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Biomedical subjects

T R Koch

Publications and source records attributed to T R Koch.

At least 55 records · Page 3Linked to original sources

Effects of substance P and vasoactive intestinal polypeptide on contractile activity and epithelial transport in the ferret jejunum.

Previous studies in the ferret demonstrated that vagal nerve stimulation induced an atropine-resistant water secretion. Substance P and vasoactive intestinal polypeptide are possible mediators of this secretory response. The objectives of this study were to investigate the in vivo effects of substance P and vasoactive intestinal polypeptide on the jejunal musculature and epithelium. Substance P caused an increase in jejunal motility, water secretion, and transmural potential difference. Cholinergic blockade did not affect the substance P-induced contractions, but did reduce the increase in transmural potential difference, suggesting an inhibition of water secretion. Vasoactive intestinal polypeptide abolished motor activity; however, it induced an increase in transmural potential difference that was atropine and tetrodotoxin resistant. By immunohistochemical methods, immunoreactive vasoactive intestinal polypeptide and immunoreactive substance P were localized to both nerve cell bodies and nerve fibers in the ferret intestine. Determination of intestinal concentrations of vasoactive intestinal polypeptide and substance P in the ferret showed concentrations of these two neuropeptides that were similar to those in human intestine and demonstrated much higher concentrations of these substances in the muscular layer than in the epithelial layer. Our data demonstrate that in the ferret substance P excites and vasoactive intestinal polypeptide inhibits jejunal motor activity. However, both peptides increase water secretion. Our results suggest that in response to vagal stimulation, neuronally released substance P or vasoactive intestinal polypeptide may participate in the atropine-resistant water secretion.

Action Potentials↗

Suitability of collection tubes with separator gels for therapeutic drug monitoring.

The purpose of this study was to determine the suitability of four collection tubes containing separation gels for collection of specimens for 15 therapeutic drugs. To blood tubes from drug-free volunteers, selected drugs were added and measured after centrifugation and storage for 6, 24, and 72 h in the collection tube. We found that the Becton Dickinson SST tube extracted phenytoin even with immediate separation of serum. For prolonged storage, the SST tube was unsuitable for quinidine (greater than 24 h) and lidocaine (greater than 6 h); the Monoject Corvac was unsuitable for lidocaine (any storage). Partially filled tubes caused additional errors. Completely filled Terumo Autosep and Monoject Corvac tubes are satisfactory for all drugs tested if serum is removed promptly.

Blood Specimen Collection↗

Accuracy and precision of methods for theophylline measurement in physicians' offices.

We tested the accuracy and precision of five theophylline methods intended for use in physicians' offices. The Syntex AccuLevel, Ames Seralyzer, and 3M Diagnostics TheoFAST methods were less reproducible (CVs 6.3% to 9.2%) than the Abbott Vision and Kodak DT-60 (CVs 2.2% to 3.3%). Caffeine interfered with the Vision, Seralyzer, and AccuLevel methods, and theobromine interfered with the Vision, Seralyzer, and TheoFAST methods. Only the DT-60 method was free from interference from any of the 24 compounds tested. Results by all methods correlated well with those by the HPLC comparison method (Clin Chem 1981;27:1931-3) and by the Abbott TDx method for assay of 100 serum (or, when appropriate, paired whole-blood) samples. The frequency of sample results differing from the comparison method by greater than 2.0 mg/L was as follows: TDx, 11%; Vision (serum), 12%; Vision (whole blood), 18%; DT-60, 14%; AccuLevel, 18%; Seralyzer, 25%; and TheoFAST, 31%. The Kodak DT-60 method was the most nearly accurate and precise among these physician's office methods. Some physician's office methods for theophylline analysis are not adequate to guide dosage adjustments.

Humans↗

Benzalkonium interference with test methods for potassium and sodium.

Six automated instruments that measure sodium and potassium were tested for interference from two compounds used in catheters. Tridodecylmethylammonium heparin did not interfere with any of the methods. However, benzalkonium heparin falsely increased sodium measurement with the Kodak Ektachem, and falsely increased potassium measurements with three instruments (Beckman Astra, Baxter Paramax, and the Instrumentation Laboratory Monarch) in which ion-selective electrodes measure potassium in diluted serum. Three instruments in which ion-selective electrodes measure serum directly--Du Pont Dimension, Abbott Spectrum, and Kodak Ektachem--experienced no interference with potassium measurements. Interference of benzalkonium with potassium measurements may result from its interaction with the electrode membranes, which is accentuated in diluted serum.

