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At least 1,729 records · Page 96Linked to original sources
PubMed1996

Map refinement of locus RP13 to human chromosome 17p13.3 in a second family with autosomal dominant retinitis pigmentosa.

In order to elucidate the genetic basis of autosomal dominant retinitis pigmentosa (adRP) in a large eight-generation family (UCLA-RP09) of British descent, we assessed linkage between the UCLA-RP09 adRP gene and numerous genetic loci, including eight adRP candidate genes, five anonymous adRP-linked DNA loci, and 20 phenotypic markers. Linkage to the UCLA-RP09 disease gene was excluded for all eight candidate genes analyzed, including rhodopsin (RP4) and peripherin/RDS (RP7), for the four adRP loci RP1, RP9, RP10 and RP11, as well as for 17 phenotypic markers. The anonymous DNA marker locus D17S938, linked to adRP locus RP13 on chromosome 17p13.1, yielded a suggestive but not statistically significant positive lod score. Linkage was confirmed between the UCLA-RP09 adRP gene and markers distal to D17S938 in the chromosomal region 17p13.3. A reanalysis of the original RP13 data from a South African adRP family of British descent, in conjunction with our UCLA-RP09 data, suggests that only one adRP locus exists on 17p but that it maps to a more telomeric position, at band 17p13.3, than previously reported. Confirmation of the involvement of RP13 in two presumably unrelated adRP families, both of British descent, suggests that this locus is a distinct adRP gene in a proportion of British, and possibly other, adRP families.

Chromosome Mapping↗
PubMed1996

Decision-making: a comparison of referral practice and primary care.

BACKGROUND: Should care by subspecialist physicians be more costly than care by primary care physicians? This article addresses diagnostic testing, one element of the answer to this question. METHODS: A theoretical analysis was conducted of the sequences of testing, treatment, or watchful waiting in patients with low, intermediate, or high probabilities of disease. This was followed by a reanalysis of data from a previously published study of patients with chest pain from two referral populations and two primary care populations. The study used a chest pain score as a summary measure of the number of suggestive findings. RESULTS: The analysis of sequences of testing, treatment, and watchful waiting suggests that patients with intermediate probabilities of disease are most likely to be referred. The study of patients with chest pain shows that the probability of disease for a given chest pain history score is higher in referred patients than it is in primary care patients, as is the proportion of patients with intermediate and high chest pain scores. This result is direct evidence that referral physicians get more patients with suspect but often uncertain histories. In general, the probability of disease given a particular history will be lower in primary care patients, and hence testing will be less fruitful. CONCLUSIONS: Subspecialists are more likely to see patients who represent a diagnostic puzzle and have intermediate probabilities of disease. Since patients with intermediate probabilities of disease are most likely to benefit from testing, a per capita rate of testing that is higher than in a primary care practice might be appropriate in a subspecialist's practice.

Adult↗
PubMed1996

The kinetics of repair of sublethal radiation-induced damage in pig skin: studies with multiple interfraction intervals.

The kinetics of the repair of radiation-induced sublethal damage (SLD) was studied for the epidermis of the pig. A total of either 7 or 14 interfraction intervals with incomplete repair was achieved by giving 28 fractions either as 7 x 2 fractions/day plus a top-up dose of 17 Gy (half tolerance) or as 14 x 2 fractions/day. The dose per fraction ranged from 1.96-4.82 Gy. A total of 9 intervals ranging from 0.17 h up to 8 h between fractions was used. The incidence of moist desquamation, as an estimate of acute epidermal response, was used as an end point to establish dose-effect relationships. The data were analyzed using either the incomplete repair model of Thames, assuming mono-exponential repair kinetics, or a modified version of the incomplete repair model, assuming bi-exponential repair of sublethal damage. Both methods of analysis allowed for the longer overnight interval between fractions. Analysis assuming mono-exponential repair gave a T1/2 of 0.74 h for the combined data, although there was a trend toward a longer half-time when only the longer interfraction intervals ( > 1.0 h) were used in the analysis. A further analysis using the modified version of an incomplete repair model gave a fast and a slow component of repair with significantly different half-times of 0.09 and 4.5 h, respectively. Varying the number of incomplete repair intervals by replacing half the number of fractions with a single half-tolerance top-up dose did not modify the kinetics of repair significantly, in terms of either the repair half-times or the proportion of repair associated with a fast and slow component. Reanalysis of data published previously for 3 and 4 fractions using the modified incomplete repair model again resulted in two components of repair, represented by the significantly different half-times of 0.17 and 3.0 h. These values were similar to those obtained from the multiple-fraction experiment. These data clearly demonstrate that an acutely responding tissue is associated with a long T1/2 for the repair of SLD which is independent of the dose per fraction. For accelerated fractionation schedules in the clinic, using multiple fractions per day, these results suggest a need to control the intervals between fractions carefully and when appropriate to reduce the total dose to avoid serious normal-tissue complications.

