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Biomedical subjects

B Brown

Publications and source records attributed to B Brown.

At least 91 records · Page 5Linked to original sources
PubMed1999

Progression to androgen independence is delayed by adjuvant treatment with antisense Bcl-2 oligodeoxynucleotides after castration in the LNCaP prostate tumor model.

Bcl-2 has emerged as a critical regulator of apoptosis in a variety of cell systems and is up-regulated during progression to androgen independence in prostate cancer cells. The objectives of this study were to characterize changes in Bcl-2 after androgen withdrawal and during progression to androgen independence in the human prostate LNCaP tumor model and determine whether adjuvant use of antisense Bcl-2 oligodeoxynucleotides (ODNs) with androgen ablation delays progression to androgen independence. Bcl-2 expression in LNCaP cells is down-regulated to undetectable levels by androgen in vitro and up-regulated after castration in vivo. Antisense Bcl-2 ODN treatment reduced LNCaP cell Bcl-2 messenger RNA and protein levels by >90% in a sequence-specific and dose-dependent manner at concentrations >50 nM. Bcl-2 mRNA levels returned to pretreatment levels by 48 h after discontinuing treatment. Athymic male mice bearing SQ LNCaP tumors were castrated and injected i.p. with 12.5 mg/kg/day with two-base mismatch ODN control, reverse polarity ODN control, or antisense Bcl-2 ODN. Tumor volume in control mice gradually increased 5-fold (range, 3-6) by 12 weeks after castration compared to a 10-50% decrease in precastrate tumor volume in mice treated with antisense Bcl-2 ODN. Changes in serum PSA paralleled changes in tumor volume, increasing 4-fold faster above nadir in controls than in mice treated with antisense Bcl-2 ODN. After decreasing 70% by 1 week after castration, PSA increased 1.6-fold above precastrate levels by 11 weeks in controls while staying 30% below precastrate levels in antisense-treated mice. In a second group of experiments, LNCaP tumor growth and serum PSA levels were 90% lower (P<0.01) in mice treated with antisense Bcl-2 ODN compared with mismatch or reverse polarity ODN controls. These results support the hypothesis that Bcl-2 helps mediate progression to androgen independence and is an appropriate target for antisense therapy.

Androgens↗
PubMed1999

How to develop a unit personnel budget.

To handle fluctuating patient census and acuity, it's imperative that nurse managers develop a fiscally responsible and workable personnel budget per assigned unit. This month, we take you back to the basics of how to develop a personnel budget.

Bed Occupancy↗
PubMed1998

PhLPs and PhLOPs in the phosducin family of G beta gamma binding proteins.

In this study, we identify new isoforms of the retinal phosducin and investigate the expression of the phosducin family, showing that an isoform, PhLP1, has sequence homology with Phd and Gbeta gamma binding capability, whereas two isoforms (phosducin-like orphan proteins, PhLOPs) share sequence homology with Phd but fail to bind Gbeta gamma. Original identification of PhLP1 and the PhLOPs was from a human retina cDNA library, using a PCR product for library hybridization screening that contained a predicted functional epitope domain. The screen identified Phd and three related, but distinct, recombinants (PhLP1, PhLOP1, and PhLOP2). By RT-PCR, all isoforms are expressed in either retina or forskolin-stimulated Y79 retinoblastoma cells; however, the new isoforms are below the level of detection on Northern blot analysis. The predicted amino acid translation of each homologue revealed major differences, arising from either splice variants or gene duplication of Phd. To test the functional interaction of all phosducin isoforms with Gbeta gamma in vitro, a glutathione S-transferase (GST) fusion protein was developed for each member. Biochemical interaction with purified retinal transducin Gbeta gamma was verified for GST-Phd and demonstrated for GST-PhLP1; however, neither GST-PhLOP1 nor GST-PhLOP2 bound Gbeta gamma. Comparable results were observed when the GST-phosducin fusion proteins selectively sequestered Gbeta gammas from retinal extracts or when functional Gbeta gamma interactions were assessed using surface plasmon resonance technology. Phosducin and its isoforms are widely distributed in body tissues where they may participate in signal transduction pathways. Phd and PhLP1 possess an 11-amino acid conserved epitope domain (TGPKGVINDWR) that controls the high-affinity binding of Gbeta gamma; these isoforms are implicated in the G-protein signaling pathway. The phosducin-like orphan proteins (PhLOPs) fail to bind Gbeta gamma, suggesting that the PhLOP isoforms may participate in still unidentified signaling pathways.

