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1.
Nature ; 607(7918): 301-306, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35831604

RESUMEN

Our understanding of the climatic teleconnections that drove ice-age cycles has been limited by a paucity of well-dated tropical records of glaciation that span several glacial-interglacial intervals. Glacial deposits offer discrete snapshots of glacier extent but cannot provide the continuous records required for detailed interhemispheric comparisons. By contrast, lakes located within glaciated catchments can provide continuous archives of upstream glacial activity, but few such records extend beyond the last glacial cycle. Here a piston core from Lake Junín in the uppermost Amazon basin provides the first, to our knowledge, continuous, independently dated archive of tropical glaciation spanning 700,000 years. We find that tropical glaciers tracked changes in global ice volume and followed a clear approximately 100,000-year periodicity. An enhancement in the extent of tropical Andean glaciers relative to global ice volume occurred between 200,000 and 400,000 years ago, during sustained intervals of regionally elevated hydrologic balance that modified the regular approximately 23,000-year pacing of monsoon-driven precipitation. Millennial-scale variations in the extent of tropical Andean glaciers during the last glacial cycle were driven by variations in regional monsoon strength that were linked to temperature perturbations in Greenland ice cores1; these interhemispheric connections may have existed during previous glacial cycles.

2.
HIV Med ; 2023 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-38087902

RESUMEN

OBJECTIVES: With management of comorbidity in people living with HIV (PLWH) a key component of clinical care, early loss of bone integrity and clinical fracture are recognized as important issues. This review aims to describe the epidemiology of fracture in PLWH, as well as summarizing the relative balance of factors that contribute to fracture. We also aim to describe fracture risk assessment and interventional strategies to modify the risk of fracture in this population. RESULTS: Data from recent meta-analyses show that PLWH have significantly more fractures than the general population, with men and injecting drug users at higher risk. Modifiable factors that contribute to fracture risk in this cohort include body mass index (BMI), drug use, concurrent medications, frailty, and hepatitis C virus infection. Relating to antiretroviral therapy, current or ever tenofovir exposure has been identified as predictive of fracture but not cumulative use, and a potentially modest protective effect of efavirenz has been observed. Fracture Risk Assessment Tool scores underestimate fracture risk in PLWH with improved accuracy when HIV is considered a cause of secondary osteoporosis and bone mineral density (BMD) included. CONCLUSION: Early consideration of risk, prompting evaluation of modifiable risk factors, frailty and falls risk with bone density imaging and prompt intervention may avert fracture in PLWH. Guidance on screening and lifestyle modification is available in international guidelines. Bisphosphonates are safe and effective in PLWH, with limited data for other agents.

3.
Public Health ; 214: 140-145, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36549023

RESUMEN

OBJECTIVES: Commercial gambling markets have undergone unprecedented expansion and diversification in territories across Sub-Saharan Africa (SSA). This gambling boom has popularised the uptake of gambling products in existing circuits of popular culture, sport and leisure and raised concerns about the extent to which state legislation is equipped to regulate the differentiated impacts of gambling on public health. STUDY DESIGN: Comparative policy analysis. METHODS: This article provides a systematic mapping of the regulatory environment pertaining to gambling across SSA. The review was conducted by obtaining and triangulating data from a desk review of online materials, consultation with regulatory bodies in each territory and the VIXIO Gambling Compliance database. RESULTS: Gambling is legally regulated in 41 of 49 (83.6%) SSA countries, prohibited in 7 (14.3%) and is not legislated for in 1 (2.0%). Of those countries that regulate gambling, 25 (61.0%) countries had dedicated regulators and 16 (39.0%) countries regulated via a government department. Only 2 of 41 (4.9%) countries have published annual reports continuously since the formation of regulatory bodies, and 3 (7.3%) countries have published an incomplete series of reports since the formation. In 36 (87.8%) countries, no reports were published. Enforcement activities were documented by all five regulators that published reports. CONCLUSION: The review uncovered a lack of coherence in regulatory measures and the need for more transparent public reporting across SSA territories. There are also variations in regulating online products and marketing, with most countries lacking apt guidelines for the digital age. Our findings suggest an urgent need to address the regulatory void surrounding online forms of gambling and the promotion of gambling products. This underlines the importance of a public health approach to protect against an increase in gambling-related harms.


