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1.
Tijdschr Psychiatr ; 65(4): 253-258, 2023.
Artículo en Holandés | MEDLINE | ID: mdl-37323045

RESUMEN

BACKGROUND: It is well known that structured short-term risk assessment tools contribute to predicting physically aggressive behavior in patients in acute psychiatry. AIM: To research whether the Brøset-Violence-Checklist (BVC), an instrument for short-term prediction of violence of psychiatric inpatients, can be used in forensic psychiatry and how the use of the BVC is experienced. METHOD: Twice every 24 hours at more or less fixed times, a BVC score was registered for all patients who stayed in a crisis department within a Forensic Psychiatric Center in 2019. The BVC total scores were then related to physically aggressive incidents. In addition, focus groups and interviews were conducted with sociotherapists to examine experiences with the use of the BVC. RESULTS: The analysis showed a significant predictive value of the BVC total score (AUC = 0.69; p < 0.01). Moreover, the sociotherapists experienced the BVC as user-friendly and efficient. CONCLUSION: The BVC has good predictive value to forensic psychiatry. This is especially true for those patients for whom personality disorder is not part of the primary classification.


Asunto(s)
Psiquiatría Forense , Trastornos Mentales , Humanos , Lista de Verificación , Violencia/psicología , Agresión/psicología , Medición de Riesgo , Trastornos Mentales/diagnóstico , Trastornos Mentales/psicología
2.
Tijdschr Psychiatr ; 64(10): 657-662, 2022.
Artículo en Holandés | MEDLINE | ID: mdl-36583275

RESUMEN

BACKGROUND: Leave is an essential part of treatment within the framework of the tbs measure (court ordered psychiatric treatment for offenders with a mental disorder). Traditionally, these leaves lead to concerns about safety. AIM: To study how often tbs-patients do not return from leave (on time) and how often they commit a crime during an unauthorized absence (UA). In addition, we investigate whether patient or offence characteristics can predict an UA. METHOD: All UA’s between 2009-2020 were examined. We also analysed the patient characteristics of 11,525 permit applications between 2010 and 2018 from the registration system of the Advisory Board for Permitting Leave TBS (AVT). RESULTS: 2.5% of the applications for leave between 2009 and 2020 involved an UA and 0.15% involved an UA with a recidivism. Patients with a cluster B personality disorder, substance use disorder, mood disorder, attention disorder, arson or a serious violent crime as an index offence had a significantly higher chance of having an UA. However, these associations were very weak. The risk factor violation of conditions (from the Dutch risk assessment tool, the HKT (Historical, Clinical, Future)) was also a significant but very weak predictor of UA. CONCLUSION: UA is a rare event. Despite the fact that some patient and offence characteristics were associated with an UA, this relationship is weak and predicting an UA is difficult.


Asunto(s)
Criminales , Trastornos Mentales , Reincidencia , Trastornos Relacionados con Sustancias , Humanos , Crimen/psicología , Trastornos Mentales/terapia , Violencia/psicología , Criminales/psicología
3.
Tijdschr Psychiatr ; 63(6): 419-424, 2021.
Artículo en Holandés | MEDLINE | ID: mdl-34231860

RESUMEN

BACKGROUND: Incidents of self-harm by forensic psychiatric patients usually have a large impact on all those involved and self-harming behavior is an important predictor for violence towards others during treatment. AIM: To describe incidents of self-harm during the treatment of patients admitted to forensic psychiatry. METHOD: All incidents of self-harm during treatment in a forensic psychiatric center that were registered between 2008 and 2019 were analyzed and coded with respect to severity with the MOAS+. RESULTS: Between 2008 and 2019 299 incidents of self-harm were registered committed by 106 patients. Most of these incidents (87,6%) were classified as non-suicidal. Methods most often used were cutting themselves with glass, broken plates or mugs, a razor or knife and swallowing dangerous objects or liquids. There were ten cases of suicide, almost all by suffocation with a rope or belt. The majority of the incidents were coded as severe or extreme with the MOAS+. Female patients were overrepresented and they caused on average three times more incidents than male patients. CONCLUSION: Incidents of self-harm happen regularly in forensic psychiatry and are usually severe. More research is needed into the impact on all those involved, motivations and triggers for self-harming behavior and effective treatment of it.


