Akin Savas Toklu

Hyperbaric Oxygen Treatment of Chronic Refractory Radiation Proctitis: A Randomized and Controlled Double-Blind Crossover Trial With Long-Term Follow-Up

PURPOSE Cancer patients who undergo radiotherapy remain at life-long risk of radiation-induced injury to normal tissues. We conducted a randomized, controlled, double-blind crossover trial with long-term follow-up to evaluate the effectiveness of hyperbaric oxygen for refractory radiation proctitis. METHODS AND MATERIALS Patients with refractory radiation proctitis were randomized to hyperbaric oxygen at 2.0 atmospheres absolute (Group 1) or air at 1.1 atmospheres absolute (Group 2). The sham patients were subsequently crossed to Group 1. All patients were re-evaluated by an investigator who was unaware of the treatment allocation at 3 and 6 months and Years 1-5. The primary outcome measures were the late effects normal tissue-subjective, objective, management, analytic (SOMA-LENT) score and standardized clinical assessment. The secondary outcome was the change in quality of life. RESULTS Of 226 patients assessed, 150 were entered in the study and 120 were evaluable. After the initial allocation, the mean SOMA-LENT score improved in both groups. For Group 1, the mean was lower (p = 0.0150) and the amount of improvement nearly twice as great (5.00 vs. 2.61, p = 0.0019). Similarly, Group 1 had a greater portion of responders per clinical assessment than did Group 2 (88.9% vs. 62.5%, respectively; p = 0.0009). Significance improved when the data were analyzed from an intention to treat perspective (p = 0.0006). Group 1 had a better result in the quality of life bowel bother subscale. These differences were abolished after the crossover. CONCLUSION Hyperbaric oxygen therapy significantly improved the healing responses in patients with refractory radiation proctitis, generating an absolute risk reduction of 32% (number needed to treat of 3) between the groups after the initial allocation. Other medical management requirements were discontinued, and advanced interventions were largely avoided. Enhanced bowel-specific quality of life resulted.

Hyperbaric oxygen therapy in adriamycin extravasation: an experimental animal study.

&NA; Adriamycin extravasation is a serious problem that can lead to severe local necrosis and damage to underlying nerves, tendon, and muscle. There are some experimental studies in which conflicting results were reported about the beneficial effects of hyperbaric oxygen (HBO) in adriamycin‐induced skin lesions. In this study the effect of HBO on the healing of adriamycin‐induced wounds was investigated in the Wistar‐Albino rat model. Ninetyfive rats underwent injection of a 0.7‐ml adriamycin solution (2 mg per milliliter) subcutaneously on the right upper hind legs. The HBO group (n = 43) received HBO treatment (at 2.5 ATA for 80 minutes) twice a day for 28 days. The control group (n = 42) did not receive any therapy. Lesion size was measured for 4 weeks. There was no significant difference in lesion size between the groups on days 7 (p = 0.1364) and 14 (p = 0.1123), but the lesion size was significantly smaller in the HBO group than in the control group on days 21 (p = 0.0251) and 28 (p = 0.0001). Of 36 animals with lesions in the HBO group, complete wound healing occurred in 16 animals by day 40. However, there was no complete wound healing in any of the 36 animals with lesions in the control group. The beneficial effect of HBO in adriamycin‐induced skin lesions was observed in this experimental study. Aktaş Ş, Toklu AS, Olgaç V. Hyperbaric oxygen therapy in adriamycin extravasation: an experimental animal study. Ann Plast Surg 2000;45: 167‐171

The effects of hyperbaric oxygen therapy on blood–brain barrier permeability in septic rats

The mechanisms underlying the changes in blood-brain barrier (BBB) integrity in septic encephalopathy are poorly understood. The present study was designed to examine whether hyperbaric oxygen therapy (HBOT) influences the response of BBB to sepsis induced by cecal ligation and puncture (CLP) in rats. Cerebral cortical and hippocampal tissue levels of tumor necrosis factor-alpha (TNF-α), malondialdehyde (MDA) and glutathione (GSH) levels were measured. BBB permeability was functionally and structurally evaluated by determining extravasation of Evans blue (EB) and horseradish peroxidase (HRP) tracers, respectively. Immunohistochemistry and western blotting for occludin were performed. HBOT did not alter TNF-α levels in CLP operated rats while a significant decrease was noted when the therapy was subjected to intact rats. MDA levels in animals subjected to CLP plus HBOT were significantly decreased. In septic rats, the decreased GSH levels were significantly increased by HBOT. While HBOT attenuated the increased BBB permeability to EB in rats subjected to CLP (P<0.01), no macroscopic alteration was observed in the enhanced HRP extravasation. An increase in HRP extravasation was also observed by HBOT in intact animals. Occludin immunoreactivity and expression remained essentially unchanged in the brain capillaries of animals in all groups. Ultrastructurally, frequent vesicles containing HRP reaction products were observed in brain capillary endothelial cells of animals treated with CLP and/or HBOT. In conclusion, our results revealed that HBOT did not provide overall protective effects on the BBB integrity in septic conditions and even led to BBB disruption in intact animals.

