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Biomedical subjects

M J van Gemert

Publications and source records attributed to M J van Gemert.

At least 19 recordsLinked to original sources

Assessment of feto-fetal transfusion flow through placental arterio-venous anastomoses in a unique case of twin-to-twin transfusion syndrome.

In vivo measurements of blood flow through arterio-venous anastomoses in monochorionic twin placentas have recently been attempted with Doppler ultrasound, but the accuracy is questionable. We present a case of twin-to-twin transfusion syndrome treated with fetoscopic laser surgery. The ex-recipient subsequently became severely anaemic and was treated with an intrauterine blood transfusion at 29 weeks' gestation. After birth, a placental injection study identified residual unidirectional arterio-venous anastomoses from the ex-recipient to the ex-donor without arterio-venous anastomoses in the opposite direction. Prospective measurements of decreasing haemoglobin levels between the intrauterine transfusion and birth allowed us to assess the net blood flow through the anastomoses as 27.9mL/24h. This finding may also explain the inaccuracy of Doppler flow measurements, as such low flow velocities cannot possibly be detected with current Doppler techniques.

Adult↗

Histologic evaluation of skin damage after overlapping and nonoverlapping flashlamp pumped pulsed dye laser pulses: A study on normal human skin as a model for port wine stains.

BACKGROUND AND OBJECTIVE: In the treatment of port wine stains (PWS) with the flashlamp pumped pulsed dye laser (FPPDL), no consensus exists about overlapping of pulses. The advantage of overlapping pulses is homogeneous lightening of the PWS; the risk is redundant tissue damage. The aim of this study was to determine the histopathologic effect on human skin of pulsed dye laser pulses with various degrees of overlap, with normal human skin as a model for PWS. STUDY DESIGN/MATERIALS AND METHODS: Eighteen healthy white volunteers were irradiated with pulsed dye laser pulses with increasing radiant exposure and with different degrees of overlap. Biopsy samples were taken and histologically analysed. RESULTS: Overlapping of pulses on normal human skin enhances depth of vascular damage with approximately 30%. Adjacent pulses also show this effect. We found no histologic signs of serious damage to epidermis or dermal connective tissue by using radiant exposure levels of 6-8 J/cm(2), regardless of pulse application. CONCLUSIONS: Reasoning that the mechanism of tissue injury is comparable for normal and PWS skin, we conclude that it is safe to treat PWS with overlapping FPPDL pulses to achieve homogeneous lightening.

Abdomen↗

Introduction of the flash-lamp pulsed-dye laser treatment of facial port-wine stains in childhood: A case of health care technology assessment.

BACKGROUND AND OBJECTIVE: Lasers have been used in the treatment of port-wine stains (PWS) for more than 30 years. With the introduction of the flash-lamp pulsed-dye laser (FPDL) it was assumed that infants could be treated safely, effectively, and probably more efficiently. Nowadays, FPDL treatment is an established form of treatment of PWS in childhood. STUDY DESIGN/MATERIALS AND METHODS: On the basis of the iterative Health Care Technology Assessment (HCTA) loop, we examined whether sufficient evidence from evaluations has been present to support the introduction of FPDL treatment for facial PWS at an early age. Such an assessment requires an interdisciplinary approach focusing on aspects of safety, efficacy, effectiveness, quality of life, costs, and the ethical issues of treatment. RESULTS: Assessment of the FPDL in PWS treatment of children did not follow the model of medical innovation and evaluation. Most assessments have been focused on laser applications that were already in clinical use. Efficacy and effectiveness of laser treatment have been the major concern in most assessments. Only a few studies have looked at costs and ethical aspects of treating children. CONCLUSIONS: The introduction and diffusion of the use of the FPDL in the treatment of PWS in childhood were uncontrolled, and the field was not prepared to use this technique properly. We believe that this nonadherence to the iterative HCTA model reflects the gradual way by which innovations find their way into clinical practice.

