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1.
Hematol Oncol Stem Cell Ther ; 16(4): 358-365, 2023 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-37363980

RESUMO

BACKGROUND AND OBJECTIVES: The aims of this study were to determine the extent to which hematopoietic cell transplantation (HCT) survivors adhere to the American Cancer Society recommendations for weekly physical activity and identify potential demographic and transplant characteristics associated with the lack of compliance. METHODS: This cross-sectional study included adults who had undergone HCT and were at least 1 year post transplantation. Physical activity was assessed using the screening tool of the Block 2014. The type of activity, frequency, and intensity were converted into the metabolic equivalent of task (MET) scores (0-499.0 MET min/week, inadequate activity; 500-1000 MET min/week, adequate activity; >1000 MET min/week, highly vigorous activity). RESULTS: Participants (n = 81) reported a median MET score of 153 min/week, and 83% failed to reach the physical activity guideline of >500 MET min/week. Only 17.3% met the ACS recommendations, with three reporting above 1000 MET min/week. Median daily moderate and vigorous physical activity minute totals were 18.0 and 5.9 min/d, with 85.2% and 60.5% of participants involved, respectively. The median total physical activity energy expenditure was 744 kcal/d. Only race was associated with MET score, with Whites reporting higher MET scores. CONCLUSION: Most HCT survivors assessed in this study did not meet the ACS physical activity recommendations. These findings reinforce the need to incorporate screening for physical activity into HCT survivorship care, offer counseling to those who do not meet the recommended levels, and encourage a physically active lifestyle among HCT survivors.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Neoplasias , Adulto , Estados Unidos , Humanos , American Cancer Society , Estudos Transversais , Exercício Físico , Sobreviventes , Neoplasias/terapia
2.
Colorectal Dis ; 12(3): 213-9, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19183329

RESUMO

OBJECTIVE: Chromosomal loss within the region of 18q and loss of SMAD4 expression have been reported to be frequent somatic events during colorectal cancer tumour progression; however, their associations with age at onset have not been widely studied. METHOD: We analysed 109 tumours from a population-based case-family study based on colorectal cancers diagnosed before the age of 45 years. These patients with early-onset colorectal cancer had been previously screened for germ-line mismatch repair gene mutations, microsatellite instability (that included the mononucleotide repeat in TGFbetaRII) and somatic k-ras mutations. We measured SMAD4 protein expression using immunohistochemistry and SMAD4 copy number using quantitative real-time PCR. RESULTS: Loss of SMAD4 protein expression was observed in 27/109 (25%) of cancers tested and was more commonly observed in rectal tumours (15/41, 36%) when compared with tumours arising in the colon (11/66, 17%) (P = 0.04). There was no association between SMAD4 protein expression and TGFbetaR11 mutation status, SMAD4 copy number, family history, MSI status, tumour stage or grade. CONCLUSION: Loss of SMAD4 expression is a common feature of early-onset colorectal tumours as it is in colorectal cancers diagnosed in other age-groups. Taken together, the molecular pathways (genetic and epigenetic) now known to be involved in early-onset colorectal cancer only explain a small proportion of the disease and require further exploration.


Assuntos
Adenocarcinoma/metabolismo , Neoplasias Colorretais/metabolismo , Proteína Smad4/metabolismo , Adenocarcinoma/genética , Adolescente , Adulto , Neoplasias Colorretais/genética , Variações do Número de Cópias de DNA , Feminino , Humanos , Masculino , Proteína Smad4/genética , Adulto Jovem
3.
J Biomed Mater Res A ; 78(1): 50-8, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16602121

