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Biomedical subjects

J de Haan

Publications and source records attributed to J de Haan.

At least 37 records · Page 2Linked to original sources
PubMed1995

Basement membranes in cervical cancer: relationship to pelvic lymph node metastasis and prognosis.

In this retrospective study, the pattern of basement membrane expressed by type IV collagen immunostaining was evaluated in 156 patients with cervical cancer FIGO stage IB-IV. Staining patterns were assessed semiquantitatively and divided into three patterns, according to intensity and continuity of staining: thick basement membranes with minimal discontinuity (pattern I), thin basement membranes with moderate discontinuity (pattern II), and fragmentary or absent basement membranes (pattern III). Correlations between basement membrane pattern, FIGO stage, and pelvic lymph node status were tested using chi 2 statistics. Kaplan-Meier estimates of disease-free survival were calculated for groups of patients with basement membrane pattern I, II, or III and compared using the log-rank test. A fragmented or absent basement membrane, pattern III, was more frequently observed in advanced cervical cancer stage IIB/IV (P = 0.02). In patients with early cervical cancer stage Ib/IIA this pattern was associated with the presence of pelvic lymph node metastasis (P < 0.0001) and significantly associated with a decreased survival rate (P = 0.05). In advanced-stage disease no prognostic value was observed. These data indicate that in patients with early-stage cervical cancer the basement membrane pattern, expressed as the type IV collagen staining pattern, may be a useful marker in predicting lymph node metastasis and survival.

Adenocarcinoma↗
PubMed1995

The T/QRS ratio of the electrocardiogram does not reliably reflect well-being in fetal lambs.

OBJECTIVE: Our purpose was to determine the diagnostic power of the T/QRS ratio of the electrocardiogram to predict fetal well-being. STUDY DESIGN: In 47 fetal lambs (3 to 5 days after surgery, gestational age 123.5 +/- 3.0 days) asphyxia was induced by restriction of uterine perfusion. Fetuses were either pretreated with an adenosine transport inhibitor (n = 16) or a calcium channel blocker (n = 12) or served as controls (n = 19). Arterial oxygen content > or = 1.5 mmol/L or pH > or = 7.15 were chosen as limits for fetal well-being. RESULTS: Arterial oxygen content was reduced from 3.3 (+/- 1.0) to 1.3 (+/- 0.5) mmol/L, and pH decreased to 7.03 (+/- 0.10). Mortality was 53%. Both drugs did not affect well-being, survival, or the T/QRS ratio. Maximum T/QRS ratios were reached at the peak of asphyxia. Sensitivity and specificity of the T/QRS ratio were 24.0% and 42.6% to predict hypoxemia and 25.1% and 45.3% to predict acidemia. Pearson correlation coefficients for T/QRS ratio versus oxygen content and pH were 0.169 and 0.192, respectively. CONCLUSIONS: (1) In fetal lambs the T/QRS ratio failed to predict hypoxemia or acidemia. (2) Fetal survival was not correlated with the height of the T/QRS ratio during or after asphyxia.

Acids↗
PubMed1995

Retransfusion of suctioned blood during cardiopulmonary bypass impairs hemostasis.

In a previous study we observed extensive clotting and fibrinolysis in blood from the thoracic cavities during cardiopulmonary bypass. We hypothesized that retransfusion of this suctioned blood could impair hemostasis. In this prospective clinical study we investigated the effect of suctioned blood retransfusion on systemic blood activation and on postoperative hemostasis. During coronary artery bypass grafting in 40 patients, suctioned blood was collected separately. It then was retransfused to the patient at the end of the operation (n = 19), or it was retained (n = 21). During the study, 12 consecutive patients, randomized in two groups of 6, were analyzed for biochemical parameters indicating blood activation and clotting. The immediate and significant increase in circulating concentrations of thrombin-antithrombin III complex, tissue-type plasminogen activator, fibrin degradation products, and free plasma hemoglobin demonstrated the effect of suctioned blood retransfusion. Moreover, the increased concentrations of thrombin-antithrombin III complex and fibrin degradation products indicated renewed systemic clotting and fibrinolysis as a direct result of the retransfusion of suctioned blood. Concentrations of all indicators mentioned remained significantly lower in the retainment group. The clinical data showed that retainment of suctioned blood resulted in significantly decreased postoperative blood loss (822 mL in the retransfusion group versus 611 mL in the retainment group; p < 0.05) and similar or even reduced consumption of blood products (513 versus 414 mL red blood cell concentrate and 384 versus 150 mL single-donor plasma; both not significant). We conclude that retransfusion of highly activated suctioned blood during cardiopulmonary bypass exacerbates wound bleeding.

