U.M. Djasim

Hyperbaric oxygen therapy in the management of radiation-induced injury in the head and neck region: a review of the literature.

PURPOSE Radiotherapy is generally used in the treatment of malignant tumors in the head and neck region. It causes a hypoxic, hypocellular, and hypovascular environment that leads to injury to surrounding normal tissue, both acute and chronic, ranging from xerostomia to osteoradionecrosis. These side effects are debilitating and greatly influence quality of life in these patients. Hyperbaric oxygen (HBO) therapy is clinically used to prevent or treat these side effects by enhancing oxygen pressure and thereby regeneration. Although this therapy is widely applied, its mechanism of action is still poorly understood, and controversy exists in the literature about its clinical use. This review therefore aims to analyze the existing experimental and clinical research on this topic. MATERIALS AND METHODS A systematic search was performed in PubMed for experimental and clinical studies conducted regarding the use of HBO therapy in previously irradiated tissue, in the period from January 1990 to June 2009. RESULTS Experimental research is scarce, and clinical studies are especially lacking in terms of randomized controlled studies. Although discussions on the subject are ongoing, most studies suggest a beneficial role for HBO in previously irradiated tissue. CONCLUSION Further research, both experimental and clinical, is necessary to unravel the working mechanism of HBO therapy and validate its clinical use.

Histomorphometric comparison between continuous and discontinuous distraction osteogenesis

INTRODUCTION Experimental research on optimising the distraction protocol has been performed extensively in the past. However, relatively little research has been done on the rhythm of distraction. Findings in the orthopaedic literature showed that the outcome of distraction osteogenesis (DO) is positively influenced by increasing the rhythm of distraction. The aim of this study is to quantitatively compare continuous with discontinuous rhythms of distraction in rabbits. MATERIALS AND METHODS Tissue blocks of regenerated bone were harvested from thirty-eight young adult female New-Zealand White rabbits. After a latency period of three days, rabbits were subjected for eleven days to either single daily activation of the distractor at a rate of 0.9 mm/d, or triple daily activation at a rate of 0.9 mm/d, or continuous activation at a rate of 0.9 mm/d. After three weeks of consolidation, bone regenerates were analysed using histomorphometry. RESULTS The continuous DO group showed significantly (p<.01) more regenerate bone volume in the central part of the regenerate than the discontinuous DO groups. Higher osteoblastic activity was seen, as well as more blood vessels (p<.05). Bone volume and the number of blood vessels correlated significantly in the central part of the regenerate (p<.05). Also, the early mineral apposition rate (MAR) was higher than the late MAR (p<.05). CONCLUSIONS Continuous DO significantly accelerates bone formation when compared with discontinuous DO.

Continuous Versus Discontinuous Distraction: Evaluation of Bone Regenerate Following Various Rhythms of Distraction

PURPOSE To investigate continuous distraction osteogenesis (DO) of the nasal bones in a rabbit model, and to compare data from this continuous DO study with data from a previously conducted discontinuous DO study. In addition, radiographic and ultrasonographic bone-fill scores were determined to investigate whether these scores provided reliable predictive value for the amount of new bone formation in the distraction area. MATERIALS AND METHODS Skeletally mature female New Zealand White rabbits were subjected to distraction of the nasal bones. A custom-made continuous distractor was used to perform automatic non-stop distraction. Bone data were obtained from radiography, ultrasonography, and microcomputed tomography. Data from this experiment were compared with data from a previous study on discontinuous distraction rhythms. RESULTS Ultrasonographic bone-fill scores correlated significantly to actual bone volume in contrast to radiographic bone-fill scores. Bone volume was significantly higher in the continuous DO group compared with the discontinuous DO groups. CONCLUSION Continuous distraction resulted in accelerated osteogenesis compared with discontinuous distraction. Furthermore, bone-fill scores based on ultrasonography showed a significant correlation with actual bone volumes.

A hyperbaric oxygen chamber for animal experimental purposes

Facilities for hyperbaric oxygen therapy that are suitable for animal experimental research are scarce. In this paper, the authors introduce a hyperbaric oxygen chamber that was developed specifically for animal experimental purposes. The hyperbaric oxygen chamber was designed to meet a number of criteria regarding safety and ease of use. The hyperbaric oxygen chamber conforms to 97/23/EC (Pressure Equipment Directive), Conformity Assessment Module G Product Group 1. It provides easy access, and can be run in manual mode, semi-automatic mode and full-automatic mode. Sensors for pressure level, oxygen level, temperature, humidity and carbon dioxide level allow full control. This state-of-the-art hyperbaric oxygen chamber for animal experimental purposes permits the investigation of the biological mechanisms through which hyperbaric oxygen therapy acts at a fundamental level.

