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Biomedical subjects

D M Hayes

Publications and source records attributed to D M Hayes.

At least 19 recordsLinked to original sources

Homophobia within schools: challenging the culturally sanctioned dismissal of gay students and colleagues.

In this paper we chronicle the prevalence of and cultural prescription for homophobia in the United States. The endemic nature of homophobia as it has been studied by behavioral scientists is reviewed. We then suggest that as social institutions reflecting cultural values, schools, colleges, and universities sanction an environment that neglects the value of gay students, staff, and faculty. Institutional homophobia dismisses the legitimacy of these individuals, thereby minimizing their contributions to learning. Addressed specifically are suggestions for training individuals who work with students to recognize, address, and challenge homophobia. We conclude that while the weight of American culture sanctions homophobia, training educators and personnel about the nuances of institutional homophobia may provide a fairer environment for gay students and colleagues. An appendix of resources describing effective programs for educational and training use is provided.

Adolescent↗

High dose toremifene for estrogen and progesterone receptor negative metastatic breast cancer: a phase II trial of the Cancer and Leukemia Group B (CALGB).

In pre-clinical and limited clinical studies, high doses ( > or = 200 mg/day) of the triphenylethylene derivative toremifene showed activity in estrogen receptor (ER) negative and ER-unknown metastatic breast cancer after progression on tamoxifen, and a mechanism of action independent of hormone receptor binding was speculated. The CALGB conducted a Phase II trial (CALGB 8945) to test the efficacy of high dose toremifene in a population of patients who had hormone receptor-negative, metastatic breast cancer with limited prior chemotherapy exposure, good performance status, and measurable disease. Twenty eligible patients received toremifene at a dose of 400 mg/day orally for 8 weeks. Toxicity was minimal. Nausea was reported by 20% of the patients, lightheadedness by 20%, weight loss by 20%, and hot flashes by 15%. There was no grade 3-4 toxicity. No objective responses were observed, and 5 of 6 patients with stable disease at 8 weeks developed progressive disease at 11 to 33 weeks. High dose toremifene (400 mg/day) is well-tolerated but imparts no detectable activity in hormone receptor-negative, metastatic breast cancer.

Administration, Oral↗

Contraceptive health programs for adolescents: a critical review.

Many adolescents are neither educated about contraception nor consistently practice it as part of their sexual health behavior. Contraceptive education has taken many forms and has been questioned as to its effectiveness. This paper reviews some of the contraceptive education programs that have been designed for adolescents. These programs, although targeting the adolescent population, differ in educational process based on the delivery setting. School-based, community-based, and college/university-based programs are reviewed and discussed in terms of their effectiveness, potential, and limitations. Educating adolescents about contraception should incorporate the cognitive, affective, and skill-based domains of learning, with outcome expectations based on the specific delivery setting. However, not all settings have the freedom to select from a variety of teaching methodologies. Thus, educational accountability in each setting should differ in terms of outcome expectations, particularly if the program evaluation includes behavioral components.

Acquired Immunodeficiency Syndrome↗

GAP-43 distribution is correlated with development of growth cones and presynaptic terminals.

GAP-43 (F1, B-50, pp46) has been associated with neuronal development and regeneration, but precise localization within neurons is not known. Pre-embedding electron microscopic immunocytochemistry using silver-enhanced 1 nm gold particles was used to localize GAP-43 label in cell cultures of cerebellar neurons. In the plasma membranes of early cultures, high levels of GAP-43 were seen in all parts of the neuron. In older cultures, consistent with previous reports, the first loss of GAP-43 label was seen in the soma and then the axon. Growth cones had high levels of GAP-43 label on the plasma membrane, with increased distribution over unattached relative to attached filopodia. The amount of GAP-43 seen over the plasma membrane of forming presynaptic terminals is lower than over growth cones, indicating a possible correlation between the presence of GAP-43 and the stage of presynaptic terminal development. Intracellular GAP-43 in axons and growth cones was highest in membranes of smooth cisternae. The levels of GAP-43 in smooth cisternae in axons fell by seven days in culture while the levels of GAP-43 in smooth cisternae of growth cones fell at 14 days. When mini-explant cerebellar cultures were examined with light microscopic immunocytochemistry, GAP-43 label of plasma membrane was highest at the periphery of the radial axonal outgrowth, suggesting that addition of GAP-43 to the plasma membrane can occur in the distal axon or at the growth cone.

