Chicken homolog of the mos proto-oncogene.

We compared the sequence and properties of the chicken mos homolog with the previously characterized mouse and human c-mos genes. Sequence analysis revealed one major open reading frame of 1,047 base pairs encoding a protein of 349 amino acids. Both the nucleotide sequence and the deduced amino acid sequence showed 62% overall homology to mouse and human c-mos, but regions of higher conservation (approximately 70%) occurred in the putative ATP-binding and kinase domains. We detected mos transcripts by Northern (RNA) analyses in RNA prepared from chicken and quail ovaries and testes. Evidence for low levels of mos RNA expression in adult chicken heart, kidney, and spleen and in the entire embryo was obtained by S1 nuclease protection experiments. In contrast to the low transforming efficiency of human c-mos when linked to a mouse retroviral long terminal repeat element, chicken c-mos transformed NIH 3T3 cells as efficiently as mouse c-mos did. We also show that chicken primary embryo fibroblasts were morphologically altered when infected with an avian retroviral vector containing the chicken c-mos coding region.

Cancer mortality in a human isolate.

Cancer mortality (1965--77) among 12,652 members of an inbred human religious isolate, the Hutterites, was compared with expectations based on mortality rates for the U.S. white population in 1970. Overall, Hutterites had significantly fewer deaths from cancer than expected (P < 0.01), due primarily to fewer lung cancers among males. Smoking is prohibited for this religious group. The most frequent types of cancers were leukemia and cancers of the digestive system, the prostate gland, and the female breast. Preliminary results suggest an association between recessive alleles and childhood leukemia. More stomach and rectal cancers were observed than expected, but differences were generally not significant. Familial aggregates of cancers of the stomach and breast are being investigated. The low frequency of cervical cancer is consistent with current evidence for an association of cervical cancer with early age at first intercourse and promiscuity, neither of which is characteristic of this population.

Interactions between angiotensin-I converting enzyme insertion/deletion polymorphism and response of plasma lipids and coronary atherosclerosis to treatment with fluvastatin: the lipoprotein and coronary atherosclerosis study.

OBJECTIVES: Our objectives were to determine whether angiotensin-1 converting enzyme (ACE) insertion/deletion (I/D) polymorphism was associated with the severity of coronary artery disease (CAD) and its progression/regression in response to fluvastatin therapy in the Lipoprotein and Coronary Atherosclerosis Study (LCAS) population. BACKGROUND: Genetic factors are involved in susceptibility to CAD. Angiotensin-1 converting enzyme I/D polymorphism, which accounts for half of the variance of plasma and tissue levels of ACE, has been implicated in susceptibility to CAD and myocardial infarction (MI). METHODS: Angiotensin-1 converting enzyme genotypes were determined by polymerase chain reaction (PCR). Fasting plasma lipids were measured and quantitative coronary angiograms were obtained at baseline and 2.5 years following randomization to fluvastatin or placebo. RESULTS: Ninety-one subjects had DD, 198 ID and 75 II genotypes. The mean blood pressure, minimum lumen diameter (MLD), number of coronary lesions and total occlusions were not significantly different at baseline or follow-up among the genotypes. There was a significant genotype-by-treatment interaction for total cholesterol (p = 0.018), low-density lipoprotein cholesterol (LDL-C) (p = 0.005) and apolipoprotein (apo) B (p = 0.045). In response to fluvastatin therapy, subjects with DD, compared with those with ID and II genotypes, had a greater reduction in total cholesterol (19% vs. 15% vs. 13%), LDL-C (31% vs. 25% vs. 21%) and apo B (23% vs. 15% vs. 12%). Definite progression was less (14%) and regression was more common (24%) in DD as compared with those with ID (32% and 17%) and II (33% and 3%) genotypes (p = 0.023). Changes in the mean MLD and lesion-specific MLD also followed the same trend. CONCLUSIONS: Angiotensin-1 converting enzyme I/D polymorphism is associated with the response of plasma lipids and coronary atherosclerosis to treatment with fluvastatin. Subjects with DD genotype had a greater reduction in LDL-C, a higher rate of regression and a lower rate of progression of CAD.

Nonsurgical septal reduction therapy for hypertrophic obstructive cardiomyopathy: one-year follow-up.

