Oesophageal pain in coronary artery disease.
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Chest Pain↗
Biomedical subjects
J Janssens
Publications and source records attributed to J Janssens.
Involvement of two different pathways in the motor effects of erythromycin on the gastric antrum in humans.
BACKGROUND: During the interdigestive state in humans, erythromycin 40 mg induces a premature activity front that starts in the stomach, while erythromycin 200 mg induces a prolonged period of enhanced antral contractile activity. AIMS: To study the involvement of a cholinergic pathway in the motor effects of erythromycin using the muscarinic antagonist atropine and the neural 5-HT1 receptor agonist sumatriptan. METHODS: In 30 healthy volunteers, fasted antroduodenojejunal motor activity was studied by stationary manometry. Placebo (n = 10), atropine (15 micrograms/kg intravenous bolus plus 15 micrograms/kg/h over 30 minutes; n = 10), or sumatriptan (6 mg subcutaneously; n = 10) was administered, followed by infusion of erythromycin 40 mg or 200 mg. RESULTS: After placebo, erythromycin 40 mg induced a premature activity front with gastric onset after 19.1 (1.7) minutes in all volunteers. After atropine, erythromycin 40 mg failed to induce a premature activity front during a 60 minute period in all volunteers (p < 0.001), while sumatriptan prevented the induction of a premature activity front during a 60 minute period in all but one volunteer (p < 0.005). The number of antral contractions and their mean amplitude in the 60 minutes after erythromycin 200 mg did not differ significantly after atropine or sumatriptan versus placebo. CONCLUSIONS: The antral motor effects of erythromycin in humans are mediated via different pathways. The induction of a premature activity front is mediated through activation of an intrinsic cholinergic pathway, while the induction of enhanced antral contractile activity may be mediated via a pathway potentially involving activation of a muscular receptor.
Anti-Bacterial Agents↗
5-Hydroxytryptamine-1 receptor activation inhibits endocrine pancreatic secretion in humans.
The selective 5-hydroxytryptamine-1 receptor agonist sumatriptan inhibits exocrine pancreatic function in humans. No data are available on the effect of sumatriptan on fasting and postprandial endocrine pancreatic function in humans. To elucidate the influence of 5-hydroxytryptamine-1 receptor activation by sumatriptan on endocrine pancreatic function and blood glucose homeostasis, we determined plasma levels of somatostatin, glucagon, pancreatic polypeptide, insulin, and C-peptide before and after subcutaneous administration of sumatriptan (6 mg) in seven healthy volunteers, and we measured blood glucose and insulin plasma levels during an oral glucose tolerance test after placebo and after subcutaneous administration of sumatriptan (6 mg) in seven healthy volunteers. Sumatriptan significantly decreased the mean plasma levels of somatostatin, glucagon, pancreatic polypeptide, insulin and C-peptide (P < 0.001) and also significantly decreased mean and peak plasma levels of insulin after an oral glucose challenge (P < 0.02 and P = 0.04, respectively) without affecting glucose homeostasis. From our study, we speculate that activation of the 5-hydroxytryptamine-1 receptor inhibits endocrine pancreatic secretion.
Adult↗
[Obstetrics and gynecology in the last 40 years].
In the Netherlands the last 40 years have seen major changes in obstetrics and gynaecology: Progressive expansion of evidence-based medicine. A measurable, greatly improved quality policy during gynaecologists' training and the subsequent period. Increase of diagnostic possibilities during pregnancy (such as real-time echography, Doppler measurements, amniocentesis and umbilical-cord puncture). Foundation of the Landelijke Verloskunde Registratie (LVR. National Obstetrical Registry) in 1982, in which by now 90% of the specialists and 80% of the midwives are participating. Implementation of the 'Dutch model' of obstetrical care. Decrease of the number of home deliveries and increase of the obstetrical interventions. More attention for sex problems. Better results in the treatment of gynaecological tumours. Great progress in the field of reproduction endocrinology (both pharmaceutical and surgical).
Female↗
Ambulatory small intestinal manometry. Detailed comparison of duodenal and jejunal motor activity in healthy man.