Asunto(s)
Juego de Azar , Deportes , Humanos , Juego de Azar/epidemiología , Políticas , África del Sur del Sahara/epidemiología , Formulación de Políticas
4.
Public Health ; 184: 89-94, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32546295

RESUMEN

OBJECTIVES: Online sports gambling has become an increasingly popular feature of male youth culture and fandom in recent decades. Fuelled by advances in mobile app technologies and the liberalisation of state regulations on advertising, this 'gamblification' of sport has given rise to a global industry promoting gambling as a knowledge-based, risk-free leisure activity. This study examined how the growth of online sports gambling has impacted on gambling behaviours among young adult men in the UK and how it may pose new risks concerning the normalisation of gambling behaviours. STUDY DESIGN: The study used a multiphased qualitative research design. METHODS: The study was conducted with 32 adult men (aged 18-35 years) across two sites, Derry, Northern Ireland, and Bristol, England. It comprised three phases of data collection: participatory focus groups, a 30-day gambling diary and semistructured interviews. RESULTS: Four main themes emerged. First, data suggest that gambling has become a normalised aspect of sports fandom for male youth demographics, many of whom view the casual wagering of money as vital to their enjoyment of sport. Second, the perceived 'facelessness' of sports gambling platforms via mobile app technologies was reported to increase inclination to engage in sports betting. Third, 'free bet' incentives and in-play promotions play a significant role as a mechanism of inducement towards sports gambling practices. Fourth was the potential role of online sports gambling as a gateway to gambling-related harms, including financial precarity, indebtedness, mortgage defaults, family breakdown, loss of employment and mental health struggles. CONCLUSION: Online sports gambling has significant public health implications, particularly for male youth demographics. Policymakers in the UK should consider stronger regulation of gambling-related advertising and sponsorship in sport, independent risk assessments of sports gambling products and a commitment to safeguarding youth demographics from gambling-related harm in a digital age.


Asunto(s)
Juego de Azar/psicología , Internet , Normas Sociales , Deportes , Adolescente , Adulto , Humanos , Masculino , Salud Pública , Investigación Cualitativa , Reino Unido , Adulto Joven
5.
Anaesthesia ; 74(2): 180-189, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30467829

RESUMEN

Major vascular surgery is frequently associated with significant blood loss and coagulopathy. Existing evidence suggests hypofibrinogenaemia develops earlier than other haemostatic deficiencies during major blood loss. The purpose of this study was to assess whether the use of an infusion of fibrinogen concentrate to prevent and treat hypofibrinogenaemia during surgery resulted in satisfactory haemostasis, removing or reducing the need for blood component transfusion. Twenty patients undergoing elective extent-4 thoraco-abdominal aortic aneurysm repair were randomly allocated to receive either fresh frozen plasma or fibrinogen concentrate to treat hypofibrinogenaemia during surgery. Coagulation was assessed during and after surgery by point-of-care and laboratory testing, respectively, and treatment was guided by pre-defined transfusion triggers. Despite blood losses of up to 11,800 ml in the patients who received the fibrinogen concentrate, none required fresh frozen plasma during surgery, and only two required platelet transfusions. The median (IQR [range]) allogeneic blood component administration during surgery and in the first 24 h postoperatively was 22.5 (14-28 [2-41]) units in patients allocated to fresh frozen plasma vs. 4.5 (3-11[0-17]) in patients allocated to fibrinogen concentrate (p = 0.011). All patients in both groups were assessed by the surgeon to have satisfactory haemostasis at the end of surgery. Mean (SD) postoperative fibrinogen concentrations were similar in patients allocated to fresh frozen plasma and fibrinogen concentrate (1.6 (0.3) g.l-1 vs. 1.6 (0.2) g.l-1 ; p = 0.36) but the mean (SD) international normalised ratio and activated partial thromboplastin time ratio were lower in patients allocated to fresh frozen plasma (1.1 (0.1) vs. 1.8 (0.3); p < 0.0001 and 1.1 (0.2) vs. 1.7 (0.5); p = 0.032, respectively). Fibrinogen concentrate may be used as an alternative to fresh frozen plasma in the treatment of coagulopathy during thoraco-abdominal aortic aneurysm repair.