Adolescent↗

Laser pulse impact on rat mesenteric blood vessels in relation to laser treatment of port wine stain.

BACKGROUND AND OBJECTIVE: To study the impact of laser pulses on animal microvasculature as a model for laser treatment of port wine stains. STUDY DESIGN/MATERIALS AND METHODS: Rat mesenteric blood vessels were irradiated with a laser pulse (585 nm, 0.2-0.6 ms pulse duration, 0.5-30 J/cm(2) radiant exposure). Video microscopy was used to assess vessel dilation, formation of intravascular thrombi, bubble formation, and vessel rupture. Changes in reflection during a laser pulse were measured by simultaneously recording the temporal behavior of the incident and reflected signals. RESULTS: A threshold radiant exposure of approximately 3 J/cm(2) was found for changes in optical properties of blood in vivo, confirming previous in vitro results. Often, laser exposure induced a significant increase in vessel diameter, up to three times the initial diameter for venules and four times for arterioles, within 200 ms after laser exposure. Arterioles were more likely to dilate than venules. Sometimes, immediately after the pulse, round structures, interpreted as being gas bubbles, were seen within the vessel lumen. CONCLUSIONS: A variety of phenomena can occur when blood vessels of sizes comparable to those in port wine stains are irradiated with laser pulses as used in port wine stain treatment. Thrombus formation and vessel rupture have been described before from histological sections of laser-irradiated port wine stains. However, vessel dilation and formation of non-transient gas bubbles as found in this study have not been described before.

Animals↗

Prediction of portwine stain clearance and required number of flashlamp pumped pulsed dye laser treatments.

BACKGROUND AND OBJECTIVE: Portwine stain (PWS) response to flashlamp pumped pulsed dye laser (FPPDL) treatment is variable and unpredictable. Our aim was to develop a model to predict treatment outcome and the required number of treatments. STUDY DESIGN/MATERIALS AND METHODS: We hypothesized that PWS clearance decreases exponentially with the number of treatments, as a consequence of the exponential decrease of laser light fluence in human skin. Of 70 patients with a PWS in the head/neck area, the color difference between normal skin and PWS was measured with a chromameter, prior to, and at several stages during FPPDL treatment. Through the obtained values of each of the four color parameters, DeltaL*, Deltaa*, Deltab*, and DeltaE, mono-exponentially decreasing functions were fitted. RESULTS: All four color parameters showed decreasing exponential functions, with decay rates that were not significantly different, and a mean R(2) of 0.6, indicating a reliable fit-quality. CONCLUSIONS: Our model suggests that individual prediction of treatment outcome and the required number of treatments is possible in an early stage of FPPDL treatment of PWS, in theory already after one single laser treatment.

Adolescent↗

Angiogenesis three months after clinical transmyocardial laser revascularization using an excimer laser.

BACKGROUND AND OBJECTIVE: We present for the first time histologic findings 3 months after clinical transmyocardial laser revascularization using a XeCl excimer laser. STUDY DESIGN/MATERIALS AND METHODS: Histology was performed on a patient who died from a noncardiac cause 3 months post-excimer TMLR. RESULTS: In the treated myocardium, no patent channels were found but scars were seen with a linear distribution and in continuity with circumscribed small fibrotic endocardial and epicardial scars. The scars were highly vascularized by new vessels, ranging from small capillaries to large thin walled, and sometimes branching ectatic vessels. Sprouting of vessels into the adjacent myocardium was also observed. CONCLUSION: These results suggest that angiogenesis might play a role in the clinical improvement after TMLR.

Aged↗

In vitro placental pressure-flow behaviour is non-linear and depends on the external pressure.

