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1.
Br Dent J ; 220(11): 581-4, 2016 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-27283565

RESUMEN

Objectives To evaluate the compliance of NHS dental practice websites in Wales, UK, with the 2012 GDC document Principles of ethical advertising, before its introduction (2011) and again after its introduction (2014).Methods All practices in Wales with an NHS contract and dental practice website were identified. The content of the website was evaluated to determine if it complied with the principles outlined in the 2012 GDC document Principles of Ethical Advertising.Results Twenty-five percent of the 446 practices sampled in 2011 had a website, compared to 44% of the 436 practices sampled in 2014. The principles best complied with were; displaying the name, geographic address, and telephone number of the practice (100% for both years). None of the websites compared the qualifications or skills of its practitioners to others, therefore 100% complied with this principle. Displaying team members' professional qualification and the country from which this is obtained was fairly well represented; 92% and 61% respectively in 2014; an improvement from only 50% and 49% respectively in 2011. Principles worst complied with were displaying the GDC's address (3% 2011; 9% 2014) or link to the GDC website (11% 2011; 7% 2014) and details of the practice complaints procedure (1% 2011; 5% 2014). Overall, no practice complied with all of the compulsory principles.Conclusion In both 2011 and 2014 no practice website was compliant with all the principles outlined in the 2012 GDC document Principles of ethical advertising. Reflecting results from previous studies, this study showed that compliance is slowly improving, yet over 4 years after the introduction of the mandatory principles, it remains that no practice website is 100% compliant.


Asunto(s)
Publicidad , Ética Odontológica , Internet , Administración de la Práctica Odontológica , Gales
2.
Anaesthesia ; 64(1): 19-22, 2009 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-19087001

RESUMEN

The aim of this study was to compare efficacy and particularly patient preference of sub-Tenon's anaesthesia with peribulbar anaesthesia in patients undergoing sequential, bilateral, cataract surgery. Fifty patients were randomised to either sub-Tenon's or peribulbar anaesthesia for their first operation and the alternative technique for their subsequent operation. Intra-ocular pressure was measured, globe and lid akinesia were scored, patients completed a visual rating score of injection and operative pain and their preference for anaesthesia was assessed. Intra-ocular pressure rose significantly following peribulbar injection (p = 0.02) but was comparable at 5 min. There was no significant difference in lid or globe movement. Injection and operative pain scores were low and comparable. Both methods provided similar anaesthesia and akinesia. The majority (86%) chose the method they received first irrespective of whether it was sub-Tenon's or peribulbar, but 10% of patients preferred sub-Tenon's, disliking the facial numbness from peribulbar anaesthesia.


Asunto(s)
Anestesia Local/métodos , Anestésicos Locales/administración & dosificación , Facoemulsificación , Anciano , Anciano de 80 o más Años , Anestesia Local/efectos adversos , Anestésicos Locales/efectos adversos , Esquema de Medicación , Femenino , Humanos , Lidocaína/administración & dosificación , Lidocaína/efectos adversos , Masculino , Persona de Mediana Edad , Movimiento/efectos de los fármacos , Dolor/etiología , Dimensión del Dolor/métodos , Satisfacción del Paciente
3.
Surg Endosc ; 18(1): 64-71, 2004 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-14625752

RESUMEN

BACKGROUND: Hypercarbia and elevated intraabdominal pressure resulting from carbon dioxide (CO2) pneumoperitoneum can adversely affect respiratory mechanics. This study examined the changes in mechanical ventilation, CO2 homeostasis, and pulmonary gas exchange in morbidly obese patients undergoing a laparoscopic or open gastric bypass (GBP) procedure. METHODS: In this study, 58 patients with a body mass index (BMI) of 40 to 60 kg/m2 were randomly allocated to laparoscopic ( n = 31) or open ( n = 27) GBP. Minute ventilation was adjusted to maintain a low normal arterial partial pressure of CO2 (PaCO2), low normal end-tidal partial pressure of CO2 (ETCO2), and low airway pressure. Respiratory compliance, ETCO2, peak inspiratory pressure (PIP), total exhaled CO2 per minute (VCO2), and pulse oximetry (SO2) were measured at 30-min intervals. The acid-base balance was determined by arterial blood gas analysis at 1-h intervals. The pulmonary gas exchange was evaluated by calculation of the alveolar dead space-to-tidal volume ratio (V(Dalv)/V(T)) and alveolar-arterial oxygen gradient (PAO2-PaO2). RESULTS: The two groups were similar in age, gender, and BMI. As compared with open GBP, laparoscopic GBP resulted in higher ETCO2, PIP, and VCO2, and a lower respiratory compliance. Arterial blood gas analysis demonstrated higher PaCO2 and lower pH during laparoscopic GBP than during open GBP ( p < 0.05). The V(Dalv)/V(T) ratio and PAO2-PaO2 gradient did not change significantly during laparoscopic GBP. Intraoperative oxygen desaturation (SO2 < 90%) did not develop in any of the patients in either group. CONCLUSIONS: Laparoscopic GBP alters intraoperative pulmonary mechanics and acid-base balance but does not significantly affect pulmonary oxygen exchange. Changes in pulmonary mechanics are well tolerated in morbidly obese patients when proper ventilator adjustments are maintained.


