PubMed HealthSearch

Biomedical subjects

F J Hoek

Publications and source records attributed to F J Hoek.

At least 19 recordsLinked to original sources

Critical difference between serial measurements of CK-MB mass to detect myocardial damage.

To assess the critical difference in serial measurements of CK-MBmass and the ability of this critical difference to detect myocardial damage, we studied 110 patients in whom an acute myocardial infarction (AMI) had been ruled out. Blood samples were drawn at 3, 4, 5, 6, 7, 8, 12, 16, 20, and 24 h after onset of symptoms. With a critical difference of 72.6%, an increase of >2.0 microg/L between two CK-MBmass measurements was determined to be significant. Twenty-three of the non-AMI patients had an increase in CK-MBmass >2.0 microg/L, but five of these did not have an abnormal concentration of troponin T (i.e., not >0.1 microg/L). Also among the 110 non-AMI patients, 22 did have an abnormal troponin T value, 18 of whom (82%) also had CK-MBmass increased by >2.0 microg/L. In 20 of the 23 patients with an increase in CK-MBmass >2.0 microg/L, this increase was detected from the values for two samples collected at 5 and 12 h after onset of symptoms. In conclusion, using the critical difference for CK-MBmass defined as an increase >2.0 microg/L detected myocardial damage in patients without AMI.

Adult

Intestinal permeability, circulating endotoxin, and postoperative systemic responses in cardiac surgery patients.

OBJECTIVES: To determine whether intestinal permeability increases during cardiac operations, and whether the degree of endotoxemia is related to this increase. Furthermore, to determine whether intestinal permeability is related to the hemodynamic state during operation and to postoperative systemic responses. DESIGN: Prospective study. SETTING: University hospital. PARTICIPANTS: Twenty-three male patients undergoing elective coronary artery bypass surgery. INTERVENTIONS: Before surgery and during the fifth postoperative day, 100 mL of a solution containing L-rhamnose and cellobiose were administered orally. MEASUREMENTS AND MAIN RESULTS: Intestinal permeability was assessed by measuring the urinary excretion of L-rhamnose and cellobiose. Endotoxin concentrations in blood and prime fluid, hemodynamics, oxygen consumption, gas exchange, fluid balance, and the dose of vasoactive drugs were measured. Systemic responses were assessed by measuring hypermetabolism, circulatory support, and gas exchange. Intestinal permeation of cellobiose, reflecting paracellular transport, significantly increased during operation (p < 0.01), and correlated with the amount of circulating endotoxin (r2 = 0.46; p < 0.01). A high dose of ephedrine administered during operation, low baseline central venous pressure, and a less positive fluid balance during operation were associated with high intestinal permeability (r2 = 0.7; p < 0.01). Intestinal permeability was related to postoperative systemic responses (r2 = 0.49; p < 0.01). CONCLUSIONS: This study shows that during elective coronary artery bypass operations intestinal permeability between cells may increase. The degree of endotoxemia is related to this increase. Increased intestinal permeability is related to the use of ephedrine, especially during hypovolemia, and to postoperative systemic responses. Although a causative relation is not shown, these results might indicate that hypovolemia and vasoconstriction should be avoided during the operation.

Aged

Quinine pharmacokinetics in young children with severe malaria.

Children less than two years of age represent a substantial proportion of severe malaria cases in Africa. The standard treatment is parenteral quinine, but little is known about the pharmacokinetics and toxicity of quinine in this age group. We have studied the pharmacokinetics of quinine after intravenous (iv) and intramuscular (im) administration in a group of 20 children less then two years of age with severe malaria. A loading dose of 20 mg/kg of quinine dihydrochloride was followed by 10 mg/kg at 12-hr intervals. The im quinine was very rapidly absorbed, reaching high peak concentrations of 16.4 +/- 3.7 mg/L (mean +/- SD) in 1.1 +/- 0.4 hr. Mean peak levels after iv administration were also high (17.5 +/- 2.4 mg/L). Free quinine levels at 4 hr postadministration ranged from 0.27 to 1.89 mg/L (0.87 +/- 0.53 mg/L). At 2 hr and 4 hr after commencing treatment, an electrocardiogram showed a significant lengthening of the QRS interval compared with baseline (15.6 +/- 21.4%; P = 0.007 and 17.3 +/- 21.9%; P = 0.006 at 2 hr and 4 hr, respectively), whereas this was not observed in a control group of nine older children (age range = 24 months to 10 years) receiving the same im dosage regimen. Free and total quinine levels were not significantly correlated with changes in the QRS interval. Levels of alpha1-acid glycoprotein, which binds quinine within the circulation, did not differ between the younger and the older children. These findings raise the possibility that young children are more susceptible to quinine toxicity than older children, and indicate the need for further evaluation of quinine dosage regimens in this age group.

