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Biomedical subjects

J B Jansen

Publications and source records attributed to J B Jansen.

At least 37 records · Page 2Linked to original sources
PubMed2000

Effect of rectal distension on gallbladder emptying and circulating gut hormones.

BACKGROUND: Abnormalities of upper gut motility, including a delay of gastric emptying and small bowel transit, found in patients with constipation may be secondary to factors originating in the colon or rectum as a result of faecal stasis. The aim was to determine if stimulation of mechanosensory function by rectal distension affects postprandial gallbladder emptying and release of gastrointestinal peptides participating in control of upper gut motility. MATERIALS AND METHODS: Eight healthy volunteers were studied with an electronic barostat and a plastic bag positioned in the rectum. Intrabag pressure was maintained at minimal distension pressure + 2 mmHg on one occasion and on a pressure that induced a sensation of urge on the other. Gallbladder volume and plasma concentrations of cholecystokinin (CCK), pancreatic polypeptide (PP) and peptide YY (PYY) were measured before and after ingestion of a 450-kcal mixed liquid meal. RESULTS: Rectal distension enhanced maximum gallbladder emptying from 66 +/- 7% to 78 +/- 5% (P < 0.05). Distension tended to increase integrated plasma PYY from 77 +/- 30 pM min to 128 +/- 40 pM min in the first hour after the meal (P = 0.08) and it suppressed integrated plasma PP from 1133 +/- 248 pM min to 269 +/- 284 pM min in the second hour (P < 0.05). Integrated plasma CCK concentrations were not significantly affected. CONCLUSION: Mechanosensory stimulation of the rectum enhances postprandial gallbladder emptying and influences postprandial release of gut hormones involved in the regulation of gastrointestinal motility in healthy subjects. These mechanisms may play a role in the pathogenesis of the upper gastrointestinal motor abnormalities observed in constipated patients.

Adult↗
PubMed2000

Effects of Helicobacter pylori infection on endocrine and exocrine mucosal functions in the upper gastrointestinal tract.

BACKGROUND: Helicobacter pylori infection affects the concentration of regulatory peptides such as gastrin, somatostatin and cholecystokinin and the concentration and activity of glutathione and glutathione S-transferases in the gastric mucosa. METHODS: Literature review. RESULTS: Although some of these peptides have been known since the beginning of this century, their action has changed since the discovery of H. pylori infection in 1983. Chronic infection with H. pylori might lead to an increased risk in developing gastric cancer. Glutathione S-transferases are involved in the cellular detoxification of xenobiotics and other toxic compounds. Since there is a close inverse relationship between the activity of glutathione S-transferase and incidence of malignancies in the gastrointestinal tract, the possible relation between H. pylori infection and activity of glutathione S-transferases in the gastric mucosa is discussed. CONCLUSION: The effect of H. pylori infection on regulatory peptides and glutathione/glutathione S-transferases might play a role in the development of neoplastic changes of the H. pylori-infected gastric mucosa.

Animals↗
PubMed1999

Polymorphic expression of the glutathione S-transferase P1 gene and its susceptibility to Barrett's esophagus and esophageal carcinoma.

Factors determining individual susceptibility to esophageal cancer or premalignant Barrett's epithelium are still largely unclear. An imbalance between phase I drug metabolism [e.g., cytochrome P450 (CYP)] and phase II detoxification [e.g., glutathione S-transferase (GST)] may contribute to the development of these diseases. Polymorphic variants in the CYP1A1 gene were described leading to increased levels of bioactive compounds, whereas polymorphisms in GST genes often resulted in impaired detoxification. We studied the frequencies of polymorphic variants in CYP1A1, GSTP1, GSTT1, and GSTM1 genes in 98 patients with Barrett's epithelium and 34 patients with esophageal cancer. The results were compared with those obtained from 247 healthy blood donors. DNA was extracted, and PCR-RFLP methods were used to detect genetic polymorphisms. Chi2 analysis, Spearman rank correlation, and Wilcoxon rank sum tests were used for statistical evaluation. Polymorphisms in CYP1A1, GSTM1, and GSTT1 occurred at an equal frequency in patients and controls. Occurrence of the polymorphic GSTP1b variant in the GSTP1 gene resulted in a significantly lower GST enzyme activity (P < 0.05), and GSTP1b was found significantly more often in patients with Barrett's epithelium (70%; P < 0.001) and patients with esophageal adenocarcinoma (76%; P = 0.005), as compared to healthy blood donors (41%). In conclusion, presence of the GSTP1b allele leads to lower GST enzyme activity levels and, consequently, impaired detoxification. This most important esophageal GST isoform may, therefore, contribute to the development of Barrett's epithelium and adenocarcinoma.