Animals↗
PubMed1996

[The effect of local control on overall survival after the breast-conserving therapy of breast carcinoma].

BACKGROUND: The impact of local control on survival in breast carcinoma has been controversially discussed depending upon the specific view of disease as being systemic from the initial onset or locally confined with spread sequentially from the primary tumor to the regional lymph nodes and then to distant sites. Results of recent studies provide a good example of why controversy persists over the benefit of local control on survival. PATIENTS AND METHODS. There are 4 recently updated randomised trials that compare conservation surgery alone or with radiation: Milan III (follow-up 3.5 years), Canada (follow-up 5 years), Uppsala/Orebro (follow-up 5 years), and NSABP-B06 (follow-up 10 to 12 years). In addition, the reanalysis of NSABP-B06-protocol reported by the EMMES Corporation has become available. Of further importance is the meta-analysis of Levitt et al. [7], which has used special statistical tools, the BAYESIAN-technique. RESULTS: All 4 trials report statistically significant increased local control and improved survival for the irradiated patients. Based on p-values and confidence intervals, survival was statistically improved in long-term follow-up of the NSABP-B06 trial, but not in the other trials, probably because of small sample sizes and short follow-up. At 10 years, the overall survival rates for the NSABP-B06 were 65 +/- 2.1% and 71 +/- 2.0% for lumpectomy alone or with radiation respectively (p = 0.04), the distant-disease-free survival 55 +/- 2.3% vs. 62 +/- 2.2% (p = 0.03), and the disease-free survival 48 +/- 2.2% vs. 56 +/- 2.2% (p < 0.01). Within the Bayesian framework, the expected advantage in 10 year survival was 6% (the mean of NSABP-B06 10 year survival) with an 83% probability that the 10-year-survival difference ranges between 2% and 10%. CONCLUSIONS: The careful analysis of these randomized trials comparing lumpectomy with or without radiation clearly indicate an improvement in overall survival for the irradiated patients which is associated with increased local control. Combination of this survival trend with the reduced psychological and economic costs associated with local recurrence provides excellent arguments for radiation therapy as the standard treatment concept in breast conservation therapy.

Bayes Theorem↗
PubMed1996

Analysis of local recurrences after breast conserving therapy using postoperative radiotherapy.

One hundred and ninety-one breast cancer patients had breast conserving therapy (lumpectomy and postoperative radiotherapy) at the Shikoku Cancer Center Hospital between July 1989 and December 1994. Seven patients developed recurrence, two of them experienced recurrence in the treated breast after a median follow-up of 27 months. One of the two patients with the local recurrence had an inflammatory cancer-like change in the treated breast which consisted of a diffuse induration in the breast and thick overlying skin with redness. It was very difficult to distinguish local recurrence from the local change due to radiation. Her primary tumor showed prominent lymphatic vessel involvement, although the surgical margins were negative histologically. We believe that the possible lymphatic retention after axillary dissection facilitated this type of progression of the residual tumor cells within the lymphatic vessels. Although this type of local recurrence is quite rare, it could cause distant metastases. Reanalysis of surgical treatment and postoperative adjuvant therapy for the patients with breast cancer showing prominent lymphatic vessel involvement is required.

Adult↗
PubMed1996

High and low fat consumers, their macronutrient intake and body mass index: further analysis of the National Diet and Nutrition Survey of British Adults.