OBJECTIVE: To study pressure-flow behaviour of in vitro placentas under normal simulated conditions and during raised external pressures, to simulate in vivo placental hemodynamic function, and as a model for polyhydramnios and the supine hypotension syndrome. DESIGN: Eleven normal term human singleton in vitro placentas were perfused under optimal physiologic conditions. Perfusion pressures varied between 5 and 90 mmHg, external pressures between 4 and 30 mmHg. Venous-external pressure (mmHg) combinations included 10-4, 10-10, 20-20, 25-25, 30-30 and 10-20. RESULTS: Pressure-flow curves varied markedly among the 11 placentas, but all showed a non-linear, perfusion pressure-dependent resistance. The in vitro placental resistances were significantly higher than estimated in vivo values. All placentas showed inevitable leakage at the maternal side due to damage during delivery. Increased external pressures increased the placental resistance at lower perfusion pressures. CONCLUSION: Placental damage reduces the number of perfused cotyledonic capillaries. This increases the placental resistance but preserves circulatory properties. Our findings therefore, represent in vivo placental function. They may explain why polyhydramnios often persists and that polyhydramnios and the supine hypotension syndrome are likely to be more detrimental in hypotensive than in normotensive or hypertensive fetuses.

Adult↗

Fetal urine and amniotic fluid in monochorionic twins with twin-twin transfusion syndrome: simulations of therapy.

OBJECTIVE: Therapy for twin-twin transfusion syndrome includes amnioreduction, septostomy, and laser ablation, but there is no accepted standard of care. Mechanisms for the reported improvement in survival are incompletely understood. We sought to model the mechanisms and predict the response of varying severities of twin-twin transfusion syndrome and placental angioarchitectures to current therapies to determine optimal clinical interventions. STUDY DESIGN: We used our mathematic model of twin-twin transfusion syndrome that predicts fetal and amniotic fluid abnormalities that are related to the placental angioarchitecture. Amnioreduction was modeled as reduction in amniotic fluid volume; septostomy was modeled as the merging of donor and recipient amniotic fluid, and laser ablation was modeled as the cessation of all placental anastomotic blood flows. RESULTS: Amnioreduction reduces amniotic fluid pressure, which improves transplacental fluid flow from mother to fetus and increases both donor and recipient blood volume. However, net arteriovenous transfusion increases, because of increased donor arterial pressure, which negates, in part, the benefit of amnioreduction. Septostomy allows amniotic fluid to be swallowed by the donor, with minimal effects on donor growth and blood volume. Laser ablation eliminates anastomotic exchange of blood and reduces discordant fetal growth. CONCLUSION: Amnioreduction may be effective in milder twin-twin transfusion syndrome pregnancies but ineffective in severe cases. Septostomy is unlikely to offer significant therapeutic efficacy. Laser ablation is equally effective in mild and severe twin-twin transfusion syndrome but has a higher spontaneous abortion rate than amnioreduction. The model indicates improved outcomes with the use of amnioreduction in mild twin-twin transfusion syndrome cases and with laser ablation in severe cases.

Amniocentesis↗

Polyhydramnios and arterio-arterial placental anastomoses may beneficially affect monochorionic twin pregnancies.

Our objective was to appraise whether an increased amniotic fluid pressure by polyhydramnios can beneficially affect monochorionic twins that are haemodynamically connected by arterio-venous plus arterio-arterial placental anastomoses. We assessed the effects of polyhydramnios in monochorionic twin placentas, combining (a) data from previous in vitro placental perfusion experiments in singleton term placentas under simulated normal and increased amniotic fluid pressures with (b) logical deduction from observations made in monochorionic twins. Our hypothesis is that in monochorionic placentas, an increased amniotic fluid pressure increases the placental microvascular resistance but not the resistance of placental chorionic plate arteries. Hence, an increased amniotic fluid pressure increases the microvascular resistance of the joint cotyledon, the arterio-venous resistance, but not the arterioarterial resistance. This proposed mechanism reduces arterio-venous but not oppositely directed arterio-arterial transfusion. Therefore, reversal of the normal direction of net foeto-foetal transfusion may develop, which will reduce the circulatory imbalance that evolved between the monochorionic foetal twins. In contrast, in monochorionic twins connected by unidirectional or bidirectional arterio-venous anastomoses reversal of the normal direction of net foeto-foetal transfusion will not occur. In conclusion, reversal of the normal direction of net foeto-foetal transfusion, induced by polyhydramnios, is protective against the onset and severity of twin-twin transfusion syndrome in monochorionic twins connected by arterio-venous plus arterio-arterial anastomoses, but not by unidirectional or bidirectional arterio-venous anastomoses.

