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Y Hao

Publications and source records attributed to Y Hao.

At least 73 records · Page 4Linked to original sources
PubMed1998

[Two-phase dynamic CT findings of gastric carcinoma and its value for tumor detection and gross classification].

OBJECTIVE: To analyze the two-phase dynamic CT features of gastric carcinoma and to assess its usefulness for tumor detection and gross classification. METHODS: Two-phase dynamic CT was performed in 63 cases of gastric carcinoma proved histologically by fibro-gastroscopic biopsy. CT features of gastric carcinoma, tumor detection, and gross classification were correlated with surgical and pathologic findings. RESULTS: The detectability by two-phase enhanced CT scanning of early and advanced gastric carcinoma was 100% and 98.2%, respectively. The overall accuracy of gross classification for advanced carcinoma was 65.4%, but for early gastric carcinoma, it was 0. The accuracy of Borrmann type II, III, IV was 85.7%, 100%, 55.6%, respectively. In the first phase (early enhancing phase) CT scan, the manifestation of early gastric carcinoma included local thickening of gastric wall, moderate or marked heterogeneous enhancement of lesions in 4 cases and mild enhancement in the other 4 cases. Local or extensive thickening of gastric wall, with or without ulceration, moderate or marked heterogeneous enhancement in early enhancing phase were shown in advanced gastric carcinoma. In the second phase, the degree of tumor enhancement in advanced carcinoma was slightly higher than that of the normal part of gastric wall. There were 4 cases with mucinous adenocarcinoma, a target or laminary appearance was present in 3 cases, and intramural calcification was present in 2 cases. CONCLUSION: 1. Enhanced dynamic CT scan plays a significant role in the diagnosis of gastric carcinoma, early enhancing phase scanning is the technique of choice nowadays for demonstrating tumor lesions. 2. Sophisticated scanning technique is mandatory in improving the diagnostic accuracy of gastric carcinoma.

Adenocarcinoma, Mucinous↗
PubMed1998

[The clinical value of intraoperative ultrasound of the liver].

OBJECTIVE: To evaluate usefulness of intraoperative ultrasound of the liver. METHODS: A 5.0 MHz ultrasound transducer was used to detect liver lesions, their number, location and relation to the intrahepatic blood vessels. RESULTS: Forty two patients with primary liver tumors received intraoperative ultrasonographic examination. Liver tumor was resected in 29 patients(69.0%). The tumors in 4 patients were unresectable due to their close relationship to the hepatic vasculature as judged by the ultrasound image. Multiple lesions were found in 6 patients during operation. CONCLUSIONS: Intraoperative ultrasound of the liver is sensitive enough to detect most liver lesions and to locate them by liver segment which makes radical tumor resection possible. It is useful to define the tumor in relation to hepatic vasculature. It can compensate for missing lesions in preoperative imaging studies. Fenestration operation for liver abscess and intervention treatment for liver cysts can be performed during operation.

Adult↗
PubMed1998

[Study on expression of Evi1 and MDS1-Evi1 genes in myelodysplastic syndromes].

OBJECTIVE: To investigate expression of Evi1 and MDS1-Evi1 genes in myelodysplastic syndromes (MDS) and its role in pathogenesis of MDS. METHODS: Expression of Evi1 and MDS1-Evi1 genes was examined in 31 MDS, 11 post MDS acute myeloid leukemia (post MDS AML) and 34 de novo AML patients by a semi-quantitative RT-PCR. RESULTS: Evi1 expression was not detected in 8 normal controls, but low MDS1-Evi1 expression levels (MDS1-Evi1/GAPDH < 0.1) detected in 3 of the 8 controls. Evi1 mRNA was expressed in 1 of 8 RA, 8 of 13 RAEB and 6 of 9 RAEB-t patients, and the percentage of Evi1 expression in RAEB(t) patients was higher than that in RA(P < 0.05). MDS1-Evi1 expression was detected in 5 of 8 RA, 9 of 13 RAEB and 5 of 9 RAEB-t patients, and MDS1-Evi1 expression levels (MDS1-Evi1/GAPDH > 0.1) in the patients were markedly higher than those in the controls. Evi1 expression was gradually increased in 4 of 5 RAEB-t patients with transformation from MDS to AML. The percentages of Evi-1 and MDS1-Evi1 expression in post MDS AML patients were higher than those in de novo AML (P < 0.01 and P < 0.05, respectively). The numbers of colony formation of progenitor cells in Evi1 and MDS1-Evi1-positive MDS patients were decreased as compared with Evi1 and MDS1-Evi1-negative patients. CONCLUSION: Abnormal expression of Evi1 and overexpression of MDS1-Evi1 might play a certain role in the pathogenesis or progression of MDS and post MDS AML.

