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Biomedical subjects

Robert White

Publications and source records attributed to Robert White.

11 recordsLinked to original sources

Effect of pilocarpine during radiation therapy: results of RTOG 97-09, a phase III randomized study in head and neck cancer patients.

Radiation therapy is an important curative modality in the treatment of patients with head and neck cancer. However, radiation-induced changes in the oral cavity, such as xerostomia and mucositis, are among the most debilitating treatment sequelae experienced by patients undergoing radiation therapy, and attempts at ameliorating these side effects have been poor at best. Pilocarpine has been approved for post-radiation xerostomia, and the effect of its use during radiation therapy on salivary flow, xerostomia, mucositis, and quality of life (QOL) was assessed in a phase III study conducted by the Radiation Therapy Oncology Group (RTOG 97-09). In total, 245 evaluable patients were randomized to pilocarpine or placebo. Selected patients were required to have > or = 50% of the volume of the major salivary glands receive > or = 50Gy; to agree to provide stimulated and unstimulated samples of saliva (measured in g) before treatment, at the end of treatment, and 3 and 6 months after completion of radiation therapy; and to complete the University of Washington Head and Neck Symptom Scale. Following the completion of radiation therapy, the average unstimulated salivary flow was statistically greater in the pilocarpine group, whereas no difference was noted following parotid stimulation. There was no effect on the amelioration of mucositis. The results of the QOL scales did not reveal any significant difference between the pilocarpine and placebo groups with regard to xerostomia and mucositis. The significant difference in unstimulated salivary flow supports the concomitant use of oral pilocarpine to decrease radiation-associated xerostomia. However, the absent correlation between improved salivary flow and QOL scores is of some concern (though not a new finding) and may be related to the existence of comorbidities and the lack of effect on mucositis.

Female↗

Identification and characterization of optimal gene expression markers for detection of breast cancer metastasis.

Sentinel lymph node (SLN) status is highly predictive of overall axillary lymph node involvement in breast cancer. Historically, SLN-positive patients have undergone axillary lymph node dissection in a second surgery. Intraoperative SLN analysis could reduce the cost and complications of a second surgery; however, existing histopathological methods lack standardization and exhibit poor sensitivity. Rapid molecular methods may lead to improved intraoperative diagnosis of SLN metastasis. In this study, we used a genome-wide gene expression analysis of breast and other tissues to identify seven putative markers for detecting breast cancer metastasis. We assessed the utility of these markers for identifying clinically actionable metastases in lymph nodes through reverse transcriptase-polymerase chain reaction analysis of SLNs from 254 breast cancer patients. Polymerase chain reaction signals were compared to pathology on a per-patient basis. The optimal two-gene combination, mammaglobin and cytokeratin 19, detected clinically actionable metastasis in breast SLNs with 90% sensitivity and 94% specificity. Application of stringent criteria for identifying presumptive hematoxylin- and eosin-positive samples increased sensitivity and specificity to 91 and 97%, respectively. This study represents the first comprehensive demonstration of the utility of gene expression markers for detecting clinically actionable breast metastases. An intraoperative molecular assay using these markers has the potential to significantly reduce second surgeries for patients undergoing SLN dissection.

Biomarkers, Tumor↗

Primate-to-human retroviral transmission in Asia.

We describe the first reported transmission to a human of simian foamy virus (SFV) from a free-ranging population of nonhuman primates in Asia. The transmission of an exogenous retrovirus, SFV, from macaques (Macaca fascicularis) to a human at a monkey temple in Bali, Indonesia, was investigated with molecular and serologic techniques. Antibodies to SFV were detected by Western blotting of serum from 1 of 82 humans tested. SFV DNA was detected by nested polymerase chain reaction (PCR) from the blood of the same person. Cloning and sequencing of PCR products confirmed the virus's close phylogenetic relationship to SFV isolated from macaques at the same temple. This study raises concerns that persons who work at or live around monkey temples are at risk for infection with SFV.

Adult↗

Nosocomial infection in the NICU: a medical complication or unavoidable problem?

Nosocomial sepsis is a serious problem for neonates who are admitted for intensive care. As it is associated with increases in mortality, morbidity, and prolonged length of hospital stay, both the human and fiscal costs of these infections are high. Although the rate of nosocomial sepsis increases with the degree of both prematurity and low birth weight, no specific lab test has been shown to be very useful in improving our ability to predict who has a "real" blood-stream infection and, therefore, who needs to be treated with a full course of antibiotics. As a result, antibiotic use is double the rate of "proven" sepsis and we are facilitating the growth of resistant organisms in the neonatal intensive care unit. The purpose of this article is to review the topic of nosocomial infections in neonates.