Amniotic Fluid↗

Twin-twin transfusion syndrome: etiology, severity and rational management.

The twin-twin transfusion syndrome is a serious complication of monochorionic twin pregnancies. Partly as a result of an inadequate understanding of the pathophysiology of the syndrome, there is a lack of consensus in clinical management. We sought to review the available information on the etiology of twin-twin transfusion syndrome, to identify parameters that contribute to the severity of the syndrome, and propose a rational management plan based on pathophysiology, clinical presentation and the efficacy of therapies. We therefore amalgamated recent advances in twin-twin transfusion syndrome computer modelling and clinical studies, particularly on therapeutic outcomes. We found that the oligo-polyhydramnios sequence that defines twin-twin transfusion syndrome prenatally represents a wide continuum of severity in the imbalance between the fetoplacental circulations of both twins. In severe twin-twin transfusion syndrome cases, in which the circulatory imbalance deteriorates beyond fetal control, fetoscopic laser therapy of all anastomoses along the placental vascular equator is predicted to have significantly better survival rates and fewer neurological sequelae than amnioreduction. In contrast, mild twin-twin transfusion syndrome cases have better outcomes after one or at most a few amnioreductions than laser therapy, as a result of significantly fewer procedure-related risks. In conclusion, optimal individual therapy may possibly achieve an 85% survival rate in twin-twin transfusion syndrome, but requires advancement in non-invasive criteria that predict the severity of the syndrome. Identifying such criteria is a future challenge. For the interim, twin-twin transfusion syndrome diagnosed before 26 weeks' gestation has significantly better survival rates and fewer neurological sequelae after laser therapy than amnioreduction. Twin-twin transfusion syndrome diagnosed after 26 weeks can best be treated by amnioreduction, or delivery. Contrary to previous claims, fetoscopic laser therapy has outgrown its experimental status. Although improvements in technique and technology are likely, laser placental ablation has a firm scientific and clinical basis.

Amniotic Fluid↗

Bioheat transfer analysis of cryogen spray cooling during laser treatment of port wine stains.

BACKGROUND AND OBJECTIVE: The thermal response of port wine stain (PWS) skin to a combined treatment of pulsed laser irradiation and cryogen spray cooling (CSC) was analyzed through a series of simulations performed with a novel optical-thermal model that incorporates realistic tissue morphology. STUDY DESIGN/MATERIALS AND METHODS: The model consisted of (1) a three-dimensional reconstruction of a PWS biopsy, (2) a Monte Carlo optical model, (3) a finite difference heat transfer model, and (4) an Arrhenius thermal damage calculation. Simulations were performed for laser pulses of 0.5, 2, and 10 ms and a wavelength of 585 nm. Simulated cryogen precooling spurts had durations of 0, 20, or 60 ms and terminated at laser onset. Continuous spray cooling, which commenced 60 ms before laser onset and continued through the heating and relaxation phases, was also investigated. RESULTS: The predicted response to CSC included maximal pre-irradiation temperature reductions of 27 degrees C at the superficial surface and 12 degrees C at the dermoepidermal junction. For shorter laser pulses (0.5, 2 ms), precooling significantly reduced temperatures in superficial regions, yet did not effect superficial vessel coagulation. Continuous cooling was required to reduce significantly thermal effects for the 10-ms laser pulse. CONCLUSIONS: For the PWS morphology and treatment parameters studied, optimal damage distributions were obtained for a 2-ms laser pulse with a 60-ms precooling spurt. Epidermal and vascular morphology as well as laser pulse duration should be taken into account when planning CSC/laser treatment of PWS. Our novel, realistic-morphology modeling technique has significant potential as a tool for optimizing PWS treatment parameters.