Asunto(s)
Derivación Gástrica , Hipercapnia/etiología , Laparoscopía , Neumoperitoneo Artificial , Intercambio Gaseoso Pulmonar , Mecánica Respiratoria , Equilibrio Ácido-Base , Adulto , Anastomosis en-Y de Roux , Índice de Masa Corporal , Dióxido de Carbono/sangre , Femenino , Humanos , Rendimiento Pulmonar , Masculino , Persona de Mediana Edad , Oximetría , Oxígeno/sangre , Presión Parcial , Neumoperitoneo Artificial/efectos adversos , Volumen de Ventilación Pulmonar
6.
Mutat Res ; 459(3): 173-86, 2000 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-10812329

RESUMEN

The Saccharomyces cerevisiae DNA2 gene encodes a DNA-stimulated ATPase and DNA helicase/nuclease essential for DNA replication. In characterizing dna2 mutants, we have found that Dna2p also participates in DNA repair or in damage avoidance mechanisms. dna2 mutants are sensitive to X rays, although they are less sensitive than rad52 mutants. The X-ray sensitivity of dna2 mutants is suppressed by overexpression of a 5' to 3' exonuclease, the yeast FEN-1 structure-specific nuclease, encoded by the RAD27 gene, which also suppresses the growth defect of dna2-ts mutants. SGS1 encodes a helicase with similar properties to Dna2 protein. Although sgs1Delta mutants are resistant to X rays, dna2-2 sgs1Delta double mutants are more sensitive to X rays than the dna2-2 mutant. Temperature sensitive dna2 mutants are only slightly sensitive to UV light, show normal levels of spontaneous and UV induced mutagenesis, and have only a 2.5-fold elevated level of dinucleotide tract instability compared to wildtype. However, dna2Delta strains kept alive by overproduction of RAD27 are highly sensitive to UV light. These phenotypes, in addition to the epistasis analysis reported, allow us to propose that Dna2 is involved in postreplication and DSB repair pathways.


Asunto(s)
Adenosina Trifosfatasas/genética , ADN Helicasas/genética , Reparación del ADN/genética , Mutación/efectos de la radiación , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae/efectos de la radiación , Adenosina Trifosfatasas/metabolismo , Ciclo Celular/efectos de la radiación , Supervivencia Celular/genética , Supervivencia Celular/efectos de la radiación , Rotura Cromosómica/genética , ADN Helicasas/metabolismo , Reparación del ADN/efectos de la radiación , Replicación del ADN/genética , Replicación del ADN/efectos de la radiación , ADN de Hongos/efectos de los fármacos , ADN de Hongos/metabolismo , ADN de Hongos/efectos de la radiación , Repeticiones de Dinucleótido/genética , Relación Dosis-Respuesta en la Radiación , Endodesoxirribonucleasas/biosíntesis , Endodesoxirribonucleasas/genética , Endonucleasas de ADN Solapado , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , RecQ Helicasas , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Temperatura , Rayos Ultravioleta
7.
J Biol Chem ; 275(22): 16518-29, 2000 Jun 02.
Artículo en Inglés | MEDLINE | ID: mdl-10748138