Amino Acid Sequence↗
PubMed1998

Comparative studies of DNA adduct formation in mice following dermal application of smoke condensates from cigarettes that burn or primarily heat tobacco.

A new cigarette (Eclipse) that primarily heats rather than burns tobacco has been developed. Since Eclipse primarily heats tobacco, the smoke chemistry is much simplified, consisting of 80% glycerol and water. With the simplified smoke chemistry, it would be expected that toxicological activity would be reduced. Smoke and smoke condensate from Eclipse have consistently yielded markedly reduced mutagenicity and cytotoxicity in in vitro tests when compared to smoke and smoke condensate from the 1R4F Kentucky reference cigarette, which is representative of typical low 'tar' cigarettes sold in the U.S. today. The objective of the present study was to evaluate the potential of mainstream cigarette smoke condensate (CSC) of Eclipse to produce DNA adducts in lung, heart and skin tissue of dermally-exposed mice and to compare the results with those obtained with CSC from the 1R4F Kentucky reference cigarette. CSC from Eclipse or 1R4F cigarettes was applied dermally to SENCAR mice three times a week for 30 weeks. Amounts of CSC applied were 30, 60 or 120 mg 'tar' per animal per week. Tissues were collected after 1, 4, 14 and 29 weeks of CSC application. DNA adducts were analyzed in lung, heart and skin tissues using the 32P-postlabeling method with P1 nuclease modification. Distinct time and dose-dependent diagonal radioactive zones (DRZ) were observed in the DNA from lung, heart and skin tissues of animals treated with 1R4F CSC. The relative adduct labeling (RAL) values of lung, heart and skin DNA from reference CSC-treated animals were significantly greater (p<0.05) than those of the solvent control animals. No corresponding DRZs were observed at any dose from the DNA of animals treated with CSC from Eclipse or solvent control (acetone) and the RAL values observed following application of Eclipse were not increased relative to the solvent control. These results provide additional evidence that the smoke condensate from the Eclipse cigarette is markedly less genotoxic than smoke condensate from tobacco-burning cigarettes representative of those currently sold in the U.S.

Administration, Cutaneous↗
PubMed1998

Use of a neural network to predict stone growth after shock wave lithotripsy.

OBJECTIVES: To determine whether a neural network is superior to standard computational methods in predicting stone regrowth after shock wave lithotripsy (SWL) and to determine whether the presence of residual fragments, as an independent variable, increases risk. METHODS: We reviewed the records of 98 patients with renal or ureteral calculi treated by primary SWL at a single institution and followed up for at least 1 year; residual stone fragment growth or new stone occurrence was determined from abdominal radiographs. A neural network was programmed and trained to predict an increased stone volume over time utilizing input variables, including previous stone events, metabolic abnormality, directed medical therapy, infection, caliectasis, and residual fragments after SWL. Patient data were partitioned into a training set of 65 examples and a test set of 33. The neural network did not encounter the test set until training was complete. RESULTS: The average follow-up period was 3.5 years (range 1 to 10). Of 98 patients, 47 had residual stone fragments 3 months after SWL; of these 47, 8 had increased stone volume at last follow-up visit. Of 51 patients stone free after SWL, 4 had stone recurrence. Coexisting risk factors were incorporated into a neural computational model to determine which of the risk factors was individually predictive of stone growth. The classification accuracy of the neural model in the test set was 91%, with a sensitivity of 91%, a specificity of 92%, and a receiver operating characteristic curve area of 0.964, results significantly better than those yielded by linear and quadratic discriminant function analysis. CONCLUSIONS: A computational tool was developed to predict accurately the risk of future stone activity in patients treated by SWL. Use of the neural network demonstrates that none of the risk factors for stone growth, including the presence of residual fragments, is individually predictive of continuing stone formation.

Follow-Up Studies↗
PubMed1998

Alteration of thyroid blood flow during the normal menstrual cycle in healthy Chinese women.

