Interrater agreement among psychiatrists regarding emergency psychiatric assessments.
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Attitude of Health Personnel↗
Biomedical subjects
J Russo
Publications and source records attributed to J Russo.
Cellular basis of breast cancer susceptibility.
Breast cancer originates in undifferentiated terminal structures of the mammary gland. The terminal duct of the Lob 1 of the human female breast is the site of origin of ductal carcinomas. Cell replication and the concentration of estrogen receptors type at in Lob 1 are at their peak during early adulthood, at a time during which the breast is more susceptible to carcinogenesis, decreasing considerably with aging. More importantly, when treated with carcinogens in vitro they express phenotypes indicative of cell transformation. These studies indicate that in humans there is a target cell of carcinogenesis, which is found in a specific compartment whose characteristics are a determinant factor in the initiation event. These target cells will become the stem cells of the neoplastic event, depending upon: a) topographic location within the mammary gland tree, b) age at exposure to a known or putative genotoxic agent, and c) reproductive history of the host. Epidemiological findings such as the higher incidence of breast cancer in nulliparous women and in women having early menarche support this concept, because it parallels the higher cancer incidence elicited by carcinogens when exposure occurs at a young age. In addition, it has been shown that increase in parity is associated with a pronounced decrease in the risk of breast cancer, each additional live birth conferring a 10% risk reduction. Thus, the protection afforded by early full-term pregnancy in women could be explained by the higher degree of differentiation of the mammary gland at the time in which an etiologic agent or agents act. The relevance of our work lies in the side by side comparison of in vivo and in vitro studies in the human breast that validates experimental data for extrapolation to the human situation. The finding that cell proliferation is of importance for cancer initiation, whereas differentiation is a powerful inhibitor, provides novel tools for developing rational strategies for breast cancer prevention and control.
Breast↗
Case report of a ramus onlay graft followed by a dental implant restoration.
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Aged↗
Go the extra step to develop a relationship between the specialist and the restorative doctor.
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Aged↗
DNA content and chromatin texture of benzo[a]pyrene-transformed human breast epithelial cells as assessed by image analysis.
DNA content and chromatin supraorganization defined in terms of patterns of chromatin texture were studied by image analysis in Feulgen-stained human breast MCF-10F epithelial cells expressing different stages of tumorigenic progression after treatment with benzo[a]pyrene (BP). Nontransformed MCF-10F, nontumorigenic transformed BP1, and tumorigenic BP1-E1 cell lines were analyzed. A relationship between changes in DNA content and chromatin texture and the expression of different stages of tumorigenesis were researched in interphase nuclei. A significant decrease in Feulgen-DNA amounts and absorbing areas suggesting aneuploidy, and first detected in nontumorigenic transformed BP1 cells, became more relevant in the tumorigenic cell line BP1-E1. Simultaneously, an increase in optical densities and a change in related parameters, demonstrating increased chromatin higher order packing states, occurred in transformed BP1 cells and extended over larger chromatin areas in tumorigenic BP1-E1 cells. The results indicate loss of DNA and a change in chromatin higher order packing states accompanying the expression of different stages of the in vitro tumorigenesis process in BP-transformed human breast epithelial cells. It is suspected that the gradually acquired chromatin "condensation" supraorganization pattern is associated with activated transcription activities previously suggested for these cells.
Benzo(a)pyrene↗
Biological and molecular basis of human breast cancer.
Human breast cancer remains the most common malignancy in the American women. The ultimate cure of this disease relies on a better understanding of the mechanisms underlying the initiation and progression of this disease. The neoplastic transformation of HBEC in vitro represents a successful model for obtaining knowledge on the molecular and biological alterations that may contribute to the tumorigenic mechanisms. We have presented here a current understanding of chemically transformed HBEC in the following aspects: 1. Factors affecting the transformation of HBEC such as genetic predisposition and differentiation status and prior immortalization; 2. New targets for studying the mechanism of cell immortalization such as alterations in telomerase activity and differential expression of cell cycle dependent genes as well as others recently isolated through differential cloning such as H-ferritin, and a calcium binding protein; 3. Epigenetic and genetic mechanisms underlying cell transformation; 4. The association of microsatellite instability in specific loci on chromosomes 11, 13, and 16 with the progression of cell transformation; and 5. The application of microcell mediated chromosome transfer technique as an approach to testing the functional role of specific genes whose dysregulation or loss of function may contribute to the ultimate cell transformation. Further efforts in this cell system will be directed to determine the roles of identified molecular changes as well as the mapping/cloning of tumor suppressor or senescence genes such as those that may reside on chromosomes 11 or 17.