Adult↗
PubMed1998

[Effect of Fusheng powder on activity of vascular endothelial cells and its adhesion to polymorphonuclear neutrophils].

OBJECTIVE: To explore the effect of Fusheng powder on the adhesion of polymorphonuclear neutrophils (PMN) in human peripheral blood to vascular endothelial cells (VEC). METHODS: Using cultured human umbilical vein cells as target cells, while being incubated with high glucose (HG, 30 mmol/L), high-lipid (HL, 20%), tumor necrosis factor-alpha (TNF-alpha, 10%) and hypoxia (95% N2, 5% CO2, 37 degrees C, 30 min, and then in the air 30 min) for 24 h, respectively, the activity of VEC and the adhesive effect of PMN to VEC were surveyed. RESULTS: It revealed that HG, HL, TNF-alpha and hypoxia could enhance obviously the adhesion of PMN to VEC, the cell attachment rate in normal control, HG group, TNF-alpha, hypoxia and HL after 30 minutes contact were 100%, 129.6%, 136.7%, 151.4% and 167.7% (all P < 0.01, compared with control group) respectively, but high and low dosage of the Fusheng powder could significantly inhibit the adhesion of PMN to VEC. CONCLUSIONS: HG, HL, TNF-alpha and hypoxia could all activate EC respectively and enhance the adhesion of PMN to VEC, but the Fusheng powder could protect VEC and partly block the effect of this adhesion. However, the effects of Fusheng powder on anti-adhesion are of great importance in clinical cardiovascular and cerebral vascular diseases.

Adult↗
PubMed1998

[Effects of Yunqitang on both esophageal mucosal morphology and esophageal motility in reflux esophagitis patients].

OBJECTIVE: To observe the effects of Yunqitang (YQT) on both esophageal mucosal morphology and esophageal motility in patients with reflux esophagitis (RE). METHODS: According to Syndrome Differentiation of TCM, 42 RE patients were divided into three groups: Disharmony of Liver and Stomach (D) group, Deficiency-Cold of Spleen and Stomach (DC) group, Heat Syndrome caused by depression of Liver Qi (H) group. No. I, II, III of YQT were taken respectively for 4 weeks. Before and after treatment scores of typical symptoms were collected, gastroscope and esophageal motility were measured. RESULTS: (1) The symptom remission rate was 81.1%, there were significant differences between the group DC with group D and Group H (P < 0.01). (2) The esophageal mucosal healing rate was 61.9%, the effective rate was 90.5%, and the ineffective rate 9.5%. There weren't significant difference of effective rates among the three groups (P < 0.05). (3) The changes of esophageal motility: lower esophageal sphictor pressure (LESP), average peristaltic pressure (APP) of group D were higher (P < 0.05), LESP, gastro-esophageal barrier pressure (GEBP) and peristaltic conduct speed (PCS) of group DC were remarkably higher (P < 0.05), GEBP of group H was improved (P < 0.05). CONCLUSIONS: YQT has a good therapeutical effect, it's not only resolving reflux symptoms, healing esophageal mucosa, but also improving esophageal motile function.

Adult↗
PubMed1998

Rhodopsin transgenic pigs as a model for human retinitis pigmentosa.

