Transcriptomic and epigenomic effects of insoluble particles on J774 macrophages.

Here we report epigenomic and transcriptomic changes in a prototypical J774 macrophage after engulfing talc or titanium dioxide particles in presence of estrogen. Macrophages are the first immune cells to engage and clear particles of various nature. A novel paradigm is emerging, that exposure to so-called 'inert' particulates that are considered innocuous is not really free of consequences. We hypothesized that especially the insoluble, non-digestible particles that do not release a known hazardous chemical can be underappreciated agents acting to affect the regulation inside macrophages upon phagocytosis. We performed gene chip microarray profiling and found that talc alone, and especially with oestrogen, has induced a substantially more prominent gene expression change than titanium dioxide; the affected genes were involved in pathways of cell proliferation, immune response and regulation, and, unexpectedly, enzymes and proteins of epigenetic regulation. We therefore tested the DNA methylation profiles of these cells via epigenome-wide bisulphite sequencing and found vast epigenetic changes in hundreds of loci, remarkably after a very short exposure to particles; ELISA assay for methylcytosine levels determined the particles induced an overall decrease in DNA methylation. We found a few loci where both the transcriptional changes and epigenetic changes occurred in the pathways involving immune and inflammatory signalling. Some transcriptomic and epigenomic changes were shared between talc and titanium dioxide, however, it is especially interesting that each of the two particles of similar size and insoluble nature has also induced a specific pattern of gene expression and DNA methylation changes which we report here.

Electroconvulsive therapy as a treatment for refractory neuropsychiatric lupus with catatonia: three case studies and literature review.

Neuropsychiatric disorders associated with systemic lupus erythematosus are very common. Treatment generally consists of glucocorticoids and immunosuppressive therapy; however, some cases are unresponsive. Electroconvulsive therapy (ECT) is a recognized treatment modality in psychiatry and is an option for refractory cases of neuropsychiatric lupus. This report describes three cases of neuropsychiatric lupus that improved with ECT after failure of antipsychotics and immunosuppressive therapy. All cases met DSM-5 criteria for catatonia (case 1: agitation, stereotypies, and grimacing; case 2: stupor, mutism, and grimacing; case 3: agitation, mutism, and stereotypies); therefore, ECT was indicated. This case series shows that ECT can be a therapeutic option in patients with neuropsychiatric lupus, especially when associated with catatonia and unresponsive to conventional treatment.

Relationship between Helicobacter pylori detection and an increased risk of infection in childhood

The risk of developing gastric cancer is believed to be related to differences among Helicobacter pylori strains and the inflammatory responses mediated by host genetic factors. H. pylori infection is acquired at an early age and in the absence of appropriate antibiotic therapy, it generally persists for life. Tp53 gene regulates the transcription of several cytokines and chemokines involved in innate immunity and its action may be influenced by the presence of different H. pylori strains. The present study aimed to detect H. pylori in pediatric patients, to access Tp53 polymorphism at codon 72 and to correlate such findings with age and histopathological results. Three hundred and forty-two patients were analyzed. DNA from their gastric biopsies was extracted and the detection of H. pylori was performed through polymerase chain reaction assays, urease test and histopathologic examination. Allelic discrimination of SNP rs1042522 (Tp53) was performed by real-time polymerase chain reaction. Our results suggest a possible relationship between the presence of H. pylori and chronic gastritis in children and young patients, and showed a significant association between ageing and positivity for H. pylori. It was verified that patients aged < 10 years were 1.3 times more likely to have infection by H. pylori when compared with those aged > 10 years. Finally, no association was found between Tp53 polymorphisms and the presence of H. pylori.

Breast malignant phyllodes tumour metastasising to soft tissues of oral cavity.

Metastases from infraclavicular neoplasms to the oral cavity are rare, and the anatomical structures most frequently affected are the maxillae. The primary sites that develop metastases to head and neck include lung, breast, liver, thyroid gland, kidney and melanomas, among others. The breast is one of the usual primary regions that can present them. In the literature, most metastases to these regions correspond to squamous cell carcinomas and adenocarcinomas; few studies report other type of neoplasms such as phyllodes tumour (PT) that present this behaviour. The importance of identifying metastatic disease to the oral cavity, be it as the first manifestation of a neoplasm from unknown origin or as a development in the course of the disease, is that it allows determination of adequate treatment, which has an effect on the patient's prognosis. The usual behaviour of PT is frequent recurrence and, when metastases are present, these are to lungs and bone. Two cases of malignant PT metastasising to tongue and lip are presented, as well as a review of the literature.