RESUMO

Acute and chronic osteomyelitis caused by staphylococci can be difficult to treat by conventional means and often has marked consequences for the patient. Current methods of treatment involve the use of systemic antibiotics, the local implantation of nondegradable drug carriers, and surgical debridement. A possible solution that could prevent initial bacterial adhesion could be to modify the implant surface with an antimicrobial coating while maintaining biocompatibility to host cells. This study describes the cytocompatibility evaluation of different coatings (poly(D,L-lactide) (PDLLA), politerefate (PTF), calcium phosphate/anodic plasma-chemical treatment (CaP/APC), polyurethane (PU), and polyvinylpyrollidone (PVP) on titanium surfaces with and without chlorhexidine diacetate (CHA) to Staphylococcus aureus, Staphylococcus epidermidis, and hTERT human fibroblasts. Surface characterization of the coatings showed no significant variation in the roughness or hydrophobicity of the coated surfaces, except the CaP/APC surface that was porous yet the smoothest, and PVP, PVP+CHA, and CaP/APC+CHA that were more hydrophilic in nature than the others. On the surfaces without CHA, both staphylococcal strains and spread fibroblasts were observed, but on the CHA impregnated surfaces few bacteria and no intact fibroblasts were seen. Flow cytometry found fewer bacteria in the media and on the surfaces containing CHA in comparison to the surfaces without CHA. The release kinetics varied from slow (over 200 h) to burst release: PDLLA>PTF>PU>CaP/APC=PVP. This study showed that PDLLA and PTF have the best potential as coatings on implants for drug delivery, as they were cytocompatible to hTERT fibroblasts, eluted CHA effectively, and passed mechanical testing. The actual release kinetics of PDLLA and PTF are important, as the amount of CHA present should remain above the minimal inhibitory concentration value for a limited time before disappearing completely.


Assuntos
Materiais Revestidos Biocompatíveis , Fibroblastos/fisiologia , Teste de Materiais , Staphylococcus aureus/crescimento & desenvolvimento , Staphylococcus epidermidis/crescimento & desenvolvimento , Titânio , Linhagem Celular Transformada , Fibroblastos/ultraestrutura , Humanos , Microscopia Eletrônica de Varredura , Staphylococcus aureus/ultraestrutura , Staphylococcus epidermidis/ultraestrutura
4.
Cancer Res ; 54(9): 2307-9, 1994 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-8162570

RESUMO

Cytogenetic analysis has indicated that deletion of chromosome 9p occurs in a significant number of non-small cell lung and mesothelioma tumors. Using paired oligonucleotide primers, we have undertaken an extensive analysis of 9p markers to determine homozygous and heterozygous loss of marker sequences. Homozygous loss of D9S169 and D9S171, both of which map centromeric to the IFN gene cluster, were noted in three cell lines (27%) and hemizygous deletions of one or both of these loci was found in a further six cell lines (54%). These data suggest the presence of a potential tumor suppressor gene for lung cancer in proximity to D9S169 and D9S171 at 9p21.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Deleção Cromossômica , Cromossomos Humanos Par 9 , Neoplasias Pulmonares/genética , Mesotelioma/genética , Heterozigoto , Homozigoto , Humanos , Reação em Cadeia da Polimerase , Células Tumorais Cultivadas
5.
J Neurosci ; 20(2): 878-86, 2000 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-10632617

RESUMO

Memory for famous faces can be used to examine the neural systems underlying retrieval from long-term memory. To date, there have been a limited number of functional neuroimaging investigations examining famous face recognition. In this study, we compared recognition of famous faces to recognition of newly learned faces. Whole-brain, event-related functional magnetic resonance imaging was used to image regional changes in neural activity in 11 subjects during the encoding of unfamiliar faces and during familiarity judgments for: (1) newly learned faces, (2) unfamiliar face distractors, and (3) famous faces. Image analyses were restricted to correct recognition trials. Recognition accuracy and response time to famous and recently learned faces were equivalent. Recognition of famous faces was associated with a widespread network of bilateral brain activations involving the prefrontal, lateral temporal, and mesial temporal (hippocampal and parahippocampal regions) regions compared to recognition of recently encoded faces or unfamiliar faces seen for the first time. Findings are discussed in relation to current proposals concerning the neural regions thought to participate in long-term memory retrieval and, more specifically, in relation to retrieval of information from the person identity semantic system.


Assuntos
Mapeamento Encefálico , Encéfalo/fisiologia , Face , Reconhecimento Visual de Modelos/fisiologia , Adulto , Encéfalo/anatomia & histologia , Feminino , Humanos , Aprendizagem , Imageamento por Ressonância Magnética/métodos , Masculino , Rede Nervosa/fisiologia
6.
Arch Intern Med ; 159(9): 957-63, 1999 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-10326937

