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1.
J Am Coll Cardiol ; 29(3): 519-25, 1997 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-9060887

RESUMO

OBJECTIVES: This study sought to correlate angiographically detected complex lesions and intracoronary thrombus with the severity of clinical presentation in unstable angina (UA). BACKGROUND: Unstable angina is usually related to acute thrombosis superimposed on a disrupted plaque. Complex and thrombotic lesions are more prevalent in UA and have been associated with a worse prognosis. The highest levels of the Braunwald classification of UA (III = rest angina within 48 h of presentation; C = postinfarction angina; and c = angina refractory to maximal medical therapy) can be used to assess the severity of clinical presentation, but they have not been directly correlated with thrombotic and complex lesions. METHODS: We conducted a prospective study of 284 patients with UA who underwent cardiac catheterization. A single angiographer with no knowledge of the clinical classifications interpreted all angiograms. Culprit lesions identified in 200 patients were classified as simple or complex. Complex lesions included the categories complex morphology, intracoronary thrombus (ICT) or total occlusion. Lesions were also quantitatively analyzed, and Thrombolysis in Myocardial Infarction (TIMI) flow was assessed. Univariate and multivariate logistic regression analyses of the angiographic findings were performed controlling for all cardiac risk factors, previous angioplasty or bypass surgery and multivessel disease, and we sequentially compared Braunwald classes III, C and c with classes < III, < C and < c, respectively. RESULTS: Class III was associated with complex lesions (p = 0.04) and decreased TIMI flow (p = 0.03). Class C angina correlated with complex lesions (p = 0.04), ICT (p = 0.005) and decreased TIMI flow (p = 0.03). Class c angina was associated with ICT (p = 0.02). The degree of stenosis by quantitative angiography was not associated with any particular Braunwald class. CONCLUSIONS: Recent rest pain and refractory or postinfarction UA, or both, are strongly associated with the general category of complex lesions and specifically with angiographically detected ICT and decreased TIMI flow.


Assuntos
Angina Instável/diagnóstico , Idoso , Angina Instável/complicações , Angina Instável/fisiopatologia , Circulação Coronária , Trombose Coronária/complicações , Trombose Coronária/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
2.
J Am Coll Cardiol ; 34(3): 663-71, 1999 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10483945

RESUMO

OBJECTIVES: The study evaluated the incidence and predictors of creatine kinase-MB isoenzyme (CK-MB) elevation after successful coronary intervention using current devices, and assessed the influence on in-hospital course and midterm survival. BACKGROUND: The CK-MB elevation after coronary intervention predominantly using balloon angioplasty correlates with late cardiac events of myocardial infarction (MI) and death. Whether CK-MB elevation after nonballoon devices is associated with an adverse short and midterm prognosis is unknown. METHODS: The incidence and predictors of CK-MB elevation after coronary intervention were prospectively studied in 1,675 consecutive patients and were followed for in-hospital events and survival. RESULTS: CK-MB elevation was detected in 313 patients (18.7%), with 1-3x in 12.8%, 3-5x in 3.5% and >5x normal in 2.4% of patients. Procedural complications or electrocardiogram changes occurred in only 49% of the CK-MB-elevation cases; CK-MB elevation was more common after nonballoon devices (19.5% vs. 11.5% after percutaneous transluminal coronary angioplasty; p < 0.01). Predictors of CK-MB elevation on multivariate analysis were diffuse coronary disease (p = 0.02), systemic atherosclerosis (p = 0.002), stent use (p = 0.04) and absence of beta-blocker therapy (p = 0.001). Adverse in-hospital cardiac events were more frequent in patients with >5x CK-MB elevation, with no significant difference between 1-5x CK-MB elevation versus normal CK-MB group. During a mean follow-up of 13 +/- 3 months, the incidence of death in the CK-MB-elevation group was 1.6% versus 1.3% in the normal CK-MB group (p = NS). CONCLUSIONS: The CK-MB elevation after coronary intervention was observed even in the absence of discernible procedural complications and was more common in patients with diffuse atherosclerosis. In-hospital clinical events requiring prolonged monitoring were higher in >5x CK-MB-elevation patients only. Midterm survival of CK-MB-elevation patients was similar to those with normal CK-MB. Our prospective analysis shows a lack of adverse in-hospital cardiac events and suggests that early discharge of stable 1-5x normal CK-MB-elevation patients after successful coronary intervention is safe.