Asunto(s)
Aneurisma de la Aorta Torácica/cirugía , Trastornos de la Coagulación Sanguínea/terapia , Fibrinógeno/uso terapéutico , Plasma , Anciano , Femenino , Humanos , Relación Normalizada Internacional , Masculino
6.
Osteoporos Int ; 26(11): 2587-95, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26025288

RESUMEN

UNLABELLED: We determined the prevalence of osteosarcopenic obesity (loss of bone and muscle coexistent with increased adiposity) in overweight/obese postmenopausal women and compared their functionality to obese-only women. Results showed that osteosarcopenic obese women were outperformed by obese-only women in handgrip strength and walking/balance abilities indicating their higher risk for mobility impairments. INTRODUCTION: Osteosarcopenic obesity (OSO) is a recently defined triad of osteopenia/osteoporosis, sarcopenia, and adiposity. We identified women with OSO in overweight/obese postmenopausal women and evaluated their functionality comparing them with obese-only (OB) women. Additionally, women with osteopenic/osteoporotic obesity (OO), but no sarcopenia, and those with sarcopenic obesity (SO), but no osteopenia/osteoporosis, were identified and compared. We hypothesized that OSO women will have the lowest scores for each of the functionality measures. METHODS: Participants (n = 258; % body fat ≥35) were assessed using a Lunar iDXA instrument for bone and body composition. Sarcopenia was determined from negative residuals of linear regression modeled on appendicular lean mass, height, and body fat, using 20th percentile as a cutoff. Participants with T-scores of L1-L4 vertebrae and/or total femur <-1, but without sarcopenia, were identified as OO (n = 99) and those with normal T-scores, but with sarcopenia, as SO (n = 28). OSO (n = 32) included women with both osteopenia/osteoporosis and sarcopenia, while those with normal bone and no sarcopenia were classified as OB (n = 99). Functionality measures such as handgrip strength, normal/brisk walking speed, and right/left leg stance were evaluated and compared among groups. RESULTS: Women with OSO presented with the lowest handgrip scores, slowest normal and brisk walking speed, and shortest time for each leg stance, but these results were statistically significantly different only from the OB group. CONCLUSION: These findings indicate a poorer functionality in women presenting with OSO, particularly compared to OB women, increasing the risk for bone fractures and immobility from the combined decline in bone and muscle mass, and increased fat mass.


Asunto(s)
Fuerza de la Mano/fisiología , Obesidad/fisiopatología , Osteoporosis Posmenopáusica/fisiopatología , Sarcopenia/fisiopatología , Caminata/fisiología , Absorciometría de Fotón/métodos , Adiposidad/fisiología , Anciano , Antropometría/métodos , Composición Corporal/fisiología , Femenino , Humanos , Persona de Mediana Edad , Actividad Motora/fisiología , Equilibrio Postural/fisiología , Vitamina D/análogos & derivados , Vitamina D/sangre
7.
Nat Commun ; 14(1): 7404, 2023 11 16.
Artículo en Inglés | MEDLINE | ID: mdl-37973878

RESUMEN

Understanding how tropical systems have responded to large-scale climate change, such as glacial-interglacial oscillations, and how human impacts have altered those responses is key to current and future ecology. A sedimentary record recovered from Lake Junín, in the Peruvian Andes (4085 m elevation) spans the last 670,000 years and represents the longest continuous and empirically-dated record of tropical vegetation change to date. Spanning seven glacial-interglacial oscillations, fossil pollen and charcoal recovered from the core showed the general dominance of grasslands, although during the warmest times some Andean forest trees grew above their modern limits near the lake. Fire was very rare until the last 12,000 years, when humans were in the landscape. Here we show that, due to human activity, our present interglacial, the Holocene, has a distinctive vegetation composition and ecological trajectory compared with six previous interglacials. Our data reinforce the view that modern vegetation assemblages of high Andean grasslands and the presence of a defined tree line are aspects of a human-modified landscape.