Absorption

The usefulness of CA15.3, mucin-like carcinoma-associated antigen and carcinoembryonic antigen in determining the clinical course in patients with metastatic breast cancer.

Levels of mucin-like carcinoma-associated antigen (MCA), CA15.3 and carcinoembryonic antigen (CEA) were measured in consecutive serum samples of 40 women with metastatic breast cancer. A change in antigen level of more than 25%, either an increase or a decrease, was considered to predict progressive or responsive disease respectively. A change of less than 25% was considered to predict stable disease. MCA, CA15.3 and CEA were elevated in the serum of 68%, 76% and 48% of the patients respectively (P < 0.05). The overall prediction of clinical course was similar for all three markers. A more than 25% increase of MCA, CA15.3, and CEA was observed in 61%, 54% and 36% respectively. The predictive value of a more than 25% increase was high for all three markers: 94%, 94%, 83%. Changes in marker levels were correlated with each other. Logistic regression analysis showed that combining MCA and CA15.3 did not improve the prediction further. In conclusion, these tumour markers may help in evaluating the disease course and there is no advantage in combining MCA and CA15.3.

Aged

Simultaneous assessments of exocrine pancreatic function by cholesteryl-[14C]octanoate breath test and measurement of plasma p-aminobenzoic acid.

Two noninvasive tests for assessing pancreatic exocrine function, the cholesteryl-[14C]octanoate breath test and the HPLCN-benzoyl-tyrosyl-p-aminobenzoic acid/p-aminosalicylic acid (NBT-PABA/PAS) test, were simultaneously performed in nine patients with pancreatic exocrine insufficiency due to chronic pancreatitis and in nine healthy volunteers. 14CO2 output in breath and plasma PABA concentration rose slowly in patients but increased rapidly in healthy subjects. The measurement time giving the best discrimination between both groups was 120 min for the cholesteryl-[14C]octanoate breath test and 90 min for the plasma PABA test. At these points, both single-sample tests had essentially identical diagnostic sensitivity. The diagnostic sensitivities of the two single-sample tests were equal to that of the cumulative 6-h urinary PABA recovery and the cumulative 6-h urinary PABA/PAS ratio. We conclude that, for both the cholesteryl-[14C]octanoate breath test and the plasma PABA test, a single test sample is sufficient for rapid detection of impaired exocrine pancreatic function.

4-Aminobenzoic Acid

Comparative effects of adjuvant cimetidine and omeprazole during pancreatic enzyme replacement therapy.

In a double-blind, randomized crossover study, the hypotheses were tested that more powerful inhibition of gastric acid secretion by adjuvant omeprazole further improves the efficacy of pancreatic enzyme replacement therapy compared to adjuvant cimetidine and that excluding the influence of pH-related factors, by virtually complete inhibition of gastric acid secretion with 60 mg omeprazole daily, does not lead to total elimination of steatorrhea. During both adjuvant cimetidine and omeprazole treatment, fecal fat excretion was significantly lower compared to pancreatin monotherapy (P < 0.01). Omeprazole showed a trend towards a more favorable decrease of fecal fat excretion compared to cimetidine but no statistically significant difference. Steatorrhea was almost never abolished, even during 60 mg omeprazole daily. Generally, pH-related factors are considered to explain an inadequate therapeutic response during pancreatic enzyme replacement therapy. However, this study indicates that in vivo other factors also play a significant role.

Adult

A prospective study of peritoneal transport in CAPD patients.

