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R W de Bruin

Publications and source records attributed to R W de Bruin.

At least 19 recordsLinked to original sources
PubMed2003

Monitoring in situ dosimetry and protoporphyrin IX fluorescence photobleaching in the normal rat esophagus during 5-aminolevulinic acid photodynamic therapy.

Experimental therapies for Barrett's esophagus, such as 5-aminolevulinic acid (ALA)-based photodynamic therapy (PDT), aim to ablate the premalignant Barrett's epithelium. However, the reproducibility of the effects should be improved to optimize treatment. Accurate irradiation with light of a proper wavelength (633 nm), fluence and fluence rate has shown to be critical for successful ALA-PDT. Here, we have used in situ light dosimetry to adjust the fluence rate measured within the esophagus for individual animals and monitored protoporphyrin IX (PpIX) fluorescence photobleaching simultaneously. Rats were administered 200 mg kg-1 ALA (n = 14) or served as control (n = 7). Animals were irradiated with an in situ measured fluence rate of 75 mW cm-2 and a fluence of 54 J cm-2. However, this more accurate method of light dosimetry did not decrease the variation in tissue response. Large differences were also observed in the dynamics of PpIX fluorescence photobleaching in animals that received the same measured illumination parameters. We found that higher PpIX fluorescence photobleaching rates corresponded with more epithelial damage, whereas lower rates corresponded with no response. A two-phased decay in PpIX fluorescence could be identified in the response group, with a rapid initial phase followed by a slower rate of photobleaching. Non-responders did not show the rapid initial decay and had a significantly lower rate of photobleaching during the second phase of the decay (P = 0.012).

Aminolevulinic Acid↗
PubMed2001

Fractionated illumination for oesophageal ALA-PDT: effect on blood flow and PpIX formation.

The effect of fractionating the 633 nm illumination of 5-aminolaevulinic (ALA)-based photodynamic therapy (PDT) of the normal rat oesophagus was studied. Fractionation of the illumination could enhance the PDT effect in two ways: (a) delay of the vascular shutdown or relaxation of the vasoconstriction induced by ALA-PDT and (b) use of newly formed protoporphyrin IX (PpIX), produced during the dark interval. Forty rats were randomly allocated to two groups of 20 animals each. To study vascular effects, in group 1 illumination with 633 nm (100 mW/cm) was performed at 3 h after oral ALA administration (200 mg/kg) either continuously with 20 J/cm diffuser length (n = 5) or fractionated 2 x 10 J/cm with a 150 s interval (n = 5), five animals served as controls. Blood flow was measured with a laser Doppler flowmeter. To study the effect of renewed PpIX forming, animals in group 2 were illuminated continuously at 3 h after ALA with 20 J/cm (n = 5) or 40 J/cm (n = 5) or fractionated 2 x 20 J/cm with a 3 h interval (n = 5), five animals served as controls. In all animals the in vivo fluence rate and PpIX fluorescence were measured during illuminations and animals were killed at 48 h after PDT. ALA-PDT did not cause any significant vasoconstriction. Fluorescence measurements and dosimetric results in group 1 did not differ between animals illuminated continuously or fractionated with a 150 s interval. In group 2, during a 3 h dark interval, PpIX fluorescence increased and was bleached during the second illumination. The tissue optical properties changed during the 3 h dark interval, resulting in a lower in vivo fluence rate (p < or = 0.001). Fractionation did not result in more oesophageal damage. It was concluded that a 150 s interval during illumination in ALA-PDT does not increase oesophageal blood flow. During an interval of 3 h new PpIX is formed. In the present study, fractionated illumination using short or long time intervals did not result in more damage. Thus, this study shows no evidence for improved PDT effect with fractionated light delivery.

Aminolevulinic Acid↗
PubMed2001

Transplantation of a single kidney per se does not lead to late graft dysfunction.