The purpose of this study was to investigate the relationship between thyroid activity and the menstrual cycle by measuring the Doppler parameters of the superior thyroid arteries in women of reproductive age. The study was performed in 27 healthy Chinese women aged between 19 and 28 y for one menstrual cycle, and 25 age-matched healthy Chinese men for 3 weeks for comparison. In women, the peak systolic velocity increased from the follicular phase to the luteal phase, and the pulsatility index decreased from the follicular phase to the ovulatory phase and increased slightly in the luteal phase. In men, alterations in the pattern of thyroid blood flow were not observed; however, the average values of Doppler parameters during the study period in women were similar to those in men. The gender difference in the pattern of flow characteristics in the superior thyroid artery suggests effects of estrogen on thyroid function.

Adolescent↗
PubMed1998

Disruption of the tear film by the application of small drops of saline and surfactant.

The effects of disrupting the tear film by placing 5 or 10 microl drops of saline and mild surfactant solution (SS) directly onto the tear films of 10 subjects were observed and are described here. Disruption of the tear film was only transient, with restoration of the film occurring within about two to three blinks for saline drops, and four to six blinks for SS drops. When a drop of SS was placed on a cornea, two types of black spots/areas may be observed: black areas apparently similar to those observed in the TBUT test, and black areas forming outside the border of the pattern of the spreading SS drop. In general, staining of the black areas formed in the fluorescein-stained tears did not occur even when blinking was inhibited for up to 13 s. Stained areas on the corneal surface did not have a tendency to form black spots first; the tear film over these areas did not appear to be less stable than on other areas of the corneal surface.

Journal Article↗
PubMed1998

Fruits without labour: the implications of Friedrich Nietzsche's ideas for the caring professions.

Seldom is the work of philosophers invoked by health professionals when examining aspects of care from a philosophical perspective. Instead, students of health care, especially nurses, have been introduced to 'philosophies' which are often superficially examined and poorly understood. This practice fails to develop in students an appreciation of the work of philosophers or to acquire the art of critical thinking. The introduction of models and theories of nursing in the past three decades has alerted nurses to the importance of possessing critical skills in order to identify sound theory and implement good practice. This paper goes beyond mere philosophising and examines aspects of mental health care from the perspectives of one of nineteenth century Europe's most notable philosophers, Friedrich Nietzsche. It argues that understanding his work can enhance one's ability to reflect on nursing practice, as well as bringing a new dimension to how we analyse 'mental health' problems. His work provides many insights into how we can improve our understanding of the effect of mental illness and mental health care on the individual, and how we conceptualise the process of care. This paper provides an overview of his life's work, his impact on the history of ideas and develops some of the more provocative implications of his work for mental health care.

Empathy↗
PubMed1998

Ministering to madness: the narratives of people who have left religious orders to work in the caring professions.

This paper examines the life stories of 14 men and women who spent time in religious communities and who subsequently took up work in the caring professions. Their accounts reflect the alignment between the ethics of care and those of religious life, the centrality of contemplation and self-examination to both Christianity and psychotherapy. There are further correspondences between their narratives and recent academic interest in the spiritual aspects of health care. They also describe profound changes and moments of uncertainty which parallel other transitional experiences like grieving or unemployment. For many respondents also, caring for others is part of caring for oneself. Disappointment with the religious life and isolation on leaving it appear to have brought the respondents into a close relationship with those who suffer mental illness. It is almost as if they seek to heal the distress in their own lives by proxy.

Adult↗
PubMed1998

The effect of a perioperative clinical pathway for knee replacement surgery on hospital costs.

UNLABELLED: Clinical pathways are being introduced by hospitals to reduce costs and control unnecessary variation in care. We studied 766 inpatients to measure the impact of a perioperative clinical pathway for patients undergoing knee replacement surgery on hospital costs. One hundred twenty patients underwent knee replacement surgery before the development of a perioperative clinical pathway, and 63 patients underwent knee replacement surgery after pathway implementation. As control groups, we contemporaneously studied 332 patients undergoing radical prostatectomy (no clinical pathway in place for these patients) and 251 patients undergoing hip replacement surgery without a clinical pathway (no clinical pathway and same surgeons as patients having knee replacement surgery). Total hospitalization costs (not charges), excluding professional fees, were computed for all patients. Mean (+/-SD) hospital costs for knee replacement surgery decreased from $21,709 +/- $5985 to $17,618 +/- $3152 after implementation of the clinical pathway. The percent decrease in hospitalization costs was 1.56-fold greater (95% confidence interval 1.02-2.28) in the knee replacement patients than in the radical prostatectomy patients and 2.02-fold greater (95% confidence interval 1.13-5.22) than in the hip replacement patients. If patient outcomes (e.g., patient satisfaction) remain constant with clinical pathways, clinical pathways may be a useful tool for incremental improvements in the cost of perioperative care. IMPLICATIONS: Doctors and nurses can proactively organize and record the elements of hospital care results in a clinical pathway, also known as "care pathways" or "critical pathways." We found that implementing a clinical pathway for patients undergoing knee replacement surgery reduced the hospitalization costs of this surgery.