Animals↗

Silver enhancement of gold antibody probes in pre-embedding electron microscopic immunocytochemistry.

In pre-embedding EM immunocytochemistry with gold probes, the gold must be small enough to penetrate through cell membranes treated with mild detergents. Antibodies labeled with small gold probes (1-1.4 nm) are too small to be resolved in thin sections but can be seen if they are silver-enhanced after the gold has bound to the antigens in the cells. We investigated several aspects of gum arabic-silver lactate-hydroquinone enhancement solution (Danscher solution) by examining gold-conjugated antibodies embedded in agar, sectioned on a vibrotome, and enhanced with different solutions. The rate of silver enhancement was optimized in 50% gum arabic and 200 mM HEPES buffer, pH 5.8. We also examined chemicals used as developers and found that N-propyl gallate (NPG) gave a more uniform development than the routinely used hydroquinone (HQ). The diameter of the silver-enhanced particles after incubation in osmium tetratoxide (OSO4) decreased somewhat with longer incubation time and higher percentages, but the density (number per unit area) of silver-enhanced particles was little changed. The loss of silver-enhanced particle diameter was reduced by lowering the concentration of OSO4 to 0.1%. Comparison of commercial small gold probes showed that NPG enhancement of Nanogold gave more uniform particle size and a better correlation between enhancement time and particle density. When this procedure was applied to cell cultures with monoclonal antibodies, the silver-enhanced particles were similar to those in the agar sections. When free-floating tissue sections were used, longer silver enhancement times were needed to obtain similarly sized particles. This new NPG-silver-enhancement procedure offers a reliable and easy method to localize proteins in cultured cells and tissue sections by pre-embedding electron microscopic immunocytochemistry.

Animals↗

Redistribution of GAP-43 during growth cone development in vitro; immunocytochemical studies.

The growth-associated protein GAP-43 (B-50, F1, pp46), has been found in elongating axons during development and regeneration, and has also been associated with synaptic plasticity in mature neurons. We have examined the loss of GAP-43 labelling from cerebellar granule cells with immunocytochemical localization of a polyclonal antibody to GAP-43. One day after plating, the plasma membrane of cell bodies, neurites and growth cones were all labelled with anti-GAP-43. By 10 days, most of the cell body labelling was lost, and by 20 days the neuritic and growth cone labelling was greatly reduced. Beginning at six days, anti-GAP-43 labelling of growth cones, which was initially uniform, became clustered. When growth cones were double-labelled with antibodies to GAP-43 and the synaptic vesicle protein, p65, inverse changes in the distribution of label was observed. While growth cone labelling with anti-p65 increased from three to 20 days in culture, GAP-43 label began to be lost from some growth cones by six days and showed continuing decline through 20 days. For individual growth cones, the loss of GAP-43 appeared to parallel the accumulation of p65, and first growth cones to lose GAP-43 appeared to be the first to accumulate p65 label. When cultures were grown on a substrate of basement membrane material, the time frames of neuritic outgrowth, loss of GAP-43 labelling, and increase in p65 labelling were all accelerated. At five days, labelling for GAP-43 was weak and labelling for p65 was strong, in a pattern comparable to that seen in older cultures on a polylysine substrate. These results suggest several conclusions concerning the expression and loss of GAP-43 in cultured cerebellar granule neurons. First, GAP-43 label is initially distributed in all parts of these cells. With increasing time in culture the label is first lost from cell bodies and later from neurites and growth cones. Second, the loss of GAP-43 label from growth cones is correlated with the appearance of the synaptic vesicle protein p65. Finally, in vitro developmental changes in the loss of GAP-43 can be altered by changing the growth substrate.

Animals↗

Appendiceal goblet cell carcinoids: a clinicopathological and immunohistochemical study.

Goblet cell carcinoids are uncommon but distinctive tumours of the appendix. We have reviewed 11 cases diagnosed within the period 1976-1990. The mean age at presentation was 58 years (range 24-76), with a female:male ratio of 8:3. At presentation, in seven patients tumour was confined to the appendix or mesoappendix (mean age 51) and in four there was extension beyond the appendix (mean age 69). Of the seven patients with localized tumour, six are alive and without clinical disease after a mean follow-up period of 32 months and one died with recurrent tumour after 10 years. Of the four with more extensive disease, two died during follow-up (at 23 months with probable liver metastases and at 16 months with intestinal obstruction) and two are alive, one with disease and one clinically disease-free. Immunohistochemistry showed that all of the tumours stained positively for either neuron-specific enolase, chromogranin A or protein gene product 9.5. No tumour stained with antiserum to substance P and none showed glucagon-like immunoreactivity, but four cases stained positively for pancreatic polypeptide, an unusual feature in midgut carcinoids.

