RESUMEN

OBJECTIVES: This study assessed associations of three theoretically different occupational class schemes with all-cause and cardiovascular mortality in Norwegian men and women. STUDY DESIGN: Pooled survey and register data from four Norwegian cohort studies. METHODS: We pooled survey data from four general population cohorts (N = 97,469) linked to national mortality registries with follow-up over 45 years. Survival was modelled using accelerated failure time models stratified by sex for three class schemes: The European Socio-Economic Classification (ESeC), The Oslo Register Data Class scheme (ORDC) and The International Socio-Economic Index (ISEI). Main analyses were adjusted for age, birth cohort, and study. Secondary analyses included smoking behaviour as a mediator. RESULTS: During median 27.6 years of observation, 37,488 participants had died (13,243 from cardiovascular disease). Hazard ratios for male all-cause mortality were lowest in the highest occupational class categories ORDC 2: 0.68 (0.65-0.72), ESeC 1: 0.76 (0.73-0.79) and ISEI 5th quintile: 0.80 (0.77-0.82) compared to working class reference categories. Female mortality risks were lowest for Cultural Lower Middle class ORDC 7: 0.84 (0.72-0.98), Small Employers and Self-employed ESeC4: 0.70 (0.50-0.97) and ISEI 5th quintile: 0.79 (0.70-0.90). Patterns for cardiovascular mortality were similar to all-cause mortality. Including smoking behaviour as a mediator attenuated associations, but overall mortality patterns according to occupational class remained unchanged. CONCLUSION: The results underline that mortality inequalities do not simply consist of higher risks in the most disadvantaged groups. The association of occupational class with mortality is found across different categories of occupational class schemes, illustrating their continued relevance for studying social determinants of health.

RESUMEN

BACKGROUND: Minimally invasive oesophagectomy (MIO) is reported to produce fewer respiratory complications than open oesophagectomy. This study assessed differences in postoperative complications between MIO and hybrid MIO (HMIO) employing thoracoscopy and laparotomy, along with the influence of co-morbidities on postoperative outcomes. METHODS: Patients with oesophageal cancer undergoing three-stage MIO or three-stage HMIO between 1999 and 2018 were identified from a prospectively developed database, which included patient demographics, co-morbidities, preoperative therapies, and cancer stage. The primary outcome was postoperative complications in the two groups. Secondary outcomes included duration of operation, blood transfusion requirement, duration of hospital stay, and overall survival. RESULTS: There were 828 patients, of whom 722 had HMIO and 106 MIO, without significant baseline differences. Median duration of operation was longer for MIO (325 versus 289 min; P < 0.001), but with less blood loss (median 250 versus 300 ml; P < 0.001) and a shorter hospital stay (median 12 versus 13 days; P = 0.006). Respiratory complications were not associated with operative approach (31.1 versus 35.2 per cent for MIO and HMIO respectively; P = 0.426). Anastomotic leak rates (10.4 versus 10.2 per cent) and 90-day mortality (1.0 versus 1.7 per cent) did not differ. Cardiac co-morbidity was associated with more medical and surgical complications. Overall survival was associated with AJCC stage and co-morbidities, but not operative approach. CONCLUSION: MIO had a small benefit in terms of blood loss and hospital stay, but not in operating time. Oncological outcomes were similar in the two groups. Postoperative complications were associated with pre-existing cardiorespiratory co-morbidities rather than operative approach.

Asunto(s)

Neoplasias Esofágicas/mortalidad , Esofagectomía/mortalidad , Esofagectomía/métodos , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Complicaciones Posoperatorias/etiología , Anciano , Fuga Anastomótica/etiología , Neoplasias Esofágicas/cirugía , Femenino , Humanos , Laparoscopía/efectos adversos , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Análisis de Supervivencia , Resultado del Tratamiento