In unraveling the pathogenesis of chronic transplant dysfunction (CTD), non-alloantigen specific factors, as ischemia/reperfusion and renal mass have been suggested to play a role in the process. The aim of the present study was to investigate the effect of the transplantation procedure per se on the development of CTD in a syngeneic kidney transplant model in the rat. Kidney transplantation was performed with the BN rat as donor and recipient, the recipient kidneys having been removed. Unilaterally nephrectomized (UNx) and native BN rats served as controls. Renal function was determined monthly (proteinuria and glomerular filtration rate/100 g body weight; GFR). The follow-up period was until 52 weeks post-transplantation. Histomorphological analysis of CTD according to the BANFF criteria was carried out. Immunohistochemical staining was performed to identify infiltrating cells (CD4, CD8, and ED1) and the expression of MHC class II and ICAM-1. Isografts had a minor, constant proteinuria during follow-up, which did not differ from that of UNx: 27 +/- 10 vs. 29 +/- 2 mg/24 h at week 52. Unilateral nephrectomy led to a significant reduction of the GFR, which was about 80% of that of native rats. The GFR of isografts did not differ from that of UNx rats. Histomorphology of renal isografts was comparable to UNx and native kidneys; some glomerulopathy and tubular atrophy leading to a total BANFF-score of 2.6 +/- 0.5. In native BN kidneys, few CD4+ cells and ED-1+macrophages (mphi) were found; MHC class II was constitutively expressed on the proximal tubules and ICAM-1 on the glomeruli and peritubular capillaries. UNx-kidneys showed a similar pattern. Isografts had significantly more CD4+ cells and Mphi, mainly localized in the glomeruli, and a more intense ICAM-1 expression in the glomeruli and interstitium. Transplantation of one kidney in itself does not lead to CTD.

Animals↗
PubMed2001

Contrast in the efficacy of hDAF mouse hearts between ex vivo perfusion and transplantation into primates.

In recent experiments, in which we compared hDAF transgenic rat hearts perfused with 15% human serum in the Langendorff device and hDAF rat hearts transplanted into cynomolgus monkeys, we demonstrated that in the ex vivo heart perfusion model both homozygous and heterozygous hDAF hearts survived longer as nontransgenic controls. Surprisingly, we found that only homozygous hDAF hearts were protected against hyperacute rejection in vivo. The first aim of this study was to determine whether perfusion of mouse hearts with higher human serum concentrations or human blood might explain some of the differences found in survival time of the recently performed experiments with rat heart xenografts. Secondly, we investigated whether the observed differences in survival times of rat xenografts between in vivo and ex vivo transplantation would also hold for mouse hearts transgenic for hDAF. An ex vivo model was used to perfuse hDAF mouse hearts and controls with human serum or blood, and hDAF transgenic hearts and controls were transplanted into cynomolgus monkeys. hDAF transgenic mouse hearts survived significantly longer than their controls when perfused with 15% human serum, but no difference was found when 30% human serum was used, or when these hearts were transplanted into cynomolgus monkeys. However, in both the in vivo and ex vivo models the amount of PMNs adhering to the vascular endothelium was significantly lower in hDAF transgenes as compared with their controls. In conclusion, in the ex vivo situation, the efficacy of hDAF transgenesis in preventing HAR is limited by serum complement concentration.

Animals↗
PubMed2001

Cold ischemia augments allogeneic-mediated injury in rat kidney allografts.

