The ANRAC competencies in context.
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Accreditation↗
Biomedical subjects
J Dent
Publications and source records attributed to J Dent.
Elevated platelet count as a cause of abnormal von Willebrand factor multimer distribution in plasma.
Twelve of 19 patients with myeloproliferative disorders showed a decrease of absence of the largest multimers of plasma von Willebrand factor (vWF) that correlated with elevated platelet counts but not with leukocyte counts. This suggested that platelets, rather than leukocytes, may be associated with the pathogenesis of the acquired vWF abnormality seen in these patients. To examine the hypothesis further, we studied 12 patients with reactive thrombocytosis after splenectomy. Increased platelet count (> 5 x 10(11)/L) after splenectomy was associated with vWF abnormalities indistinguishable from those detected in patients with myeloproliferative disorders. Accordingly, there was an inverse correlation between proportion of large vWF multimers and platelet, but not leukocyte, number: normalization of the platelet count was accompanied by restoration of a normal vWF multimeric pattern. These findings suggest that an increase in the number of platelets circulating in blood may favor the adsorption of larger vWF multimers onto the platelet membrane, resulting in their removal from the circulation and subsequent degradation.
Adult↗
HTLV-I among Northern Territory blood donors.
OBJECTIVE: Human T-lymphotropic virus type I (HTLV-I) is known to be endemic among Northern Territory (NT) Aborigines, therefore evidence was sought of HTLV-I infection in NT blood donors. DESIGN: Samples were screened for HTLV-I antibodies using the Serodia HTLV-I particle-agglutination assay. Repeatedly reactive sera were tested by western blot. Viro- logical and molecular investigations were also performed. SERA: Aliquots from all 11,121 blood donations collected between June 1991 and August 1992. RESULTS: Four (0.036% of total) blood donations, each from different donors, were repeatedly reactive by particle-agglutination assay. One (0.009%) sample, from a 52-year-old non-Aboriginal man with no verified risk factors, was confirmed as HTLV-I seropositive by western blot. A viral isolate and a 431 base pair polymerase chain reaction product from the env gene were obtained from a culture of his peripheral blood mononuclear cells. Sequencing of the polymerase chain reaction product demonstrates that this isolate is a prototype strain and not the variant identified among Aborigines. The remaining three repeatedly reactive donors, including the positive donor's wife, were western blot indeterminate. CONCLUSIONS: There is a low prevalence of HTLV-I carriage among blood donors in the NT, and presumably in other States. However, most repeatedly reactive donations prove to be western blot indeterminate, therefore additional tests are required to detect or exclude HTLV-I infection. Although universal screening of donations would virtually eliminate HTLV-I transmission by transfusion, it has disadvantages, including financial cost.
Adult↗
Analysis of structure-function relationships in the platelet membrane glycoprotein Ib-binding domain of von Willebrand's factor by expression of deletion mutants.
We have used a series of Escherichia coli-expressed deletion mutants of the glycoprotein (GP) Ib-binding domain of von Willebrand factor (vWF) to study the structural basis of its function. In addition to the prototypic molecule (rvWF441-733), we constructed 11 mutants; seven had deletions of sequence on the amino- and/or carboxyl-terminal side of the Cys509-Cys695 intrachain disulfide loop, and four had limited deletions inside the loop. Other cysteine residues in addition to 509 and 695, when present in the corresponding native sequence, were mutated to glycine; all molecules were purified in the oxidized as well as reduced and alkylated state. The smallest species retaining the ability to interact with GP Ib in the absence of modulators was the oxidized rvWF508-696; the latter, as well as rvWF441-696, became inactive after reduction and alkylation. In contrast, all the other fragments with deletions outside of the loop, but extending at least to residue 700, showed better binding to platelets after reduction and alkylation than when the Cys509-Cys695 disulfide bond was oxidized. Any limited deletion of sequence inside the loop caused complete loss of GP Ib-binding function both in the absence or in the presence of botrocetin, and this persisted even after reduction and alkylation. In contrast, all mutants with intact sequence between residues 509 and 695 bound to GP Ib in the presence of botrocetin, regardless of whether the 2 cysteine residues were oxidized or reduced and alkylated. Ristocetin, unlike botrocetin, appeared to have no effect in modulating the binding of any of the expressed fragments to platelets. Our findings suggest that the GP Ib-binding domain of vWF contains multiple interaction sites, but integrity of the sequence 509-695 is important for function.