The aim of this study were to provide a detailed comparison of duodenal and jejunal motor activity in healthy individuals by utilizing prolonged ambulatory manometry in combination with computer-aided analysis. Intraluminal pressure profiles were studied in the duodenum and jejunum of 18 healthy volunteers over 24 hr. The subjects ingested two meals, both of 800 kcal and of equal chemical composition, at two different times of the day. Over the whole interdigestive period, phase III motor activity started more frequently distal than proximal to the ligament of Treitz. However, an increasing time of fasting was linearly related to an increasing number of phase IIIs originating proximal to the ligament of Treitz (r = 0.95). Both meals induced a postprandial motor pattern of similar duration and contractile activity. As compared to the jejunum, individual duodenal contractions during the postprandial period and during phase II had a higher duration and amplitude. Propagated clustered contractions occurred more frequently in the duodenum than in the jejunum, both in the interdigestive and digestive state. Jejunal clusters comprised a higher number of individual contractions of lower amplitude and duration. In healthy man duodenal and jejunal motor activity are different, both in the digestive and interdigestive state. The differences include the number of activity fronts traversing these segments of the gut, the number and organization of propagated clustered contractions, and subtle changes in the amplitude, duration, and coordinated propagation of individual contractions. These changes presumably reflect a regulatory capability of the small intestine to modulate the rate of transit of intraluminal content through different segments of the gut.
Adult↗
Sumatriptan, a selective 5-HT1 receptor agonist, induces a lag phase for gastric emptying of liquids in humans.
Sumatriptan, a 5-hydroxytryptamine1 (5-HT1) receptor agonist at enteric neuronal 5-HT receptors, causes a relaxation of the gastric fundus and inhibition of antral contractile activity. The present study examined the effect of sumatriptan on gastric emptying of solids and liquids in humans. In eight healthy subjects the gastric emptying rate for liquids and solids was measured using the carbon-labeled glycine and octanoic acid breath test after subcutaneous administration of placebo or sumatriptan. Sumatriptan increased the gastric half-emptying time of liquids (P < 0.0005) and induced a prolonged lag phase for liquids (P < 0.0005) in all subjects. Sumatriptan increased gastric half-emptying time (P < 0.005) and the lag phase of solids (P < 0.05) in all subjects. In two healthy subjects gastric emptying of liquids and solids after subcutaneous administration of sumatriptan was studied by radioscintigraphy. Radioscintigraphy confirmed the delayed emptying and the prolonged lag phases after sumatriptan. In conclusion, sumatriptan delays gastric emptying of solids and liquids in healthy subjects. Moreover, sumatriptan induces a lag phase for liquids. The mechanism by which sumatriptan alters gastric emptying remains to be studied.
Adult↗
Capillary electrophoresis system for hemoglobin A1c determinations evaluated.
Hb A1c is the analyte of choice for monitoring metabolic control in patients with diabetes mellitus. Here we present a new analytical technique for measuring Hb A1c, capillary electrophoresis. The Hb A1c determination is not influenced by the labile Hb A1c fraction or by carbamylated or acetylated hemoglobin derivatives. Also, hemoglobin variants (Hb F, Hb S, and Hb C) do not interfere. This new application of capillary electrophoresis seems to be a valuable analytical tool for measuring Hb A1c in the clinical laboratory.
Blood Protein Electrophoresis↗
New insights in the pathophysiology of primary motility disorders of the esophagus.
Primary esophageal motility disorders (i.e. achalasia, diffuse spasm and related conditions) but also gastroesophageal reflux disease are characterised by a more or less pronounced dysfunction of esophageal body peristalsis and gastroesophageal sphincter relaxation. A normal interplay between inhibitory and excitatory peripheral nerves in the smooth muscle part of the esophagus is essential for the generation of esophageal peristalsis. The inhibitory nerve pathway determines the timing of the contraction; its neurotransmitter is NO. The excitatory pathway mainly determines the strength of the contraction; the neurotransmitter is acetylcholine. We have recently developed a technique to visualize the effect of the inhibitory nerves in the human tubular esophagus as a manometric relaxation of an artificial high pressure zone. We used this technique in patients with achalasia, diffuse spasm and related conditions and found an inverse relationship between percent inhibition and progression velocity of the contractions. We have examined with the same technique patients with reflux disease and found in these patients that the occurrence of acid reflux during TLESR's is accompanied by inhibition of the esophagus, whereas in normal controls it is accompanied by excitation. From a pathogenetic viewpoint we conclude as follows. Disorders of the inhibitory nerve pathway result in achalasia, diffuse spasm or related condition. We do not know exactly what happens when the excitatory pathway is diseased; there are arguments that these patients may have reflux disease.
Esophageal Achalasia↗
[Does flattening of the skull have lasting sequelae for brain development?].
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Brain↗
Computer-supported analysis of continuous ambulatory manometric recordings in the human small bowel.