Breast Neoplasms↗
A brief medical necessity scale for mental disorders: reliability, validity, and clinical utility.
Managed care organizations (MCOs) use the concept of "medical necessity" to decide whether a prescribed treatment is warranted for a given medical condition. Because mental disorders lack the objective disease criteria common to medical illness, behavioral health administrators need a validated means to identify and quantify the severity of "medically important" aspects of mental disorders. The authors developed and tested a brief medical necessity scale for mental disorders in 205 patients presenting for initial evaluation. The scale had a factor structure with four subscales; good internal consistency, interrater reliability, and concurrent and predictive validity; and modest ability to identify patients requiring hospitalization and, in hospitalized patients, those requiring involuntary hospitalization. The authors propose use of the scale to better clarify decisions about level of care assignments and to better assess patient characteristics predictive of good outcome.
Adult↗
Longitudinal changes associated with improvement in chronic fatigue patients.
Tertiary care patients with chronic fatigue were followed for 2.5 years to determine if changes in physical and psychological status were associated with improvements in chronic fatigue, physical functioning, and return to work. Results indicated that improvement in psychological symptoms, DSM-III-R disorders, physical examination signs, and changes in whether the patient continued to meet criteria for chronic fatigue syndrome (CFS) were associated with recovery from fatigue, improved functioning, and return to work. Patients who never met CFS criteria or only met criteria at the initial assessment, reported improved physical functioning. Patients whose psychiatric disorders and physical examination signs were still present at a mean follow-up time of 2.5 years were more likely to have persistent fatigue and work disability. Loss of physical examination signs was a significant independent predictor of improved functioning and return to work. These results suggest that psychiatric status, as well as physical status, are associated with recovery from chronic fatigue.
Adult↗
Impact of improved depression treatment in primary care on daily functioning and disability.
BACKGROUND: Few data are available regarding the impact of improved depression treatment on daily functioning and disability. METHODS: In two studies of more intensive depression treatment in primary care, patients initiating antidepressant treatment were randomly assigned to either usual care or to a collaborative management programme including patient education, on-site mental health treatment, adjustment of antidepressant medication, behavioural activation and monitoring of medication adherence. Assessments at baseline as well as 4 and 7 months included several measures of impairment, daily functioning and disability: self-rated overall health, number of bodily pains, number of somatization symptoms, changes in work due to health, reduction in leisure activities due to health, number of disability days and number of restricted activity days. RESULTS: Average data from the 4- and 7-month assessments in both studies, intervention patients reported fewer somatic symptoms (OR 0.68, 95% CI 0.46, 0.99) and more favourable overall health (OR 0.50, 95% CI 0.28, 0.91). While intervention patients fared better on other measures of functional impairment and disability, none of these differences reached statistical significance. CONCLUSIONS: More effective acute-phase depression treatment reduced somatic distress and improved self-rated overall health. The absence of a significant intervention effect on other disability measures may reflect the brief treatment and follow-up period and the influence of other individual and environmental factors on disability.
Absenteeism↗
Role of hormones in mammary cancer initiation and progression.