Amino Acid Sequence↗
Acid pump blockers: what are their current therapeutic roles?
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Anti-Inflammatory Agents, Non-Steroidal↗
Cholecystokinin octapeptide stimulates phasic and tonic pyloric motility in healthy humans.
Stimulation of localised pyloric contractions may be an important mechanism in the slowing of gastric emptying by cholecystokinin infusion. The effect of cholecystokinin octapeptide on fasting pyloric motility was investigated in 14 healthy volunteers. Antral, pyloric, and duodenal pressure responses to normal saline and graded injections of cholecystokinin octapeptide (5, 10, and 20 ng/kg) were measured. Injections were given double blind and in randomised order. All doses of cholecystokinin octapeptide initially stimulated (p < 0.05 cf saline) phasic pressure waves localised to the pylorus--the median number of pyloric pressure waves in the 5 minutes after injection being 0, 3.5, 6, and 7 for the saline and the 5, 10, 20 ng/kg cholecystokinin octapeptide injections respectively. The phasic pyloric motor response to 20 ng/kg cholecystokinin octapeptide injection was greater than that to 5 ng/kg (p < 0.05). Basal pyloric pressure increased after 20 ng/kg (1.0 v 0.2 mm Hg, p < 0.05 cf saline). Antral and duodenal pressure waves were suppressed initially by all doses of cholecystokinin (p < 0.05 cf saline). Subsequently, 20 of the 42 cholecystokinin octapeptide, injections but none of the saline injections, were followed by antropyloric pressure waves. Atropine, 15 micrograms/kg iv as a bolus, and then 4 micrograms/kg/hour iv as an infusion, had no effect on the stimulation of localised phasic pyloric pressure waves by cholecystokinin octapeptide 10 ng/kg. It is concluded that stimulation of pyloric contractions and suppression of antral and proximal duodenal motility may contribute to the slowing of gastric emptying produced by cholecystokinin.
Adolescent↗
Mechanisms underlying the antireflux action of fundoplication.
The effect of fundoplication on patterns of gastro-oesophageal reflux and the underlying motor mechanisms were investigated in 18 patients with symptomatic reflux. Oesophageal motility and pH were recorded concurrently after a standard meal. Studies were performed preoperatively and from 5 to 27 months after surgery. Fundoplication virtually eliminated reflux in all but three patients. Control of reflux was associated with a 50% fall in the number of transient lower oesophageal sphincter relaxations, a fall in the proportion of transient lower oesophageal sphincter relaxations accompanied by reflux from 47% to 17%, and an increase in the mean residual pressure at the gastro-oesophageal junction during swallow induced lower oesophageal sphincter relaxation from 0.7 mm Hg to 6.0 mm Hg. Basal pressure at the gastro-oesophageal junction rose from 10.9 mm Hg to 14.5 mm Hg, however, there was no correlation between postoperative reflux and basal gastro-oesophageal junction pressure. These findings suggest that the anti-reflux effects of fundoplication result from changes in the mechanical behaviour of the gastro-oesophageal junction that result in incomplete abolition of the high pressure zone during lower oesophageal sphincter relaxation, and reduced triggering of transient lower oesophageal sphincter relaxations.
Adult↗
Effect of gastro-oesophageal reflux on upper oesophageal sphincter motility in children.
