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Biomedical subjects

J E Kellow

Publications and source records attributed to J E Kellow.

At least 55 records · Page 3Linked to original sources

Prolonged ambulant recordings of small bowel motility demonstrate abnormalities in the irritable bowel syndrome.

Continuous 72-h recordings of duodenojejunal contractile activity were obtained from 20 freely ambulant subjects; pressure was detected by two strain-gauge sensors incorporated in a transnasal catheter attached to an encoder and a miniature tape recorder. The subjects were 12 patients with irritable bowel syndrome, 6 of whom were constipation predominant and 6 of whom were diarrhea predominant, and 8 healthy controls. The procedure was well tolerated by all subjects and did not interfere with sleep or normal activity. In all subjects, the diurnal migrating motor complex cycle was characterized by a brief phase 1 and a prolonged phase 2; this was reversed during sleep when phase 2 was virtually absent. All subjects showed a circadian variation in migrating motor complex propagation velocity, and there was no difference in the patterns of motor activity during sleep between any of the groups. During the day, the duration of postprandial motor activity was shorter in irritable bowel syndrome patients than in controls, and diurnal migrating motor complex intervals were shorter in diarrhea-predominant than in constipation-predominant irritable bowel syndrome. In 11 of 12 inflammatory bowel syndrome patients, episodes of clustered contractions recurring at 0.9-min intervals were noted; these episodes had a mean duration of 46 min and were often associated with transient abdominal pain and discomfort. In both groups of irritable bowel syndrome patients, defecation was significantly (p less than 0.01) prolonged with a greater number of voluntary abdominal contractions (p less than 0.01) than in controls. Prolonged ambulant monitoring of proximal bowel motor activity in subjects who are free to move, eat, and sleep as they choose has, for the first time, clearly defined the striking difference in motility between the sleeping and waking state and shown that abnormalities associated with irritable bowel syndrome are confined to the latter.

Adult↗

The use of intraluminal strain gauges for recording ambulant small bowel motility.

Perfused-tube manometry has hitherto been the standard technique for recording intraluminal intestinal pressure in humans, but it is unsuitable for ambulant use. The aim of our study was to evaluate the ability of resistive strain gauge transducers attached to a fine catheter to detect pressure change. Simultaneous strain gauge and perfused-tube manometry was performed on six fasting subjects; in four, strain gauge activation was continuous and in two, the transducers were activated in a pulsed mode with data encoded as a pulse train with an approximate frequency of 20 Hz. Eight thousand eight hundred eighty-eight pressure waves were recorded by strain gauge, of which 96% were detected by perfused-tube manometry. There was good agreement in both phases II and III of the migrating motor complex. The amplitude of pressure waves recorded by strain gauge was slightly but significantly greater. A proportion (14-17%) of pressure waves recorded by strain gauge were bifid; this was not seen with the perfused tube. These differences are best explained by the greater sensitivity and more rapid rise time of the strain gauges. There was no loss of fidelity in the pulse-interval recording mode. A seventh subject underwent a continuous 72-h recording with the strain gauge catheter attached to a battery-operated encoder and magnetic tape cassette recorder and was freely ambulant during this period. The procedure was well tolerated and motility patterns could be clearly identified. We conclude that intraluminal strain gauge catheters are suitable for prolonged use in ambulant subjects and produce data that are closely comparable to the data acquired from perfused-tube manometry under laboratory conditions.

Adult↗

Non Campylobacter pylori spiral organisms in the gastric antrum.

Colonisation of the human gastric antrum with non Campylobacter pylori spiral organisms is described. A moderately severe histological gastritis was present despite the fact that these organisms, in contrast to C. pylori, were not closely associated with the epithelial cell surface. Although in vitro culture of the organisms was unsuccessful, in vivo culture was achieved in the mouse stomach. Further study of these spiral organisms should provide important clues to the role of bacteria in upper gastrointestinal disease.

Adult↗

Dysmotility of the small intestine in irritable bowel syndrome.