The effects of hyperbaric air and hyperbaric oxygen on blood-brain barrier integrity in rats.

Hyperbaric oxygen (HBO) treatment yields conflicting results on blood-brain barrier (BBB) integrity under various pathological conditions and the effects of HBO on healthy brain is poorly understood. In this experimental study, the effects of HBO on BBB integrity were investigated in comparison with hyperbaric air (HBA) in intact rats. Four sessions of HBA or HBO were applied to intact rats in 24h. BBB integrity was functionally and structurally evaluated by determining extravasation of Evans blue (EB) dye and horseradish peroxidase (HRP) tracers. In immunohistochemical evaluation, relative staining intensity for occludin, a tight junction (TJ) protein, and aquaporin 4 (AQP4), a water-channel protein, was detected in the barrier type of microvessels of brain by image analysis. BBB permeability to EB dye significantly increased in animals in HBO treatment group compared to those in HBA and control groups (p<0.05). The immunoreactivity of occludin, a tight junction protein, remained essentially unaltered in capillaries of hippocampus in all groups. In animals exposed to HBO, AQP4 immunoreactivity significantly increased in parietal cortex compared to those in HBA and control groups (p<0.01). Ultrastructurally, frequent vesicles containing HRP reaction products were observed in capillary endothelial cells in cerebral cortex and hippocampus of rats subjected to both HBA and HBO. Our results indicate that the HBO administration to intact rats increased BBB permeability to both EB and HRP while HBA increased only HRP extravasation in these animals. The results of this study suggest that HBA also impairs the BBB integrity in intact rats as well as HBO.

Combination hyperbaric oxygen and temozolomide therapy in c6 rat glioma model

PURPOSE Temozolomide (TMZ) has anti-tumor activity in patients with malignant glioma. Hyperbaric oxygen (HBO) may enhance the efficacy of certain therapies that are limited because of the hypoxic tumor microenvironment. We examined the combined effects of TMZ-HBO in a rat glioma model. METHODS After stereotactic injection of C6/LacZ rat glioma cells into the Wistar rats brain, the rats were randomly assigned to three treatment groups [group 1, control treatment; group 2, TMZ alone; group 3, a combination of TMZ and HBO]. Rats were sacrificed 18 days after treatment, and number of intra-/peri-tumoral vessels, microendothelial proliferations, immunohistochemistry and necrotic area were evaluated. RESULTS Tumoral tissue was stained only sparsely with GFAP. Temozolomide treatment was significantly decreased in tumor tissue intratumoral vessel number / total tumor area level. The level of Ki67 was significantly decreased in the tumor tissue of the group 3. Additionally, the total necrotic area / total tumor volume (%) was decreased significantly in tumor tissue of the group 3 rats compared to group 1 and 2. CONCLUSION The combination of hyperbaric oxygen with temozolomide produced an important reduction in glioma growth and effective approach to the treatment of glioblastoma.

Paranasal sinus mucosal hypertrophy in experienced divers.

INTRODUCTION Due to the increasing popularity in recreational diving long-term health consequences of this sport have aroused interest in the diving community. Although not as important as dysbaric osteonecrosis, ischemic brain lesions, or neurophysiological symptoms, paranasal sinus mucosal hypertrophy (PSMH) has also been discussed as being more prevalent among divers. In this study, we used magnetic resonance imaging (MRI) to compare asymptomatic divers with control subjects for PSMH. METHODS We enrolled 79 male divers (34.0 +/- 5.7 yr) and 79 nondiving age- and sex-matched controls (33.8 +/- 6.1 yr). We used a questionnaire to elicit diving history. Divers with a history of sinus barotrauma, subjects with a history of chronic sinusitis or nasal allergies, and those with retention cysts, nasal polyps, or mastoiditis were excluded. T1-, T2-weighted axial and coronal images of the paranasal sinuses were taken with a 1.5-T MRI device. The threshold for PSMH was defined as mucosal thickness above 3 mm. RESULTS MRI revealed PSMH in 33 (41.8%) divers and 18 (22.8%) controls. There were no significant differences between the groups with respect to age, smoking history, or alcohol consumption. PSMH identified in divers did not show an association with age or diving history. DISCUSSION The higher rate of PSMH identified in divers suggests that diving may cause changes in the paranasal sinus mucosa.