An algorithm has been developed for the offline analysis of prolonged manometric recordings in the upper small intestine of humans. Sample data are acquired in the human duodenum and jejunum six solid-state strain-gauge transducers mounted on a silicon catheter that is connected to a portable digital recording device. The data are sampled at 4 Hz and filtered. For accurate calculations, the filtered signals are converted to cubic B-spline functions of order four. Based on an exponential weighted moving average, a base-line is calculated from the signal. Contractions are recognised on the basis of thresholds for minimum amplitude and duration. The developed algorithm calculates properties of these contractions, such as amplitude, duration, area and a motility index. In addition, the program automatically recognises normal motor patterns of the fasted human small intestine, such as the migrating motor complex, and aids in the identification of the postprandial motor pattern. Motor patterns are defined in terms of properties such as contraction frequency and propagation. In a validation procedure using conventional manual analysis, the program correctly identifies the number of individual contractions with a 98% confidence interval and also correctly recognises 96% of phase 3 motor activity.
Algorithms↗
Transient lower esophageal sphincter relaxations and esophageal body muscular contractile response in normal humans.
BACKGROUND & AIMS: Gastroesophageal reflux frequently occurs during spontaneous transient lower esophageal sphincter relaxations (TLESRs). The aim of this study was to determine the motor activity in the body of the esophagus during TLESRs in 10 healthy subjects. METHODS: Esophageal contractions were recorded 13,8,and 3 cm above a sleeve that measured LES pressure. A balloon was inflated 8 cm above the sleeve to induce an esophageal tonic contraction (artificial high-pressure zone). RESULTS: No relaxation of the artificial high-pressure zone was detected at the onset or during spontaneous TLESRs before gastroesophageal reflux. Esophageal acidification provoked no changes or increased the pressure in the artificial high-pressure zone by 47.9% +/- 12% When gastroesophageal reflux abruptly distended the esophagus (common cavity), a relaxation of the artificial high-pressure zone of 51.1% +/- 6.6% was observed in 78% of the instances. Deglutitive or secondary contractions during spontaneous TLESRs traveled down the esophagus in 96.5% of the instances. CONCLUSIONS: Stimuli that induced spontaneous TLESRs did not by themselves inhibit muscle contractility in the body of the esophagus. Acidification without distention of the lower esophagus frequently increased esophageal tonic contractility. Abrupt lower esophageal distention by reflux of air or acid partially relaxed the artificial high-pressure zone in the esophageal body, probably to assist gastric venting.
Adolescent↗
Update on the pathophysiology and management of gastro-oesophageal reflux disease: the role of prokinetic therapy.
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Drug Therapy, Combination↗
Secondary peristaltic contractions, like primary peristalsis, are preceded by inhibition in the human esophageal body.
Swallow-induced esophageal peristalsis is preceded by a wave of inhibition in the esophageal body. The aim of this study was to determine whether a similar wave of inhibition precedes secondary peristalsis. Primary and secondary peristalsis were studied in 6 healthy subjects. Inhibition was visualized as relaxation of an artificial high-pressure zone which was created in the esophageal body by the inflation of a small intraesophageal balloon. Secondary peristaltic contractions induced by injection of 10 ml of air in the proximal esophagus or secondary peristaltic contractions spontaneously occurring after repeated swallowing were preceded by inhibition similar to that observed in primary peristalsis (96.4 +/- 2.8%, 93.2 +/- 4.2% and 91.5 +/- 3.3%) respectively. It is concluded that physiologically triggered secondary peristaltic contractions are preceded by inhibition in the esophageal body.
Adult↗
Ambulatory manometry of the small bowel: indications and analysis.
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Diagnosis, Differential↗
Mono- and bispecific single-chain antibody fragments for cancer therapy.
Especially when dealing with solid cancers, single-chain antibody fragments (scFvs) have a lot of advantages. Due to their small size (27 kDa), these proteins clear more rapidly from the blood, and penetrate faster and deeper into tissues, than whole antibodies. Furthermore, the lack of constant regions ensures that they are not retained in tissues such as the liver and kidney. This reduces possible toxic side-effects. Single-chain construction is normally done by polymerase chain reaction (PCR). To decrease the overall cost of oligonucleotide primer synthesis, time-consuming primer design, multiple PCR reactions and individual PCR optimization, we designed a universal single-step overlap extension PCR protocol using hybridoma cDNA as a template. To overcome the lack of effector function, bispecific scFvs, consisting of an scFv produced against a tumour-associated antigen fused to a T cell marker-specific scFv, are being created, starting from already assembled scFv, by means of two additional PCR reactions. In this paper we describe both PCR methods that were successfully used to create scFvs against the human transferrin receptor, the human interleukin-2 receptor, the human CD3 molecule, a breast tumour-associated antigen and an anti-transferrin-anti-CD3 bispecific scFv.