OBJECTIVE: The objective of this study is to evaluate the one-year outcome of the first 50 patients who underwent nonsurgical septal reduction for symptomatic hypertrophic obstructive cardiomyopathy at our institution. BACKGROUND: Left ventricular outflow tract obstruction is an important determinant of clinical symptoms in patients with hypertrophic obstructive cardiomyopathy. Nonsurgical septal reduction is a new therapy that has been shown to result in left ventricular outflow tract gradient reduction and resolution of symptoms immediately after the procedure and on midterm follow-up. METHODS: Fifty patients with hypertrophic obstructive cardiomyopathy who underwent nonsurgical septal reduction at our institution and completed 1-year follow-up are described. Complete history, physical examination, two-dimensional echocardiography with Doppler and exercise treadmill testing have been analyzed. RESULTS: The mean age of the study group was 53 +/- 17 years. All patients had refractory symptoms before enrollment. Ninety-four percent had class III or IV New York Heart Association class symptoms at baseline compared to none at 1 year (p < 0.001). The exercise duration increased by 136 s at 1 year (p < 0.021). Only 20% of patients were either receiving beta-blockers or calcium-channel blockers on follow-up. The resting left ventricular outflow tract gradient decreased from 74 +/- 23 mm Hg to 6 +/- 18 mm Hg (p < 0.01) and from 84 +/- 28 mm Hg to 30 +/- 33 mm Hg (p < 0.01) in patients with dobutamine-provoked gradient at one year. These changes are associated with decreased septal thickness and preserved systolic function. CONCLUSION: Nonsurgical septal reduction therapy is an effective therapy for symptomatic patients with hypertrophic obstructive cardiomyopathy with persistence of the favorable outcome up to one year after the procedure.

Factors determining improvement in left ventricular function after reperfusion therapy for acute myocardial infarction: primacy of baseline ejection fraction.

Improvement in left ventricular ejection fraction is a measure of salvage of ischemic myocardium after reperfusion therapy for acute myocardial infarction. The degree of improvement in left ventricular ejection fraction may be influenced by many factors. Therefore, 137 patients in whom paired radionuclide angiograms were obtained within 24 h of acute infarction and before hospital discharge were retrospectively evaluated to determine which factors most affect improvement in ejection fraction. Only baseline ejection fraction correlated significantly with improvement in ejection fraction by both univariate analysis (ejection fraction as a continuous variable; p less than 0.001; ejection fraction as a categorical variable, less than or equal to 45% versus greater than 45%, p less than 0.0001) and multivariate analysis (p less than 0.0001). Reperfusion status (patent versus occluded infarct artery) and extent of coronary artery disease (one, two or three vessel) were significant factors by multivariate but not by univariate analysis. Location of infarction, treatment modality and time to treatment did not correlate with change in ejection fraction by either statistical technique. Thus, of those factors tested, baseline left ventricular ejection fraction is the most potent predictor of improvement in ventricular function after acute infarction. Knowledge of baseline ejection fraction may be helpful in deciding whether to treat some patients with equivocal indications or contraindications for reperfusion therapy. Clinical trials of reperfusion strategies should stratify patients on the basis of baseline ejection fraction if ejection fraction is to be used as an end point for myocardial salvage.

Apolipoprotein E genotypes and response of plasma lipids and progression-regression of coronary atherosclerosis to lipid-lowering drug therapy.

OBJECTIVES: We sought to examine the association of apolipoprotein (apo) E genotypes with baseline plasma lipid levels and severity of coronary artery disease (CAD), as well as the response to treatment with fluvastatin in the Lipoprotein and Coronary Atherosclerosis Study (LCAS). BACKGROUND: Apo E genotypes have been associated with plasma lipid levels and CAD. However, the influence of apo E genotypes on the response of plasma lipids and CAD progression or regression to statin treatment in patients with mildly to moderately elevated cholesterol remains unknown. METHODS: Apo E genotypes were determined by polymerase chain reaction and restriction mapping. Plasma lipids were measured at baseline and 12 weeks after therapy with fluvastatin or placebo in 320 subjects. In 287 subjects, quantitative coronary angiography was performed at baseline and after 2.5 years of treatment. RESULTS: Subjects with the 3/3 genotype had greater reductions in total cholesterol (20.4% vs. 15.4%, p = 0.01) and low density lipoprotein (LDL) cholesterol (28.8% vs. 22.7%, p = 0.03) than did the subjects with the 3/4 or 4/4 genotype. In contrast, subjects with the 2/3 genotype (n = 10) had a greater increase in high density lipoprotein cholesterol (19.1%) than did the subjects with the 3/3 genotype (4.3%, p = 0.002) and those with the 3/4 or 4/4 genotype (7.0%, p = 0.02). Subjects with the 3/4 or 4/4 genotype had an increased frequency of previous angioplasty, but other measures of baseline CAD severity and baseline lipids did not differ significantly among the genotypes, nor did CAD progression or clinical events. CONCLUSIONS: Although subjects with the epsilon4 allele had less reduction in LDL cholesterol with fluvastatin, they had similar benefit in terms of CAD progression.