PURPOSE: To further characterize the retinas of Pro3471Leu rhodopsin transgenic pigs, a model for human retinitis pigmentosa. METHODS: Retinas from normal and transgenic pigs, newborn to 20 months old, were processed for light and electron microscopic immunocytochemical examination. RESULTS: At birth, rod numbers were normal in the transgenic retinas, but their outer segments were short and disorganized and their inner segments contained stacks of rhodopsin-positive membranes. The newborn rod synapses lacked synaptic vesicles and ribbons and had numerous rhodopsin-positive, filopodia-like processes that extended past the cone synapses into the outer plexiform layer. Rod cell death was apparent by 2 weeks and was pronounced in the mid periphery and central regions by 6 weeks. Far peripheral rods were initially better preserved, but by 9 months virtually all rods had degenerated. Cones degenerated more slowly than rods, but by 4 weeks the cone synapses were shrunken and some mid peripheral cones had lost their immunoreactivity for phosphodiesterase-gamma, arrestin, and recoverin. From 9 months to 20 months, the cone outer segments shortened progressively, and more cones lost immunoreactivity for these proteins. CONCLUSIONS: The rhodopsin transgenic pig retina shares many cytologic features with human retinas with retinitis pigmentosa and provides an opportunity to examine the earliest stages in photoreceptor degeneration, about which little is known in humans. The finding of abnormal rhodopsin localization in newborn rods is consistent with misrouting of mutant rhodopsin as an early process leading to rod cell death. Novel changes in the photoreceptor synapses may correlate with early electrophysiological abnormalities in these retinas.

Animals↗
PubMed1998

Enhanced expression of anti-apoptotic proteins in human papillomavirus-immortalized and cigarette smoke condensate-transformed human endocervical cells: correlation with resistance to apoptosis induced by DNA damage.

Apoptosis plays an important role in various biological processes including embryogenesis, differentiation, homeostasis, and oncogenesis. We have developed a system composed of primary human endocervical cells (HEN), HEN immortalized by human papillomavirus (HPV) type 16, and their counterparts subsequently malignantly transformed by cigarette smoke condensate (CSC). To understand the role of apoptosis in the multistep oncogenesis of human cervical cells, we examined the expression of apoptosis-associated proteins in our in vitro model system. The results showed no significant difference in the levels of apoptosis-inducing proteins bak and bax among all the cell types examined. On the other hand, the levels of apoptosis-inhibiting proteins bcl-2, bcl-xL and BAG-1 increased progressively after immortalization and transformation. The p53 protein level decreased in the HPV16-immortalized HEN and increased in one of two lines of the CSC-transformed HEN. Further, the increased levels of apoptosis-inhibiting proteins in the HPV16-immortalized and the CSC-transformed HEN correlated with progressively increased resistance of these cells to apoptosis induced by staurosporine or cisplatin. This study provided the first evidence that overexpression of apoptosis-inhibiting proteins is important for both multistep oncogenesis and resistance of human endocervical cells to apoptosis induced by DNA-damaging reagents.

Antineoplastic Agents↗
PubMed1998

Asymmetry of the mean-variability tradeoff raises questions about the model in investigations of individual bioequivalence.

Tradeoff between changes of intraindividual variations of 2 drug formulations and of the difference between their means is a characteristic of a procedure suggested for the determination of individual bioequivalence [Schall and Luus 1993] and to be proposed by the Food and Drug Administration for adoption. Hauck et al. [1996] investigated properties of the tradeoff. Their procedure was applied and extended in the present study. The tradeoff was shown to be asymmetric. Notably, a small change in intrasubject variations can elicit, under various conditions, a comparatively large change in the allowable difference between means which can still be compatible with the declaration of bioequivalence. For instance, when the intraindividual coefficients of variations are 40% and 38% for the reference and test formulations, respectively, the allowable difference between means may increase, as a benefit, by 12.3%. A penalty by 11.2% is elicited if the intrasubject variations of the reference and test products are 40 and 42%, respectively. In addition, 4-period crossover trials were simulated. Ratios of estimated variances of the 2 formulations followed an F-distribution. Distributions of changes in allowable deviations between means were calculated from the tradeoff relationships; generally substantial changes were noted with high probabilities. For example, with an intraindividual variation of 30% there is an estimated 37% probability that a benefit of 10% increase, or larger, is gained by chance in the allowable difference between means, and an additional 36% probability that a penalty of a 10%, or larger, decrease in the allowable difference is suffered. With an intrasubject variation of 40%, the estimated probabilities are 42% and an additional 42% for a 10% expansion and contraction, respectively, of the allowable difference between means. Consequently, the strong asymmetry of the tradeoff could result in very large probabilities for benefits and penalties. Therefore, the investigated model assessing individual bioequivalence does not appear to be suitable for implementation.

