Search PubMed⌕ Search

Biomedical subjects

R M Elashoff

Publications and source records attributed to R M Elashoff.

At least 19 recordsLinked to original sources
PubMed2001

CancerVax, an allogeneic tumor cell vaccine, induces specific humoral and cellular immune responses in advanced colon cancer.

BACKGROUND: The immunogenicity of the polyvalent tumor cell vaccine CancerVax has been correlated with the survival of patients receiving active immunotherapy for melanoma. Because the various antigens expressed on the vaccine are common to colon adenocarcinoma cells, we examined the survival impact of immune responses elicited by CancerVax in patients with advanced colon cancer refractory to standard therapy. METHODS: Twenty-seven patients with American Joint Committee on Cancer (AJCC) stage IV colorectal adenocarcinoma were entered prospectively into the study. CancerVax was coadministered with bacille Calmette-Guerin (BCG) for the first 2 weeks of vaccine treatment. Blood was drawn at the start of therapy and every 2 weeks thereafter to measure serum titers of immunoglobulin (Ig)G and IgM against TA90 (a 90-kD immunogen common to colon cancer and CancerVax cells) and against purified protein derivative (PPD), a nontumor control antigen. Cellular immune responses were evaluated by delayed-type hypersensitivity (DTH) reaction to vaccine cells and to PPD. Mean follow-up time was 17.5 months. RESULTS: There was a significant (P = .0001) increase in anti-TA90 IgG and IgM titers and in DTH response to vaccine cells. Humoral and skin responses to TA90 did not correlate with responses to PPD (P = .199 for IgM, P = .958 for IgG, and P = .149 for DTH). This suggests that these responses are not a manifestation of general immune competence. The median overall survival (OS) was 21.9 months for the entire group. Overall survival was higher among patients whose IgMTA90 titer was >800 (P = .003) or whose disease-free interval exceeded 12 months (P = .031). Multivariate Cox regression analysis-using age, sex, disease-free interval, disease status, extent of metastasis, humoral responses, and DTH responses-found only peak IgMTA90 titer to be a significant predictor of overall survival (P = .0365). CONCLUSIONS: CancerVax can induce measurable humoral and cellular immune responses to tumor-associated antigens in patients with advanced-stage colon cancer. These responses correlate with overall survival. This novel therapeutic regimen for patients with advanced colon cancer merits further investigation.

Adenocarcinoma↗
PubMed2001

Synchronicity of frequently sampled thyrotropin (TSH) and leptin concentrations in healthy adults and leptin-deficient subjects: evidence for possible partial TSH regulation by leptin in humans.

Leptin signals the status of energy reserves to the brain. Leptin stimulates biosynthesis of TRH in vitro and influences the activity of the hypothalamic-pituitary-thyroid axis in vivo in rodents. Because blood levels of both leptin and TSH display diurnal variation with a distinct nocturnal rise, we sought to determine whether a relationship exists between fluctuations in circulating leptin and TSH. We measured serum leptin and TSH levels every 7 min for 24 h in five healthy men and found that both leptin and TSH levels are highly organized and pulsatile. A similar pattern of leptin and TSH rhythms was observed, with TSH and leptin levels reaching a nadir in late morning and a peak in the early morning hours. Importantly, cosinor analysis on the absolute leptin and TSH levels revealed a statistically significant fit for a 24-h period and the two hormones showed similar probabilities of rhythm and superimposable peak values. Furthermore, this study shows a strong positive Pearson correlation between the 24-h patterns of variability of leptin and TSH in healthy subjects. Finally, the ultradian fluctuations in leptin levels showed pattern synchrony with those of TSH as determined by cross-correlation analysis, by cross-approximate enthropy and Bayessian analysis applied independently. To further explore whether these associations could reflect an underlying regulation of TSH secretion by leptin, we also studied frequently sampled leptin and TSH levels in four brothers, members of a family with leptin deficiency (one normal homozygote, two heterozygotes, and one leptin-deficient homozygote). Leptin levels of the homozygous leptin-deficient subject are detectable but bioinactive, and the rhythm of his TSH is disorganized. 24-h pattern of leptin and TSH variability in the heterozygous subjects, although significantly correlated, showed a weaker correlation compared with the strong correlation in the normal subjects. These data are consistent with the possibility that leptin may regulate TSH pulsatility and circadian rhythmicity, but interventional studies are needed to definitively prove whether leptin regulates the minute-to-minute oscillations and ultradian rhythm of TSH levels.

Adult↗
PubMed2000

Coronary-artery calcification in young adults with end-stage renal disease who are undergoing dialysis.