Benzalkonium Compounds↗

Physician visits in the United States for constipation: 1958 to 1986.

Since 1958, the National Disease and Therapeutic Index (NDTI) has provided annual statistics summarizing the frequency physicians throughout the United States are visited for different disease conditions. In our present study, these data were used to examine the epidemiology of constipation. Since NDTI statistics are available for a longer time period than other U.S. statistics, they might confirm or disprove the relevance of recent environmental changes on the occurrence of this disorder. The average number of physician visits for constipation in the United States was 2.5 million per year, corresponding to a prevalence of 1.2%. The largest number of these patients (31%) was seen by general and family practitioners, followed in declining order by internists (20%) and pediatricians (15%). Only 4% of all these patients was seen by gastroenterologists. Eight-five percent of these patients received a prescription for medication, with laxatives and cathartics being the most frequently prescribed drugs. Among physician visits for constipation, female prevalence was 1.6% compared with 0.8% for males (P less than 0.001). In both sexes, there was a significant age-related increase in the rate of physician visits, with the steepest rise from 1.3% to 4.1% occurring between the age groups 60-64 and over 65. From 1958 to 1986, the rate of all physician visits for constipation remained unchanged. However, during this time period, there was a twofold rise in physician visits for those patients ages 0-9 years, while a smooth decline occurred in all of the older age groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Constipation↗

Period and generation effects on mortality from idiopathic inflammatory bowel disease.

To test the hypothesis that environmental factors play a role in idiopathic inflammatory bowel disease (IBD), age, period, and generation (cohort) effects on IBD mortality in the United Kingdom and the United States were examined. The crude death rate of ulcerative colitis has declined since 1930. Plotted versus the year of birth, its age-specific death rates showed an initial rise in successive generations born between 1850 and 1900, followed by a fall in all later generations. The crude death rate of Crohn's disease increased from 1950 to 1974 and then declined. When the age-specific death rates for Crohn's disease and ulcerative colitis were superimposed, the mortality from Crohn's disease in each age group or sex began to decline at a different time, but always upon reaching the level of mortality from ulcerative colitis. It appears as if the gradual disappearance of an ulcerative colitis-associated factor in a birth-cohort fashion prevented a further rise in mortality from Crohn's disease after 1974.

Adolescent↗

Epidemiology of constipation in the United States.

In the present study, the epidemiology of constipation in the United States and an assessment of its impact on national health are presented. This analysis was based on four different surveys, i.e., the National Health Interview Survey, the National Hospital Discharge Survey, the National Ambulatory Medical Care Survey, and the Vital Statistics of the United States. These surveys have estimated that over 4 million people in the United States have frequent constipation, corresponding to a prevalence of about 2 percent. Constipation was the most common digestive complaint in the United States, outnumbering all other chronic digestive conditions. Cathartics and laxatives were prescribed to 2 to 3 million patients yearly by general and family practitioners or internists. In 92,000 annual hospitalizations, constipation was listed among the discharge diagnoses. About 900 persons die annually from diseases associated with or related to constipation. Constipation was three times more common in women than men. It showed a marked increase after the age of 65 years. It appeared to affect nonwhites 1.3 times more frequently than whites. In addition, constipation was more frequent in people living in the South than elsewhere in the United States, and in people from families with low income or brief education of the head of family than in people from families with high income or a high educational level of their family head. These data suggest that there are other factors involved in the cause of constipation in addition to dietary fiber content and psychogenic influences. The frequent occurrence of constipation and its impact on public health stress the need for further studies devoted to the epidemiology and basic pathophysiology of this condition.

Age Factors↗

Clinical epidemiology of chronic constipation.