Breast malignant phyllodes tumour metastasising to soft tissues of oral cavity

Metastases from infraclavicular neoplasms to the oral cavity are rare, and the anatomical structures most frequently affected are the maxillae. The primary sites that develop metastases to head and neck include lung, breast, liver, thyroid gland, kidney and melanomas, among others. The breast is one of the usual primary regions that can present them. In the literature, most metastases to these regions correspond to squamous cell carcinomas and adenocarcinomas; few studies report other type of neoplasms such as phyllodes tumour (PT) that present this behaviour. The importance of identifying metastatic disease to the oral cavity, be it as the first manifestation of a neoplasm from unknown origin or as a development in the course of the disease, is that it allows determination of adequate treatment, which has an effect on the patient's prognosis. The usual behaviour of PT is frequent recurrence and, when metastases are present, these are to lungs and bone. Two cases of malignant PT metastasising to tongue and lip are presented, as well as a review of the literature (AU)

Tumores odontogénicos malignos. Estudio retrospectivo y colaborativo de 7 casos / Malignant odontogenic tumors. A retrospective and collaborative study of seven cases

Se presenta la frecuencia, características clínico-patológicas y evolución de los tumores odontogénicos malignos diagnosticados en tres servicios de patología de la Ciudad de México, de acuerdo a los criterios vigentes de la O.M.S. En total, se encontraron siete casos (5 en varones y 2 en mujeres), lo que representa menos del 4 por ciento de todos los tumores odontogénicos diagnosticados. Hubo seis carcinomas (dos ameloblastomas malignos, dos carcinomas odontogénicos de células claras, un carcinoma primario intra-óseo y un carcinoma originado del revestimiento de quiste odontogénico) y un fibrosarcoma ameloblástico. El intervalo de edad fue de 25 a 72 años (media: 43.8). Los carcinomas odontogénicos de células claras se presentaron en la región caninopremolar en maxilar y en mandíbula (un hombre y una mujer), mientras que el resto de lesiones se localizaron en la zona posterior de la mandíbula, con predominio por el sexo masculino (4:1), lo que concuerda con lo reportado en la literatura. El tratamiento en todos los carcinomas consistió en la resección quirúrgica, mientras que el fibrosarcoma fue tratado con quimioterapia debido a su gran extensión, sin respuesta favorable. El paciente con carcinoma primario intraóseo presentó metástasis submaxilar y cervical y la neoplasia fue causa de fallecimiento. A pesar de su rareza, los tumores odontogénicos malignos constituyen una causa importante de intervenciones quirúrgicas extensas en la región maxilofacial. (AU)

Improving cancer pain management using a performance improvement framework.

Pain is an important issue in quality of care and is increasingly cited as an outcome used to evaluate effectiveness of nursing care. Research indicates that nurses are not well prepared to care for patients with pain. Thus many patients are inadequately assessed and treated and consequently receive less than optimal pain management. The article describes the development, implementation, and evaluation of a pain education program designed to provide clinical nurses with the knowledge necessary to use appropriate pain management techniques. Program content stresses the use of a performance improvement framework for changing clinical practice in individual clinical settings.

p53, p21, Rb, and MDM2 proteins in tongue carcinoma from patients < 35 versus > 75 years.