Clinical Trials as Topic↗
PubMed1997

Anatomic considerations of the lumbar isthmus.

STUDY DESIGN: A morphometric study of lumbar isthmus from L1 to L5 on 30 dried lumbar spines was conducted. OBJECTIVE: To provide anatomic data about the lumbar isthmus and to quantitatively evaluate structural features of the lumbar isthmus and its relationship to adjacent anatomic structures. SUMMARY OF BACKGROUND DATA: There are very few anatomic studies about the lumbar isthmus, and no study describes the relationship of the lumbar isthmus to its adjacent structures. METHODS: Direct measurements using digital calipers and a goniometer were taken from 30 dried lumbar spines. Anatomic evaluation focused on the lumbar isthmus and its related structures, the isthmus pedicle, and superior and inferior facets. Seven linear and four angular parameters of the lumbar isthmus were determined. RESULTS: The length of the superior edge of the isthmus gradually increased from L2 to L5 (from 8.22 +/- 1.43 mm at L2 to 10.44 +/- 1.90 mm at L5), and that of its inferior edge progressively decreased from L2 to L5 (from 8.67 +/- 1.76 mm at L2 to 6.34 +/- 1.74 mm at L5). The superoinferior diameter of the isthmus decreased from L3 to L5 (from 13.87 +/- 1.77 mm at L3 to 13.26 +/- 2.49 mm at L5). The superior edge of the isthmus was the thinnest at L4 (1.62 +/- 0.58 mm), and its thickness inferiorly increased from L1 to L5 (from 6.71 +/- 1.47 mm at L1 to 7.76 +/- 1.08 mm at L5). The medial and caudal inclination of the isthmus with respect to the pedicle gradually increased from L1 to L5 (from 112.3 degrees +/- 13.8 degrees at L1 to 119.2 degrees +/- 11.2 degrees at L5 medial inclination and from 132.5 degrees +/- 8.8 degrees at L2 to 139.0 degrees +/- 12.1 degrees at L5 caudal inclination, respectively). The dimensions of the lumbar isthmus were positively correlated to dimensions of the pedicle and orientations of the facets. CONCLUSIONS: This study provides detailed anatomic data of the lumbar isthmus. Anatomic parameters of the lumbar isthmus are related to the vertebral levels and have a significant correlation with the angles of the facets and the dimensions of the pedicles. The vulnerability of the pars interarticularis of the fifth lumbar vertebra has been anatomically confirmed.

Analysis of Variance↗
PubMed1997

Correlation of DNA fragmentation and chromatin condensation in apoptotic nuclei of the Ser 6 mouse retina.

The form of cell death known as apoptosis was first described in thymocytes. The hallmarks of apoptosis include chromatin condensation, membrane blebbing, formation of apoptotic bodies, and DNA fragmentation. DNA fragmentation can be visualized morphologically by the TdT-mediated dUTP-biotin nick end labeling (TUNEL) method that labels the cut DNA ends. However, at the light microscopic (LM) level, TUNEL-positive nuclei cannot readily be correlated with the other hallmarks of apoptosis. In the retina, chromatin condensation and DNA fragmentation are the major features of developmental cell death as well as photoreceptor degeneration. We performed TUNEL at the electron microscopic (EM) level, which permitted correlation of DNA fragmentation with chromatin condensation. We studied the retinas of transgenic mice (Ser 6) expressing the Pro347Ser mutant rhodopsin gene during developmental cell death (age 7 days) and photoreceptor degeneration (age 21 days). We found that 90% of the nuclei showing chromatin condensation were TUNEL positive as well. Our results demonstrated DNA fragmentation and chromatin condensation in the same cells as they underwent apoptosis in vivo, confirming the notion that these processes are concomitant events, and by implication, that activation of an endogenous endonuclease is an important step in the death process of retinal neurons.