Adult↗

Phase II study of oral idarubicin in favorable histology non-Hodgkin's lymphoma.

Idarubicin, a new analogue of daunorubicin, was administered p.o. for 3 consecutive days every 3 weeks at a dose of 45 mg/m2 in 46 patients (45 eligible and evaluable) with previously treated, favorable histology, non-Hodgkin's lymphoma. Median clinical characteristics included an age of 66 years, a performance status of 1, and one prior chemotherapeutic regimen. Forty-one patients were relapsing from prior therapy, and 37 had stage IV disease. Patients with prior anthracycline therapy were excluded. Responses were observed in 58% of patients (10 complete and 16 partial), with a median duration of 6+ months (2-41+ months). Idarubicin was well tolerated. Nonhematological toxicities (nausea/vomiting, mucositis/diarrhea, alopecia, and anorexia) were observed in less than or equal to 50% of patients. Median hematological values during the first cycle include a WBC of 4100/mm3 and a platelet count of 147,000/mm3. With dose escalation, hematological toxicity was the dose-limiting toxicity. Symptomatic cardiac toxicity was not observed. Median values for the resting left ventricular ejection fraction during the course of therapy were 0.65 (initial) and 0.63 (final). Idarubicin in oral form is an active drug in previously treated patients with favorable histology non-Hodgkin's lymphoma.

Administration, Oral↗

Phase II trial of etoposide and cisplatin for refractory small cell lung cancer: a Cancer and Leukemia Group B Study.

A phase II trial of etoposide and cisplatin for patients with previously treated small cell lung cancer was carried out by CALGB from June 1983 to May 1984. Thirty-five evaluable patients who had failed one prior chemotherapy regimen were treated with etoposide 80 mg/m2 and cisplatin 20 mg/m2 days 1-5 every 3 weeks. Objective responses were seen in 7 patients (20%) with 1 complete response and 6 partial responses. The median duration of response was 5.1 months. Fifteen patients (43%) had stable disease. Overall survival was 49% at 6 months and 14% at 1 year. The median survival was 6 months. Toxicity was mainly hematologic with severe and life-threatening leukopenia and thrombocytopenia seen in 71% and 66% of patients, respectively. Two treatment-related deaths caused by infection were seen. This cooperative group study fails to confirm the high response rates previously reported in institutional pilot studies.

Adult↗

Self-esteem and health instruction: challenges for curriculum development.

A review of literature on self-esteem and its role in health education raises questions about the extent to which health education can influence student self-esteem through direct and indirect instruction. This article operationally defines self-esteem, discusses the role of health education in developing self-esteem through direct and indirect instruction, interprets evidence that self-esteem is affected by health education curricula, and discusses challenges facing health educators in curriculum development, instruction, and evaluation of self-esteem as a realistic component of health education curricula.

Curriculum↗

A neutral pH silver development method for the visualization of 1-nanometer gold particles in pre-embedding electron microscopic immunocytochemistry.

The availability of 1-nm gold particles permits the use of a particulate label with standard pre-embedding electron microscopic immunocytochemical techniques. We have employed these particles to localize a synaptic vesicle protein, p65, and a growth-associated protein, GAP-43, in neuron cell cultures. To be detected by standard transmission electron microscopy, these ultra-small gold particles must be enlarged. We have applied a commercially available silver development kit (IntenseM), the method of Danscher, and a neutral pH development procedure which we developed to effect this enlargement. Although IntenseM permits development with good preservation of morphology, it is limited by lack of reproducibility and by variability of final particle size. The method of Danscher provides well-controlled and reproducible enlargement, but is limited with respect to preservation of ultrastructural details. The neutral pH development procedure reproducibly enlarges gold particles with superior preservation of morphology. The use of this development procedure in conjunction with 1-nm gold probes should permit precise ultrastructural localization of a variety of intracellular antigens.

Animals↗

Highly basic 30- and 32-kilodalton proteins associated with synapse formation on polylysine-coated beads in enriched neuronal cell cultures.