RESUMEN

Saccharomyces cerevisiae Dna2 protein is required for DNA replication and repair and is associated with multiple biochemical activities: DNA-dependent ATPase, DNA helicase, and DNA nuclease. To investigate which of these activities is important for the cellular functions of Dna2, we have identified separation of function mutations that selectively inactivate the helicase or nuclease. We describe the effect of six such mutations on ATPase, helicase, and nuclease after purification of the mutant proteins from yeast or baculovirus-infected insect cells. A mutation in the Walker A box in the C-terminal third of the protein affects helicase and ATPase but not nuclease; a mutation in the N-terminal domain (amino acid 504) affects ATPase, helicase, and nuclease. Two mutations in the N-terminal domain abolish nuclease but do not reduce helicase activity (amino acids 657 and 675) and identify the putative nuclease active site. Two mutations immediately adjacent to the proposed nuclease active site (amino acids 640 and 693) impair nuclease activity in the absence of ATP but completely abolish nuclease activity in the presence of ATP. These results suggest that, although the Dna2 helicase and nuclease activities can be independently affected by some mutations, the two activities appear to interact, and the nuclease activity is regulated in a complex manner by ATP. Physiological analysis shows that both ATPase and nuclease are important for the essential function of DNA2 in DNA replication and for its role in double-strand break repair. Four of the nuclease mutants are not only loss of function mutations but also exhibit a dominant negative phenotype.


Asunto(s)
Desoxirribonucleasas/metabolismo , Proteínas de Escherichia coli , Exodesoxirribonucleasas/metabolismo , Proteínas Fúngicas/metabolismo , Saccharomyces cerevisiae/metabolismo , Secuencia de Aminoácidos , Baculoviridae/genética , Secuencia de Bases , Daño del ADN , Cartilla de ADN , Reparación del ADN , Exodesoxirribonucleasa V , Proteínas Fúngicas/genética , Datos de Secuencia Molecular , Mutagénesis , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo
8.
J Invest Surg ; 11(4): 281-8, 1998.
Artículo en Inglés | MEDLINE | ID: mdl-9788670

RESUMEN

Clinical use of staple lung volume reduction surgery (LVRS) has proliferated for treatment of emphysema despite limited data regarding efficacy or optimal techniques. Recent studies in animal models of obstructive lung disease describe the decrease in lung compliance and increase in airway support as mechanisms of an improvement in pulmonary functions analogous to human data. We describe contrasting results in an animal model of bullous lung disease with a mixed but predominantly restrictive pattern of lung disease. Mixed restrictive and bullous lung disease was induced in 17 New Zealand white rabbits with i.v. Sephadex beads and endotracheally instilled carrageenan. Unilateral stapled lung volume reduction surgery was performed at 5 weeks postinduction of emphysema on the right lower lobe by lateral thoracotomy using a pediatric stapler. Static trans-pleural pressures were measured at 60, 40, and 20 cm3 inflation at preinduction (baseline), pre- and postoperatively, and 1 week postoperatively in anesthetized animals. Lungs were then harvested en bloc and examined histopathologically. The effects of volume reduction surgery on static lung compliance, lung conductance, and forced expiratory flows (FEF) were assessed. Five weeks after induction of lung disease, the animals had no significant change in static compliance and forced expiratory volume in 0.5 s (FEV0.5) or lung conductance compared to baseline. Immediately following LVRS, the animals showed a significant decrease in static compliance, FEV0.5, and conductance. One week postoperatively, compliance increased to approximately baseline levels along with a slight increase in FEFs and conductance toward preoperative levels. Histology examination revealed restrictive and bullous lung disease. Thus, we have demonstrated the feasibility of using an animal model for evaluation of volume reduction therapy for restrictive-obstructive lung disease. Physiologically, this model showed decrease conductance and decreased forced expiratory flows following lung volume reduction despite increased recoil. This is in contrast to increased conductance and flows seen in humans with severe emphysema following surgery and suggests that current criteria excluding patients with a significant restrictive component to their lung disease from LVRS surgery may be justified.


