Hospital develops policies to avoid future incidents.
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Accidents, Occupational↗
Biomedical subjects
J Williamson
Publications and source records attributed to J Williamson.
Radiation therapy morbidity in carcinoma of the uterine cervix: dosimetric and clinical correlation.
PURPOSE: To quantitate the impact of total doses of irradiation, dose rate, and ratio of doses to bladder or rectum and point A on sequelae in patients treated with irradiation alone for cervical cancer. METHODS AND MATERIALS: Records were reviewed of 1456 patients (Stages IB-IVA) treated with external-beam irradiation plus two low-dose rate intracavitary insertions to deliver 70 to 90 Gy to point A. Follow-up was obtained in 98% of patients (median, 11 years; minimum, 3 years; maximum, 30 years). The relationships among various dosimetry parameters and Grade 2 or 3 sequelae were analyzed. RESULTS: In Stage IB, the frequency of patients developing Grade 2 morbidity was 9%, and Grade 3 morbidity, 5%; in Stages IIA, IIB, III, and IVA, Grade 2 morbidity was 10% to 12% and Grade 3 was 10%. The most frequent Grade 2 sequelae were cystitis and proctitis (0.7% to 3%). The most common Grade 3 sequelae were vesicovaginal fistula (0.6% to 2% in patients with Stage I-III tumors), rectovaginal fistula (0.8% to 3%), and intestinal obstruction (0.8% to 4%). In the bladder, doses below 80 Gy correlated with less than 3% incidence of morbidity and 5% with higher doses (p = 0.31). In the rectosigmoid, the incidence of significant morbidity was less than 4% with doses below 75 Gy and increased to 9% with higher doses. For the small intestine, the incidence of morbidity was less than 1% with 50 Gy or less, 2% with 50 to 60 Gy, and 5% with higher doses to the lateral pelvic wall (p = 0.04). When the ratio of dose to the bladder or rectum in relation to point A was 0.8 or less, the incidence of rectal morbidity was 2.5% (8 of 320) vs. 7.3% (80 of 1095) with higher ratios (p < or = 0.01); bladder morbidity was 2.3% (7 of 305) and 5.8% (64 of 1110), respectively (p = 0.02). The incidence of Grade 2 and 3 bladder morbidity was 2.9% (10 of 336) when the dose rate was less than 0.80 Gy/h, in contrast to 6.1% (62 of 1010) with higher dose rates (p = 0.07). Rectal morbidity was 2% to 5% in Stage IB, regardless of dose rate to the rectum; in Stages IIA-B and III, morbidity was 5.2% (28 of 539) with a dose rate of 0.80 Gy or less and 10.7% (37 of 347) with higher dose rates (p < 0.01). Multivariate analysis showed that dose to the rectal point was the only factor influencing rectosigmoid sequelae, and dose to the bladder point affected bladder morbidity. CONCLUSIONS: Various dosimetric parameters correlate closely with the incidence of significant morbidity in patients treated with definitive irradiation for carcinoma of the uterine cervix. Careful dosimetry and special attention to related factors will reduce morbidity to the lowest possible level without compromising pelvic tumor control.
Brachytherapy↗
Survival versus years of healthy life: which is more powerful as a study outcome?
Studies of interventions that are intended to improve patients' health are often evaluated with survival as the primary outcome, even when a measure adjusted for quality of survival, such as years of healthy life (YHL), would seem more appropriate. The purpose of this article is to determine whether studies based on survival are more or less powerful than studies based on YHL in clinical trials where either measure might be appropriate. We used data from the Cardiovascular Health Study (CHS) to estimate the sample size that would be needed in studies of 156 different health conditions, for the two outcome measures. The median sample size for a 5-year study was 687 if survival was the endpoint and 484 for YHL. YHL usually required lower sample sizes than survival, although survival was more powerful for some health conditions. We also found that lengthy studies, and studies with many follow-up measures per person, did not have appreciably higher power than less intensive studies. We conclude that clinical investigations in which the goal is to improve health may often be performed more efficiently with YHL rather than survival as the primary outcome measure. Such studies can be short in duration, with relatively few measures per person of health status.
