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Biomedical subjects

L Bernstein

Publications and source records attributed to L Bernstein.

At least 109 records · Page 6Linked to original sources

Mechanism and significance of precordial ST-segment depression during inferior wall acute myocardial infarction associated with severe narrowing of the dominant right coronary artery.

The mechanism and significance of precordial ST depression during inferior wall acute myocardial infarction (AMI) is debated. This study assessed the location and extent of arterial perfusion distribution responsible for this electrocardiographic finding. Intracoronary thallium-201 was injected in 11 patients with 1-vessel right coronary disease to delineate perfusion distribution that was quantitated by a new angiographic distribution score. The angiographic score correlated with posterior (r = 0.84), posterolateral (r = 0.88) and total (r = 0.73) extent of intracoronary thallium distribution. The angiographic distribution score was related to electrocardiographic changes in 16 patients showing an inferior ST-segment elevation during angioplasty (7 with and 9 without precordial ST depression), of which 6 received intracoronary thallium injection. None had thallium distribution in the anterior or septal segment, but there was a trend toward a greater angiographic distribution score and posterior segment thallium score in patients with precordial ST depression. In another 77 patients with inferior wall AMI due to right coronary occlusion (24 with concomitant left anterior descending narrowing), precordial ST depression was present in 16 with and 31 without left anterior descending narrowing (p = NS). The angiographic distribution score was higher in those with than without precordial ST depression (0.59 +/- 0.10 vs 0.44 +/- 0.11, p < 0.001) in both patients with and without left anterior descending disease. The magnitude of both inferior ST elevation and precordial ST depression correlated with the angiographic distribution score, but only precordial ST depression was independently related in multivariate analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Angiography↗

Epstein-Barr virus-associated non-Hodgkin's lymphoma in patients infected with the human immunodeficiency virus.

Lymphoproliferations associated with Epstein-Barr virus (EBV) commonly arise in settings of immune dysfunction, including human immunodeficiency virus (HIV) infection. In this study, EBV was associated with 39 of 59 (66%) HIV-related systemic lymphomas. Unlike the lymphoproliferations that arise in the setting of transplantation, the HIV-related lymphomas were monoclonal, as evaluated by Ig heavy chain rearrangements and EBV termini analysis, and associated (40%) with c-MYC rearrangements. Furthermore, analysis of multiple lymphoma tissues from one autopsy showed evidence that a single lymphoma clone was responsible for dissemination. The latent EBV nuclear antigen (EBNA-1) transcripts detected in the HIV-related lymphomas were characteristic of the pattern found in Burkitt lymphoma (g1 EBNA1) and not in transplant-related lymphoproliferations. However, unlike Burkitt lymphoma, EBV latent membrane-associated protein (LMP) transcripts were also detected, thereby constituting an EBV expression pattern (g1 EBNA1+, LMP+) not previously observed in B-cell lymphomas. These findings demonstrate a high frequency of EBV-associated lymphomas in the setting of HIV infection that are distinct from the lymphoproliferations that arise during iatrogenic transplant-associated immuno-suppression or in the general population. However, it is also apparent that HIV-related lymphomas are biologically heterogeneous, which may reflect the multiple mechanisms or steps necessary for eventual malignant transformation.

Antigens, Viral↗

Racial differences in risk of oral and pharyngeal cancer: alcohol, tobacco, and other determinants.

