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Biomedical subjects

J Dent

Publications and source records attributed to J Dent.

At least 253 records · Page 14Linked to original sources

Manometry of canine ileocolonic sphincter: comparison of sleeve method to point sensors.

Tonic and phasic pressures at the canine ileocolonic sphincter (ICS) were recorded by a manometric assembly that combined a sleeve sensor with multiple side-hole pressure ports. By aligning the side holes precisely it was possible to evaluate in vivo the fidelity of the sleeve relative to simultaneous pressure records from the point sensors. The ICS exhibited tonic and phasic pressures, often in excess of 100 cmH2O of pressure. The sleeve sensor was tolerant of small, but potentially important, movements of the assembly relative to the ICS. Point sites of recording moved in and out of the high-pressure zone and side holes were, therefore, not ideal sensors of sphincteric tone. The anticipated properties of this sleeve, that it would display reduced fidelity for rapid changes in pressure at sites away from its point of perfusion, were confirmed in vivo. The sleeve also "summarized" phasic bursts and was unable to monitor propagation of such events. However, the combined assembly proved excellent for examining overall function of the canine ICS.

Animals↗

Epitope mapping of the von Willebrand factor subunit distinguishes fragments present in normal and type IIA von Willebrand disease from those generated by plasmin.

A small but consistent proportion of the von Willebrand factor (vWF) in normal plasma is composed of 189, 176, and 140 kD fragments cleaved from the 225 kD subunit. A monoclonal antibody map of vWF, based on the reactivity of individual antibodies with cyanogen bromide and tryptic fragments of known carboxy and/or amino termini, showed that in normal and IIA von Willebrand disease (vWD) plasmas the 140 kD fragment was derived from the amino-terminal region, whereas the 176 kD fragment was derived from the carboxy-terminal region of the subunit. In type IIA vWD, however, the fragments comprised a greater proportion of circulating vWF. In contrast, plasmin cleaved a 176 kD fragment from the amino terminus and a 145 kD fragment from the carboxy terminus of the subunit. Species similar to these plasmin-cleaved fragments were demonstrated in plasmas from four patients treated with fibrinolytic agents, but not in IIA vWD.

Antibodies, Monoclonal↗

Hydatidiform mole in England and Wales 1973-83.

The number of cases of hydatidiform mole (HM) registered annually in England and Wales has risen since 1973 to 1.54 per 1000 live births in 1983. For women over 50 the risk per pregnancy was 411 times and for girls under 15 it was six times greater than that for women aged 25-29. 7.75% of patients had chemotherapy for invasive mole or choriocarcinoma. Patients who had had oxytocin-induced or prostaglandin-induced uterine evacuation or hysterotomy were more likely to need chemotherapy. Human chorionic gonadotropin (HCG) was undetectable by 56 days after evacuation in 42% of patients, none of whom required chemotherapy; a considerable reduction in follow-up time for this subgroup is proposed. For patients whose HCG values became normal more than 56 days after evacuation and stayed normal for 6 months the risk of recrudescent disease was 1 in 286. In subsequent pregnancies the risk of a second HM was 1 in 76 and that of a third was 1 in 6.5. 11 (0.2%) patients died, 2 from drug-resistant choriocarcinoma.

Adolescent↗

Radioimmunolocalization and selection for surgery in recurrent colorectal cancer.

The value of radioimmunolocalization (RIL) of cancer depends on its performance in situations where the result determines the choice of management. A rise in serum carcinoembryonic antigen (CEA) values after apparently curative resection of colorectal cancer implies localized, resectable recurrence in some patients and widespread unresectable tumour in others. This study investigated the ability of RIL with radiolabelled antibody to CEA and a novel numerical method for analysis of results to determine the extent of disease in 31 patients with raised serum CEA but no physical signs of recurrence. Surgical exploration or conventional radiology later confirmed the presence of tumour in 94 per cent of sites which were positive by RIL. Negative RIL predicted the absence of disease in 53 per cent of patients. The investigation could discriminate between localized and disseminated disease and often performed better than conventional radiology. RIL appears useful in selection of patients for second look laparotomy.

Carcinoembryonic Antigen↗

Upper esophageal sphincter function during belching.

