Effect of age on the radiation-induced repopulation in mouse lip mucosa

The acute macroscopic radiation reactions in mouse lip mucosa were used as a biological model to evaluate the influence of aging on the radiosensitivity and more specifically on the repopulation capacity after irradiation of rapidly proliferating epithelial tissues. No difference in the mucosa response after single dose irradiations was observed for animals ranging between one and twelve months of age. There was a trend for decreased radiosensitivity of the lip mucosa comparing 18 months old (early-senescence) with young adult mice. The repopulation experiments involved two equal sized radiation doses delivered with an interval of ten days. Again, in all age-groups, not only was the 50% incidence-dose for mucosa desquamation similar, but also the full biphasic course of radiation reactions. These data therefore demonstrate that the capacity of the lip mucosa basal cells to restore the radiation damage was not modified by the phenomenon of aging.     

Effect of EGFR-inhibition on the radiation response of oral mucosa: experimental studies in mouse tongue epithelium

The aim was to quantify the effect of selective inhibition of the epidermal growth factor receptor (EGFR) on the radiation response of mouse oral mucosa to daily fractionated irradiation. Irradiation comprised graded single doses of 25 kV X-rays to the lower tongue surface or fractionated doses of 5 x 3 Gy week(-1) (200 kV X-rays) over 1 or 2 weeks, followed by graded local doses, to generate full dose-effect curves. For selective inhibition of EGFR, BIBX1382BS, a tyrosine kinase inhibitor, was administered orally at a dose of 50 mg kg(-1), for the entire overall treatment time. The ED50 (the dose expected to induce ulcer in 50% of the mice) for untreated mucosa was 11.9 +/- 1.2 Gy. Fractionated irradiation administered over 1 or 2 weeks yielded ED50 values for the concluding test irradiation of 6.7 +/- 2.1 and 6.5 +/- 1.9 Gy, respectively. Administration of BIBX1382BS resulted in a non-significant increase of the top-up ED50 to 8.3 +/- 1.6 Gy (p = 0.1197) after 1 week and to 7.6 +/- 1.6 Gy (p = 0.2263) after 2 weeks. EGFR inhibition does not alter the radiation response of oral mucosa to fractionated irradiation or interfere with mucosal repopulation processes. This indicates that the regulation of mucosal repopulation is largely independent of EGFR activation.     

Repopulation in mouse oral mucosa: changes in the effect of dose fractionation

PURPOSE: To define the fractionation effect, including the magnitude and kinetics of dose compensation, on days 3 and 8 after a single priming dose of 8 Gy. MATERIALS AND METHODS: Graded radiation doses were given to the snouts of C3H/Neu mice in 1 to 5 fractions within a time period of < or = 36 h, or in four fractions with intervals from 5 min to 4 h. Each protocol was terminated by a top-up dose of 2.5 Gy to a 3 x 3 mm2 test area in order to precipitate the subclinical damage induced by the snout treatment and to generate the full dose response. RESULTS: No significant increase in isoeffective dose by increasing fraction numbers or by increasing interfraction intervals could be detected at each time point after the priming treatment. This indicates that the effect of dose fractionation was entirely lost. CONCLUSIONS: The loss of fractionation effect may be interpreted as a substantial impairment of the processes underlying recovery from sublethal damage as a consequence of a repopulation-inducing priming dose given 3 days or 8 days in advance.     

Modulation of radiation-induced oral mucositis by pentoxifylline: Preclinical studies

Background and purpose

Oral mucositis is a frequent early side effect of radio(chemo)therapy of head-and-neck malignancies. The epithelial radiation response is accompanied by inflammatory reactions; their interaction with epithelial processes remains unclear. The aim of the present study was to investigate the effect of pentoxifylline (PTX) on the oral mucosal radiation response in the mouse tongue model.

Materials and methods

Irradiation comprised fractionation (5 fractions of 3 Gy/week) over 1 (days 0–4) or 2 weeks (days 0–4, 7–11), followed by graded local top-up doses (day 7/14), in order to generate complete dose–effect curves. PTX (15 mg/kg subcutaneously) was applied once daily over varying time intervals. Ulceration of mouse tongue epithelium, corresponding to confluent mucositis, was analyzed as the clinically relevant endpoint.

Results

With fractionated irradiation over 1 week, PTX administration significantly reduced the incidence of mucosal reactions when initiated before (day???5) the onset of fractionation; a trend was observed for start of PTX treatment on day 0. Similarly, PTX treatment combined with 2 weeks of fractionation had a significant effect on ulcer incidence in all but one experiment. This clearly illustrates the potential of PTX to ameliorate oral mucositis during daily fractionated irradiation.