Asunto(s)
Enfisema/cirugía , Enfermedades Pulmonares Obstructivas/cirugía , Neumonectomía , Animales , Modelos Animales de Enfermedad , Enfisema/patología , Enfisema/fisiopatología , Estudios de Evaluación como Asunto , Flujo Espiratorio Forzado , Volumen Espiratorio Forzado , Humanos , Rendimiento Pulmonar , Enfermedades Pulmonares Obstructivas/patología , Enfermedades Pulmonares Obstructivas/fisiopatología , Masculino , Presión , Conejos
9.
J Invest Surg ; 11(2): 129-37, 1998.
Artículo en Inglés | MEDLINE | ID: mdl-9700621

RESUMEN

Stapled lung volume reduction surgery (LVRS) has recently been described for treatment of emphysema. Many questions arise regarding physiologic mechanisms of response from surgical treatment of emphysema. The objective of this study was to develop an animal model for the study of lung volume reduction surgery in diffuse heterogeneous emphysema. We hypothesized that elastic recoil would increase, static respiratory system compliance would decrease, and expiratory flows would increase after lung volume reduction surgery in animals with emphysema. In the study, emphysema was induced in 31 New Zealand White rabbits (3-5 kg) with endotracheally aerosalized porcine elastase (10,000-12,000 U). Lateral thoracotomies were performed 4-6 weeks postinduction under general anesthesia and mechanical ventilatory support. Stapled volume reduction was performed on the right lower lobe using a standard multirow pediatric stapler (U.S. Surgical). Pulmonary function tests were performed at baseline (preinduction), before stapling LVRS (postemphysema induction), immediately post stapling LVRS, and 1 week poststapling. Static respiratory system compliance, flow, conductance and forced expiratory flows, and peak flows at 20 and 40 cm3 of exhaled volume were analyzed. Animals were sacrificed 1 week poststapling, and bilateral lungs were harvested for histopathology. Diffuse but heterogeneous pulmonary emphysema was seen in these animals treated with high-dose aerosolized elastase. Static compliance increased, while expiratory flows and conductance decreased after induction of emphysema. Immediately post stapled volume reduction therapy, animals had decreased static compliance. By 1 week following surgery, animals showed increased forced expiratory flows and decreased expiratory resistance, although compliance was similar to preoperative levels. In conclusion, we describe initial results in an animal model of obstructive emphysema suitable for the study of lung volume reduction surgery. Changes in pulmonary function indicate that unilateral lower lobe LVRS increases airway conductance in the rabbits. Findings from LVRS studies in animal models such as this may help explain clinical improvement following LVRS in humans.


Asunto(s)
Neumonectomía/métodos , Enfisema Pulmonar/cirugía , Animales , Modelos Animales de Enfermedad , Volumen Espiratorio Forzado , Humanos , Pulmón/patología , Rendimiento Pulmonar , Masculino , Elastasa Pancreática/administración & dosificación , Enfisema Pulmonar/etiología , Enfisema Pulmonar/fisiopatología , Conejos , Pruebas de Función Respiratoria , Mecánica Respiratoria
12.
Gen Hosp Psychiatry ; 19(4): 251-8, 1997 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-9327254

RESUMEN

A large proportion of patients present to primary care with chronic, stress-related symptoms having no organic cause. Biomedical treatment of these patients is usually ineffective and expensive. A 6-week behavioral medicine intervention designed to provide adjunctive treatment to primary care was evaluated in a randomized, controlled study. Thirty-eight individuals receiving treatment and 44 waiting for treatment completed the SCL-90-R at times corresponding to 1 week before (time 1) and 1 week after the course (time 2). The treatment group was then followed up at 6 months. After correction for initial levels, the treatment group reported significantly less somatization, anxiety, and depression than did the wait-list group at time 2. Within the treatment group, decreases in somatization, anxiety, and depression were statistically significant and were maintained 6 months later. Within the wait-list group, distress remained unchanged. A review of relevant literature reveals that a general behavioral medicine course such as the one studied here has an important adjunctive role in primary care, since 1) subsyndromal psychological distress is common in primary care; 2) physicians are reluctant to address psychosocial issues; 3) negative mood is associated with poor health; 4) negative mood is associated with high, inappropriate medical utilization; and 5) negative mood is associated with help-seeking behavior.