Asunto(s)
Bosques , Árboles , Humanos , Árboles/fisiología , Polen , Fósiles , Cambio Climático , Ecosistema
8.
Sci Adv ; 5(1): eaav1887, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30613782

RESUMEN

Reconstructions of past Saharan dust deposition in marine sediments provide foundational records of North African climate over time scales of 103 to 106 years. Previous dust records show primarily glacial-interglacial variability in the Pleistocene, in contrast to other monsoon records showing strong precessional variability. Here, we present the first Saharan dust record spanning multiple glacial cycles obtained using 230Th normalization, an improved method of calculating fluxes. Contrary to previous data, our record from the West African margin demonstrates high correlation with summer insolation and limited glacial-interglacial changes, indicating coherent variability in the African monsoon belt throughout the late Pleistocene. Our results demonstrate that low-latitude Saharan dust emissions do not vary synchronously with high- and mid-latitude dust emissions, and they call into question the use of existing Plio-Pleistocene dust records to investigate links between climate and hominid evolution.

9.
Sci Adv ; 4(11): eaav0118, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-30498784

RESUMEN

Lake and cave records show that winter precipitation in the southwestern United States increased substantially during millennial-scale periods of Northern Hemisphere winter cooling known as Heinrich stadials. However, previous work has not produced a clear picture of the atmospheric circulation changes driving these precipitation increases. Here, we combine data with model simulations to show that maximum winter precipitation anomalies were related to an intensified subtropical jet and a deepened, southeastward-shifted Aleutian Low, which together increased atmospheric river-like transport of subtropical moisture into the western United States. The jet and Aleutian Low changes are tied to the southward displacement of the intertropical convergence zone and the accompanying intensification of the Hadley circulation in the central Pacific. These results refine our understanding of atmospheric changes accompanying Heinrich stadials and highlight the need for accurate representations of tropical-extratropical teleconnections in simulations of past and future precipitation changes in the region.

10.
Psychon Bull Rev ; 24(6): 1870-1878, 2017 12.
Artículo en Inglés | MEDLINE | ID: mdl-28321819

RESUMEN

"Vast" is a word often applied to environmental terrain that is perceived to have large spatial extent. This judgment is made even at viewing distances where traditional metric depth cues are not useful. This paper explores the perceptual basis of vast experience, including reliability and visual precursors. Experiment 1 demonstrated strong agreement in ratings of the spatial extent of two-dimensional (2D) scene images by participants in two countries under very different viewing conditions. Image categories labeled "vast" often exemplified scene attributes of ruggedness and openness (Oliva & Torralba, 2001). Experiment 2 quantitatively assessed whether these properties predict vastness. High vastness ratings were associated with highly open, or moderately open but rugged, scenes. Experiment 3 provided evidence, consistent with theory, that metric distance perception does not directly mediate the observed vastness ratings. The question remains as to how people perceive vast space when information about environmental scale is unavailable from metric depth cues or associated scene properties. We consider possible answers, including contribution from strong cues to relative depth.


Asunto(s)
Percepción de Distancia/fisiología , Percepción Visual/fisiología , Adulto , Femenino , Humanos , Masculino , Adulto Joven
11.
J Natl Cancer Inst ; 82(22): 1769-72, 1990 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-2231773

RESUMEN

An important determinant in interpreting the results of colorectal polyp chemoprevention trials is the rate of polyps missed during colonscopic examination. We prospectively examined 90 patients by tandem colonoscopy performed by two alternating examiners. In 69 (76.7%) patients, 221 neoplastic lesions were documented histologically. Of a total of 58 lesions detected in 31 patients, no neoplastic lesion greater than or equal to 10 mm in size was missed; 16% of diminutive (less than or equal to 5 mm) neoplastic polyps and 12.3% of medium-sized (6-9 mm) neoplastic polyps were missed by the first examiner. We conclude that an experienced colonoscopist will miss about 15% of colorectal neoplastic polyps less than 10 mm in size in the setting of adequate bowel preparation. Large (greater than or equal to 10 mm) polyps were rarely missed, however, with the "miss" rate in our study equal to 0, with a 95% confidence limit of 4.64%.