Assuntos
Angioplastia Coronária com Balão , Ensaios Enzimáticos Clínicos , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/terapia , Creatina Quinase/sangue , Alta do Paciente , Idoso , Angioplastia Coronária com Balão/efeitos adversos , Angioplastia Coronária com Balão/instrumentação , Angioplastia Coronária com Balão/métodos , Aterectomia Coronária/efeitos adversos , Ensaios Enzimáticos Clínicos/estatística & dados numéricos , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/mortalidade , Eletrocardiografia , Feminino , Seguimentos , Humanos , Isoenzimas , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Estudos Prospectivos , Segurança , Stents , Fatores de Tempo
3.
Arch Intern Med ; 151(11): 2201-5, 1991 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-1953223

RESUMO

Meaningful comparison of patient outcomes requires an assessment of the severity of illness for the patients being compared. The more severe the underlying illness, the worse the expected outcome. We studied several severity of illness indicators derived from different methodologies in a medical intensive care unit. We compared the Acute Physiologic and Chronic Health Evaluation II, the accepted benchmark indicator for intensive care units, with one complex indicator, Computerized Severity Score, and three simpler indicators, Comorbidity, McCabe-Jackson, and American Society of Anesthesiologists. We found that all correlated well with a comorbidity index. We conclude that the Acute Physiologic and Chronic Health Evaluation II, the Computerized Severity Score, and the McCabe-Jackson scoring systems appear to be comparable predictors of comorbidity in a medical intensive care unit. Selection of a severity indicator will depend on the resources available and the intended uses.


Assuntos
Comorbidade , Unidades de Terapia Intensiva/estatística & dados numéricos , Índice de Gravidade de Doença , Idoso , Infecção Hospitalar/epidemiologia , Estudos de Avaliação como Assunto , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , New Jersey , Avaliação de Resultados em Cuidados de Saúde , Estudos Prospectivos
4.
Arch Intern Med ; 148(3): 559-61, 1988 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-3341856

RESUMO

We observed an influenza epidemic caused by influenza A/Arizona/82 (H3N2) in a nursing home during 1982 to 1983. A survey indicated that 59% of the residents were immunized before the outbreak. The outbreak was observed to begin in November, peak in February, and disappear in April. A significant level of herd immunity may have accounted for the slow progression through the nursing home. In addition, serologic evidence of concurrent infection with respiratory syncytial virus, parainfluenza virus, and Mycoplasma pneumoniae was present in many residents. Epidemics of influenza in a closed, partially immunized population in a nursing home may proceed at a slower rate than in an open, largely unimmunized community. By monitoring for infection with other respiratory agents, the complex nature of the outbreak in this nursing home became evident.


Assuntos
Surtos de Doenças , Instituição de Longa Permanência para Idosos , Influenza Humana/epidemiologia , Casas de Saúde , Infecções Respiratórias/epidemiologia , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antibacterianos/análise , Testes de Inibição da Hemaglutinação , Humanos , Influenza Humana/imunologia , Influenza Humana/prevenção & controle , Estudos Prospectivos , Vacinação
5.
Arch Intern Med ; 148(3): 562-5, 1988 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-3341857

RESUMO

We prospectively studied the efficacy of influenza vaccine during an influenza A/Arizona/80 (H3N2) outbreak at the Jewish Home and Hospital for the Aged in New York in the winter season of 1982 to 1983. All patients had been offered influenza vaccine before the outbreak; 181 chose to be vaccinated and 124 refused vaccination but agreed to participate in the study. Among those with serologic evidence of influenza infection, respiratory illness was significantly more common in the unvaccinated group (six of 14 vs one of 22). The overall mortality was 13 (7.2%) of 181 in the vaccinated group and 22 (17.7%) of 124 in the control group. The vaccinated and the control groups were examined for comparability. A logistic regression analysis, which controlled for differences in sex and level of nursing care, indicated that the difference in mortality was still significant, with a summary odds ratio of 2.7. The relative risk of death in the unvaccinated group was comparable at 2.18. Influenza vaccine reduced the mortality by 59% in the vaccinated group compared with the control group.


Assuntos
Surtos de Doenças , Imunização , Influenza Humana/mortalidade , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/análise , Instituição de Longa Permanência para Idosos , Humanos , Influenza Humana/epidemiologia , Influenza Humana/imunologia , Influenza Humana/prevenção & controle , Casas de Saúde , Estudos Prospectivos
6.
J Bone Miner Res ; 11(11): 1801-7, 1996 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-8915789

RESUMO

Skeletal involvement is a major source of complications in patients with Type 1 Gaucher disease. To investigate the bone density and potential usefulness of bone densitometry in Gaucher disease, dual-energy X-ray absorptiometry was used to measure the density of the lumbar spine, femoral neck, trochanter, and distal radius in 61 adult patients ranging in age from 22 to 77 years. The mean bone density at each site was significantly lower than expected for age and sex. The severity of the osteopenia correlated significantly with other clinical indicators of disease severity, including the N370S/84GG genotype, prior splenectomy, and hepatomegaly. The bone density measurements also correlated significantly with the severity of skeletal disease as assessed by skeletal radiography. Vertebral density remained an independent predictor of the severity of bone involvement even after controlling for age, sex, weight, genotype, splenectomy, and hepatomegaly. These findings suggest that bone density measurements provide a quantitative assessment of bone involvement in Type 1 Gaucher disease, which may permit serial, noninvasive monitoring of bone changes in this progressive disorder.