BACKGROUND: Some clinical studies demonstrate that kidney grafts with prolonged cold ischemia experience early acute rejection more often than those with minimal ischemia. The mechanism, however, is putative. Therefore, the aim of this study was to unravel the impact of ischemia on the immune response in rat kidney allografts compared with that in isografts. METHODS: To induce ischemic injury, donor kidneys were preserved for 24 hours in 4 degrees C University of Wisconsin solution before transplantation. No immunosuppression was administered. The histomorphology according to the BANFF criteria for acute rejection and infiltrating cells were assessed at days 1, 2, 3, 4, 6, and 8 post-transplantation. RESULTS: In allografts, exposure of the kidney to ischemia led to a significantly earlier onset of interstitial cell infiltration and tubulitis compared with nonischemic allografts. The BANFF score of interstitial cell infiltration was 1 +/- 0 vs. 0.25 +/- 0.29 at day 3 and 2 +/- 0 vs. 1.25 +/- 0.25 at day 4. In contrast, in isografts, the effect of ischemia on the histology was not significant. From day 6, the histologic differences between ischemic and nonischemic grafts disappeared. Ischemia led to a more intense expression of P-selectin (day 1), intercellular adhesion molecule-1 (ICAM-1; day 2), and major histocompatibility complex (MHC) class II on endothelium and proximal tubular cells (day 2) in both allografts and isografts. Concurrently with the up-regulated ICAM-1 and MHC expression, significantly more CD4(+) cells and macrophages infiltrated the ischemic allografts at days 2 and 3 and the ischemic isografts at day 4. Importantly, the influx of these cells after ischemia was significantly greater in allografts than in isografts. CONCLUSIONS: Cold ischemia augments allogeneic-mediated cell infiltration in rat kidney allografts. The earlier onset of acute rejection in 24-hour cold preserved allografts may be prevented by better preservation or treatment using tailored immunosuppression.

Animals↗
PubMed2000

Functional, histological, and inflammatory changes in chronically rejecting small bowel transplants.

Our aim was to develop a model of chronic rejection (CR) in small bowel allografts, and to study the changes occurring in these grafts. Small bowel transplantation was performed using the DA to AS rat strain combination. Short-term (5 mg/kg intramuscular, from days -2 to +9), or long-term cyclosporin treatment (5 mg/kg, 3 times a week until day 50) was given to prevent acute rejection. Controls were untreated allografts, DA isografts with and without cyclosporin, and normal DA and AS rats. They were followed for 50 and 100 days after transplantation. Recipients of a syngeneic graft lost weight during the first week after transplantation, but started to regain weight and kept growing thereafter. Histology showed normal bowel architecture with normal mesenteric lymph nodes and Peyers patches. Vigorous acute rejection occurred in the untreated allografts. Animals had persistent weight loss, and were killed between 6-13 days after transplantation. No clinical signs of graft-versus-host disease were seen. Histology showed end-stage acute rejection. In both cyclosporin-treated allografted groups the postoperative course was as in the isografted animals. However, all animals had histologic signs of CR by 50 and 100 days after transplantation. Changes were most prominent in the mesentery. Serositis with increased vascularity, inflammation with sclerosis, and patchy myointimal proliferation with endothelialitis of the mesenteric vessels were found. Changes in the bowel were patchy and included some thickening of the muscle coat, crypt hyperplasia, scattered necrotic cells in the crypts, slight blunting of villi and loss of goblet cells. Infiltrating cells in the mesentery and bowel consisted mainly of CD 4+ cells, CD 8- T-cells and monocytes/macrophages. Lactulose-mannitol urinary excretion ratio was significantly increased in short-term cyclosporin treated allografts at days 50 and 100 posttransplant. Serum albumin levels were significantly lowered in this group at both time points examined. We developed two models in which CR occurs after small bowel transplantation. Long-term cyclosporin treatment delayed the development of CR, since functional abnormalities were only seen in the animals that were treated with short-term cyclosporin.

Animals↗
PubMed2000

Negligible role for NK cells and macrophages in delayed xenograft rejection.

Hyperacute rejection (HAR) of a discordant xenograft can be avoided by complement manipulation, but delayed xenograft rejection (DXR) still leads to graft loss. It is generally assumed that macrophages and NK cells play key roles in DXR. In the present study the survival times and cellular infiltrate following guinea pig to rat heart transplantation was analyzed in the course of DXR, following aspecific and specific manipulation of macrophages and NK cells. HAR was overcome by a single injection of cobra venom factor 1 day before heart transplantation. To aspecifically reduce the inflammatory response dominating DXR, dexamethasone (DEXA) was given. Treatment with DEXA markedly reduced infiltration by NK cells, macrophages, and granulocytes. It also led to prolonged graft survival times (median survival of 0.4 days, n = 10, P < 0.05). In the second series of experiments the specific roles of NK cells and macrophages in DXR were further assessed. Monoclonal antibody 3.2.3 was used to selectively deplete NK cells. Liposome-encapsulated dichloromethylene biphosphonate was given to achieve macrophage depletion. Neither of these specific treatments, alone or combined, led to prolonged graft survival. Immunohistology revealed that at day 2 after transplantation no NK cells or macrophages were present in grafts from the combined treatment group. Only a mild infiltration of granulocytes was observed. Collectively, these results strongly suggest that NK cells and macrophages are not likely to be pivotal cell types in DXR.