Using health statistics from the United States and England and Wales, we review the epidemiology of constipation and possible etiologies of this disorder as suggested by its epidemiologic distribution. The analysis revealed that constipation is one of the most common chronic digestive disorders in the United States, affecting one of every 50 people. The occurrence of constipation increased with advancing age, showing an exponential increase in prevalence after the age of 65. The age distribution of constipation was similar in both sexes, but overall constipation was three times more common in women than in men. Constipation more frequently affected nonwhites than whites, and people from families with low income or less formal education. The characteristic epidemiologic pattern of constipation suggests the influence of environmental factors. Insufficient dietary fiber is widely believed to be a major cause of constipation, yet it is difficult to devise a mechanism by which dietary fiber alone could produce the marked differences observed between gender, race, and socioeconomic status. Recent evidence suggests that disruption of neural regulation of colonic motility plays an important role in the development of chronic constipation. This loss of neural regulation may result from mechanical damage to the pelvic nerves due to childbirth or pelvic surgery, exposure to environmental toxins (e.g., organochlorine insecticides or heavy metals), or possibly exposure to an infectious agent. Other environmental factors that may play a role in the pathogenesis of chronic constipation have not yet been elucidated. Consequently, studies examining the epidemiology of chronic constipation are important for providing insight into potential environmental risk factors relevant to the etiology of this disorder.

Age Factors↗

Decreased colonic peptide histidine-methionine in idiopathic inflammatory bowel diseases.

The sequence for peptide histidine-methionine is present within the same preprohormone as vasoactive intestinal polypeptide. Since our previous study using radioimmunoassay had demonstrated significantly decreased colonic concentrations of vasoactive intestinal polypeptide in ulcerative colitis and Crohn's colitis compared to normal colon, we determined the distribution and quantitation of peptide histidine-methionine. Fresh surgical specimens were dissected into mucosal-submucosal and muscularis externa layers prior to acid extraction and specific radioimmunoassay. One immunoreactive species that appeared to coelute with peptide histidine-methionine was separated by reverse-phase high-performance liquid chromatography. Mucosal-submucosal concentrations of peptide histidine-methionine were significantly decreased in ulcerative colitis and Crohn's colitis, compared to those in normal colon. In normal ileum and colon, linear correlation analysis showed no relationship between patient age and tissue concentrations of peptide histidine-methionine. However, a parallel decrease in molar concentrations of peptide histidine-methionine and vasoactive intestinal polypeptide in ulcerative colitis and Crohn's colitis was demonstrated by linear correlation analysis. These results are consistent with the hypothesis that peptide histidine-methionine and vasoactive intestinal polypeptide are colocalized within the same neural structures that have been altered in the idiopathic inflammatory bowel diseases.

Adolescent↗

Peptide YY concentrations in normal ileum and colon and in idiopathic inflammatory bowel disease.

Concentrations of the candidate endocrine and paracrine peptide, peptide YY, were measured by specific radioimmunoassay in tissue extracts prepared from normal ileum, normal colon, Crohn's disease, and ulcerative colitis. In both the ascending and descending colon, there were significantly decreased mean concentrations of peptide YY in Crohn's colitis and ulcerative colitis, compared to mean concentrations in normal colon. There was no age-related decrease of concentrations of peptide YY in normal colon. The decrease in concentrations of peptide YY in colon obtained from patients with inflammatory bowel disease did not appear related either to the duration of the clinical symptoms of the disease or to the severity of colonic inflammation. Further studies of the physiological function of peptide YY in man are needed to determine whether these findings might be useful in understanding a component of the pathophysiology of idiopathic inflammatory bowel disease.

Adolescent↗

Somatostatin in the idiopathic inflammatory bowel diseases.

To study the effect of mucosal inflammation on tissue concentrations of somatostatin, the distribution and concentration of somatostatin in specimens of normal and abnormal (ulcerative colitis and Crohn's disease) ileum and colon were determined by a specific radioimmunoassay. Each tissue specimen obtained at surgery was separated by microdissection into the mucosa-submucosa and the muscularis externa. Immunoreactive somatostatin was acid-extracted from each layer before measurement. Gel chromatography was used to characterize immunoreactive somatostatin measured by radioimmunoassay; somatostatin-28 was the major immunoreactive species measured in human intestine. In normal colon, concentrations of somatostatin were not related to patient age. Concentrations of immunoreactive somatostatin in the mucosa-submucosa of the descending colon were significantly decreased in ulcerative colitis and in Crohn's colitis, compared with normal colon. There was no apparent relationship between concentrations of somatostatin and the duration of inflammatory bowel disease. However, somatostatin concentrations appeared to be lower in patients with severe colitis than in patients with minimal colitis. The decrease in mucosal-submucosal concentrations of somatostatin is in agreement with previous morphologic studies, which have suggested diminished populations of endocrine cells in ulcerative colitis. The possible role of somatostatin in the colon suggests that further studies of the alteration of this gut peptide may be useful in understanding a component of the pathophysiology of idiopathic inflammatory bowel disease.