OBJECTIVES: To explore the different characteristics of high and low fat consumers, in particular their macronutrient intake and body mass index. DESIGN: Reanalysis of data from the Dietary and Nutritional Survey of British Adults. Comparisons were made between groups defined as high and low fat consumers on the basis of 7-day weighed food records considered to be valid for energy intake. Individuals were classified in two ways according to the percentage energy from fat (FAT%) and the absolute amount of fat consumed (FATg). The criteria for classification of the high FAT% being > 45% (high fat) and < or = 35% (low fat). For the FATg group the threshold for the high fat group was > 138 g/day (men) and > 102 g/day (women), and for the low fat group < 85 g/day (men) and < 70 g/day (women). SETTING: Dietary data was collected from private households in Great Britain between 1986 and 1987. SUBJECTS: From the total population of 2197, individuals who were slimming, ill or had an EI: BMR of < 1.2 were excluded in order to use data which was most likely to represent habitual energy intakes. From the remaining 1240 subjects, 10.8% of this sample (6.1% of the total population) were classified as low fat consumers (76 men and 58 women) and 15.4% high fat (8.7% of the total population, 93 men and 98 women). MAIN OUTCOME MEASURES: Macronutrient consumption and body mass index (BMI). RESULTS: 30% of the subjects changed fat group classification when the criteria of defining high and low fat groups altered from FAT% to FATg. Nutrient intakes differed according to definition of the groups. The high fat FATg group ate significantly more of all nutrients than the low fat FATg group. However, this was not seen for the FAT% analysis, with the high fat group eating more fat and less carbohydrate. The average BMI tended to be higher in the high fat than the low fat groups, particularly in the FATg analysis. However, the high fat group contained a wide range of BMIs. Further exploration of BMI in the high fat groups, showed that age (an 11-year difference) was the only variable to distinguish individuals in the top and bottom quartiles of BMI. CONCLUSIONS: High and low fat consumers differ according to a number of variables, and this is affected by how these groups are defined (FAT% or FATg). High fat consumers tend to have a higher BMI than low fat consumers, but not all high fat consumers are overweight or obese.

Adult↗
PubMed1996

Cytochrome P450 CYP1A1 MspI polymorphism and lung cancer susceptibility.

We conducted a case-control study of 207 lung cancer patients and 283 controls to estimate the association of the MspI polymorphism in the cytochrome P450 CYP1A1 gene with lung cancer. The analysis of the CYP1A1 gene polymorphism was performed by RFLP analysis of PCR-amplified DNA. The association of the CYP1A1 polymorphism with lung cancer was assessed by logistic regression using the generalized additive modeling technique to adjust for race, education, smoking status, pack years, time since quitting smoking, asbestos exposures, and family cancer history. The frequencies of the MspI homozygote and heterozygote variant genotypes of CYP1A1 were 1% and 17%, respectively, in both lung cancer patients and controls. A significant association was found between the combined heterozygous and homozygous MspI variant of the CYP1A1 gene and lung cancer; the estimated odds ratio was 2.08 (95% confidence interval, 1.15-3.73). The association remained significant when we excluded the homozygous MspI variant individuals, the non-Caucasians, or the long-time tobacco quitters, and it was not modified by gender or cumulative cigarette consumption. In a specific histological cell type analysis, a positive association was found for each subtype of lung cancer, with no appreciable difference between cell types. In summary, our study demonstrated that the MspI variant CYP1A1 genotype is significantly associated with an increased risk of lung cancer among Caucasians with the odds ratio approximately, equivalent to 2 after controlling for important confounding factors. These results are similar to those obtained from reanalysis of published data on the combined CYP1A1 genotypes in a Japanese population (combined odds ratio, 1.95; 95% confidence interval, 1.17-3.28). Moreover, the elevated risk is noted in heterozygotes, i.e., individuals who carry only one copy of the variant gene.

Aged↗
PubMed1996

Impact of ganciclovir prophylaxis on heart-lung and lung transplant recipients.

