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Biomedical subjects

Martin J C van Gemert

Publications and source records attributed to Martin J C van Gemert.

At least 19 recordsLinked to original sources
PubMed2007

Deep-hidden anastomoses in monochorionic twin placentae are harmless.

OBJECTIVES: Our objective was to identify the clinical consequences of deep-hidden anastomoses that occur underneath the placental surface. METHODS: Twelve placentae that underwent intrauterine laser ablation of placental anastomoses for twin-twin transfusion syndrome (TTTS) and 14 non-TTTS controls were investigated for deep-hidden anastomoses. Additionally, we investigated the inter-twin haemoglobin differences as an indicator for fetofetal transfusion. Placentae were divided into four groups: TTTS placentae without residual chorionic-plate anastomoses without deep-hidden anastomoses (group 1) and with deep-hidden anastomoses (group 2), and non-TTTS placentae with chorionic-plate anastomoses without deep-hidden anastomoses (group 3) and with deep-hidden anastomoses (group 4). RESULTS: Deep-hidden anastomoses were identified in 58% (7/12) of the TTTS placentae after laser surgery and in 64% (9/14) of the non-TTTS placentae. Groups 1 and 2 had equal inter-twin haemoglobin differences: medians 1.4 and 1.2 gr/dL, respectively (p = 0.48). In group 3, the median inter-twin haemoglobin difference without deep-hidden anastomoses was 2.6 gr/dL (group 3) and with deep-hidden anastomoses (group 4) it was 5.1 gr/dL (p = 0.26). CONCLUSION: Both comparisons imply that deep-hidden anastomoses did not cause any additional increase in Hb difference. In conclusion, haematological and additional hemodynamical analysis show that deep-hidden anastomoses are likely to occur without any clinical consequences.

Female↗
PubMed2006

A mathematical model of twin-twin transfusion syndrome with pulsatile arterial circulations.

The twin-twin transfusion syndrome (TTTS) is a severe complication of monochorionic twin pregnancies caused by a net transfusion of blood from one twin (the donor) to the other (the recipient) through placental anastomoses. To examine the pathophysiology of TTTS evolving through clinical stages I to IV, we extended our mathematical model to include pulsating circulations propagating along the arterial tree as well as placental and cerebral vascular resistances, and arterial wall thickness and stiffness. The model demonstrates that abnormal umbilical arterial flow (TTTS stage III) in the donor twin results from increased placental resistance as well as reduced resistance in the cerebral arteries. In contrast, recipient twin abnormal umbilical arterial flow requires a significantly greater increase in placental resistance, resulting from the compressive effects of high amniotic fluid pressure. Thus simulated abnormalities of donor umbilical arterial pulsations occur in the donor more commonly and earlier than in the recipient. The "normal" staging sequence (I, II, III, IV) correlates with the presence of compensating placental anastomoses, constituting the majority of monochorionic twin placentas. However, TTTS stage III may occur before manifestations of stage II (lack of donor bladder filling), in our model correlating with severe TTTS from a single arteriovenous anastomosis, an infrequent occurring placental angioarchitecture. In conclusion, this mathematical model describes the onset and development of the four stages of TTTS, reproduces a variety of clinical manifestations, and may contribute to identifying the underlying pathophysiology of the staging sequence in TTTS.

Chorion↗
PubMed2006

Modeling severely discordant hematocrits and normal amniotic fluids after incomplete laser therapy in twin-to-twin transfusion syndrome.

Our objective was to explain the clinical presentations of sustained arteriovenous anastomotic transfusion of blood after incomplete laser therapy in twin-to-twin transfusion syndrome (TTTS). We extended our mathematical model of TTTS by adding the dynamics of hematocrit, and simulated incomplete laser therapy, first, by leaving one patent opposite arteriovenous anastomosis from the recipient to the donor and, second, by leaving one patent arteriovenous anastomosis from the donor to the recipient. In both simulations we reproduced the clinical observation of severe hematocrit discordance preceding delayed amniotic fluid imbalance. In conclusion, incomplete laser therapy may cause a severe circulatory imbalance between the twins which presents predominantly as discordant hematocrits rather than discordant amniotic fluid volumes as in primary TTTS. These results imply that the anemia-polycythemia sequence is a sensitive mechanism to identify transfusion reversal after complicated laser therapy, confirming the suggested role of middle cerebral artery peak systolic velocity Doppler measurements as a useful method of follow-up.