Animals↗
PubMed1997

Long-term recovery kinetics of radiation damage in rat spinal cord.

PURPOSE: This study aimed to assess the influence of the level of initial injury on the long-term recovery kinetics of radiation damage in the central nervous system using a rat spinal cord model. METHODS AND MATERIALS: The adult rat spinal cord (C2-T2) was initially given two or three daily fractions of 9 Gy, or three daily fractions of 10.25 Gy. At day 4 or weeks 6, 8, 12, 20, 28, 40, or 52, animals were reirradiated with graded single doses of X rays. The end point was forelimb paralysis caused by white-matter necrosis. RESULTS: Latent times to paralysis as measured from the date of the initial treatment increased with increasing time interval between initial treatment and reirradiation but decreased with increasing size of initial injury. Retreatment ED50s were 14.1, 14.8, 15.4, 16.3, and 16.2 Gy for animals reirradiated at day 4 and weeks 8, 12, 20, and 28, respectively, after an initial dose of 9 Gy x 2. After 9 Gy x 3, the retreatment ED50s at day 4 and weeks 6, 8, 12, 20, 28, 40, and 52 were 10.0, 9.9, 9.8, 12.0, 13.9, 14.6, 14.7, and 15.5 Gy, respectively. For an initial dose of 10.25 Gy x 3, the retreatment ED50s at day 4 and weeks 8, 12, 20, 28, and 40 were 5.8, 6.1, 8.4, 10.6, 12.2, and 13.3 Gy, respectively. Using the linear-quadratic (LQ) model, alpha/beta of 3.0 Gy, to quantitate the biological effect of the different retreatment schedules, the initial doses of 9 Gy x 2 or 3, or 10.25 Gy x 3 were found to represent 47, 71, and 89% of the extrapolated response dose (ERD), respectively, and no significant increase in tolerance was observed for retreatment given within 8 weeks of initial treatment. Significant long-term recovery was observed thereafter and increased with increasing time interval to retreatment. The retreatment tolerance and radiation damage recovered at different intervals were influenced by the initial dose. Using direct analysis, the recovery kinetics could be best described by introducing a time function consisting of a linear and quadratic time component dependent on initial dose to the LQ model. CONCLUSION: These results are consistent with the presence of significant long-term recovery of radiation damage in rat spinal cord, and suggest that the size of the initial damage influences the recovery kinetics, and hence the retreatment tolerance.

Animals↗
PubMed1997

Abnormal change of p53 gene in gastric and precancerous lesions and APC gene deletion in gastric carcinoma and near tissues.

p53 gene mutation (exon4, 5, 6, 7, 8 and intron6) in gastric cancer and precancerous lesions and p53 gene (exon4 and ontron6), APC gene deletion in gastric carcinomas were studied by PCR/SSCP and PCR/RFLP. Results showed mutation rate of p53 in metaplasia, dysplasia and gastric carcinoma was 37.5% (3/8), 42.17% (8/19), 53.33 (16/30) respectively. There was significant difference among groups of metaplasia, dysplasia, cancer and normal controls. No exon8 mutation was found in metaplasia and dysplasia, but 4 cases were found to have exon8 mutation in cancer group. It is suggested that exon8 mutation occurs at the late stage of gastric cancer, but exon 5, 6, 7 mutation occur in the course of precancerous lesion to cancer. Loss of heterozygosity (LOH) of exon4, intron6, APC was 47, 37% (9/19), 8.73% (2/23), 16.67% (3/18) respectively. LOH of exon4 had something to do with poor differentiation, lymph node metastasis, depth of invasion. LOH of exon4 may be of prognostic marker of gastric cancer. We are led to conclude that p53 gene mutation is an early event and perhaps work together with ras oncogene in gastric carcinogenesis.

Gastric Mucosa↗
PubMed1997

Molecular dynamics study of free energy profiles for organic cations in gramicidin A channels.

