Biomedical subjects

Johan F Beek

Publications and source records attributed to Johan F Beek.

9 recordsLinked to original sources

PubMed2006

Mitochondrial PO2 measured by delayed fluorescence of endogenous protoporphyrin IX.

Molecular oxygen is the primary oxidant in biological systems. The ultimate destination of oxygen in vivo is the mitochondria where it is used in oxidative phosphorylation. The ability of this process to produce an amount of high-energy phosphates adequate to sustain life highly depends on the available amount of oxygen. Despite a vast array of techniques to measure oxygen, major (patho)physiological questions remain unanswered because of the unavailability of quantitative techniques to measure mitochondrial oxygen in situ. Here we demonstrate that mitochondrial PO(2) can be directly measured in living cells by harnessing the delayed fluorescence of endogenous protoporphyrin IX (PpIX), thereby providing a technique with the potential for a wide variety of applications. We applied this technique to different cell lines (V-79 Chinese hamster lung fibroblasts, HeLa cells and IMR 32-K1 neuroblastoma cells) and present the first direct measurements of the oxygen gradient between the mitochondria and the extracellular volume.

Animals↗

PubMed2005

Invited commentary.

Explore the source record for details and available documents.

Angina, Unstable↗

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

The vascular response induced by transmyocardial laser revascularization is determined by the size of the channel scar: Results of CO2, holmium and excimer lasers.

BACKGROUND AND OBJECTIVES: To investigate the angiogenic effect of CO2, Ho:YSGG, and XeCl excimer TMLR in a rat model with morphologic characteristics of chronic myocardial ischemia. STUDY DESIGN/MATERIALS AND METHODS: Two channels (200-320 microm) were created per rat heart. After 14 days, vessel numbers and densities in and around laser scars were assessed. RESULTS: Capillary densities in the laser scars were equal between the three lasers ( approximately 130 vessels/mm2) but much lower than in control areas ( approximately 2,100 vessels/mm2). Vessel densities excluding capillaries were significantly higher in Ho:YSGG and CO2 scars compared to excimer scars, while only Ho:YSGG scars contained significantly more large vessels (diameter > or = 20 microm) than control areas. Only rarely, extension of vascular growth into adjacent myocardium was observed in any of the three groups. CONCLUSIONS: These results indicate that the angiogenic response following TMLR is limited to the channel scar and related to the scar size rather than the specific laser type.

Animals↗

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

Carbon dioxide laser-assisted nerve repair: effect of solder and suture material on nerve regeneration in rat sciatic nerve.

In order to further improve and explore the role of lasers for nerve reconstruction, this study was designed to investigate regeneration of sharply transected peripheral nerves repaired with a CO(2) milliwatt laser in combination with three different suture materials and a bovine albumin protein solder as an adjunct to the welding process. Unilateral sciatic nerve repair was performed in 44 rats. In the laser group, nerves were gently apposed, and two stay sutures (10-0 nylon, 10-0 polyglycolic acid, or 25 microm stainless steel) were placed epi/perineurially. Thereafter, the repair site was fused at 100 mW with pulses of 1.0 s. In the subgroup of laser-assisted nerve repair (LANR), albumen was used as a soldering agent to further reinforce the repair site. The control group consisted of nerves repaired by conventional microsurgical suture repair (CMSR), using 4-6 10-0 nylon sutures. Evaluation was performed at 1 and 6 weeks after surgery, and included qualitative and semiquantitative light microscopy. LANR performed with a protein solder results in a good early peripheral nerve regeneration, with an optimal alignment of nerve fibers and minimal connective tissue proliferation at the repair site. All three suture materials produced a foreign body reaction; the least severe was with polyglycolic acid sutures. CMSR resulted in more pronounced foreign-body granulomas at the repair site, with more connective-tissue proliferation and axonal misalignment. Furthermore, axonal regeneration in the distal nerve segment was better in the laser groups. Based on these results, CO(2) laser-assisted nerve repair with soldering in combination with absorbable sutures has the potential of allowing healing to occur with the least foreign-body reaction at the repair site. Further experiments using this combination are in progress.

Albumins↗

PubMed2002

35 years of experimental research in transmyocardial revascularization: what have we learned?

In the past 35 years many experimental studies have been performed to investigate the revascularization potential of transmyocardial revascularization and the possible working mechanisms underlying the observed clinical improvement in angina pectoris after this treatment. In this review of the experimental literature, the various methods that have been used to create transmyocardial channels and the most supported hypotheses on the working mechanism (channel patency, angiogenesis and myocardial denervation) are discussed and evaluated.

Animals↗