Withholding medical treatment from the severely demented patient. Decisional processes and cost implications.

We performed an observational study to determine the prevalence of severe dementia in a general medicine unit, the categories of acute medical care provided to these patients, the process by which treatment decisions are made, and their cost implications. The prevalence of severe dementia was 4.4%. The patients from whom some form of acute medical care was withheld (26 [45.6%] of 57) were more severely ill at admission and had a mortality rate five times higher than those who received full care. Physicians cited family wishes in 75.9% of the decisions to limit care but in only 10.9% of the decisions to give full care. The only differences in charges incurred were due to differential mortality rates in individuals from whom care was withheld. We recommend that hospitals develop and implement protocols for decision making in the care of the severely demented to promote open discussions among providers and families and to increase family contributions to decision making. We believe that the extension of this consultative approach to decisions involving severely demented patients may have the virtue of combining more humane care with more cost-effective care.

Effects of beef and chicken consumption on plasma lipid levels in hypercholesterolemic men.

BACKGROUND: The recommendation to lower saturated fat intake is often interpreted as requiring the elimination of beef to control or lower serum cholesterol levels. The study hypothesis was that the Step I Diet (8% to 10% of energy intake from saturated fatty acids) containing beef would have the same effect on plasma lipid levels of hypercholesterolemic men as a like diet containing chicken. METHODS: Thirty-eight free-living hypercholesterolemic (otherwise healthy) men completed a 13-week dietary intervention study. Subjects consumed their usual diets for 3 weeks, followed by a 5-week stabilization diet (18% of energy intake from saturated fatty acids), before randomization to one of two test diets for 5 weeks. The test diets contained either 85 g of cooked beef (8% fat) or 85 g of cooked chicken (7% fat) per 4184 kJ and had 7% to 8% of energy from saturated fatty acids. All food was supplied during the stabilization and test diets. RESULTS: The beef and chicken test diets both produced significant decreases in average plasma total cholesterol level (0.54 mmol/L [7.6%] for beef and 0.70 mmol/L [10.2%] for chicken) and low-density lipoprotein cholesterol level (0.46 mmol/L [9%] for beef and 0.55 mmol/L [11%] for chicken). Changes in average levels of plasma total cholesterol, high-density lipoprotein cholesterol, triglyceride, and low-density lipoprotein cholesterol were not statistically different (smallest P = .26) between the beef and chicken test diets. The average triglyceride level did not change for either test diet group. CONCLUSIONS: In this short-term study, comparably lean beef and chicken had similar effects on plasma levels of total, low-density lipoprotein, and high-density lipoprotein cholesterol and triglyceride. We concluded that lean beef and chicken are interchangeable in the Step I Diet.

Selective dendritic alterations in the cortex of Rett syndrome.

Rett syndrome, the commonest condition associated with severe mental retardation in girls, is diagnosed only by its clinical phenotype, because, to date, there is no consistent characteristic alteration in genetic, biochemical, neurotransmitter or morphologic marker. The clinical features at various ages suggest involvement of most parts of the nervous system, however, the brain in Rett syndrome is reduced in weight, without other obvious morphologic alterations. Because of the relative microcephaly, hypotheses regarding failure of development have been suggested. Supporting such hypotheses are the quantitative studies by Jellinger, Seitelberger and Kitt defining a decrease in the amount of melanin in the substantia nigra and by Bauman defining a global decrease in the size of the neurons. In this study the cerebral cortex has been examined using the rapid Golgi technique with the purpose of investigating dendrites of pyramidal neurons in six cortical regions of Rett girls from ages 2.9-35 years. Camera lucida drawings of apical and basal dendrites of two cortical layers and CA1 were prepared. These were submitted to the Sholl analysis. The Sholl analyses were tested for significance using the repeated measures analysis of covariance, with age as a covariate. The studies demonstrate that from our samples there is no evidence that the pyramidal neurons in Rett syndrome degenerate progressively with increasing age but that the basal dendrites of layers three and five pyramidal neurons in the motor and frontal cortex, the apical dendrites of layer five of the motor cortex, and the basal dendrites of layer four of the subiculum are significantly shorter than in non-Rett brains.(ABSTRACT TRUNCATED AT 250 WORDS)

A method for estimating progression rates in Alzheimer disease.