Though the pathophysiology of the irritable bowel syndrome (IBS) is commonly attributed to dysfunction of the large intestine, evidence exists to incriminate the small bowel. In order to further explore the role of the small bowel in IBS several stimuli were applied, in an attempt to unmask the dysmotility of the jejunum and ileum. These included infusions of cholecystokinin-octapeptide (CCK-OP), a high fat meal, neostigmine and balloon distension of the ileum. Three groups (n = 8) each of age and sex matched healthy volunteers were studied; patients with IBS complained of predominant constipation (n = 8) or diarrhoea (n = 8). Patients with IBS responded excessively to stimulation by CCK-OP, fatty meal, and ileal distension. In general patients with diarrhoea were more sensitive to stimuli than those with constipation. The ileum responded more to stimulation than the jejunum. As in the large bowel, stimuli appear to unmask intestinal dysmotility in patients with IBS. Motor abnormalities were often accompanied by abdominal symptoms, raising the possibility that dysfunction of the small bowel contributes to the symptoms of IBS.

Adult↗

Altered small bowel motility in irritable bowel syndrome is correlated with symptoms.

The pathogenesis of irritable bowel syndrome (IBS) has been related more to dysmotility of the colon than to abnormalities of the small intestine. To look for small bowel abnormalities, we recorded ultraluminal pressures in 16 patients with IBS. All patients complained of abdominal pain, and diarrhea (n = 8) or constipation (n = 8) were also prominent symptoms. Comparable studies were performed on 16 age-matched controls. The observations include diurnal and nocturnal fasting recordings and the response to a fatty meal. Periodicities of the interdigestive migrating myoelectric complexes were shorter in IBS (p less than 0.05); this was due to much shorter diurnal cycles in patients with diarrhea (77 +/- 10 min) than those with constipation (118 +/- 15 min) or controls (113 +/- 10 min, both p less than 0.05). All groups exhibited circadian changes, with nocturnal cycles being more frequent. Two specific patterns of small bowel motor activity were more common in IBS--ileal propulsive waves and clusters of jejunal pressure activity (both p less than 0.05 compared to controls). Moreover, cramping abdominal pain was usually noted in IBS when ileal motility was propulsive; jejunal bursts were also sometimes associated with abdominal symptoms. We conclude that motility of the small intestine is modified in some patients with IBS and that certain motor patterns are related to their symptoms.

Abdomen↗

Modulation of human upper gastrointestinal motility by rectal distension.

The effects of rectal distension on upper gastrointestinal motility were investigated in six healthy subjects. On a control day, gastric and duodenal motor activity was recorded for nine hours of fasting and for four hours after a meal, duodeno-caecal transit being assessed in both interdigestive and digestive states. Motor activity and transit were also measured on a test day during which the rectum was distended for one hour during fasting and for one hour postprandially. Control and test days were randomised. During fasting, rectal distension increased the incidence of migrating motor complexes (0.8 +/- 0.3 v 0.5 +/- 0.2 h; p less than 0.01) and reduced the duodenal phase 2 motility index to 66 +/- 45% of that observed on the control day (p less than 0.01). Further, duodeno-caecal transit time was increased by rectal distension (99 +/- 30 v 71 +/- 35 min; p less than 0.05). Postprandially, the period of rectal distension was marked by a reduction in the duodenal motility index to 24 +/- 13% of that observed during the comparable period on the control day (p less than 0.001) and a concomitant increase in duodeno-caecal transit time (113 +/- 22 v 80 +/- 17 min; p less than 0.01). We conclude that upper gastrointestinal motor activity, the effector of luminal transit, may be profoundly influenced by stimulation of distal afferents.

Action Potentials↗

Gastro-oesophageal reflux and the migrating motor complex.

Distal oesophageal pH and gastroduodenal motor activity were recorded simultaneously throughout nocturnal (23 30-08 30 h) and diurnal (08 30-17 30 h) periods of fasting in seven healthy subjects. At night, episodes of gastro-oesophageal reflux (GOR) accounted for 1.2 +/- 0.7% of recording time. Periods of gastric motor activity, representing the gastric component of the migrating motor complex (MMC), recurred every 78 +/- 31 min during the night and were interspersed with periods of gastric motor quiescence. Nocturnal episodes of GOR during periods of gastric motor activity were of longer duration (p less than 0.001) and more frequent (p less than 0.005) than during periods of gastric motor quiescence. At night, periodic gastric motor activity was thus correlated (p less than 0.001) with an increase in the duration and number of GOR episodes and associated with a 100-fold increase in oesophageal acid exposure. During the day, the gastric component of the MMC, recurring every 131 +/- 64 min, was correlated (p less than 0.02) with an increase in the duration and number of GOR episodes, and a three fold increase in oesophageal acid exposure. Further, 89% of nocturnal, and 83% of diurnal gastric MMCs were temporally associated with episodes of GOR. We conclude that fasting episodes of GOR occur coincidentally with the gastric component of the MMC.