Bacterial Infections↗

Prevention and treatment of nosocomial sepsis in the NICU.

Nosocomial sepsis is a serious problem for neonates who are admitted for intensive care. It is associated with an increase in mortality, morbidity, and prolonged length of hospital stay. Thus, both the human and fiscal costs of these infections are high. Although the rate of nosocomial sepsis increases with the degree of both prematurity and low birth weight, no specific lab test has been shown to be very useful in improving our ability to predict who has a "real" blood-stream infection and, therefore, who needs to be treated with a full course of antibiotics. As a result, antibiotic use is double the rate of "proven" sepsis and we are facilitating the growth of resistant organisms in the neonatal intensive care unit. The purpose of this article is to describe simple changes in process, which when implemented, can reduce nosocomial infection rates in neonates and improve outcomes.

Anti-Bacterial Agents↗

Discourse analysis and social constructionism.

Discourse analysis (DA) is underpinned by a social constructionist orientation to knowledge. Social constructionism rests on the philosophical assumptions that multiple versions of the world are legitimate; that texts are open to multiple readings; and that language is non-representational. As social constructionism is relativistic, the status of 'evidence' generated by DA is questionable from more traditional research perspectives. On a common-sense level, people obviously construct meaning in relation to their lives. Thus, DA can help us to examine constructions of meaning in relation to nursing care. Equally the discourse analyst constructs one possible meaning in relation to a phenomenon that may compete with other versions. Multiplicity does not necessarily entail anarchy and competing versions prevent authoritarianism and loss of freedom. However, judgements have to be made about competing versions, for example, by assessing the level of 'facticity', or referring to the ethics embedded in the cultural context. In this paper, Bob White discusses DA as a form of qualitative research that offers promise for nursing research. Subsequent papers will examine the methodology and methods of DA and its application to nursing research.

Attitude to Health↗

Pelvic embolization for intractable postpartum hemorrhage: long-term follow-up and implications for fertility.

OBJECTIVE: To determine the long-term sequelae of pelvic embolization for postpartum hemorrhage and to study the effect on fertility and menses. METHODS: Twenty-eight consecutive patients who underwent pelvic embolization for postpartum hemorrhage between the years 1977 and 2002 were included in the study. Chart review and telephone interviews were conducted to gather data regarding the type of delivery, causative factors of the bleeding, preembolization treatments, total blood loss, length of time between delivery and embolization, complications, long-term side effects, and subsequent pregnancies. RESULTS: The average (+/- standard deviation) time to follow-up was 11.7 +/- 6.9 years. The most common causes of hemorrhage were vaginal/cervical laceration, placenta accreta, and placenta previa. In only one case was the embolization unsuccessful, during which there was an accidental perforation of an internal iliac artery resulting in a retroperitoneal hematoma and subsequent total abdominal hysterectomy. All of the interviewed patients that desired to get pregnant after embolization were able to do so. Six patients reported a total of six uncomplicated pregnancies and deliveries in the years after their embolization. Of the remaining patients interviewed, none made subsequent attempts to get pregnant. The most commonly reported long-term side effects were transient buttock numbness (n = 2) and urinary frequency (n = 2). In no patients were the side effects severe enough to seek further medical attention. CONCLUSION: Pelvic arterial embolization is a safe and effective procedure and offers patients a fertility-preserving alternative to hysterectomy for treatment of intractable postpartum hemorrhage.

Adolescent↗

Marshall, Mannheim and contested citizenship.

In this paper we address tensions in Marshall's account of the successive emergence of civil, political and social rights in citizenship. These tensions were Marshall's implicit and typically modern assumption of human nature, his privileging of the analytical rationality that follows from it, and the disjunction between the fixity of that rationality and the 'evolution' of his central metaphor. When he returned to it by emphasizing strains between democratic, welfare and capitalist moments that were co-present in the 'hyphenated society' rather than successive, he did so in a pessimistic tone at odds with the progressive modernism of his first schema. Although Marshall noted that conflicting principles in citizenship arose 'from the very roots of our social order', he did not elaborate the point in this first tripartite model. We argue that by adopting a single and typically modern form of rationality Marshall foreclosed on the contradictions that he held to be characteristic of academic disputes over citizenship. Since Mannheim had focused on the effects of such contradictions, his work allows a fruitful revisiting of Marshall's themes. To blend the two models we read Marshall through Karl Mannheim's early studies of political knowledge. Here Mannheim had anticipated the shift from stages to co-presence, and had prefigured a resolution of Marshall's sense of impasse. In his account of liberal, socialist and conservative thought-styles--the ways of seeing and knowing that are characteristic of particular ways of life--he saw political change as a dynamic interactive effect of individually calculating, dialectically collective and culturally symbolic forms of rationality.