The free energy profiles for four organic cations in right-handed single-helix gramicidin A dimers were computed by using umbrella sampling molecular dynamics with CHARMM. Ion-water column translocations were facilitated by using a novel "water-tunnel" approach. The overlapping pieces of free energy profile for adjacent windows were selected from three trajectories that differed in initial ion rotation and were aligned by the method of umbrella potential differences. Neglected long-range electrostatic energies from the bulk water and the bilayer were computed with DelPhi and added to the profile. The approach was corroborated for the formamidinium-guanidinium pair by using perturbation dynamics at axial positions 0, 6, 12, and 15 A from the channel center. The barrier to ethylammonium entry was prohibitive at 21 kcal/mol, whereas for methylammonium it was 5.5 kcal/mol, and the profile was quite flat through the channel, roughly consistent with conductance measurements. The profile for formamidinium was very similar to that of methylammonium. Guanidinium had a high entry barrier (deltaF = +8.6 kcal/mol) and a narrow deep central well (deltaF = -2.6 kcal/mol), qualitatively consistent with predictions from voltage-dependent potassium current block measurements. Its deep central well, contrasting with the flat profile for formamidinium, was verified with perturbation dynamics and was correlated with its high propensity to form hydrogen bonds with the channel at the dimer junction (not shared by the other three cations). Analysis of the ensemble average radial forces on the ions demonstrates that all four ions undergo compressive forces in the channel that are at maximum at the center of the monomer and relieved at the dimer junction, illustrating increased flexibility of the channel walls in the center of the channel.

Amidines↗
PubMed1997

Predicting the outcome of postasphyxial hypoxic-ischemic encephalopathy within 4 hours of birth.

OBJECTIVE: To build models that predict severe adverse outcome within 4 hours of birth in patients with postasphyxial hypoxic-ischemic encephalopathy. The goal was to develop models for selecting patients for therapeutic trials of neuroprotective medications. STUDY DESIGN: Retrospective cohort study with follow-up to a minimum age of 12 months of 164 "outborn" term infants admitted to a tertiary neonatal intensive care unit, and 14 "inborn" term infants in the two tertiary perinatal centers in a regionalized setting. After performing univariate screening tests, multivariate models of association between risk factors and "severe adverse outcome" (death or major neurosensory impairment) were constructed. RESULTS: Of 178 infants with postasphyxial hypoxic-ischemic encephalopathy of defined severity admitted consecutively between 1985 and 1992, 48 died, 40 survived with major neurosensory impairment, and 13 were lost to follow-up. The important predictors of severe adverse outcome in the first 4 hours were delayed onset of breathing, administration of chest compressions, and seizures. At 60 minutes of age, based on predicted probabilities of > 0.50, the sensitivity of the predictive model was 85% and specificity 68%. The parameter estimates of the predictive models are reported. CONCLUSIONS: Age of onset of breathing, administration of chest compressions, and age of onset of seizures were the most important variables predictive of adverse outcome in this study. Although fairly sensitive and specific, these predictive models should be applied with caution. To build more accurate models, a template for the conduct of a large, multicenter prospective study is provided.

Apgar Score↗
PubMed1997

Improvement in total positioning error for lateral prostatic fields using a soft immobilization device.

PURPOSE: To prospectively measure the total positioning error present in lateral pelvic fields of patients undergoing prostatic irradiation, and to evaluate the effect of a rigid table insert and soft immobilization on the magnitude of the measured error. MATERIALS AND METHODS: Sixty-one consecutive patients receiving radical prostatic irradiation with a four field technique underwent a total of 234 lateral portal films during the first, third, fifth and seventh week of treatment. The position of the isocentre was compared to the isocentre on the corresponding simulator films and the magnitude and direction of deviations recorded. The patients were divided in to three cohorts of 15 patients, 15 patients and 31 patients. The first cohort was treated on a standard treatment couch, the second cohort treated with the table top stiffened using a 1 cm polycarbonate insert, and the third cohort treated with a soft immobilization device supporting the lower legs, and the polycarbonate insert. RESULTS: There was no difference in the mean deviation of the vector of the isocentre displacement in the y and z directions identified at any of the four times when measurements were taken during therapy between the cohorts treated with or without the polycarbonate insert, but without immobilization. The overall mean deviation for these first two cohorts of patients was 3.9 mm. The positioning of patients treated with immobilization was compared to those treated without, and the immobilized patients had a significantly improved overall mean deviation of 2.6 mm (P = 0.002). This was a result of improvement in both the random and systematic components of the total error. In addition, the proportion of errors greater than 5 mm was reduced from 17% of set-ups to 8% of set-ups. The time during the course of treatment when the measurement was taken had no effect on positioning error for any of the treatment groups. CONCLUSION: Stiffening the treatment couch with a 1 cm thick polycarbonate insert had no effect on reducing total positioning error, but immobilization with an inexpensive and non-customized foam rubber leg support reduced total positioning error in a statistically significant way.