Assuntos
Envelhecimento/fisiologia , Densidade Óssea/fisiologia , Doença de Gaucher/fisiopatologia , Absorciometria de Fóton , Adulto , Idoso , Peso Corporal/fisiologia , Feminino , Fêmur/diagnóstico por imagem , Colo do Fêmur/diagnóstico por imagem , Antebraço/diagnóstico por imagem , Doença de Gaucher/diagnóstico por imagem , Genótipo , Humanos , Fígado/patologia , Vértebras Lombares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Distribuição por Sexo , Baço/patologia , Esplenectomia
7.
J Bone Miner Res ; 7(10): 1181-9, 1992 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-1456086

RESUMO

The disparity in fracture incidence and bone mass in women of European (white) and African (black) ancestry is of unknown etiology. To determine if racial differences in bone mass reflected racial differences in the mechanisms of bone turnover underlying bone mineral loss, we measured serum osteocalcin, serum alkaline phosphatase, fasting urinary calcium and hydroxyproline excretion, 24 h urinary excretion of calcium and sodium, and dietary intakes of calcium and vitamin D in 263 healthy pre-, peri-, and postmenopausal white and black women. In addition, radial and spinal bone density were measured cross-sectionally for comparison with biochemical measures of bone turnover. The biochemical parameters thought to reflect bone resorption (fasting urinary calcium and hydroxyproline excretions) were lower in black than in white women throughout the age and menopausal stages studied. The parameters thought to reflect bone formation (alkaline phosphatase and osteocalcin), were similar in the two racial groups among the premenopausal women, but osteocalcin was significantly lower among the peri- and postmenopausal blacks. Cross sectionally measured radial bone density increased with age in premenopausal black women, but it did not change with age in the white premenopausal subjects, a statistically significant difference. In peri- and postmenopausal women radial density declined significantly with years after menopause in both racial groups, but the rate of decline was significantly slower in the black women. Lumbar bone density in premenopausal white and black women did not change with age. After menopause lumbar bone density declined significantly and similarly in both racial groups.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
População Negra , Densidade Óssea , Osso e Ossos/metabolismo , Menopausa , População Branca , Adulto , Idoso , Fosfatase Alcalina/sangue , Cálcio/urina , Feminino , Homeostase , Humanos , Hidroxiprolina/urina , Vértebras Lombares , Pessoa de Meia-Idade , Osteocalcina/sangue
8.
J Clin Endocrinol Metab ; 81(8): 2948-56, 1996 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-8768857

RESUMO

Although bone loss occurs universally with age, the incidence of age-related osteoporotic fractures varies widely among ethnic groups. In the U.S., age-adjusted hip fracture incidence is 50% lower in African-American than in white women. Adult African-American women also have higher bone mass, but it is not known whether this difference is entirely due to higher peak bone mass or also results from slower rates of bone loss. Rates of bone loss were measured prospectively in 122 white and 121 African-American healthy, nonobese, pre- and postmenopausal women. Bone density was measured at 6-month intervals over a mean of 3-4 yr using single and dual photon absorptiometry of the forearm (cortical bone) and spine (trabecular bone). Similar rates of premenopausal bone loss were documented in both white and African-American women. However, in early menopause, bone loss was faster in the white women in the forearm (-2.4%/yr in whites vs. -1.2%/yr in African-Americans; P = 0.045), with a similar trend in the spine (-2.2%/yr in whites vs. -1.3/yr in African-Americans; P = 0.27). In women more than 5 yr postmenopause, the rates of bone loss did not differ by ethnic group. Our results indicate that the higher bone mass in African-American women is largely due to the attainment of a greater peak bone mass by early adulthood. However, slower rates of bone loss in the early postmenopausal period may also contribute to the higher bone density of older African-American women. Although bone loss occurs in both groups, there are ethnic differences in bone loss rates which indicate that data derived from white women cannot be simply extrapolated to nonwhite populations. Ethnic group-specific data on the determinants of bone homeostasis are needed.