RESUMO

BACKGROUND: Obesity in middle age is a well-known risk factor for the development of type 2 diabetes mellitus. However, the importance of weight and weight gain at younger ages is less certain. OBJECTIVE: To determine the relationship of body weight patterns from 20 to 49 years of age with the subsequent risk for type 2 diabetes mellitus. SETTING: An ongoing longitudinal study of former medical students. PARTICIPANTS: Nine hundred sixteen white men without diabetes at 50 years of age. MEASUREMENTS: Weight and height measured in medical school, then assessed by mailed questionnaire to 49 years of age. MAIN OUTCOME: Incident type 2 diabetes mellitus based on physician self-report. RESULTS: During 14 255 person-years of follow-up, there were 35 incident cases of type 2 diabetes mellitus (2.5 per 1000 person-years). After simultaneous adjustment for age, physical activity, lifetime maternal history of diabetes, and smoking, body mass indexes (BMIs; calculated as weight in kilograms divided by the square of height in meters) at 25, 35, and 45 years of age were all strongly associated with diabetes risk (relative risks for overweight [BMI> or =25.0] vs. not overweight, >3.0; all Ps<.05), as were maximum and average BMI to 49 years of age. The relationship of BMI at 25 years of age to diabetes risk was substantially attenuated by adjustment for BMI at 45 years of age and average BMI, but was independent of weight change, weight variability, or maximum BMI. CONCLUSION: In men, overweight at 25 years of age strongly predicts diabetes risk in middle age, largely through its association with overweight at 45 years of age and high average BMI to 49 years of age.


Assuntos
Peso Corporal , Diabetes Mellitus Tipo 2/etiologia , Obesidade/complicações , Aumento de Peso , Adulto , Índice de Massa Corporal , Feminino , Humanos , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Médicos , Estudos Prospectivos , Estudantes de Medicina , Inquéritos e Questionários
7.
Arch Intern Med ; 160(21): 3209-14, 2000 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-11088080

RESUMO

BACKGROUND: Little is known about the regular source of care (RSOC) among physicians, a group whose self-care may reflect the attitudes and recommendations they convey to their patients. METHODS: We performed a cohort study of physicians who graduated from the Johns Hopkins School of Medicine from 1948 through 1964 to identify predictors of not having an RSOC, and to determine whether not having an RSOC was associated with subsequent receipt of preventive services. The RSOC was assessed in a 1991 survey; use of cancer screening tests and the influenza vaccine was assessed in 1997. RESULTS: The response rate in 1991 was 77% (915 respondents); 35% (312) had no RSOC. Internists (odds ratio [OR], 3.26; 95% confidence interval [CI], 1.58-6.74), surgeons (OR, 2.42; 95% CI, 1.17-5.02), and pathologists (OR, 5.46; 95% CI, 2.09-14.29) were significantly more likely to not have an RSOC than pediatricians. Not having an RSOC was inversely related to the belief that health is determined by health professionals (OR, 0.45; 95% CI, 0.29-0.68) and directly related to the belief that chance (OR, 1.90; 95% CI, 1.28-2.82) determines health. Not having an RSOC in 1991 predicted not being screened for breast, colon, and prostate cancer, as well as not receiving an influenza vaccine at 6 years of follow-up. CONCLUSIONS: A large percentage of physicians in our sample had no RSOC, and this was associated with both medical specialty and beliefs about control of health outcomes. Not having an RSOC was significantly associated with failure to use preventive services several years later. Arch Intern Med. 2000;160:3209-3214.


Assuntos
Atitude do Pessoal de Saúde , Médicos/estatística & dados numéricos , Serviços Preventivos de Saúde/estatística & dados numéricos , Autocuidado/estatística & dados numéricos , Idoso , Estudos de Coortes , Endoscopia do Sistema Digestório , Feminino , Humanos , Vacinas contra Influenza/administração & dosagem , Masculino , Mamografia , Pessoa de Meia-Idade , Análise Multivariada , Sangue Oculto , Razão de Chances , Médicos/psicologia , Medicina Preventiva/estatística & dados numéricos , Antígeno Prostático Específico/sangue , Estados Unidos
8.
Arch Intern Med ; 158(13): 1422-6, 1998 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-9665350