A prospective two year follow-up study of the functional characteristics of the peritoneal membrane was conducted in 61 CAPD patients. Peritoneal transport of solutes, calculated by mass transfer area coefficients for urea and creatinine, peritoneal clearances for proteins, percentage of absorption of glucose, as well as net ultrafiltration were measured every four months. After five months on CAPD a decrease was found for the transport of most solutes (P < 0.05, mean values, ml/min/1.73 m2): urea 18.1 to 16.2, creatinine 9.5 to 8.4, IgG 0.049 to 0.040 and alpha 2-macroglobulin 0.020 to 0.015, as well as for the absorption of glucose (57.9 to 53.2%, P < 0.05). Net ultrafiltration increased simultaneously from 44.6 to 100.5 ml/4 hr/1.73 m2, P < 0.05. From five months to two years on CAPD a significant increase in the transport of all solutes except alpha 2-macroglobulin was found, as well as a decrease in net ultrafiltration. Peritoneal transport at the end of the study was not significantly different from the starting values. Our findings indicate an initial effect of CAPD itself on peritoneal transport, probably due to the recent start of the treatment. Baseline values were reached after five months on CAPD. Thereafter a gradual increase in peritoneal solute transport occurred during two years of treatment. This can be explained by an increase in the effective peritoneal surface area.

Adult

Model for whole body production of tumour necrosis factor-alpha in experimental endotoxaemia in healthy subjects.

1. Tumour necrosis factor-alpha is considered an important mediator in the pathophysiology of several diseases. Although much information is available about the serum concentrations of this cytokine in these illnesses, little is known about the production of tumour necrosis factor-alpha in disease in vivo. 2. In the present study we aimed to estimate the extent and the kinetics of whole body tumour necrosis factor-alpha synthesis in experimental endotoxaemia in six healthy humans. For this purpose we first examined the pharmacokinetic behaviour of an intravenously injected bolus of recombinant human tumour necrosis factor-alpha (50 micrograms/m2) in another group of six normal subjects. We then calculated the total amount of tumour necrosis factor-alpha produced after intravenous injection of endotoxin (2 ng/kg) as the product of the systemic clearance of recombinant human tumour necrosis factor-alpha (9.5 +/- 5.0 ml min-1 kg-1) and the area under the tumour necrosis factor-alpha concentration-time curves in the endotoxaemic subjects. 3. Recombinant human tumour necrosis factor-alpha showed evident two-compartment kinetics with an initial rapid disappearance (t1/2 5.1 +/- 2.2 min) and a terminal slower elimination (t1/2 49 +/- 5 min). Tumour necrosis factor-alpha synthesis after endotoxin varied markedly between individuals, ranging from 11.8 to 114.1 micrograms (52.7 +/- 34.7 micrograms). The changes in time of the serum concentrations of tumour necrosis factor-alpha after administration of endotoxin could be accurately described with an adapted two-compartment open model that incorporated both rapid tumour necrosis factor-alpha production (74% of the total amount) and slow tumour necrosis factor-alpha production (26%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Mucosal tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-8 production in patients with Helicobacter pylori infection.

We investigated whether tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and interleukin-8 (IL-8) are involved in the inflammatory reaction of Helicobacter pylori infection. In 23 patients with H. pylori infection and 16 patients with negative cultures for H. pylori and normal antral mucosa, the mucosal production of TNF-alpha, IL-1 beta, and IL-8 was measured in antral biopsy specimens after 23 h of in vitro culture. The levels of TNF-alpha and IL-1 beta appeared to be significantly higher in H. pylori-positive patients (p = 0.0002 for both TNF-alpha and IL-1 beta). IL-8 production was also higher in H. pylori-infected subjects, but this difference did not reach statistical significance (p = 0.057). No significant differences were found between the level of the cytokines in H. pylori-infected patients with or without duodenal ulcer disease. A strong correlation was found between the production of IL-1 beta and IL-8. The biologic effects of these cytokines may explain the conspicuous recruitment, influx, and activation of neutrophils in the gastric mucosa during H. pylori infection.

Adult

Cancer antigen 125 is locally produced in the peritoneal cavity during continuous ambulatory peritoneal dialysis.

