Biomedical subjects
Publications and source records attributed to D L Berry.
The DHAIR software system is a database-driven, web-based survey platform. It implements the delivery of survey instruments in packaged assessments, creation and editing of those assessments, researcher access to the results of the survey application, and a flexible authorization framework.
We have implemented a customized Internet decision support system designed to engage men in the decision-making process for the management of localized prostate cancer. The system is delivered to patients in the patient education room of the UWMC Prostate Oncology Center. The system interactively guides the patient through a series of surveys, and delivers multi-media interaction modeling and decision support output, both of which are customized for the patient's preferences. The system is currently implemented on an open source platform.
This study evaluated the feasibility of an innovative computerized symptom assessment tool, SymptomReport, and a computerized, tailored education tool, SymptomConsult, in a sample of 41 outpatients with cancer. After patients completed the computerized programs, an audiotaped telephone interview was conducted to assess patients' impressions. The study found that patients required less than 40 minutes on average to complete SymptomReport. The mean acceptability score was high 11 +/- 2. The 12 patients who completed SymptomConsult did so in an average of 20 minutes. The majority of participants indicated that the computer programs were easy, enjoyable, and informative tools. Initial formative research supports further study of these feasible computerized programs.
The repressor REST/NRSF restricts expression of a large set of genes to neurons by suppressing their expression in non-neural tissues. We find that REST repression involves two distinct repressor proteins. One of these, CoREST, interacts with the COOH-terminal repressor domain of REST (Andres, M. E., Burger, C., Peral-Rubio, M. J., Battaglioli, E., Anderson, M. E., Grimes, J., Dallmanm J., Ballas, N. , and Mandel, G. (1999) Proc. Natl. Acad. Sci. U. S. A. 96, 9873-9878). Here we show that the co-repressor mSin3A also interacts with REST. The REST-mSin3A association involves the NH(2)-terminal repressor domain of REST and the paired amphipathic helix 2 domain of mSin3A. REST forms complexes with endogenous mSin3A in mammalian cells, and both mSin3A and CoREST interact with REST in intact mammalian cells. REST repression is blocked in yeast lacking Sin3 and rescued in its presence. In mammalian cells, repression by REST is reduced when binding to mSin3A is inhibited. In mouse embryos, the distribution of mSin3A and REST transcripts is largely coincident. The pattern of CoREST gene expression is more restricted, suggesting that mSin3A is required constitutively for REST repression, whereas CoREST is recruited for more specialized repressor functions.
Adult Xenopus laevis frogs made transgenic by restriction enzyme-mediated integration were bred to test the feasibility of establishing lines of frogs that express transgenes. All of the 19 animals raised to sexual maturity generated progeny that expressed the transgene(s). The patterns and levels of expression of green fluorescent protein transgenes driven by a viral promoter, rat promoter, and four X. laevis promoters were all unaffected by passage through the germ line. These results demonstrate the ease of establishing transgenic lines in X. laevis.
PURPOSE: No standardized therapeutic interventions have been reported for patients diagnosed with breast cancer during pregnancy. Of the potential interventions, none have been prospectively evaluated for treatment efficacy in the mother or safety for the fetus. We present our experience with the use of combination chemotherapy for breast cancer during pregnancy. PATIENTS AND METHODS: During the past 8 years, 24 pregnant patients with primary or recurrent cancer of the breast were managed by outpatient chemotherapy, surgery, or surgery plus radiation therapy, as clinically indicated. The chemotherapy included fluorouracil (1,000 mg/m2), doxorubicin (50 mg/m2), and cyclophosphamide (500 mg/m2), administered every 3 to 4 weeks after the first trimester of pregnancy. Care was provided by medical oncologists, breast surgeons, and perinatal obstetricians. RESULTS: Modified radical mastectomy was performed in 18 of the 22 patients, and two patients were treated with segmental mastectomy with postpartum radiation therapy. This group included patients in all trimesters of pregnancy. The patients received a median of four cycles of combination chemotherapy during pregnancy. No antepartum complications temporally attributable to systemic therapy were noted. The mean gestational age at delivery was 38 weeks. Apgar scores, birthweights, and immediate postpartum health were reported to be normal for all of the children. CONCLUSION: Breast cancer can be treated with chemotherapy during the second and third trimesters of pregnancy with minimal complications of labor and delivery.