Blood Transfusion, Autologous↗
PubMed1995

p53 tumor suppressor gene protein expression in cervical cancer: relationship to prognosis.

OBJECTIVE: Mutation of the p53 gene can be found in several human tumors. We tested the hypothesis whether overexpression of p53 protein is a parameter of more aggressive disease in patients with cervical cancer. STUDY DESIGN: In this study, we describe the effects of p53 overexpression in 156 patients with cervical cancer (Figo stage IB-IV) by assessing expression patterns of the p53 gene product using a monoclonal anti-p53 antibody (DO7). RESULTS: Overexpression of p53 tumor suppressor gene protein was observed in 30.2% of the tumors, low expression in 30.7% and 39.1% of the tumors showed no p53 immunoreactivity. With increase in stage, p53 overexpression raised from 20.1% in stage IB to 60% in stage IV. A significant correlation between p53 overexpression and disease-free survival of patients was observed, however, after stratification for stage, this effect disappeared. CONCLUSIONS: The p53 mutation expressed as p53 tumor suppressor gene protein overexpression is a late event in cervical cancer genesis and does not appear to be of prognostic significance in cervical cancer.

Antibodies, Monoclonal↗
PubMed1995

Gelatin use impairs platelet adhesion during cardiac surgery.

Artificial colloids based on gelatin are used as plasma expander to replace donor blood products. In laboratory experiments, gelatin reduced both the velocity and extend of platelet agglutination by ristocetin, and only the agglutination velocity by polybrene (p < 0.05). Furthermore, gelatin delayed the in-vitro platelet plug formation under shear-stress in the absence of ADP (p < 0.05), whereas gelatin induced no delay in the presence of ADP. Thus, after induction of vWF release from platelets by polybrene or ADP, platelet function was normal. These results indicate that gelatin affects in particular the functionality of plasma-vWF and partly inhibits platelet adhesion. These negative effects of gelatin on hemostasis were demonstrated in two clinical studies during cardiac surgery. In a randomized study of sixty patients undergoing cardiac surgery, gelatin as prime in the heart-lung machine appeared to result in diminished efficacy of aprotinin on hemostasis, whereas it did not affect hemostasis in non-aprotinin patients. An additional retrospective clinical study showed that only high dose of gelatin affected hemostasis. This suggests a limited role of plasma-vWF and a strong back-up mechanism of platelet-vWF in achieving hemostasis.

Aprotinin↗
PubMed1994

Systemic blood activation during and after autotransfusion.

To evaluate the extent of shed blood activation in two autotransfusion systems and the effect of circulating blood activation upon autotransfusion, we performed a prospective study in 18 patients undergoing internal mammary artery bypass operation and a control group of 10 patients. The autotransfusion systems were from Sorin (n = 9) consisting of a hard shell reservoir with a filter having a small contact area (0.32 m2), and from Dideco (n = 9) consisting of a hard shell reservoir with a filter having a larger contact area (4.64 m2). We found high concentrations of thromboxane, fibrinogen degradation products, complement split product C3a, and elastase in the shed blood and, with the exception of C3a, in the circulating blood of autotransfused patients. There was no such activation in control patients. The degree of the systemic inflammatory reaction was determined by the type of autotransfusion system and by the amount of infused shed blood. The Dideco system provoked more inflammatory response than did the Sorin. This was reflected by the larger shed blood loss during autotransfusion in the Dideco patients than in Sorin patients, resulting in infusion of more shed blood (means, 737 mL versus 566 mL; not significant). After autotransfusion, Dideco patients shed significantly more blood than did Sorin or control patients (p < 0.05). Dideco patients also needed more colloid/crystalloid solution per 24 hours than Sorin patients (p < 0.05). This became clinically relevant only after infusion of more than 800 mL of shed blood (p < 0.001): hemodilution indicated the need for packed cells in 4 Dideco patients and in 1 Sorin patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Loss, Surgical↗
PubMed1994

Effects of surgery and asphyxia on levels of nucleosides, purine bases, and lactate in cerebrospinal fluid of fetal lambs.