Conclusion

PTX resulted in a significant reduction of oral mucositis during fractionated irradiation, which may be attributed to stimulation of mucosal repopulation processes. The biological basis of this effect, however, needs to be clarified in further, detailed mechanistic studies.

     

Cytogenetic biomonitoring in oral mucosa cells following dental X-ray

Objectives

In the past decades, X-rays have been used widely for diagnosis in dentistry. However, it is well known that ionizing radiation causes damage (including single- and double-strand breaks) to deoxyribonucleic acid (DNA) and DNA–protein crosslinks, and induces cellular death. Therefore, outlining the cytogenetic effects induced by X-ray is necessary to identify the degree of cancer risk and minimize potential risks to patients and clinicians. To date, a variety of assays have been proposed in cytogenetic biomonitoring studies, including those that assess metaphase chromosomal aberrations and sister chromatid exchanges, and micronucleus and single-cell gel (comet) assay.

Methods

Cytogenetic biomonitoring studies focusing on oral mucosa cells in individuals exposed to dental X-ray were reviewed.

Results

Dental X-ray can induce DNA damage and cytotoxicity in oral mucosa cells.

Conclusion

These results will contribute to a better understanding of X-ray-induced effects upon the cellular system in individuals continually exposed to known genotoxic/cytotoxic agents.     

Benefit of time-of-flight in PET: experimental and clinical results

Significant improvements have made it possible to add the technology of time-of-flight (TOF) to improve PET, particularly for oncology applications. The goals of this work were to investigate the benefits of TOF in experimental phantoms and to determine how these benefits translate into improved performance for patient imaging. METHODS: In this study we used a fully 3-dimensional scanner with the scintillator lutetium-yttrium oxyorthosilicate and a system timing resolution of approximately 600 ps. The data are acquired in list-mode and reconstructed with a maximum-likelihood expectation maximization algorithm; the system model includes the TOF kernel and corrections for attenuation, detector normalization, randoms, and scatter. The scatter correction is an extension of the model-based single-scatter simulation to include the time domain. Phantom measurements to study the benefit of TOF include 27-cm- and 35-cm-diameter distributions with spheres ranging in size from 10 to 37 mm. To assess the benefit of TOF PET for clinical imaging, patient studies are quantitatively analyzed. RESULTS: The lesion phantom studies demonstrate the improved contrast of the smallest spheres with TOF compared with non-TOF and also confirm the faster convergence of contrast with TOF. These gains are evident from visual inspection of the images as well as a quantitative evaluation of contrast recovery of the spheres and noise in the background. The gains with TOF are higher for larger objects. These results correlate with patient studies in which lesions are seen more clearly and with higher uptake at comparable noise for TOF than with non-TOF. CONCLUSION: TOF leads to a better contrast-versus-noise trade-off than non-TOF but one that is difficult to quantify in terms of a simple sensitivity gain improvement: A single gain factor for TOF improvement does not include the increased rate of convergence with TOF nor does it consider that TOF may converge to a different contrast than non-TOF. The experimental phantom results agree with those of prior simulations and help explain the improved image quality with TOF for patient oncology studies.     

Laser-induced thermal occlusion of berry aneurysms: initial experimental results

An intravascular laser-catheter technique was used to occlude 12 experimental berry aneurysms, ranging in size from 4 X 3 mm to 8 X 6 mm (length X width), while the patency of adjacent arteries was preserved. A small steel cap on the end of an optical fiber was fluoroscopically positioned within the aneurysm. The cap was rapidly heated by the optical transmission of laser energy. This produced a thermal tissue reaction within the aneurysm, resulting in its occlusion. After treatment, the steel cap was detached atraumatically from the fiber and left as a permanent implant within the occluded aneurysm. This method has an advantage over the use of a bare-ended intravascular optical fiber because the steel cap provides a uniform distribution of thermal energy, thereby reducing the risk of unexpected perforation during treatment. The radiologic and histologic results of using this laser-catheter system were evaluated 1-21 weeks after treatment.     