Adenocarcinoma↗
PubMed1999

Characterization of the reactivity pattern of murine monoclonal antibodies against wild-type hepatitis B surface antigen to G145R and other naturally occurring "a" loop escape mutations.

The hepatitis B surface antigen (HBsAg) "a" domain harbors major B-cell epitopes. Viruses with mutations in this region emerge after vaccination or during hepatitis B immune globulin (HBIg) prophylaxis. A strain with G145R replacement has been almost invariably isolated as a major escape mutant. We investigated mutant antigen-antibody interactions with direct binding assays. G145R and 16 other naturally occurring recombinant HBsAg mutants were expressed in mammalian Cos-1 cells. The reactivity of a panel of 28 murine anti-hepatitis B surface antigen (anti-HBs) monoclonal antibodies to mutant antigens was measured with enzyme immunoassay and expressed as percentage compared with the wild-type (wt) HBsAg signal for each antibody. All point-mutated proteins displayed diffuse intracellular immunofluorescent labeling corresponding to a secretory pathway. Monoclonal antibodies (mAbs) were classified according to different binding patterns. The effect of mutations on antibody binding differs depending on the amino acid involved and on the location within the "a" loop. As expected, most antibodies had absent or negligible binding (<40%), notably with residue 145 replacements. However, we identified antibodies that reacted with conformational epitopes but nevertheless had adequate reactivity (>40%) with all mutant antigens, including G145R. The effect of G145R was more pronounced than that of G145A. A subgroup of antibodies had substantially increased recognition (>120%) of antigens with mutations in the first loop. We demonstrated that antibodies can be selected or combined that react with all mutants investigated, including G145R. These data offer perspectives for improving anti-HBs-based protection against hepatitis B.

Amino Acid Substitution↗
PubMed1999

Depression of plasma levels of cytokines and ex-vivo cytokine production in relation to the activity of the pituitary-adrenal axis, in patients undergoing major vascular surgery.

The relation between the immune and neuroendocrine response during surgery was studied. In 18 patients undergoing major vascular surgery, circulating interleukin (IL)-1beta and ex-vivo production of IL-1beta and tumour necrosis factor (TNF)-alpha were lower on day 1 after surgery compared to pre-operation values (-14+/-5%, P<0.05; -62+/-9%, P<0.05; and -31+/-54%, P<0.005, respectively). Circulating IL-1 receptor antagonist (IL-1ra) was higher on the 5th day post-operatively compared to pre-operation values (mean +640%+/-400, P<0.05). In a more detailed study in six patients, the ex-vivo production of IL-1beta and TNF-alpha started to decrease at induction of general anaesthesia and dropped to under 10% of initial values at the end of surgery. Circulating IL-1ra and ex-vivo production of IL-1ra started to increase at the end of surgery and remained elevated up to 6 days post-operatively. Plasma antidiuretic hormone (ADH) and adrenocorticotropic hormone (ACTH) increased during surgery, but cortisol remained unchanged. We demonstrate a depression of circulating pro-inflammatory IL-1beta and an increase of circulating anti-inflammatory IL-1ra during surgical stress. The ex-vivo production of IL-1beta and TNF-alpha was suppressed, indicating a downregulation of the production of these cytokines. This parallelled the hormonal reaction with high ADH and ACTH, but not of cortisol, suggesting that glucocorticoid is not the key-factor in downregulation of production and release of pro-inflammatory cytokines.