BACKGROUND: Cytomegalovirus infection threatens pulmonary allograft survival and function. This retrospective study details the experience of ganciclovir prophylaxis against cytomegalovirus infection and its sequelae. METHODS: Eight-nine lung and heart-lung transplant recipients with positive cytomegalovirus serology were analyzed. The 37 recipients who underwent transplantation before September 1989 received no prophylaxis. The 52 subsequent recipients received ganciclovir prophylaxis. RESULTS: Thirty-six non-prophylaxed versus 42 prophylaxed patients had cytomegalovirus events with cumulative incidences of 100% and 86% (p < < 0.01), and median onsets of 37 +/- 21 versus 85 +/- 35 days, respectively (p < < 0.01); 22 non-prophylaxed versus 27 prophylaxed patients had cytomegalovirus pneumonitis with cumulative incidences of 60% and 55% (p < < 0.01), and median onsets of 34 +/- 14 and 84 +/- 26 days, respectively (p < < 0.01). Respiratory failure caused by cytomegalovirus pneumonitis developed in nine of the non-prophylaxed versus two of the prophylaxed patients (p < < 0.01). The significant estimated survival benefit in patients who received prophylaxis (p = 0.04) was not apparent when reanalysis was performed after exclusion of patients with respiratory failure (p = 0.36). Ganciclovir prophylaxis produced a significant delay in the development of obliterative bronchiolitis with a median time to onset of 1072 +/- 280 days versus 432 +/- 189 days for the non-prophylaxis cohort (p < < 0.01). CONCLUSIONS: Ganciclovir prophylaxis (1) improves recipient survival by reducing the severity of disease and essentially eliminating respiratory failure caused by cytomegalovirus pneumonitis, (2) reduces the incidence and delays the onset of cytomegalovirus events and pneumonitis, and (3) delays the onset of obliterative bronchiolitis.

Adolescent↗
PubMed1996

A reaction-diffusion model of cancer invasion.

We present mathematical analyses, experimental data, and clinical observations which support our novel hypothesis that tumor-induced alteration of microenvironmental pH may provide a simple but complete mechanism for cancer invasion. A reaction-diffusion model describing the spatial distribution and temporal development of tumor tissue, normal tissue, and excess H+ ion concentration is presented. The model predicts a pH gradient extending from the tumor-host interface, which is confirmed by reanalysis of existing experimental data. Investigation of the structure and dynamics of the tumor-host interaction within the context of the model demonstrates a transition from benign to malignant growth analogous to the adenoma-carcinoma sequence. The effect of biological parameters critical to controlling this transition are supported by experimental and clinical observations. Tumor wave front velocities determined via a marginal stability analysis of the model equations are consistent with in vivo tumor growth rates. The model predicts a previously unrecognized hypocellular interstitial gap at the tumor-host interface which we demonstrate both in vivo and in vitro. A direct correlation between the interfacial morphology and tumor wave front velocity provides an explicit, testable, clinically important prediction.

Carcinoma, Squamous Cell↗
PubMed1997

Neurophysiological aspects of language processing.

Neurophysiological studies of language processing in the intact brain have identified 3 major event-related potential (ERP) components correlating with different aspects of language: (1) an early left anterior negativity (ELAN) obtained in correlation with early syntactic processes, primarily processes of structuring the language input, (2) a centroparietal negativity around 400 ms (N400) reflecting lexicalsemantic integration processes, and (3) a late centroparietal positivity (P600) observed in correlation with secondary syntactic processes such as reanalysis and repair. These components manifest themselves approximately around 200 ms, 400 ms and 600 ms post onset of a critical word. Their variation in latency and magnitude can be used as a diagnostic criterion for language impairment.

Electroencephalography↗
PubMed1997

Pharmacologic intervention for the diagnosis of acute cholecystitis: cholecystokinin pretreatment or morphine, or both?