Amniotic Fluid↗
PubMed2006

Abnormal arterial flows by a distributed model of the fetal circulation.

Modeling the propagation of blood pressure and flow along the fetoplacental arterial tree may improve interpretation of abnormal flow velocity waveforms in fetuses. The current models, however, either do not include a wide range of gestational ages or do not account for variation in anatomical, vascular, or rheological parameters. We developed a mathematical model of the pulsating fetoumbilical arterial circulation using Womersley's oscillatory flow theory and viscoelastic arterial wall properties. Arterial flow waves are calculated at different arterial locations from which the pulsatility index (PI) can be determined. We varied blood viscosity, placental and brain resistances, placental compliance, heart rate, stiffness of the arterial wall, and length of the umbilical arteries. The PI increases in the umbilical artery and decreases in the cerebral arteries, as a result of increasing placental resistance or decreasing brain resistance. Both changes in resistance decrease the flow through the placenta. An increased arterial stiffness increases the PIs in the entire fetoplacental circulation. Blood viscosity and peripheral bed compliance have limited influence on the flow profiles. Bradycardia and tachycardia increase and decrease the PI in all arteries, respectively. Umbilical arterial length has limited influence on the PI but affects the mean arterial pressure at the placental cord insertion. The model may improve the interpretation of arterial flow pulsations and thus may advance both the understanding of pathophysiological processes and clinical management.

Arteries↗
PubMed2005

Increasing cardiac output and decreasing oxygenation sequence in pump twins of acardiac twin pregnancies.

An acardiac twin pregnancy is a rare but serious complication of monochorionic twinning and consists of an acardiac twin and a pump twin. The acardiac twin is a severely malformed fetus that lacks most organs, particularly a heart, but grows during pregnancy because it is perfused by the developmentally normal pump twin via a set of arterioarterial and venovenous placental anastomoses. Pump twins die intrauterine or neonatally in about 50% of the cases. Because the effects of an acardiac mass on the pump twin's development are incompletely known, methods for outcome prognosis are currently not available. We sought to derive simple relations for the pump twin's excess cardiac output and decreased oxygenation and to use available clinical cases for a preliminary test of the model. As a method, we used a theoretical flow model to represent the fetoplacental circulation of an acardiac twin pregnancy and estimated blood deoxygenation and reoxygenation following perfusion of the two bodies and placentas, respectively. The results show the pump twin's excess cardiac output and decrease of venous oxygen saturation to depend on the ratio of pump twin to acardiac twin umbilical blood flow, whose ratio can be measured by ultrasonography. The clinical cases show a decreasing umbilical flow ratio with gestation. In conclusion, prospective serial study is necessary to test whether measurement of umbilical flow ratios allows monitoring the pump twin's pathophysiologic development, possibly resulting in a guideline for prognosis of pump twin survival.

Abnormalities, Severe Teratoid↗
PubMed2005

Simulation of therapy in a model of a nonhydropic and hydropic recipient in twin-twin transfusion syndrome.