Aged↗
Factor structure of the Neurobehavioral Cognitive Status Exam (COGNISTAT) in healthy, and psychiatrically and neurologically impaired, elderly adults.
This study reports the results of factor analyses of COGNISTAT (NCSE) in a sample of elderly persons comprised of "healthy" participants with no psychiatric or neurological impairments (n = 153), individuals with psychiatric impairments (n = 70), and those with neurological impairments (n = 80). Our findings support a unitary factor structure for COGNISTAT, though a separate factor of unclear clinical or theoretical significance was suggested.
Adult↗
Novel locus for autosomal dominant hereditary spastic paraplegia, on chromosome 8q.
Hereditary spastic paraplegia (HSP) is a clinically and genetically heterogeneous group of disorders characterized by insidiously progressive spastic weakness in the legs. Genetic loci for autosomal dominant HSP exist on chromosomes 2p, 14q, and 15q. These loci are excluded in 45% of autosomal dominant HSP kindreds, indicating the presence of additional loci for autosomal dominant HSP. We analyzed a Caucasian kindred with autosomal dominant HSP and identified tight linkage between the disorder and microsatellite markers on chromosome 8q (maximum two-point LOD score 5.51 at recombination fraction 0). Our results clearly establish the existence of a locus for autosomal dominant HSP on chromosome 8q23-24. Currently this locus spans 6.2 cM between D8S1804 and D8S1774 and includes several potential candidate genes. Identifying this novel HSP locus on chromosome 8q23-24 will facilitate discovery of this HSP gene, improve genetic counseling for families with linkage to this locus, and extend our ability to correlate clinical features with different HSP loci.
Adult↗
Temporal trends in AIDS-related survival.
Although research indicates that AIDS-related survival has improved over calendar time, studies of temporal AIDS-related survival patterns are often confounded by the stage of AIDS diagnosis. The objective of the present study was therefore to assess temporal trends in AIDS-related survival from clinical indicators other than point of AIDS diagnosis. The study sample consisted of 2126 adult HIV-positive patients who were treated between 1987 and 1996 at a large southwestern academic medical center. Proportional hazards analyses indicate that survival from each of the following clinical baselines improved in a linear fashion over calendar period: first CD4 count, first CD4 count of 200 or greater, first CD4 count less than 200, and diagnosis of Pneumocystis carinii pneumonia, cytomegalovirus, and Mycobacterium avium complex. These findings indicate that previously estimated survival trajectories have persisted through the mid-1990s, even when defining survival from clinical indicators other than AIDS diagnosis.
Acquired Immunodeficiency Syndrome↗
Determinants of HIV-related survival among Texas prison inmates.
Research indicates that being incarcerated adversely affects disease progression and overall health status. Because HIV infection is a growing problem among prison populations in the United States, understanding how incarceration affects HIV-related survival patterns is critical. The present study examined determinants of HIV-related survival in a cohort of 2380 Texas Department of Criminal Justice (TDCJ) inmates who were treated for HIV/AIDS, dating from January 1, 1992 and June 31, 1997. Assessment of the study factors indicated that there were no substantial violations of the assumptions of the Cox's proportional hazards (PH) model in the present study population. Furthermore, to address the potential problem of censoring-related bias, mortality information was collected on all inmates who were paroled on the basis of disease status. The present study's findings indicate that the following factors were associated with significant decreases in HIV-related survival in the TDCJ prison population: male gender, older age, self-report of no known HIV transmission risk factors, and presence of cytomegalovirus (CMV), Mycobacterium avium complex (MAC), and Pneumocystis carinii pneumonia. Moreover, survival decreased in a monotonic fashion with decrease in baseline CD4 count. While the majority of the present study's findings were consistent with those reported for non-incarcerated populations, it will be important for investigators to assess whether these findings persist among future cohorts of prison inmates.
Acquired Immunodeficiency Syndrome↗
Missing-data in epidemiological studies of age-associated cognitive decline.
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Aged↗
Hyperbaric oxygen in the prevention of osteoradionecrosis of the jaws.