Relatively rare squamous cell carcinomas of the tongue in young patients may be associated with different etiologic factors and pathogenetic mechanisms than carcinomas from the same site in older patients. Alterations in cell cycle proteins likely contribute to the biologic behavior of these neoplasms. The purpose of this investigation was to evaluate cell cycle proteins (p53, p21, Rb, MDM2) in lateral tongue cancers from patients at the two ends of the age spectrum. All available archived lateral tongue carcinomas from patients < 35 years (n = 36, 23 males and 13 females) were sectioned, immunohistochemically stained, and evaluated. Protein expression was scored as percent positive nuclei. An equal number of sequentially accessioned lateral tongue specimens from patients > 75 years (23 males and 13 females) were stained and compared. Positive p53 staining was seen in 18/36 of the < 35-year group versus 24/36 of the > 75-year group (p = 0.149). Increased p21 staining (both percent of positive cells and intensity) was evident in 25/32 of the < 35-year group versus 24/32 of the > 75-year group (p = 1.0). Increased p21 expression was seen in both p53-positive and -negative cases in both age groups. Rb protein was increased in 16/29 of the < 35-year group versus 17/26 of the > 75-year group (p = 0.58). Fourteen cases (4/35 vs 10/36, p = 0.135) showed positive MDM2 staining; MDM2-positive cases were also p53 positive in 4/4 younger and 8/10 older patients. We conclude that p53, p21, Rb, and MDM2 are over-expressed in lateral tongue cancers, and that immunohistochemical profiles are heterogeneous. A p53-independent pathway of p21 induction is supported by the results; p53 suppression may be associated with MDM2 protein expression in a subset of cancers. Significant differences in the expression of p53, p21, Rb, and MDM2 proteins are not evident in lateral tongue carcinomas from patients < 35 years as compared to patients > 75 years.

Blood cell transplantation: its impact on one family.

OBJECTIVES: To share a story about being the wife of a cancer survivor who had a blood cell transplantation (BCT). DATA SOURCES: Personal experience, and published articles related to the impact of cancer on the family. CONCLUSIONS: Cancer affects not only the patient but the entire family unit. Yet, family members are a forgotten population. With advances in cancer treatment, survivorship has increased resulting in caregiving demands that can last for years. The lack of research related to the impact of BCT on family members must be addressed. IMPLICATIONS FOR NURSING PRACTICE: There are many ways that nurses can provide holistic care to family members who have a loved one going through a BCT. Physical, psychological, social, and spiritual aspects of care can make a tremendous impact on the lives of patients and family members.

Cancer pain education for patients.

OBJECTIVES: To review the basic principles of patient education, models of innovative approaches to patient education, and needs for future development in patient education. DATA SOURCES: Review articles, research studies, book chapters, personal communication, and standards pertaining to cancer pain education. CONCLUSIONS: Patient education based on principles of effective teaching and learning is the cornerstone of effective pain management. Improved methods of patient teaching combined with novel approaches to delivering appropriate pain content can lead to enhanced patient compliance with the prescribed pain medication regimen. IMPLICATIONS FOR NURSING PRACTICE: Nurses are essential to improving the care of cancer patients in pain by providing patient education as a care component of professional nursing practice. The challenge remains to overcome significant barriers of limited time and resources to achieve these goals.

Angiocentric lymphomas of the palate: clinico-pathological considerations in 12 cases.

Angiocentric lymphomas (AL) involving the mid-face are infrequent lesions. Their incidence seems to be higher in certain Asian and Latin American countries, where most of the reported series reveal a predominance of T-cell lineage and a high frequency of EBV-positive cells. The clinical and pathological features of 12 AL that affected the palate are presented. Immunophenotypic studies were performed in nine of these cases. Seven (77%) demonstrated T-cell lineage, one was of B-cell origin and one could not be classified. The high incidence of T-cell lesions in this and other studies supports the existence of geographical and possibly of etiological differences in these neoplasms.

Odontogenic tumors in Mexico: a collaborative retrospective study of 349 cases.

Reports about the frequency of odontogenic tumors are scarce, and diagnostic criteria used in the reports are not uniform. This article presents the results of a retrospective study of odontogenic tumors recorded in four services of diagnostic pathology in Mexico City (two dental schools, one cancer hospital, and one private oral pathology service). The final diagnosis in each case was based on the 1992 histologic criteria of the World Health Organization. The frequency of odontogenic tumors, expressed as a percent of all oral and maxillofacial specimens, ranged from 0.8% in the cancer hospital (0.02% of all biopsies) to 3.7% in the private oral pathology service. The frequency was identical for the two dental schools (2.5%). We found a total of 349 odontogenic tumors; of these, 345 were benign (98.8%), and 4 (1.1%) were malignant (3 were primary intraosseous carcinomas and 1 was a malignant ameloblastoma). The most frequently occurring tumors were odontoma (34.6%), ameloblastoma (23.7%), myxoma (17.7%), adenomatoid odontogenic tumor (7.1%), and calcifying odontogenic cyst (6.8%). Although relatively rare, odontogenic tumors are still an important cause of extensive surgical procedures in Mexico.

Unscheduled readmissions for uncontrolled symptoms. A health care challenge for nurses.

