Search PubMed⌕ Search

Biomedical subjects

D K Nelson

Publications and source records attributed to D K Nelson.

At least 37 records · Page 2Linked to original sources
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.

Animals↗
PubMed1994

Postprandial release of cholecystokinin and pancreatic polypeptide in health and in gallstone disease: relationships with gallbladder contraction.

OBJECTIVES: The present study investigated endogenous postprandial release of cholecystokinin (CCK) and pancreatic polypeptide (PP) in relation to gallbladder dynamics in healthy subjects and patients with gallstones. METHODS: Gallbladder volume (by ultrasonography) and plasma concentrations of CCK and PP (by radioimmunoassay) were evaluated in 18 patients with gallstones and 14 healthy controls before and after administration of a semi-liquid test meal (250 ml, 1450 kJ). Gallbladder contractility was previously assessed on a separate day by intravenous infusion of ceruletide (2.5 ng/kg/min). RESULTS: Basal gallbladder volume was not different in patients (32 +/- 5.9 cm3) and controls (26 +/- 2.7 cm3). Postprandial gallbladder contractility was impaired in gallstone patients, who showed a reduced integrated response (-3718 +/- 349 vs. -5251 +/- 376 cm3/2 h, p < 0.01) and a delayed time to maximal gallbladder contraction (67 +/- 7.4 min vs. 37 +/- 2.4 min, p < 0.002). Maximal gallbladder contraction after ceruletide infusion was also reduced (44.1 +/- 5.0% vs. 72.5 +/- 3.2%, p < 0.001), but not delayed (15.8 +/- 2.4 vs. 15.7 +/- 1.4 min) in gallstone patients. Basal CCK and PP plasma levels were similar in both groups. Postprandial CCK release was impaired in gallstone patients, predominantly due to a decreased response over the first 30 min (3.8 +/- 1.8 vs. 20.0 +/- 4.9 pmol/L/30 min, p < 0.005). Postprandial PP release was not different between groups. A direct linear correlation between postprandial release of CCK and PP was found in healthy controls but not in patients with gallstones. Postprandial gallbladder volume at any moment was inversely correlated with CCK plasma levels in healthy subjects, but not in gallstone patients. No correlation between postprandial PP response and gallbladder dynamics was observed. CONCLUSIONS: Based on a multivariate logistic approach, a reduced and delayed postprandial gallbladder contractility and an impaired CCK release in the early postprandial phase are significantly associated with gallstone disease. Our data provide further evidence for the predominant role of endogenous postprandial CCK release in gallbladder contraction. A role for PP in modulating postprandial gallbladder dynamics is not supported.

Cholecystokinin↗
PubMed1993

Enteroendocrine peptides in a canine model of orthotopic jejunoileal autotransplantation.

The enteroendocrine cells of the small bowel provide a rich source of regulatory peptides involved in the modulation of gastrointestinal function. Recent work from our laboratory showed that in situ neural isolation (autotransplantation) of the jejunoileum produced marked changes in tissue expression of several neuropeptides. In the present study, we examined the influence of extrinsic innervation on the tissue expression of endocrine peptides localized to various regions of the gastrointestinal tract. Concentrations of immunoreactive gastric inhibitory polypeptide (GIP), neurotensin (NT) and peptide tyrosine tyrosine (PYY) in fasting plasma and regional tissue biopsies were determined before and at varying time points (2, 6, 12 weeks) after a model of canine orthotopic jejunoileal autotransplantation. GIP was not altered in plasma or tissue at any time point. Plasma concentrations of NT and PYY increased after autotransplantation. Following a decrease in tissue concentrations two weeks after autotransplantation, NT increased progressively from 2 to 6 to 12 weeks, reaching a maximal increase of 895% over baseline in proximal ileum. Tissue concentrations of PYY followed much the same pattern as NT, but these trends never achieved statistical significance. Chromatographic characterization of tissue biopsy extracts revealed molecular heterogeneity of NT-like immunoreactivity, while GIP and PYY immunoreactivity coeluted as single species with authentic standards. Taken together with our earlier observations, it appears that disruption of extrinsic and intrinsic neural continuity to the jejunoileum (autotransplantation) does not affect gut endocrine peptides such as GIP and PYY to the same extent as enteric neuropeptides. NT has been localized to neural as well as endocrine cells and is involved in the temporal adaptive response to autotransplantation.