Biopsy↗

Classification of discordant fetal growth may contribute to risk stratification in monochorionic twin pregnancies.

OBJECTIVES: To determine whether classification of discordant growth between fetal twins allows risk stratification in monochorionic twin pregnancies. METHODS: In 12 twin-to-twin transfusion syndrome (TTTS) pregnancies and 12 cases that were suspected of developing the syndrome, fetal growth was determined by serial standard sonography. Fetal growth was expressed as the difference-average-ratio (DAR), defined as the difference in estimated fetal weight between both twins divided by their average weight. In each case, we determined the maximum value of DAR and the rate of change of DAR using a least squares linear fit of the estimated fetal weights. RESULTS: For the TTTS cases the maximum value of DAR was 0.44 +/- 0.21 versus 0.52 +/- 0.13 for the suspected TTTS cases (P = 0.25). The rate of change of DAR was 0.052 +/- 0.034 per week for the TTTS versus 0.0055 +/- 0.0092 for the suspected TTTS cases (P = 0.0004). After laser therapy, DAR decreased in four successful cases, with a rate of change of -0.0146 +/- 0.0093 per week, but increased further in one unsuccessful case, due to patent anastomoses. In the seven TTTS cases treated with amnioreduction, DAR did not decrease; in one of two suspected TTTS cases the DAR decreased slightly. In the nine amnioreduction cases, the average rate of change of DAR was 0.067 +/- 0.083 per week. This was significantly different from the four successful laser cases (P = 0.01). CONCLUSIONS: The rate of change of DAR, but not DAR itself, has prognostic value for the development of suspected TTTS pregnancies, for the onset and severity of TTTS and for the efficacy of therapy. This parameter is derived from routine sonography examination and may contribute to risk stratification in monochorionic twin pregnancies.

Female↗

Modelling multiple laser pulses for port wine stain treatment.

Many port wine stains (PWS) are still resistant to pulsed dye laser treatment. However, anecdotal information suggests that multiple-pulse laser irradiation improves patient outcome. Our aims in this note are to explain the underlying mechanism and estimate the possible thermal effects of multiple pulses in vascular structures typical of PWS. Based on linear response theory, the linear combination of two thermal contributions is responsible for the total increase in temperature in laser irradiated blood vessels: direct light absorption by blood and direct bilateral thermal heat conduction from adjacent blood vessels. The latter contribution to the increase in temperature in the targeted vessel can be significant, particularly if some adjacent vessels are in close proximity, such as in cases of optical shielding of the targeted vessel, or if the vessels are relatively distant but many in number. We present evidence that multiple-pulse laser irradiation targets blood vessels that are optically shielded by other vessels. Therefore, it may be a means of enhancing PWS therapy for lesions that fail to respond to single-pulse dye laser treatment.

Blood Vessels↗

Trends of discordant fetal growth in monochorionic twin pregnancies.

We derived simple analytical relations representing trends of discordant fetal growth in monochorionic twins developing the twin-twin transfusion syndrome from an approximation of previously developed model equations. In severe twin-twin transfusion syndrome cases, the difference between the estimated fetal weights of both twins increases proportional to (t - 5)5 (t denotes gestational age in weeks) and the sum of both weights increases proportional to t3. Hence, the ratio between the difference of estimated fetal weights and the average of the two weights (difference average ratio) increases in proportion to (t - 5)5/t3. In mild cases, the difference between estimated fetal weights as well as the sum of the two weights increases proportional to t3. Therefore, the difference average ratio becomes a constant. Comparison with clinical data of severe and mild cases showed surprisingly good agreement except after laser coagulation of placental anastomoses. These relations may therefore enable us to distinguish between severe and mild developing twin-twin transfusion syndrome cases.