Assuntos
População Negra , Osteoporose/etnologia , Osteoporose/metabolismo , População Branca , Adulto , Densidade Óssea , Feminino , Humanos , Estudos Longitudinais , Vértebras Lombares/metabolismo , Pessoa de Meia-Idade , Estudos Prospectivos , Rádio (Anatomia)/metabolismo
9.
J Clin Endocrinol Metab ; 74(3): 496-503, 1992 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-1740483

RESUMO

Clinical and epidemiologic observations, including the association of Graves' disease (GD) and Hashimoto's thyroiditis (HT) with the HLA gene complex, support a role for specific disease-related genes in the development of autoimmune thyroid disease (AITD). The combination of HLA and immunoglobulin heavy chain allotypes (Gm) has previously been reported to be predictive of AITD in multiply affected Japanese families. We have investigated the immunogenetics of AITD in families in the United States. Twenty-seven pedigrees including 15 with GD, 8 with HT, and 4 with both HT and GD were immunogenetically typed and analyzed for population and within family disease associations. The majority of families (63%) were multiplex for AITD. HLA-DR3 was increased in affected family members with GD and HLA-DR5 was increased in affected family members with HT. Formal linkage analysis was applied to test for coinheritance of disease with the HLA locus within families. The LIPED computer program was used to calculate the probability of linkage in terms of the lod score. Evidence from linkage analysis was consistently against linkage of either GD or HT to the HLA region under various penetrances and different modes of inheritance. The combination of HLA and Gm was not found to be predictive of disease in 7 selected multiplex families with multigenerational instances of AITD. T cell function was also examined in 3 pairs of siblings genetically identical for HLA and Gm but discordant for disease expression. We found no evidence of a global T cell defect in the small number of patients examined. We conclude that whereas there is an association of AITD with the HLA region, our linkage analysis demonstrates that alleles of the HLA region are not cosegregating with either GD or HT within these families. Thus, whereas HLA may increase susceptibility to AITD, as shown by the existence of an HLA association, the major genetic influence on the inheritance of AITD must be at another locus.


Assuntos
Doença de Graves/genética , Antígenos HLA/genética , Tireoidite Autoimune/genética , Linfócitos B/imunologia , Feminino , Ligação Genética , Doença de Graves/diagnóstico , Doença de Graves/imunologia , Antígenos HLA-DR/análise , Antígenos HLA-DR/genética , Antígenos de Histocompatibilidade Classe I/análise , Antígenos de Histocompatibilidade Classe I/genética , Humanos , Masculino , Linhagem , Valores de Referência , Linfócitos T/imunologia , Tireoidite Autoimune/diagnóstico , Tireoidite Autoimune/imunologia
10.
J Clin Endocrinol Metab ; 72(3): 703-10, 1991 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-1997523

RESUMO

The etiology of the racial disparity in bone mass and fracture rate is unknown. Since the PTH-vitamin D endocrine system is a major regulator of calcium metabolism and bone turnover, this cross-sectional study examined the relationship of radial and lumbar bone density to vitamin D metabolite and PTH concentrations and to calcium intake and excretion in 67 white and 70 black highly comparable, healthy, premenopausal women. Bone density at both radial and lumbar sites was higher in blacks than in whites. Serum 25-hydroxyvitamin D was slightly but not statistically significantly (P = 0.08), lower in blacks than in whites, but there were no racial differences in 1,25-dihydroxyvitamin D, PTH, or renal tubular maximum for reabsorption of phosphate. The mean 25-hydroxyvitamin D concentration in blacks was well within the normal range and was not associated with evidence of secondary hyperparathyroidism. There were no correlations of bone density to vitamin D or PTH concentrations. Although there were no racial differences in dietary intake of calcium and vitamin D or in sodium excretion, 24-h urinary calcium excretion was significantly lower in blacks than in whites, and calcium excretion was inversely associated with radial bone density. In contrast to previous reports, in healthy, normal weight, premenopausal black women there is no evidence of vitamin D deficiency or secondary hyperparathyroidism, suggesting that factors other than the vitamin D-PTH axis are responsible for racial differences in bone mass.