Breast cancer, the most frequent spontaneous malignancy diagnosed in women in the Western world, is a classical model of hormone dependent malignancy. There is substantial evidence that breast cancer risk is associated with prolonged exposure to female hormones, since early onset of menarche, late menopause, hormone replacement therapy and postmenopausal obesity are associated with greater cancer incidence. Among these hormonal influences a leading role is attributed to estrogens, either of ovarian or extra-ovarian origin, as supported by the observations that breast cancer does not develop in the absence of ovaries, ovariectomy causes regression of established malignancies, and in experimental animal models estrogens can induce mammary cancer. Estrogens induce in rodents a low incidence of mammary tumors after a long latency period, and only in the presence of an intact pituitary axis, with induction of pituitary hyperplasia or adenomas and hyperprolactinemia. Chemicals, radiation, viruses and genomic alterations have all been demonstrated to have a greater tumorigenic potential in rodents. Chemical carcinogens are used to generate the most widely studied rat models; in these models hormones act as promoters or inhibitors of the neoplastic process. The incidence and type of tumors elicited, however, are strongly influenced by host factors. The tumorigenic response is maximal when the carcinogen is administered to young and virgin intact animals in which the mammary gland is undifferentiated and highly proliferating. The atrophic mammary gland of hormonally-deprived ovariectomized or hypophysectomized animals does not respond to the carcinogenic stimulus. Administration of carcinogen to pregnant, parous or hormonally treated virgin rats, on the other hand, fails to elicit a tumorigenic response, a phenomenon attributed to the higher degree of differentiation of the mammary gland induced by the hormonal stimulation of pregnancy. In women a majority of breast cancers that are initially hormone dependent are manifested during the postmenopausal period. Estradiol plays a crucial role in their development and evolution. However, it is still unclear whether estrogens are carcinogenic to the human breast. The apparent carcinogenicity of estrogens is attributed to receptor-mediated stimulation of cellular proliferation. Increased proliferation could result in turn in accumulation of genetic damage and stimulation of the synthesis of growth factors that act on the mammary epithelial cells via an autocrine or paracrine loop. Alternatively estrogens may induce cell proliferation through negative feedback by removing the effect of one or several inhibitory factors present in the serum. Multidisciplinary studies are required for the elucidation of the mechanisms responsible for the initiation of breast cancer. Understanding of such mechanisms is indispensable for developing a rational basis for its prevention and control.
Animals↗
Neoplastic progression of breast epithelial cells--a molecular analysis.
Molecular changes associated with breast cancer progression were characterized using the MCF-10F cell series. MCF-10F was established from fibrous mastectomy tissue of a patient without detectable cancer. In vitro treatment of MCF-10F cells with benzo(a)pyrene resulted in a transformed subclone MCF-10F-BP1 (BP1). Transfection of clone BP1 with T24-Hras resulted in the tumorigenic line MCF-10F-BP1-Tras (BP1-Tras). Using flow cytometry, the expression of HLA I, ERBB-2 and MUC-1 was found to be comparable in 'normal' MCF-10F, transformed BP1 and tumorigenic BP1-Tras cells. Glycosylated mucin is elevated in BP1 but reduced in BP1-Tras cells. Using mRNA differential display analysis, cDNA profiles of the 'normal', transformed and tumorigenic cell lines were strikingly similar, yet distinct and elevated expression of several common cDNA fragments was detected in BP1 and BP1-Tras when compared with MCF-10F cells. These fragments were cloned and sequenced. The sequences of clones T1-360 and C4-310 are homologous to two reported EST cDNA clones from human fetal tissue and were further characterized. Elevated expression of the genes corresponding to clones T1-360 and C4-310 was verified using Northern blotting. High-level expression of these genes was also detected in the breast cancer cell line MCF-7 that was derived from the pleural effusion of a patient with advanced breast cancer. Therefore, specific molecular changes associated with breast cancer development were identified and may be indicators of neoplastic progression.
Base Sequence↗
The MOS 36-Item Short Form Health Survey: reliability, validity, and preliminary findings in schizophrenic outpatients.
