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Biomedical subjects

R Hayden

Publications and source records attributed to R Hayden.

16 recordsLinked to original sources
PubMed2005

Histone deacetylases in acute myeloid leukaemia show a distinctive pattern of expression that changes selectively in response to deacetylase inhibitors.

Histone deacetylase inhibitors (HDIs) are a new class of drugs with significant antileukemic activity. To explore mechanisms of disease-specific HDI activity in acute myeloid leukaemia (AML), we have characterised expression of all 18 members of the histone deacetylase family in primary AML blasts and in four control cell types, namely CD34+ progenitors from umbilical cord, either quiescent or cycling (post-culture), cycling CD34+ progenitors from GCSF-stimulated adult donors and peripheral blood mononuclear cells. Only SIRT1 was consistently overexpressed (>2 fold) in AML samples compared with all controls, while HDAC6 was overexpressed relative to adult, but not neo-natal cells. HDAC5 and SIRT4 were consistently underexpressed. AML blasts and cell lines, exposed to HDIs in culture, showed both histone hyperacetylation and, unexpectedly, specific hypermethylation of H3 lysine 4. Such treatment also modulated the pattern of HDAC expression, with strong induction of HDAC11 in all myeloid cells tested and with all inhibitors (valproate, butyrate, TSA, SAHA), and lesser, more selective, induction of HDAC9 and SIRT4. The distinct pattern of HDAC expression in AML and its response to HDIs is of relevance to the development of HDI-based therapeutic strategies and may contribute to observed patterns of clinical response and development of drug resistance.

Acetylation↗
PubMed1997

Reliability audit of a regional cardiac surgery registry.

OBJECTIVE: The British Columbia Provincial Cardiac Registry collects demographic and clinical data on all patients who undergo cardiac surgery procedures in the province. The purpose of this study was to compare the reliability of data contained in Registry with data contained in hospital charts. METHODS: Registry and hospital charts were compared for 480 cases. Thirty cases were randomly selected for the province's 16 cardiac surgeons. For each case, 10 distinct fields were selected for analysis and classified as consistent, inconsistent, or rejected (data unavailable in one or other source). RESULTS: The overall rate of consistency between charts and the Registry was 86.4%, with an inconsistency rate of 9.9% and a rejection rate of 3.7%. Consistency rates varied significantly across the 10 fields and among the 16 surgeons. Pairwise comparisons of rates between fields indicated that specific field types were problematic and should be targeted for improvement. In addition, pairwise comparisons of rates between surgeons indicated that further education on Registry use is required. CONCLUSIONS: Recommendations for database design and management include provision of standard definitions for all fields; education of users; extension of the number of mandatory fields; revision of check-off box fields to yes/no/unsure fields; and collection of data close to the time that it is generated.

British Columbia↗
PubMed1996

Expression of the double-stranded RNA-dependent protein kinase (p68) in human breast tissues.

P68 is a potent inhibitor of protein synthesis in virally infected cells and has been suggested to function in noninfected cells as a tumor suppressor gene. We have previously demonstrated that p68 expression correlates directly with cellular differentiation and inversely with proliferative activity in normal epithelium and in several human tumor systems. In order to determine the role of p68 in human breast cancer, we utilized immunohistochemistry and mapped the expression of p68 in tissue from 200 breast biopsy specimens. A total of 434 foci, ranging from normal breast tissue to infiltrating carcinoma were examined. We found that p68 was present at basal levels in normal lobular and luminal ductal epithelial cells, with higher levels present in myoepithelial cells. Nonproliferative fibrocystic lesions showed variable expression of p68, with high levels seen within foci of apocrine metaplasia and low levels in cystically dilated terminal duct units. Low levels of p68 were seen in typical ductal proliferations, lobular neoplasia (atypical lobular hyperplasia and lobular carcinoma in situ), and in fibroadenomas. Foci of atypical ductal hyperplasia in situ and invasive ductal carcinoma generally showed higher levels of p68 expression. Among the infiltrating carcinomas, p68 expression correlated with nuclear grade. This suggests that the ability of p68 to inhibit cellular proliferation may be impaired in breast cancer and that its expression, although modestly paralleling cellular differentiation, is not a predictive indicator of improved survival.

Breast↗
PubMed1995

Intraoperative diagnostic techniques for stereotactic brain biopsy: cytology versus frozen-section histopathology.