Chromatography, Gel↗

Spontaneous contractions and some electrophysiologic properties of circular muscle from normal sigmoid colon and ulcerative colitis.

Spontaneous contractions, inhibitory responses produced by electrical field stimulation, and some electrophysiologic properties of circular smooth muscle from normal sigmoid colon and from sigmoid colon of ulcerative colitis patients were compared in vitro using simultaneous recordings of mechanical and intracellular electrical activity. In normal colonic circular muscle obtained from 21 patients, the frequency of spontaneous summation contractions ranged from 3 to 7 per 4 min, whereas in circular muscle from 13 patients with ulcerative colitis, the frequency of these contractions ranged from 1 to 9 per 4 min. Nonadrenergic, noncholinergic relaxation produced by electrical field stimulation was recorded in the majority of circular smooth muscle strips from both normal colon and colon from patients with ulcerative colitis. There were no significant differences in mean resting membrane potential, mean slow-wave frequency, mean maximum slow-wave amplitude, or inhibitory-junction potential amplitudes recorded using circular smooth muscle from both normal colon and colon from patients with ulcerative colitis. There appeared to be a weak association in patients with ulcerative colitis between increasing duration of symptoms and decreasing frequency of spontaneous summation contractions, but there were no associations between the frequency of these contractions and the severity of colonic inflammation, patient age, or the frequency of stools. The mechanism accounting for a wider range in the frequency of summation contractions recorded from colonic circular smooth muscle in ulcerative colitis remains to be determined.

Adult↗

Idiopathic chronic constipation is associated with decreased colonic vasoactive intestinal peptide.

To investigate the reported association between idiopathic chronic constipation and morphologic abnormalities of enteric nerves, we measured the concentrations of six neuropeptides, vasoactive intestinal peptide, peptide histidine-methionine, substance P, methionine5-enkephalin, neuropeptide Y, and the bombesinlike intestinal peptides, in descending colon from 4 patients with idiopathic chronic constipation. Decreased concentrations of vasoactive intestinal peptide (707 +/- 112 ng/g wet tissue) and peptide histidine-methionine (543 +/- 58 ng/g) were found in the muscularis externa obtained from constipated patients compared with normal concentrations (40 patients) of vasoactive intestinal peptide (1199 +/- 47 ng/g) and peptide histidine-methionine (815 +/- 45 ng/g). Vasoactive intestinal peptide was identified by immunocytochemistry in nerve fibers within the circular smooth muscle layer of descending colon obtained from 6 control patients, but not in nerve fibers within the circular smooth muscle of descending colon obtained from 3 patients with idiopathic chronic constipation. By contrast, the distribution of immunoreactive met5-enkephalin was similar in normal descending colon and in descending colon obtained from patients with idiopathic chronic constipation. Decreased colonic concentrations of vasoactive intestinal peptide (a candidate nonadrenergic, noncholinergic inhibitory neurotransmitter) may be associated with diminution of inhibitory innervation of colonic circular smooth muscle in some patients with idiopathic chronic constipation.

Adult↗

Distribution, quantitation, and origin of immunoreactive neuropeptide Y in the human gastrointestinal tract.

A radioimmunoassay for measurement of immunoreactive neuropeptide Y has been developed using antiserum from a rabbit (221) immunized with porcine neuropeptide Y. Antibody 221 has been characterized for both sensitivity and specificity. To determine the distribution of neuropeptide Y in the human gastrointestinal tract, fresh tissue specimens were separated by microdissection into the muscularis externa and the mucosa-submucosa. To examine the origin of neuropeptide Y in human colon, specimens of aganglionic and ganglionic colon were obtained from patients with Hirschsprung's disease. Immunoreactive neuropeptide Y in human gut was present in highest concentrations in the muscularis externa of the stomach and in lowest concentrations in the muscularis externa of the ileum and descending colon. Neuropeptide Y in the stomach was present in higher concentrations in the muscularis externa than in the mucosa-submucosa, but in the descending colon there were lower concentrations of neuropeptide Y in the muscularis externa than in the mucosa-submucosa. In Hirschsprung's disease, concentrations of neuropeptide Y were increased in aganglionic colon in both the muscularis externa and the mucosa-submucosa, compared to corresponding layers from proximal ganglionic colon. Extracts of the gastric muscularis externa and the colonic mucosa-submucosa were separated by C18 reverse-phase high-performance liquid chromatography. One major immunoreactive species was identified by radioimmunoassay which eluted in a position similar to synthetic human neuropeptide Y. These results demonstrated both regional and layer differences in concentrations of neuropeptide Y in human gut. Increased concentrations of neuropeptide Y in aganglionic colon from Hirschsprung's disease most likely result from enlargement of neuropeptide Y-containing extrinsic nerve fibers in both the mucosa-submucosa and the muscularis externa.