Are pulmonary bleb and bullae a contraindication for hyperbaric oxygen treatment

BACKGROUND Air cysts or blebs in the lungs may predispose pulmonary barotrauma (PBT) by causing air trapping when there is a change in environmental pressure. The changes in the environmental pressure are also seen during hyperbaric oxygen treatments (HBOT). AIM The aim of this study was to determine how patients were evaluated for pulmonary blebs or bullae, and PBT prevalence in different HBOT centers. METHODS HBOT centers were asked to participate in this study and a questionnaire was send via e-mail. A total of 98 centers responded to our questionnaire. RESULTS Sixty-five HBOT centers (66.3%) reported that they applied HBOT to the patients with air cysts in their lungs. X-ray was the most widely used screening method for patients with a history of a lung disease. The prevalence of PBT in theses centers was calculated as 0.00045%. CONCLUSIONS Our survey demonstrated that (1) a significant portion of the HBO centers accept patients with pulmonary bleb or bullae, (2) although insufficient, X-ray is the mostly used screening tool for patients with a history of pulmonary disease and (3) the prevalence of pulmonary barotrauma is very low in HBOT.

Hyberbaric oxygen increases atresia in normal & steroid induced PCO rat ovaries

BackgroundIn this study, we investigated the effect of hyperbaric oxygen therapy (HBOT) on the morphology of estradiol valerate (EV) induced polycystic ovary (PCO) to find a new treatment modality for improvement of PCO.MethodsThe rats were divided into four groups. Group1, control; group 2, PCO group; group 3, PCO with HBOT group and group 4, normal ovary with HBOT. PCO was induced by a single intramuscular injection of 4 mg EV in adult cycling rats. Other rats with normal ovaries had oil injection as placebo. HBOT was applied to third and fourth groups for six weeks. Histopathologic evaluation of ovaries of all groups were performed & compared.ResultsSix weeks of HBOT was resulted in increase in follicular atresia, decrease in the number of primary, secondary, tertiary follicles and decrease in the number of fresh corpus luteum in normal rat ovary. HBOT on polycystic rat ovary, resulted in significant increase in atretic follicles which were already present.ConclusionsHBOT of six weeks itself, changed ovarian morphology in favor of atresia both in PCO group and control group. This result of aggravated follicular atresia after HBOT on EV induced PCO may be due to long-term exposure in our protocol which with this state seems to be inapplicable in the improvement of PCO morphology.

Remission of endometriosis by hyperbaric oxygen treatment in rats.

We designed this prospective, randomized controlled animal study to determine the effects of hyperbaric oxygen (HBO) on experimentally induced endometriosis in a rat model. Surgical induction of endometriosis was performed in 40, nonpregnant, female, Wistar-Albino rats at the Experimental Medicine Research Center of Istanbul University (DETAE). Four weeks later, the first and second laparotomies for volume measurement and peritoneal fluid (PF) collection were performed, and the rats were divided randomly into the study and control groups. The study group was exposed to HBO treatment for 6 weeks. Then, a third laparotomy was performed on all of the rats. The volume, histopathologic scores, Ki-67 labeling of the endometriotic implants, and the levels of tumor necrosis factor-α (TNF-α) in the PF were measured. The mean volume of the endometriotic implants in the study group was significantly lower than that of the control group at the end of the study (57.4 ± 12.5 vs 94.6 ± 17.2 mm3). The mean histopathological scores (1.60 ± 0.50 vs 2.42 ± 0.51), Ki-67 immunohistochemical scores (1.50 ± 0.51 vs 2.37 ± 0.49) of the endometriotic implants, and the TNF-α levels (5.33 ± 1.02 vs 8.16 ± 1.76 pg/mL) were significantly lower in the study group than in the control group. Hyperbaric oxygen treatment for 2 hours a day for 6 weeks resulted in significant remission of endometriosis in rats.

Aural Barotrauma in Submarine Escape: Is Mastoid Pneumatization of Significance?

Objective: Submarine escape training is carried out by preselected, healthy young men under strictly controlled conditions regarding exposure to pressure and the rate of pressure change. This provides a unique opportunity to investigate the relations between middle ear characteristics and susceptibility to barotrauma while avoiding possible confounding parameters. We examined a possible association between mastoid pneumatization and middle ear barotrauma (MEB) in submarine escape trainees.