Recent data and reanalysis of the literature suggest that nonvisualization of the gallbladder on the delayed images of cholescintigraphy is a nonspecific finding. Morphine augmentation has a reasonably good, though imperfect, specificity and positive predictive value, that are significantly better than for delayed imaging, in addition to its logistical advantage (shortening the imaging time). The technique is recommended, therefore, for routine clinical use in patients with nonvisualization of the gallbladder at 1 hr. Further study seems to be necessary to assess the effect of variable or no visible effect of low-dose morphine among patients on the efficacy of morphine-augmented cholescintigraphy. Sincalide pretreatment, when administered at the physiologic rate, is helpful in conditions in which functional resistance to tracer flow into the gallbladder are present. The results from the series by Chen et al. and by Kim et al. suggest that morphine augmentation can further improve the efficacy of the test even after CCK pretreatment. A comparison between the efficacy of delayed imaging and that of imaging for 60-90 min after CCK pretreatment is not available. Therefore, the latter does not obviate the need for delayed imaging when the morphine augmentation technique is not used. Finally, the nuclear medicine physician should use the most optimal technique for the pharmacologic intervention, in other words, the dose and the rate of administration. Certain conditions and medications may affect gallbladder contraction. It is also important to be aware of the various physiologic and pharmacologic effects on imaging findings, not only those findings that are normal but also the undesirable variants. Failure to recognize such effects can lead to incorrect interpretations.

Acute Disease↗
PubMed1997

Detection and isolation of gene-corrected cells in Gaucher disease via a fluorescence-activated cell sorter assay for lysosomal glucocerebrosidase activity.

Gaucher disease type 1 results from the accumulation of glucocerebroside in macrophages of the reticuloendothelial system, as a consequence of a deficiency in glucocerebrosidase (GC) activity. Recent improvements in the methodologies for introducing foreign genes into bone marrow stem cells have prompted several groups to test the efficacy of gene transfer therapy as a curative treatment for Gaucher disease. Limitations of this approach include the potential for insufficient engraftment of gene-corrected cells and incomplete transduction of hematopoietic stem cells using retroviral gene transfer. Overcoming these obstacles may be critical in the case of treatment for Gaucher disease type 1, because GC transduced cells have not been shown to have a growth advantage over noncorrected cells. Here, we describe the development and application of a novel, fluorescence-activated cell sorter based assay that directly quantitates GC activity at the single cell level. In a test of this application, fibroblasts from a Gaucher patient were transduced, and high expressing cells sorted based on GC activity. Reanalysis of cultured sorted fibroblasts reveals that these cells maintain high levels of enzymatic activity, compared with the heterogeneous population from which they were sorted. The assay is sufficiently sensitive to distinguish GC activity found in Gaucher patient monocytes from that in normal controls. Furthermore, preliminary results indicate that increased GC activity can be detected in transduced, CD34+ enriched peripheral blood mononuclear cells isolated from a Gaucher patient. This method should be a useful addition to current gene therapy protocols as a means to quantitatively assess gene correction of relevant cell populations and potentially purify transduced cells for transplantation.

Cell Separation↗
PubMed1977

The impact of breast feeding patterns on the biometric analysis of infant mortality.

A major assumption of the biometric analysis of infant mortality as developed by Bourgeois-Pichat is that the age structure of infant deaths after the first month of life is virtually constant across time and cultures. Reanalysis of results from studies which compare the mortality of infants according to the type of feeding indicated that the relationship between mortality and age within the first year of life followed different patterns for breast fed and artificially fed infants. Historical data for populations with different breast feeding customs reveal similar differences in the age pattern of infant mortality. In populations where breast feeding was uncommon or of very short duration, infant mortality rises particularly steeply during the early months of the first year of life. The age structure of infant mortality in less developed countries where breast feeding is decreasing rapidly may bsimilarly affected. When substantial deviations from the linear relationship are evident, particular caution is required in applying the biometric technique, since in such situations the estimated endogenous mortality is very much affected by the particular set of data points within the first year of life which are chosen for the basis of the estimates.

Age Factors↗
PubMed1997

Fully parametric and semi-parametric regression models for common events with covariate measurement error in main study/validation study designs.