RESUMEN

BACKGROUND: Several types of psychotherapy have been proven successful in the treatment of personality disorders in younger age groups, however studies among older patients are lacking. We developed a group schema-focused therapy (SFT) enriched with psychomotor therapy (PMT) for older adults with cluster B and/or C personality disorders. This paper describes the design of a randomized controlled trial (RCT). We will evaluate the (cost-)effectiveness of this therapy protocol in specialized mental health care. We hypothesize that our treatment program is cost-effective and superior to treatment as usual (TAU) in reducing psychological distress and improving quality of life in older adults treated to specialized mental healthcare. METHODS: A multicenter RCT with a one-year follow-up comparing group schema-focused therapy enriched with psychomotor therapy (group SFT + PMT) and TAU for adults aged 60 years and older who suffer from either a cluster B and/or C personality disorder. The primary outcome is general psychological distress measured with the 53-item Brief Symptom Inventory. Secondary outcomes are the Schema Mode Inventory (118-item version) and the Young Schema Questionnaire. Cost-effectiveness analysis will be performed from a societal perspective with the EuroQol five dimensions questionnaire and structured cost-interviews. DISCUSSION: This study will add to the knowledge of psychotherapy in later life. The study specifically contributes to the evidence on (cost-) effectiveness of group SFT enriched with PMT adapted to the needs of for older adults with cluster b and/or c personality. TRIAL REGISTRATION: Netherlands Trial Register NTR 6621 . Registered on 20 August 2017.

Asunto(s)

Ejercicio Físico/psicología , Trastornos de la Personalidad/terapia , Psicoterapia de Grupo/métodos , Psicoterapia/métodos , Anciano , Análisis Costo-Beneficio/estadística & datos numéricos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Países Bajos , Trastornos de la Personalidad/economía , Trastornos de la Personalidad/psicología , Psicoterapia/economía , Psicoterapia de Grupo/economía , Calidad de Vida , Resultado del Tratamiento

RESUMEN

BACKGROUND: This was an 8-year follow-up of an RCT comparing ultrasound-guided foam sclerotherapy (UGFS) with high ligation and surgical stripping (HL/S) of the great saphenous vein (GSV). METHODS: Patients were randomized to UGFS or HL/S of the GSV. The primary outcome was the recurrence of symptomatic GSV reflux. Secondary outcomes were patterns of reflux according to recurrent varices after surgery, Clinical Etiologic Anatomic Pathophysiologic (CEAP) classification, Venous Clinical Severity Score (VCSS) and EuroQol Five Dimensions (EQ-5D™) quality-of-life scores. RESULTS: Of 430 patients originally randomized (230 UGFS, 200 HL/S), 227 (52·8 per cent; 123 UGFS, 103 HL/S) were available for analysis after 8 years. The proportion of patients free from symptomatic GSV reflux at 8 years was lower after UGFS than HL/S (55·1 versus 72·1 per cent; P = 0·024). The rate of absence of GSV reflux, irrespective of venous symptoms, at 8 years was 33·1 and 49·7 per cent respectively (P = 0·009). More saphenofemoral junction (SFJ) failure (65·8 versus 41·7 per cent; P = 0·001) and recurrent reflux in the above-knee GSV (72·5 versus 20·4 per cent; P = 0·001) was evident in the UGFS group. The VCSS was worse than preoperative scores in both groups after 8 years; CEAP classification and EQ-5D® scores were similar in the two groups. CONCLUSION: Surgical stripping had a technically better outcome in terms of recurrence of GSV and SFJ reflux than UGFS in the long term. Long-term follow-up suggests significant clinical progression of venous disease measured by VCSS in both groups, but less after surgery. Registration number: NCT02304146 (http://www.clinicaltrials.gov).

Asunto(s)

Vena Safena , Escleroterapia/métodos , Ultrasonografía Intervencional , Várices/terapia , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Vena Safena/diagnóstico por imagen , Vena Safena/cirugía , Resultado del Tratamiento , Ultrasonografía Intervencional/métodos , Várices/diagnóstico por imagen , Várices/cirugía

RESUMEN

Malignant small intestinal lymphoma is a quite rare disease that often has an atypical presentation with symptoms of abdominal pain, nausea and weight loss. However, as illustrated in the following cases, acute abdomen due to an intestinal perforation can be the first sign of malignant lymphoma.