During severe oxygen shortage, the fetal brain resorts to anaerobic metabolism and ATP becomes catabolized. High levels of nucleosides, hypoxanthine, and xanthine (ATP catabolites) in cerebrospinal fluid (CSF) may therefore be associated with increased neonatal neurologic morbidity. In 22 fetal lambs (3 to 5 d after surgery, gestational age 123.5 +/- 3.5 d), arterial oxygen content was progressively reduced to 35% of the baseline value with a balloon occluder around the maternal common internal iliac artery. This resulted in a 1-h period of asphyxia, leading to a pH of 7.02 +/- 0.03 and a base excess of -17.0 +/- 1.0 mM. Mortality was 50%. CSF was sampled from the spinal cistern and analyzed using HPLC. During reoxygenation, hypoxanthine and xanthine may serve as substrate for xanthine oxidase with concomitant production of oxygen-derived free radicals, which may aggravate cerebral damage. The main difference between surviving and nonsurviving animals was the speed of increment of ATP catabolites in CSF: in the surviving group levels increased steadily, recovery values being significantly elevated compared with asphyxia values, whereas in the nonsurviving group the rise was rapid and levels during asphyxia did not differ significantly from levels during recovery. We conclude that 1) catheterization of the spinal cistern leads to increased levels of CSF hypoxanthine, xanthine, and inosine, and 2) during fetal asphyxia, levels of these ATP catabolites and lactate in CSF increase. 3) Maximum levels are reached during the recovery period and are similar for surviving and nonsurviving animals, but during asphyxia CSF levels of hypoxanthine and lactate were higher in the nonsurviving fetuses.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1993

Effects of asphyxia on the fetal lamb brain.

OBJECTIVE: Our purpose was to study the effect of fetal asphyxia on the release of hypoxanthine and xanthine in cerebrospinal fluid and on brain histologic characteristics. STUDY DESIGN: In seven fetal lambs (3 to 5 days after surgery, gestational age 124.3 +/- 2.6 days) asphyxia was induced by restriction of uterine blood flow. RESULTS: Fetal pH and base excess were reduced to 6.99 +/- 0.02 and -17.6 +/- 0.9 mmol/L, respectively. Cerebral blood flow increased during asphyxia and returned to normal in the recovery phase. Maximum concentrations of cerebrospinal fluid hypoxanthine and xanthine were reached in the normoxemic recovery phase. This high level of substrates during normoxemia facilitates oxygen free radical formation and may thus aggravate postasphyctic brain damage. Histologic evaluation of the brain 3 days after the insult showed a variable degree of edema. Coagulative neuronal changes, characteristic of irreversible cell death, were only occasionally detected. These changes were most obvious in the Purkinje cells of the cerebellum. CONCLUSIONS: Fetal asphyxia induced by uterine blood flow restriction is associated with high levels of cerebrospinal fluid hypoxanthine and xanthine in the recovery phase. Microscopically detectable brain damage, although not extensive, is mainly located in the cerebellum.

Animals↗
PubMed1993

The effect of adenosine transport inhibition on cardiovascular function and survival after severe asphyxia in fetal lambs.

When the energy demand exceeds the energy supply, anaerobic metabolism takes over and the ATP catabolite adenosine is generated. Adenosine acts as a coronary vasodilator, thereby increasing the oxygen supply to the heart. Its potential, however, is poorly exploited due to extensive catabolism. R-75231 inhibits transport of adenosine into endothelial cells, where it is catabolized, resulting in an elevation of interstitial adenosine concentrations. In 14 fetal lambs (3 to 5 d after surgery, gestational age 124.1 +/- 1.1 d), seven fetuses were pretreated with R-75231 (0.1 mg/kg estimated fetal weight as a bolus injection in the inferior vena cava), whereas the other seven served as controls. After 1 h of severe asphyxia, induced by restriction of uterine blood flow, those fetuses treated with R-75231 showed a faster normalization of aortal pH and, in contrast to the control group, did not develop tachycardia. The percentage increase in myocardial blood flow during asphyxia, measured with radioactive microspheres, was significantly higher in the R-75231-treated group compared with the control group (437 and 284%, respectively). In the control group, only three fetuses recovered and survived, whereas in the R-75231 group, all seven animals recovered after severe asphyxia. It is concluded that fetal lambs pretreated with R-75231 before the onset of severe asphyxia have an enhanced increase in myocardial blood flow during asphyxia, recover faster, and survive longer.

Adenosine↗
PubMed1993

Possible neuroprotective properties of flunarizine infused after asphyxia in fetal lambs are not explained by effects on cerebral blood flow or systemic blood pressure.