Asunto(s)
Conducta Autodestructiva , Suicidio , Conducta Peligrosa , Femenino , Psiquiatría Forense , Humanos , Masculino , Conducta Autodestructiva/epidemiología , Violencia
4.
Tijdschr Psychiatr ; 62(5): 332-339, 2020.
Artículo en Holandés | MEDLINE | ID: mdl-32484561

RESUMEN

BACKGROUND: Substance abuse is an important risk factor for (violent) offending, but is mostly studied in male populations. More knowledge about women is needed.
AIM: To gain insight into possible gender differences in substance abuse and offending in forensic psychiatric patients.
METHOD: Files were analysed of 275 women and 275 men who have been admitted between 1984 and 2014 to one of four Dutch forensic psychiatric facilities and related to incidents of violence during treatment or recidivism after discharge (for 78 women).
RESULTS: Although substance abuse was common in women (57%), it was significantly more prevalent in men (68%). Men were more often diagnosed with substance dependency and more often committed the index-offense whilst intoxicated. Predictive accuracy for violent incidents during treatment was better for men. Both women and men with substance abuse had significantly more historical risk factors compared to those without substance abuse. A history of substance abuse was not a significant predictor for recidivism after discharge in women.
CONCLUSION: There are gender differences in substance abuse and the relationship with offending was stronger for men. These differences may have implications for substance use treatment in forensic mental health services.


Asunto(s)
Trastornos Mentales , Trastornos Relacionados con Sustancias , Femenino , Humanos , Masculino , Trastornos Mentales/epidemiología , Factores de Riesgo , Caracteres Sexuales , Factores Sexuales , Trastornos Relacionados con Sustancias/epidemiología , Violencia
5.
Am J Physiol Regul Integr Comp Physiol ; 315(2): R369-R379, 2018 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-29641232

RESUMEN

Based on studies of fast skeletal muscles, hibernating black and brown bears resist skeletal muscle atrophy during months of reduced physical activity and not feeding. The present study examined atrophy sparing in the slow soleus muscle, known to be highly prone to disuse atrophy in humans and other mammals. We demonstrated histochemically that the black bear soleus is rich in slow fibers, averaging 84.0 ± 6.6%. The percentages of slow fibers in fall (87.3 ± 4.9%) and during hibernation (87.1 ± 5.6%) did not differ ( P = 0.3152) from summer. The average fiber cross-sectional area to body mass ratio (48.6 ± 11.7 µm2/kg) in winter hibernating bears was not significantly different from that of summer (54.1 ± 11.8 µm2/kg, P = 0.4186) and fall (47.0 ± 9.7 µm2/kg, P = 0.9410) animals. The percentage of single hybrid fibers containing both slow and fast myosin heavy chains, detected biochemically, increased from 2.6 ± 3.8% in summer to 24.4 ± 24.4% ( P = 0.0244) during hibernation. The shortening velocities of individual hybrid fibers remained unchanged from that of pure slow and fast fibers, indicating low content of the minority myosins. Slow and fast fibers in winter bears exhibited elevated specific tension (kN/m2; 22%, P = 0.0161 and 11%, P = 0.0404, respectively) and maintained normalized power. The relative stability of fiber type percentage and size, fiber size-to-body mass ratio, myosin heavy chain isoform content, shortening velocity, power output, and elevated specific tension during hibernation validates the ability of the black bear to preserve the biochemical and performance characteristics of the soleus muscle during prolonged hibernation.


Asunto(s)
Hibernación , Contracción Muscular , Fuerza Muscular , Músculo Esquelético/fisiología , Atrofia Muscular/prevención & control , Ursidae/fisiología , Animales , Complejo IV de Transporte de Electrones/metabolismo , Metabolismo Energético , Femenino , Glucógeno/metabolismo , Masculino , Mitocondrias Musculares/metabolismo , Fibras Musculares de Contracción Rápida/fisiología , Fibras Musculares de Contracción Lenta/fisiología , Músculo Esquelético/citología , Músculo Esquelético/metabolismo , Atrofia Muscular/metabolismo , Atrofia Muscular/fisiopatología , Cadenas Pesadas de Miosina/metabolismo , Fenotipo , Factores de Tiempo , Ursidae/metabolismo
6.
Tijdschr Psychiatr ; 56(7): 439-47, 2014.
Artículo en Holandés | MEDLINE | ID: mdl-25070568

RESUMEN

BACKGROUND: Violence perpetrated by women has attracted more and more attention in the past few years. However, there is lack of background information about women admitted to forensic psychiatric hospitals and about risk factors for recidivism. AIM: To conduct a multicenter study which will give more insight into female psychiatric patients and which will probably have implications for psychodiagnostics, risk assessment and treatment in (forensic) psychiatric settings. METHOD: We coded the files of 297 women who, between 1984 and 2013, had been admitted to one of four Dutch forensic psychiatric facilities by reason of violent delinquent behaviour. We used an extensive coding list and several risk assessment tools including the recently developed Female Additional Manual (fam) for women. RESULTS: The general picture that emerged was one of severely traumatised women with complex pathology and a high level of comorbidity. Many of the women had experienced previous treatment failures and had caused many incidents during treatment. CONCLUSION: Female forensic psychiatric patients are a complex group that deserves more specific attention. Attention for traumas from the past, intensive supervision in relationships and training for staff in dealing with, for instance, manipulative behaviour are the most important implications from this study.