Asunto(s)

Abdomen Agudo/etiología , Neoplasias Intestinales/complicaciones , Perforación Intestinal/etiología , Intestino Delgado , Linfoma de Células B Grandes Difuso/complicaciones , Linfoma de Células T/complicaciones , Anciano , Resultado Fatal , Humanos , Neoplasias Intestinales/cirugía , Intestino Delgado/cirugía , Linfoma de Células B Grandes Difuso/cirugía , Linfoma de Células T/cirugía , Masculino , Persona de Mediana Edad

RESUMEN

Desmoplakin is the major linker in desmosomes in epithelia and myocardium, anchoring intermediate filaments by the C-terminus to plakoglobin and plakophilin in the desmosomal plaque. Mutations in the gene DSP encoding desmoplakin have been associated with various phenotypes affecting skin and/or heart. One of these phenotypes, lethal acantholytic epidermolysis bullosa (LAEB), is characterized by extensive postnatal shedding of epidermis leading to early demise and is caused by recessive mutations in the gene DSP resulting in truncation of the desmoplakin C-terminus. Here we describe two infants born to the same consanguinous parents who suffered extensive epidermal dislodgment and died shortly after birth. In addition, universal alopecia, anonychia, malformed ears and cardiomyopathy were observed. As the clinical diagnosis was LAEB, DSP mutation analysis was performed. A homozygous deletion (c.2874del5) abrogating the donor splice site of exon 20 was found. The deletion is predicted to cause read-through in intron 20 with subsequent recognition of a premature termination codon, resulting in desmoplakin lacking its rod domain and C-terminus (p.Lys959MetfsX5). Electron microscopic analysis of skin biopsies showed absence of the desmosomal inner dense plaque and lack of tonofilament insertion. This is the second report of LAEB. These findings suggest DSP mutations as the aetiology of LAEB and cardiomyopathy as part of the phenotype. Furthermore, they indicate that in addition to the desmoplakin C-terminus, the rod domain is dispensable for intrauterine development but is essential for the inner dense plaque of desmosomes.

Asunto(s)

Cardiomiopatía Hipertrófica Familiar/genética , Desmoplaquinas/genética , Epidermólisis Ampollosa/genética , Consanguinidad , Epidermólisis Ampollosa/patología , Resultado Fatal , Humanos , Inmunohistoquímica , Recién Nacido , Masculino , Fenotipo , Análisis de Secuencia de ADN , Eliminación de Secuencia

RESUMEN

STUDY DESIGN: A cross-sectional study of all patients with traumatic SCI admitted to Sunnaas Rehabilitation Hospital, Norway between 1961 and 1982. OBJECTIVES: To assess health-related quality of life (HRQOL) in persons with long-standing traumatic spinal cord injury (SCI) in Norway. SETTING: Sunnaas Rehabilitation Hospital, Norway. METHODS: Survey data and clinical examination of 165 persons with traumatic SCI of more than 20 years duration. HRQOL was assessed with the Norwegian 36-item short-form [corrected] (SF-36) Health Survey. The SF-36 results were compared with Norwegian norm data adjusted to age and gender. Differences in HRQOL between subgroups were studied. RESULTS: The persons with SCI exhibited significantly decreased HRQOL in the subscales for Physical Functioning, Bodily Pain, General Health, Social Functioning [corrected] and Vitality compared to the normal population. There were relatively small differences in HRQOL when comparing persons with paraplegia versus tetraplegia and persons with AIS (ASIA Impairment Scale; ASIA, American Spinal Injury Association) A-C versus D-E. Employed persons reported higher HRQOL compared to unemployed persons. HRQOL of individuals reporting health problems or symptoms was worse than those of individuals reporting no health problems at all. CONCLUSION: HRQOL is decreased in persons with long-standing SCI and especially in persons with comorbidity conditions.

Asunto(s)

Estado de Salud , Calidad de Vida , Traumatismos de la Médula Espinal/rehabilitación , Encuestas y Cuestionarios , Adulto , Factores de Edad , Enfermedad Crónica , Estudios Transversales , Femenino , Humanos , Masculino , Salud Mental/estadística & datos numéricos , Persona de Mediana Edad , Noruega , Factores de Tiempo