Asunto(s)
Terapia Conductista/métodos , Medicina de la Conducta/métodos , Medicina Familiar y Comunitaria/métodos , Trastornos Psicofisiológicos/terapia , Adulto , Afecto , Análisis de Varianza , Ansiedad/terapia , Depresión/terapia , Femenino , Estudios de Seguimiento , Humanos , Masculino , Aceptación de la Atención de Salud , Trastornos Psicofisiológicos/diagnóstico , Trastornos Psicofisiológicos/psicología , Resultado del Tratamiento , Listas de Espera
13.
HMO Pract ; 11(2): 88-94, 1997 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-10168114

RESUMEN

The objective of this evaluation is to examine the clinical utility of a behavioral medicine intervention for treatment of prevalent, ill-defined physical symptoms in primary care. Commonly known as somatization, these symptoms have no known organic or psychiatric cause, and are poorly treated by biomedicine alone. Designed to treat these mood-related physical symptoms, the Personal Health Improvement Program (PHIP) is a 6-week structured group intervention which includes classroom videos, exercises and home study assignments. Data were collected from 21 PHIP courses offered at both staff and group model delivery sites at Harvard Pilgrim Health Care. One hundred and seventy-one participants filled out questionnaires at the first and last session of the course, and returned follow-up questionnaires by mail 3 months later. In order to obtain clinical data, medical charts were reviewed for the periods 1 year before and 1 year after the course. Questionnaire data included a Medical Symptoms Checklist, the Brief Symptom Inventory, the SF-36, a course satisfaction form, and visits to the health care site. After PHIP, participants reported decreases in emotional and physical distress, increases in functional status, and high levels of satisfaction. Patient improvement was also reflected in decreased use of medical resources after a long-standing pattern of high utilization. These data suggest that by addressing physical complaints that are resistant to biomedical treatment alone, PHIP has practical utility, promoting increased quality of care, increased patient satisfaction, and better allocation of health care resources.


Asunto(s)
Medicina de la Conducta , Sistemas Prepagos de Salud/estadística & datos numéricos , Promoción de la Salud/organización & administración , Atención Primaria de Salud/normas , Trastornos Somatomorfos/terapia , Encuestas de Atención de la Salud/métodos , Salud Holística , Humanos , Massachusetts , Visita a Consultorio Médico , Innovación Organizacional , Satisfacción del Paciente , Evaluación de Programas y Proyectos de Salud , Resultado del Tratamiento
14.
Mol Cell Biol ; 17(4): 2136-42, 1997 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-9121462

RESUMEN

We have recently described a new helicase, the Dna2 helicase, that is essential for yeast DNA replication. We now show that the yeast FEN-1 (yFEN-1) nuclease interacts genetically and biochemically with Dna2 helicase. FEN-1 is implicated in DNA replication and repair in yeast, and the mammalian homolog of yFEN-1 (DNase IV, FEN-1, or MF1) participates in Okazaki fragment maturation. Overproduction of yFEN-1, encoded by RAD27/RTH1, suppresses the temperature-sensitive growth of dna2-1 mutants. Overproduction of Dna2 suppresses the rad27/rth1 delta temperature-sensitive growth defect. dna2-1 rad27/rth1 delta double mutants are inviable, indicating that the mutations are synthetically lethal. The genetic interactions are likely due to direct physical interaction between the two proteins, since both epitope-tagged yFEN-1 and endogenous yFEN-1 coimmunopurify with tagged Dna2. The simplest interpretation of these data is that one of the roles of Dna2 helicase is associated with processing of Okazaki fragments.


Asunto(s)
Adenosina Trifosfatasas/metabolismo , ADN Helicasas/metabolismo , Endodesoxirribonucleasas/metabolismo , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae/enzimología , Adenosina Trifosfatasas/genética , Secuencia de Bases , Quinasa 1 Reguladora del Ciclo Celular (Checkpoint 1) , ADN Helicasas/genética , Reparación del ADN , Replicación del ADN , ADN de Hongos/biosíntesis , ADN de Hongos/genética , Endodesoxirribonucleasas/genética , Endonucleasas de ADN Solapado , Genes Fúngicos , Mutación , Fenotipo , Proteínas Quinasas/genética , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Supresión Genética
15.
J Clin Laser Med Surg ; 15(3): 103-8, 1997.
Artículo en Inglés | MEDLINE | ID: mdl-9612156