RESUMO

BACKGROUND: Several studies have found that depression is an independent predictor of poor outcome after the onset of clinical coronary artery disease. There are few data concerning depression as a risk factor for the development of coronary artery disease. OBJECTIVE: To determine if clinical depression is an independent risk factor for incident coronary artery disease. PATIENTS AND METHODS: The Johns Hopkins Precursors Study is a prospective, observational study of 1190 male medical students who were enrolled between 1948 and 1964 and who continued to be followed up. In medical school and through the follow-up period, information was collected on family history, health behaviors, and clinical depression. Cardiovascular disease end points have been assessed with reviews of annual questionnaires, National Death Index searches, medical records, death certificates, and autopsy reports. RESULTS: The cumulative incidence of clinical depression in the medical students at 40 years of follow-up was 12%. Men who developed clinical depression drank more coffee than those who did not but did not differ in terms of baseline blood pressure, serum cholesterol levels, smoking status, physical activity, obesity, or family history of coronary artery disease. In multivariate analysis, the men who reported clinical depression were at significantly greater risk for subsequent coronary heart disease (relative risk [RR], 2.12; 95% confidence interval [CI], 1.24-3.63) and myocardial infarction (RR, 2.12; 95% CI, 1.11-4.06). The increased risk associated with clinical depression was present even for myocardial infarctions occurring 10 years after the onset of the first depressive episode (RR, 2.1; 95% CI, 1.1-4.0). CONCLUSION: Clinical depression appears to be an independent risk factor for incident coronary artery disease for several decades after the onset of the clinical depression.


Assuntos
Doença das Coronárias/psicologia , Depressão/complicações , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Risco , Fatores de Risco
9.
Arch Intern Med ; 157(13): 1436-40, 1997 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-9224221

RESUMO

BACKGROUND: Patients with gout are encountered frequently in clinical practice. Previous studies have suggested that hyperuricemia and gout may represent risk factors for coronary heart disease (CHD), the most common cause of death in American men. METHODS: Prospectively collected data from 2 longitudinal cohort studies of former medical students--371 black men in the Meharry Cohort Study and 1181 white men in the Johns Hopkins Precursors Study--were analyzed. The development of gout and of CHD was determined by physician self-report, and validated by using published criteria. The risk for CHD associated with gout was evaluated using Cox proportional hazards analysis. RESULTS: During a median follow-up of 30 years, there were 38 gout cases and 44 CHD events among the Meharry men, and 68 gout cases and 138 CHD events among the Hopkins men. Prior gout was not associated with an increased risk for incident CHD (relative risk = 1.20; 95% confidence interval, 0.37-3.92) among the Meharry men or among the Hopkins men (relative risk = 0.66; 95% confidence interval, 0.24-1.79). Multivariate analysis adjusted for known CHD risk factors did not alter these findings. CONCLUSION: These results, in black and white male physicians, do not suggest a role in men for targeting gout identification in the primary prevention of CHD.


Assuntos
Doença das Coronárias/etiologia , Gota/complicações , Adulto , Humanos , Incidência , Estudos Longitudinais , Masculino , Análise Multivariada , Modelos de Riscos Proporcionais , Estudos Prospectivos , Risco , Fatores de Risco
10.
J Med Screen ; 22(2): 106-8, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25753487

RESUMO

OBJECTIVE: Increasing uptake of cancer screening is a priority for health systems internationally, however, some patients may not attend because they are undergoing active treatment for the cancer of interest or have other medical reasons that mean participation would be inappropriate. This study aims to quantify the proportion of non-participants who have a medical reason for not attending cancer screening. METHODS: Medical reasons for not participating in breast and bowel screening were defined a priori on the basis of a literature review and expert opinion. The notes of 700 patients at two GP practices in Scotland were reviewed, to ascertain the prevalence of medical reasons amongst non-participants. Simple proportions and confidence intervals were calculated. RESULTS: 17.4% of breast and 2.3% of bowel screening non-participants had a medical reason to not participate. The two most common reasons were previous breast cancer follow up (8.86%) and recent mammogram (6.57%). CONCLUSION: These patients may not benefit from screening while also being distressed by receiving an invitation. This issue also makes accurate monitoring and target-setting for improving uptake difficult. Further work is needed to estimate robustly the extent to which medical reasons account for screening non-participation in a larger population.