Asunto(s)
Psiquiatría Forense , Violencia/psicología , Mujeres/psicología , Adolescente , Adulto , Anciano , Femenino , Humanos , Persona de Mediana Edad , Recurrencia , Medición de Riesgo , Factores de Riesgo , Violencia/estadística & datos numéricos , Adulto Joven
7.
Mol Ecol ; 21(16): 4106-21, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22776029

RESUMEN

In their invasive ranges, Argentine ant populations often form one geographically vast supercolony, genetically and chemically uniform within which there is no intraspecific aggression. Here we present regional patterns of intraspecific aggression, cuticular hydrocarbons (CHCs) and population genetics of 18 nesting sites across Corsica and the French mainland. Aggression tests confirm the presence of a third European supercolony, the Corsican supercolony, which exhibits moderate to high levels of aggression, depending on nesting sites, with the Main supercolony, and invariably high levels of aggression with the Catalonian supercolony. The chemical analyses corroborated the behavioural data, with workers of the Corsican supercolony showing moderate differences in CHCs compared to workers of the European Main supercolony and strong differences compared to workers of the Catalonian supercolony. Interestingly, there were also clear genetic differences between workers of the Catalonian supercolony and the two other supercolonies at both nuclear and mitochondrial markers, but only very weak genetic differentiation between nesting sites of the Corsican and Main supercolonies (F(ST) = 0.06). A detailed comparison of the genetic composition of supercolonies also revealed that, if one of the last two supercolonies derived from the other, it is the Main supercolony that derived from the Corsican supercolony rather than the reverse. Overall, these findings highlight the importance of conducting more qualitative and quantitative analyses of the level of aggression between supercolonies, which has to be correlated with genetic and chemical data.


Asunto(s)
Agresión , Hormigas/fisiología , Variación Genética , Hidrocarburos/análisis , Especies Introducidas , Animales , Hormigas/genética , Europa (Continente) , Francia , Genética de Población , Repeticiones de Microsatélite , Datos de Secuencia Molecular
8.
Tijdschr Psychiatr ; 54(4): 329-38, 2012.
Artículo en Holandés | MEDLINE | ID: mdl-22508350

RESUMEN

BACKGROUND: Violence perpetrated by women is a growing problem. Research has shown that the risk factors associated with women differ from those associated with men and that the risk assessments currently in use are not adequate for predicting violence in women. AIM: To develop a clinically relevant, useful tool for an accurate, gender-sensitive assessment of risk of violent behaviour in women and to offer guidelines for risk management in women. METHOD: On the basis of literature research, clinical expertise and the results of a pilot study, we adapted the much-used 'Historical Clinical Risk management-20 (HCR-20) for use with female (forensic) psychiatric patients who have a record of violence towards other people. RESULTS: The 'Female Additional Manual (FAM) supplemented and added value to the HCR-20 for assessing the risk of violent behaviour by women. CONCLUSION: The fam is a valuable addition to the currently available risk assessment tools in that it provides a more accurate gender-specific risk assessment with regard to female (forensic) psychiatric patients. Future research will have to further demonstrate the value of the FAM.


Asunto(s)
Psiquiatría Forense , Medición de Riesgo/métodos , Violencia/psicología , Mujeres/psicología , Adolescente , Adulto , Femenino , Humanos , Valor Predictivo de las Pruebas , Factores de Riesgo , Adulto Joven
9.
Breast Cancer Res Treat ; 125(2): 441-6, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21046232

RESUMEN

Aromatase inhibitors (AIs) have become the standard adjuvant therapy of postmenopausal breast cancer survivors. AIs induce a reduction of bioavailable estrogens by inhibiting aromatase, which would be expected to induce alterations in body composition, more extensive than induced by menopause. The objectives are to examine the impact of AIs on (1) DXA-scan derived body composition and (2) gonadal hormone levels. This is a sub-analysis of a 2-year double-blind, placebo-controlled, randomized trial of 82 women with nonmetastatic breast cancer, newly menopausal following chemotherapy, who were randomized to risedronate (35 mg once weekly) versus placebo, and stratified for their usage of AI versus no AI. Outcomes included DXA-scan derived body composition and gonadal hormone levels. As a group, total body mass increased in women over 24 months. Women on AIs gained a significant amount of lean body mass compared to baseline as well as to no-AI users (P < 0.05). Women not on an AI gained total body fat compared to baseline and AI users (P < 0.05). Free testosterone significantly increased and sex hormone binding globulin (SHBG) significantly decreased in women on AIs compared to no AIs at 24 months (P < 0.01) while total estradiol and testosterone levels remained stable. Independent of AI usage, chemotherapy-induced postmenopausal breast cancer patients demonstrated an increase of total body mass. AI users demonstrated maintenance of total body fat, an increase in lean body mass and free testosterone levels, and a decrease in SHBG levels compared to no-AI users. The mechanisms and implications of these changes need to be studied further.