Motor events of the upper oesophageal sphincter associated with gastro-oesophageal reflux were evaluated in 53 symptomatic children (median age 13 months) who were studied recumbent and unsedated. Children were divided into four groups according to symptoms, and then into two groups according to the presence or absence of neurological deficit. No grouping had basal upper oesophageal sphincter pressure that differed significantly from any other. Oesophageal distention due to gastro-oesophageal reflux, which was recognisable as oesophageal common cavity episodes, was associated with augmentation of mean basal upper oesophageal sphincter pressure from 36.5 (SD 18) mm Hg to 48.5 (18) mm Hg (p < 0.0001), irrespective of whether gastro-oesophageal reflux caused oesophageal acidification. Abrupt relaxations of the upper oesophageal sphincter independent of swallowing and lasting up to three seconds occurred during 54% of common cavity episodes. Forty nine per cent of these relaxations occurred within four seconds after the onset of distention. The oesophageal distention caused by gastro-oesophageal reflux is a potent stimulus of transient upper oesophageal sphincter relaxations in children. These relaxations are a more likely explanation for oesophagopharyngeal reflux than defective basal upper oesophageal sphincter tone.
Child↗
Dual effects of cisapride on gastric emptying and antropyloroduodenal motility.
There is little information about the effects of cisapride on human antropyloroduodenal motility, despite its documented efficacy for increasing the rate of gastric emptying in patients with gastroparesis. Cisapride has been reported to have little effect on gastric emptying in normal subjects. Antral, pyloric, and duodenal pressures were recorded simultaneously with gastric emptying in 20 healthy volunteers. Thirty minutes after the solid component of the meal had started to empty from the stomach, each subject received either 10 mg cisapride i.v. (11 subjects) or intravenous saline (9 subjects). Intravenous saline had no effect on either motility or gastric emptying. In contrast, cisapride administration was associated with a dual effect on motility, with initial suppression of antral pressure waves (P < 0.05) followed by stimulation of associated antropyloroduodenal pressure waves (P < 0.01). Gastric emptying slowed in the first 30 min after cisapride (P < 0.05), and this was followed by more rapid gastric emptying (P < 0.01). The amount of the meal emptied in the 60 min after cisapride correlated with the number of associated antroduodenal pressure waves (r = 0.75, P < 0.001) but not with the number of antral waves (r = 0.42, NS). These results indicate that cisapride in a dose of 10 mg i.v. has dual effects on gastric emptying and gastric motility. The stimulation of associated antral pressure waves is a plausible mechanism for the efficacy of cisapride in the treatment of gastroparesis.
Adolescent↗
Changes in oesophageal pH associated with gastro-oesophageal reflux. Are traditional criteria sensitive for detection of reflux?
Traditionally, gastro-oesophageal reflux is deemed to have occurred when oesophageal pH falls below 4. Other 'non-traditional' pH changes that do not fall below pH 4, that fall below 4 for only brief intervals, or that occur when basal pH is less than 4 are usually disregarded. The aim of this study was to determine whether these non-traditional pH changes represent gastro-oesophageal reflux or are artefactual. The 3-h postprandial combined oesophageal pH and manometric records of 22 patients referred for investigation of suspected gastro-oesophageal reflux were reviewed. All pH falls of > or = 0.5 pH units were analysed for manometric evidence of reflux that was classified as definite, probable, or possible. In total, 196 traditional and 223 non-traditional pH events were scored and analysed. The majority of traditional (80%) and non-traditional (60%) events were associated with definite manometric evidence of reflux, although a greater proportion of non-traditional events were associated with only probable evidence of reflux (33%) compared with traditional events (18%). The proportions of possible reflux were similar in the two groups. Limiting pH events to only those satisfying traditional criteria excluded an additional 32% with definite manometric evidence of reflux and 49% with definite or probable evidence of reflux. Most pH falls that remained above 4 or fell across 4 for < 15 sec occurred in the 1st h postprandially, compared with traditional pH events, which occurred equally throughout the 3-h period. We conclude that traditional criteria for scoring pH episodes substantially underestimate the number of reflux episodes.
Adolescent↗
Gastric polyposis: onset during long-term therapy with omeprazole.
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Gastroscopy↗
Computer system for assisting with clinical interpretation of tumour marker data.