PURPOSE/OBJECTIVES: To compare patient reports of present and worst cancer-related pain intensity to the recalled intensity of several commonly experienced types of pain. DESIGN: A secondary analysis on baseline data from patients with cancer pain. SETTING: Tertiary-care facilities and patients' homes. Patients were enrolled between 1988 and 1995. SAMPLE: Patients who were diagnosed with either primary lung cancer or cancer metastatic to bone, able to read and write English, over 18 years of age, and able to provide written informed consent. The sample of 125 patients was 62% male with a mean age of 60 years (SD = 11). METHODS: Patients completed the McGill Pain Questionnaire as a baseline measure in a pain research study. Investigators conducted comparisons among pain intensity scores reported for present pain intensity and worst cancer pain with the worst toothache, headache, and stomachache ever experienced using the Stuart test of marginal homogeneity. MAIN RESEARCH VARIABLES: Present cancer pain intensity and worst toothache, headache, and stomachache pain intensity. FINDINGS: Only 14% of the subjects reported that their present pain intensity was distressing, horrible, or excruciating, but 83% of them reported that their worst cancer pain was at these levels. The subjects reported that they experienced (a) significantly more intense pain with their worst toothache than either their present pain intensity (p < 0.001) or their worst cancer pain (p < 0.001), (b) significantly more intense pain with their worst headache than their present pain intensity (p < 0.001), and (c) significantly more intense pain with their worst stomachache than their present pain intensity (p < 0.001). In contrast, subjects reported that their worst cancer pain was significantly more intense than their worst headache (p = 0.047) or stomachache (p = 0.001). CONCLUSIONS: The findings suggest that present cancer pain is not only experienced at lower intensity levels than common pains, but at lower levels than expected by patients, their families, and the public. Consistent with common beliefs though, the worst cancer pain is severe and not adequately controlled for 9 out of 10 patients. IMPLICATIONS FOR NURSING PRACTICE: Healthcare professionals could use study findings to inspire hope in patients with lung cancer or bone metastasis and their families that present pain in cancer can be controlled successfully. Clinicians should devote greater efforts to relieve the worst cancer pain to levels achieved for the present pain experienced by people with cancer.
Expression of genes up-regulated by thyroid hormone (TH) during amphibian tail resorption was localized by in situ hybridization. The constitutive thyroid hormone receptor (TRalpha) and its heterodimeric partners (RXRalpha and RXRbeta) are expressed ubiquitously in the resorbing tail. A group of early response genes, including those encoding transcription factors, are expressed at greatest levels within tissues whose cells attempt to grow and differentiate in the tail, but eventually succumb to the resorption program. The TH-inducible TR isoform, TRbeta, is expressed ubiquitously in the tail, but especially high in fibroblasts. Similarly, a group of delayed response genes including two proteolytic enzymes that appear to execute the tail resorption program, is expressed specifically in fibroblasts that line and surround the notochord and lie beneath the epidermal lamella (subepidermal fibroblasts). During active tail resorption these fibroblasts invade their neighboring epidermal and notochord lamellae as part of the resorption process. Expression analysis implicates the single layer of invasive subepidermal fibroblasts as crucial in tail resorption. Stromelysin-3 is up-regulated by TH with early kinetics, and is expressed most actively in fibroblasts within the tail fins. None of the proteases are expressed in the tadpole epidermis, which will be replaced entirely during metamorphosis. While very few TH response genes are expressed in tadpole muscle, many are activated in fibroblasts that surround muscle and could induce muscle cell death by proteolysis of the extracellular matrix. These distinct localization patterns suggest that the common fate of all cell types within the tail is the result of multiple genetic programs.
Thyroid hormone (TH) induces dramatic skeletal and tissue remodeling of the anuran head and body at metamorphosis. The expression pattern of TH up-regulated genes has been correlated with tissues that either grow or resorb at metamorphosis. Whereas the expression of the thyroid hormone receptors in Xenopus laevis tadpoles is ubiquitous, the locations where many of the TH up-regulated genes are activated fall into distinct classes. Genes in the early response class are expressed predominantly in cartilage and brain regions undergoing cell proliferation and at a higher level in the remodeling and growing body than in the resorbing tail. In contrast, expression of genes in the delayed response class is highest in resorbing tissues and higher in the tail than in the body within the subepidermal fibroblast layer, further indicating that this single cell layer is involved in tissue resorption. The expression boundary of delayed response class genes in the subepidermal fibroblasts in the body correlates with epidermal lamella invasion and subsequent adult skin differentiation. Differences in the expression patterns of stromelysin-3 and the delayed response proteinases in the head delineate separate programs of tissue resorption, one for the loss of epithelial structures, and one for the loss of cartilages. Expression of the type III deiodinase is up-regulated in growing tissues nearing completion of their metamorphic changes, suggesting a role for the deiodinase in modulating the influence of TH on these tissues.