OBJECTIVE: This study was undertaken to model the sequence of events that occurs after amnioreduction, laser therapy, and digoxin administration in twin-twin transfusion syndrome (TTTS) with and without a hydropic recipient twin. STUDY DESIGN: We added amnioreduction, laser therapy, and digoxin administration to our mathematical TTTS model and simulated combinations of these therapies. RESULTS: With a nonhydropic recipient, simulated amnioreduction delays the onset of hydrops. Conversely, with a hydropic recipient, amnioreduction aggravates the degree of hydrops. Furthermore, amnioreduction increases the transplacental fluid flow and may temporarily cause a hydropic donor. Laser therapy terminates the cause of recipient hydrops. Digoxin reduces the degree of recipient hydrops, but increases arteriovenous fetofetal transfusion. CONCLUSION: Laser therapy is superior in TTTS with a hydropic recipient, because simulated amnioreduction aggravates the recipient's cardiovascular status. Digoxin benefits a hydropic recipient but slightly worsens the donor's condition. Therefore, TTTS presenting with a hydropic recipient prior to fetal viability (approximately 26 weeks) may be best treated with laser therapy, whereas more advanced gestations may be offered digoxin administration plus amnioreduction, to delay the progression of TTTS.

Cardiotonic Agents↗
PubMed2005

Towards optimization of selective photothermolysis: prothrombotic pharmaceutical agents as potential adjuvants in laser treatment of port wine stains. A theoretical study.

For the past two decades much research on selective photothermolysis of port wine stain vasculature has been devoted to optimizing laser parameters. Unfortunately, 60% of patients still respond suboptimally to laser therapy, despite significant innovations in treatment strategies and laser technology. Here we present a novel treatment approach based on combining selective photothermolysis with the administration of prothrombotic and/or anti-fibrinolytic pharmaceutical agents, with the aim of enhancing vaso-occlusion and post-treatment remodelling in difficult-to-target vessels. A hypercoagulable state of blood will instill laser-induced occlusive thrombosis in a wider array of vessel diameters at greater dermal depths, whereby larger vascular segments will ultimately undergo the chronic inflammatory processes that result in blood volume reduction, and thus lesional blanching. With thrombosis as a primary trigger for these inflammatory processes, we have extrapolated the threshold damage profile that is required for clinically relevant thrombus formation. Consequently, a recently proposed model of thrombus organization, in which recanalization is associated with endothelial progenitor cell-mediated neovasculogenesis, is elaborated in the framework of lesional blanching and juxtaposed to angiogenic reconstruction of affected dermal vasculature. Since neovasculogenesis and angiogenesis are regulated by the degree of vaso-occlusion and corollary drop in local oxygen tension, both can be manipulated by the administration of procoagulant pharmaceuticals. Lastly, in an effort to optimally balance selective photothermolysis with pharmacokinetics and clinical safety, the use of a gold nanoshell drug delivery system, in which the procoagulant drugs are encapsulated by a wavelength-modulated, gold-coated polymer matrix, is proposed. We have termed this modality site-specific pharmaco-laser therapy.

Adjuvants, Pharmaceutic↗
PubMed2004

Modeling a hydropic recipient twin in twin-twin transfusion syndrome.

We developed a mathematical model of twin-twin transfusion syndrome (TTTS) that includes a hydropic recipient twin, adding interstitial and intracellular fluid compartments, fetal congestive cardiac failure, and the dynamics of renin-angiotensin system (RAS) mediators to our previous TTTS model. Ten differential equations for each twin, coupled by the net fetofetal transfusion of blood and blood components, i.e., colloids, osmoles, and RAS mediators, describe the development of fetal arterial and venous blood volumes, blood osmolality and colloid osmotic pressure (COP), interstitial fluid volume and COP, intracellular fluid volume, amniotic fluid volume and osmolality, and RAS mediator concentration. We included varying placental anastomoses, placental sharing, and amnionicity. The 20 differential equations were solved numerically from 0 to 40 wk with a 0.6-s time step. Consistent with clinical experience, model predictions are as follows. Unidirectional arteriovenous anastomoses and arteriovenous anastomoses inadequately compensated by oppositely directed anastomoses cause severe TTTS that includes a hydropic recipient. Adequately compensated arteriovenous anastomoses simulated TTTS without hydrops. The probability that oppositely directed anastomoses prevent onset of a hydropic recipient after TTTS onset, i.e., the largest interval between onset of TTTS and onset of hydrops in the recipient, was best for a venovenous anastomosis, closely followed by an arterioarterial and finally an oppositely directed arteriovenous anastomosis. Hydropic recipients have decreased amniotic fluid volume. Unequal placental sharing and amnionicity modify hydrops onset. In conclusion, our model simulates a sequence of events that results in a hydropic recipient twin in severe TTTS. The model may allow an assessment of the efficacy of current therapeutic interventions for TTTS cases that include a hydropic recipient twin.