Assuntos
População Negra , Hormônio Paratireóideo/análise , Vitamina D/análise , População Branca , Adulto , Densidade Óssea , Cálcio da Dieta/administração & dosagem , Dieta , Proteínas Alimentares/administração & dosagem , Feminino , Humanos , Menopausa , Estado Nutricional , Fosfatos/administração & dosagem , Fatores Socioeconômicos , Vitamina D/administração & dosagem
11.
J Clin Endocrinol Metab ; 74(3): 645-53, 1992 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-1740500

RESUMO

Immune function in normal pregnancy and the postpartum period remains poorly defined. We hypothesized that a comparative study between pregnant women with normal and abnormal immune function would further our understanding of the immune mechanisms of pregnancy. We chose to study a cohort of pregnant women at risk for the development of postpartum thyroid dysfunction (PPTD) as well as a group of normal controls. We chose PPTD as the model for abnormal immune function because of the relative ease of monitoring disease development and the relatively high prevalence for PPTD reported in earlier studies. Five hundred and fifty-two women were screened for the presence of thyroid autoantibodies in the first trimester of pregnancy. Thirty-three thyroid autoantibody-positive women and 28 thyroid autoantibody-negative women were followed prospectively throughout pregnancy and 6 months into the postpartum period. Lymphocyte subset analyses, thyroid function tests, and thyroid autoantibodies (antihuman thyroglobulin and antithyroid peroxidase) were performed at defined intervals. All patients were HLA serotyped. Normal pregnancy was principally characterized by decreased CD4+ T-cells and increasing CD8+ T-cells, causing a significant fall in the CD4+/CD8+ ratio in late pregnancy and into the postpartum period. Women who developed PPTD had 1) a higher CD4+/CD8+ ratio (P = 0.04), 2) activation of T-cells in the postpartum period (P = 0.02), and 3) significantly higher thyroid autoantibody titers (antihuman thyroglobulin, P = 0.02; antithyroid peroxidase, P = 0.0018). We found an overall incidence for PPTD of 8.8%. These data demonstrated that women who were thyroid autoantibody positive in the first trimester of pregnancy had a one in three chance of developing PPTD. We observed a significant fall in the T-cell helper/suppressor ratio in normal pregnant women, which was associated with distinct T-cell subset changes. This pregnancy-initiated T-cell regulation reflected an overall suppression of immune function. The development of PPTD was a frequent postpartum event in our population and was associated with a triad of immune markers: a reduction in the normal immune suppression of pregnancy (as indicated by higher T-cell helper/suppressor ratios), enhanced postpartum T-cell activation, and elevated thyroid autoantibodies. The reduction in the degree of immune suppression was, therefore, a major factor in the development of PPTD. Our results define immunological changes that occur in normal pregnancy and distinct immunological abnormalities necessary for the development of PPTD.


Assuntos
Autoanticorpos/análise , Tolerância Imunológica , Gravidez/imunologia , Transtornos Puerperais/imunologia , Linfócitos T/imunologia , Doenças da Glândula Tireoide/imunologia , Glândula Tireoide/imunologia , Relação CD4-CD8 , Feminino , Humanos , Primeiro Trimestre da Gravidez , Estudos Prospectivos , Transtornos Puerperais/etiologia , Valores de Referência , Doenças da Glândula Tireoide/etiologia , Testes de Função Tireóidea , Glândula Tireoide/fisiologia , Tiroxina/sangue , Proteínas de Ligação a Tiroxina/análise
12.
Clin Pharmacol Ther ; 37(5): 589-96, 1985 May.
Artigo em Inglês | MEDLINE | ID: mdl-3987183

RESUMO

Meptazinol is an agonist-antagonist opioid analgesic believed to be unique in its selectivity for mu1 (high affinity) receptors and its cholinergic activity. Our objectives were to determine the relative analgesic potency of intramuscular meptazinol and morphine and to compare mood and side effects in 102 patients with cancer who have postoperative pain. Meptazinol (50, 100, and 200 mg) and morphine (4, 8, and 16 mg) were given for moderate to severe pain in a double-blind, randomized but balanced, incomplete block design. Serial multiple assessments of pain, relief, mood, and side effects were made. The most precise estimates of relative analgesic potency indicate that meptazinol is equivalent to 10 mg morphine at 120 mg (95% confidence interval 80 to 170 mg) for peak effect and at 175 mg (95% confidence interval 125 to 270 mg) for total effect. Mean (+/- SE) times to peak effect and to remedication were 0.9 +/- 0.1 and 3.6 +/- 0.2 hours for meptazinol and 1.4 +/- 0.1 and 4.8 +/- 0.4 hours for morphine at equianalgesic peak effects. The percentages of subjects with one or more side effects were 18, 49, and 73 for graded meptazinol doses and 32, 49, and 65 for graded morphine doses. Mean numbers of side effects per subject were 0.3, 1.5, and 3.5 for meptazinol and 0.5, 0.7, and 1.7 for morphine. Profiles of side effects differed. Mood improvement and overall satisfaction were dose related and greater for morphine than for meptazinol. Side effects may limit the use of meptazinol in doses that relieve severe postoperative pain.