The derivation of the likelihood function for binary data from two types of main study/validation study designs where model covariates are measured with error is elaborated. Rather than limiting consideration to a restricted family of models with convenient mathematical properties, we suggest that empirical considerations, customized to the data at hand, should drive model choices. The joint likelihood function for the main study, in which the covariates are measured with error, and the validation study, in which they are not, is maximized, and estimation and inference proceeds using standard theory. Although the choice of the measurement error model is driven by empirical considerations, the relatively small validation study sizes typically seen may lead to misspecification, resulting in bias in estimation and inference about exposure-disease relationships. By using a nonparametric form for the measurement error model, the resulting semi-parametric methods suggested by Robins, Rotnitzky, and Zhao (1994, Journal of the American Statistical Association 89, 864-866) and Robins, Hsieh, and Newey (1995, Journal of the Royal Statistical Society, Series B 57, 409-424) are free from bias due to misspecification of the measurement error model, trading efficiency for robustness as usual. These fully and semi-parametric methods are illustrated with a detailed example from a main study/validation study of the health effects of occupational exposure to chemotherapeutics among pharmacists (Valanis et al., 1993, American Journal of Hospital Pharmacy 50, 455-462). A constant, prevalence ratio model for common binary events, with gamma covariate measurement error, is derived and empirically verified by the available data. A careful reanalysis of the data, taking measurement error fully into account, leads to a threefold increase in the log relative risk and no loss of statistical power. The semi-parametric estimates are consistent with the parametric results, providing reassurance that important bias due to misspecification of the measurement error model is unlikely.

Analysis of Variance↗
PubMedDate not supplied

Mesothelioma surveillance to locate sources of exposure to asbestos.

To determine whether there were previously unrecognized sources of asbestos exposure in British Columbia, incident mesothelioma cases (n = 51) and population-based controls (n = 154) were interviewed about their occupational histories and asbestos exposures. The following occupations were at elevated risk: sheet metal workers (OR = 9.6, 95% CI: 1.5-106), plumbers and pipefitters (OR = 8.3, 95% CI: 1.5-86), shipbuilding workers (OR = 5.0, 95% CI: 1.2-23), painters (OR = 4.5, 95% CI: 1.0-24), welders (OR = 3.9, 95% CI: 0.8-22), gardeners (OR = 3.9, 95% CI: 0.8-22), bricklayers (OR = 3.5, 95% CI: 0.9-14), miners (OR = 3.4, 95% CI: 0.9-13), machinists (OR = 3.2, 95% CI: 1.0-11), construction foremen (OR = 3.1, 95% CI: 0.9-11), and electricians (OR = 3.0, 95% CI: 0.8-12). In a reanalysis excluding subjects who worked in occupations or processes considered strongly a priori at risk, three groups remained of interest: non-asbestos miners (OR = 9.6, 95% CI: 1.8-53), bricklayers (OR = 5.4, 95% CI: 1.0-28), and construction labourers (OR = 2.8, 95% CI: 0.7-10.6).

Adult↗
PubMed1997

Measles vaccine efficacy in India: a review.

Different workers have used different designs to assess effectiveness of live, further attenuated measles vaccine i.e., seroconversion studies, outbreak investigations, field trials and coverage survey methods. The results were often contradictory. We reanalyzed data from these studies to find out optimum vaccine efficacy (VE) and its determinants in the Indian context. Although nutritional status and sex of the subjects did not affect seroconversion rates, the rates were greater among initially seronegative and older children. Overall seroconversion rates in 9-11 months children ranged between 56 and 96%. Studies showing poor seroconversion had an inadequate sample size and/or technical flaws that detracted from the reliability of results. However, appropriately designed studies demonstrated seroconversion rates of more than 90% in 9-11 months children who were initially seronegative. Since 5-10% of 9-11 months old infants had persistent measles maternal antibody, measles vaccine may be around 85-90% effective in this age group. These results are in agreement with the findings observed in outbreak investigations. These outbreaks fulfilled all the criteria which are considered necessary for optimum estimation of VE in such settings; VE was found to be more than 90% in outbreak settings. Conversely, retrospective coverage surveys grossly under estimated VE (about 60%) which was probably due to misclassification of vaccination status of enrolled children. The surveys were undertaken in areas where immunization records were grossly incomplete and only few mothers retained immunization cards. Unfortunately, VE was also under estimated in field trials which were neither randomized nor blind, and no placebo injections were used in control children; many observations were on record which could explain the under estimation of VE. Reanalysis of data from different types of studies indicates that efficacy of measles vaccine given at 9-11 months of age is of the order of 85-90% in the Indian context.