RESUMEN

OBJECTIVE: To determine the relative efficacy and morbidity of Ho:YAG versus Nd:YAG laser treatment of bullous lung disease in an animal model. SUMMARY BACKGROUND DATA: Laser coagulation procedures for treatment of emphysematous pulmonary bullae and heterogeneous emphysema continue to evolve. The role of lasers in lung volume reduction surgery remains controversial due to issues of relative efficacy and morbidity. The Nd:YAG laser is most commonly used for these procedures. We hypothesized that the shallower penetration of the Ho:YAG laser may be better suited for laser bullae coagulation and emphysema lung volume reduction with increased efficacy and reduced lung injury. METHODS: Thirty New Zealand White rabbits (15 normal rabbits; 15 with bullous lung disease) were evaluated with Ho:YAG compared to Nd:YAG laser exposures. Bullae were coagulated by either Ho:YAG or Nd:YAG treatment. In all animals (bullous-induced and normals), unaffected lung tissue in the upper lobes and contralateral lungs were treated with 5 spot exposures of Nd:YAG and Ho:YAG, each to assess depth of lung injury. Animals were sacrificed at Days 0, 7, and 21 and their lungs were examined histologically. RESULTS: Ho:YAG and Nd:YAG exposures caused equivalent lung injury to normal lung tissue. In the acute phase, parenchymal necrosis depth was similar for both Ho:YAG and Nd:YAG (850 +/- 273 microns vs. 900 +/- 270 microns respectively, p = 0.7). By Day 7, lung necrosis depth was 925 +/- 133 microns Ho:YAG vs. 1225 +/- 235 microns Nd:YAG (p = 0.33), and lung fibrosis depth was 300 +/- 134 microns Ho:YAG vs. 558 +/- 127 microns Nd:YAG (p = 0.11). By Day 21, pulmonary parenchymal necrosis was not seen. Pleural fibrosis depth was maximal at Day 21, reaching 250 +/- 102 microns for Ho:YAG vs. 300 +/- 156 microns Nd:YAG (P = 0.88). Pleural necrosis depth was 67 +/- 42 microns Ho:YAG vs 48 +/- 34 microns Nd:YAG (p = 0.42) on Day 7 and resolved by Day 21. During surgical coagulation procedures, the Ho:YAG laser was dramatically more efficient in coagulating bullae. The Ho:YAG laser required less exposure at equivalent power and resulted in immediate desiccation of bullae, in sharp contrast to the Nd:YAG laser. CONCLUSIONS: Because the Ho:YAG was more effective and did not result in more acute lung injury than the standard Nd:YAG laser in this study, Ho:YAG lasers may have improved potential for laser treatment of bullae or lung volume reduction surgery (LVRS) compared to Nd:YAG lasers.


Asunto(s)
Vesícula/cirugía , Endoscopios , Coagulación con Láser/métodos , Terapia por Láser , Enfermedades Pulmonares/cirugía , Animales , Estudios de Evaluación como Asunto , Holmio , Masculino , Neodimio , Conejos
16.
Toxicol Ind Health ; 12(3-4): 403-17, 1996.
Artículo en Inglés | MEDLINE | ID: mdl-8843557

RESUMEN

Because of the decline in central nervous system function that occurs with age, older people may be at greater risk of neurological dysfunction following exposure to neurotoxic contaminants in the environment. This study was designed to assess the neuropsychological functioning of a group of 50-90-year-old fisheaters exposed to polychlorinated biphenyls (PCBs) through Great Lakes fish consumption, and a group of age- and sex-matched nonfisheaters selected from the Michigan Department of Public Health's established cohort of fisheaters and nonfisheaters. A neuropsychological assessment battery, demographic interview, and fish consumption questionnaire were developed and piloted on similarly aged men and women in the Lansing and Detroit, Michigan, areas. The assessment battery included tests of motor function, memory and learning, executive functions, and visual-spatial functions, and took approximately two hours to administer. Most of the tests included in the battery have been shown to be sensitive to subtle, age-related declines in cognitive and motor function. The demographic questionnaire included questions on a number of important control variables that could influence the neuropsychological end points that were assessed in the study. These included demographic background, alcohol consumption, tobacco use, prescription and nonprescription drug use, medical history (including psychiatric illnesses), employment history, and activity level. The fish consumption questionnaire asked about historical and current consumption of specific fish species from each of the Great Lakes and its tributaries and was based on the fish consumption advisories published in the 1992 Michigan Fishing Guide. The questionnaire also asked about consumption of wild game, fish preparation and cooking methods, serving size, and changes in fish consumption patterns over time. After each subject completed the neuropsychological assessment, demographic interview, and fish consumption questionnaire, a blood sample was collected for analysis of PCBs, dichloro diphenyl dichloroethene (DDE), and ten other contaminants frequently detected in Great Lakes fish. Subject recruitment for the study began in July 1993 and was completed in November 1995. The data will be analyzed in two steps: first, to assess differences in confounding variables between fisheaters and nonfisheaters; and secondly, to determine the independent effects of Great Lakes fish consumption, as well as serum PCB and DDE levels, on cognitive and motor function after controlling for all identified covariates. Three indices of PCB exposure-total PCBs, total ortho-substituted PCBs and total coplanar PCBs-will be assessed. These studies should shed light on three questions: 1) Does consumption of contaminated fish from the Great Lakes exacerbate or accelerate the normal age-related decline in cognitive and motor function? 2) Do serum PCB or DDE concentrations predict the degree of behavioral dysfunction? and 3) If PCB exposure is related to behavioral outcomes, which class of PCB congeners, ortho-substituted or coplanar, are responsible for the cognitive and motor deficits?