Adrenocorticotropic Hormone↗
PubMed1999

Evaluation of treatment regimens to cure Helicobacter pylori infection--a meta-analysis.

OBJECTIVE: To assess effectiveness of treatment to cure Helicobacter pylori infection. DATA SYNTHESIS: Meta-analysis of 666 manuscripts (full papers, abstracts, letters to the editor) identified through Medline and a manual search (1986 to January 1998). Data were overviewed by regression analysis with weighted random effects models. SUBJECTS: 53 228 patients with H. pylori infection. INTERVENTIONS: Patients were treated with 132 different medication combinations. MAIN OUTCOME MEASURE: Cure of H. pylori infection per protocol and intention-to-treat basis at least 28 days after treatment. RESULTS: The nationality of the patients and therapeutic regimen have a significant impact on the results, after correction for the heterogeneity in the precision of the cure rate caused by different study sizes and random effect for study. On the basis of the original sample size, cure rates of 80-85% were achieved using combinations of a proton-pump inhibitor or ranitidine bismuth citrate with two antibiotics including clarithromycin, amoxycillin and metronidazole or tinidazole. Comparable cure rates were also achieved using a combination of a proton-pump inhibitor or H2-receptor antagonist with bismuth subcitrate or tripotassium dicitrato bismuthate, metronidazole and tetracycline. The dose of clarithromycin influenced cure rates. Treatment duration did not influence the outcome. CONCLUSION: Several therapeutic regimens are eligible to cure H. pylori infection. However, none of the medication combinations were able to cure H. pylori infection in more than 85% of the patients assessed by intention-to-treat. The countries in which the studies were performed also had a significant impact on eradication rates.

Antacids↗
PubMed1999

Standard-dose lansoprazole is more effective than high-dose ranitidine in achieving endoscopic healing and symptom relief in patients with moderately severe reflux oesophagitis. The Dutch Lansoprazole Study Group.

BACKGROUND: In the treatment of reflux oesophagitis, H2-receptor antagonists are still widely used in spite of the apparent higher efficacy of proton pump inhibitors. In an attempt to compensate for the lower efficacy, H2-receptor antagonists are now increasingly being used at a higher dose. OBJECTIVE: To assess whether or not standard-dose lansoprazole (30 mg o.d.) is more effective than high-dose ranitidine (300 mg b.d.) in moderately severe reflux oesophagitis (grades II-III). METHODS: Lansoprazole or ranitidine was given to 133 patients for 4-8 weeks in a double-blind, randomized, parallel group, multicentre trial. RESULTS: The percentage of patients with endoscopically-verified healing was significantly higher on lansoprazole than on ranitidine both after 4 weeks (79% vs. 42%) and 8 weeks (91% vs. 66%), though smoking had a negative impact on oesophagitis healing with lansoprazole. Heartburn, retrosternal pain and belching improved significantly better with lansoprazole than with ranitidine, as did the patient-rated overall symptom severity. Relief of heartburn appeared somewhat faster with ranitidine, but was more pronounced with lansoprazole. The number of patients with adverse events was similar in both treatment groups. CONCLUSION: Standard-dose lansoprazole is better than high-dose ranitidine in moderately severe reflux oesophagitis.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1999

Influence of structurally different lipid emulsions on human neutrophil oxygen radical production.