OBJECTIVES: The authors test the reliability and validity of the Medical Outcomes Study Short Form 36-Item Health Survey (SF-36) as a written, self-administered survey in outpatients with chronic schizophrenia. METHODS: Thirty-six schizophrenic outpatients completed a written and oral form of the SF-36. A psychiatrist rated the patients using the Brief Psychiatric Rating Scale to determine severity of psychopathology. Cognitive functioning and academic achievement were also assessed. Internal consistency, test-retest reliability, concurrent and discriminative validity of the oral and written versions were determined. RESULTS: The SF-36 in both forms was shown to have good internal consistency, stability, and concurrent validity. The mental health SF-36 subscales had poor discriminant validity, compared with the physical functioning scale that demonstrated good discriminant validity. CONCLUSIONS: The validity of using the written form of the SF-36 on a sample of patients with chronic mental illness was demonstrated. The SF-36 appears to be an appropriate outcome measure for changes in physical and role functioning in consumers of outpatient mental health programs.
Adult↗
Nuclear and nucleolar image analysis of human breast epithelial cells transformed by benzo[a]pyrene and transfected with the c-Ha-ras oncogene.
Changes in nuclear and nucleolar morphometric parameters were investigated by image analysis procedures in human breast MCF-10F epithelial cells expressing different stages of the tumourigenic progression after benzo[a]pyrene (BP) transformation (BP1, BP1-E, and BP1-E1 cell lines), and additionally transfected with the c-Ha-ras oncogene (BP1-Tras cell line). Nuclear pleomorphism was evident in all the transformed cells. The analysis of different morphometric parameters did not show a clear relationship between specific nuclear and nucleolar changes and the expression of the different stages of the tumourigenesis, with the exception of the nucleolar size, which could be associated to the expression of the tumourigenic phenotype, and a nucleolar area/nuclear area ratio, which discriminated the immortalized, the transformed, and the tumourigenic phenotypes from one another. The nuclear morphometric data established for the BP-transformed cells and for the cells additionally transfected with the c-Ha-ras oncogene were suggestive of complex and distinct morphofunctional mechanisms involving the in vitro transformation of the MCF-10F cells. The nuclear changes found in the BP1-Tras cell line were assumed to be related to the additional effects and/or enhanced genomic instability induced by transfection with the ras oncogene.
Benzo(a)pyrene↗
Randomized, placebo-controlled trial of paroxetine versus imipramine in depressed HIV-positive outpatients.
OBJECTIVE: This study examined whether a selective serotonin reuptake inhibitor (paroxetine) had comparable efficacy but greater tolerability than a tricyclic antidepressant (imipramine) in depressed patients with HIV infection. METHOD: Seventy-five HIV-positive patients (45% of whom had AIDS) were blindly and randomly assigned to receive paroxetine (N = 25), imipramine (N = 25), or placebo (N = 25) in a 12-week trial. The Hamilton Anxiety Rating Scale, the Hamilton Depression Rating Scale, the Clinical Global Impression scale, and the SAFETEE general inquiry (for safety and tolerability) were administered at weeks 2, 4, 6, 8, and 12. RESULTS: Fifty-six (75%) of the 75 patients completed 6 weeks and 34 (45%) completed 12 weeks of the trial. The mean daily doses of both paroxetine (33.9 mg) and imipramine (162.5 mg) were significantly more effective than placebo; they were comparably effective at weeks 6, 8, and 12 according to the intent-to-treat analysis and at week 8 according to the analysis for the subjects who completed the trial (for them, only imipramine was superior to placebo at week 12). There were significantly more dropouts due to side effects from imipramine (48%) than from both paroxetine (20%) and placebo (24%). CONCLUSIONS: Depressed patients with HIV infection responded to imipramine or paroxetine at a higher rate than to placebo irrespective of severity of immunosuppression. Because paroxetine was much better tolerated than imipramine, its overall effectiveness may be greater. However, because of the small study group and the high attrition rate, these findings cannot be generalized and may need replication in a larger study group.
Acquired Immunodeficiency Syndrome↗
Cognitive functions and complaints in HIV-1 individuals treated for depression.