Animals↗
PubMed2000

Etiology and pathophysiology of chronic transplant dysfunction.

Chronic transplant dysfunction (CTD) is the predominant cause of late graft failure. The common histopathological feature in all transplanted organs is intimal hyperplasia accompanied by organ specific lesions. The knowledge about CTD is incomplete, and there is no therapy to prevent or treat it. This review describes the current knowledge on the etiology of CTD, with emphasis on kidney transplants, and postulates a pathophysiologic route through which CTD may develop.

Acute Disease↗
PubMed1999

Late graft dysfunction after prolonged cold ischemia of the donor kidney: inhibition by cyclosporine.

BACKGROUND: The present study was devised to elucidate the influence of prolonged cold ischemia on the development of chronic transplant dysfunction (CTD) in kidney isografts (Brown Norway-->Brown Norway; BN-->BN) and in kidney allografts (BN-->Wistar Agouti/ Rij [WAG]) under temporary cyclosporine (CsA) therapy. METHODS: To induce ischemic injury, BN donor kidneys were preserved for 24 hr in 4 degrees C University of Wisconsin solution before transplantation. Renal function (proteinuria), histomorphology according to the BANFF criteria for CTD, and infiltrating cells were assessed. Grafts were examined both early at days 2, 3, 6, and 10, and late at week 26 (allografts) or at week 52 (isografts). RESULTS: Nonischemic isografts preserved a normal function and morphology. Ischemic isografts developed a progressive proteinuria over time and demonstrated significantly more glomerulopathy with macrophage (Me) infiltration and intimal hyperplasia than nonischemic controls at week 52. During the initial 10 days, there was an increased infiltration of MHC class II+ cells, predominantly CD4+ cells and Mphi, coinciding with up-regulated intercellular adhesion molecule-1 expression. CsA treatment in ischemic isografts inhibited infiltration of MHC II+ cells in the early stage, which was accompanied by significantly less renal damage at week 52 compared with untreated controls (proteinuria: 59+/-8 vs. 134+/-19 mg/24 hr; BANFF score: 2.8+/-0.4 vs. 4.3+/-1.0). Under CsA therapy, 24-hr cold ischemia of the allograft affected neither the onset or progress of proteinuria, nor the histomorphology (BANFF score: 7.8+/-2.4 vs. 7.3+/-1.9). In both ischemic and nonischemic allografts, intercellular adhesion molecule-1 expression and mononuclear cell infiltration (CD4, CD8, Mphi was abundantly present during the first 10 days and function deteriorated rapidly. CONCLUSIONS: Prolonged cold ischemia plays a role in the induction of CTD, but its deleterious effect can be successfully inhibited by CsA. Therefore, the alloantigeneic stimulus is the overriding component in the multifactorial pathogenesis of CTD.

Adenosine↗
PubMed1999

Kinetics, localization, and mechanism of 5-aminolevulinic acid-induced porphyrin accumulation in normal and Barrett's-like rat esophagus.