BACKGROUND: In the United States, Blacks have increasingly higher rates of oral and pharyngeal cancer (oral cancer) than Whites, but determinants of the racial disparity have not been clear. PURPOSE: The purpose of this study was to explore reasons for the higher incidence of oral cancer among Blacks than Whites. METHODS: We used data from a large, population-based case-control study of oral cancer risk factors conducted in four areas of the United States. On the basis of interviews that ascertained characteristics of 1065 oral cancer patients (871 Whites and 194 Blacks) and 1182 controls (979 Whites and 203 Blacks), we examined racial differences in exposure prevalences and relative risks for a number of known etiologic factors, including tobacco and alcohol consumption, diet, and socioeconomic and other variables. To evaluate the extent to which the major risk factors explained the excess risk of oral cancer among Blacks, population-attributable risks were calculated. RESULTS: Differences with respect to alcohol consumption, especially among current smokers, emerged as the most important explanatory variables. After adjusting for smoking, heavy drinking (> or = 30 drinks/week) resulted in a 17-fold increased risk among Blacks and a ninefold increase among Whites. Among drinkers, Blacks tended to drink more than Whites. Also, a higher (P = .01) percentage of Blacks (37%) than Whites (28%) were current smokers, although there were little or no racial differences in relative risks or patterns of use for other smoking variables, including number of cigarettes smoked per day, years of smoking, and age started smoking. From population-attributable risk calculations, we estimated that differences in alcohol and tobacco use account for the bulk of the higher incidence of oral cancer among Blacks in the United States and that, in the absence of alcohol and tobacco, the rates of this cancer according to race (Black, White) and gender would be nearly equal. With regard to other potential etiologic factors, protective effects provided by higher dietary intake of fruits and vitamin C were more pronounced for Whites, while Blacks more often tended to be in sociodemographic and medical or dental health categories associated with increased risk. CONCLUSIONS: These analyses provide evidence that various environmental or lifestyle determinants of oral cancer may contribute to the higher oral cancer rates in Blacks than in Whites in the United States, but that patterns and risks associated with alcohol consumption, particularly among current smokers, are the most important contributors to the excess risk in Blacks. IMPLICATIONS: These findings suggest that the key to prevention of oral and pharyngeal cancers among both Blacks and Whites is reduced intake of alcoholic beverages and, because of strong interactive effects, the cessation of smoking.

Adult↗

Comparison of target organs of carcinogenicity for mutagenic and non-mutagenic chemicals.

A comparison of target organs for mutagens and non-mutagens is presented for 351 rodent carcinogens in the Carcinogenic Potency Database (CPDB) with mutagenicity evaluations in Salmonella. Results are consistent with the hypotheses that in high-dose rodent tests mitogenesis is important in the carcinogenic response for mutagens and non-mutagens alike, and that mutagens have a multiplicative interaction for carcinogenicity because they can both damage DNA directly and cause cell division at high doses. These hypotheses would lead one to expect several results that are found in the analysis: First, a high proportion of both mutagens and non-mutagens induce tumors in rodent bioassays at the MTD. Second, mutagens compared to non-mutagens are: (a) more likely to be carcinogenic; (b) more likely to induce tumors at multiple target sites; and (c) more likely to be carcinogenic in two species. Among carcinogens that induce tumors at multiple sites in both rats and mice, 81% are mutagens; in comparison, among carcinogens that are positive at only a single target site in one species and are negative in the other, 42% are mutagens. Since tissue distribution and pharmacokinetics would not be expected to differ systematically between mutagens and non-mutagens, one would not expect systematic differences in the particular organs in which tumors are induced. Results do not support the idea that mutagens and non-mutagens induce tumors in different target organs. Both mutagens and non-mutagens induce tumors in a wide variety of sites, and most organs are target sites for both. Moreover, the same sites tend to be the most common sites for both: 79% or more of both mutagenic and non-mutagenic carcinogens are positive in each species in at least one of the 8 most frequent target sites: liver, lung, mammary gland, stomach, vascular system, kidney, hematopoietic system and urinary bladder. Species differences are discussed as well as results for particular target organs: liver, Zymbal's gland and kidney.

Animals↗

Cytogenetic studies of composite lymphomas: monocytoid B-cell lymphoma and other B-cell non-Hodgkin's lymphomas.

Monocytoid B-cell lymphoma (MBCL) is a newly recognized, morphologically and immunologically distinct, low-grade B-cell neoplasm that may exist as a pure morphologic entity or as a component of a composite lymphoma. To determine whether cytogenetic abnormalities exist in cases of MBCL, fresh tissue from four lymphoma specimens in which MBCL was a substantial component were analyzed by classic cytogenetics; no pure MBCL cases were available for study. One monoclonal neoplastic population was found in each case by immunophenotyping studies and classic cytogenetics. Clonal cytogenetic abnormalities included -X or +X, t(14;18)(q32;q21), del(6q), t(11;14)(q13;q32), dup(12q), dup(1q), t(2;3)(q13;q29), and der(8)t(8;9)(p11.2;q13). The abnormal clone usually reflected the underlying lymphomatous process, namely, follicular lymphoma [t(14;18)], mantle cell lymphoma [t(11;14)], or small lymphocytic lymphoma (partial trisomy 12). There were no cytogenetic abnormalities common to all neoplasms. Taken together, the cytogenetic and immunologic data suggest that although MBCL may exist as a pure entity, it also may commonly represent a morphologic variant or a component of other primary lymphomatous processes.

