Mild hypercholesterolemia and premature heart disease: do the national criteria underestimate disease risk?

OBJECTIVES: To determine the frequency of hospital admissions for acute coronary syndrome in young adults and to examine the risk factors that predispose to the development of premature heart disease. BACKGROUND: Significant coronary heart disease (CHD) is considered rare in the young adult. Current guidelines do not recommend treatment of mild cholesterol abnormalities for primary prevention of CHD in the young. METHODS: This is a large case series of 449 adults (< or =50 years) admitted to the hospital with acute coronary syndrome. A history of cardiovascular risk factors and lipid profile were recorded. The presence and extent of CHD were established. RESULTS: Mean patient age was 44 +/- 6 years. Documented CHD was present in 61% of hospital admissions. Multivariate analysis revealed that history of hypercholesterolemia, history of smoking and diabetes were independently associated with premature CHD. The fasting lipid profiles were only borderline to mildly abnormal. Serum total cholesterol, low-density lipoprotein (LDL) and triglyceride levels were not different in cases compared with control subjects. Nearly half (49%) of those with LDL levels of > or =160 mg/dl had only one additional risk factor or none. Despite this, a history of hypercholesterolemia had independent and incremental value on other risk factors for the likelihood of premature CHD. CONCLUSIONS: The magnitude of hospital admissions relating to premature CHD is high. In this population, the presence of borderline or mild hypercholesterolemia has significant effects on the development of premature CHD. These observations have significant implications in the development of guidelines for primary prevention of premature CHD.     

Clinical findings of irritation among chromium chemical production workers

BACKGROUND: Several reports of workers in chromate production and chromeplating have indicated that exposure to hexavalent chromium is associated with skin and nasal irritation. METHODS: A cohort of 2, 357 workers first employed between 1950 and 1974 at a chromate production plant was identified. Clinical findings of irritation were identified by a physician as a result of routine examinations or visits to the medical clinic by members of the cohort. Percentages of the cohort with various clinical findings, the time from hire to occurrence of the first finding, and the mean and median annual hexavalent chromium (measured as CrO(3)) concentration for the job title where the clinical finding first occurred were determined. A proportional hazards model was used to evaluate the relationship between hexavalent chromium exposure and first occurrence of each of the clinical findings. RESULTS: Nasal irritation and nasal ulceration were the most common clinical findings reported, occurring in more than 60% of the cohort. The average time to first occurrence of these findings was less than 3 months, whereas the time to first occurrence of the other findings ranged from 10 to 22 months. Median exposure to hexavalent chromium at the time of occurrence for most of the findings was about 20 microg/m(3). The proportional hazards model indicated that ulcerated nasal septum, irritated skin, and perforated eardrum were significantly associated with ambient hexavalent chromium exposure; all clinical findings with the exception of conjunctivitis and irritated skin were associated with the calendar year of hire, with the risk being lower as the calendar year of hire became more recent. Annual average ambient hexavalent chromium concentrations generally dropped in the plant over the period of the study. CONCLUSIONS: Workers in the chromate production plant in this study experienced a variety of nasal and skin irritations. Irritated and ulcerated nasal septa, in particular, were quite common clinical findings, occurring in over 60% of the cohort, and they occurred in relatively short periods of time-less than 3 months from date of hire. Annual average concentrations of chromium may not be a good predictor of clinical findings of irritation. Am. J. Ind. Med. 38:127-131, 2000. Published 2000 Wiley-Liss, Inc.     

Abruptio placentae: Perinatal outcome in normotensive and hypertensive patients

OBJECTIVE: The objective of this study was to compare perinatal outcomes of hypertensive and normotensive women experiencing abruptio placentae. Our hypothesis is that hypertensive women have a less favorable perinatal outcome than do normotensive women. STUDY DESIGN: Women with the diagnosis of abruptio placentae delivered between July 1, 1988, and May 31, 1992, composed the study group (n = 226) in this case-control study. The incidence of abruptio placentae was 0.7% during this time. Those women with either multifetal gestations (n = 4) or delivery before 20 weeks' gestation (n = 2) were excluded from data analysis. The remaining 220 patients were divided according to their hypertensive (n = 29) or normotensive (n = 191) status. Maternal and neonatal medical records were reviewed and abstracted for demographic variables, antepartum complications, delivery route, abruptio placentae grade, neonatal gender, birth weight, Apgar score, cord pH, and perinatal mortality. These perinatal outcome variables were compared between the hypertensive and normotensive patient groups. RESULTS: Black women with abruptio placentae were significantly more likely to be hypertensive (p = 0.0078). Hypertensive women with abruptio placentae had the antepartum complication diabetes mellitus significantly more often than did normotensive women (p = 0.032). However, they were similar to normotensive women with regard to the frequency of positive urine drug screen and trauma. Hypertensive women were no more likely to be delivered before 32 or 37 weeks' gestation, have neonates weighing <1500 or 2500 gm, or to be delivered by cesarean section. Abruptio placentae grades 2 and 3 occurred more often in hypertensive women (p = 0.053), as did significantly lower umbilical cord artery (p = 0.005) and venous (p = 0.003) pH values. Neonates from hypertensive women were no more likely to have low 5-minute Apgar scores or to die than those from normotensive women. CONCLUSION: Although hypertensive women experiencing abruptio placentae are more likely to have higher-grade abruptio placentae and lower umbilical cord pH values, the overall perinatal outcome was not significantly different from that of normotensive women experiencing abruptio placentae. (AM J Obstet Gynecol 1994;170:1595-9.)     