Asunto(s)
Sistema Nervioso Central/efectos de los fármacos , Diclorodifenil Dicloroetileno/efectos adversos , Enfermedades Transmitidas por los Alimentos/epidemiología , Hexaclorobenceno/efectos adversos , Insecticidas/efectos adversos , Bifenilos Policlorados/efectos adversos , Anciano , Anciano de 80 o más Años , Envejecimiento/patología , Carga Corporal (Radioterapia) , Estudios de Cohortes , Recolección de Datos , Diclorodifenil Dicloroetileno/sangre , Exposición a Riesgos Ambientales , Femenino , Productos Pesqueros , Contaminación de Alimentos , Great Lakes Region , Hexaclorobenceno/sangre , Humanos , Insecticidas/sangre , Estilo de Vida , Masculino , Persona de Mediana Edad , Bifenilos Policlorados/sangre , Estadística como Asunto
17.
Toxicol Ind Health ; 12(3-4): 499-505, 1996.
Artículo en Inglés | MEDLINE | ID: mdl-8843566

RESUMEN

Interest in environmental contaminants and their effect on human health emerged as a primary focus in the 1970s following the discovery of significant levels of mercury, dichloro diphenyl trichloroethane (DDT), and polychlorinated bihpenyls (PCBs) in recreationally caught Great Lakes fish. In response to these findings, the Michigan Department of Public Health, in 1971, initiated a series of "fisheater" cohort studies. These studies continue to be conducted today. The evolution of human exposure assessment by serum PCB determination parallels the evolution of more precise and sensitive analytical laboratory procedures over the past 25 years. Early work quantitated PCB with Aroclor 1254 standards. By 1980, the Webb and McCall packed-column method (Webb and McCall, 1972, 1973), which quantitates total PCB with Aroclor 1016 and 1260 standards, had gained the Association of Official Analytical Chemists (AOAC) approval and became the accepted method. This method was used in the 1978-1980 Michigan Great Lakes Fisheater Study, the first sizable study of this kind in the nation. The study confirmed that fisheaters had significantly more exposure (median 21.4 ppb vs 6.6 ppb) than controls. Toxicology studies have indicated the need to quantitate individual PCB congeners, in order to correlate exposure with possible toxicological and health outcomes. Today, capillary column gas chromatography and gas chromatography/mass spectrometry are used to search for trace components of the total PCB dose (Mullen et al., 1984). Because of the legacy of the earlier analytical data, Michigan also continues to conduct packed-column analysis for longitudinal comparisons. The Michigan fisheater study database and registry provide a significantly exposed and historic foundation for research testing health outcome hypotheses.


Asunto(s)
Exposición a Riesgos Ambientales , Enfermedades Transmitidas por los Alimentos/epidemiología , Estudios de Cohortes , Productos Pesqueros/normas , Contaminación de Alimentos , Cromatografía de Gases y Espectrometría de Masas , Humanos , Insecticidas , Michigan , Proyectos Piloto , Bifenilos Policlorados/envenenamiento , Estudios Prospectivos , Contaminantes Químicos del Agua
18.
J Biol Chem ; 270(45): 26766-9, 1995 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-7592912