Assuntos
Neoplasias da Mama/diagnóstico , Detecção Precoce de Câncer , Neoplasias Intestinais/diagnóstico , Programas de Rastreamento/estatística & dados numéricos , Participação do Paciente/estatística & dados numéricos , Idoso , Neoplasias da Mama/epidemiologia , Comorbidade , Feminino , Humanos , Neoplasias Intestinais/epidemiologia , Mamografia , Prevalência , Escócia
11.
Hypertension ; 19(2 Suppl): II218-23, 1992 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-1735583

RESUMO

Cardiovascular reactivity in response to the cold pressor test has been associated with an increased risk of coronary heart disease in middle-aged men. We studied 905 white male medical students, median age 22 years, in the Johns Hopkins Precursors Study. Systolic blood pressure, systolic blood pressure change during the cold pressor test, smoking, cholesterol, Quetelet index, and family history of coronary heart disease were measured on enrollment during 1948-1964. Incidence of cardiovascular morbidity and mortality was ascertained by annual questionnaires and death certificates. There was no association between change in systolic blood pressure during the cold pressor test, whether examined as a continuous variable or a 20 mm Hg or more rise, and the risk of subsequent cardiovascular disease or coronary heart disease. These findings did not change after adjustment for cardiovascular disease risk factors. Previously reported associations may have been due to preexisting arteriosclerosis, which increases the rise in systolic blood pressure during the cold pressor test. We conclude that cardiovascular reactivity to the cold pressor test in young adulthood is not a strong predictor of future cardiovascular disease.


Assuntos
Doenças Cardiovasculares/epidemiologia , Resistência Vascular/fisiologia , Adulto , Doenças Cardiovasculares/fisiopatologia , Colesterol/sangue , Humanos , Masculino , Estudos Prospectivos
12.
Hypertension ; 14(5): 524-30, 1989 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-2807514

RESUMO

Cardiovascular reactivity to stress is hypothesized to be a marker for subsequent neurogenic cardiovascular disease, but few prospective studies of this hypothesis are available. We studied 910 white male medical students who had their blood pressure and pulse rate measured before and during a cold pressor test in the years 1948-1964. Hypertensive status (requiring drug treatment) was ascertained by annual questionnaires in the 20- to 36-year follow-up period. An association was observed between maximum change in systolic blood pressure and later hypertension, with a cumulative incidence of hypertension by age 44 of 6.7%, 3.0%, and 2.4% for a change in systolic blood pressure in the upper, middle two, and lowest quartiles, respectively (Kaplan-Meier, p less than 0.02). After adjustment for study entry age, Quetelet Index, cigarette smoking, pretest systolic blood pressure, and paternal or maternal history of hypertension in a Cox model, the association persisted. The excess risk associated with systolic blood pressure reactivity was not apparent until the population aged some 20 years and was most apparent among those in whom hypertension developed before age 45 (relative risk = 2.5, 95% confidence intervals = 1.47, 4.71 for a 20 mm Hg change). Diastolic blood pressure and heart rate changes were not associated with later hypertension. These data suggest that persons prone to later hypertension manifest an altered physiology at a young age.


Assuntos
Pressão Sanguínea , Fenômenos Fisiológicos Cardiovasculares , Temperatura Baixa , Hipertensão/etiologia , Adulto , Envelhecimento/fisiologia , Estudos de Coortes , Previsões , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Estatística como Assunto
13.
Evolution ; 55(11): 2287-302, 2001 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-11794788

RESUMO

The plethodontid salamander Desmognathus orestes, a member of the D. ochrophaeus species complex, is distributed in southwestern Virginia, eastern Tennessee, and western North Carolina. Previous allozyme analyses indicate that D. orestes consists of two distinct groups of populations (D. orestes 'B' and D. orestes 'C') with extensive intergradation and probable gene flow between these two groups. Spatially varying allele frequencies can reflect historical associations, current gene flow, or a combination of population-level processes. To differentiate among these processes, we use multiple markers to further characterize divergence among populations of D. orestes and assess the degree of intergradation between D. orestes 'B' and D. orestes 'C', specifically investigating variation in allozymes, mitochondrial DNA (mtDNA), and reproductive behavior among populations. On a broad scale, the mtDNA genealogies reconstruct haplotype clades that correspond to the species identified from previous allozyme analyses. However, at a finer geographic scale, the distributions of the allozyme and mtDNA markers for D. orestes 'B' and D. orestes 'C' are discordant. MtDNA haplotypes corresponding to D. orestes 'B' are more broadly distributed across western North Carolina than predicted by allozyme data, and the region of intergradation with D. orestes 'C' indicates asymmetric gene flow of these markers. Asymmetric mating may contribute to observed discordance in nuclear versus cytoplasmic markers. Results support describing D. orestes as a single species and emphasize the importance of using multiple markers to examine fine-scale patterns and elucidate evolutionary processes affecting gene flow when making species-level taxonomic decisions.