Adult↗

Sensitivities of human jejunum, ileum, proximal colon, and gallbladder to cholecystokinin octapeptide.

We compared in humans simultaneous motor responses of the jejunum, ileum, proximal colon, and gallbladder (GB) to intravenous cholecystokinin octapeptide (CCK-OP). To gauge the physiological relevance of the doses of CCK-OP, intestinal motility and GB contraction were also quantified after a fatty meal. Eight healthy volunteers participated in both experiments. Six graded, 30-min intravenous infusions had a mean range of 2.2 to 73.2 pmol X kg-1 X h-1 of CCK-OP; these spanned from subphysiological (negligible contraction of GB) to pharmacological (producing intestinal symptoms and a 70-99% contraction of GB) levels. CCK-OP inhibited interdigestive cycles of motility, though in some persons fasting patterns persisted with doses of CCK-OP, which produced up to 50% reduction in GB volume. Motility indices of the ileum and proximal colon responded to CCK-OP by decreasing initially but then increasing with larger doses; motility of the jejunum increased gradually at all doses. Judged by the gallbladder's response to food (reduction in volume down from 74 to 29% of original volume), the physiological range of infused CCK-OP was approximately 5-16 pmol X kg-1 X h-1. Within this range of doses of CCK-OP, motility of the jejunum increased, whereas motility of the proximal colon was reduced. These data are consistent with CCK being a "physiological" mediator of intestinal motility in humans; responses of the intestine to the peptide appear to vary regionally.

Adult↗

Altered sensitivity of the gallbladder to cholecystokinin octapeptide in irritable bowel syndrome.

We compared responses of the gallbladder to graded intravenous infusions of cholecystokinin octapeptide (CCK-OP) in normal controls (n = 8) and patients with irritable bowel syndrome (IBS) with predominant constipation (n = 8) or diarrhea (n = 8). The doses of CCK-OP ranged from subphysiological (negligible contraction of the gallbladder) to supraphysiological (90% contraction of gallbladder and abdominal side effects) amounts. All gallbladders contracted progressively in response to CCK-OP, and a Weibull model (power exponential function) described precisely the gallbladder's response to CCK-OP. Patients with IBS responded differently from normal patients; those with constipation contracted their gallbladders more and those with diarrhea contracted less in response to the peptide. Gallbladders were also stimulated with a high-fat, liquid meal; all patients' gallbladders contracted, but clear differences between groups could not be demonstrated postprandially. The results suggest that the smooth muscle of the gallbladder in IBS has an abnormal sensitivity to CCK-OP, and the results support the concept that IBS can be a generalized abnormality of the smooth muscle of the digestive tract.

Adult↗

Human interdigestive motility: variations in patterns from esophagus to colon.

In most fasting mammals, motility of the foregut and small intestine undergoes regular cycles of activity. Much of the expanding knowledge of this phenomenon comes from species other than humans; however, disorders of these patterns are proposed as being clinically important. We report studies in 16 healthy humans in whom motility was recorded from intraluminal pressure sensors, both when fasting and after a meal, for prolonged periods. The recording system spanned the area from stomach to proximal colon in all subjects and included the lower esophagus in 11 of the 16 studied. Half the interdigestive cycles involved the esophagus, approximately one-third began in the gastroduodenal region, and the remainder commenced more distally. Fewer than half the migrating motor complexes were recognizable beyond the midpoint of the small bowel, and less than 10% reached the distal ileum. The migrating motor complex was more prominent at night; and its progression through the jejunum was then slower. Small meals (345-395 kcal) interrupted fasting patterns for 90-240 min, but the amount of fat did not influence the duration of these disruptions. Motility varied widely between and within individuals, and differences between normal patterns in the jejunum and ileum were particularly striking. Thus, levels of recordings must be defined accurately if putative abnormalities, of possible clinical significance, are to be interpreted correctly. Relating local motor patterns to the maximal rate of rhythmic contractions, which reflects the frequency of slow waves and is a guide to the level of the small bowel, may be helpful in this regard.

Adult↗

Sulfapyridine appearance in plasma after salicylazosulfapyridine. Another simple measure of intestinal transit.