Adult↗
PubMed2004

Haemodynamic resistance model of monochorionic twin pregnancies complicated by acardiac twinning.

An acardiac twin is a severely malformed monochorionic twin fetus that lacks most organs, particularly a heart. It grows during pregnancy, because it is perfused by its developmentally normal co-twin (called the pump twin) via a set of placental arterioarterial and venovenous anastomoses. The pump twin dies intrauterine or neonatally in about 50% of the cases due to congestive heart failure, polyhydramnios and prematurity. Because the pathophysiology of this pregnancy is currently incompletely understood, we modified our previous haemodynamic model of monochorionic twins connected by placental vascular anastomoses to include the analysis of acardiac twin pregnancies. We incorporated the fetoplacental circulation as a resistance circuit and used the fetal umbilical flow that perfuses the body to define fetal growth, rather than the placental flow as done previously. Using this modified model, we predicted that the pump twin has excess blood volume and increased mean arterial blood pressure compared to those in the acardiac twin. Placental perfusion of the acardiac twin is significantly reduced compared to normal, as a consequence of an increased venous pressure, possibly implying reduced acardiac placental growth. In conclusion, the haemodynamic analysis may contribute to an increased knowledge of the pathophysiologic consequences of an acardiac body mass for the pump twin.

Biophysics↗
PubMed2004

Oxygen saturation-dependent absorption and scattering of blood.

We report on the scattering properties of oxygenated and deoxygenated whole blood from 250 to 1000 nm. We determine the complex refractive index of oxygenated and deoxygenated hemoglobin using a Kramers-Kronig analysis and optical coherence tomography measurements. Combining these data with Mie theory, the scattering properties are calculated. The strong oxygen saturation dependent scattering effects should be taken into account in the data analysis of optical oxymetry.

Absorption↗
PubMed2004

Modelling the influence of amnionicity on the severity of twin-twin transfusion syndrome in monochorionic twin pregnancies.

Clinical treatment for diamniotic-monochorionic twin-twin transfusion syndrome (TTTS) may include conversion of diamniotic pregnancies to a monoamniotic-monochorionic state by disrupting the amnion septum. We sought to test the underlying hypothesis, i.e. that a monoamniotic state reduces the severity of TTTS. With use of our previously developed mathematical model of two equal fetoplacental circulatory units connected by various sizes and types of placental anastomoses, we compared the haemodynamic and amniotic fluid dynamics of monoamniotic and diamniotic twins that develop TTTS. We used three anastomotic patterns that produce severe, moderate or mild forms of TTTS, respectively, in our diamniotic-monochorionic twin model. Monoamnionicity was modelled by adding the two amniotic fluid volumes and using the volume-averaged amniotic fluid osmolality. The results were as follows: for severe TTTS, small differences develop between diamniotic and monoamniotic donor twins in fetal urine production, swallowed volume, blood volume, blood pressures, net fetofetal transfusion, and blood and amniotic fluid osmolality. However, the circulatory imbalance between the monoamniotic twins deteriorates similar to that of diamniotic twins. The pathophysiological differences tend to disappear for milder TTTS. In conclusion, our model suggests that the uncommon finding of TTTS in monoamniotic twins is not due to the presence of a single amniotic sac. Rather, clinically significant differences in anastomotic patterns and the delayed or lack of identification of manifestations in monoamniotic twins account for the reduced rate of TTTS diagnosis. Based on these results we expect the clinical disruption of the amnion septum in diamniotic-monochorionic TTTS pregnancies to have only minimal benefits.