BACKGROUND: The aim of this study was to evaluate immunomodulatory properties of lipid emulsions applied in parenteral nutrition by measuring neutrophil oxygen radical production (the 'respiratory burst') after lipid incubation. MATERIALS AND METHODS: Neutrophils, isolated from the blood of 10 healthy individuals, were incubated in medium or in lipid emulsions in a physiological concentration (2.5 mmol L-1) containing long-chain [Intralipid (LCT)], mixed medium and long-chain [Lipofundin (LCT/MCT)] or structured triglycerides (SL). After washing and stimulation with phorbol 12-myristate 13-acetate (PMA) or serum-treated zymosan (STZ) particles, the respiratory burst was evaluated by measuring maximum oxygen uptake, superoxide and hydrogen peroxide production rates and chemiluminescence. RESULTS: Unlike LCT and SL, LCT/MCT increased PMA- and STZ-induced oxygen uptake rate by 45% and 31% respectively (both P = 0.006 compared with medium) as well as superoxide (+56%, P = 0.006) and hydrogen peroxide (+14%, P = 0.04) production, within 5 min after stimulation. Increased LCT/MCT-mediated early respiratory burst was confirmed by decreased PMA- (-65%) and STZ-stimulated (-54%) chemiluminescence peak time (time after stimulation to peak) in combination with unchanged peak height (maximum rate of radical production). Late respiratory burst (within 2 h) of LCT/MCT, indicated by overall luminescence (overall radical production), remained unchanged (PMA) or decreased (STZ, P = 0.02). The addition of 2.5 mmol L-1 LCT/MCT or MCT emulsion to unstimulated neutrophils, in contrast to LCT and SL, resulted in significant luminescence. CONCLUSIONS: Early neutrophil respiratory burst is accelerated by the LCT/MCT emulsion Lipofundin, whereas LCT (Intralipid) and structured lipid emulsions exert no effect. MCT-containing emulsions, contrary to LCT and structured lipid emulsions, can induce oxygen radical production in unstimulated neutrophils.

Adult↗
PubMed1999

Glutathione and glutathione-related enzymes in decidua and placenta of controls and women with pre-eclampsia.

Pre-eclampsia is a major complication of pregnancy with high morbidity and mortality rates. The aetiology is still unclear but impaired detoxification or enhanced levels of reactive (oxygen) metabolites may contribute to the development or maintenance of pre-eclampsia. Glutathione and glutathione-related enzymes, as one of the major detoxificating and free-radical scavenging systems, may play a role in controlling the disease. Seventeen normotensive pregnant women and 24 pre-eclamptic women were investigated prospectively with respect to placental and decidual levels of total glutathione (GSH), glutathione S-transferase activity (GST), selenium-dependent glutathione peroxidase (SeGPX) and total glutathione peroxidase activity (TGPX, both selenium- and non-selenium-dependent GPX). Decidual levels of glutathione and related enzymes were compared with placental levels, and the investigated parameters in pre-eclampsia were compared with those in normotensive pregnancy by the Mann-Whitney U -test. Clinical data were correlated with biochemical parameters by Spearman's correlation test. Glutathione levels were significantly higher in decidua as compared with placenta. Glutathione levels were elevated in pre-eclampsia and HELLP (haemolysis, elevated liver enzymes, low platelets) as compared to normotensive pregnancy for decidua and in the placenta of patients with pre-eclampsia only. Glutathione S-transferase activity was not different between the two groups. In the placenta of patients with pre-eclampsia+HELLP, total glutathione peroxidase activity was elevated versus controls. Selenium-dependent glutathione peroxidase activity was higher in decidua versus placenta and in decidua of pre-eclamptic versus control subjects. Enhanced glutathione concentrations and glutathione peroxidase activities were often found in placenta and decidua in pre-eclampsia, probably as a compensatory mechanism to prevent further damage by peroxides, (oxygen) radicals or other toxins in the placenta or in the feto-placental interface.

Adult↗
PubMed1999

Impaired release of peptide YY in patients with proctocolectomy and ileal pouch-anal anastomosis.

BACKGROUND: Peptide YY (PYY) is a gut hormone produced by endocrine cells in the distal small bowel, colon, and rectum. PYY inhibits upper gastrointestinal secretory and motor functions. The aim of this study was to determine whether basal and postprandial plasma PYY levels in patients with proctocolectomy and ileal pouch-anal anastomosis (IPAA) are reduced and to determine the relationship between plasma PYY and plasma cholecystokinin (CCK) levels. METHODS: Plasma concentrations of PYY and CCK were measured before and after ingestion of a standardized breakfast in 14 IPAA patients and in 12 healthy control subjects. RESULTS: Basal PYY was slightly lower in the IPAA patients than in the controls (8.3 +/- 0.3 versus 9.3 +/- 1.1 pM; not significant). Ingestion of the meal induced a small but significant increase of PYY to a maximum of 10.9 +/- 0.9 pM in patients. Integrated postprandial PYY was markedly reduced in patients when compared with the controls (1725 +/- 66 pM*180min versus 3194 +/- 480 pM*180 min; P < 0.005). Plasma PYY concentrations were inversely correlated with plasma CCK concentrations in the 2nd and 3rd h after the meal (r = -0.86; P = 0.0001). CONCLUSION: PYY release in response to meal ingestion is markedly reduced but not completely absent in patients with proctocolectomy and ileal pouch-anal anastomosis. The inverse relationship between circulating PYY and CCK in the late postprandial phase is compatible with a negative feedback regulation of CCK release by endogenous PYY.