We studied the mechanism of belching with specific attention to the upper esophageal sphincter (UES) in 14 normal volunteers. Belching occurred by the following sequence of events: lower esophageal sphincter relaxation; gastroesophageal gas reflux, recorded manometrically as a gastroesophageal common cavity phenomenon; UES relaxation; esophagopharyngeal gas reflux; and restoration of intraesophageal pressure to baseline by a peristaltic contraction. Upper esophageal sphincter relaxations comparable to those associated with belches were induced by abrupt esophageal distention with air boluses. In contrast, fluid boluses injected into the midesophageal body either had no effect on UES pressure or increased UES pressure. Thus, the UES responded to esophageal body distention in two distinct ways: abrupt relaxation in response to air boluses and pressure augmentation in response to fluid boluses. Mucosal anesthesia did not alter the UES response to esophageal boluses of gas or liquid thereby making it unlikely that these substances are differentiated by a mucosal receptor. Rapid distention of the proximal esophagus with a cylindrical balloon (15 cm long) elicited UES relaxation. These findings suggest that the rapidity and spatial pattern of esophageal distention, rather than discrimination of the type of material causing the distention, determines whether or not UES relaxation occurs.

Adult↗

Abolition of gas reflux and transient lower esophageal sphincter relaxation by vagal blockade in the dog.

In the present study we have examined the hypothesis that transient lower esophageal sphincter relaxations are under vagal control. Fasting esophageal motor function was monitored with a manometric sleeve catheter passed via a cervical esophagostomy. Gastric insufflation with oxygen resulted in intermittent venting of gas into the esophagus during transient lower esophageal sphincter relaxations. Such venting of gas was associated with the occurrence of esophageal body common cavities and gas venting from the esophageal stoma, all of which increased with increasing rates of gastric insufflation. The optimal insufflation rate, 80 ml/min, produced stomal gas venting at a rate of 10.3 +/- 1.1/h (mean +/- SE). The time and pressure profiles of transient lower esophageal sphincter relaxations induced by gastric insufflation were similar to those relaxations seen with spontaneous postprandial gastroesophageal reflux and belching in dogs. Sphincteric relaxation started 10 s before the onset of common cavities. In all 4 dogs, cooling of cervical subcutaneous vagosympathetic loops abolished transient lower esophageal sphincter relaxations, common cavities, and stomal gas venting. Within 1-4 min of cessation of vagal cooling, all three markers of gastroesophageal gas venting returned. Atropine, 50 and 200 micrograms/kg i.v., did not block transient lower esophageal sphincter relaxations or gas reflux. Gastric gaseous distention is a potent and consistent trigger of transient lower esophageal sphincter relaxations in the dog. This effect can be used as a model for study of control mechanisms of transient sphincter relaxation-dependent gastroesophageal reflux. Our observations with this model indicate that transient lower esophageal sphincter relaxations are under vagosympathetic control, but that muscarinic mechanisms are not important mediators of this control.

Animals↗

Integrity of cholinergic innervation to the lower esophageal sphincter in achalasia.

The human lower esophageal sphincter (LES) is believed to be innervated by nonadrenergic, noncholinergic inhibitory nerves, and cholinergic excitatory nerves. In idiopathic achalasia, LES relaxation is abnormal because the inhibitory nerves to the sphincter are either absent or functionally impaired. The integrity of cholinergic excitatory nerves to the LES, however, has not been thoroughly evaluated. In 27 patients with untreated idiopathic achalasia, and 21 healthy volunteers, we investigated the hypothesis that postganglionic cholinergic nerves to the LES are functionally intact in achalasia. The LES responses to atropine, edrophonium, methacholine, amyl nitrite, and pentagastrin were assessed. In 2 achalasia patients, patterns of fasting motor activity in the LES were investigated during overnight manometric studies. Resting LES pressure was significantly greater in the achalasia patients, 41 +/- 4 mmHg (mean +/- SE), than in the normal subjects, 20 +/- 2 mmHg. Atropine significantly reduced LES pressure in both groups by 30%-75%. Edrophonium increased LES pressure in the achalasia patients but had negligible effect on the normal subjects. The LES in achalasia patients exhibited an increased sensitivity to both methacholine and pentagastrin compared with the normal subjects. In both patients who underwent an overnight manometric study, the LES exhibited cyclic phasic contractile activity synchronous with gastric contractions during the migrating motor complex. We conclude that the study findings support the hypothesis that postganglionic cholinergic LES innervation in achalasia patients is either normal or only minimally impaired, in contrast to the marked impairment of the inhibitory nerves governing LES relaxation.