Stereotactic brain biopsy has gained widespread acceptance as a primary diagnostic tool for the evaluation of intracranial lesions. Intraoperative evaluation of such specimens has included the use of both cytological and frozen section histologic techniques. The current study seeks to compare the diagnostic utility of frozen section histopathology and cytology in the intraoperative evaluation of stereotactic brain biopsies in HIV-seropositive patients. Seventy-five HIV-seropositive patients undergoing stereotactic brain biopsy for the evaluation of intracranial lesions were evaluated; intracranial diseases were predominantly infectious or hematologic malignancies. Comparison of frozen section and cytology as a means of intraoperative evaluation showed cytology to have a greater sensitivity (86 vs. 78%), positive (95 vs. 90%) and negative (50 vs. 39%) predictive values and a greater overall diagnostic efficiency (84 vs. 75%) than frozen section. Thus, cytology is a highly effective tool equaling and in some cases surpassing frozen section in terms of sensitivity, predictive value, and overall accuracy. Cytologic examination may often be used as the sole means of intraoperative diagnosis, obviating the need for the freezing and sectioning of fresh tissue and potentially reducing specimen turn around time as well. In other cases, cytology can be used in conjunction with other methodologies for arriving at both intraoperative and final diagnoses in these often difficult cases.

Biopsy↗
PubMed1993

Effects of power and electrical current density variations in an in vitro endometrial ablation model.

OBJECTIVE: To investigate the thermal effects of electrical power and waveform on uterine tissue in vitro, using the gynecologic resectoscope with a 2.5-mm roller-bar electrode. METHODS: The power setting was increased in a serial fashion using both the modulated or damped (coagulating) and unmodulated or undamped (cutting) current to ablate endometrial uterine tissue, using a technique similar to that employed in clinical situations. The power setting ranged from 20-75 W with the modulated waveform and 40-160 W with the unmodulated waveform. Measurements of tissue damage were made by staining for hematoxylin and eosin and the respiratory enzyme dehydronicotinamide adenine dinucleotide phosphate diaphorase. RESULTS: The amount of thermal injury present correlated linearly with the amount of wattage used for either current. Regardless of the power used, the maximum amount of injury into the myometrium was 4.2 mm, representing 19% of the uterine wall thickness, well within the limits of safety. Destruction to 3 mm of myometrium was achieved significantly more often using an unmodulated waveform at greater than 90 W (chi 2, P = .03). CONCLUSIONS: Although the correlation between power and tissue damage achieved statistical significance, the relationship was weak; less than 12% of the observed variation was attributable to increasing wattage. Power and waveform alone do not appear to be clinically significant determinants of the amount of thermal injury occurring during endometrial ablation.

Burns↗
PubMed1991

Tolerance of gastric mucosal flap to postoperative irradiation.

When malignant lesions of the oral cavity, base of tongue, and oropharynx are treated with radical resection, adequate reconstruction is required. The free gastric mucosal flap with microvascular transfer is being used with increasing frequency at Washington University Medical Center. Because of the advanced nature of the primary lesions, most patients also require postoperative radiation therapy. In this paper the tolerance of the gastric mucosal flap to postoperative radiation therapy is reviewed. The changes resulting from radiation therapy in the mucosal flap were found to be acceptable, and no major complications were encountered.

Aged↗
PubMed1991

Supraglottic carcinoma: impact of radiation therapy on outcome of patients with positive margins and extracapsular nodal disease.

Seventy-nine patients with supraglottic carcinoma treated between 1966 and 1985 are reviewed. All patients were treated with surgery and postoperative radiation therapy. Thirty-five percent of the patients had positive margins at the site of resection of the primary tumor. Of the 25 patients who had positive nodal disease, 13 patients (52%) had either extracapsular extension or soft-tissue or adjacent organ invasion, referred to in composite as "grave signs." The median follow-up of the patients was 4.9 years and all patients were followed for a minimum of 3 years. The disease-free survival for all patients was 76% at 2 years and 71% at 3 years. The locoregional control rate for all patients was 70%. This study demonstrates that there is no difference in local recurrence or disease-free survival, or time to recurrence relative to the status of the surgical margins, which may be a benefit of the postoperative radiation therapy. This study also demonstrates that there is an increase in the number of patients with grave signs with increasing nodal stage. The rate of neck recurrence in patients with grave signs was substantially higher (54%) than in patients without grave signs (8%), even though these patients also had positive lymph nodes. Interestingly, there was also a higher rate of local recurrence among patients who had grave signs. Patients receiving doses higher than 6000 cGy to the primary site had fewer local failures, although within each group of patients with positive or negative surgical margins the differences in survival were minimal.

Adult↗
PubMed1984

The neck after vertical hemilaryngectomy: computed tomographic study.

Computed tomographic scans in 22 postoperative vertical hemilaryngectomy patients were analyzed retrospectively to determine the normal postoperative appearance and to evaluate the role of CT in assessing recurrent neoplasm. Twelve patients without clinical evidence of recurrence illustrated the normal postoperative changes: loss of the preepiglottic space fat and the aryepiglottic fold on the operated side, convexity of the residual true vocal cord, and regeneration of the resected thyroid cartilage ala. In the six patients with recurrent neoplasm, the CT manifestations included increased width of the remaining true vocal cord, convexity of the surgically formed pseudocord at glottic level, subglottic tumor, and extralaryngeal neck masses. Recurrence was mimicked in four patients by bulky soft tissue at the endolaryngeal operative site at both CT and laryngoscopy; this was due to hyperkeratosis or granulation tissue in three cases and an inclusion cyst in one case. CT supplemented the physical examination and indirect laryngoscopy, providing information regarding the presence and extent of tumor that was useful in planning the mode or scope of subsequent therapy.