Assuntos
DNA Mitocondrial/análise , Isoenzimas/genética , Urodelos/genética , Animais , Feminino , Frequência do Gene , Variação Genética , Haplótipos , Funções Verossimilhança , Masculino , Filogenia , Comportamento Sexual Animal , Urodelos/classificação , Urodelos/fisiologia
14.
Am J Med ; 88(4): 332-6, 1990 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-2327420

RESUMO

PURPOSE: This study was designed to determine youthful precursors of alcohol abuse in physicians. SUBJECTS AND METHODS: We analyzed data from an ongoing prospective study of 1,014 male medical students enrolled in the graduating classes of 1948-1964 at the Johns Hopkins School of Medicine. The cohort, now physicians aged 52 to 68 years, has been contacted regularly since medical school to identify major disease. In 1986, the CAGE alcoholism screening questionnaire was administered. Alcohol abuse was defined as self-admitted alcoholism, excessive consumption of four or more beverages per day on average, or a score of 2 or higher on the CAGE questionnaire. RESULTS: By these criteria, 131 of 1,014 (12.9%) patients abused alcohol. Medical school precursors associated (p less than 0.05) with subsequent alcohol abuse were as follows: non-Jewish ancestry (relative odds [RO] = 3.1), lack of religious affiliation (RO = 4.1), cigarette use of one pack or more per day (RO = 2.6), regular use of alcohol (RO = 3.6), anxiety (RO = 1.8) or anger (RO = 1.8) as a reaction to stress, frequent use of alcohol in nonsocial settings (RO = 1.6), past history of alcohol-related difficulty (RO = 3.1), and maternal alcoholism or mental illness (RO = 1.9). Precursors found not to be associated with alcohol abuse included sleep habits, use of sedatives or amphetamines, interest in athletics or hobbies, and parental relationship. CONCLUSION: Our results suggest that there are several identifiable medical school precursors of alcohol abuse in physicians.


Assuntos
Alcoolismo/etiologia , Família , Médicos , Adulto , Consumo de Bebidas Alcoólicas , Alcoolismo/epidemiologia , Cristianismo , Estudos de Coortes , Emoções , Feminino , Humanos , Judeus , Masculino , Estudos Prospectivos , Análise de Regressão , Fumar , Inquéritos e Questionários
15.
Am J Med ; 107(6): 542-8, 1999 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-10625021

RESUMO

PURPOSE: Obesity in middle age is associated with an increased risk of osteoarthritis of the knees in later life. We sought to determine whether body mass index in young men was a risk factor for the subsequent development of osteoarthritis of the knee and hip. SUBJECTS AND METHODS: Body mass index was assessed in 1,180 male medical students at age 23 +/- 2 (mean +/- SD) years and at several times during follow-up. The incidence of knee and hip osteoarthritis was ascertained by self-report and corroborated with information on symptoms and radiographic findings. RESULTS: During a median follow-up of 36 years, 62 participants developed knee osteoarthritis and 27 developed hip osteoarthritis. The incidence of knee, but not hip, osteoarthritis was strongly associated with body mass index assessed at ages 20 to 29 years and 30 to 39 years (both P <0.001). For body mass index assessed at ages 20 to 29 years, the incidence of knee osteoarthritis at age 65 years was 12.8% among the heaviest subjects (range 24.7 to 37.6 kg/m2), threefold greater than the incidence of 4.0% in the leanest (15.6 to 22.8 kg/m2) category of body mass index (P = 0.0001). Thus, for a man who was 180 cm (5'11") tall, each 8 kg (18 lb) greater weight at ages 20 to 29 years was associated with an increased risk of subsequent knee osteoarthritis (relative risk = 1.7, 95% confidence interval 1.3 to 2.1), after adjustment for year of birth, physical activity, and knee injury. Body mass index at ages 20 to 29 years was more predictive of future osteoarthritis than at ages 30 to 39 or 40 to 49 years. CONCLUSION: Greater body mass index in young men ages 20 to 29 years is associated with an increased risk of subsequent knee, but not hip, osteoarthritis, suggesting that cumulative exposure to greater weight during young adult life is an important cause of osteoarthritis.