Neuroprotective properties of the calcium channel blocker flunarizine have been reported after hypoxic-ischemic insults in immature, infant, and adult rats. However, its effect on fetal regional cerebral blood flow (rCBF) and systemic blood pressure after severe asphyxia is not known. In 15 fetal lambs (3 to 5 d after surgery; gestational age at the experiment, 123.2 +/- 2.5 d), arterial oxygen content was progressively reduced to 30% by restriction of uterine blood flow with an inflatable balloon occluder around the maternal common internal iliac artery. The rCBF was measured with radioactive microspheres at baseline condition, after 1 h of severe asphyxia, and at 30 and 120 min in the recovery phase. Immediately after the end of the occlusion period, fetuses randomly received either flunarizine or its solvent (0.5 mg/kg estimated fetal weight). No differences in rCBF changes between groups were observed during and after asphyxia. Changes in arterial blood pressure or fetal heart rate due to flunarizine could not be demonstrated either. Only five fetuses (33%) survived this degree of asphyxia longer than 24 h: four of the flunarizine-treated group and one of the control group. It is unlikely that this possible protective property of the drug is caused by its influence on rCBF, arterial blood pressure, or fetal heart rate in the phase immediately after asphyxia.

Acid-Base Imbalance↗
PubMed1993

Activation of fibrinolysis in the pericardial cavity during cardiopulmonary bypass.

The clotting and fibrinolytic systems are activated by tissue factor and by tissue-type plasminogen activator in the pericardial cavity, where the thrombogenicity is greater than that of the surface of modern extracorporeal circuits. This local activation may have consequences for the systemic activation processes during cardiopulmonary bypass. To test this hypothesis, we investigated blood activation by interrupting the blood suction from the pericardial cavity during cardiopulmonary bypass in clinical coronary artery bypass operations. In blood collected in the pericardial cavity, thrombin-antithrombin III complex (p < 0.01), tissue-type plasminogen activator antigen (p < 0.05), fibrinogen degradation products (p < 0.01), and fibrin degradation products (p < 0.01) were significantly higher than in the systemic blood. Plasma heparin was significantly consumed in the pericardial cavity (p < 0.01). Once the pericardial blood was returned to the systemic circulation after resumed suction during cardiopulmonary bypass, thrombin-antithrombin III complex (p < 0.05), fibrinogen degradation products (p < 0.05), and fibrin degradation product (p < 0.05) concentrations increased significantly in the systemic blood. The effects of pericardial tissue on activation of clotting and fibrinolysis were also studied in vitro. When human plasma was incubated for 5 minutes with rabbit pericardium at reduced heparin concentrations, we found significant generation of thrombin (p < 0.05) and plasmin (p < 0.05). If the thrombin inhibitor hirudin was added, plasmin generation was also inhibited (p < 0.05). The results of the clinical and experimental study are in agreement with our hypothesis that tissue factor and tissue-type plasminogen activator accelerate the activation of clotting and sequentially of fibrinolysis under conditions of low heparin concentrations in the pericardial cavity and that this local activation contributes highly to the systemic activation, affecting hemostasis during cardiopulmonary bypass. Topical use of heparin in the pericardial cavity therefore seems indicated to reduce blood activation during cardiopulmonary bypass.

Blood Coagulation Factors↗
PubMed1993

Tissue-type plasminogen activator and fibrin monomers synergistically cause platelet dysfunction during retransfusion of shed blood after cardiopulmonary bypass.

Reduced hemostasis and bleeding tendency after cardiopulmonary bypass results from platelet dysfunction induced by the bypass procedure. The causes of this acquired platelet dysfunction are still subject to discussion, although, recently, greater emphasis has been placed on an overstimulated fibrinolytic system as a probable cause. In the first part of this study we assessed the effects of postoperative retransfusion of shed blood on blood loss to patients undergoing cardiopulmonary bypass. We observed that increasing concentrations of fibrinogen degradation products and tissue-type plasminogen activator stimulating activity in shed blood correlated significantly with a higher postoperative bleeding tendency (p < 0.05 for both). We further noted that retransfusion of shed blood increased the total postoperative blood loss by 43% (925 versus 1320 ml, p < 0.05). On the basis of these clinical observations, we hypothesized that the increased bleeding tendency was caused by fibrinolysis. In the second part of this study we collected evidence in support of this hypothesis by an in vitro study, in which we introduced similar (pro)fibrinolytic activity to platelet-rich plasma and measured the influence of this treatment on platelet function indicated by ristocetin agglutination. Tissue-type plasminogen activator and fibrin monomers (tissue-type plasminogen activator stimulator) together induced severe platelet damage, resulting in a decreased ristocetin agglutination response. Therefore, we propose a fibrinolysis-related mechanism for platelet dysfunction during cardiopulmonary bypass, dependent on fibrinolytic factors such as fibrin monomers, D-dimers, and tissue-type plasminogen activator.