RESUMEN

OBJECTIVE: Maternal and paternal psychological distress influence children's development and health beyond the perinatal period. The aim of our study was to describe psychological health during a 5-year period in parents of preschool children. Secondarily, we wanted to explore differences between mothers and fathers and identify predictors for increased psychological distress in parents. DESIGN: Prospective cohort study. SETTING: A county in Southern Norway 1998-2004. POPULATION: One hundred and twenty-three mothers and 112 fathers were candidates for the follow-up study. METHODS: Parental psychological responses were assessed using the General Health Questionnaire (GHQ-28), State Anxiety Inventory-X1 and Impact of Event Scale at 0-4 days, 6 weeks, 6 months and 5 years after delivery of a healthy child. MAIN OUTCOME MEASURE: Parental psychological distress defined by GHQ-28 Likert sum score at 5-year follow-up. RESULTS: Clinically important psychological distress (GHQ case score > or = 6) was reported by more mothers (29%) than by fathers (11%) (P = 0.004). In multivariate analysis, psychological distress (GHQ-28 Likert sum score) after 5 years was predicted by initial psychological distress, being single and low educational level in mothers, and unemployment and low quality of relationship with partner in fathers. CONCLUSIONS: Fathers reported significantly lower frequency of clinically important psychological distress and more stable scores than mothers throughout the period. The results indicate that selected psychometric screening may be warranted for parents with known psychosocial risk factors.

Asunto(s)

Preescolar , Padre/psicología , Madres/psicología , Estrés Psicológico/etiología , Adulto , Escolaridad , Relaciones Familiares , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Familia Monoparental , Apoyo Social , Desempleo

RESUMEN

OBJECTIVES: Pre-existing conditions have been postulated as possible causes of the J-shaped relationship between alcohol intake and cardiovascular disease. Two research questions have been addressed in this paper. First, whether never drinkers and former drinkers differ from moderate drinkers in terms of health, and if so, which health problems contribute to this difference. Second, whether the U-shaped relationship between current alcohol intake and cardiovascular disease or all-cause mortality could in part be explained by difference in pre-existing disease burden. DESIGN, SETTING AND PARTICIPANTS: A prospective case-cohort, the Lifestyle and Health Study, consisting of 16,210 men and women aged between 45 and 70 years. Alcohol intake and risk factors were assessed at baseline with a self-administered questionnaire. Medical information was obtained from general practitioners. Cardiovascular events and mortality were followed for a period of 5 years (1996-2001). MAIN RESULTS: Never drinkers and former drinkers were less healthy than moderate drinkers. They rated their health more often as poor, and often had more diseases, such as cardiovascular disease, diabetes, and also alcohol-related diseases. The difference in disease burden did not change the observed relationship between alcohol intake and cardiovascular events, and only partially changed the U-shaped relationship between alcohol intake and all-cause mortality. CONCLUSIONS: The found difference in health between never drinkers and former drinkers compared with moderate drinkers appeared to be only a partial explanation of the observed relationships between alcohol intake and cardiovascular disease, and between alcohol intake and all-cause mortality.

Asunto(s)

Consumo de Bebidas Alcohólicas/efectos adversos , Enfermedades Cardiovasculares/etiología , Estado de Salud , Anciano , Enfermedades Cardiovasculares/mortalidad , Causas de Muerte , Factores de Confusión Epidemiológicos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Países Bajos/epidemiología , Estudios Prospectivos , Factores de Riesgo , Templanza

RESUMEN

OBJECTIVE: The primary aim was to assess the association between response behavior and health status at baseline, and survival in a 5-year follow-up period. A secondary aim was to assess whether reasons for nonresponse were associated with health status at baseline. STUDY DESIGN AND SETTING: Data came from a prospective study cohort consisting of 31,349 men and women aged 45-70 years. Objective retrospective and prospective health information derived from general practitioner registries was available for both respondents and nonrespondents. RESULTS: Results show that among respondents coronary heart disease was more prevalent. Compared with respondents, noncontacts had a higher mortality risk during follow-up. Refusals had hypercholesterolemia more often than did noncontacts, and coronary heart disease or diabetes mellitus less often. CONCLUSION: The paradoxical results that respondents are less healthy at baseline but prospectively have a lower mortality risk may point to a selection effect indicating that the 'worried ill' are more inclined to participate. This effect could imply that observed relationships between risk factors or behaviors and outcomes in cohort studies may be attenuated.