Assuntos
Azepinas/uso terapêutico , Meptazinol/uso terapêutico , Morfina/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Adolescente , Adulto , Idoso , Relação Dose-Resposta a Droga , Método Duplo-Cego , Avaliação de Medicamentos , Emoções/efeitos dos fármacos , Feminino , Humanos , Injeções Intramusculares , Masculino , Meptazinol/efeitos adversos , Pessoa de Meia-Idade , Morfina/efeitos adversos , Distribuição Aleatória , Inquéritos e Questionários
13.
Clin Pharmacol Ther ; 44(3): 335-42, 1988 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-2458208

RESUMO

Ongoing interest in the improvement of pain management with opioid analgesics had led to the investigation of sublingual opioid absorption. The present report determined the percent absorption of selected opioid analgesics from the oral cavity of normal subjects under conditions of controlled pH and swallowing when a 1.0 ml aliquot of the test drug was placed under the tongue for a 10-minute period. Compared with morphine sulfate at pH 6.5 (18% absorption), buprenorphine (55%), fentanyl (51%), and methadone (34%) were absorbed to a significantly greater extent (p less than 0.05), whereas levorphanol, hydromorphone, oxycodone, heroin, and the opioid antagonist naloxone were not. Overall, lipophilic drugs were better absorbed than were hydrophilic drugs. Plasma morphine concentration-time profiles indicate that the apparent sublingual bioavailability of morphine is only 9.0% +/- 11.9% (SD) of that after intramuscular administration. In the same subjects the estimated sublingual absorption was 22.4% +/- 9.2% (SD), indicating that the sublingual absorption method may overestimate apparent bioavailability. When the oral cavity was buffered to pH 8.5, methadone absorption was increased to 75%. Thus, an alkaline pH microenvironment that favors the unionized fraction of opioids increased sublingual drug absorption. Although absorption was found to be independent of drug concentration, it was contact time dependent for methadone and fentanyl but not for buprenorphine. These results indicate that although the sublingual absorption and apparent sublingual bioavailability of morphine are poor, the sublingual absorption of methadone, fentanyl, and buprenorphine under controlled conditions is relatively high.


Assuntos
Analgésicos Opioides/farmacocinética , Boca/metabolismo , Administração Sublingual , Adulto , Analgésicos Opioides/administração & dosagem , Análise de Variância , Disponibilidade Biológica , Buprenorfina/farmacocinética , Fentanila/farmacocinética , Heroína/farmacocinética , Humanos , Hidromorfona/farmacocinética , Levorfanol/farmacocinética , Metadona/farmacocinética , Morfina/sangue , Morfina/farmacocinética , Naloxona/farmacocinética , Oxicodona/farmacocinética , Fatores de Tempo
14.
Cancer Epidemiol Biomarkers Prev ; 6(2): 105-12, 1997 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9037561

RESUMO

Inheritance of certain germ line haplotypes consisting of three biallelic polymorphisms of p53 has been proposed as a risk factor for breast cancer and colorectal cancer [A. Själander et al., Carcinogenesis (Lond.), 17: 1313-1316, 1996, and Carcinogenesis (Lond.), 16: 1461-1464, 1995]. In their studies, pairwise haplotypes of these three polymorphisms were estimated. Extended haplotypes were further projected from the pairwise combinations. To overcome the necessity to estimate pairwise and extended haplotype frequencies, a PCR method has been developed to determine the absolute extended p53 haplotypes in diploid genomes. The method requires allele-specific PCR, confirmed by restriction analysis, and successive amplicon analysis. It has been applied to a nested case-control study of breast cancer (284 subjects; 99 cases and 185 controls; 182 Caucasians, 56 Hispanics, and 46 African-Americans). Evidence is presented that minor variants of the intron 3, codon 72, and intron 6 polymorphisms were moderately elevated in Caucasian breast cancer cases (intron 3, P = 0.03 for genotype and P = 0.01 for allelic frequency; codon 72, P = 0.07 for genotype and P = 0.054 for allelic frequency; and intron 6, P = 0.02 for genotype and P = 0.02 for allele frequency). Accordingly, analysis of haplotype distributions suggested an association of minor p53 haplotypes with breast cancer risk in Caucasians (P = 0.07). The relative allelic frequencies in breast cancer cases compared with controls also differed by age and menopausal status; the 1-2-1 haplotype was overrepresented in postmenopausal cases (P = 0.02) and cases older than 50 years (P = 0.02), whereas the other minor haplotypes (1-1-2 and rare variants) were overrepresented in premenopausal cases (P = 0.003) and cases 50 years of age and younger (P = 0.02). Genotype distributions at each locus and for all control groups were consistent with Hardy-Weinberg equilibria. Differences in haplotype distribution were associated with ethnicity (Caucasians versus African-Americans and Caucasians versus Hispanics, P < 0.001). The new haplotyping method may be useful in the study of gene-environment interactions.