The purpose of this study was to measure the impact of nursing strategies to improve cancer pain management on hospital readmission for uncontrolled pain. Strategies include implementing a pain resource nurse program (PRN), making pain management a focus in the continuous quality improvement process of the institution and creating a supportive care service. Admissions were compared before and after implementation of the strategies. Results for 1989 to 1990 revealed 5772 total admission with 4.4% (255) admissions for uncontrolled pain; results for 1992 to 1993 revealed 4066 total admissions with 3.0% (121) admissions for uncontrolled pain. Findings indicate that strategies were effective in reducing the number of readmissions for uncontrolled pain.

Anorexia, cachexia, and dysphagia: the symptom experience.

OBJECTIVES: To review the symptoms of anorexia, cachexia, and dysphagia and to provide information on nutritional assessment and interventions. DATA SOURCES: Published studies of anorexia, cachexia, and dysphagia, research abstracts, and review articles. CONCLUSIONS: Anorexia, cachexia, and dysphagia can cause severe alterations in nutrition in cancer patients that may lead to irreversible nutritional compromise and death. Nursing research must focus on symptom management of these three symptoms, the needs of the patient and family, and the impact of dysphagia on quality of life. IMPLICATIONS FOR NURSING PRACTICE: Assessment, objective evaluation, pharmacological interventions, and nutritional counseling are important interventions for patients with anorexia and cachexia. Swallowing therapy, food intake adjustments, oral hygiene, and supportive care are important measures needed by the patient with dysphagia.

Ethical decision making in oncology: a case study approach.

Every day healthcare professionals are involved in making difficult clinical decisions. This has become more apparent as society changes, in part due to technologic growth and diminishing resources. This article identifies basic principles of bioethics, applies those principles to situations that occur in the process of providing care to oncology patients, and identifies concerns expressed by nurses attending an oncology conference that are related to those patient situations. Bioethical principles are described and include autonomy, beneficence, nonmaleficence, and justice. A decision-making model is provided as a tool to resolve ethical dilemmas.

Diagnostic value of fasting plasma peptide concentrations in patients with chronic diarrhea.

To evaluate the utility of screening for multiple gastrointestinal peptides in the evaluation of patients with chronic diarrhea, we studied 193 patients referred for evaluation of chronic diarrhea and eight patients with known peptide-secreting tumors as a reference group. Fasting plasma samples were assayed for motilin, neurotensin, pancreatic polypeptide, somatostatin, substance P, vasoactive intestinal polypeptide, gastrin-releasing peptide, and calcitonin during a protocol evaluation for causes of chronic diarrhea. Although none of the referred patients were found to have tumors, abnormal levels of one or more peptides were found in 86 of 193 patients (45%). Abnormal plasma peptide levels were sometimes as high in these patients as in patients with known peptide-secreting tumors and would have led to mistaken diagnoses of tumors much more often than they would have led to correct diagnoses. The positive predictive value of elevation of any assayed peptide was < 2% at realistic prevalence rates for peptide-secreting tumors; the negative predictive value of a series of normal results was > 99%, but much of this was due to the rarity of these tumors. Patients with chronic diarrhea should not be screened routinely with a panel of plasma peptide assays in an effort to detect tumors; instead, peptide levels should be ordered selectively. Elevated fasting concentrations of the plasma peptides measured in this study are most likely epiphenomena due to diarrhea and should not be the sole basis for invasive diagnostic or surgical management of these patients.

The pain resource nurse training program: a unique approach to pain management.

Adequate pain management is a 24 hr a day responsibility for health-care professionals working with cancer patients. Because nurses spend more time with patients in pain than any other member of the health-care team, they play a central role in pain assessment and pain management. The City of Hope National Medical Center, a clinical cancer center, developed a pain management course for staff nurses entitled "The Pain Resource Nurse (PRN) Training Program." The purpose of this innovative course was to prepare staff nurses to assume an active role in pain management. Twenty-six registered nurses participated in the 40-hr didactic and clinical course. The curriculum included information on pain assessment, pharmacology, nondrug interventions, and cultural, ethical, and psychosocial issues related to pain. After completion of the course, program staff have remained available to the PRNs to provide current information on pain management, and to assist with role implementation and guidance on interfacing with staff. This paper reports on the development, implementation, and 3-mo evaluation of this unique program.