BACKGROUND: Cardiovascular disease is common in older adults with end-stage renal disease who are undergoing regular dialysis, but little is known about the prevalence and extent of cardiovascular disease in children and young adults with end-stage renal disease. METHODS: We used electron-beam computed tomography (CT) to screen for coronary-artery calcification in 39 young patients with end-stage renal disease who were undergoing dialysis (mean [+/-SD] age, 19+/-7 years; range, 7 to 30) and 60 normal subjects 20 to 30 years of age. In those with evidence of calcification on CT scanning, we determined its extent. The results were correlated with the patients' clinical characteristics, serum calcium and phosphorus concentrations, and other biochemical variables. RESULTS: None of the 23 patients who were younger than 20 years of age had evidence of coronary-artery calcification, but it was present in 14 of the 16 patients who were 20 to 30 years old. Among those with calcification, the mean calcification score was 1157+/-1996, and the median score was 297. By contrast, only 3 of the 60 normal subjects had calcification. As compared with the patients without coronary-artery calcification, those with calcification were older (26+/-3 vs. 15+/-5 years, P<0.001) and had been undergoing dialysis for a longer period (14+/-5 vs. 4+/-4 years, P< 0.001). The mean serum phosphorus concentration, the mean calcium-phosphorus ion product in serum, and the daily intake of calcium were higher among the patients with coronary-artery calcification. Among 10 patients with calcification who underwent follow-up CT scanning, the calcification score nearly doubled (from 125+/-104 to 249+/-216, P=0.02) over a mean period of 20+/-3 months. CONCLUSIONS: Coronary-artery calcification is common and progressive in young adults with end-stage renal disease who are undergoing dialysis.

Adolescent↗
PubMed1999

Cholesterol-lowering effects of a proprietary Chinese red-yeast-rice dietary supplement.

BACKGROUND: We examined the cholesterol-lowering effects of a proprietary Chinese red-yeast-rice supplement in an American population consuming a diet similar to the American Heart Association Step I diet using a double-blind, placebo-controlled, prospectively randomized 12-wk controlled trial at a university research center. OBJECTIVE: We evaluated the lipid-lowering effects of this red-yeast-rice dietary supplement in US adults separate from effects of diet alone. DESIGN: Eighty-three healthy subjects (46 men and 37 women aged 34-78 y) with hyperlipidemia [total cholesterol, 5.28-8.74 mmol/L (204-338 mg/dL); LDL cholesterol, 3.31-7.16 mmol/L (128-277 mg/dL); triacylglycerol, 0.62-2.78 mmol/L (55-246 mg/dL); and HDL cholesterol 0.78-2.46 mmol/L (30-95 mg/dL)] who were not being treated with lipid-lowering drugs participated. Subjects were treated with red yeast rice (2.4 g/d) or placebo and instructed to consume a diet providing 30% of energy from fat, <10% from saturated fat, and <300 mg cholesterol daily. Main outcome measures were total cholesterol, total triacylglycerol, and HDL and LDL cholesterol measured at weeks 8, 9, 11, and 12. RESULTS: Total cholesterol concentrations decreased significantly between baseline and 8 wk in the red-yeast-rice-treated group compared with the placebo-treated group [(x+/-SD) 6.57+/-0.93 mmol/L (254+/-36 mg/dL) to 5.38+/-0.80 mmol/L (208+/-31 mg/dL); P < 0.001]. LDL cholesterol and total triacylglycerol were also reduced with the supplement. HDL cholesterol did not change significantly. CONCLUSIONS: Red yeast rice significantly reduces total cholesterol, LDL cholesterol, and total triacylglycerol concentrations compared with placebo and provides a new, novel, food-based approach to lowering cholesterol in the general population.

Adult↗
PubMed1999

Decreased growth of human prostate LNCaP tumors in SCID mice fed a low-fat, soy protein diet with isoflavones.

Epidemiological studies suggest that high intake of dietary fat is a risk factor for the development of clinical prostate cancer. Soy protein has also been proposed to play a role in the prevention of prostate cancer, and one of the isoflavones in soy protein, genistein, inhibits the growth of human prostate cancer cell lines in vitro. This study was designed to evaluate whether altering dietary fat, soy protein, and isoflavone content affects the growth rate of a human androgen-sensitive prostate cancer cell line (LNCaP) grown in severe-combined immunodeficient (SCID) mice. SCID mice were randomized into four dietary groups: high-fat (42.0 kcal%) + casein, high-fat (42.0 kcal%) + soy protein + isoflavone extract, low-fat (12.0 kcal%) + casein, and low-fat (12.0 kcal%) + soy protein + isoflavone extract. After two weeks on these diets, the mice were injected subcutaneously with 1 x 10(5) LNCaP tumor cells and placed in separate cages (1 mouse/cage) to strictly control caloric intake. Isocaloric diets were given 3 days/wk, and tumor sizes were measured once per week. The tumor growth rates were slightly reduced in the group that received the low-fat + soy protein + isoflavone extract diet compared with the other groups combined (p < 0.05). In addition, the final tumor weights were reduced by 15% in the group that received the low-fat + soy protein + isoflavone extract diet compared with the other groups combined (p < 0.05). In this xenograft model for prostate cancer, there were statistically significant effects on tumor growth rate and final tumor weight attributable to a low-fat + soy protein + isoflavone extract diet.

Animals↗
PubMed1999

Disenrollment from an HMO and its relationship with the characteristics of Medicare beneficiaries.