Asunto(s)

Cardiopatías/epidemiología , Selección de Paciente , Negativa a Participar , Distribución por Edad , Anciano , Métodos Epidemiológicos , Medicina Familiar y Comunitaria , Femenino , Estado de Salud , Cardiopatías/mortalidad , Cardiopatías/psicología , Humanos , Hipercolesterolemia/epidemiología , Masculino , Persona de Mediana Edad , Países Bajos/epidemiología , Sesgo de Selección

RESUMEN

OBJECTIVE: To investigate how much of the variance in data on nurse evaluation of different aspects of hospital work can be attributed to individual, ward, department and hospital levels, and to discuss the implication of the findings on quality improvement strategies. DESIGN AND METHOD: National survey data of work experiences were collected from hospital nurses working at 124 hospital wards in 36 departments in 15 hospitals across Norway during the autumn of 1998. The multilevel structure of the variation of nine indices of job satisfaction was explored by fitting four-level random intercept models (nurse, ward, department and hospital). RESULTS: A total of 2606 nurses (66%) responded. The indices showed varying clustering to organizational units. Intraclass correlations (ICCs) varied from 0.05 to 0.38, representing considerable higher level variation. The ward level was the dominating level for the clustering of nurses' job aspect evaluations. CONCLUSION: Multilevel modelling of staff work experiences may identify which improvement goals can be addressed at which organizational level. Improvement efforts should be directed specifically towards each aspect of work and at its most relevant organizational level. Strategies aimed at the micro-organizational level (ward management) rather than the individual level or the macro level (hospital top management) might prove worthwhile.

Asunto(s)

Hospitales/normas , Satisfacción en el Trabajo , Personal de Enfermería en Hospital , Garantía de la Calidad de Atención de Salud , Adulto , Análisis por Conglomerados , Recolección de Datos , Interpretación Estadística de Datos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Noruega , Encuestas y Cuestionarios

RESUMEN

Prior epidemiologic research revealing cardioprotective effects of alcohol intake has systematically neglected lifetime exposure to alcohol, which may cause serious bias in conclusions regarding drinking and heart disease risk. Departing from use of an earlier interview schedule, the authors of the present 1996-2001 cohort study developed a self-administered Lifetime Drinking History questionnaire (LDH-q). A total of 16,211 Dutch men and women older than age 45 years participated by completing the baseline questionnaire. A random sample of 3,255 men and women was used to determine the reliability and validity of the LDH-q. Test-retest reliability was assessed by means of the intraclass correlation coefficient and kappa scores. Correlations between lifetime and current intake scores were used to assess discriminant and convergent validity. Both reliability and validity appeared to be reasonably high compared with results obtained by using interview formats to measure lifetime alcohol intake. Reliability of the LDH-q was higher for men than for women, probably because of the more frequent and regular drinking of men. Indices of validity were similar for men (0.75) and women (0.70). Results show that the LDH-q can be a useful instrument in large-scale cohort studies.

Asunto(s)

Consumo de Bebidas Alcohólicas/epidemiología , Autorrevelación , Encuestas y Cuestionarios , Adulto , Anciano , Estudios de Cohortes , Femenino , Humanos , Masculino , Recuerdo Mental , Persona de Mediana Edad , Países Bajos/epidemiología , Reproducibilidad de los Resultados

RESUMEN

Loss of heterozygosity (LOH) of the distal part of the short arm of chromosome 1 in neuroblastoma is a well characterised phenomenon. In addition, previous reports have described interstitial deletions outside the common region of loss on chromosome 1p36, suggesting additional tumour suppressor loci. In this study, we have searched extensively for interstitial 1p deletions in a panel of 67 neuroblastoma samples from clinically-detected cases. We used three VNTR probes and 10 dinucleotide markers from the 1p32-36 regions reported to show interstitial deletions. Fifteen (22%) tumours showed telomeric LOH without evidence for more proximal interstitial deletions. Forty-five tumours showed no LOH or allelic imbalance. Seven (10%) tumours demonstrated allelic imbalance for one or more markers. These tumours were subsequently analysed by fluorescent in situ hybridisation (FISH) and flow cytometry. The patterns found in all seven tumours were consistent with copy number changes of the entire chromosome 1, without evidence for interstitial deletions. This study indicates that interstitial deletions of chromosome 1p are rare in clinically-detected neuroblastoma when analysed by a combination of molecular and cytogenetic techniques.