Four genes were identified in a screen for thyroid hormone-induced down-regulation of gene expression in Xenopus laevis tadpole tails. All four encode extracellular glycoproteins that are expressed exclusively in the apical cell layer of the entire tadpole epidermis, which is the equivalent of the mammalian fetal periderm. The onset of the four novel genes' expression late in embryogenesis, their activity throughout the life of the tadpole, their repression by exogenously added thyroid hormone, and the spontaneous cessation of their expression at the end of tadpole life are closely coordinated. These facts suggest that the protein products of these genes form a novel albeit temporary barrier or other structure in the tadpole epidermis that functions in lieu of the cornified, stratified epithelium of the adult epidermis. We have exploited the cloning of these genes for use as cell-specific markers to follow the appearance and loss of apical cells during development. We were able to demonstrate directly that the apical cells are derived from a stratification of the embryonic ectoderm at the onset of the formation of a true epidermis. The apical cells uniformly cover the surface of the tadpole until metamorphosis, when the expression of the four larval epidermis-specific genes is lost coordinately over the entire tadpole. In contrast, the adult epidermis develops with a distinct regional specificity: adult keratin is first expressed up to a line separating the body and tail epidermis and finally appears in the tail only at metamorphic climax. Finally, our analysis reveals that the TH-induced down-regulated gene expression program during metamorphosis is very different from the previously described up-regulated program which involves multiple cell types and several waves of gene expression changes. The down-regulated program only consists of the repression of a small number of genes which are expressed in larval cells preprogrammed to die during the larval to adult transition at metamorphosis.
BACKGROUND: Placenta percreta can create life-threatening hemorrhage at the time of delivery. The additional challenge of patient refusal of blood transfusion for religious reasons requires the use of comprehensive blood-conserving strategies. CASE: A Jehovah's Witness with two previous cesarean deliveries and a placenta previa was diagnosed antenatally as having placenta percreta. Acute normovolemic hemodilution was performed in conjunction with cesarean hysterectomy with no maternal or fetal side effects. CONCLUSION: Acute normovolemic hemodilution can be used safely in the pregnant woman at high risk for excessive intraoperative blood loss and should be considered in obstetric patients who strictly adhere to religious convictions prohibiting the acceptance of blood products.
The rate and pattern of sequence substitutions in the mitochondrial DNA (mtDNA) control region (CR) is of central importance to studies of human evolution and to forensic identity testing. Here, we report a direct measurement of the intergenerational substitution rate in the human CR. We compared DNA sequences of two CR hypervariable segments from close maternal relatives, from 134 independent mtDNA lineages spanning 327 generational events. Ten substitutions were observed, resulting in an empirical rate of 1/33 generations, or 2.5/site/Myr. This is roughly twenty-fold higher than estimates derived from phylogenetic analyses. This disparity cannot be accounted for simply by substitutions at mutational hot spots, suggesting additional factors that produce the discrepancy between very near-term and long-term apparent rates of sequence divergence. The data also indicate that extremely rapid segregation of CR sequence variants between generations is common in humans, with a very small mtDNA bottleneck. These results have implications for forensic applications and studies of human evolution.
BACKGROUND: While the efficacy of bacillus Calmette-Guérin (BCG) immunotherapy has been demonstrated, the relative benefit, given a seemingly high incidence and severity of toxicities, remains an issue. Adequate understanding and management of toxicities can maximize the safety of the treatment and enable the administration of required doses of BCG intravesical therapy. METHODS: All week-to-week symptoms recorded for the 143 immunotherapy-naive participants assigned to the BCG arm of SWOG-8216, BCG vs. Doxorubicin in Superficial Bladder Cancer were analyzed in order to document the pattern of toxicities in the first six week induction course of intravesical BCG treatments. The statistical analysis consisted of fitting logistic regression models to these data for the probability of irritative bladder symptoms (IBS). RESULTS: In the optimal model, the probability of IBS depends only on whether there was IBS associated with the previous treatment, and not on which treatment. The estimated probability of having IBS when there were no IBS associated with the previous instillation is 0.136, whereas the estimated probability of having IBS when there was IBS associated with the previous instillation is 0.689. CONCLUSIONS: Irritative bladder symptoms are unlikely in the week after the first intravesical BCG treatment. Once a patient experiences IBS, he or she is more likely to have IBS with the next and subsequent treatments. Clinicians can use the findings of this analysis when informing their patients about the treatment course and when making decisions about continuing treatments.