Neuronal proteins involved in axonal outgrowth and synapse formation were examined in an enriched neuronal cell culture system of the cerebellum. In rat cerebellar cell cultures, 98.9% of the cells are neurons and the remaining 1.1% of the cells are flat nonneuronal cells. These enriched neuronal cultures, examined with two-dimensional gel electrophoresis, showed protein patterns similar to those of neonatal cerebellum, but very different patterns from glial enriched cultures. High levels of a neuronal membrane acidic 29-kilodalton (kD) protein were found. It has been shown previously that neuronal cultures incubated with polylysine-coated beads will develop numerous presynaptic elements on the bead surface. We report here that isolation of the beads from enriched neuronal cell cultures incubated with [35S]methionine showed, with two-dimensional nonequilibrium pH gradient gel electrophoresis (2D-NEPHGE), levels of a basic 32-kD protein (pI 8) note detected in cultures alone, and increased levels of a 30-kD protein (pI 10). When culture medium was examined with 2D-NEPHGE, three acidic proteins were identified that were secreted by the cultured neurons. In summary, a neuronal enriched cell culture system was used with isolated polylysine-coated beads to identify basic 30-kD and 32-kD proteins that may be involved in synapse formation.

Animals↗

Diffuse well-differentiated lymphocytic lymphoma: chemotherapy with BCNU, cyclophosphamide, vincristine, melphalan and prednisone.

Twenty patients with stage III and IV diffuse well-differentiated lymphocytic lymphoma were treated with combination chemotherapy consisting of BCNU, cyclophosphamide, vincristine, melphalan and prednisone (M-2). Treatment was given every 5 weeks for 11 cycles in responding patients. The median age of the patients was 62 years (range 45-76). There were 12 complete remissions and 6 partial remissions for an overall response rate of 90%. The median duration of remission was 24 months (range 12-79 months) and was identical for complete responders and partial responders. All but 2 responding patients have been subsequently retreated for relapse. The median survival was 84 months (range 1-108 months). Myelosuppression was mild. Nausea/vomiting, neuropathy, alopecia and gastrointestinal symptoms from prednisone were seen in the minority of patients. One patient expired from sepsis/neutropenia during the first cycle of therapy. The M-2 protocol produces effective remissions in diffuse well-differentiated lymphocytic lymphoma. The relapse and survival pattern are similar to the results achieved with other chemotherapy regimens in low-grade lymphoma.

Adult↗

Development and elimination of presynaptic elements on polylysine-coated beads implanted in neonatal rat cerebellum.

Polylysine-coated sepharose beads were implanted in the cerebellum of neonatal rats and examined at 3 hr, 3 days, 7 days, 14 days, and 21 days after surgery. Previous studies at 5 or 8 days after implantation showed that axons formed neuronal swellings that appeared to be presynaptic elements, with the bead surface in the position of a postsynaptic element. Results reported here show that no beads at 3 hr had presynaptic elements, whereas the number of beads with presynaptic elements increased to high levels at 3 and 7 days but dropped to low values at 14 and 21 days after implantation. Presynaptic elements were seen on beads regardless of their distance from cerebellar tissue except at 3 hr, when no axons were seen in the implant, indicating that axons first grew into the implant and then formed presynaptic elements. The morphological measurements of presynaptic elements on beads at 3 to 7 days after implantation showed increases in area and number of synaptic vesicles, which then decreased at 14 and 21 days after implantation. These results show that axons can grow into implants of polylysine-coated beads and form presynaptic elements that do not survive with increased time after implantation. The survival of presynaptic elements on beads can be used as a model for investigations into regeneration of axons and presynaptic elements in the injured brain.

Animals↗

Incendiary characteristics of a new laser-resistant endotracheal tube.

Endotracheal tube fires are the most frequent complication of laser surgery of the larynx. We investigated the incendiary characteristics of a new laser-resistant endotracheal tube, compared to polyvinyl chloride (PVC) and red rubber (RR) tubes, with different gas mixtures. A CO2 laser was focused on each tube and the probability of fire was assessed with oxygen fractions (FiO2) of 30%, 40%, 50%, 70%, and 100%, the balance being N2 or N2O. The laser-resistant tube could not be penetrated by a single laser pulse, regardless of laser energy or gas composition. PVC and RR tubes were readily ignited, the probability of ignition being related to oxygen concentration and laser energy. Nitrous oxide readily supported combustion. We suggest that laser surgery of the larynx can be most safely performed with a laser-resistant endotracheal tube and with gas mixtures containing the minimal safe O2 concentration (without nitrous oxide).

Anesthesia, Inhalation↗