The local production of cancer antigen (CA) 125 in the peritoneal cavity of 14 continuous ambulatory peritoneal dialysis patients was studied. In addition, the relationship between the concentration of mesothelial cells and CA 125 in the peritoneal dialysate effluent was examined. The median results and ranges were as follows: plasma CA 125 14 U/mL (range 10-23), dialysate CA 125 18 U/mL (range 5.2-76), dialysate/plasma ratio 1.9 (range 0.61-5.4), and number of mesothelial cells 400/mL (range 10-5000). Peritoneal concentrations of mesothelial cells and CA 125 were positively correlated (r = 0.50, p < 0.01). Using a monoclonal antibody, CA 125-positive cells were found in the cytospin preparations of the cells of dialysis effluents. All these CA 125 positive cells were also positive for cytokeratin used as a mesothelial cell marker. In vitro experiments using mesothelial cells in monolayers showed a linear increase in CA 125 concentration both in time and in relation to the number of mesothelial cells. From these experiments a production rate of 24 U/hour/10(6) cells could be calculated. It is therefore concluded that CA 125 is locally produced in the peritoneal cavity during CAPD and that the mesothelial cells are the major source of this CA 125.

Antigens, Tumor-Associated, Carbohydrate

Interleukin-6 mediates host defense responses induced by abdominal surgery.

BACKGROUND: Cytokines have been implicated as pivotal mediators of the host defense reaction. In patients undergoing surgery we investigated the relationship between such mediators and postoperative host defense responses. METHODS: Tumor necrosis factor (TNF) was determined with an immunoradiometric assay, interleukin (IL)-6 by a B9-cell bioassay, and endotoxin by a chromogenic limulus lysate assay. C-reactive protein, alpha 1-antitrypsin, and alpha 2-macroglobulin were quantified by nephelometric assay. RESULTS: In 19 consecutive patients undergoing pancreaticoduodenectomy, a large increase in portal, and a significantly lower increase in peripheral, IL-6 levels was observed. No significant increase in TNF levels was noted. Fever developed in 16 patients within 24 hours (84%). The highest peripheral IL-6 levels correlated logarithmically (R = 0.59; p = 0.0039) with the peak body temperatures. C-reactive protein levels correlated with IL-6 levels (R = 0.49; p = 0.020). Increased IL-6 levels were observed in all nine patients undergoing either hemihepatectomy, breast reduction, or extensive breast reconstruction; however, only patients undergoing hemihepatectomy had endotoxemia. CONCLUSIONS: We conclude that abdominal surgery causes acute release of IL-6, but not TNF, in the portal circulation. IL-6 seems to be a major endogenous mediator of fever and the acute-phase response. The presence of endotoxin might be synergistic but is not obligatory for the host defense response after surgical trauma.

Acute-Phase Proteins

The initial decrease in effective peritoneal surface area is not caused by an increase in hematocrit.

The possible relationship between initial changes in functional characteristics of the peritoneal membrane in time and hemoglobin (Hb) or hematocrit (Ht) was analyzed as part of a prospective longitudinal study. The patients were investigated twice: the first time within 3 months after the start of continuous ambulatory peritoneal dialysis (CAPD), and again 4 months later. Mass transfer area coefficients (MTC) for low molecular weight solutes and net fluid removal were calculated during a 4-hour dwell, glucose 1.36%. Thirty-four patients were analyzed. MTC (mean +/- SD, mL/min/1.73 m2), were higher during the first examination: urea 22.6 versus 19.9, p < 0.05; lactate 15.6 versus 13.8, p < 0.001; creatinine 10.5 versus 9.3, p < 0.05; glucose 9.4 versus 7.9, p < 0.001. Net fluid removal was lower during the first examination: 28 versus 99 mL/min/1.73 m2, p < 0.05. Hb and Ht increased between the two examinations (Hb: 5.4 vs 6.1 mmol/L, p < 0.001: Ht: 0.26 vs 0.29, p < 0.001). No relation was found between the absolute or relative change in Hb or Ht and the absolute or relative change in solute and fluid transport between the same examinations. In conclusion, Hb and Ht increased between the first and second examinations. The simultaneously observed changes in peritoneal transport kinetics could not be attributed to changes in Hb or Ht. Therefore, the changes in transport kinetics during the first months on CAPD are probably due to the recent start of the treatment, possibly by an increase in peritoneal surface area. Local irritation by the dialysate may be the causative mechanism.

Adult

A comparison of CA-549 with CA 15-3 and MCA in patients with metastatic breast cancer.