Adult↗

Relationship of transient lower esophageal sphincter relaxation to postprandial gastroesophageal reflux and belching in dogs.

Methods have been developed for the recording of patterns of motor function associated with spontaneous gastroesophageal reflux and belching in trained, unsedated dogs. Pharyngeal, esophageal body, lower esophageal sphincter (LES), and gastric pressures were monitored in 3 dogs with a manometric assembly inserted through a cervical esophagostomy. Spontaneous changes in esophageal pH were recorded simultaneously with a glass electrode. Each dog was studied three times for 3 h starting directly after completion of a full-sized meal. Acid reflux was recorded on 40 occasions; on 35 of these occasions it was possible to analyze, in detail, motor events at the time of reflux. This analysis showed that the LES was completely relaxed at the time of reflux and that the relaxation occurred within the 15 s before the onset of esophageal acidification. In 77% of the reflux episodes LES relaxation occurred independently of swallowing or any other motor event. The remainder of the LES relaxations associated with reflux were secondary to a swallowing salvo or a single swallow that did not trigger an esophageal body peristaltic wave. Straining was associated with reflux during many episodes of LES relaxation, but did not induce reflux if there was measurable LES pressure. Belching was also related to complete LES relaxations with a pattern identical to that associated with acid reflux. In the dog, liquid and gas reflux occurred during transient LES relaxations that were very similar to those that allow reflux to occur in humans. The dog is a suitable model for investigation of the nature and control of reflux associated with transient LES relaxation.

Animals↗

Fertility in patients with gestational trophoblastic tumors treated with etoposide.

The effect of etoposide containing drug combinations on reproductive performance was studied in women successfully treated for gestational trophoblastic disease between 1977 and 1984. Of the 74 women who wished to get pregnant 57 (77.0%) succeeded in having at least one live birth while five (6.8%) have ongoing pregnancies. Of eight (19.8%) women who have not become pregnant two (2.7%) had previous infertility problems antedating the development of gestational trophoblastic disease. The miscarriage rate was 124/1000. There was only one case of foetal death and one congenital abnormality (microcephaly possibly associated with cytomegalovirus infection) among 79 live births and stillbirths. This study indicates that etoposide (VP16-213) as is currently used in this unit for the treatment of gestational trophoblastic tumour is unlikely to have any long-term effect on fertility in most women.

Adult↗

Gallbladder emptying in man related to fasting duodenal migrating motor contractions.

Animal studies have shown that the gallbladder (GB) empties partially during fasting in relation to phase II of the interdigestive motor cycle (IDMC). It has been assumed that in man the GB remains inert during fasting, although there have been no studies in which repeated sequential measurements of gallbladder volume have been made and related to the IDMC. In this study the possibility of linkage between the IDMC and GB volume has been examined in nine fasting human volunteers (five males/four females). A multilumen constantly perfused manometry catheter was positioned in the duodenum and motor activity recorded continuously. Phase III of the IDMC was characterized by phasic contractions, with a frequency of 10-12/min for at least 2 min, which had a distal propagative pattern and were followed by a motor quiescence (Phase I). GB volume was calculated at 15 min intervals from ultrasound measurements of the maximal length and diameter of the GB by the summation of cylinders method, and related to the time of onset of each phase III of the IDMC. In all nine subjects GB volume decreased prior to the onset of phase III and increased following its passage (P less than 0.01). GB volume decrease ranged between 6 and 56% of maximal GB volume (median 18%) and subsequent filling ranged from 14 to 53% (median 27%). The maximal volume decrease occurred 30 min prior to the onset of phase III (P less than 0.02). These studies have demonstrated that the human GB empties partially during phase II of the IDMC.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Developments in chemotherapy for medium- and high-risk patients with gestational trophoblastic tumours (1979-1984).