Amnion↗
PubMed2004

Transmyocardial revascularization using an XeCl excimer laser: results of a randomized trial.

BACKGROUND: CO2 and holmium:yttrium aluminum garnet (YAG) transmyocardial laser revascularization (TMLR) are used to treat patients with refractory angina. A randomized trial to investigate the efficacy and safety of XeCl excimer TMLR was performed. METHODS: Thirty patients with refractory angina were randomized in pairs to excimer TMLR or maximal medication. We assessed angina, quality of life (QOL), exercise time, myocardial perfusion, and ventricular wall motion at base line and at 3, 6, and 12 months after TMLR. RESULTS: TMLR patients manifested a significantly better outcome with respect to angina class and quality of life. One TMLR patient died perioperatively versus none in the control group. After TMLR angina decreased from class 3.8 +/- 0.4 at base line to 1.9 +/- 0.9 at 12 months versus 3.9 +/- 0.3 to 3.7 +/- 0.6 in the control group, respectively (p = 0.000001). At 12 months a decrease of greater than or equal to two angina classes was indicated in 11 out of 14 TMLR patients versus none in the control group (p = 0.00001). Improved myocardial perfusion or exercise time was not indicated despite a small decrease in reversible wall motion abnormality score. CONCLUSIONS: Excimer TMLR significantly relieves angina and improves QOL without evidence of improved cardiac perfusion or function.

Adrenergic beta-Antagonists↗
PubMed2004

Cardiac denervation after clinical transmyocardial laser revascularization: short-term and long-term iodine 123-labeled meta-iodobenzylguanide scintigraphic evidence.

OBJECTIVES: This study was designed to investigate whether transmyocardial laser revascularization induces myocardial denervation and to correlate this with myocardial perfusion and clinical status. METHODS: Transmyocardial laser revascularization was performed with a Holmium:YAG (n = 3) or xenon chloride excimer laser (n = 5). Preoperative and postoperative iodine 123-labeled meta-iodobenzylguanide SPECT scintigraphy to assess cardiac innervation and perfusion scintigraphy were also performed. Furthermore, New York Heart Association functional angina class and quality of life were assessed. RESULTS: In all patients postoperative iodine 123-labeled meta-iodobenzylguanide SPECT showed significantly decreased uptake and therefore sympathetic myocardial denervation at up to 16 months' follow-up (average preoperative and postoperative summed defect scores of 14.8 +/- 5.3 and 24.5 +/- 4.2, respectively; P =.00005). In 86% of segments, the decreased meta-iodobenzylguanide uptake could be correlated to the treated area. In all patients angina was reduced by 2 or more classes at 12 months' follow-up, and quality of life improved significantly. CONCLUSIONS: Transmyocardial laser revascularization-induced improvement of angina and quality of life can be explained by destruction of nociceptors or cardiac neural pathways, changing the perception of anginal pain.

3-Iodobenzylguanidine↗
PubMed2003

Improved quality of life after XeCl excimer transmyocardial laser revascularization: results of a randomized trial.

BACKGROUND AND OBJECTIVES: We assessed quality of life (QOL) after XeCl transmyocardial laser revascularization (TMLR). STUDY DESIGN/MATERIALS AND METHODS: Thirty patients were randomized to receive XeCl excimer TMLR or optimal cardiac medication (controls). QOL was assessed at baseline, 1, 3, 6, and 12 months using three different questionnaires: The Medical Outcomes Study Short Form-24 (MOS SF-24), the EuroQol Standardized Questionnaire, and the Seattle Angina Questionnaire (SAQ). The primary outcome measure was the change in score between baseline and 12 months. RESULTS: TMLR patients scored significantly better compared to controls in the MOS SF-24 social functioning, energy, general health, and bodily pain domains, in the EuroQol usual activity domain and the EuroQol Visual Analogue Scale, and in the SAQ physical limitation, angina frequency and disease perception domains. CONCLUSIONS: QOL significantly improved after XeCl excimer TMLR compared to medication. These results are similar to reported improvements in QOL after CO(2) and Ho:YAG TMLR.