Adult↗
PubMed1998

The expanded Trail Making Test: rationale, development, and psychometric properties.

Many procedures have been employed to determine the specific cognitive components necessary for successful Trail Making Test (TMT) performance. Yet, there is still considerable disagreement in the literature as to what these components might be. The present study explores an alternative methodology to address this problem. By systematically varying the stimuli within the TMT format, it may eventually be possible to isolate the cognitive demands of this test. As the first step toward this goal, two experimental forms of the TMT, forms X and Y, were developed and subjected to empirical validation. The results indicate that this Expanded Trail Making Test possesses adequate concurrent and criterion validity to support the proposed methodology. The results also suggest that the psychometric properties of the TMT format are robust to alterations in test stimuli. Secondary benefits of this methodology, in terms of explaining between-group variance and in terms of cross-cultural assessment, are discussed.

Journal Article↗
PubMed1998

Investigation of multifocal visual evoked potential in anisometropic and esotropic amblyopes.

PURPOSE: To investigate the variation of visual evoked potential (VEP) function at different eccentricities of the visual field in esotropic amblyopes and anisometropic amblyopes. METHODS: Data from 5 esotropic amblyopic eyes, 6 anisometropic amblyopic eyes, and 45 control eyes were analyzed. A VERIS system was used to generate a stimulus matrix containing 61 hexagons on a computer monitor. Each hexagon of the display contained a number of small black and white hexagonal patches that reversed in polarity during stimulation according to a pseudorandom binary m-sequence. The VERIS system extracted the local responses by cross-correlating the input and output signals. The latencies and amplitudes of the responses from the central 8.6 degrees of arc in the visual field were analyzed. RESULTS: In esotropic amblyopia, the multifocal VEP latency is prolonged, and the amplitude is reduced in the central region of the visual field. The mean amplitude is significantly smaller, and the mean latency is significantly longer in the temporal visual field than in the nasal visual field. In anisometropic amblyopia, latencies are markedly prolonged, and the amplitudes of multifocal VEP are attenuated in the central region of the visual field, and these effects are lessened in the periphery. CONCLUSIONS: The results are in agreement with psychophysical studies reporting a greater foveal deficit in amblyopia and a greater visual loss in the temporal field than in the nasal field in esotropic amblyopia.

Adolescent↗
PubMed1998

Effectiveness of megestrol acetate in patients with advanced cancer: a randomized, double-blind, crossover study.

PURPOSE: To evaluate the effect of megestrol acetate at a lower dose than previously investigated on the symptoms of cachexia in patients with advanced cancer. METHODS: A total of 84 patients with advanced, solid tumours not responsive to hormone therapy were enrolled in this double-blind, crossover study. During phase 1, patients were randomly assigned to receive megestrol acetate (160 mg 3 times daily) for 10 days or placebo. During phase 2, after a 2-day washout period, patients received the alternate treatment for 10 days. Patients underwent daily assessments of activity, nausea, appetite and well-being by means of a visual analogue scale (VAS). In addition, nutritional status (weight, tricep skinfold measure, arm muscle circumference), energy intake, fatigue (Piper Fatigue Scale) and quality of life (Functional Living Index-Cancer [FLIC]) were assessed. RESULTS: Among the 53 evaluable patients megestrol acetate resulted in a significant improvement in appetite (p = 0.005), activity (p = 0.007) and well-being (p = 0.03). There was no significant change in the intensity of nausea, nutritional parameters, energy intake or FLIC scores. There was a significant improvement in 2 of the 3 factors measured by the Piper Fatigue Scale and in the overall fatigue score. Upon completion of the study, while still blind to the treatment condition, 30 patients indicated that they felt better overall after megestrol, 15 said they felt better after placebo, and 10 indicated no preference (p = 0.001). CONCLUSION: Treatment with megestrol acetate results in rapid and significant improvement of symptoms in terminally ill patients at lower doses than previously reported. The effects are not secondary to nutritional changes. The FLIC quality-of-life questionnaire was unable to detect these changes.