Patients who have had their jaws irradiated as part of management of head and neck malignancy are at risk of osteoradionecrosis (ORN) following tooth extraction. Thirty-seven patients with a history of irradiation to the jaws were managed during a four year period. Twenty-nine patients received hyperbaric oxygen therapy (HBO) consisting of 20 treatments before surgery and ten treatments after. Only one (4 per cent) developed ORN. Seven patients who did not have HBO and one who did (15 per cent) developed ORN. The need for prophylactic treatment with HBO is discussed. It is recommended that prophylactic HBO is used prior to surgery for irradiated facial bones.
Adult↗
At least three genes account for familial papillary thyroid carcinoma: TCO and MNG1 excluded as susceptibility loci from a large Tasmanian family.
Recent studies have mapped two susceptibility loci which appear to account for familial multinodular goitre (MNG1) and a variant of familial papillary thyroid cancer (PTC), with associated multinodular goitre (TCO). A Tasmanian family (Tas1) has been identified with an autosomal dominant form of PTC. This study has examined the MNG1 and TCO loci to determine if they are similarly predisposing the Tas1 family to PTC. Linkage analysis using identical microsatellite markers described in the two previous studies was used to determine the significance of these loci in the Tasmanian family. The resultant LOD scores were sufficiently negative using multipoint parametric analysis to exclude these two loci from involvement in the Tasmanian family. In addition, six candidate genes, RET, TRK, MET, TSHR, APC and PTEN were also excluded as susceptibility genes in Tas1 by using microsatellites that are positioned in or in close proximity to these genes. These results suggest that there are at least three susceptibility genes that predispose families to familial PTC.
Carcinoma, Papillary↗
The human polycomb group complex associates with pericentromeric heterochromatin to form a novel nuclear domain.
The Polycomb group (PcG) complex is a chromatin-associated multiprotein complex, involved in the stable repression of homeotic gene activity in Drosophila. Recently, a mammalian PcG complex has been identified with several PcG proteins implicated in the regulation of Hox gene expression. Although the mammalian PcG complex appears analogous to the complex in Drosophila, the molecular mechanisms and functions for the mammalian PcG complex remain unknown. Here we describe a detailed characterization of the human PcG complex in terms of cellular localization and chromosomal association. By using antibodies that specifically recognize three human PcG proteins- RING1, BMI1, and hPc2-we demonstrate in a number of human cell lines that the PcG complex forms a unique discrete nuclear structure that we term PcG bodies. PcG bodies are prominent novel nuclear structures with the larger PcG foci generally localized near the centromeres, as visualized with a kinetochore antibody marker. In both normal fetal and adult fibroblasts, PcG bodies are not randomly dispersed, but appear clustered into defined areas within the nucleus. We show in three different human cell lines that the PcG complex can tightly associate with large pericentromeric heterochromatin regions (1q12) on chromosome 1, and with related pericentromeric sequences on different chromosomes, providing evidence for a mammalian PcG-heterochromatin association. Furthermore, these heterochromatin-bound PcG complexes remain stably associated throughout mitosis, thereby allowing the potential inheritance of the PcG complex through successive cell divisions. We discuss these results in terms of the known function of the PcG complex as a transcriptional repression complex.
Cell Line↗
Isolation and characterization of mouse minisatellites.
Minisatellites provide the most informative system for analyzing processes of tandem repeat turnover in humans. However, little is known about minisatellites and the mechanisms by which they mutate in other species. To this end, we have isolated and characterized 76 endogenous mouse VNTRs. Fifty-one loci have been localized on mouse chromosomes and, unlike in humans, show no clustering in proterminal regions. Sequence analysis of 25 loci revealed the majority to be authentic minisatellites with GC-rich repeat units ranging from 14 to 47 bp in length. We have further characterized 3 of the most polymorphic loci both in Mus musculus subspecies and in inbred strains by using minisatellite variant repeat mapping (MVR) by PCR to gain insight into allelic diversity and turnover processes. MVR data suggest that mouse minisatellites mutate mainly by intra-allelic nonpolar events at a rate well below 10(-3) per gamete, in contrast to the high-frequency complex meiotic gene conversion-like events seen in humans. These results may indicate a fundamental difference in mechanisms of minisatellite mutation and genome turnover between mice and humans.
Alleles↗
Dermal fibropapillomas in cats.