BACKGROUND: Hereditary hemorrhagic telangiectasia is a rare, inherited disease characterized by abnormal visceral and superficial blood vessel anastomoses. These telangiectasias predispose the patient to a lifelong history of recurrent bleeding for the nasal and gastrointestinal mucosa. Less commonly involved organs include the liver, brain and lung. To date there is no cure for this disease. Management requires many palliative minor surgical procedures to stop actively bleeding sites. Major surgery is often contraindicated in these patients due do coexisting medical sequelae of their underlying disease. CASE: Menorrhagia was diagnosed in a 42 year-old multipara with known history of hereditary hemorrhagic telangiectasia. The bleeding was unresponsive to hormonal therapy. Substantial preexisting conditions, including profound anemia, history of multiple strokes, a seizure disorder and ventricular arrhythmias, precluded major surgical intervention, including hysterectomy. Serial injections of leuprolide acetate injections were followed by hysteroscopic "rollerball" electrocoagulation of the endometrium under regional anesthesia. On long-term follow up, the patient was cured of her menorrhagia. CONCLUSION: Endometrial ablation provides patients who have significant medical complications with an effective, minimally invasive alternative to hysterectomy for control of menorrhagia.
PURPOSE/OBJECTIVES: To review the issues related to informed consent in a clinical cancer care setting and suggest strategies to improve the informed consent process. DATA SOURCES: Published books, journal articles, and clinical research experience. DATA SYNTHESIS: Clinicians and researchers are ethically obligated to maintain the informed consent process when treating participants in clinical cancer research. Nurse clinicians, clinical trial nurses, and nurse researchers often encounter dilemmas while ensuring proper informed consent. Nurses involved in pediatric cancer care must address specific consent issues relevant to children and youth. CONCLUSIONS: Informed consent does not end with a patient's signature on a form. Establishing and maintaining informed consent is a multidisciplinary effort in cancer clinical trials. Nurses can improve the informed consent process by ensuring adequate time for patient consideration and understanding and by reassessing consent during the study. IMPLICATIONS FOR NURSING PRACTICE: Clinical trial nurses and nurse investigators in both adult and pediatric oncology have a duty and obligation to maintain continued informed consent throughout a study and to be involved in all aspects of study planning and implementation.
To establish the seroprevalence of the human immunodeficiency virus (HIV) in our county hospital obstetric patients, and to assess the predictive value of screening questionnaires for high-risk behaviors attributing to HIV infection, we conducted written surveys and blinded HIV testing over a 4-month period ending February 1993. Blinded HIV antibody testing was performed on 1348 patients upon admission to labor and delivery. The coded blood samples were matched to similarly coded surveys of patient demographics and behaviors implicated in HIV transmission. The overall HIV prevalence in our regional population remains virtually unchanged at a rate of 0.22% (2.2 per 1000 patients). Questionnaires regarding health history were not predictive for HIV infection in our patients. Universal screening questionnaires cannot predict HIV infection. Similarly, routine mandatory testing for HIV performed on obstetric patients on the day of delivery are not cost-effective and do not provide clinically meaningful information needed to alter management protocols.
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LNF-209 is a glycoside, similar to digoxin, which has potential for use in the treatment of congestive heart failure. However, unlike digoxin it exhibits virtually no useful UV absorption spectra, making detection difficult. One means of detection is the refractive index detector, but like most bulk property detectors it has certain limitations. Its sensitivity is limited and it is sensitive to small changes in a number of parameters, such as temperature, mobile phase composition, and flow-rate. These parameters must be closely controlled to obtain a stable baseline. This paper describes the steps taken to control the system and the development and validation of an assay for LNF-209 in dosing solutions. The method developed is capable of quantitating LNF-209 in solutions of sterile water and 5% dextrose at concentrations ranging from 8 to 6000 micrograms/ml. The method is linear over this range and quantitative recovery is obtained. The overall average relative standard deviation for replicate analysis of several samples at various concentrations assayed over two days was 2.3%.