BACKGROUND AND OBJECTIVES: Photodynamic therapy may selectively destroy Barrett's epithelium in the esophagus. To optimize photosensitizer administration, the kinetics of 5-aminolevulinic acid (ALA)-induced porphyrin accumulation in the normal and Barrett's-like esophagus were studied in the rat. STUDY DESIGN/MATERIALS AND METHODS: Animals received 200 mg/kg ALA intravenously (n = 21) or orally (n = 21). Six rats served as controls. At t = 1, 2, 3, 4, 6, 12, and 24 hr, porphyrin concentration in the esophagus was measured by using chemical extraction, and porphyrin localization was determined by laser scanning microscopy (LSM). In addition, in 20 animals, porphobilinogen deaminase, ferrochelatase, and iron concentration were determined. In a second group (n = 24), an esophagojejunostomy was performed to induce a Barrett's-like esophagus. After 18 weeks, animals received ALA, and LSM was performed at t = 1, 2, 3, 4, 6, 8, and 12 hr. RESULTS: Porphyrin accumulation in normal mucosa was 3.5-fold higher than in muscularis, with a maximum at 3 hr after ALA administration. With LSM, strong homogeneous fluorescence of the squamous epithelium was shown, with minor fluorescence of submucosa and muscularis. In Barrett's-like epithelium, fluorescence was heterogeneous but was also restricted to epithelial cells. There was no difference in fluorescence intensity between Barrett's-like and adjacent squamous epithelium. Porphobilinogen deaminase activity was higher and iron concentration was lower in the mucosa than in the muscularis (P < 0.001). CONCLUSION: ALA-induced porphyrin accumulation selectively occurs in esophageal mucosa, whether normal or Barrett's-like, compared with the muscularis, with a maximum at 3 hr after ALA administration. Selectivity may be caused by a different activity of heme-synthetic enzymes or relative iron deficiency in the mucosa.

Administration, Oral↗
PubMed1999

Increased expression of basic fibroblast growth factor during chronic rejection in intestinal transplants is associated with macrophage infiltrates.

Long-term survival of intestinal transplants is hampered by chronic rejection (CR). Since transplants with CR demonstrate fibrotic changes, the cytokine basic fibroblast growth factor (bFGF) may be involved in the tissue remodelling of chronic intestinal rejection. The aim of this study was to investigate the bFGF gene and protein expression and distribution in chronically rejecting intestinal allografts. Orthotopic small bowel transplantation was performed in the allogeneic DA-to-AS rat combination. Cyclosporin was administered temporarily to prevent acute rejection. Controls were DA isografts and normal DA. bFGF gene expression was evaluated using reverse transcriptase polymerase chain reaction (RT-PCR) of the ileum RNA and was standardized against Glyceraldehyde-3-phosphate-dehydrogenase (GAP-DH) expression. bFGF protein was determined using immunohistochemistry. To identify the bFGF-positive cell type, sequential sections were stained for cell markers. Allografts showed histological features of CR, whereas isografts preserved normal architecture. bFGF gene expression was present in normal ileum and significantly upregulated in allografts. Immunohistochemical staining showed a significant increase in bFGF protein compared to isografts. Most bFGF-positive cells were localized in the submucosa and muscularis, particularly around the neural plexus. bFGF-positive cells appeared to be ED-2-positive macrophages, strongly suggesting that the site of bFGF production is the activated macrophage. This study demonstrates increased bFGF mRNA and protein in chronically rejecting intestinal allografts that appear to be produced by macrophages.

Animals↗
PubMed1999

Photodynamic therapy for esophageal lesions: selectivity depends on wavelength, power, and light dose.

BACKGROUND: Photodynamic therapy with 5-aminolevulinic acid-induced photosensitization could selectively eliminate esophageal epithelial lesions. This study aimed at optimizing laser parameters for 5-aminolevulinic acid photodynamic therapy of the normal rat esophagus. METHODS: Sixty rats received 200 mg/kg 5-aminolevulinic acid orally and were illuminated 3 hours later with either 633 or 532 nm light (n = 30 for each group) through an endoesophageal balloon catheter. Rats received either 8.3 or 25 J/cm diffuser, applied with a 33, 100, or 300 mW/cm diffuser. During illumination, tissue fluorescence measurements and light dosimetry were done. Rats were sacrificed at 48 hours after photodynamic therapy. RESULTS: During illumination, protoporphyrin IX fluorescence declined faster when a higher power output was used. Fluence rate at the esophageal surface was highest for 633-nm light. At 532 nm, light caused less damage to the epithelium and muscle than 633-nm light. Illumination with 33 mW resulted in selective epithelial ablation, whereas illumination with 300 mW caused muscle damage with minor epithelial damage. CONCLUSIONS: The assumed selective epithelial damage of 5-aminolevulinic acid photodynamic therapy in the esophagus largely depends on the combination of wavelength, power, and light dose applied. Most selective epithelial damage was found when low-power 633-nm light was used.