Adult↗

Angle versus Case.

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History, 19th Century↗

Prevalence of human immunodeficiency virus types 1 and 2 infections in Nigeria.

The prevalence of human immunodeficiency virus (HIV) types 1 and 2 infections in Nigeria was estimated from 3854 serum samples collected at 21 locations from 1985 to 1990. Seventy-eight samples (2.0%) were reactive for HIV-1 and 49 (1.3%) for HIV-2 antibodies; 5 samples were reactive for both viruses. The prevalence of HIV-1 and -2 infections, respectively, was highest among 60 female prostitutes, with 10% and 6.7% positive. For other groups the respective rates of positivity were 4.1% and 3.4% in 610 patients with sexually transmitted diseases, 3.6% and 1.4% in 140 tuberculosis patients, 1.6% and 0.6% of 1253 other medical patients, and 1.2% and 0.9% of 1640 volunteer blood donors. Of 153 health care workers, 1.3% were positive for HIV-1 only. The age group from 20 to 29 years had the highest prevalences of HIV-1 (3.3%) and -2 (2.2%). In Nigeria, antibody prevalence for both viruses appears to have increased > 10-fold between 1986 and 1990.

Adolescent↗

Endogenous hormones and breast cancer risk.

There is substantial evidence that high estrogen levels in postmenopausal women are associated with an increase in breast cancer risk, but such a relation has not yet been established in premenopausal women, despite biologic evidence that breast epithelial cell division rates are high during the luteal phase of the menstrual cycle when estradiol and progesterone levels are high. The lack of total consistency among studies that have assessed estrogen differences, whether in breast cancer patients versus controls or in subgroups of the population characterized by different risk profiles for breast cancer, is not unexpected given the extraordinarily complex methodological issues that must be addressed in these studies. There has been a clear evolution over time in the level of sophistication of these types of studies, further decreasing the likelihood of finding consistent patterns in the literature. Other hormones may play an important role in breast cancer development as well. Experimental data are particularly compelling for a role of progesterone and prolactin, but hormonal studies in women are not entirely convincing regarding the role of these two hormones, nor is the literature nearly as extensive as it is for the estrogens. Studies of various androgens are even less consistent. Moreover, such studies suffer from a lack of precise hypotheses regarding how these hormones might directly alter risk.

Breast Neoplasms↗

The epidemiology of AIDS-related malignancies.

Immunosuppression resulting from HIV infection does not explain the unique distribution of Kaposi's sarcoma across risk groups. A majority of cases occur among homosexual men, particularly those with oral-anal contact, those with sexual contacts in high-risk cities, and those frequently use nitrite inhalants, suggesting a currently unidentified etiologic cofactor. Risk of non-Hodgkin's lymphoma among HIV-infected persons continues to increase over time. Because all HIV-infected groups are at high risk of non-Hodgkin's lymphoma, environmental cofactors may be less important in the disease's etiology. Because data on risk factors for AIDS-related non-Hodgkin's lymphoma are limited, further studies are needed. Cohort studies suggested that the risk of Hodgkin's disease is greater among HIV-infected persons; however, the number of cases reported has been small. Hodgkin's disease occurring among HIV-infected persons is more aggressive than and differs in presentation from that among noninfected persons. The addition of invasive cervical cancer to the US Centers for Disease Control definition of AIDS is based on data showing that HIV-infected women have a high prevalence of cervical disease. Although no conclusions can yet be drawn regarding the temporal relationship of cervical disease and HIV infection, there is evidence of a direct relationship between the degree of HIV-induced immunosuppression and the extent of cervical disease. Other cancers are being diagnosed among AIDS patients, and monitoring of the risk of solid tumors among various cohorts of high-risk and HIV-infected persons continues.

Acquired Immunodeficiency Syndrome↗

Prior medication use and health history as risk factors for non-Hodgkin's lymphoma: preliminary results from a case-control study in Los Angeles County.