Adult↗
PubMed1999

Effects of age on concentrations of plasma cholecystokinin, glucagon-like peptide 1, and peptide YY and their relation to appetite and pyloric motility.

BACKGROUND: Aging is associated with a decrease in appetite and a slowing of gastric emptying. The gastrointestinal hormones cholecystokinin (CCK), glucagon-like peptide 1 (GLP-1), and peptide YY (PYY) may mediate these changes. OBJECTIVE: We investigated whether aging influenced the secretion of CCK, GLP-1, and PYY and their effects on appetite and pyloric motility. DESIGN: Eight healthy older (65-80 y) and 7 younger (20-34 y) men received isoenergetic (12.1 kJ/min) intraduodenal infusions of lipid and glucose for 120 min on separate days. Plasma CCK, GLP-1, and PYY concentrations were measured. RESULTS: Plasma CCK concentrations were higher in older than in younger subjects (P = 0.004) as a result of higher baseline values (4.7+/-0.2 compared with 3.2+/-0.2 pmol/L; P < 0.0001) and a greater rise during lipid infusion (increase from baseline: 7.1+/-0.5 compared with 5.3+/-0.6 pmol/L; P = 0.048). Plasma GLP-1 and PYY concentrations were not significantly different between groups. The decrease in hunger during intraduodenal lipid infusion was inversely related to the increase in CCK, GLP-1, and PYY in younger but not older subjects. During intraduodenal lipid infusion, the increase in isolated pyloric pressure wave (IPPW) frequency was positively related to GLP-1 and PYY and the increase in IPPW amplitude was positively related to CCK in older but not younger subjects, whereas the increase in IPPW amplitude and pyloric tone was negatively related to GLP-1 and PYY in younger subjects. CONCLUSIONS: Human aging is associated with increased CCK concentrations, which may contribute to the slowing of gastric emptying, mediated by increased pyloric motility. The role of increased plasma CCK concentrations in mediating the age-related decrease in appetite remains to be established.

Adult↗
PubMed1999

The prognostic value of gastrointestinal morbidity for gastric cancer.

OBJECTIVE: A history of gastrointestinal disease is a risk factor for organic gastrointestinal disorders overall. We conducted a retrospective case-control study to explore whether a history of gastrointestinal disease is of prognostic value for gastric cancer. METHODS: Forty-six patients with gastric cancer were identified from a dynamic population of approximately 12,000 patients followed since 1971 in four general practices. The control subjects without gastric cancer were matched one-on-one according to age, general practice, sex and observation period. Data on gastrointestinal morbidity in the period before gastric cancer was diagnosed were obtained from the Continuous Morbidity Registration. RESULTS: The mean observation period between the date of enrolment in the registration and the first diagnosis of gastric carcinoma was 12 years. Although every patient with gastric cancer ultimately will develop gastrointestinal complaints, 28 of these patients had no previous gastrointestinal morbidity, in comparison with 26 control subjects. Furthermore, patients who developed gastric cancer did not have more frequent gastrointestinal morbidity in their past than the control subjects (odds ratio 0.80, 95% CI 0.32-2.03). CONCLUSIONS: Our results suggest that a history of gastrointestinal morbidity is not of prognostic value for gastric cancer. Focusing attention on patients with a past history of gastrointestinal symptoms to detect gastric cancer may be of little value.