Asunto(s)

Deleción Cromosómica , Cromosomas Humanos Par 1/genética , Neuroblastoma/genética , Adolescente , Adulto , Anciano , Southern Blotting , Núcleo Celular/química , Niño , Preescolar , ADN/genética , Genes myc/genética , Humanos , Hibridación Fluorescente in Situ , Lactante , Interfase , Pérdida de Heterocigocidad , Persona de Mediana Edad , Ploidias , Reacción en Cadena de la Polimerasa/métodos , Polimorfismo de Longitud del Fragmento de Restricción

RESUMEN

BACKGROUND: Supplementation of folic acid prior to and in the beginning of pregnancy may prevent neural tube defects (NTDs) in newborns--such as spina bifida--and possibly other congenital malformations. OBJECTIVE: To estimate cost effectiveness of periconceptional supplementation of folic acid using pharmaco-economic model calculation. METHOD: Probabilities for NTDs, risk reductions through periconceptional supplementation of folic acid and lifetime costs of care for children with spina bifida were estimated using Dutch registrations and international literature. MAIN OUTCOME MEASURE: Cost effectiveness was expressed in net costs per discounted life-year gained. Cost effectiveness was calculated in the baseline and in sensitivity analysis. RESULTS: Estimated cost effectiveness of periconceptional supplementation of folic acid amounts to NLG 3900 ([symbol: see text] 1800) in the base case. In sensitivity analysis cost effectiveness mostly remains below NLG 10,000 ([symbol: see text] 4500). CONCLUSION: Periconceptional supplementation of folic acid shows a favorable cost effectiveness. From pharmaco-economic point of view this justifies further stimulation of folic-acid supplementation prior to pregnancy. This can be done through targeted education by health-care workers, such as pharmacists.

Asunto(s)

Suplementos Dietéticos , Ácido Fólico/administración & dosificación , Defectos del Tubo Neural/prevención & control , Costo de Enfermedad , Análisis Costo-Beneficio , Femenino , Humanos , Embarazo , Disrafia Espinal/economía

RESUMEN

Purification and reconstitution of the active Vibrio parahaemolyticus Na+/galactose transporter (vSGLT) enables us to do protein chemistry studies on a representative member of this class of membrane transporters. By measuring intrinsic tryptophan (Trp) fluorescence, conformational changes on the binding of substrates could be investigated. Trp fluorescence increased by 6% on the addition of saturating levels of both Na+ and D-galactose, with a K0.5 for D-galactose of 0.6 mM. No change was seen on the addition of Na+ alone or by adding D-galactose in the presence of K+. The Trp fluorescence could be quenched by acrylamide, but not by Cs+or I?. In the presence of Na+ or K+ alone, of Na+ or K+ and D-galactose, of Na+ and L-glucose, or in the absence of ligands, the fluorescence quenches by acrylamide were similar. This indicated that the tryptophan exposure to acrylamide was unchanged in the presence or absence of ligands. No shifts in lem maximum were observed. To find the Trp responsible for the change in fluorescence, Trp 448 in transmembrane helix 11 in the putative sugar-binding pocket was mutated. It was found that W448F showed a similar change in Trp fluorescence upon the addition of D-galactose in the presence of Na+. We conclude that the Trp fluorescence properties of the purified and reconstituted Na+/galactose cotransporter are selectively changed by the transported substrates Na+ and D-galactose, but it is not the Trp (W448) in the sugar translocation pathway that is involved.