Assuntos
Neoplasias da Mama/etnologia , Neoplasias da Mama/genética , Frequência do Gene , Genes p53 , Adulto , Idoso , Estudos de Casos e Controles , Códon , Diploide , Etnicidade/genética , Feminino , Haplótipos , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo Genético , Grupos Raciais/genética , Fatores de Risco
15.
Pain ; 15(2): 191-200, 1983 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-6844027

RESUMO

Our objective was to identify and quantify sources of variation in the relief of chronic pain with morphine. Relief scores were extracted from records obtained during controlled trials of analgesics in cancer patients with chronic pain in which intramuscular morphine was the assay standard. Relief data from 715 patients after 565 8-mg and 538 16-mg doses were segregated according to age, race, sex, pre-drug pain intensity, character and site. Middle-aged patients obtained relief after 8 mg comparable to relief obtained by younger patients after 16 mg; oldest patients obtained relief after 8 mg comparable to relief obtained by middle-aged patients after 16 mg. Blacks receiving 8 mg obtained relief comparable to whites receiving 16 mg. Sex-related differences were not significant. Patients with moderate, as compared to severe, pre-drug pain obtained significantly greater relief only after 16 mg. Patients reporting dull pain obtained relief after 8 mg comparable to relief obtained with sharp pain after 16 mg. Patients with abdominal pain obtained relief after 8 mg comparable to relief of pain in the chest or arms after 16 mg. These results provide dose-related evidence of variation in relief with morphine in chronic cancer pain and establish particular patient and pain characteristics as variables for which controls should be provided in analgesic assays.


Assuntos
Morfina/uso terapêutico , Neoplasias/fisiopatologia , Dor/tratamento farmacológico , Adolescente , Adulto , Fatores Etários , Idoso , Analgesia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
16.
Pediatrics ; 77(2): 158-66, 1986 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-3753759

RESUMO

Preterm infants of normal birth weight (born before 37 completed weeks of gestation and weighing more than 2,250 g) experience a neonatal mortality risk almost four times higher than do term infants in the same weight range. In an analysis of the effect of hospital level of birth on neonatal mortality, such preterm normal weight infants were found to experience higher mortality if born outside of a Level 3 (tertiary care) center. For all singleton infants in this weight-gestation category born in New York City maternity services during a 3-year period (N = 23,257), the relative mortality risk for Level 1 births (compared with Level 3) was 1.72 (P less than .01) and for Level 2 births 1.47 (P less than .05). The excess mortality at Level 1 and Level 2 units was almost entirely due to a more than twofold higher death rate in black infants born in these units. Several potentially confounding socioeconomic, demographic, and biologic variables entered into a logistic regression model could not account for the higher mortality rates for black infants born in Level 1 and Level 2 units. Among black infants born at Level 1 units, deaths in preterm normal birth weight infants were less likely to occur in a receiving tertiary care center than were either deaths in low birth weight infants or deaths in term normal weight infants, suggesting that the need for special care of preterm normal birth weight infants is underestimated in some hospitals without newborn intensive care units.


Assuntos
Recém-Nascido Prematuro , Análise de Variância , Peso ao Nascer , Feminino , Idade Gestacional , Hospitais , Humanos , Cuidado do Lactente , Mortalidade Infantil , Recém-Nascido , Cidade de Nova Iorque , Complicações do Trabalho de Parto , Gravidez , Complicações na Gravidez , Encaminhamento e Consulta , Fatores Socioeconômicos
17.
Am J Cardiol ; 79(4): 505-8, 1997 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-9052361

RESUMO

The purpose of this study was to assess several indexes of cardiovascular risk in men and women with moderate to severe hypertension. We found that women with moderate and severe hypertension have lower ambulatory blood pressure and less cardiac hypertrophy than men with similar clinic blood pressure.


Assuntos
Pressão Sanguínea , Hipertensão/fisiopatologia , Assistência Ambulatorial , Catecolaminas/sangue , Colesterol/sangue , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Hipertensão/sangue , Hipertensão/complicações , Hipertrofia Ventricular Esquerda/complicações , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores Sexuais
18.
Leuk Res ; 18(8): 565-7, 1994 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-8065158

RESUMO

We and others have reported an increased incidence of chronic lymphocytic leukemia (CLL) among Ashkenazi (ASH) Jews of European origin. We performed HLA Class I typing on all 50 CLL patients seen by us and compared them with 3886 controls consisting of healthy blood donors from the New York Blood Center. Thirty of our CLL patients were ASH Jews, 17 of whom (57%) expressed the B35 antigen compared with 462 ASH controls (26%). Seven (39%) of the CLL Caucasian patients expressed the B35 antigen compared with 305 (14.5%) of the Caucasian controls. Combining the information from the ASH Jews and the Caucasians the difference is highly significant, (p = 0.0001). The summary odds ratio was 3.7. These results indicate an increased incidence of the antigen B35 amongst ASH and Caucasian patients with CLL.