Aged↗
PubMed1999

Mortality trend from cancer of the gastric cardia in The Netherlands, 1969-1994.

BACKGROUND: Time trends of cancer of the gastric cardia differ between populations and the reasons are not fully understood. The object of this study was to investigate the occurrence of cancer of the gastric cardia in descriptive relation to age at death, calendar period, birth cohort and gender in the Netherlands between 1969 and 1994. METHODS: Data on the number of people with cancer of the gastric cardia as the underlying cause of death from 1969 to 1994 were obtained from annual publications by the National Causes of Death Registry of Statistics Netherlands. To estimate the separate effects of age, calendar period and birth cohort on the trend in mortality, a simultaneous analysis of these factors was performed using a log-linear Poisson model. RESULTS: In 1969, the mortality rates from cancer of the gastric cardia for males and females per 100,000 people were 2.1 and 1.1; in 1994 the mortality rates were 1.5 and 0.7, respectively. Examination of the time trend suggested that mortality for cancer of the gastric cardia may reflect a period phenomenon, although a cohort effect may have also contributed to the observed time trend. Furthermore, more males than females died from cancer of the gastric cardia. The difference was most striking in the younger age categories. CONCLUSION: In this Dutch population, the age-period-cohort-gender analysis indicated that the mortality rates decreased after the period 1975-1979 which might be explained by a decrease in exposure to risk factor(s) or an increase in exposure to protective factor(s).

Adult↗
PubMed1999

Abnormalities of upper gut motility in patients with slow-transit constipation.

OBJECTIVE: To further delineate motor activity of the upper gastrointestinal tract in patients with slow-transit constipation. DESIGN: A prospective study comparing healthy volunteers with patients with a clinical diagnosis of slow-transit constipation. METHODS: Eighteen patients with clinical diagnosis of slow-transit constipation and 10 healthy controls were included in the study. Fasting antroduodenal motility was measured by perfusion manometry for at least one complete cycle of the migrating motor complex or a maximum of 300 min. Oesophageal manometry, gastric emptying and orocaecal transit time measurements were also performed. RESULTS: At least one complete cycle of the migrating motor complex was observed in all controls, but in only nine patients (P < 0.01 versus control). The migrating motor complex cycle was incomplete (n = 5) or phase 3 activity was absent (n = 4) in the other patients. The incidence of clustered contractions was significantly increased in slow-transit constipation (P = 0.05 versus controls). The area under the contraction curve during late phase 2 (1509+/-296 mmHg x s) in patients with a complete cycle was significantly smaller than that in controls (2997+/-614 mmHg x s; P = 0.05). Orocaecal transit time was not significantly different among patients and controls, but oesophageal motility was abnormal in five of 18 patients and gastric emptying was abnormal in eight of 15 patients. CONCLUSION: Abnormalities of upper gut motility occur frequently in patients with slow-transit constipation. Interdigestive antroduodenal motility is characterized by (i) absence or prolonged duration of the migrating motor complex, (ii) an increased number of clustered contractions, or (iii) a decreased motility during late phase 2 of the migrating motor complex.

Adult↗
PubMed1999

Low glutathione and glutathione S-transferase levels in Barrett's esophagus as compared to normal esophageal epithelium.

Patients with Barrett's esophagus, wherein squamous epithelium has been replaced by columnar epithelium, have an increased risk for developing esophageal adenocarcinoma as compared to the general population. Glutathione S-transferase (GST), a family of detoxification enzymes consisting of class alpha, mu, pi, and theta isoforms, is involved in detoxification of carcinogens and low levels of these enzymes correlated with high cancer risk. We have now compared GST enzyme activity, GST isoenzyme composition and glutathione (GSH) content of Barrett's mucosa with that of adjacent normal squamous epithelium. Biopsy specimens of 98 patients with Barrett's esophagus were taken from both Barrett's and adjacent normal squamous epithelium. GST enzyme activity towards 1-chloro-2,4-dinitrobenzene was measured, and GST isoenzyme levels were determined by densitometrical analyses of western blots after immunodetection with monoclonal antibodies. Total GSH content was determined by high-performance liquid chromatography after conjugation with monobromobimane. Wilcoxon's signed rank test and Spearman correlation analyses were used for statistical evaluation. As compared with adjacent normal squamous epithelium, GST enzyme activity in Barrett's epithelium was reduced by 35%, and GST mu, GST pi and GSH levels were reduced by 24%, 30%, and 63%, respectively. However, the minor GST alpha and GST theta levels were higher in Barrett's epithelium (by 625% and 33%, respectively). High levels of GSH and GSTs in general are correlated with protection against cellular or cytogenetic damage. The observed reduction in GSTs and GSH in Barrett's epithelium may therefore contribute to the increased cancer risk in this tissue.