Asunto(s)

Proteínas de Unión al Calcio , Galactosa/metabolismo , Proteínas de Transporte de Monosacáridos/química , Proteínas de Unión Periplasmáticas , Sodio/metabolismo , Triptófano/química , Vibrio parahaemolyticus/química , Fluorescencia , Transporte Iónico/fisiología , Proteínas de Transporte de Monosacáridos/metabolismo , Mutagénesis Sitio-Dirigida , Conformación Proteica , Proteolípidos/química , Especificidad por Sustrato , Triptófano/genética

RESUMEN

A previous loss of heterozygosity (LOH) study of a series of 91 neuroblastomas suggested that the 1p35-36 region encodes at least two tumor suppressor genes (TSGs) of importance in neuroblastoma development. Here we present the results of a study including 205 neuroblastomas that were analyzed for LOH at chromosome 1 and MYCN amplification. The results corroborate the existence of two TSGs on 1p. Distinct 1p loci seem to be involved in MYCN single copy vs. MYCN amplified neuroblastoma, as these tumors display a different type of shortest region of overlap (SRO). About 15% of MYCN single copy neuroblastomas show 1p deletions of variable length with an SRO of 47 cR at 1p36.3. The lost alleles are preferentially of maternal origin (P = 0.0002), suggesting parental imprinting of the locus. MYCN amplified neuroblastomas have a contrasting pattern of 1p loss. These tumors display much larger deletions of at least 89 cR comprising the region from 1p36.1 to the telomere. LOH of 1p is detected in 86% of the cases. The lost alleles are of random parental origin, suggesting inactivation of a non-imprinted TSG.

Asunto(s)

Cromosomas Humanos Par 1/genética , Genes Supresores de Tumor/genética , Impresión Genómica/genética , Neuroblastoma/genética , Bandeo Cromosómico , Femenino , Amplificación de Genes/genética , Eliminación de Gen , Dosificación de Gen , Genes myc/genética , Humanos , Pérdida de Heterocigocidad/genética , Masculino

RESUMEN

The cholate-resistant Lactococcus lactis strain C41-2, derived from wild-type L. lactis MG1363 through selection for growth on cholate-containing medium, displayed a reduced accumulation of cholate due to an enhanced active efflux. However, L. lactis C41-2 was not cross resistant to deoxycholate or cationic drugs, such as ethidium and rhodamine 6G, which are typical substrates of the multidrug transporters LmrP and LmrA in L. lactis MG1363. The cholate efflux activity in L. lactis C41-2 was not affected by the presence of valinomycin plus nigericin, which dissipated the proton motive force. In contrast, cholate efflux in L. lactis C41-2 was inhibited by ortho-vanadate, an inhibitor of P-type ATPases and ATP-binding cassette transporters. Besides ATP-dependent drug extrusion by LmrA, two other ATP-dependent efflux activities have previously been detected in L. lactis, one for the artificial pH probe 2',7'-bis-(2-carboxyethyl)-5(and 6)-carboxyfluorescein (BCECF) and the other for the artificial pH probe N-(fluorescein thio-ureanyl)-glutamate (FTUG). Surprisingly, the efflux rate of BCECF, but not that of FTUG, was significantly enhanced in L. lactis C41-2. Further experiments with L. lactis C41-2 cells and inside out membrane vesicles revealed that cholate and BCECF inhibit the transport of each other. These data demonstrate the role of an ATP-dependent multispecific organic anion transporter in cholate resistance in L. lactis.

Asunto(s)

Proteínas Portadoras/metabolismo , Colatos/metabolismo , Lactococcus lactis/metabolismo , Adenosina Trifosfato/metabolismo , Proteínas de Transporte de Anión , Colatos/farmacología , Farmacorresistencia Microbiana , Metabolismo Energético , Glucosa/metabolismo , Lactococcus lactis/efectos de los fármacos , Vanadatos/farmacología

RESUMEN

OBJECTIVE: To map the prescribing habits of physicians in two different regions in the Netherlands with respect to antidepressant drug choice for first users. DESIGN: Retrospective follow-up study. METHODS: All persons who received an antidepressant drug for the first time during October 1994 to September 1995 were identified from 29 community pharmacies situated in two regions in the Netherlands. Age, gender, type of prescriber, region and the concomitant use of certain groups of drugs as marker for certain diseases were evaluated as determinants for prescribing either a "classic" or a "second generation" antidepressant drug to first users using logistic regression analysis. RESULTS: We identified 4,637 first users during the study period corresponding with an overall incidence density of 16 per 1,000 person-years. For the majority of first users of both regions, the same five antidepressants were prescribed. However, the two regions differed markedly with regard to the frequency of prescription of the individual antidepressants. Region of living was identified as the most important determinant of prescribing a certain category of antidepressant drugs to first users (OR 2.9 [95% CI 2.5-3.3]). Just a few patient characteristics were associated with antidepressant drug choice. The elderly were more likely to receive a classic antidepressant, as were patients concomitantly using anti-epileptics (OR 0.4 [95% CI 0.3-0.6]). Patients concomitantly using cardiac glycosides were more likely to receive a second generation antidepressant (OR 1.8 [95% CI 1.2-2.1]). With respect to age and the other patient characteristics studied, the same pattern was observed in both regions. CONCLUSION: Regional differences contributed more to differences in prescribing habits than individual patient characteristics. In order to improve pharmacotherapy with antidepressant drugs relevant patient characteristics should more be taken into account.