Animals↗
PubMed1993

A fast protein liquid chromatography (FPLC) method for study of thyrotropin-releasing hormone (TRH) and its metabolite histidyl-proline diketopiperazine (CHP) in human blood: degradation in liver and pancreatic diseases.

We have developed a convenient method combining fast protein liquid chromatography (FPLC) with sensitive radioimmunoassay (RIA) for thyrotropin-releasing hormone (TRH) to separate and identify TRH and its metabolite histidyl-proline diketopiperazine (CHP) and applied this to study inactivation of TRH by blood extracts from patients with liver cirrhosis (LC) and acute edematous pancreatitis (AP). Blood samples spiked with TRH and CHP were extracted by cold methanol and injected on a reverse-phase FPLC column. A linear gradient was applied for separation. Subsequent analyses of fractions by RIA for TRH revealed that only fractions 9-10 contained TRH. Separation by retention time (9.9 +/- 0.8 min for TRH, 10.5 +/- 0.6 min for CHP, mean +/- SEM) was highly reproducible. For degradation studies, pooled sera from patients with LC and AP were incubated with TRH and CHP for 60 min. Inactivation of TRH was less rapid in the presence of blood extract from LC patients than that from normal subjects or AP patients. CHP was more stable than TRH. These data suggest that activity of TRH-degrading enzymes is reduced in liver disease, whereas it does not appear to be altered in AP. Degradation of CHP does not closely reflect metabolic processing of its major precursor. This rapid and sensitive method may be applicable for further investigations on the metabolism of TRH in organic fluids.

Acute Disease↗
PubMed1993

Evaluation of thyrotropin secretion before and after TRH by third generation chemiluminescent assay. Assessment of subclinical hyperthyroidism.

The recent introduction of third generation assays for TSH has led to a considerable improvement of assay sensitivity. To assess the clinical significance of subnormal basal TSH (b-TSH) values (< 0.2 microU/ml), we investigated b-TSH and TRH-stimulated TSH (r-TSH) by means of a new, highly sensitive immunochemiluminometric assay in 105 euthyroid subjects, 45 patients with overt hyperthyroidism and 18 patients suspected of having subclinical hyperthyroidism. A weak, albeit statistically significant, correlation (r = 0.48) was found between b-TSH and r-TSH and also between b-TSH and delta-TSH (r = 0.31) in euthyroid subjects. Consideration of b-TSH alone correctly identified 90 % of euthyroid subjects in this group; 10 of 105 apparently euthyroid subjects presented delta-TSH suggesting subclinical hyperthyroidism. While b-TSH was detectable (> 0.04 microU/ml) in 8 of 45 (18%) of hyperthyroid patients, all (100%) were abnormal in both b-TSH and r-TSH. 14 of 18 (78%) of patients with subclinical hyperthyroidism exhibited a blunted TSH response to stimulation (delta-TSH < 2 microU/ml). These results suggest that although the new generation of TSH assays can be a valuable addition to the diagnostic arsenal of thyroid function tests, certain limitations must still be accepted. Specifically, b-TSH in the "grey zone" (0.1-0.2 microU/ml) appears to be a less than reliable predictor of thyroid function.

Adult↗
PubMed1993

Exocrine pancreatic secretion in man following one week of M1-muscarinic receptor blockade.

A double-blind, randomized, placebo-controlled crossover study was performed to assess the influence of one week of selective M1-muscarinic receptor blockade on pancreatic exocrine secretion in man. Ten healthy subjects received telenzepine (3 mg p.o.) and placebo each for 8 days, with a 6-day drug-free washout interval between treatment sequences. On Day 8 of each sequence, pancreatic secretion was stimulated for 2 h by infusion of submaximal secretin (0.2 U.kg/h) followed by maximal stimulation with secretin (1.0 U.kg/h) and ceruletide (120 ng.kg/h). Telenzepine had no significant effect on secretory parameters during submaximal stimulation with secretin. During maximal stimulation, total protein, secretory volume, and output of amylase, trypsin and bicarbonate were unexpectedly increased by telenzepine. These findings might be partially explained by removal of the inhibitory influence of pancreatic polypeptide, which was depressed by telenzepine. Acute studies have shown that M1-receptor antagonists inhibit exocrine secretion. Our results suggest that adaptation of physiological mechanisms governing the exocrine pancreas may occur after one week of receptor blockade by a therapeutic dosage of telenzepine, to the extent that M1-blockade no longer inhibits secretion.

Adult↗