To determine whether non-Hodgkin's lymphoma (NHL) is related to prior medication use or health history, a population-based case-control study was conducted. A total of 619 male and female residents of Los Angeles County who were diagnosed with NHL between January 1, 1979, and June 30, 1982, were compared to individually age-, race-, and sex-matched neighborhood controls with regard to history of use of 49 different medications, 47 chronic and infectious diseases or other conditions, 15 types of immunizations, and 15 specific allergic reactions. Based on preliminary analyses, long-term regular use of aspirin and other pain relievers and greater than or equal to 2 mo of treatment with penicillin and other antibiotics were associated with significantly increased risk of NHL. Other drugs associated with greater risk of NHL were use of digitalis and estrogen replacement therapy by women, use of corticosteroids, and greater than or equal to 2 mo of use of tranquilizers. NHL was strongly associated with a prior history of cancer. Cases more frequently reported histories of kidney infections and anemia than did controls; a history of eczema appeared to be protective against NHL. Women who had been immunized against polio by injectable vaccine were at significantly lower risk of NHL than women who had not received this immunization. Among men, cholera immunization and allergy to nuts and berries were significantly protective. Subjects who had received a yellow fever immunization also had lower NHL risk. Further analyses of these data will attempt to establish the relative importance of these potential risk factors and to determine whether any are markers of early symptoms of NHL.

Adult↗

Risk of leukemia after chemotherapy and radiation treatment for breast cancer.

BACKGROUND: Few studies have evaluated the late effects of adjuvant chemotherapy for breast cancer. Moreover, the relation between the risk of leukemia and the amount of drug given and the interaction of chemotherapy with radiotherapy have not been described in detail. METHODS: We conducted a case-control study in a cohort of 82,700 women given a diagnosis of breast cancer from 1973 to 1985 in five areas of the United States. Detailed information about therapy was obtained for 90 patients with leukemia and 264 matched controls. The dose of radiation to the active marrow was estimated from individual radiotherapy records (mean dose, 7.5 Gy). RESULTS: The risk of acute nonlymphocytic leukemia was significantly increased after regional radiotherapy alone (relative risk, 2.4), alkylating agents alone (relative risk, 10.0), and combined radiation and drug therapy (relative risk, 17.4). Dose-dependent risks were observed after radiotherapy and treatment with melphalan and cyclophosphamide. Melphalan was 10 times more leukemogenic than cyclophosphamide (relative risk, 31.4 vs. 3.1). There was little increase in the risk associated with total cyclophosphamide doses of less than 20,000 mg. CONCLUSIONS: Although leukemia occurs in few patients with breast cancer, significantly elevated risks were linked to treatments with regional radiation and alkylating agents. Melphalan is a more potent leukemogen than cyclophosphamide or radiotherapy. Low risks were associated with the levels of cyclophosphamide in common use today. Systemic drug therapy combined with radiotherapy that delivers high doses to the marrow appears to enhance the risk of leukemia.

Aged↗

5-alpha-reductase activity and risk of prostate cancer among Japanese and US white and black males.

The incidence of prostate cancer varies widely between countries and ethnic groups. Black-Americans have the highest incidence rates world wide, whereas native Japanese have among the lowest. The reasons for this risk differential are unknown, although we have previously shown that higher circulating testosterone concentrations in young adult black men compared with young adult white men may explain the underlying differences in subsequent prostate cancer incidence between these two populations. We have now compared serum testosterone concentrations in young adult Japanese men with those of young adult whites and blacks, but found no significant differences. However, these white and black men had significantly higher values of 3 alpha, 17 beta androstanediol glucuronide (31% and 25% higher, respectively) and androsterone glucuronide (50% and 41% higher, respectively) than Japanese subjects. These two androgens are indices of 5 alpha-reductase activity. Our results raise the possibility that reduced 5 alpha-reductase activity has a role in producing the low prostate cancer incidence rates among Japanese. This finding may have important implications for prostate cancer prevention.

Adult↗

Prospects for the primary prevention of breast cancer.

In this paper, the rationale, stage of development, and known or potential adverse effects of three potential strategies for the prevention of breast cancer are reviewed. Two methods--the use of tamoxifen in postmenopausal women and the use of luteinizing hormone (LH)-releasing hormone agonists in premenopausal women--involve hormonal manipulation. In the premenopausal period, the goal is to reduce the number of ovulatory menstrual cycles a woman experiences in order to reduce her exposure to estrogen and progesterone. Physical activity during adolescence is proposed as a nonhormonal method of accomplishing this. The use of LH-releasing hormone agonists to produce a reversible menopause can also reduce a woman's cumulative exposure to ovarian steroid hormones. Tamoxifen, which is effective in breast cancer therapy, provides endocrine control of estrogen-regulated breast tumor growth. Breast cancer chemoprevention trials using tamoxifen among postmenopausal women have been proposed, and pilot studies are under way.

Adolescent↗