Asunto(s)
Neoplasias Colorrectales/diagnóstico , Pólipos Intestinales/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias del Colon/diagnóstico , Neoplasias del Colon/epidemiología , Colonoscopía , Neoplasias Colorrectales/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Neoplasias del Recto/diagnóstico , Neoplasias del Recto/epidemiología
12.
J Psychiatr Ment Health Nurs ; 13(3): 330-6, 2006 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-16737500

RESUMEN

The purpose of this study was to explore the meaning of spirituality and how the spiritual needs of psychiatric nurses could be supported at work during a hospital amalgamation. Forty-six nurses completed the General Information Questionnaire and described the meaning of spirituality and how their spiritual needs could be supported. Data were analysed by the double-coding qualitative method. The themes identified for the meaning of spirituality included: being hopeful, having belief/belief systems, maintaining relatedness/connectedness and the expression of spirituality. The major themes identified to support nursing staffs' spiritual needs at work included communication, offering hope, being valued and support from spiritual sources. Nurses expressed the importance of spirituality in their lives and the need for spiritual support at work. Data for addressing staff spiritual needs are reported; however, further studies are needed to understand the spiritual needs of nursing staff at work during hospital amalgamations.


Asunto(s)
Instituciones Asociadas de Salud , Personal de Enfermería en Hospital/psicología , Apoyo Social , Espiritualidad , Adulto , Canadá , Femenino , Humanos , Masculino , Persona de Mediana Edad , Evaluación de Necesidades , Enfermería Psiquiátrica
13.
Cancer Res ; 51(1): 422-33, 1991 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-1988102

RESUMEN

Cytogenetic analysis of short-term cultures was carried out on 109 lipomas from 92 patients. Clonal chromosomal abnormalities were present in 50% of the tumors analyzed. Based on the results, three main cytogenetic groups were identified and included: (a) tumors with normal karyotypes, (b) tumors with abnormalities involving region q13-15 on chromosome 12, and (c) tumors with other clonal aberrations. Within each of these groups, cytogenetic subgroups could be identified, each characterized by a specific anomaly. Tumors with abnormalities of 12q included specific subgroups with t/ins(1;12)(p32-33;q13-15), t(2;12)(p21-22;q13-14), t(3;12)(q28;q14), t(12;21)(q13;q21), complex, and nonrecurrent aberrations. The group containing heterogeneous clonal aberrations included subgroups with del(13)(q12q22), der(6)(p21-23), der(11)(q13), and nonspecific aberrations. Chromosome bands 1p36, 1p32-33, 2p21-22, 3q27-28, 6p21-23, 11q13, 12q13-15, 13q12, 13q22, 17p13, 17q21, and 21q21-22 were preferentially involved in structural rearrangements in lipomas. The identification of these sites of nonrandom rearrangements may serve to identify genes (at or near the junctions of chromosomal aberrations) involved in normal cellular growth control. Statistical analysis of the data revealed a correlation among karyotypic abnormalities and clinical data, such as age and sex of the patient, and tumor depth, site, and size.


Asunto(s)
Aberraciones Cromosómicas/genética , Lipoma/genética , Bandeo Cromosómico , Cromosomas Humanos Par 11 , Cromosomas Humanos Par 12 , Cromosomas Humanos Par 13 , Cromosomas Humanos Par 2 , Cromosomas Humanos Par 21 , Cromosomas Humanos Par 3 , Cromosomas Humanos Par 6 , Citogenética , Humanos , Lipoma/patología , Translocación Genética
14.
J Am Coll Cardiol ; 27(3): 678-82, 1996 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-8606281

RESUMEN

OBJECTIVES: This study sought to examine the relation between body height and incidence of myocardial infarction, coronary heart disease, overall mortality and mortality from cardiovascular disease. BACKGROUND: An association between short stature and increased risk of fatal and nonfatal cardiovascular disease has been observed in several studies, attracting considerable attention. METHODS: We used data from the First National Health and Nutrition Examination Survey (NHANES I) Epidemiologic Follow-Up Study, a prospective study of a large random sample of the U.S. population, to examine the association between height and risk of four end points. RESULTS: Baseline data were collected from 1971 to 1975 for 13,031 respondents (5,296 men, 7,735 women), and the average follow-up period was 13 years, through 1987. Height was inversely associated with risk of all four of the end points studied in both men and women. However, after adjustment for age and years of education in Cox proportional hazards analyses, the relation no longer existed. Using the same adjustment procedures, persons in the lowest height quintile had no increase in risk compared with those in the highest category. The findings were consistent for men and women, blacks and whites and different age groups. CONCLUSIONS: Data from this study in a national sample do not support the hypothesis of an inverse height-heart disease relation.