BACKGROUND: The ability to predict progression of disease in patients with Alzheimer disease (AD) would aid clinicians, improve the validation of biomarkers, and contribute to alternative study designs for AD therapies. OBJECTIVE: To test a calculated rate of initial decline prior to the first physician visit (preprogression rate) for its ability to predict progression during subsequent follow-up. METHODS: We calculated preprogression rates for 298 patients with probable or possible AD (using the criteria of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Associations (NINCDS-ADRDA) with a formula using expected Mini-Mental State Examination (MMSE) scores, scores at presentation, and a standardized estimate of duration. The patients are being followed up longitudinally in our Alzheimer Disease Research Center. The time to clinically meaningful deterioration, defined as an MMSE score drop of 5 or more points, was compared for patients stratified as slow, intermediate, and rapid progressors based on the preprogression rate. Cox regression analysis was used to examine the contribution of demographic variables (age, sex, ethnicity, and level of education), initial MMSE scores, estimated symptom duration, and the calculated preprogression rate to the time it took to reach the end point across the groups. RESULTS: Both initial MMSE (hazard ratio, 0.95 (0.002); z = 4.19; P<.001) and the calculated preprogression rate (hazard ratio, 1.06 (0.019); z = 3.16; P =.002) were significant in determining time to clinically meaningful decline during longitudinal follow-up (Cox regression analysis). Slow, intermediate, and rapid progressors (based on preprogression rates) experienced significantly different time intervals to clinically meaningful deterioration, with the slow progressors taking the longest time, the intermediate progressors in the middle, and the rapid progressors reaching the end point first (log rank chi(2)(1) = 9.81, P =.002). CONCLUSION: An easily calculable rate of early disease progression can classify patients as rapid, intermediate, or slow progressors with good predictive value, even at initial presentation.

Lipoprotein lipase gene mutations, plasma lipid levels, progression/regression of coronary atherosclerosis, response to therapy, and future clinical events. Lipoproteins and Coronary Atherosclerosis Study.

Mutations in human lipoprotein lipase (LPL) gene are potential risk factors for susceptibility to coronary artery disease (CAD). The objectives of this study were to determine the influence LPL mutations Asn291Ser and Ser447Ter on plasma lipid levels, regression and progression of CAD, clinical events rate, and response to fluvastatin therapy in the Lipoprotein and Coronary Atherosclerosis Study (LCAS) population. LCAS is a double blind, randomized, placebo-controlled study designed to test the influence of fluvastatin on progression or regression of CAD. The Asn291Ser and Ser447Ter genotypes were determined by polymerase chain reaction (PCR) and restriction enzyme digestion. Fasting plasma lipid profiles were measured and quantitative coronary angiography was performed at baseline and 2.5 years following randomization. Fatal and non-fatal cardiovascular events during the follow-up period were recorded. A total of 4% (14/363) and 18% (62/352) of the subjects had the Asn291Ser and Ser447Ter mutations, respectively. Overall, there was no statistically association between the Asn291Ser and Ser447Ter mutations and the baseline or final mean plasma levels of lipids, number of coronary lesions, total occlusions, the mean minimal lumen diameter (MLD) stenoses and the clinical events rate. However, patients with the Ser447Ter variant had a slightly higher baseline high density lipoprotein-cholesterol (HDL-C) level (46.2 +/- 12 vs 43.2 +/- 11, P = 0.057), less increase in plasma HDL levels in response to fluvastatin therapy (3 vs 11%, P = 0.056) and a higher cardiovascular events rate (23 vs 13%, P = 0.056). Thus, the Ser447Ter variant had a modest influence on plasma HDL levels and the rate of cardiovascular events. These changes were of borderline statistical significance. Neither the Ser447Ter nor the Asn291Ser mutation had a major impact on susceptibility to CAD, progression or regression of CAD, clinical events rate or response to fluvastatin therapy in LCAS population.