Animals↗

Inaccuracies in digoxin measurement.

Six commercial digoxin immunoassay kits were evaluated for their accuracy of calibration and their extent of interference by digoxin-like immunoreactive substance (DLIS). Calibration accuracy was investigated with digoxin reference standards in pooled human serum. The Abbott and Becton Dickinson kits underestimate while the other kits overestimate digoxin concentration. The magnitude of this bias generally increases with increasing concentration of digoxin. Sera from digoxin-free patient populations with potential DLIS interference--pregnant women, newborns, hypertensives, and uremics--were analyzed with each kit. Healthy subjects not on digoxin therapy served as controls. Groups with DLIS interference, as exemplified by a significant difference of p less than 0.05 from controls, are: Abbott--newborns and pregnant women; Becton Dickinson--newborns and pregnant women; Dade--no difference; Dupont--newborns, uremics, pregnant women, and hypertensives; Kallestad--newborns; and Syva--newborns. The limitations of each individual digoxin method should be realized for DLIS interference and bias, and patient results from that method should be interpreted accordingly.

Adult↗

Identification and distribution of immunoreactive peptide YY in the human, canine, and murine gastrointestinal tracts: species-related antibody recognition differences.

A radioimmunoassay using two antisera (antibody 80 and antibody 213) from rabbits immunized with porcine peptide YY has been characterized for both sensitivity and specificity. To determine the distribution of peptide YY in the gut, fresh tissue specimens from the human and canine gut were separated into mucosal-submucosal and muscularis externa layers by microdissection. These tissues and transmural specimens from murine gut were acid-extracted and neutralized, followed by radioimmunoassay using each antiserum. Immunoreactive peptide YY in canine and murine gut was present in similar concentration and distribution using each antiserum, with highest concentrations in the mucosal-submucosal layer of the descending colon. Using antibody 213, immunoreactive peptide YY throughout the human gut was measured only at the lower detection limit of the radioimmunoassay. By contrast, using antibody 80, peptide YY in human gut was present in a distribution similar to canine and murine gut. Using antibody 80, one major immunoreactive species was identified with C18 reverse-phase high-performance liquid chromatography in extracts of human, canine, and murine colon. These results suggest species-related antibody recognition differences. The similar concentrations of peptide YY in canine and murine gut determined with the two antisera are consistent with the hypothesis that the amino acid sequences of canine and murine peptide YY are similar to porcine peptide YY. Using antibody 213, the low concentrations of immunoreactive peptide YY found in human gut are consistent with the hypothesis that human and porcine peptide YY have different amino acid sequences. Antisera prepared by immunization with porcine PYY must therefore be carefully characterized prior to studies using human sera or human tissue extracts.

Animals↗

Distribution and quantitation of gut neuropeptides in normal intestine and inflammatory bowel diseases.

To study hyperplasia of peptidergic nerves purported to be diagnostic of Crohn's disease, we determined the distribution and concentrations of gut neuropeptides in specimens of normal intestine, ulcerative colitis, and Crohn's disease. Tissue specimens obtained at surgery were dissected into the mucosal-submucosal and muscularis externa layers, and immunoreactive gut neuropeptides were acid-extracted for measurement by radioimmunoassay. The immunoreactive species were characterized by column chromatography. Mucosal-submucosal layer concentrations of vasoactive intestinal peptide were significantly decreased in Crohn's colitis and ulcerative colitis, while mucosal-submucosal layer concentrations of substance P were significantly increased in left-sided ulcerative colitis. Muscularis externa layer concentrations of vasoactive intestinal peptide and met5-enkephalin were decreased in left-sided Crohn's colitis. These neuropeptide concentration abnormalities did not clearly differentiate between Crohn's colitis and ulcerative colitis, and no increase in concentration of a neuropeptide diagnostic of Crohn's disease was identified.

Adult↗