Blood Flow Velocity↗

Modeling laser treatment of port wine stains with a computer-reconstructed biopsy.

BACKGROUND AND OBJECTIVE: The efficacy of laser treatment of port wine stains (PWS) has been shown to be highly dependent on patient-specific vasculature. The effect of tissue structure on optical and thermal mechanisms was investigated for different pulse durations by using a novel theoretical model that incorporates tissue morphology reconstructed tomographically from a PWS biopsy. STUDY DESIGN/MATERIALS AND METHODS: An optical-thermal numerical model capable of simulating arbitrarily complex, three-dimensional tissue geometries was developed. The model is comprised of (1) a voxel-based Monte Carlo optical model, (2) a finite difference thermal model, and (3) an Arrhenius rate process calculation to predict the distribution of thermal damage. Simulations based on previous computer-based reconstruction of a series of 6 microm sections from a PWS biopsy were performed for laser pulse durations (taup) of 0.5, 5.0, and 10.0 ms at a wavelength of 585 nm. RESULTS: Energy deposition rate in the blood vessels was primarily a function of vessel depth in skin, although shading effects were evident. Thermal confinement and selectivity of damage were seen to be inversely proportional to pulse duration. The model predicted blood-specific damage for taup = 0.5 ms, vascular and perivascular damage for taup = 5 ms, and widespread damage in superficial regions for taup = 10 ms. The effect of energy deposition in the epidermis was most pronounced for longer pulse durations, resulting in increased temperature and extent of damage. CONCLUSION: Pulse durations between 0.5 and 5 ms are likely optimal for the PWS analyzed. The incorporation of a tomographically reconstructed PWS biopsy into an optical-thermal model represents a significant advance in numerical modeling of laser-tissue interaction.

Adult↗

Simulation of color of port wine stain skin and its dependence on skin variables.

BACKGROUND AND OBJECTIVE: The understanding of why Port Wine Stain (PWS) skin is redder and darker as compared to normal skin has so far been based on qualitative analysis. This study aims at quantitatively analyzing the influence of skin anatomy variables on perceived skin color. STUDY DESIGN/MATERIALS AND METHODS: Reflectance spectra for visible light from normal and Port Wine Stain skin have been calculated using a Monte Carlo algorithm applied to a multi-layered skin model. Skin parameters that were varied are pigmentation, dermal scattering, dermal blood concentration, blood oxygenation, vessel diameter, and vessel depth. The CIE 1976 color system was used to interpret the resulting spectra as colors. RESULTS: A reduced dermal blood content results in a less red and lighter color. Distribution of a constant volume of blood in smaller vessels results in a redder and darker color. Skin with higher dermal scattering was calculated to be yellower and lighter and skin with increased epidermal pigmentation results in a yellower and darker color. CONCLUSIONS: Redness of PWS skin depends on both the concentration of dermal blood as well as on how it is distributed.

Blood Vessels↗

Long-term results of isotretinoin in the treatment of 68 patients with hidradenitis suppurativa.

BACKGROUND: Oral isotretinoin has been used to treat mild to severe hidradenitis suppurativa (HS). OBJECTIVE: We reviewed the results of low-dose isotretinoin for 4 to 6 months in the treatment of 68 patients with HS. METHODS: This is a retrospective study. Data are presented in terms of response rate, long-term follow-up, and the relation between response rate and severity. RESULTS: In 16 patients (23.5%), the condition completely cleared during initial therapy and 11 patients (16.2%) maintained their improvement during the follow-up period. Treatment was more successful in the milder forms of HS. CONCLUSION: Monotherapy with isotretinoin for patients with HS usually has a limited therapeutic effect.

Adult↗