Asunto(s)

Antidepresivos/uso terapéutico , Trastorno Depresivo/tratamiento farmacológico , Adolescente , Adulto , Anciano , Antidepresivos de Segunda Generación/uso terapéutico , Antidepresivos Tricíclicos/uso terapéutico , Trastorno Depresivo/complicaciones , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Inhibidores de la Monoaminooxidasa/uso terapéutico , Países Bajos , Estudios Retrospectivos

RESUMEN

We report on a large Dutch family with a syndrome characterized by severe hand and/or foot anomalies, and hypoplasia/aplasia of the mammary gland and nipple. Less frequent findings include lacrimal-duct atresia, nail dysplasia, hypohydrosis, hypodontia, and cleft palate with or without bifid uvula. This combination of symptoms has not been reported previously, although there is overlap with the ulnar mammary syndrome (UMS) and with ectrodactyly, ectodermal dysplasia, and clefting syndrome. Allelism with UMS and other related syndromes was excluded by linkage studies with markers from the relevant chromosomal regions. A genomewide screening with polymorphic markers allowed the localization of the genetic defect to the subtelomeric region of chromosome 3q. Haplotype analysis reduced the critical region to a 3-cM interval of chromosome 3q27. This chromosomal segment has not been implicated previously in disorders with defective development of limbs and/or mammary tissue. Therefore, we propose to call this apparently new disorder "limb mammary syndrome" (LMS). The SOX2 gene at 3q27 might be considered an excellent candidate gene for LMS because the corresponding protein stimulates expression of FGF4, an important signaling molecule during limb outgrowth and development. However, no mutations were found in the SOX2 open reading frame, thus excluding its involvement in LMS.

Asunto(s)

Anomalías Múltiples/genética , Cromosomas Humanos Par 3 , Deformidades Congénitas del Pie/genética , Deformidades Congénitas de la Mano/genética , Neoplasias Mamarias Animales/genética , Anomalías Múltiples/diagnóstico por imagen , Anomalías Múltiples/fisiopatología , Animales , Mapeo Cromosómico , Proteínas de Unión al ADN/genética , Femenino , Deformidades Congénitas del Pie/diagnóstico por imagen , Deformidades Congénitas del Pie/fisiopatología , Ligamiento Genético , Proteínas HMGB , Deformidades Congénitas de la Mano/diagnóstico por imagen , Deformidades Congénitas de la Mano/fisiopatología , Humanos , Masculino , Neoplasias Mamarias Animales/diagnóstico por imagen , Neoplasias Mamarias Animales/fisiopatología , Mutación , Proteínas Nucleares/genética , Linaje , Radiografía , Factores de Transcripción SOXB1 , Síndrome , Factores de Transcripción

RESUMEN

Placenta percreta is a serious complication of pregnancy. A 38-year-old nullipara presented at 25 weeks gestation with preterm labour. Spontaneous delivery was followed by retained placenta. During an attempt to remove the placenta manually placental tissue could not be distinguished. Initially, placenta increta was considered as the most likely diagnosis and conservative management was planned, but progressive shock emerged due to intra-abdominal hemorrhage and laparotomy was performed. Placenta percreta was diagnosed, followed by a supracervical hysterectomy. A review of risk factors, diagnostic tools and treatment possibilities is given.

Asunto(s)

Placenta Accreta/complicaciones , Hemorragia Posparto/etiología , Abdomen , Adulto , Femenino , Humanos , Placenta Accreta/cirugía , Embarazo