RESUMEN

Although a number of eukaryotic DNA helicases have been identified biochemically and still more have been inferred from the amino acid sequences of the products of cloned genes, none of the cellular helicases or putative helicases has to date been implicated in eukaryotic chromosomal DNA replication. By the same token, numerous eukaryotic replication proteins have been identified, but none of these is a helicase. We have recently identified and characterized a temperature-sensitive yeast mutant, dna2ts, defective in DNA replication, and have cloned the corresponding gene (Kuo, C.-L., Huang, C,-H., and Campbell, J. L. (1983) Proc. Natl. Acad. Sci. U. S. A. 30, 6465-6469; Budd, M. E., and Campbell, J. L. (1995) Proc. Natl. Acad. Sci. U. S. A. 92, 7642-7646). The DNA2 gene is essential and encodes a 172-kDa protein with DNA helicase motifs in its C-terminal half and an N-terminal half with no similarity to any previously described protein (Budd, M. E., and Campbell, J. L. (1995) Proc. Natl. Acad. Sci. U. S. A. 92, 7642-7646). Here we show that the helicase domain is required in vivo and that a 3' to 5' DNA helicase activity specific for forked substrates is intrinsic to the Dna2p. The N terminus is also essential for DNA replication. Thus, the structure of this new helicase is different from all previously characterized replicative helicases, which is consistent with the complex organization of eukaryotic replication forks, where the activities of not one but three essential DNA polymerases must be coordinated.


Asunto(s)
Adenosina Trifosfatasas/genética , ADN Helicasas/genética , Replicación del ADN , Proteínas de Saccharomyces cerevisiae , Adenosina Trifosfatasas/metabolismo , Sitios de Unión/genética , Mapeo Cromosómico , ADN Helicasas/metabolismo , Replicación del ADN/genética , ADN de Hongos/genética , ADN de Hongos/metabolismo , Genes Fúngicos , Mutagénesis Sitio-Dirigida , Saccharomyces cerevisiae/enzimología , Saccharomyces cerevisiae/genética
19.
Proc Natl Acad Sci U S A ; 92(17): 7642-6, 1995 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-7644470

RESUMEN

A yeast gene has been identified by screening for DNA replication mutants using a permeabilized cell replication assay. The mutant is temperature sensitive for growth and shows a cell cycle phenotype typical of DNA replication mutants. RNA synthesis is normal in the mutant but DNA synthesis ceases upon shift to the nonpermissive temperature. The DNA2 gene was cloned by complementation of the dna2ts gene phenotype. The gene is essential for viability. The gene encodes a 172-kDa protein with characteristic DNA helicase motifs. A hemagglutinin epitope-Dna2 fusion protein was prepared and purified by conventional and immunoaffinity chromatography. The purified protein is a DNA-dependent ATPase and has 3' to 5' DNA helicase activity specific for forked substrates. A nuclease activity that endonucleolytically cleaves DNA molecules having a single-stranded 5' tail adjacent to a duplex region copurifies through all steps with the fusion protein.


Asunto(s)
Adenosina Trifosfatasas/biosíntesis , ADN Helicasas/biosíntesis , Replicación del ADN/genética , Genes Fúngicos , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae/metabolismo , Adenosina Trifosfatasas/química , Adenosina Trifosfatasas/genética , Secuencia de Aminoácidos , Secuencia de Bases , Clonación Molecular , ADN Helicasas/química , ADN Helicasas/genética , Prueba de Complementación Genética , Datos de Secuencia Molecular , Oligodesoxirribonucleótidos , Fenotipo , Plásmidos , Saccharomyces cerevisiae/genética , Homología de Secuencia de Aminoácido
20.
HMO Pract ; 9(2): 53-6, 1995 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-10143151

RESUMEN

It is reported that behavioral and mood-related problems are associated with more than 25% of medical visits. Many patients seeking help are misdiagnosed or not effectively treated by their physicians. We believe that medical education has not prepared primary care providers to evaluate and treat behavioral problems. The traditional medical or biological model needs to be replaced by a more integrated and comprehensive biopsychosocial approach. HMO delivery systems should take the lead in developing this new framework for care.


Asunto(s)
Sistemas Prepagos de Salud/estadística & datos numéricos , Necesidades y Demandas de Servicios de Salud , Trastornos Mentales/epidemiología , Humanos , Trastornos Mentales/diagnóstico , Trastornos Mentales/terapia , Modelos Educacionales , Médicos de Familia/educación , Médicos de Familia/normas , Estados Unidos/epidemiología
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