Asunto(s)
Estatura , Enfermedades Cardiovasculares/epidemiología , Adulto , Negro o Afroamericano/estadística & datos numéricos , Distribución por Edad , Anciano , Enfermedades Cardiovasculares/etiología , Causas de Muerte , Femenino , Estudios de Seguimiento , Encuestas Epidemiológicas , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Factores de Riesgo , Distribución por Sexo , Factores Socioeconómicos , Estados Unidos/epidemiología , Población Blanca/estadística & datos numéricos
15.
J Am Coll Cardiol ; 30(5): 1200-5, 1997 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-9350915

RESUMEN

OBJECTIVES: We sought to estimate the coronary heart disease (CHD) and cardiovascular disease (CVD) mortality experience of U.S. Hispanics. BACKGROUND: Limited information is available concerning the mortality from CHD among U.S. Hispanics, the nation's second largest minority group. METHODS: The study used data from the National Health Interview Survey (1986 to 1994), including representative national samples of 246,239 non-Hispanic whites, 38,042 blacks and 14,965 Hispanics who were > or = 45 years old at baseline. Mean follow-up of mortality was 5 years (range 1 to 10). RESULTS: During the follow-up period, 27,702 whites (11%), 4,976 blacks (13%) and 1,061 Hispanics (7%) died. Among men, the age-adjusted total mortality per 100,000 person-years was 3,089 in whites and 2,466 in Hispanics, and among women, it was 1,897 and 1,581 in whites and Hispanics, respectively. The Hispanic/white mortality rate ratio for CHD was 0.77 (95% confidence interval [CI] 0.64 to 0.93) and 0.82 (95% CI 0.66 to 1.01) for men and women, respectively. The rate ratio was 0.79 (95% CI 0.68 to 0.91) and 0.80 (95% CI 0.69 to 0.94), respectively, for mortality from cardiovascular diseases. Given the lower all-cause mortality in Hispanics, the proportion of total deaths due to CHD and CVD was similar between the two populations for the same gender and were, respectively, 29.7% and 44.7% in white men, 28.1% and 44.3% in Hispanic men, 24.9% and 43.2% in white women and 24.1% and 41% in Hispanic women. CONCLUSIONS: These data from a cohort of a large national sample are consistent with vital statistics that show that all-cause, CHD and CVD mortality is approximately 20% lower among adult Hispanics than among whites in the United States.


Asunto(s)
Enfermedades Cardiovasculares/mortalidad , Enfermedad Coronaria/mortalidad , Hispánicos o Latinos , Anciano , Población Negra , Enfermedades Cardiovasculares/etnología , Enfermedad Coronaria/etnología , Femenino , Encuestas Epidemiológicas , Humanos , Masculino , Persona de Mediana Edad , Análisis de Supervivencia , Estados Unidos/epidemiología , Población Blanca
16.
J Am Coll Cardiol ; 24(6): 1547-51, 1994 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-7930289

RESUMEN

OBJECTIVES: This study compared the survival of patients with heart failure who have waited > 6 months for heart transplantation with that patients who undergo heart transplantation after a similarly prolonged waiting period. BACKGROUND: There are little data describing outcome in patients with severe heart failure who have waited for extended periods of time on the heart transplant waiting list. METHODS: Sixty-three consecutive patients who spent > 6 months on the heart transplant waiting list were examined. Mean (+/- SD) age was 53 +/- 9 years, mean left ventricular ejection fraction was 19 +/- 6%, and all were taking digoxin and diuretic and vasodilator agents. Patients who underwent transplantation during the follow-up period were censored from the pretransplantation analysis, and their survival was examined as part of the posttransplantation phase of the study. RESULTS: Of the 63 original patients examined, 25 underwent transplantation, 10 during inotropic or mechanical circulatory support. The pretransplantation mortality rate was 6% at 6 months after the 6-month milestone on the waiting list, 12% at 12 months and 22% at 18 months. The posttransplantation mortality rate was 5% at 6 months, 10% at 12 months and 24% at 18 months. There were no differences in survival at any time between the two phases of the study. CONCLUSIONS: Survival of patients who have survived > 6 months on the heart transplant waiting list is generally good. Although heart transplantation did not appear to confer additional survival advantage over medical therapy, a large proportion of the patients who underwent transplantation were critically ill at the time of transplantation and would undoubtedly have died of progressive heart failure had they not undergone transplantation. We conclude that heart transplantation should still be considered a therapeutic alternative in patients with heart failure even after a prolonged waiting period on the heart transplant waiting list.