Selective Cytotoxicity to Human Leukemic Myeloblasts Produced by Oligodeoxyribonucleotide Phosphorothioates Complementary to p53 Nucleotide Sequences

Cells were treated in vitro with oligodeoxyribonucleotide phosphorothioates (ODNs) complementary to sites common to both wild-type and mutant p53 nucleotide sequences. Acute myelogenous leukemia (AML) blasts from peripheral blood were exposed to four different p53 ODNs and showed anti-leukemic effects in suspension culture. This effect continued after removal of the ODN from the medium. Blocking of self-renewal of the leukemic blast stem cells in secondary plating of cells from cloning assays by two of the p53 ODNs was also observed. Control ODNs had no effect on leukemic blasts. Treatment of normal bone marrow cells with the four p53 ODNs did not influence their growth, nor was there any effect by the p53 ODNs on the leukemic cell-line, HL60, that does not express p53. These data suggest that p53 ODNs are selectively toxic to primary myelogenous blasts and may be therapeutically useful in AML.     

Droloxifene,a new antiestrogen: Its role in metastatic breast cancer

Droloxifene, a new antiestrogen, has theoretical advantages over tamoxifen based on preclinical data. These include higher affinity to the estrogen receptor, higher antiestrogenic to estrogenic ratio, and more effective inhibition of cell growth and division in ER positive cell lines, as well as less toxicity, including reduced carcinogenicity in animal models. Droloxifene also exhibits more rapid pharmacokinetics, reaching peak concentrations and being eliminated much more rapidly than tamoxifen. A phase II study compared droloxifene in dosages of 20, 40, and 100 mg daily in postmenopausal women with metastatic, or inoperable recurrent, or primary locoregional breast cancer who had not received prior hormonal therapy. Of 369 patients randomized, 292 were eligible and 268 evaluable for response. Response rates (CR + PR) were 30% in the 20 mg group, 47% in the 40 mg group, and 44% in the 100 mg group (40 mg vs 20 mg, p = 0.02; 100 mg vs 20 mg, p = 0.04; pooled 40 + 100 mg vs 20 mg, p = 0.01). Median response duration also favoured the higher dosages (20 mg group = 12 months; 40 mg group = 15 months; 100 mg group = 18 months). When adjusted for prognostic factors, time to progression was significantly better for the 100 mg (p = 0.01) and the 40 mg (p = 0.02) group compared to the 20 mg group. Droloxifene increased SHBG and suppressed FSH at all dosages and suppressed LH at the 40 and 100 mg dosages. These hormonal effects increased with increasing dosage. Shortterm toxicity was generally mild, and similar to that seen with other antiestrogens. Droloxifene appears active and tolerable. It may have a particular role in situations in which rapid pharmacokinetics, or an increased antiestrogenic to estrogenic ratio, are required.     

Characterization of lymphocyte subpopulations in warthin's tumor

Cell suspensions from six Warthin's tumors (WTs) were characterized with fluorescence-labeled cell cytometry. WT lymphocyte subsets were identified with monoclonal antibodies directed against lymphocyte-associated cell antigens including T lymphocyte subsets, B lymphocytes, and natural killer (NK) cells. Results showed that T cell proportions were 58% and B cell proportions were 39%. The T cell helper:cytotoxic-suppressor ratio was 5.7:1 and the B to T cell ratio was 0.8:1. NK cells represented 1.3% of cells. When compared to peripheral blood lymphocytes (PBLs) in the same patients, statistically significant differences were noted between PBLs and WT lymphocytes in the percentage of B lymphocytes (P<.01), T cytotoxic-suppressor lymphocytes (P<.02), NK cells (P<.01), and in the ratios of B to T lymphocytes (P<.01) and T helper to T cytotoxic-suppressor lymphocytes (P<.03). Comparing these data to retrospective data on lymphocyte distribution in normal and reactive lymph nodes, the epithelial component does not appear to exert a local effect on the lymphoid component of WT.     

Reconsidering a Paradigm: The Spread of Supraglottic Carcinoma to the Glottis

This study was performed to evaluate the spread of supraglottic carcinoma to the glottic level. Whole organ sections of total laryngectomy specimens from 37 patients with previously untreated supraglottic carcinomas were reviewed retrospectively. Of the 37 specimens, 20 (54%) were noted to have extension of cancer to the glottic level. A significant relationship was noted between glottic extension and abnormal cord motion (P= .0002). A statistically significant trend was noted for the relationship between inferior extension along the supraglottic mucosa and glottic level extension (P< .0001). Contrary to the prevailing model of the spread of supraglottic carcinoma, in which there is a distinct barrier to spread at the ventricle, this analysis of selected supraglottic carcinomas revealed a continuum of spread from the supraglottis to the glottis.     

FEARS AND WORRIES OF YOUNG CHILDREN AS EXPRESSED IN A CONTEXTUAL PLAY SETTING

One hundred 5- and 6-year-old children were studied with a contextual play technique in order to gain insight into their fears and worries. Sex differences and differences relating to questioning procedure were examined. The discussion included the potential usefulness of the method and some implications for parents and teachers.