CA 15-3, MCA, and CA-549 levels were determined in the serum of 56 patients with metastatic breast cancer, all of whom had visceral and/or bone metastases. CA 15-3 was positive in the serum of 37 patients, MCA in the serum of 38 patients, and CA-549 in the serum of 39 patients. All 3 markers were positive in 36 patients, and all 3 were negative in 16 patients. In the serum of 4 patients only 1 or 2 markers were slightly elevated. Thus, the results were identical in 52 of the 56 patients. It is concluded that CA 15-3, MCA, and CA-549 are sensitive markers for advanced breast cancer, and that no advantage can be expected by combining them.

Antigens, Neoplasm

Evidence of metabolic activity of adult and fetal rat hepatocytes transplanted into solid supports.

This study was undertaken to assess the metabolic effect of fetal and adult hepatocyte transplantation in the Gunn rat, genetically incapable of bilirubin conjugation. A comparison was made between fetal and adult hepatocytes transplanted into the spleen, and those injected into polytetrafluoroethylene (PTFE) solid supports that had previously been implanted intraperitoneally. Between 4 and 12 weeks after intrasplenic transplantation of adult liver cells, serum bilirubin was significantly decreased when compared with control animals (39.6 +/- 5.6%; P less than 0.01 vs. controls). Intrasplenic transplantation of fetal hepatocytes resulted in a maximal decrease of 33.2 +/- 9.1% at 8 weeks postoperatively (P less than 0.02 vs. controls). Similar declines of serum bilirubin levels were found after transplantation of adult or fetal liver cells into the solid supports. At 12 weeks after transplantation, bilirubin conjugates were detectable in the bile of all animals that underwent intrasplenic hepatocyte transplantation and in 60% of those that underwent the solid support procedure, whereas none could be detected in control animals. Histological evidence of surviving cells was obtained in all but one animal at 12 weeks, and confirmed at 12 months postoperatively. It is concluded that the PTFE solid support technique offers an attractive alternative to the intrasplenic route, and that both fetal and adult hepatocytes, transplanted in either way still exert their conjugating activity after 12 weeks.

Animals

Evaluation of the performance of commercial test kits for detection of Helicobacter pylori antibodies in serum.

We have compared the sensitivities, specificities, and predictive values of three commercial serological assays for the diagnosis of Helicobacter pylori infection. A qualitative latex method (Pyloriset; Orion Diagnostics), a semiquantitative enzyme-linked immunosorbent assay (ELISA) (GAP test IgG; Bio-Rad), and a quantiative ELISA (Helico-G; Porton Cambridge) were used in 109 untreated dyspeptic patients. The presence of H. pylori was established when the results of culture and/or histology of the gastric biopsies taken were positive. The prevalence of H. pylori infection was 62% (52% in 42 patients younger than 45 years of age and 69% in 67 patients older than 45 years of age). Sensitivities and specificities were 68 and 76% for Pyloriset, 89 and 77% for GAP test IgG, and 82 and 83% for Helico-G. The positive predictive values for all three tests were between 85 and 90%. The predictive values for the absence of disease with a negative result were 62, 82, and 74% for Pyloriset, the GAP test, and Helico-G, respectively. With Helico-G in the younger group (less than 45 years), sensitivity significantly lower (71 versus 87%) and a positive predictive value lower than those for the older group (greater than 45 years) were found. Either the sensitivities and specificities of commercial methods for the measurement of antibodies to H. pylori in serum must be improved or the relationship between the presence of antibodies and the presence of bacteria in the stomach at the time of investigation is too weak to allow the use of serological techniques instead of culture and histological investigation of gastric biopsy material.

Adult

Umbilical vein administration of oxytocin for the management of retained placenta: is it effective?

In a multicenter randomized controlled trial involving 220 women with retained placenta no beneficial effects could be established of intraumbilical vein administration of 10 IU of oxytocin in 20 ml of saline solution. A reduction was not gained in the rate of manual removal of the placenta and there was no decrease in the amount of blood loss. Oxytocin only induced a minor shortening of the median time interval from administration to the spontaneous expulsion of the placenta as compared with a placebo injection. Maternal serum alpha-fetoprotein levels before and after intraumbilical vein injection did not show evidence of fetomaternal transfusion.

Adult