Identification of various prognostic factors at the start of chemotherapy allows patients with gestational trophoblastic tumours to be categorized into low-, medium- and high-risk groups so that they can be given the minimum treatment necessary to eliminate their disease. Most patients in the low-risk category can be treated with minimal toxicity using a methotrexate/folinic acid regimen and these patients are not considered in this report. Before 1979 patients in the medium-risk category were treated with a sequence of drugs which included, hydroxyurea, methotrexate, 6-mercaptopurine, actinomycin D, vincristine and cyclophosphamide. Since 1979 etoposide has been substituted for vincristine and cyclophosphamide. The 76 patients treated between 1979 and 1983 are all alive and in remission 1.1.85. Three patients (4%) relapsed and required retreatment and all are in remission. Fifty-six patients in the high-risk group, most at risk of developing drug resistance, were treated with a regimen incorporating etoposide with methotrexate, actinomycin D (EMA) and vincristine and cyclophosphamide (CO). EMA and CO were given on alternate weeks, resulting in an overall survival rate of 84%. Patients who had received prior chemotherapy had a survival rate of 74% and a relapse rate of 19% compared with 93% survival and 3% relapse rate in those who had not received prior chemotherapy. Toxicity with the EMA/CO regimen was significantly less than with an earlier regimen (CHAMOCA) used in the high-risk group.

Adult↗

1-Deamino-8-D-arginine vasopressin and cryoprecipitate in variant von Willebrand disease.

The effect of infusing DDAVP and cryoprecipitate either singly or in combination was studied in a patient with variant von Willebrand disease. Both DDAVP and cryoprecipitate caused only partial correction in the hemostatic defect when used as a single agent. A combination of DDAVP and cryoprecipitate induced a complete correction of the hemostatic defect as well as factor VIII related properties.

Deamino Arginine Vasopressin↗

Sphincter of Oddi motility disorders in patients with idiopathic recurrent pancreatitis.

Motor disorders of the sphincter of Oddi (SO) may play a role in the pathogenesis of idiopathic recurrent pancreatitis. We have compared manometric records from the SO in 28 patients with idiopathic recurrent pancreatitis with those from 10 control subjects. Patients with idiopathic recurrent pancreatitis had presented with episodes of upper abdominal pain associated with abnormal serum levels of amylase on at least two occasions, in the absence of alcohol abuse and biliary disease. Retrograde pancreatography was either normal or showed only minor changes in pancreatic ducts. A triple lumen low compliance manometric system was used to obtain a 5 min recording of spontaneous SO motor activity. From this recording were determined the SO basal pressure, SO phasic contraction amplitude, SO wave frequency and direction of wave propagation. The SO response to intravenous cholecystokinin-octapeptide (CCK-OP) 20 ng/kg was then recorded for at least 3 min. Twenty-five of the twenty-eight patients demonstrated one or more manometric abnormality when compared with data from the ten controls. The most frequent abnormality was an elevated SO basal pressure in 16 patients. In addition, excess of retrograde contractions in nine patients, high frequency of SO phasic contractions in nine patients, absence of phasic contractions in three patients, and paradoxical response to CCK-OP administration in two patients were recorded. This study has demonstrated a spectrum of sphincter of Oddi manometric disorders in patients with idiopathic recurrent pancreatitis and suggests that motility disorders of the sphincter of Oddi may be associated with episodes of pancreatitis.

Adult↗

Manometric disorders in patients with suspected sphincter of Oddi dysfunction.

Sphincter of Oddi (SO) manometry was conducted in 48 subjects who had previously undergone cholecystectomy. Ten of these subjects had no detectable biliary or pancreatic disease and served as controls. The other 38 patients were presumed to have SO dysfunction and had presented with episodes of severe biliary-type pain with either dilatation of the bile duct on a retrograde cholangiogram, transient changes in liver function tests, or both of these abnormalities. A triple-lumen low-compliance manometric system was used to record the SO basal pressure, SO phasic contraction amplitude, SO wave frequency, direction of wave propagation, and SO response to intravenously administered cholecystokinin-octapeptide 20 ng/kg. Satisfactory manometric recordings were obtained from 32 of 38 patients and of these, 25 patients showed one or more abnormalities when compared with data from the 10 controls. The abnormalities included excess of retrograde contractions (12), high frequency of SO phasic contractions (11), elevation of the SO basal pressure (8), and paradoxical cholecystokinin-octapeptide response (10). The study has demonstrated a spectrum of manometric abnormalities in the SO of patients with suspected SO dysfunction.

Adult↗

Susceptibility of clinical isolates of Campylobacter pyloridis to 11 antimicrobial agents.

