normal postprandial release of pancreatic (PP, insulin) and gut peptides (gastric inhibitory peptide, GIP; cholecystokinin octapeptides, CCK-8; neurotensin; and gastrin). Consequently, we measured plasma concentration of pancreatic and gut hormones in normal and duodenectomized dogs after gavage feeding of a 250-ml liquid formula diet in conscious animals. After completing the experiments, pancreatic tissue concentrations of PP and insulin were measured. Removal of the duodenum was associated with decreases in postprandial plasma concentrations of PP (p < 0.05) and insulin (p < 0.05) and in pancreatic tissue concentrations of insulin (p = 0.01). Duodenectomy, however, did not alter postprandial plasma concentrations of GIP, CCK-8, neurotensin, or gastrin nor pancreatic tissue concentrations of PP. These effects of duodenectomy may be due to disruption of duodenopancreatic neural connections or loss of vagus sensitive (non-GIP) humoral factors. Decreased postprandial insulin concentrations may be due to lack of a neural or humoral insulinotropic factor arising from the duodenum.

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