Blood Loss, Surgical↗
PubMed1993

Umbilical artery flow velocity waveform analysis and assessment of fetal oxygenation.

Assessment of the fetal condition is an important but also difficult problem. During the last decades a number of new fetal monitoring techniques have been introduced into clinical practice without proper evaluation regarding its value for clinical practice beforehand. The last fetal monitoring technique introduced into clinical practice in such a way is the assessment of the fetal condition with umbilical artery flow velocity waveform analyses. Although in cases with zeroflow or reverse flow during diastole the complication rate is high, it is not possible to assess the fetal oxygenation by means of recording the umbilical artery pulsatility index and its changes. Moreover no adequate treatment of fetal hypoxia is yet available, except termination of pregnancy. It is important in this context to realize that prematurity in itself is still the most powerful determining factor for the further development of the child.

Animals↗
PubMed1992

Early stage cervical cancer: aborted versus completed radical hysterectomy.

In a retrospective study, the treatment results of patients with stage IB and IIA cervical cancer were evaluated. In 26 patients radical hysterectomy was discontinued after intra-operative finding of positive lymph nodes. These patients received radiotherapy. In 57 patients lymph nodes were negative, and radical hysterectomy was completed. Of these, 13 patients received adjuvant radiotherapy because of positive surgical margins or parametrial involvement, and 44 patients received no adjuvant therapy. Five-year survival was 61% in patients with positive pelvic lymph nodes and 88% in patients with negative pelvic lymph nodes, comparable with the results mentioned in the literature. The complication rate did not differ from similar other reports. This management shows treatment results comparable with other reports with minimal morbidity.

Adult↗
PubMed1992

The acute response of the umbilical artery pulsatility index to changes in blood volume in fetal sheep.

This experimental study was designed to test the effects of acute changes in fetal circulating blood volume on the umbilical artery pulsatility index (PI). Six fetal sheep were provided with an electromagnetic flow meter for measurement of umbilical venous blood flow, with catheters for determination of arterial blood pressure and umbilical venous pressure, and with a 5 MHz Doppler transducer around one umbilical artery for flow velocity waveform analysis. A catheter in the inferior vena cava was used to infuse 50 ml of maternal blood (hypervolemia) into the fetal circulation or to withdraw 50 ml of fetal blood (hypovolemia) after volume correction. Hypervolemia resulted in a rise in arterial pressure and umbilical venous pressure, without an effect on PI, umbilical blood flow or placental vascular resistance. Hypovolemia resulted in a decrease in fetal heart rate, arterial pressure, umbilical venous pressure and umbilical blood flow. Calculated placental vascular resistance was not changed, whereas the PI increased by 42%. We conclude that volume loading with 10-15% of fetal circulating volume does not affect the umbilical artery PI, whereas acute reduction of fetal blood volume with the same amount is associated with an increase in the umbilical artery PI, without changes in calculated placental vascular resistance.

Animals↗
PubMed1992

Oestrogen and progesterone receptor immunocytochemistry in human hyperplastic and neoplastic endometrium.

Proliferative disorders of the endometrium may be associated with autocrine and paracrine actions between stromal and epithelial cells. To determine whether the stromal-epithelial relation with respect to oestrogen receptor (OR) and progesterone receptor (PR) is disturbed in (pre)malignant endometrium immunocytochemical OR and PR expression was quantitated by computerized image analysis. This was studied in the stromal and epithelial cells of endometrial specimens diagnosed as hyperplasia (n = 14), atypical hyperplasia (n = 16), and adenocarcinoma (n = 33). Paraffin sections were used for optimal preservation of histomorphology. A progressive loss of OR and PR content occurred with increasing malignant transformation. Stromal cells in atypical hyperplasia (P = 0.0007) and well-differentiated adenocarcinoma (P = 0.0008) exhibited a relative loss of PR content as compared with epithelial cells (P = 0.036 and P = 0.17, respectively). In atypical hyperplasia, the decrease in stromal PR content was not in parallel with persistent stromal OR immunostaining. Furthermore, stromal PR expression in atypical hyperplasia was significantly (P = 0.004) lower than in the surrounding hyperplasia, whereas the stromal OR staining as well as the epithelial OR and PR staining did not differ significantly. These observations may reflect a disturbance in hormonal interrelationships between endometrial cells in the development of endometrial neoplasia, indicating that stroma may modulate epithelial growth by paracrine mechanisms.

Adenocarcinoma↗