Asunto(s)
Insuficiencia Cardíaca/cirugía , Trasplante de Corazón , Análisis Actuarial , Factores de Confusión Epidemiológicos , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/mortalidad , Humanos , Persona de Mediana Edad , Pronóstico , Análisis de Supervivencia , Factores de Tiempo , Resultado del Tratamiento , Listas de Espera
17.
Curr Top Microbiol Immunol ; 241: 155-80, 1999.
Artículo en Inglés | MEDLINE | ID: mdl-10087661

RESUMEN

Since the discovery of H. pylori in 1982 (MARSHALL 1983; WARREN 1983), research on the mechanisms of virulence of H. pylori has advanced substantially. It is now well established that urease and flagella are virulence factors of H. pylori. Although known for some time to be toxic to epithelial cells in vitro, VacA has only recently been established as a virulence factor. The cag pathogenicity island has also emerged as another virulence contender, although the specific genes involved in virulence are still being determined. Other possible virulence factors, not yet confirmed by gene disruptions, are hapA, katA, sodA, cagA, and iron-regulated genes. As of yet, no adhesins have been confirmed as being important for in vivo survival of H. pylori. With the sequence of the H. pylori genome in hand, it should be possible to more easily determine the role of specific genes in virulence. Genes of immediate interest are the OMPs, which may under go phase and antigenic variation and may represent adhesins. Additionally, virulence-related orthologs and vacA-related genes may provide some interesting findings. Once we define the genes that contribute to H. pylori virulence, we may be able to more easily develop novel therapeutic drugs or vaccines to treat and prevent H. pylori infection.


Asunto(s)
Antígenos Bacterianos , Infecciones por Helicobacter/microbiología , Helicobacter pylori/patogenicidad , Adhesinas Bacterianas/genética , Adhesinas Bacterianas/metabolismo , Proteínas Bacterianas , Catalasa/metabolismo , Helicobacter pylori/genética , Helicobacter pylori/inmunología , Helicobacter pylori/metabolismo , Hemaglutininas/genética , Hemaglutininas/metabolismo , Humanos , Lactoferrina/genética , Lactoferrina/metabolismo , Lectinas , Lipopolisacáridos/inmunología , Lipoproteínas , Movimiento , Mutación , Sideróforos/genética , Sideróforos/metabolismo , Superóxido Dismutasa/metabolismo , Ureasa/genética , Ureasa/metabolismo , Virulencia
18.
Chem Biol ; 8(11): 1107-21, 2001 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-11731301

RESUMEN

BACKGROUND: Involved or implicated in a wide spectrum of diseases, trypsin-like serine proteases comprise well studied drug targets and anti-targets that can be subdivided into two major classes. In one class there is a serine at position 190 at the S1 site, as in urokinase type plasminogen activator (urokinase or uPA) and factor VIIa, and in the other there is an alanine at 190, as in tissue type plasminogen activator (tPA) and factor Xa. A hydrogen bond unique to Ser190 protease-arylamidine complexes between O gamma(Ser190) and the inhibitor amidine confers an intrinsic preference for such inhibitors toward Ser190 proteases over Ala190 counterparts. RESULTS: Based on the structural differences between the S1 sites of Ser190 and Ala190 protease-arylamidine complexes, we amplified the selectivity of amidine inhibitors toward uPA and against tPA, by factors as high as 220-fold, by incorporating a halo group ortho to the amidine of a lead inhibitor scaffold. Comparison of K(i) values of such halo-substituted and parent inhibitors toward a panel of Ser190 and Ala190 proteases demonstrates pronounced selectivity of the halo analogs for Ser190 proteases over Ala190 counterparts. Crystal structures of Ser190 proteases, uPA and trypsin, and of an Ala190 counterpart, thrombin, bound by a set of ortho (halo, amidino) aryl inhibitors and of non-halo parents reveal the structural basis of the exquisite selectivity and validate the design principle. CONCLUSIONS: Remarkable selectivity enhancements of exceptionally small inhibitors are achieved toward the uPA target over the highly similar tPA anti-target through a single atom substitution on an otherwise relatively non-selective scaffold. Overall selectivities for uPA over tPA as high as 980-fold at physiological pH were realized. The increase in selectivity results from the displacement of a single bound water molecule common to the S1 site of both the uPA target and the tPA anti-target because of the ensuing deficit in hydrogen bonding of the arylamidine inhibitor when bound in the Ala190 protease anti-target.