Natural history, determinants, and clinical relevance of conduction abnormalities following orthotopic heart transplantation.

To study the long-term evolution, determinants, and clinical relevance of the conduction abnormalities after orthotopic heart transplantation, 87 patients, followed for a mean of 105 +/- 72 weeks, were divided into 3 groups according to the characteristics of their electrocardiograms compared with their initial electrocardiogram recorded at study entry. The first group consisted of 24 patients whose initial electrocardiogram was normal, and subsequent electrocardiograms remained normal throughout the study. The second group included 27 patients who developed electrocardiographic evidence of progressive conduction system damage. The third group comprised 36 patients whose initial electrocardiogram was abnormal and subsequent electrocardiograms remained unchanged during follow-up. Although the hemodynamic and echocardiographic evaluation of right and left ventricular function were initially similar among the 3 groups, groups 2 and 3 demonstrated a significant deterioration of left ventricular ejection fraction (62 +/- 12% to 55 +/- 16% and 62 +/- 8% to 57 +/- 14%, respectively; p < 0.05) and cardiac index (2.7 +/- 0.6 to 2.3 +/- 0.5 and 3.0 +/- 0.9 to 2.5 +/- 0.9 L/min/m2, respectively; p < 0.05) while patients in group 1 maintained their normal baseline indices. Incidence and progression of coronary artery disease, as well as frequency of rejection episodes, were comparable among the groups. Mortality was higher in the 2 groups with evidence of conduction defects. Sudden death associated with complete heart block (2 patients) or ventricular arrhythmias (3 patients) was exclusively confined to patients with evidence of progressive electrocardiogram abnormalities. We conclude that, following orthotopic heart transplantation, stable or progressive conduction system damage on the electrocardiogram is associated with left ventricular dysfunction and increased mortality. Sudden death is not uncommon among patients demonstrating worsening cardiac conduction and, in some cases, is related to the development of potentially preventable complete heart block.

Once-daily, extended-release gemfibrozil in patients with dyslipidemia. The Lopid SR Work Group I.

This randomized, parallel-group, multicenter clinical trial compared a newly developed, once-daily, extended-release formulation of gemfibrozil (Lopid SR) and gemfibrozil twice daily (Lopid) in terms of lipid-regulating effects and toxicity. Patients were men and women with elevations of low-density lipoprotein cholesterol and low levels of high-density lipoprotein cholesterol. The trial consisted of a 1-week screening period, an 8-week diet baseline period (Step One Diet), and a 24-week double-blind treatment period (extended-release gemfibrozil 1,200 mg once daily vs gemfibrozil 600 mg twice daily). At the end of the trial, the 2 treatment groups showed comparable improvements in all primary lipid factors: mean percent changes in triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol were -32, +10 and -10% for extended release (n = 325) and -36, +11 and -10% for twice daily (n = 330). The 90% confidence interval for the relative difference between the treatment means fell within the equivalence bounds of +/- 35% for all 3 factors, demonstrating equivalence of efficacy. Adverse events were reported at low rates and were similarly distributed in frequency and intensity between treatment groups; they were preponderantly mild or moderate, and gastrointestinal effects were the most frequent. The once-daily formulation of gemfibrozil may afford better control of dyslipidemia through improved compliance by patients who have this asymptomatic disease.

Frequency of apoptotic bodies positively correlates with Gleason grade in prostate cancer.

Tissue samples from patients with carcinoma of the prostate of various Gleason grades were examined for the frequency of apoptotic bodies. Apoptotic bodies were scored by morphometric methods using hematoxylin-eosin (HE)-stained sections from surgical specimens of prostate cancer. Non-neoplastic prostate tissue adjacent to foci of cancer showed a very low frequency of apoptotic bodies. Significantly larger numbers of apoptotic bodies were observed in the areas of carcinoma than in the non-neoplastic control tissues, regardless of Gleason grade. Interestingly, a positive correlation was noted between apoptotic bodies and increasing Gleason grade. The positive correlation suggests that increased programmed cell death is a feature of the increasing malignant potential that is associated with higher Gleason grade in prostate cancer.

Immunohistochemical identification of tumor markers in metastatic adenocarcinoma. A diagnostic adjunct in the determination of primary site.