Aminolevulinic Acid↗
PubMed1999

Genetic susceptibility of the donor kidney contributes to the development of renal damage after syngeneic transplantation.

Solitary kidneys, especially in rats, appear vulnerable to develop functional and structural damage. However, differences in susceptibility exist between strains. It is not clear whether this is intrinsic to the kidney or due to environmental factors. Therefore, the aim of the present study was to investigate possible differences in genetic susceptibility for renal damage. By transplanting different rat donor kidneys into a normotensive, histocompatible recipient, the kidneys were exposed to the same blood pressure profiles, metabolic and hormonal environment. Kidneys from young adult hypertensive fawn-hooded (FHH) rats, a strain showing early onset renal damage, normotensive, renal damage-resistant August x Copenhagen-Irish (ACI), and (ACI x FHH) F1 donors were transplanted into male F1 recipients. The native kidneys of the recipients were removed 1 week after transplantation. The results were mutually compared and to their unilaterally nephrectomized littermates. Systolic blood pressure (SBP) and albuminuria (UaV) were determined at the time of transplantation and at 8 and 16 weeks. The histomorphologic analysis included the incidence of focal glomerulosclerosis (FGS), and determination of chronic transplant dysfunction according to the BANFF criteria. A negative impact of the transplantation technique in this syngeneic situation could not be detected as F1 transplants did not differ functionally and morphologically from their UNx controls. Transplanting an ACI kidney did not result in significant changes of SBP, UaV, and incidence of FGS compared to F1 transplants and ACI-UNx. In contrast, FHH kidneys did show a progressive increase of UaV and glomerulosclerosis and a significantly higher BANFF score, whereas the SBP did not differ from F1 transplants. The moderate hypertension seen in FHH did not travel with the kidney. Compared to the FHH-UNx rats, transplantation of a FHH kidney did significantly attenuate the increase of UaV and FGS. The susceptibility of the donor kidney appears to be an important factor in the development of chronic renal damage. This may play a role in the long-term functional changes seen after clinical renal transplantation.

Albuminuria↗
PubMed1999

EGF and TGF-beta1 gene expression in chronically rejecting small bowel transplants.

Long-term survival of small bowel transplants is hampered by chronic rejection. Epidermal growth factor (EGF) and transforming growth factor beta (TGF-beta) have opposing, regulatory roles in normal intestinal physiology and may be involved in the pathogenesis of chronic intestinal rejection. Our aim was to investigate the expression of EGF and TGF-beta1 in chronically rejecting small bowel transplants. Orthotopic small bowel transplantation was performed in the allogeneic DA-to-AS rat combination; Cyclosporin was administered temporarily to prevent acute rejection. Controls were DA isografts and normal DA rats. PreproEGF and TGF-beta1 gene expression was evaluated by northern blot analysis of the ileum RNA and standardized against glyceraldehyde-3-phosphate-dehydrogenase expression. Allografts demonstrated functional impairment and histological features of chronic rejection, whereas isografts appeared normal. Allografts demonstrated a significant reduction of EGF mRNA when compared to DA isografts. No significant changes were detected in TGF-beta1 expression in either allogeneic or syngeneic grafts. In conclusion, this study demonstrates reduced preproEGF and preserved TGF-beta1 gene expression in chronically rejecting small bowel transplants.

Analysis of Variance↗
PubMed1999

Timing of illumination is essential for effective and safe photodynamic therapy: a study in the normal rat oesophagus.