Asunto(s)
Inhibidores de la Aromatasa/administración & dosificación , Composición Corporal/efectos de los fármacos , Índice de Masa Corporal , Densidad Ósea/efectos de los fármacos , Hormonas Gonadales/sangre , Tejido Adiposo/fisiología , Inhibidores de la Aromatasa/uso terapéutico , Neoplasias de la Mama/sangre , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/fisiopatología , Método Doble Ciego , Ácido Etidrónico/análogos & derivados , Ácido Etidrónico/uso terapéutico , Femenino , Humanos , Persona de Mediana Edad , Placebos , Posmenopausia , Ácido Risedrónico , Globulina de Unión a Hormona Sexual/análisis
10.
Tijdschr Psychiatr ; 53(2): 83-93, 2011.
Artículo en Holandés | MEDLINE | ID: mdl-21319065

RESUMEN

BACKGROUND: Instruments for assessing the risk of violent behaviour have proved their worth in the field of forensic psychiatry. However, it is not certain whether such instruments provide an accurate assessment of recidivism when used with psychiatric patients who have an intellectual disability. AIM: To find out whether these instruments - or which of these instruments - can provide a reliable assessment of the risk of violent sexual recidivism if used with forensic psychiatric patients who have an intellectual disability. method We searched PubMed, PsycINFO and Google Scholar for studies in English or Dutch, published between 1980 and 2010, concerning the reliability of instruments for assessing the risk of recidivism in forensic psychiatric patients with an intellectual disability. RESULTS: The studies show that several of the risk assessment instruments currently in use provide reliable predictions concerning patients with an intellectual disability. CONCLUSIONS: The HCR-20 and HKT-30 are recommended for assessing the risk of violent recidivism in patients with an intellectual disability. The Static-99 is the preferred instrument for assessing the risk of sexual recidivism. Further research is needed for assessing to what extent SVR-20, ARMIDILO, DROS, and PCL-R are applicable to forensic psychiatric patients in the Netherlands who have an intellectual disability.


Asunto(s)
Psiquiatría Forense/instrumentación , Discapacidad Intelectual , Medición de Riesgo , Delitos Sexuales/psicología , Crimen/psicología , Humanos , Recurrencia , Factores de Riesgo , Violencia/psicología
11.
Int J Pharm ; 347(1-2): 109-17, 2008 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-17681686

RESUMEN

Nanoparticles prepared from human serum albumin (HSA) are versatile carrier systems for drug delivery and can be prepared by an established desolvation process. A reproducible process with a low batch-to-batch variability is required for transfer from the lab to an industrial production. In the present study the batch-to-batch variability of the starting material HSA on the preparation of nanoparticles was investigated. HSA can build dimers and higher aggregates because of a free thiol group present in the molecule. Therefore, the quality of different HSA batches was analysed by size exclusion chromatography (SEC) and analytical ultracentrifugation (AUC). The amount of dimerised HSA detected by SEC did not affect particle preparation. Higher aggregates of the protein detected in two batches by AUC disturbed nanoparticle formation at pH values below 8.0. At pH 8.0 and above monodisperse particles between 200 and 300 nm could be prepared with all batches, with higher pH values leading to smaller particles. Besides human derived albumin a particle preparation was also feasible based on recombinant human serum albumin (rHSA). Under comparable preparation conditions monodisperse nanoparticles could be achieved and the same effects of protein aggregates on particle formation were observed. For nanoparticulate drug delivery systems the enzymatic degradation is a crucial parameter for the release of an embedded drug. For this reason, besides the particle preparation process, particle degradation in the presence of different enzymes was studied. Under acidic conditions HSA as well as rHSA nanoparticles could be digested by pepsin and cathepsin B. At neutral pH trypsin, proteinase K, and protease were suitable for particle degradation. It could be shown that the kinetics of particle degradation was dependent on the degree of particle stabilisation. Therefore, the degree of particle stabilisation will influence drug release after cellular accumulation of HSA nanoparticles.