Assuntos
Antígeno HLA-B35/análise , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Europa Oriental/etnologia , Feminino , Humanos , Incidência , Judeus , Masculino , Pessoa de Meia-Idade , New York/epidemiologia , Razão de Chances , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/etnologia , População Branca
19.
J Thorac Cardiovasc Surg ; 107(5): 1323-32; discussion 1332-3, 1994 May.
Artigo em Inglês | MEDLINE | ID: mdl-8176976

RESUMO

Because improved understanding of the natural history of thoracic aneurysms would enhance our ability to determine in which cases the risk of surgical treatment is justified, the rate of enlargement of thoracic aneurysms and thoracoabdominal aneurysms was studied in 67 patients by means of serial computer-generated three-dimensional reconstructions of computed tomographic scans. Patients were followed for a mean of 1.5 +/- 0.15 years (0.2 to 5.35 years) with an average interval between examinations of 0.9 +/- 0.1 year (0.2 to 5.0 years). Thirty-nine patients continue to be followed; 7 were lost to follow-up; 14 died during follow-up (4 after aneurysm rupture), and 10 underwent an operation. Indications for operation included the presence of pain, an absolute aortic diameter larger than 8 cm, an increase in aortic diameter of more than 1 cm per year, or marked irregularity of aneurysm contour. Aortic diameter and volume data were generated from the aortic silhouette obtained by tracing each computed tomographic slice with a translucent digitizing tablet. Estimated change in aortic diameter after 1 year was 0.43 cm; estimated change in aortic volume was 88.1 ml. The impact of possible risk factors on the enlargement of aneurysms was examined by analysis of variance (p < 0.05). A significantly higher rate of aneurysm expansion was found in patients with a larger aortic diameter (> 5 cm) at diagnosis (change in diameter = 0.17 cm versus 0.79 cm; change in volume = 40 ml versus 141.8 ml), and in smokers (change in diameter = 0.35 cm versus 0.70 cm; change in volume = 78.3 ml versus 120.8 ml). Changes in diameter and volume for aneurysms of different initial diameters and volumes was predicted by exponential regression by the equations: change in diameter = 0.0167 (initial aortic diameter)2.1; change in volume = 0.0356 (initial aortic volume)1.322. No correlation was noted between the rate of enlargement and age, sex, or the presence of dissection. A history of hypertension correlated with a greater aortic diameter at diagnosis but did not significantly affect the rate of enlargement.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Aneurisma da Aorta Torácica/diagnóstico por imagem , Processamento de Imagem Assistida por Computador , Tomografia Computadorizada por Raios X/métodos , Idoso , Análise de Variância , Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/epidemiologia , Aneurisma da Aorta Torácica/cirurgia , Ruptura Aórtica/epidemiologia , Feminino , Seguimentos , Humanos , Tábuas de Vida , Masculino , Fatores de Risco , Fatores de Tempo
20.
Int J Epidemiol ; 23(6): 1185-9, 1994 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-7721521

RESUMO

BACKGROUND: The extent to which clusters of attempted suicides occur is a significant problem that is complementary to the current available research on the clustering of completed suicide. However, little systematic research on clusters of attempted suicides exists. The present study examines the extent and nature of clustering of suicide attempts. METHOD: The occurrence of clustering of attempted suicide was examined in nationwide data for all New Zealand hospitals, obtained from the New Zealand Health Statistics Services for the years 1988-1990. The Scan statistic and Knox procedure were employed for testing the significance of clusters in time and time-space, respectively. RESULTS: The analyses indicated that significant time clustering occurred in younger age groups, specifically among 15-19 and 20-24 year olds. The results could not be accounted for by seasonal variations in admissions. Age specificity of time-space clusters emerged, exhibiting a similar pattern to that reported for completed suicides in the US. CONCLUSIONS: The results suggest a similar underlying mechanism for the clustering of parasuicide and completed suicides and provide support for the existence of contagion of suicidal behaviour. The implications for prevention are discussed.


Assuntos
Sistema de Registros , Tentativa de Suicídio/estatística & dados numéricos , Adolescente , Adulto , Distribuição por Idade , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nova Zelândia/epidemiologia , Conglomerados Espaço-Temporais , Tentativa de Suicídio/tendências , Estatísticas Vitais
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