Peripheral atherectomy: experimental results with a new device

The size of present rotational atherectomy devices is limited in part by a tendency to produce vessel torsion. The authors designed and investigated a large-bore rotational atherectomy device for peripheral atherectomy in a single pass without significant torsion. A plaque was retrieved from 36 of 40 cadaveric iliac arteries. The mean plaque size was 8.4 x 3.9 mm, and the average number retrieved per artery was two. Thirty of 34 severely calcified arteries were treated successfully. Effluent study revealed no distal embolization; however, six perforations and four dissections occurred. Preliminary results suggest that a cutting surface with a relatively large diameter can be designed to be effective without producing vessel torsion. Changes in future designs will include added flexibility and expandable cutting surfaces to enhance safety and minimize entry diameter.     

Percutaneous removal of ureteral calculi: clinical and experimental results

Between May 1983 and October 1984, 51 patients who had 68 ureteral stones underwent treatment at the University of Minnesota. All 68 stones were removed successfully using percutaneous techniques. The 100% success rate is a great improvement over previous results at our institution. The primary factors appear to be the development of the retrograde-flush technique, familiarity with and access to a wider range of methods, and the increasing use of the retrograde ureterorenoscope to see stones in the lower ureter. The average patient was a 45-year-old man who had no other medical problems. The average hospital stay was 6.8 days. Experimental studies with dogs indicate that injection rates of up to 30 ml/sec of contrast material through a retrograde catheter in the ureter are safe if a vent is present in the upper collecting system.     

鼻咽癌调强适形放疗中口腔粘膜反应的护理干预

鼻咽癌（nasopharyngeal carcinoma，NPC）是我国常见的恶性肿瘤，放射治疗是其首选治疗方法。随着临床疗效的提高和生存期的延长，放疗后的生存质量已成为关注的热点问题。传统放射治疗所致的口腔粘膜反应严重影响患者的生存质量和放疗的进程，给患者带来巨大的痛苦。20世纪末出现的调强适形放射治疗（intensity modulated radiation therapy，IMRT）是放射技术、放射物理、     

Perimortem fixation of the gastric and duodenal mucosa: a diagnostic indication for oral poisoning

Two cases of fatal oral poisoning are presented. In the first case, a 40-year-old man died due to a lethal dose of mercury (blood concentration 113.8 μg/ml) and in the second, a 34-year-old man died of chloralhydrate overdose with a lethal blood concentration of trichloroethanol (52 μg/ml), the active metabolite of chloralhydrate. In both cases gross examination and histology showed an unusually well preserved gastrointestinal mucosa in addition to unspecific signs of intoxication. The two cases demonstrate that the phenomenon of perimortal fixation is a useful indication for the forensic pathologist and should direct the suspicion to oral poisoning. The detection of fixation facilitates toxicology screening by indicating that the relevant substance must have the capability to precipitate proteins. Received: 24 November 1998 / Received in revised form: 18 February 1999     

Achilles tendon rupture: experimental results on spontaneous repair in a sheep-model

We studied the course of spontaneous healing of Achilles tendons in a sheep model after transection and partial resection of the tendon by means of histological and biomechanical analyses. In 18 sheep used for another animal study the operated knee had to be excluded from weight-bearing; therefore the Achilles tendons were transected and for 1.5 cm partially resected in the middle substance of the tendon. For evaluation these spontaneously healed tendons (n = 18) were compared with the contralateral noninvolved tendons (n = 18). Specimens were analyzed 3, 6, and 12 months postoperatively by means of histology, polarized light, angiography, and mechanically analyzing the specific tensile strength and absolute tensile strength. We found that in all animals the resected tendon healed spontaneously. All animals exhibited a normal gait pattern at least 6 weeks postoperatively. Histologically, the tendinous area of healing demonstrated after 3 months a fibrous collagenous tissue with a loose fiber orientation. The cross-sectional area had at 3 months increased to maximum but decreased later. Concomitantly the fiber orientation improved with time and 12 months after transection the specimens showed a nearly normal histological structure of the healed tendon. Biomechanically the specimens exhibited a rather low specific rupture force after 3 months (28.8% of normal tendons) and 6 months (30.2%) but increased after 12 months (56.7%). In regard to the resulting total rupture force the decrease in the spontaneously healed tendons was less (75.6% after 3 months, 56.1% after 6 months, 81.18% after 12 months), because the cross-sectional area of the healing tendon had significantly (P < 0.05) increased to maximum after 3 and 6 months. Sheep Achilles tendons thus healed spontaneously without any immobilization. The initial healing mechanism is thickening of the scar tissue with improvement of the fiber orientation towards a tendonlike structure within 1 year. Parallel to this, the specific rupture force increased and the thickness of the newly tendonlike area decreased.