Aged↗
PubMed2003

Monoamniotic-versus diamniotic-monochorionic twin placentas: anastomoses and twin-twin transfusion syndrome.

OBJECTIVE: The purpose of this study was to compare monoamniotic-monochorionic and diamniotic-monochorionic twin placentas and to estimate the incidence of twin-twin transfusion syndrome in monoamniotic-monochorionic twin pregnancies. STUDY DESIGN: We analyzed the angioarchitecture and cord insertion distance in 24 monoamniotic-monochorionic and 200 diamniotic-monochorionic placentas. RESULTS: Compared with diamniotic-monochorionic placentas, monoamniotic-monochorionic placentas had significantly more arterioarterial anastomoses (20/20 vs 159/200, respectively; P=.013), significantly less opposite arteriovenous anastomoses (10/20 vs 165/200, respectively; P=.002), similar venovenous anastomoses (6/20 vs 46/200, respectively; P=.323), and arteriovenous anastomoses (20/20 vs 187/200 respectively; P=.279) and significantly shorter umbilical cord distances (median [+/-SD], 5.0+/-6.9 cm vs 17.5+/-6.8 cm; P<.001). CONCLUSION: Monoamniotic-monochorionic and diamniotic-monochorionic placentas have different anastomotic patterns. The (virtually) 100% incidence of arterioarterial anastomoses in monoamniotic-monochorionic placentas explains the reason that twin-twin transfusion syndrome rarely occurs in monoamniotic-monochorionic twin pregnancies and predicts that twin-twin transfusion syndrome manifestations are approximately 5 times less often recognized in monoamniotic-monochorionic pregnancies than in diamniotic-monochorionic pregnancies.

Amnion↗
PubMed2002

Does amniotic fluid volume affect fetofetal transfusion in monochorionic twin pregnancies? Modelling two possible mechanisms.

Clinical evidence suggests that increased amniotic fluid volume due to polyhydramnios increases placental vascular resistance. We have sought to model the possible effects of an increased amniotic fluid volume on the net fetofetal transfusion in monochorionic twin pregnancies. We wanted to compare these effects with the results of previous simulations, which aimed to explain why the twin-twin transfusion syndrome (TTTS) placentas more often include bidirectional arteriovenous (AV) rather than AV plus arterioarterial (AA) anastomoses. We extended our mathematical model of TTTS by simulating two different mechanisms that increase the placental vascular resistance as a consequence of polyhydramnios. First, there is an increase in the placental capillary resistance and hence in deep AV and opposite AV (denoted as VA) resistances due to polyhydramnios. Second, there is an increase in the resistance of chorionic veins due to polyhydramnios, assuming that these veins act as Starling resistors. We then simulated the effects of polyhydramnios on different placental anastomotic patterns. The results were as follows. In the first mechanism (polyhydramnios affects AV-VA resistances), an increased amniotic fluid volume hardly affected bidirectional AV, but slightly decreased fetofetal transfusion in AV plus AA anastomoses. However, for these effects to change the natural development of the pregnancy, polyhydramnios needed to persist for approximately 4 weeks, and by comparing the effects of polyhydramnios with the effects of amnioreduction, amnioreduction was more beneficial for normalizing the donor amniotic fluid volume. Therefore, these beneficial effects due to polyhydramnios have no practical clinical significance. In the second mechanism (Starling resistor for chorionic veins), polyhydramnios slightly increased fetofetal transfusion and hence slightly increased TTTS severity in bidirectional AV and AV plus VV, but did not affect AV plus AA anastomoses. In conclusion, we hypothesize that the simulated effects of polyhydramnios are not the primary cause of the fact that TTTS placentas more often include bidirectional AV than AV plus AA anastomoses. Rather, the more likely explanation is the previously identified larger range of AA than VA anastomotic diameters that adequately compensate for the effects of the AV.

Amniotic Fluid↗