Asunto(s)
Nanopartículas/química , Péptido Hidrolasas/química , Albúmina Sérica/química , Catepsina B/química , Composición de Medicamentos/métodos , Glutaral/química , Humanos , Concentración de Iones de Hidrógeno , Cinética , Peso Molecular , Tamaño de la Partícula , Pepsina A/química , Péptido Hidrolasas/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Reproducibilidad de los Resultados , Albúmina Sérica/genética , Albúmina Sérica/metabolismo , Electricidad Estática , Propiedades de Superficie , Tripsina/química
12.
Radiat Prot Dosimetry ; 125(1-4): 523-6, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-17314090

RESUMEN

After the Chernobyl reactor accident wide areas of Belarus were contaminated with radioactive fallout. The verification and documentation of the long-term development of radiation doses is still going on. A population group of special concern are the children living in contaminated regions. The annual dose limit of 1 mSv is still exceeded in some cases, essentially due to high body burdens of 137Cs as indicated by screening measurements with portable incorporation monitors. In this situation the evaluation of possible dose reduction measures in addition to the control of food contamination is being investigated. Special attention is given to the therapeutic application of a pectin preparation (Vitapect), for which a dose-lowering effect is presumed by Belarusian scientists. In a placebo-controlled double-blind study, several groups of contaminated children received a pectin compound named Vitapect for a two-week period during their stay in a sanatorium. For comparison the same number of control groups were given a placebo preparation. The 137Cs body burden of the children was measured at the beginning and the end. The mean relative reduction of the specific activity within the Vitapect groups was found to be approximately 33%, whereas the specific activity of the children who received a placebo decreased only by approximately 14%, due to clean food supply. It is known that pectins chemically bind cations like caesium in the gastrointestinal tract and thereby increase faecal excretion. Theoretical calculations based on this assumption and considering metabolism processes are qualitatively consistent with the experimentally found retention of radiocaesium in the human body after pectin treatment.


Asunto(s)
Carga Corporal (Radioterapia) , Radioisótopos de Cesio/farmacocinética , Accidente Nuclear de Chernóbil , Bases de Datos Factuales , Exposición a Riesgos Ambientales/análisis , Modelos Biológicos , Monitoreo de Radiación/métodos , Algoritmos , Bioensayo/métodos , Radioisótopos de Cesio/análisis , Niño , Simulación por Computador , Femenino , Humanos , Internacionalidad , Masculino , Dosis de Radiación , Protección Radiológica/métodos , Reproducibilidad de los Resultados , República de Belarús , Sensibilidad y Especificidad
13.
J Natl Cancer Inst ; 86(8): 620-5, 1994 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-8003106

RESUMEN

BACKGROUND: Gail et al. developed a statistical model for estimating the risk of developing breast cancer in white women screened annually with mammography. This model is used for counseling and for admission to clinical trials. PURPOSE: We evaluated the model prospectively in a cohort of women with a family history of breast cancer. METHODS: We followed women who participated in the American Cancer Society 1987 Texas Breast Screening Project. The model was evaluated by comparing the observed (O) and expected (E) numbers of breast cancers using composite background rates from both the Breast Cancer Detection and Demonstration Project and the Surveillance, Epidemiology, and End Results program of the National Cancer Institute. Data were partitioned by adherence to American Cancer Society screening guidelines. RESULTS: The Gail et al. model predicted the risk well among women who adhered to the American Cancer Society guidelines (O/E = 1.12; 95% confidence interval = 0.75-1.61) but overpredicted risk for women who did not adhere to the guidelines. There was an indication that the model overpredicted risk for women younger than 60 years old and underpredicted risk in women aged 60 years and older. CONCLUSIONS: Overall, the Gail et al. model accurately predicts risk in women with a family history of breast cancer and who adhere to American Cancer Society screening guidelines. Thus, the model should be used as it was intended, for women who receive annual mammograms.


Asunto(s)
Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/genética , Modelos Estadísticos , Adulto , Anciano , American Cancer Society , Neoplasias de la Mama/prevención & control , Estudios de Casos y Controles , Femenino , Humanos , Mamografía , Tamizaje Masivo , Persona de Mediana Edad , National Institutes of Health (U.S.) , Cooperación del Paciente , Valor Predictivo de las Pruebas , Estudios Prospectivos , Factores de Riesgo , Texas/epidemiología , Estados Unidos
14.
J Natl Cancer Inst ; 91(21): 1829-46, 1999 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-10547390