Adenocarcinoma that metastasizes from an unknown primary site is a significant oncologic problem. With the exception of prostate-specific antigen and thyroglobulin, no single immunohistochemical marker is entirely site-specific. A retrospective study was undertaken to determine whether a panel of markers could accurately predict the site of origin of common metastatic adenocarcinomas. On the basis of reports of their relatively restricted specificity for carcinomas of colon, breast, lung, ovary, and upper gastrointestinal tract (stomach, pancreas, and bile duct), eight markers were selected for simultaneous evaluation: gross cystic disease fluid protein-15, breast cancer antigen 225 (BCA225), B72.3, DF3 (CA15-3), carcinoembryonic antigen (CEA), CA19-9, CA125, and estrogen receptor. The study population consisted of 128 metastatic nonmucinous adenocarcinomas for which the primary site was known. Staining was performed on formalin-fixed, paraffin-embedded tissue using an enhanced-sensitivity avidin-biotin peroxidase complex detection system. The most informative markers were CEA, CA19-9, CA125, and BCA225. With this four-marker panel, the most predictive multiple-marker phenotypes, as determined by a combination of area under the receiver operating characteristic curve, specificity, and percent correct predictions, were CEA+, BCA225-, and CA125- for colon tumors; BCA225+, CEA-, and CA125- for breast tumors; BCA225+, CEA+, and CA19-9- for lung tumors; CA125+ and CEA- for ovarian tumors; and CEA+, CA19-9+, and CA125+ for upper gastrointestinal tract tumors. Overall, these phenotypes correctly predicted the known primary site in 66% of cases. Until single highly sensitive and specific markers are developed for adenocarcinomas other than prostate and thyroid tumors, the origin of a metastatic adenocarcinoma can best be suggested or excluded with clinicopathologic data combined with a panel of selected immunohistochemical markers.

Development of cholesterol homeostatic memory in the rat is influenced by maternal diets.

The hypothesis that dietary factors in early life modify the extent of adaptive responses in adult life was tested in rats. During the gestational and lactational periods, pregnant rats were fed either a high-fat (HF) or low-fat (LF) diet (corn oil, 15% or 2%, wt/wt) until 30 days postpartum. The offspring were maintained on standard chow for an additional 100 days and fed a HF diet for 1, 3, 7, or 21 days. Upon challenge for 3 days, rats born to dams fed the HF diet showed a more rapid hypercholesterolemic response when compared with rats born to dams fed a LF diet (mean +/- S.D., 151 +/- 14 mg/dL v 122 +/- 6 mg/dL; P less than .001). Higher levels of cholesterol were associated with elevated levels of apolipoprotein (apo) B (24.0 +/- 4 mg/dL v 15.8 +/- 3 mg/dL; P less than .05) and apo E (31.0 +/- 4 mg/dL v 24.7 +/- 3 mg/dL; P less than .05). Further comparison of the hypercholesterolemic response between the two groups of animals showed increases in cholesterol in all major lipoprotein classes, cholesterol enrichment at the expense of triglyceride (TG) in very-low-density lipoprotein (VLDL), and elevation of apo E-containing high-density lipoprotein (HDL). Examination at longer time periods of HF challenge showed that apo E levels of the HF-exposed animals remained elevated compared with similarly challenged rats born to dams fed the LF diet (35 +/- 3.8 mg/dL v 26 +/- 2.7 mg/dL; P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Physiologic estradiol replacement therapy and cardiac structure and function in normal postmenopausal women: a randomized, double-blind, placebo-controlled, crossover trial.

OBJECTIVE: To assess the effect of estradiol (E2) replacement therapy on cardiac structure and function in healthy postmenopausal women. METHODS: We conducted a randomized, double-blind, placebo-controlled, crossover study of 31 healthy postmenopausal female volunteer study subjects (55-65 years) using 12 weeks of micronized E2 replacement therapy (2 mg/day). Echocardiography and Doppler techniques were used to assess the cardiac effects of E2 at rest and during graded bicycle ergometry. RESULTS: Crossover analysis demonstrated no carryover effects of estrogen treatment (which increased serum E2 15-fold to 37.6 pmol/L) on the cardiac characteristics measured. Estradiol treatment did not affect measurements of systolic function, diastolic function, left ventricular mass, or pulmonary artery pressure at rest or during bicycle ergometry. Left ventricular end-diastolic volume at rest was slightly higher with E2 treatment (P = .03). However, this change was not reflected by changes in stroke volume, ejection fraction, or cardiac output. CONCLUSIONS: Estrogen replacement therapy, which results in physiologic serum concentrations, does not affect cardiac structure or function in normal postmenopausal women after 12 weeks of treatment.