Humans↗
PubMed1997

Lack of influence of sequence of top-up doses on repair kinetics in rat spinal cord.

BACKGROUND AND PURPOSE: The rat spinal cord model was used to determine whether repair kinetics changed during a course of fractionated radiotherapy if twice daily doses were given either at the initial or final period of a concomitant boost irradiation schedule. MATERIALS AND METHODS: The rat cervical spinal cord was irradiated from C2-T2 in 870 animals with top-up doses of three daily fractions of 9 Gy representing 75% of the biologic dose at the ED50 level for white matter necrosis. To simulate concomitant boost protocols, these top-up doses were given either preceding (initial top-up) or following (final top-up) a b.i.d. schedule of 1 Gy/F delivered at 0, 1, 2, 4, 8 or 24 h interfraction intervals. The end point was forelimb paralysis secondary to white matter necrosis. RESULTS: For interfraction intervals of 0, 1, 2, 4, 8 and 24 h, the initial top-up schedules yielded ED50 values of 18.2, 19.2, 23.7, 21.3, 27.2 and 29.7 Gy, respectively; the corresponding ED50s from the final top-up schedules were 17.5, 19.0, 20.7, 21.2, 26.9 and 30.3 Gy, respectively. A 10% reduction in the ED50 value from pooled data was observed when the interfraction interval was reduced from 24 (ED50 = 30.3 Gy) to 8 h (ED50 = 27.1 Gy). Fitting the incomplete repair (IR) version of the LQ model with mono-exponential repair kinetics gave alpha/beta values of 1.4 and 1.5 Gy, and similar repair half-times of 4.3 and 5.0 h for the initial and final top-up experiments, respectively. The IR model with bi-exponential repair kinetics did not provide a better fit to the data. CONCLUSIONS: We conclude that the sequence of top-up doses has no apparent influence on radiation sensitivity or repair kinetics in the rat spinal cord. The clinical implication is that the interfraction interval but not the timing of the boost is a critical determinant of spinal cord tolerance in concomitant boost protocols.

Animals↗
PubMed1997

Interobserver variation in prostate cancer Gleason scoring: are there implications for the design of clinical trials and treatment strategies?

A series of prostate cancer histological slides from 71 patients were used to measure the interobserver variation among three pathologists awarding a Gleason score. The study was prompted on account of the use of histological grade to stratify patients prior to randomization within two clinical trials currently recruiting at our centre, and a proposed study that would allocate treatment depending upon the score awarded. The pathologists were expected to award a score based upon their day to day experience, there being no consensus meeting before-hand to agree on the grey areas of the Gleason grading system. We used the kappa statistic to assess the level of agreement. This was calculated both for comparison of the raw scores awarded by the three observers, as well as the grouped scores corresponding to those groupings used for the purposes of stratification in the two trials. The extent of the interobserver variation (weighted kappa) for the raw scores (Gleason scores 2-10) was 0.16 to 0.29 and for the grouped scores (Gleason scores < or = 7 or > or = 8), kappa was 0.15 to 0.29. For the raw scores, the total agreement rate was 9.9% and the total disagreement 26.8%; for the grouped scores the total agreement rate was 43.7%. It is concluded that, despite this level of agreement there is no concern regarding stratification using the Gleason score, because of the subsequent randomization. However, using a reported Gleason score to determine treatment might be inappropriate. These data indicate the value of a central review process for pathology grading in clinical trials, especially where the treatment is directly affected by this information.

Adenocarcinoma↗