RESUMEN

BACKGROUND: In response to findings from the Breast Cancer Prevention Trial that tamoxifen treatment produced a 49% reduction in the risk of invasive breast cancer in a population of women at elevated risk, the National Cancer Institute sponsored a workshop on July 7 and 8, 1998, to develop information to assist in counseling and in weighing the risks and benefits of tamoxifen. Our study was undertaken to develop tools to identify women for whom the benefits outweigh the risks. METHODS: Information was reviewed on the incidence of invasive breast cancer and of in situ lesions, as well as on several other health outcomes, in the absence of tamoxifen treatment. Data on the effects of tamoxifen on these outcomes were also reviewed, and methods were developed to compare the risks and benefits of tamoxifen. RESULTS: The risks and benefits of tamoxifen depend on age and race, as well as on a woman's specific risk factors for breast cancer. In particular, the absolute risks from tamoxifen of endometrial cancer, stroke, pulmonary embolism, and deep vein thrombosis increase with age, and these absolute risks differ between white and black women, as does the protective effect of tamoxifen on fractures. Tables and aids are developed to describe the risks and benefits of tamoxifen and to identify classes of women for whom the benefits outweigh the risks. CONCLUSIONS: Tamoxifen is most beneficial for younger women with an elevated risk of breast cancer. The quantitative analyses presented can assist health care providers and women in weighing the risks and benefits of tamoxifen for reducing breast cancer risk.


Asunto(s)
Anticarcinógenos/uso terapéutico , Neoplasias de la Mama/prevención & control , Moduladores de los Receptores de Estrógeno/uso terapéutico , Moduladores Selectivos de los Receptores de Estrógeno/uso terapéutico , Tamoxifeno/uso terapéutico , Factores de Edad , Anticarcinógenos/efectos adversos , Neoplasias de la Mama/patología , Carcinoma in Situ , Catarata/prevención & control , Ensayos Clínicos Controlados como Asunto , Consejo , Educación , Neoplasias Endometriales/inducido químicamente , Moduladores de los Receptores de Estrógeno/efectos adversos , Femenino , Fracturas Óseas/epidemiología , Fracturas Óseas/prevención & control , Humanos , National Institutes of Health (U.S.) , Invasividad Neoplásica , Educación del Paciente como Asunto , Embolia Pulmonar/inducido químicamente , Riesgo , Factores de Riesgo , Moduladores Selectivos de los Receptores de Estrógeno/efectos adversos , Accidente Cerebrovascular/inducido químicamente , Tamoxifeno/efectos adversos , Estados Unidos , Trombosis de la Vena/inducido químicamente
15.
J Natl Cancer Inst ; 90(18): 1371-88, 1998 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-9747868

RESUMEN

BACKGROUND: The finding of a decrease in contralateral breast cancer incidence following tamoxifen administration for adjuvant therapy led to the concept that the drug might play a role in breast cancer prevention. To test this hypothesis, the National Surgical Adjuvant Breast and Bowel Project initiated the Breast Cancer Prevention Trial (P-1) in 1992. METHODS: Women (N=13388) at increased risk for breast cancer because they 1) were 60 years of age or older, 2) were 35-59 years of age with a 5-year predicted risk for breast cancer of at least 1.66%, or 3) had a history of lobular carcinoma in situ were randomly assigned to receive placebo (n=6707) or 20 mg/day tamoxifen (n=6681) for 5 years. Gail's algorithm, based on a multivariate logistic regression model using combinations of risk factors, was used to estimate the probability (risk) of occurrence of breast cancer over time. RESULTS: Tamoxifen reduced the risk of invasive breast cancer by 49% (two-sided P<.00001), with cumulative incidence through 69 months of follow-up of 43.4 versus 22.0 per 1000 women in the placebo and tamoxifen groups, respectively. The decreased risk occurred in women aged 49 years or younger (44%), 50-59 years (51%), and 60 years or older (55%); risk was also reduced in women with a history of lobular carcinoma in situ (56%) or atypical hyperplasia (86%) and in those with any category of predicted 5-year risk. Tamoxifen reduced the risk of noninvasive breast cancer by 50% (two-sided P<.002). Tamoxifen reduced the occurrence of estrogen receptor-positive tumors by 69%, but no difference in the occurrence of estrogen receptor-negative tumors was seen. Tamoxifen administration did not alter the average annual rate of ischemic heart disease; however, a reduction in hip, radius (Colles'), and spine fractures was observed. The rate of endometrial cancer was increased in the tamoxifen group (risk ratio = 2.53; 95% confidence interval = 1.35-4.97); this increased risk occurred predominantly in women aged 50 years or older. All endometrial cancers in the tamoxifen group were stage I (localized disease); no endometrial cancer deaths have occurred in this group. No liver cancers or increase in colon, rectal, ovarian, or other tumors was observed in the tamoxifen group. The rates of stroke, pulmonary embolism, and deep-vein thrombosis were elevated in the tamoxifen group; these events occurred more frequently in women aged 50 years or older. CONCLUSIONS: Tamoxifen decreases the incidence of invasive and noninvasive breast cancer. Despite side effects resulting from administration of tamoxifen, its use as a breast cancer preventive agent is appropriate in many women at increased risk for the disease.