Asunto(s)
Serina Endopeptidasas/química , Inhibidores de Serina Proteinasa/síntesis química , Animales , Sitios de Unión , Cristalografía por Rayos X , Diseño de Fármacos , Humanos , Enlace de Hidrógeno , Unión Proteica , Serina Endopeptidasas/metabolismo , Inhibidores de Serina Proteinasa/química , Inhibidores de Serina Proteinasa/farmacología , Relación Estructura-Actividad , Activador de Tejido Plasminógeno/antagonistas & inhibidores , Activador de Tejido Plasminógeno/química , Activador de Plasminógeno de Tipo Uroquinasa/antagonistas & inhibidores , Activador de Plasminógeno de Tipo Uroquinasa/química , Agua/química , Agua/metabolismo
19.
Arch Intern Med ; 149(5): 1169-72, 1989 May.
Artículo en Inglés | MEDLINE | ID: mdl-2719508

RESUMEN

Reported coffee consumption during 1954 to 1958 and 1971 to 1973 was used to test for association with cardiovascular disease (CVD) incidence and lipid values in the Framingham cohort. Multivariate analysis was employed, regressing CVD on age, systolic pressure, cigarette use, body mass index, total cholesterol, and coffee intake. In pooled analyses (2648 men with 549 CVD cases and 3566 women with 462 CVD cases) coffee intake was not associated with CVD incidence in either smokers or nonsmokers, irrespective of sex. Similarly, multivariate analyses for individuals with existing cardiovascular disease showed no association between coffee intake and subsequent cardiovascular disease. In men significant negative associations between coffee and total cholesterol, and very-low-density lipoprotein cholesterol were seen, whereas in women positive associations with low-density lipoprotein cholesterol were observed. Although inconsistent effects on the lipid profile were seen, no increase in primary or secondary CVD was seen with coffee drinking.


Asunto(s)
Enfermedades Cardiovasculares/etiología , Café/efectos adversos , Adulto , Anciano , Presión Sanguínea , Colesterol/sangre , LDL-Colesterol/sangre , Estudios de Cohortes , Femenino , Humanos , Lipoproteínas VLDL/sangre , Masculino , Persona de Mediana Edad , Riesgo , Factores de Riesgo , Fumar/efectos adversos
20.
Diabetes Care ; 2(2): 120-6, 1979.
Artículo en Inglés | MEDLINE | ID: mdl-520114

RESUMEN

This report examines prospectively, in the Framingham cohort, the relation of diabetes and impaired glucose tolerance to each of the cardiovascular sequelae, taking into account age, sex, and associated cardiovascular risk factors. The incidence of cardiovascular disease, as well as the levels of cardiovascular risk factors, were found to be higher in diabetic than in nondiabetic men and women. The relative impact of diabetes on coronary heart disease, peripheral vascular disease, or stroke incidence was the same in men and women, but for cardiovascular mortality and cardiac failure the impact is greater for women. Present evidence suggests that alleviation of associated cardiovascular risk factors is the most promising course in reducing cardiovascular sequelae in diabetic patients.


Asunto(s)
Enfermedades Cardiovasculares/etiología , Complicaciones de la Diabetes , Factores de Edad , Anciano , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Masculino , Massachusetts , Persona de Mediana Edad , Estudios Prospectivos , Riesgo , Factores Sexuales
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