Attitude↗

Nursing practice should be informed by the best available evidence, but should all first-level nurses be competent at research appraisal and utilization?

The United Kingdom Central Council for Nursing, Midwifery and Health Visiting (UKCC) has for many years sought to promote the development of research knowledge and skills in registered nurses and has based its efforts on a particular model of the professional practitioner. This model has each registered nurse as a competent finder, appraiser and utilizer of research evidence. It has a vision of all registered nurses acting as autonomous practitioners, able to adapt their practice according to their own expert assessment of current research findings. Through its powers of strategic direction of nurse training and education, the UKCC has required the national boards to have approved education institutions prepare nurses for this role at both pre- and post-registration level. In this paper we argue that this model has proven ineffective. Our argument suggests that the technical complexity of research, and the skills and time required to find and integrate research evidence, renders such a model unattainable. Evidence from studies of clinical nurses indicates that little progress has in any case been made. Furthermore, the development of the apparatus of clinical governance and the basis of professional accountability further undermine the grounds for this approach. A modified approach is advocated based on the development of research specialists within nursing and the greater use of research-based clinical guidelines.

Attitude of Health Personnel↗

A mouse model of inflammatory root resorption induced by pulpal infection.

OBJECTIVE: The present study was undertaken to determine the frequency and extent of apical root resorption associated with induced periradicular lesions in mice. STUDY DESIGN: Bone and root resorption was quantified by using two- and three-dimensional micro-computed tomography (mu-CT) in the lower first molars of mice subjected to pulp exposure and infection. RESULTS: mu-CT measurements showed significant apical resorption in exposed and infected teeth, resulting in an average distal root shortening of 12.7% (P <.001 vs unexposed). These findings were confirmed with three-dimensional reconstituted images that showed thinning and shortening of the distal root. Tartrate-resistant acid phosphatase clastic cells were associated with resorption lacunae on the cementum of root apices, as well as on bone at the periphery of the periradicular lesions. Brown and Brenn staining showed the presence of bacteria in dentinal tubules adjacent to resorbed cementum. CONCLUSIONS: Apical root resorption is a prominent and consistent finding associated with periradicular infection in the mouse. This species represents a convenient model for studying the pathogenesis of inflammatory root resorption in vivo.

Acid Phosphatase↗

Capture and transfer of simian immunodeficiency virus by macaque dendritic cells is enhanced by DC-SIGN.

Dendritic cells (DCs) are among the first cells encountered by human and simian immunodeficiency virus (HIV and SIV) following mucosal infection. Because these cells efficiently capture and transmit virus to T cells, they may play a major role in mediating HIV and SIV infection. Recently, a C-type lectin protein present on DCs, DC-specific ICAM-3-grabbing nonintegrin (DC-SIGN), was shown to efficiently bind and present HIV and SIV to CD4(+), coreceptor-positive cells in trans. However, the significance of DC-SIGN for virus transmission and pathogenesis in vivo remains unclear. Because SIV infection of macaques may represent the best model to study the importance of DC-SIGN in HIV infection, we cloned and characterized pig-tailed macaque DC-SIGN and generated monoclonal antibodies (MAbs) against it. We demonstrate that, like human DC-SIGN, pig-tailed macaque DC-SIGN (ptDC-SIGN) is expressed on DCs and macrophages but not on monocytes, T cells, or B cells. Moderate levels of ptDC-SIGN expression were detected on the surface of DCs, and low-level expression was found on macrophages. Additionally, we show that ptDC-SIGN efficiently binds and transmits replication-competent SIVmne variants to CD4(+), coreceptor-positive cells. Moreover, transmission of virus between pig-tailed macaque DCs and CD4(+) T cells is largely ptDC-SIGN dependent. Interestingly, MAbs directed against ptDC-SIGN vary in the capacity to block transmission of different SIVmne variants. These data demonstrate that ptDC-SIGN plays a central role in transmitting virus from macaque DCs to T cells, and they suggest that SIVmne variants may differ in their interactions with ptDC-SIGN. Thus, SIVmne infection of pig-tailed macaques may provide an opportunity to investigate the significance of DC-SIGN in primate lentiviral infections.

Animals↗