Antibodies, Bispecific↗
Immunotherapy for cancer: construction, expression and functional characterization of chimeric antibodies.
Monoclonal antibodies (Mabs) are a potential key component for the treatment of cancer, because of their specificity and multiple effector functions. Hybridoma technology and progress in genetic engineering made it possible to customize antibody molecules, rendering them more suitable for selective application. A widely used technique is the construction of mouse-human hybrid molecules by recombinant DNA techniques. These so-called chimeric antibodies contain the murine variable (V) regions fused to the human constant (C) regions. In this report, a general approach is described for the production of chimeric antibodies. The gene segments encoding the murine variable heavy and light chain are isolated by the polymerase chain reaction and cloned into expression vectors containing the human gamma 1 heavy chain gene and the human K light chain gene, respectively. Subsequently, these constructs are transfected into a non-Ig-producing murine hybridoma, eg SP2/0 cells. The in vitro study of the functional characteristics and biological properties of the thus obtained chimeric antibodies are discussed.
Antibodies, Monoclonal↗
Is lung cancer associated with asbestos exposure when there are no small opacities on the chest radiograph?
This study was designed to test the hypothesis that the risk of lung cancer from asbestos exposure is confined to persons with radiographic evidence of pulmonary fibrosis. Occupational and smoking histories were obtained from 271 patients with a confirmed diagnosis of primary lung cancer and 678 referents (279 with other respiratory disease and 399 with cardiac disease). Histories were reviewed blind to assess the timing, duration, and probability of exposure to asbestos. To allow for a lag between asbestos exposure and the development of lung cancer, subjects were classified by the time they had spent in an occupation entailing definite or probable exposure more than 15 years before diagnosis. The presence and extent of fibrosis was assessed blindly from chest radiographs by three readers and scored for small opacities with the ILO 1989 International Classification of Radiographs of the Pneumoconioses. 93 (34.3%) cases had worked in an occupation with definite or probable asbestos exposure compared with 176 (25.8%) referents (crude odds ratio for lung cancer 1.49, 95% CI 1.09-2.04). After adjustment for age, sex, smoking history, and area of referral, the odds ratio (95% CI) was 2.03 (1.00-4.13) in the subgroup of 211 with a median ILO score for small parenchymal opacities of 1/0 or more, and 1.56 (1.02-2.39) in the 738 with a score of 0/1 or less (ie, those without radiological evidence of pulmonary fibrosis). These results suggest that asbestos is associated with lung cancer even in the absence of radiologically apparent pulmonary fibrosis.
Aged↗
Successful treatment of a squamous papilloma of the hypopharynx-esophagus by local injections of (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine.
Human papillomaviruses (HPV) are associated with benign lesions and show specificity towards the location or tissues that they infect. HPVs are responsible for warts. Among more than 60 different HPV types known to occur in humans, a strong association has been found between types 16 and 18 and cervical cancer, and such an association is also suspected for types 31, 33, 35, 45, 51, 52, and 56. We describe the effects of (S)-1-(3-hydroxy-2-phosphonyl-methoxypropyl)cytosine (HPMPC), following local intratumoral injection, in a 69-year-old woman with hypopharyngeal and esophageal papillomatous lesions, polymerase chain reaction (PCR) positive for HPV types 16 and 18, that relapsed after surgery and that also failed to respond to Nd-Yag laser photocoagulation and alpha-interferon treatment (6 x 10(6) U five times a week for 4 weeks followed by three times a week for 2 months). HPMPC was given at 1.25 mg/kg, with a sclerosing needle, through the biopsy channel of a video-endoscope, directly into the tumor, from March until July 1993 at seven different occasions. The first four injections were given at an interval of 1 week at the level of the hypopharynx. The next three injections were given at an interval of 3 to 5 weeks. During the fourth to the seventh session, half of the dose was injected into the hypopharyngeal and the other half into the esophageal tumor. Three further injections of HPMPC were administered at the level of the esophageal tumor in September 1993 with 2-week intervals. After HPMPC treatment, the lesions became smaller and flat until they completely disappeared.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