Child, Preschool↗
PubMed1997

Tests of the double-strand break, lethal-potentially lethal and repair-misrepair models for mammalian cell survival using data for survival as a function of delayed-plating interval for log-phase Chinese hamster V79 cells.

Our data (Reddy et al., Radiat. Res. 141, 252-258, 1995) on the kinetics of the repair of potentially lethal damage in log-phase Chinese hamster V79 cells are used to test some predictions which arise from the different assumptions of the repair-misrepair (RMR) (C. A. Tobias, Radiat. Res. 104, S77-S95, 1985), lethal-potentially lethal (LPL) (S. B. Curtis, Radiat. Res. 106, 252-270, 1986) and double-strand break (DSB) (J. Y. Ostashevsky, Radiat. Res. 118, 437-466, 1989) models. The LPL model defines the time available for repair of PLD (t(rep)) as the time taken to reach maximal survival in a delayed-plating recovery experiment. Those data show that after this time has elapsed, contrary to the expectation of the LPL model, survival can be increased by changing the medium used for delayed plating from fresh growth medium to conditioned medium. According to the RMR model, all potentially lethal lesions should also be committed by that time and be unavailable for repair in the new medium. Only the DSB model correctly predicted that PLD (= DSBs) would still be available for repair after that time. Second, data for split-dose recovery are used to predict the first-order kinetics time constant for DSB repair (tau(DSBR)) using the DSB model (24 +/- 1.5 min). This value is nearly identical to the value of 27 +/- 1 min determined from the data obtained by Cheong et al. using pulsed-field gel electrophoresis (PFGE) (Mutat. Res. 274, 111-122, 1992). The value based on PFGE is used to calculate the value of t(rep) predicted by the DSB model (2.6 +/- 0.1 h), which agrees with the value determined experimentally as the time when changing the delayed-plating medium from growth medium to conditioned medium no longer gives the full recovery seen with delayed plating in conditioned medium (2.5 h). However, some recovery was seen for a change in the medium (growth medium to conditioned medium) up to 5-6 h postirradiation. Reanalysis of the original data on DSB repair shows that they are consistent with two first-order repair rates (18 +/- 7 min and about 52 min). These results are consistent with two pools of DSBs (or cells), each with their own t(rep). The early t(rep), associated with tau(fast), is predicted to be 1.7 +/- 0.7 h, and the late t(rep), associated with tau(slow), is predicted to be about 5 h. Both values are in excellent agreement with the times at which changing from growth medium to conditioned medium no longer gives the full recovery seen in conditioned medium only (the early t(rep)), and the time when changing from growth medium to conditioned medium produces no further increase in survival (the late t(rep)), respectively. It is noted that attempts to correlate radiosensitivity with the rates of DSB repair, rather than using an explicit model such as the DSB model, are unlikely to be productive since survival depends on both tau(DSBR) and t(rep) (as defined in the DSB model) and the latter may be the more important determinant of radiosensitivity (as it appears to be for ataxia telangiectasia cells compared to normal fibroblasts and for irs compared to V79 cells).

Animals↗
PubMed1997

Differential rates of age of seizure onset between sexes and between hemispheres?

In a descriptive analysis of 158 patients with temporal lobe epilepsy, Taylor (1969) reported that the age of first seizure varied systematically as a function of laterality and sex. We conducted inferential analyses of Taylor's original data which (1) provided support for his proposal of disproportionate left hemisphere vulnerability to seizure onset in early life, but (2) failed to provide evidence of sex differences in age of onset of unilateral seizures. Examination of these effects in a larger sample of 844 patients drawn from the Bozeman Epilepsy Consortium provided some additional support for findings from the inferential analysis. Specifically, the left hemisphere appeared more vulnerable to seizure onset in childhood, this increased vulnerability extending to about age 5 years. Age of onset of seizures was not different when males and females were compared. Thus, reanalysis of Taylor's original data as well as examination of data from a larger, more contemporary sample suggest that seizure onset varies as a function of laterality, but not sex.

Adult↗