OBJECTIVE: To design and evaluate a computer advisory system for the treatment of gestational trophoblastic tumour. DESIGN: A comparison of clinicians' treatment decisions with those of the computer system. Two datasets were used: one to calibrate the system and one to independently evaluate it. SETTING: Department of medical oncology. PATIENTS: Computerised records of 290 patients with low risk gestational trophoblastic tumour for whom the advisory system could predict the adequacy of treatment. The calibration set comprised patients admitted during 1979-86(227) and the test set patients during 1986-89(63). MAIN OUTCOME MEASURES: The system's accuracy in predicting need to change treatment compared with clinicians' actions. The mean time faster that the system was in predicting the need to change treatment. RESULTS: On the calibration dataset the system was 94% (164/174) accurate in predicting patients whose treatment was adequate, recommending change when none occurred in only 10 (6%) patients. In patients whose treatment was changed the system recommended change earlier than clinicians in 39/53 cases (74%), with a mean time advantage of 14.9 (SE 2.02) days. On the test dataset the system had an accuracy of 91% (31/34) in predicting treatment adequacy and a false positive rate of 9% (3/34). The system recommended change earlier than clinicians in 22/29 cases (76%), with a mean time advantage of 12.5 (2.22) days. CONCLUSIONS: The computer advisory system could improve patient management by reducing the time spent receiving ineffective treatment. This has implications for both patient time and clinical costs.
Biomarkers, Tumor↗
Heartburn--lifting the veil of mythology.
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Antacids↗
Muscle excitation in elderly adults: the effects of training.
Muscle membrane excitability is thought to decline with aging; the extent of this decline may be noninvasively assessed by measurement of the electrically evoked compound muscle action potential (M-wave). The intent of this study was two-fold: (1) to compare the M-wave in the brachioradialis (BR), tibialis anterior (TA), and thenar (TH) muscles of elderly (mean age = 66.3 +/- 3.7 years) and young (mean age = 31.2 +/- 4.9 years) adults, and (2) to determine the effects of 12 weeks of resistance training on M-wave characteristics in elderly adults. Prior to training, the elderly subjects had significantly smaller (P less than 0.05) resting M-waves than the young adults in the BR (4.8 mV vs. 8.7 mV), TA (8.8 mV vs. 11.0 mV), and TH (5.2 mV vs. 10.2 mV) muscles. During a 2-minute voluntary fatigue paradigm (3 seconds MVC per 2 seconds rest for 2 minutes), there was no evidence of excitability failure in either group. Following training, there was a significant increase (P less than 0.05) in the size of the M-wave of the TH (pretraining: 5.2 mV; posttraining: 8.96 mV) and BR (pretraining: 4.8 mV; posttraining: 6.1 mV), and a nonsignificant increase in the M-wave of the TA, but there was no change in the relative behavior of the M-wave during the 2-minute voluntary fatigue paradigm. It is suggested that the decline in muscle membrane excitation with aging may be due, at least in part, to the effects of a decreased membrane potential on the muscle fiber action potential.(ABSTRACT TRUNCATED AT 250 WORDS)
Action Potentials↗
Influence of sleep on anal sphincteric pressure in health and after ileal pouch-anal anastomosis.
Fecal incontinence at night may be a disturbing consequence of ileal pouch-anal anastomosis (IPAA). The hypothesis was that decreases in anal canal resting pressure occur as sleep deepens and that the decreases are more profound in pouch patients with incontinence than in controls. Using a sleeve catheter assembly for recording intraluminal and canal pressure and polysomnographic recordings of sleep stages, progressive decreases in anal canal resting pressure with deepening sleep occurred in 11 healthy controls (mean +/- SEM: 57 +/- 3 mm Hg to 43 +/- 3 mm Hg: P less than 0.05) and in 11 patients after IPAA (55 +/- 3 mm Hg to 42 +/- 4 mm Hg; P less than 0.05). Minute-to-minute variations in mean pressure were also found in both controls and IPAA patients, and they were greater at night in patients (P less than 0.05), except during rapid eye movement (REM) sleep. In three patients, resting pressure during REM sleep decreased markedly to 31 +/- 8 mm Hg. This decrease plus the variations in pressure during REM sleep led to incontinence. In conclusion, decreases in anal resting pressure coupled with marked minute-to-minute variations in pressure during sleep occurred in controls and in patients after IPAA and, when profound, led to nocturnal fecal incontinence in some patients.
Adult↗
Intravenous erythromycin overcomes small intestinal feedback on antral, pyloric, and duodenal motility.