The appearance of sulfapyridine in plasma after oral administration of salicylazosulfapyridine (SASP) was evaluated as a method for defining arrival time in the cecum, an index of small bowel transit. After direct instillation of SASP and lactulose into the cecum, the appearances of their metabolites (sulfapyridine in plasma and hydrogen in breath) were rapid (1-10 min) and simultaneous. When a mixture of SASP and lactulose was taken by mouth, times of the respective "signals" varied among individuals from 40 to 180 min (n = 8) but were correlated within individuals. Salicylazosulfapyridine transit times from duodenum to cecum were also very similar to simultaneous measurements of transit by scintigraphic monitoring of technetium 99m. Timing of the sulfapyridine signal corresponded to the arrival of 5%-13% of technetium 99m DTPA in the cecum. Exemplifying the use of this new technique, simultaneous administration of lactulose into the stomach and SASP into the duodenum yielded consistently longer stomach-to-cecum than duodenum-to-cecum transits, attributable to the delay caused by gastric emptying. Therapeutic doses of morphine delayed small bowel transit of SASP. Transit of SASP offers a second marker technique for the cecal arrival of the "head" of a bolus; the approach may be useful as an inexpensive, noninvasive measurement of transit.

Adult↗

Ventilatory function in chronic peptic ulcer. A controlled study of ventilatory function in patients with gastric and duodenal ulcer.

The aim of this study was to determine if a defect in ventilatory function is present in patients with chronic peptic ulcer and if so, is it present in both gastric and duodenal ulcer and is it related to smoking. Fifty-six patients with peptic ulceration (27 gastric ulcer, 29 duodenal ulcer), together with 56 healthy controls matched for age, sex, and smoking status, were studied. Ventilatory function was measured and the ABH blood group antigen secretor status was determined. Vital capacity and forced expiratory volume in 1 s were significantly reduced in both smokers and nonsmokers with gastric ulcer when compared with controls; total lung capacity was lower than controls only in smokers with gastric ulcer. In duodenal ulcer patients, a trend similar to that observed in gastric ulcer patients was present. It is concluded that a defect in ventilatory function is present in patients with chronic gastric ulcer; a lesser defect is present in patients with duodenal ulcer.

ABO Blood-Group System↗

Cloning and sequence analysis of an Ig lambda light chain mRNA expressed in the Burkitt's lymphoma cell line EB4.

A cDNA library was constructed from the mRNA of the Ig lambda producing Burkitt's lymphoma cell line, EB4. Overlapping clones encompassing the coding sequence of the Ig lambda mRNA were isolated and sequenced. The predicted amino acid sequence shows a short hydrophobic leader peptide and a mature polypeptide of 217 residues in which V, J and C regions can be distinguished. The V region belongs to subgroup VI and has greatest homology (80%) with the Amyloid-AR protein. The constant region is the Kern- Oz+ isotype. Probing normal human DNA with the subcloned V lambda coding sequence detects one gene at high stringency and a family of 11 members at low stringency. To date, no restriction enzyme site polymorphisms have been detected. The V lambda VI gene is rearranged on both chromosomes of EB4 and is deleted on both chromosomes in the Burkitt's lymphoma cell line BL2.

Base Sequence↗

Salmonella food poisoning.

During an outbreak of Salmonella typhimurium food poisoning in September 1983, in Sydney, 10 affected subjects were admitted to the same hospital. On admission to hospital, all patients were severely dehydrated; two patients developed acute tubular necrosis, while a third patient had myopericarditis. Bacteraemia was confirmed in two patients, in one of whom no organisms were isolated from stool cultures. Antibiotic agents were administered to all patients, because of the unusually severe nature of the infection. This outbreak illustrates that salmonella gastroenteritis, although usually fairly mild and self-limiting, can be a virulent disease resulting in serious complications. Appropriate management should include careful initial assessment of suspected cases, vigorous correction of fluid and electrolyte disturbances, and judicious use of antibiotic agents when bacteraemia or severe toxaemic features are present.

Adolescent↗

Isolation of a series of HLA class I clones from a human chromosome 6 genomic library.

Human metaphase chromosomes were fractionated by a fluorescent-activated cell sorter (FACS II) and the chromosome 6 fraction was sorted. A genomic library was constructed in lambda gtWES cloning arms using a partial EcoRI digest of the chromosomal DNA. We estimate that at least 60% of our library represents chromosome 6 material, and as 1.2 x 10(5) recombinants were obtained, this indicates that the majority of clonable chromosome 6 sequences are represented. The library was screened with a mouse H-2 class I clone and 18 HLA class I recombinants were isolated from 4 x 10(4) plaques.

Cell Fractionation↗