Asunto(s)
Antineoplásicos Hormonales/uso terapéutico , Neoplasias de la Mama/etiología , Neoplasias de la Mama/prevención & control , Antagonistas de Estrógenos/uso terapéutico , Tamoxifeno/uso terapéutico , Adulto , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Causas de Muerte , Femenino , Humanos , Persona de Mediana Edad , Invasividad Neoplásica , Oportunidad Relativa , Calidad de Vida , Riesgo , Factores de Riesgo , Resultado del Tratamiento
16.
Cancer Res ; 49(12): 3215-7, 1989 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-2720675

RESUMEN

The Ca2+- and phospholipid-dependent protein kinase, protein kinase C (PKC), is a critical enzyme in the regulation of cell growth. In this report, we demonstrate elevated expression of PKC activity in surgical specimens of eight of nine spontaneous human breast tumors, as compared with the expression of PKC activity in normal breast tissue obtained from the same patients. The mean PKC specific activity in histologically normal breast tissue was 166 +/- 63 pmol 32P/min/mg, whereas the mean PKC specific activity in the breast tumors was 460 +/- 182 pmol 32P/min/mg (P = 0.0003; Student's t test). The low interpatient variability among the PKC levels observed in the histologically normal breast tissue specimens and the significant elevation of PKC levels observed in the tumors indicate that elevated expression of PKC activity in breast tissue is a potential marker for malignant disease in the breast.


Asunto(s)
Biomarcadores de Tumor/análisis , Neoplasias de la Mama/enzimología , Mama/enzimología , Proteína Quinasa C/análisis , Biopsia , Mama/patología , Neoplasias de la Mama/clasificación , Neoplasias de la Mama/patología , Humanos , Proteína Quinasa C/metabolismo
17.
Biochim Biophys Acta ; 957(1): 131-7, 1988 Nov 02.
Artículo en Inglés | MEDLINE | ID: mdl-2972321

RESUMEN

The Ca2+-regulated lipid-binding properties of the H- and L-forms of calelectrin present in the electric organ of Torpedo marmorata have been compared. Binding of H-calelectrin required Ca2+ in millimolar concentrations, whereas that of L-calelectrin occurred in the micromolar range. Dissociation of H-calelectrin previously bound to lipids in the presence of 2 mM Ca2+ took place only when the Ca2+ concentration was reduced to micromolar concentrations. Binding was most effective to acidic phospholipids such as phosphatidylserine. Both forms of calelectrin promoted the aggregation of membrane vesicles in the presence of Ca2+.Mg2+, Na+ and K+ inhibited the Ca2+-induced binding to phospholipid, decreasing in effectiveness in that order. Binding was also inhibited by high pH. The surface activity and hydrophobicity index showed that H-calelectrin is a hydrophilic molecule. It may represent a less active, more highly phosphorylated "down-regulated" form of L-calelectrin. The role of calcium in H-calelectrin binding to lipid appeared to be consistent with the formation of a ternary complex of the protein, an acidic lipid and Ca2+, rather than with a direct interaction of lipid with hydrophobic sequences in H-calelectrin whose accessibility is Ca2+-regulated.


Asunto(s)
Proteínas de Unión al Calcio/metabolismo , Calcio/metabolismo , Fosfolípidos/metabolismo , Aminoácidos/análisis , Animales , Anexinas , Cationes , Agregación Celular , Órgano Eléctrico/metabolismo , Concentración de Iones de Hidrógeno , Luz , Fusión de Membrana , Fosfatidilserinas , Dispersión de Radiación , Solubilidad , Propiedades de Superficie , Torpedo
18.
Biochim Biophys Acta ; 1380(1): 31-45, 1998 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-9545525

RESUMEN

Oriented calcium oxalate crystals have been grown beneath phospholipid monolayers at the air-solution interface from supersaturated calcium oxalate solutions. Mature calcium oxalate crystals grown beneath zwitterionic dipalmitoylphosphatidylcholine (DPPC) monolayers exhibit the characteristic morphology of calcium oxalate monohydrate (COM) crystals with the elongated (101) crystal face preferentially oriented parallel to the plane of the monolayer. Calcium oxalate crystals grown beneath negatively-charged dimyristoylphosphatidylserine (DMPS) monolayers also show a preferential orientation with respect to the monolayer; they do not, however, exhibit the characteristic COM morphology. Raman spectroscopy strongly suggests that the crystals grown beneath either DPPC or DMPS monolayers are the monohydrate phase of calcium oxalate; therefore, differences in crystal morphology are not due to differences in the crystalline phase. Dimyristoylphosphatidylethanolamine (DMPE), dimyristoylphosphatidic acid (DMPA), eicosanoic acid (C20), and eicosanol (C20-OH) monolayers have also been studied to help elucidate the mechanisms of interaction between the lipid monolayers and the calcium oxalate crystals. We discuss the roles of lattice matching, hydrogen bonding, stereochemistry and electrostatics on crystal orientation and morphology.