Is prostate-specific antigen density more useful than prostate-specific antigen levels in the diagnosis of prostate cancer?

OBJECTIVES: To compare the performance of prostate-specific antigen (PSA) levels with the performance of PSA density (PSAD), the ratio of the serum to the size of the prostate, as predictors of the presence of prostate cancer. METHODS: We analyzed the results of digital rectal examination (DRE), transrectal ultrasonography (TRUS), serum PSA levels, and PSAD in 244 patients who had a needle biopsy of the prostate. RESULTS: Cancer was detected in 110 patients (45%). Compared with DRE, TRUS and serum PSA levels 4.0 ng/mL or higher, PSAD at a cutoff point of 0.15 ng/mL/cm3 was significantly more specific and had a higher positive predictive value than each of the other tests but was significantly less sensitive than TRUS and PSA (P < 0.05 for each). In a receiver operating characteristic analysis, PSAD was significantly more accurate than PSA (P < 0.001). In 80 patients with a normal PSA, PSAD added no additional information, and PSAD was not able to identify a subset at low risk. In 82 patients with a high PSA level (10 ng/mL or higher), 15% had a PSAD less than 0.15 and only 8% had a cancer. CONCLUSIONS: Overall, PSAD was significantly more accurate than PSA for predicting the results of needle biopsy of the prostate, but in practice PSAD proved useful in only a small subset of patients. If the serum PSA level was high but the PSAD was low, cancer was rarely detected. These patients may be suitable candidates for careful follow-up rather than early repeat biopsy.

Cigarette smoking and other vascular risk factors in vasculogenic impotence.

A total of 132 consecutive patients with erectile impotence underwent extensive evaluation, including vascular evaluation with intracavernous injection of papaverine and penile duplex ultrasonography, to determine the etiology of impotence. Three vascular risk factors, smoking, diabetes mellitus and hypertension, were investigated for their impact on vasculogenic impotence. The patients were divided into four groups: one with no risk factors, one with one vascular risk factor, one with two vascular risk factors, and one with all three risk factors. The results of penile vascular evaluation in these patient groups were compared. The incidence of penile vascular impairment was found to be higher in patients with one vascular risk factor than in those with none. The proportion of abnormal penile vascular findings significantly increased as the number of risk factors increased. These data confirm the important role of vascular risk factors, smoking, diabetes mellitus, and hypertension, in the pathogenesis of organic impotence.

Cholesterol-related knowledge, attitudes, and behaviors in a low-income, urban patient population.

To determine knowledge, attitudes, behaviors, and self-reported cholesterol measurement in a low-income, urban patient population, we conducted an interview survey of users and potential users of primary care services in a public health care system for low-income Harris County, Texas, residents. The response rate was 93%, with a final sample of 547 randomly selected subjects 18 years of age and older, who were Hispanic (54%), black (28%), non-Hispanic white (14%), and Asian, Native American, or other (4%). Results indicated that 76% had heard of serum or blood cholesterol, and 30% reported past cholesterol measurement. Knowledge that dietary saturated fat can raise blood cholesterol ranged from 11% in Hispanic men to 51% in non-Hispanic white men and women. A lower percentage of Hispanics correctly answered all knowledge questions, and Hispanics reported higher-fat food choices than blacks and non-Hispanic whites. More than 90% of the respondents expressed interest in more information on diet, 60% reported that they read nutrition labels, and 15% said they have been trying to reduce blood cholesterol levels. A lower percentage of Hispanics reported previous cholesterol measurement than blacks or non-Hispanic whites, a difference that persisted after adjusting for multiple factors associated with cholesterol measurement. Older age (older than 50) and more physician visits in the past year also were associated with past cholesterol measurement. Comparisons with national surveys show that cholesterol knowledge and actual measurement in this low-income sample lag behind those of the national population. Yet, despite gaps in knowledge and cholesterol measurement, respondents showed positive attitudes about and interest in cholesterol-lowering interventions.