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Animals↗
A novel unstable mouse VNTR family expanded from SINE B1 elements.
Human hypervariable minisatellites provide highly informative loci for analyzing processes of tandem repeat turnover, but little is known about mechanisms of instability in other species. We have therefore screened the mouse genome for analogous VNTR loci. One of the probes we isolated, MMS10, detects a highly variable rodent-specific family of multiple loci derived by expansion of a common GGCAGA repeat unit from within a subset of B1 short interspersed elements. The mean germline mutation rate for loci detected by MMS10 was estimated at 1.7% per offspring band, though analysis of individual loci showed substantial variation in germinal instability apparently related to repeat array size. This MMS10 family of expanded hexanucleotide repeat loci provides a novel resource for investigating mechanisms of tandem repeat turnover in the mouse and an efficient means for monitoring germline mutations induced by external agents such as ionizing radiation.
Animals↗
The human homologue of the ninjurin gene maps to the candidate region of hereditary sensory neuropathy type I (HSNI).
The human ninjurin gene was isolated from a cDNA library enriched for transcripts from band 9q22. A 1.2-kb message was detected for ninjurin in all human tissues studied. The full-length sequence codes for a putative 152-amino-acid protein with 89% identity to the rat ninjurin protein. The mouse homologue was isolated and showed 98% amino acid identity to the rat protein. Mapping by FISH localized mouse ninjurin to mouse chromosome 13, a region that shows synteny with human chromosome 9q22. Genomic characterization of the human gene revealed four exons covering less than 10 kb. The map position of the human gene is between the genetic markers D9S196 and D9S197 on human chromosome band 9q22. This places the gene within the candidate regions for the degenerative neurological disorder hereditary sensory neuropathy type I and the cancer predisposition syndrome multiple self-healing squamous epitheliomata.
Amino Acid Sequence↗
The ubiquitin-homology gene PIC1: characterization of mouse (Pic1) and human (UBL1) genes and pseudogenes.
The human ubiquitin-homology domain protein PIC1 interacts with the acute promyelocytic leukemia protein PML, and both proteins form part of the large, nuclear, multiprotein complexes known as PML nuclear bodies. The normal punctate immunohistochemical staining pattern of these complexes is disrupted by viral infection or interferon treatment and in blast cells from patients with acute promyelocytic leukemia. We have characterized the murine homologue of PIC1 and have found that the predicted amino acid sequences of the mouse and human proteins are identical. High levels of Pic1 mRNA were detected in a range of mouse tissues. Pic1 genomic clones were isolated, and the organization of the gene was determined. Two processed Pic1 pseudogenes were also isolated and characterized. Through FISH, the chromosomal localizations of the mouse Pic1 gene and the two pseudogenes were determined. Human PIC1 (HGMW-approved symbol UBL1)-related sequences were isolated from human genomic DNA and were shown to represent processed pseudogenes. The role of PIC1 in a variety of cellular processes is discussed.
3T3 Cells↗
The prevalence and impact of self-reported hip fracture in elderly community-dwelling women: the Women's Health and Aging Study.
To estimate the prevalence and impact of self-reported hip fracture in elderly women an age-stratified random sample of 3841 community-dwelling women aged 65 years and above were interviewed to determine the occurrence of 13 chronic conditions and difficulty performing 15 tasks. Associations were examined using multiple logistic regression analysis. The weighted prevalence of hip fracture was 4.7 per 100. Prevalence increased with increasing age from 2.9 per 100 in women aged 65-74 years to 12.6 per 100 in women aged 85 years and above, and was higher in white women than black women. Women with hip fracture were significantly more likely to report concomitant Parkinson's disease (age-adjusted odds ratio [aOR] = 2.8) and stroke (aOR = 1.8). After adjustment for potential confounding variables, women with hip fracture were significantly more likely to report difficulty performing 11 activities that map into domains of mobility/exercise tolerance, self-care tasks and higher functioning domains. Hip fracture is common among elderly community-dwelling women and is associated with difficulty in performing activities of daily living.
Activities of Daily Living↗
cDNA cloning and chromosomal mapping of a mouse gene with homology to NTPases.
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Acid Anhydride Hydrolases↗