Assuntos
Índice de Massa Corporal , Osteoartrite do Quadril/etiologia , Osteoartrite do Joelho/etiologia , Adulto , Idoso , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Risco , Estudantes de Medicina
16.
Am J Surg Pathol ; 25(7): 936-41, 2001 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11420466

RESUMO

The Muir-Torre syndrome (MTS) is an autosomal dominantly inherited disorder, characterized by visceral malignancies and sebaceous skin lesions. In a subset of MTS families the disease is due to an underlying DNA mismatch-repair defect. We have identified a MTS family whose spectrum of reported neoplasia included adenocarcinomas of numerous gastrointestinal sites, carcinomas of the endometrium, ovary and breast, papillary transitional cell carcinoma of the ureter, a range of cutaneous tumors, as well as keratoacanthomas. All tumors were tested for microsatellite instability and immunohistochemically stained for expression of MLH1 and MSH2 proteins. All tumors were found to be microsatellite unstable and lacking in MSH2 protein expression. The subsequent mutation detection focused on hMSH2, and a germline mutation was identified (CAA-->TAA, Gln-->STOP, codon 337). This mutation was subsequently found in a family member with a single skin lesion only. We propose that the combination of immunohistologic and microsatellite instability analysis can be exploited to screen individuals with characteristic skin lesions even before development of visceral tumors and to direct the subsequent germline mutation search. The profile of microsatellite instability and the genes rendered dysfunctional differed between tumor samples, suggesting that the molecular pathogenesis varied between lesions, despite a common germline mutation.


Assuntos
Proteínas de Ligação a DNA , Síndromes Neoplásicas Hereditárias/diagnóstico , Síndromes Neoplásicas Hereditárias/genética , Neoplasias das Glândulas Sebáceas/diagnóstico , Neoplasias das Glândulas Sebáceas/genética , Adulto , Feminino , Mutação em Linhagem Germinativa/genética , Humanos , Imuno-Histoquímica , Masculino , Repetições de Microssatélites , Pessoa de Meia-Idade , Proteína 2 Homóloga a MutS , Síndromes Neoplásicas Hereditárias/terapia , Linhagem , Valor Preditivo dos Testes , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Neoplasias das Glândulas Sebáceas/terapia , Vísceras
17.
J Med Chem ; 18(3): 272-5, 1975 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-1169322

RESUMO

The following new 2,4-diamino-6-methylpyrimidines, 5-cyclohexylmethyl, 5-cyclohexylethyl,and 5-(2-naphthyl), as well as 2,6-diaminopurines, 8-adamantyl and8-adamantylmethyl, were synthesized as potential antifolates. Tese, as well as three known compounds, 2,4-diamino-5-cyclohexyl-6-methylpyrimidine, 2,4-diamino-5-(1-naphthyl) -6- methylpyrimidine, and 2,6-diaminopurine, were compared with respect to the inhibition of growth of mammalian cells in culture (TA 3) and with respect to the inhibition of partially purified dihydrofolate reductase. All of the pyrimidines except for the 5-(1maphthyl) derivative were competitive inhivitors of dihydrofolate reductase, with K values ranging from 0.07 to 0.04 pM. They were 2-5 times better as inhibitors of the isolated dihydrofolate reductase than of the cell growth. 2,4-Diamino-5-(1-naphthyl)-6-methylpyrimidine was a noncomptive inhivitor of the enzyme with a Kvalue of 56 pM. This compound was more potent in inhibiting cell growth than the isolated enzyme. indicating that its biological activity was not related to the inhibition of dihydrofolate reductse. All of the purine derivatives were poor growth inhibitors and although some of them inhibited isolated dihydrofolate reductase, their mode of action in cellular system did not seem to concern folate metabolism, as judged by the inability of hypoxanthine, and glycine to provide protection. The implication of these findings as to the structural requirements for inhibition of dihydrofolate reductase is discussed. The implication of these findings as to the structural requirements for inhibition of dihydrofolate reductase is discussed. The pitfalls of the determinition of ID-50 values instead of a complete kinetic analysis in structure-activity studies are emphasized.