Progressive neuropsychological dysfunction and complaints of cognitive difficulty frequently accompany HIV-1 infection. Providing appropriate treatment to HIV-1 patients requires determination of the extent to which the presentation of cognitive complaints reflects HIV-1-associated neuropsychological abnormalities or represents expression of depressive symptomatology. We prospectively treated 75 HIV-1 patients who were not demented but met criteria for major mood disorder with antidepressants for 12 weeks and compared pretreatment and posttreatment measures of depression, cognitive complaints, and neuropsychological performance. Complaints of difficulty with memory and attention were found to be independent of neuropsychological impairment, whereas memory complaints were highly correlated with severity of depression. Cognitive complaints declined significantly across the course of treatment for those patients who responded to antidepressant treatment. All patients, regardless of antidepressant treatment response, exhibited parallel improvement on 12-week follow- up neuropsychological examination. These findings suggest that treatment of depression affects cognitive complaints in HIV-1 individuals and that cognitive complaints of patients in asymptomatic or early symptomatic stages of HIV-1 infection may signal the need for evaluation of depression. In patients with more advanced HIV-1 infection, investigation into the basis of cognitive complaints may require a dual assessment of mood disturbance and neuropsychological status.
Journal Article↗
Health effects associated with sulfuryl fluoride and methyl bromide exposure among structural fumigation workers.
OBJECTIVES: This study assessed the health effects associated with occupational exposure to methyl bromide and sulfuryl fluoride among structural fumigation workers. METHODS: A cross-sectional study of 123 structural fumigation workers and 120 referents in south Florida was conducted. Nerve conduction, vibration, neurobehavioral, visual, olfactory, and renal function testing was included. RESULTS: The median lifetime duration of methyl bromide and sulfuryl fluoride exposure among workers was 1.20 years and 2.85 years, respectively. Sulfuryl fluoride exposure over the year preceding examination was associated with significantly reduced performance on the Pattern Memory Test and on olfactory testing. In addition, fumigation workers had significantly reduced performance on the Santa Ana Dexterity Test of the dominant hand and a nonsignificantly higher prevalence of carpal tunnel syndrome than did the referents. CONCLUSIONS: Occupational sulfuryl fluoride exposures may be associated with subclinical effects on the central nervous system, including effects on olfactory and some cognitive functions. However, no widespread pattern of cognitive deficits was observed. The peripheral nerve effects were likely caused by ergonomic stresses experienced by the fumigation workers.
Adult↗
Increased expression of estrogen receptor beta in chemically transformed human breast epithelial cells.
Recent molecular cloning of estrogen receptor beta (ERbeta) suggests alternative pathways of estrogen signaling, but little is known concerning the role of ERbeta in the development of human breast cancer. In the present study, expression of ERalpha and ERbeta mRNA was determined in a series of chemically transformed human breast epithelial cells as well as various normal and malignant breast cancer cell lines. We observed a very low level of ERbeta expression in the mortal S130 and the spontaneously immortalized MCF10-F human breast epithelial cell lines. As MCF-10F cells were treated with environmental chemical carcinogens, an elevated level of ERbeta expression was observed in the resultant transformed BP1, D3 and BP1-ras cells. An even higher level of ERbeta expression was detected in the more transformed BP1-E, D3-1 and D3-1-ras cell lines. Therefore, results from our study indicate that expression of ERbeta can be induced in chemical carcinogen-transformed human breast epithelial cells, and the more transformed cells showed higher levels of ERbeta expression, regardless of which chemical carcinogens were initially used for cell transformation. These results suggest that expression of ERbeta may contribute to the initiation and progression of chemical carcinogen-induced neoplastic transformation.
9,10-Dimethyl-1,2-benzanthracene↗
Correlation between cell cycle regulators and the immortalization and transformation of human breast epithelial cell lines.
Cellular proliferation, essential for normal development, may result in neoplastic growth when the cell cycle clock is disrupted. In order to determine whether the protein expression of cell cycle regulators differs among normal, immortalized non-tumorigenic and malignant human breast epithelial cells (HBECs), we analyzed the protein expression of cyclins D1, D3, A and E, cyclin-dependent kinase (cdk) 4 and c-fos in exponentially growing MCF-10M, MCF-10F, and MCF-7 cells. The tumorigenicity of HBECs in vivo correlated with both cell cycle regulators and early-gene protein expression in vitro. The differential expression of cyclin E- and cyclin A-related proteins and their putative relevance in the tumorigenic properties of HBECs are also discussed.
Breast↗