Adult↗
PubMed1999

Plasma glutathione S-transferase Pi 1-1 measurements in the study of hemolysis in hypertensive disorders of pregnancy.

OBJECTIVE: To investigate the value of plasma glutathione S-transferase Pi1-1(GSTP1-1) measurements in the assessment of hemolysis in hypertensive disorders of pregnancy. METHODS: Plasma GSTP1-1 and haptoglobin levels and serum lactate dehydrogenase (LDH) activity were measured in 81 healthy nonpregnant female blood donors between 20 and 40 years of age, 41 women during uncomplicated normotensive pregnancy, 35 women with pregnancy-induced hypertension, 67 women with preeclampsia, and 34 women with the HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome. Levels in hypertensive pregnancies were compared to levels in normotensive pregnancy, and levels in normotensive pregnancy were compared to levels in blood donors by the Mann-Whitney U-test. RESULTS: Median GSTP1-1 and LDH levels were significantly increased (p < 0.01) and haptoglobin significantly decreased (p < 0.01) in preeclampsia and the HELLP syndrome as compared to normotensive pregnancy. Both GSTP1-1 and LDH levels were significantly higher in normotensive pregnant women as compared to nonpregnant women (p < 0.0001). The percentage of preeclamptic patients (26.9%) or patients with the HELLP syndrome (73.5%) with elevated GSTP1-1 levels was lower than those with elevated LDH (38.8% and 100%, respectively) or decreased haptoglobin levels (41.8% and 97%, respectively). CONCLUSIONS: We conclude that plasma GSTP1-1 levels may provide useful information on hemolysis in hypertensive disorders of pregnancy in addition to serum LDH activity and plasma haptoglobin levels and that the degree of hemolysis in hypertensive disorders of pregnancy, especially in the HELLP syndrome, is probably less prominent than generally assumed.

Adult↗
PubMed1998

Effect of lintitript, a new CCK-A receptor antagonist, on gastric emptying of a solid-liquid meal in humans.

The role of cholecystokinin (CCK) in the regulation of gastric emptying of physiological meals containing solids and liquids in humans remains controversial. We studied the role of endogenous CCK in the emptying of a solid/liquid meal administering the new, highly specific and potent CCK-A receptor antagonist lintitript. Gastric emptying was assessed in nine healthy male volunteers using a randomized, double blind, two-period crossover design with oral lintitript (15 mg 1 h prior to meal intake) or placebo on two different days. After ingestion of a pancake (570 kcal) labelled with 500 microCi of 99mTc-sulfur colloid and 500 ml 10% dextrose containing 80 microCi. 111In-DTPA, subjects were studied in a sitting position, using a dual-headed gamma camera. Plasma CCK and pancreatic polypeptide (PP) were measured by a specific RIA. Lintitript distinctly accelerated gastric emptying of solids, while gastric emptying of liquids was not significantly altered. The lag period was shortened by 20% (P<0.05), AUC and half emptying time of solid emptying were lowered by 12% and 13%, respectively (P<0.03). Lintitript markedly increased postprandial plasma CCK release (P<0.001) while distinctly reducing postprandial PP levels (P<0.01) as compared to placebo. These data provide further evidence for a significant role of CCK in the regulation of gastric emptying of solids. The study demonstrates for the first time the marked gastrokinetic properties of the new CCK-A receptor antagonist lintitript in humans.

Adult↗