Assuntos
Antagonistas do Ácido Fólico/síntese química , Purinas/síntese química , Pirimidinas/síntese química , Animais , Linhagem Celular , Células Cultivadas , Diaminas/síntese química , Diaminas/farmacologia , Antagonistas do Ácido Fólico/farmacologia , Neoplasias Mamárias Experimentais , Camundongos , Camundongos Endogâmicos , Purinas/farmacologia , Pirimidinas/farmacologia , Sarcoma 180/enzimologia , Relação Estrutura-Atividade
18.
Am J Cardiol ; 65(1): 1-5, 1990 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-2294675

RESUMO

The National Cholesterol Education Program treatment guidelines define a plasma total cholesterol of less than 200 mg/dl as "desirable" and recommend no further evaluation of plasma lipid or lipoprotein levels in patients with coronary artery disease (CAD). To determine the prevalence of dyslipidemias in the presence of coexistent CAD and total cholesterol less than or equal to 200 mg/dl, a retrospective case-control study of 1,000 patients who underwent diagnostic coronary angiography was performed. Of 351 patients with total cholesterol less than or equal to 200 mg/dl, 76% of the men (244) and 44% of the women (107) had angiographically demonstrated CAD. In men with CAD and total cholesterol less than or equal to 200 mg/dl, there was a significantly greater prevalence of low levels of high density lipoprotein (HDL) cholesterol (less than or equal to 35 mg/dl), age greater than 50 years, systemic hypertension and diabetes mellitus compared to non-CAD control subjects. In women with CAD and total cholesterol less than or equal to 200 mg/dl, HDL cholesterol less than or equal to 45 mg/dl and diabetes mellitus were also significantly prevalent. Multiple logistic regression analyses revealed that HDL cholesterol, hypertension and age in men and very low density lipoprotein cholesterol in women were significantly associated with CAD after adjustment for other risk factors. These results suggest that a complete lipid and lipoprotein analysis be obtained in all patients with CAD, irrespective of the plasma (or serum) total cholesterol level.


Assuntos
Colesterol/sangue , Doença das Coronárias/sangue , Lipídeos/sangue , Lipoproteínas/sangue , Adulto , Idoso , Estudos de Casos e Controles , Angiografia Coronária , Doença das Coronárias/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Risco
19.
Ann Epidemiol ; 3(4): 442-7, 1993 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-8275223

RESUMO

To determine the accuracy of self-reported risk factors in 78 physicians, self-reported information was compared to findings on a standardized examination. Measured weight (r = 0.98), height (r = 0.95), body mass index (r = 0.96), systolic blood pressure (SBP) (r = 0.72), and diastolic blood pressure (DBP) (r = 0.60) were highly correlated with self-reported values (all P < 0.0001). Mean self-reported SBP and DBP did not differ from measured values; measured weight was 1.5 kg greater and measured height 1.4 cm less than self-reported values (both p < 0.0001). Regression of measured on self-reported values indicated excellent agreement except for DBP and heart rate. Differences between measured and self-reported values were not associated with a variety of variables except for a greater difference in SBP at higher levels of SBP. None of the 60 self-reported nonsmokers had expired carbon monoxide levels greater than 10 ppm. These results indicate that physicians' self-reports of height, body mass index, SBP, and smoking are extremely accurate and suitable for research purposes.


Assuntos
Doenças Cardiovasculares/etiologia , Autorrevelação , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Fatores de Risco , Inquéritos e Questionários
20.
Ann Epidemiol ; 4(6): 425-33, 1994 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-7804496

RESUMO

We examined the risk of coronary heart disease (CHD) associated with coffee intake in 1040 male medical students followed for 28 to 44 years. During the follow-up, CHD developed in 111 men. The relative risks (95% confidence interval) associated with drinking 5 cups of coffee/d were 2.94 (1.27, 6.81) for baseline, 5.52 (1.31, 23.18) for average, and 1.95 (0.86, 4.40) for most recent intake after adjustment for baseline age, serum cholesterol levels, calendar time, and the time-dependent covariates number of cigarettes, body mass index, and incident hypertension and diabetes. Risks were elevated in both smokers and nonsmokers and were stronger for myocardial infarction. Most of the excess risk was associated with coffee drinking prior to 1975. The diagnosis of hypertension was associated with a subsequent reduction in coffee intake. Negative results in some studies may be due to the assessment of coffee intake later in life or to differences in methods of coffee preparation between study populations or over calendar time.


Assuntos
Café/efeitos adversos , Cardiopatias/epidemiologia , Adulto , Análise de Variância , Pressão Sanguínea/efeitos dos fármacos , Colesterol/sangue , Café/fisiologia , Fatores de Confusão Epidemiológicos , Relação Dose-Resposta a Droga , Seguimentos , Cardiopatias/induzido quimicamente , Humanos , Incidência , Masculino , Modelos de Riscos Proporcionais , Fatores de Risco , Fumar , Análise de Sobrevida
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