The retardation of gastric emptying caused by intraduodenal lipid is associated with suppression of antral contractions and stimulation of localized pyloric contractions. Similar patterns of motility have been described in patients with gastroparesis. The effect of erythromycin on the antropyloroduodenal motor responses to intraduodenal lipid was investigated. In 17 volunteers an intraduodenal lipid infusion (10% Intralipid) was given at 1 mL/min for 50 minutes. Either erythromycin (3 mg/kg) or saline was administered IV for 15 minutes, beginning 20 minutes after the start of the intraduodenal lipid infusion. Antral, pyloric, and duodenal motility were measured with a sleeve/sidehole manometric assembly. Intraduodenal lipid stimulated localized pyloric contractions. Erythromycin suppressed localized phasic (P less than 0.003) and tonic (P less than 0.002) pyloric pressure waves and stimulated antral (P less than 0.003) and duodenal pressure waves (P less than 0.02). After erythromycin antral pressure waves were usually of high amplitude (greater than 50 mm Hg) and often associated with duodenal pressure waves. It was concluded that erythromycin overcomes the effects of intraduodenal lipid on antral, pyloric, and duodenal motility. These effects probably contribute to the gastrokinetic properties of erythromycin.
Adult↗
Adaptive changes in the pyloric motor response to intraduodenal dextrose in normal subjects.
Gastric emptying of glucose is faster after dietary supplementation of glucose, suggesting specific adaptation to changes in nutrient intake. In the present study, the effects of a continuous long-term (0-120-minute) and two short-term (0-20- and 80-100-minute) intraduodenal infusions of dextrose (2.4 kcal/min) on antropyloroduodenal motility and blood glucose, plasma gastric inhibitory polypeptide, and insulin concentrations were evaluated in nine volunteers. In four volunteers, an intraduodenal infusion of triglyceride (2.4 kcal/min) was administered immediately after the long-term dextrose infusion. The long-term dextrose infusion initially increased isolated pyloric pressure waves (IPPWs) and basal pyloric pressure (P < 0.05 for both), but after about 30 minutes IPPWs and basal pyloric pressure decreased and returned to baseline within 80 minutes. Each short-term infusion increased IPPWs and basal pyloric pressure (P < 0.05 for both). Antral pressure waves remained suppressed during the long-term dextrose infusion. Intraduodenal triglyceride increased IPPWs and basal pyloric pressure (P < 0.05 for both). The long-term dextrose infusion was associated with a sustained increase, and both short-term dextrose infusions were associated with peaks in glucose, insulin, and gastric inhibitory polypeptide levels. There was no significant relationship between biochemical measurements and antropyloroduodenal motility. It is concluded that specific adaptive changes occur rapidly in the phasic and tonic pyloric motor response, but not the antral motor response, to intraduodenal dextrose.
Adaptation, Physiological↗
Pharyngeal (Zenker's) diverticulum is a disorder of upper esophageal sphincter opening.
Pharyngeal coordination, sphincter opening, and flow pressures during swallowing were investigated in patients with pharyngeal (Zenker's) diverticula. Fourteen patients with diverticula and 9 healthy age-matched controls were studied using simultaneous videoradiography and manometry. Pharyngeal and upper esophageal sphincter pressures were recorded by a perfused side hole/sleeve assembly. Temporal relationships among swallowing events, extent of sphincter opening during swallowing, and intrabolus pressure during bolus passage across the sphincter were measured. The timing among pharyngeal contraction and sphincter relaxation, opening, and closure did not differ between patients and controls. Sphincter opening was significantly reduced in patients compared with controls in sagittal (P = 0.0003) and transverse (P = 0.005) planes. Manometric sphincter relaxation was normal in patients. Intrabolus pressure was significantly greater in patients than in controls (P = 0.001). It is concluded that Zenker's diverticulum is a disorder of diminished upper esophageal sphincter opening that is not caused by pharyngosphincteric incoordination or failed sphincter relaxation. Incomplete sphincter opening is likely to cause dysphagia. Increased hypopharyngeal pressures during swallowing are probably important in the pathogenesis of the diverticulum.
Aged↗