Humans↗
PubMed1982

Leukocyte effects on the dimorphism of Coccidioides immitis.

To assess the influences of leukocytes on the dimorphism of Coccidioides immitis, mycelial elements (arthroconidia) or spherules were incubated with polymorphonuclear leukocytes (PMNLs) or mononuclear leukocytes. In the presence of human leukocytes, arthroconidia became separated spherules as determined by electron microscopy but grew as mycelia when viable leukocytes were absent. Plasma was not required for this effect. In a new assay, PMNLs, lymphocytes, or monocytes from human blood as well as rabbit alveolar macrophages inhibited spherules from forming germ tubes. In flat-bottomed glassware, maximal inhibition occurred with PMNL:spherule ratios above 15:1, whereas in conical-bottomed glassware a ratio of 3:1 was maximally suppressive with PMNLs as well as mononuclear leukocytes. Cytochalasin B and colchicine blocked the effect of PMNLs but not that of other blood leukocytes on spherules. These studies indicate that leukocytes influence coccidioidal dimorphism toward the spherule phase. This effect may be important in host defenses against C. immitis.

Coccidioides↗
PubMed1980

Cancer of the anterior floor of the mouth. Selective choice of treatment and analysis of failures.

From 1971 through 1975, 104 patients with squamous carcinoma of the anterior and anterolateral floor of the mouth underwent surgery, irradiation therapy or a combination of both with the purpose of eliminating their tumors. No patient had received treatment before, and this effort was considered primary and definitive. Fifty-five patients were free of cancer at the time of this analysis, 21 had died of intercurrent disease or new primary tumors, 1 patient was alive although suffering from another primary cancer, and in 27 patients the treatment failed and they died of recurrent carcinoma of the head and neck or with distant metastases. The ultimate determinate rate of control for all stages of disease was 66 percent. A rational approach to the problem of selecting a particular form of treatment for patients with cancer of the anterior floor of the mouth in different clinical manifestations is presented.

Carcinoma, Squamous Cell↗
PubMedDate not supplied

The concept of assisted management of large-scale disasters by horizontal organizations.

Management of large-scale disasters is impeded by inadequately designed organizational infrastructure. The vertical organizational structures of most agencies responding to disasters contribute to a poorly integrated response, especially when collaboration, information sharing, and coordination are required. Horizontal (or lateral) organizations have assisted traditionally vertical civilian and military agencies by enhancing their capacity to operate successfully in complex human emergencies and large-scale natural disasters. Because of the multiagency and highly technical multidisciplinary requirements for decision-making in chemical and biological disasters, similar horizontal management options must be considered.

Disaster Planning↗
PubMedDate not supplied

Role of cytology in the intraoperative diagnosis of HIV-positive patients undergoing stereotactic brain biopsy.

OBJECTIVE: To determine the accuracy of cytology in the intraoperative diagnosis of central nervous system (CNS) lesions in human immunodeficiency (HIV)-positive patients. STUDY DESIGN: We prospectively studied 75 cases of computed tomography- or magnetic resonance imaging-guided brain biopsies performed with stereotactic instrumentation and a Nashold biopsy cannula over the course of five years. Biopsy samples were sent for both frozen section and immediate cytologic evaluation. Crush preparations (Papanicolaou and Diff-Quik stained) were used for cytologic assessment. There were 23 cases of progressive multifocal leukoencephalopathy (PML), 8 of toxoplasmosis (toxo), 3 of herpes simplex virus, 26 of lymphoma, 3 of HIV encephalitis, 1 of melanoma, 1 of hamartoma and 10 of nonspecific changes (paraffin section). RESULTS: Using permanent hematoxylin and eosin-stained histologic sections as the "gold standard," frozen section had a sensitivity of 78% and a specificity of 90%, while cytology had a sensitivity of 88% and specificity of 90%. Most of the false negative cases in cytology and frozen section were due to the predominance of necrosis and/or gliosis, present in six cases of toxo. Two of the false positive cases in frozen section (diagnosed as lymphoma) showed toxo, while two false positive cases in cytology (diagnosed as PML) showed only gliosis with negative immunoperoxidase staining for PML in the permanent sections. CONCLUSION: First, cytology had higher sensitivity that frozen section. Second, cytology provided faster results in most instances, primarily due to the nature of specimen preparation. Third, most misdiagnoses occurred in infectious diseases, especially toxo; this should therefore be kept in mind when nonspecific changes with an atypical lymphocytic infiltrate are seen. Fourth, cytology can be an alternative to frozen section for the intraoperative diagnosis of CNS lesions in HIV-positive patients. Another advantage of cytology is elimination of the need for cutting potentially infectious fresh tissue.

Biopsy↗