Rabbits as a model for research into craniofacial distraction osteogenesis

Various factors affect the choice of the appropriate animal for craniofacial research. We have evaluated the rabbit as a suitable animal for research on craniofacial distraction osteogenesis. We describe our experience with housing and handling them, surgical and experimental protocols, and compare them with other animals. We introduce, and describe the use of, a continuous hydraulic distractor on the nasal bones of the rabbit. Fifty-two skeletally mature New Zealand White rabbits were used. Forty-two of the 52 operations were uneventful. Ten of the fifty-two developed complications, of which two were animal-related, and the other eight distractor-related. During the experiments the animals stayed healthy, and the distraction procedures were well tolerated. Rabbits are excellent for use in biological research on craniofacial distraction osteogenesis. Specifically, their nasal bones are easily accessible, the size and shape of the nasal bones allow various commercially available as well as custom-made distractors to be attached to the bones easily, their care and housing are relatively simple and inexpensive, and harvesting of tissue for further analyses is no problem because their skulls are of a manageable size and shape compared with other laboratory animals.

Single versus triple daily activation of the distractor: No significant effects of frequency of distraction on bone regenerate quantity and architecture

OBJECTIVES To study the effect of two different frequencies of distraction on the quantity and architecture of bone regenerate using micro-computed tomography, and to determine whether radiographic and ultrasonographic bone-fill scores provide reliable predictive value for the amount of new bone in the distraction area. MATERIAL AND METHODS Twenty-six skeletally mature rabbits underwent three full days of latency, after which midface distraction was started. Low-frequency group (n=12): a distraction rate of 0.9 mm/d achieved by one daily activation for 11 days to create a 10mm distraction gap. High-frequency group (n=12): idem, but three daily activations were used instead of one. Control group (n=2) underwent no distraction. After 21 days of consolidation, bone-fill in the distraction area was assessed by means of ultrasonography and radiography. Micro-computed tomography was used to quantify new bone formation and bone architecture. RESULTS Relative bone volume (BV/TV) showed a tendency towards a difference (P=0.09) between the low and high-frequency groups. No significant differences were found for bone architecture. No significant correlation between BV/TV values and bone-fill scores was found. CONCLUSIONS An increase in rhythm from one to three activations daily does not create significantly more bone. Bone-fill score values provided no reliable predictive value for the amount of new bone formation.

The effects of heparan sulphate mimetic RGTA-OTR4120 on irradiated murine salivary glands

BACKGROUND This study focuses on the potential of ReGeneraTing Agent OTR4120 (RGTA-OTR4120) to treat radiation-induced damage of salivary glands. RGTAs are biopolymers designed to mimic the effects of heparan sulphate, thereby stimulation tissue repair and regeneration. METHODS C3H mice were irradiated with a single dose of 15 Gy in the head and neck region. RGTA-OTR4120 was injected 24 h after radiotherapy, followed by weekly injections. At 2, 6 and 10 weeks after radiotherapy, salivary flow rates were measured and animals were sacrificed to obtain parotid and submandibular glands for histology. Periodic acid Schiff stain was performed to visualize mucins that are produced by acinar cells. Amylase and total protein content were measured in saliva samples. RESULTS Salivary flow rates were increased at 2 weeks, but not at 6 and 10 weeks after radiotherapy with RGTA-OTR4120 administration, compared to irradiated controls. Two and 10 weeks after radiotherapy, the mucin production activity of acinar cells was increased under influence of RGTA administration. RGTA-OTR4120 did not influence amylase or total protein secretion. CONCLUSION RGTA-OTR4120 administration has a positive effect on salivary flow rates in irradiated mice on the short term. The effect was absent 10 weeks after radiotherapy, while at that time point, mucin producing activity of acinar cells was elevated by RGTA-OTR4120 administration. Given these results and the advantages of RGTA use in irradiated patients, further investigation on the potential of this drug to treat radiation-induced salivary gland damage, alone or in combination with other drugs, such as amifostine, is suggested.