5-Aminolaevulinic acid (ALA)-induced, protoporphyrin IX (PpIX)-mediated photodynamic therapy (PDT) is an experimental treatment modality for (pre)malignant oesophageal lesions. This study aimed to optimize the time of illumination after ALA administration. Six groups of eight rats received 200 mg kg(-1) ALA orally, eight rats served as controls. Illumination was performed at 1, 2, 3, 4, 6 or 12 h after ALA administration with a 1-cm cylindrical diffuser placed in a balloon catheter (laser parameters: 633 nm, 25 J radiant energy, power output 100 mW). During illumination, fluorescence measurements and light dosimetry were performed. Animals were sacrificed at 48 h (n = 4) or 28 days (n = 4) after PDT. At day 28, an oesophagogram was performed. Largest PpIX fluorescence was found at 3 h after ALA administration. In vivo fluence rate was three times higher than the calculated incident fluence rate. At 48 h after PDT, major epithelial damage was found in all animals illuminated at 2 h, whereas less epithelial damage was found at 3-6 h and none at 1 and 12 h. In animals illuminated at 4, 6 and 12 h, but not at 2 h, oesophagograms showed severe dilatations and histology showed loss of Schwann cells. These results demonstrate that the choice of time interval between ALA administration and illumination is critical for achieving epithelial damage without oesophageal functional impairment. A short interval of 2-3 h seems to be most appropriate.

Aminolevulinic Acid↗
PubMed1999

Endoscopic ablation therapy for Barrett's esophagus with high-grade dysplasia: a review.

Besides esophagectomy and antireflux therapy with intensive endoscopic surveillance, endoscopic ablation therapy is a new treatment modality for Barrett's esophagus (BE) with high-grade dysplasia (HGD). Endoscopic surgical ablation can be performed by either a thermal, chemical, or mechanical method. This article describes the current management of patients with BE and HGD and the various methods of endoscopic ablation, including multipolar electrocoagulation, argon plasma beam coagulation, contact laser photoablation, and photodynamic therapy. It also summarizes the results of 37 patient studies, case reports, and abstracts on experimental endoscopic therapies for BE. The advantages and disadvantages of the various treatment possibilities are considered, and the future direction of the management of BE is discussed.

Barrett Esophagus↗
PubMed1998

5-Aminolaevulinic acid-induced protoporphyrin IX accumulation in tissues: pharmacokinetics after oral or intravenous administration.

UNLABELLED: In this study, the biodistribution of 5-aminolaevulinic acid (ALA) and accumulation of protoporphyrin IX (PpIX) in rats have been examined. Two groups of 21 WAG/Rij rats are given 200 mg/kg ALA orally or intravenously. Six rats serve as controls. At 1, 2, 3, 4, 6, 12 and 24 h after ALA administration, ALA and porphyrin concentrations are measured in 18 tissues and fluids. Liver enzymes and renal-function tests are measured to determine ALA toxicity. In both groups ALA concentration is highest in kidney, bladder and urine. After oral administration, high concentrations are also found in duodenal aspirate and jejunum. Mild, short-lasting elevation of creatinine is seen in both treatment groups. Porphyrins, especially PpIX, accumulate mainly in duodenal aspirate, jejunum, liver and kidney (> 10 nmol/g tissue), less in oesophagus, stomach, colon, spleen, bladder, heart, lung and nerve (2-10 nmol/g tissue), and only slightly in plasma, muscle, fat, skin and brain (< 2 nmol/g tissue). In situ synthesis of porphyrins rather than enterohepatic circulation contributes to the PpIX accumulation. Confocal laser scanning microscopy shows selective porphyrin fluorescence in epithelial layers. Peak levels and total production of porphyrins are equal after oral and intravenous ALA administration. IN CONCLUSION: administration of 200 mg/kg ALA results in accumulation of photosensitive concentrations of PpIX, 1 to 6 h after ALA administration, in all tissues except muscle, fat, skin and brain. Knowledge of the time-concentration relationship should be helpful in selecting dosages, routes of administration and timing of ALA photodynamic therapy.

Administration, Oral↗