The activities of 11 antimicrobial agents, including two bismuth salts, against 70 strains of Campylobacter pyloridis isolated from gastric biopsy specimens were tested. The isolates were very susceptible to penicillin (the MIC for 90% of the strains tested [MIC90] was 0.03 microgram/ml), erythromycin, cefoxitin (MIC90, 0.12 microgram/ml), gentamicin, and ciprofloxacin (MIC90, 0.25 microgram/ml). The bismuth salts and nalidixic acid had moderate activity (MIC90, 16 to 64 micrograms/ml). Twenty percent of the isolates were resistant to metronidazole (MIC, greater than 1 micrograms/ml), and all were resistant to sulfamethoxazole and trimethoprim (MIC90, greater than 256 micrograms/ml).

Anti-Bacterial Agents↗

Morphometric assessment of reflux oesophagitis in fibreoptic biopsy specimens.

The oesophageal epithelium of patients with reflux oesophagitis has been studied by means of computer aided morphometry. Measurements of histological features were made on biopsies from six cases before and after treatment. The size and elongation of the nuclei and their variation, the number of nuclei per unit length or per unit sectioned area, and the size and number of nucleoli per nucleus were measured for two zones of the epithelium, the base layer and the intermediate layer, which were independent of section orientation. The measurements were analysed using discriminant analysis. Significant discrimination was found between the two groups. The most important parameters were the number of intermediate layer nuclei per sectioned square millimetre, the mean intermediate layer nuclear area, and the number of nuclei per millimetre of base epithelium. These parameters are consistent with increased cell turnover of the non-ulcerated epithelium before treatment.

Anti-Ulcer Agents↗

Sleeve device functions as a Starling resistor to record sphincter pressure.

In 1976 Dent (Gastroenterology 71: 263-267) introduced a sleeve-catheter device for obtaining continuous recording of lower esophageal sphincter pressure. The infused sleeve accommodates for axial sphincter movement by providing a large surface of collapsible membrane that is capable of sensing maximal sphincter pressure at any point along the sleeve. Although sleeve performance was tested previously, the precise physical principal of its function has not been delineated. This study tests the hypothesis that the sleeve device functions as a Starling resistor. The term "Starling resistor" is an eponym that designates the physics of fluid flow through collapsible tubes. When pressure at any point along an infused collapsible conduit is greater than the intraluminal pressure at the distal end of the conduit, partial collapse occurs at some axial location along the conduit where the transmural pressure equals zero. The location of zero transmural pressure is termed the "equal pressure point" (EPP). The partial collapse at the EPP causes a local change in luminal resistance that is directly related to the magnitude of the external pressure at the EPP and accompanied by a corresponding change in the pressure upstream from the EPP. A correlate to the performance of Starling resistors is that the pressure upstream to the EPP is not affected by the downstream pressure, so long as the downstream pressure is less than the external pressure. To test our hypothesis, we evaluated sleeve performance in vitro using a two-chambered model that allowed application of static or oscillatory pressures at one or two sites along the sleeve.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Variability of lower esophageal sphincter pressure in the fasted unanesthetized opossum.

The opossum has served as a useful animal model for in vivo studies of lower esophageal sphincter (LES) function. Previous investigations, however, have been confined to studies on anesthetized animals. In 10 opossums we investigated LES pressure during fasting cycles of the gastrointestinal migrating myoelectric complex (MMC) and examined the influences of anesthesia and feeding on LES pressure. Intraluminal pressure from the esophageal body, LES, and gastric antrum was recorded by a manometric assembly that incorporated a sleeve device. Myoelectric activity was recorded from the gastric antrum and duodenum via implanted electrodes. MMCs were readily recorded from all animals. MMC cycle length was 86 +/- 2.9 (SE) min. The LES exhibited cyclic changes in intraluminal pressure that occurred in synchrony with the gastric MMC cycle. During phase I of the gastric MMC cycle, LES pressure was essentially stable, although intermittent spontaneous oscillations at 3-4/min were sometimes noted. Forceful phasic LES contraction started during phase II of the gastric MMC, became maximal during phase III, and disappeared during phase I. The MMC-related phasic LES contraction occurred at a maximal rate of 1.4 +/- 0.05/min with amplitudes of 60-150 mmHg and were temporally associated with spike bursts and contractions in the gastric antrum. Pentobarbital sodium-induced anesthesia abolished MMC-related phasic LES activity and caused a transient rise in basal sphincter pressure. Phasic LES activity was also inhibited by atropine and feeding.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Intravenous↗