Asunto(s)
Oxalato de Calcio/química , Fosfolípidos/química , 1,2-Dipalmitoilfosfatidilcolina/química , Calcificación Fisiológica , Cristalización , Enlace de Hidrógeno , Técnicas In Vitro , Modelos Químicos , Fosfatidilserinas/química , Espectrometría Raman , Electricidad Estática , Estereoisomerismo
19.
J Clin Oncol ; 19(18 Suppl): 87S-92S, 2001 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-11560980

RESUMEN

Validated quantitative models are available that permit the accurate estimation of a woman's risk of developing invasive breast cancer during a specified period of time. Data from the National Surgical Adjuvant Breast and Bowel Project Breast Cancer Prevention Trial indicate that tamoxifen can reduce the risk of developing breast cancer by at least 49% in women who are at increased risk. All premenopausal women whose 5-year risk of developing breast cancer is 1.67% or greater derive a net benefit from taking tamoxifen for risk reduction. Women who have either lobular carcinoma-in-situ or atypical ductal or lobular hyperplasia derive an even greater net benefit. Women who carry mutations in either the BRCA1 or BRCA2 gene will also experience reduced incidence of breast cancer with tamoxifen. Although postmenopausal women derive a net benefit from tamoxifen through the reduction of both breast cancer and bone fracture event rates, the risks of both invasive endometrial cancer and thromboembolic events must be balanced in older women. Physicians should identify appropriate candidates with whom to discuss the possible benefits of tamoxifen for reducing the risk of breast cancer.


Asunto(s)
Anticarcinógenos/uso terapéutico , Neoplasias de la Mama/prevención & control , Predisposición Genética a la Enfermedad , Tamoxifeno/uso terapéutico , Adulto , Anciano , Proteína BRCA2 , Neoplasias de la Mama/genética , Análisis Costo-Beneficio , Femenino , Genes BRCA1 , Humanos , Persona de Mediana Edad , Proteínas de Neoplasias , Posmenopausia , Lesiones Precancerosas , Premenopausia , Medición de Riesgo , Factores de Transcripción
20.
J Clin Oncol ; 16(1): 133-8, 1998 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-9440734

RESUMEN

PURPOSE: To assess preferences for the content and process of genetic counseling and testing for breast-ovarian cancer susceptibility among women at high risk for breast cancer. METHODS: Ninety-eight healthy women who had a family history of breast cancer in at least two first-degree relatives participated in a structured telephone survey that evaluated preferences for type of provider and the content and process of pretest education and posttest genetic counseling. RESULTS: Forty-two percent of women preferred that pretest education be delivered by a genetic counselor, while 22% preferred an oncologist. This preference was positively associated with a desire to discuss psychosocial issues during the session (P = .001). For posttest counseling, 38% of women preferred an oncologist, while 20% preferred a genetic counselor. However, women who desired supportive counseling during this session were significantly more likely to prefer a genetic counselor to an oncologist (P = .02). Fewer women wished to see a primary care physician or gynecologist for pretest education (11%) or posttest counseling (22%). With regard to the counseling process, 82% of women wished to self-refer for genetic counseling, but 63% desired advice and recommendations about whether to be tested. CONCLUSION: When feasible, the optimal approach may be for oncologists to work with genetic counselors to provide pretest education and medical recommendations. Elicitation of patients' preferences may be useful to determine the level of counseling services needed.


Asunto(s)
Neoplasias de la Mama/genética , Asesoramiento Genético/normas , Neoplasias Ováricas/genética , Satisfacción del Paciente , Adulto , Factores de Edad , Anciano , Neoplasias de la Mama/diagnóstico , Susceptibilidad a Enfermedades , Escolaridad , Salud de la Familia , Femenino , Asesoramiento Genético/métodos , Asesoramiento Genético/psicología , Genética Médica , Encuestas de Atención de la Salud , Humanos , Oncología Médica , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Neoplasias Ováricas/diagnóstico , Educación del Paciente como Asunto/normas
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