Adult↗
PubMed1998

Investigation of retinitis pigmentosa using the multifocal electroretinogram.

Retinitis pigmentosa (RP) patients have pathological changes in both the macula and the periphery, and are known to have abnormal electroretinograms (ERGs). The response densities measured by the multifocal electroretinogram (MERG) in the macula and pericentral retina were greatly reduced in RP. In photopic conditions, some patients had relatively better ERG responses in the macula than in the pericentral retina, and this agreed with the finding that there is usually relatively well-preserved macular function in RP. In scotopic conditions, both macula and pericentral retina gave poor responses. There was very little increase in response as stimulus luminance increased in RP. The topographical mapping of the MERG results can provide objective, localized assessment of retinal function.

Adult↗
PubMed1998

10 trends for the new year.

Nurse managers can expect their new year's agenda to include issues related to span of control, Y2K compliance, recruitment and retention activities, and more.

Attitude of Health Personnel↗
PubMed1997

Long-term outcome of treatment for Ann Arbor stage 1 Hodgkin's disease: patterns of failure, late toxicity and second malignancies.

PURPOSE: Radiation therapy results in excellent short-term survival in patients with early-stage Hodgkin's disease. However, the optimal therapeutic scheme that achieves the highest disease-free survival with the minimum long-term toxicity is yet to be determined. An analysis of the patterns of failure and late complications after radiation therapy was conducted to address this question. METHODS AND MATERIALS: A retrospective study was conducted of 145 patients with Stage I Hodgkin's disease treated at M. D. Anderson Cancer Center from 1967 through 1987. Follow-up extended from a minimum of 30 to 339 months, with a median period of observation of 16.5 years. All the patients were treated with radiation therapy and, and 16 received combination MOPP-based chemotherapy as part of their initial treatment. The radiotherapy technique, was involved/regional in 71 (49%), extended in 62 (43%), and subtotal nodal irradiation in 12 patients. The median total dose was 40 Gy. RESULTS: The actuarial freedom from progression at 10 and 20 years was 76% and 69%, respectively. Forty of 145 patients relapsed (27.6%). The site of primary disease was cervical adenopathy in 30 (75%), axillary in 7 (17.5%), mediastinal in 2 patients and subdiaphragmatic in one patient. Twenty-two patients were treated with involved/regional technique (55%), 17 with extended (42.5%), and 1 with subtotal nodal irradiation technique. There were three in field and four marginal recurrences. Six relapses occurred in non-irradiated nodal regions at the same side of the diaphragm and 17 in non-irradiated transdiaphragmatic lymph nodes (57.5%). Nine patients (22.5%) relapsed with visceral disease. Nineteen patients (47.5%) relapsed within the first 2 years, 15 (37.5%) 3 to 10 years after diagnosis and the remaining 6 (15%) after 10 years. Eleven of 40 patients died of disease after the first or subsequent relapses (27.5%). Three of six patients with late relapses had progression in viscera but only two died with disease. Thirty-eight of 145 patients developed late toxicity from the treatment (26.2%). Twenty-three patients experienced ischemic heart disease (15.9%), only 13 of whom received mediastinal irradiation (9%). Fifteen patients developed secondary malignant solid tumors (10.3%). Nine of those (6.2%) occurred within the irradiation field (two were also treated with chemotherapy). Two additional patients, one of whom received chemotherapy as part of the initial treatment, died of acute myelogenous leukemia. Non-Hodgkin's lymphoma and lung cancer were the most common second malignancies. CONCLUSIONS: Limited field radiotherapy results in a significant number of relapses in non-irradiated, especially transdiaphragmatic lymph nodes. Subtotal nodal irradiation can prevent some relapses and therefore improve freedom from progression. Careful design of the treatment fields may decrease the risk of morbidity and mortality from coronary artery disease and second malignancies in early-stage Hodgkin's disease. Careful long-term surveillance may permit early detection and management of late relapses and treatment complications.

Adolescent↗