To examine the relationship between Medicare beneficiaries' characteristics and disenrollment, a longitudinal study was conducted in an HMO in California. Approximately 10 percent of the Medicare beneficiaries disenrolled within the first year of enrollment. There was no difference between those who continuously enrolled and those who disenrolled in terms of age, gender, mental and physical health status, previous utilization, and anticipated utilization in the coming year. However, people with limited social activities and people not living in a single-family house were more likely to disenroll. The authors also examined the disenrollment rates among physicians groups. The rates were significantly different.

Age Distribution↗
PubMed1998

Preventive pharmacologic therapy among asthmatics: five years after publication of guidelines.

BACKGROUND: Guidelines from the National Heart, Lung, and Blood Institute first published in 1991 have recommended anti-inflammatory (AI) agents as a first-line therapy and the bronchodilator as an acute reliever of symptoms. OBJECTIVE: To examine the current usage of anti-inflammatory steroids (inhaled corticosteroids, Cromolyn, systemic steroids) and bronchodilators and compare them with the national guidelines. The relationship between preventive AI usage and the characteristics of the asthma patients and their providers was also examined. METHODS: Cross-sectional survey data linked with 6-month pharmacy claims of asthmatic members at an HMO in California. RESULTS: AI usage increased with current severity (mild, 36.9%; moderate, 47.3%; and severe, 56.8%), though a large percentage are not receiving this emphasized treatment. Bronchodilators were used at a higher rate and 24% of asthmatics relied solely on bronchodilators. Use of bronchodilators without AI (BWAI) was present at all severity levels (mild, 19.5%; moderate, 24.6%; and severe, 24.7%). Advancing age, increasing severity, care by an asthma specialist, and not smoking increased the likelihood of using AIs. Increasing severity, longer duration of asthma, smoking, younger age group, care by a generalist, and no chronic bronchitis increased the likelihood of BWAI. CONCLUSIONS: These results suggest that there is a low level of AI usage despite emphasis in guidelines. Current asthma management in a community-based setting depicts a significant underutilization of long-term control agents and, conversely, an overutilization of symptom relief agents compared with guidelines published 5 years ago. Actively involving patients in the guideline dissemination process, rather than just the medical community, may increase preventive medication usage.

Adolescent↗
PubMed1998

Hospital- and patient-related characteristics determining maternity length of stay: a hierarchical linear model approach.

OBJECTIVES: The purpose of this study was to identify factors related to pregnancy and childbirth that might be predictive of a patient's length of stay after delivery and to model variations in length of stay. METHODS: California hospital discharge data on maternity patients (n = 499,912) were analyzed. Hierarchical linear modeling was used to adjust for patient case mix and hospital characteristics and to account for the dependence of outcome variables within hospitals. RESULTS: Substantial variation in length of stay among patients was observed. The variation was mainly attributed to delivery type (vaginal or cesarean section), the patient's clinical risk factors, and severity of complications (if any). Furthermore, hospitals differed significantly in maternity lengths of stay even after adjustment for patient case mix. CONCLUSIONS: Developing risk-adjusted models for length of stay is a complex process but is essential for understanding variation. The hierarchical linear model approach described here represents a more efficient and appropriate way of studying interhospital variations than the traditional regression approach.

Adult↗
PubMed1997

Censoring issues in survival analysis.

A key characteristic that distinguishes survival analysis from other areas in statistics is that survival data are usually censored. Censoring occurs when incomplete information is available about the survival time of some individuals. We define censoring through some practical examples extracted from the literature in various fields of public health. With few exceptions, the censoring mechanisms in most observational studies are unknown and hence it is necessary to make assumptions about censoring when the common statistical methods are used to analyze censored data. In addition, we present situations in which censoring mechanisms can be ignored. The effects of the censoring assumptions are demonstrated through actual studies.

Bias↗
PubMed1997

Validity of clinical information from a maternity survey.

This research was designed to validate data collected through a survey--an inexpensive way to provide information for quality measurement. The survey was sent to health maintenance organization (HMO) enrollees who had given birth(s) between October 1, 1994, and May 31, 1995. The responses were compared with the medical records. A sample of 407 women was randomly selected from the completed surveys. Medical records were reviewed for 89.9% (362/407) of the sample based on medical record availability. Over 98% of responses agreed with the medical record information regarding whether there were cesarean sections for previous deliveries (kappa = 1.0), cesarean section for recent delivery (kappa = 0.95), and vaginal birth after cesarean section (kappa = 0.96). Over 99% of the mothers agreed with the information regarding whether the newborn birth weight was under 2500 g (kappa = 0.91). The findings strongly support the validation of this instrument. Using this validated instrument enables health plans to cost-effectively obtain crucial information.

Adult↗
PubMed1996

A three-state disease model with interval-censored data: estimation and applications to AIDS and cancer.

In presence of interval-censored data, we propose a general three-state disease model with covariates. Such data can arise, for example, in epidemiologic studies of infectious disease where both the times of infection and disease onset are not directly observed, or in cancer studies where the time of disease metastasis is known up to a specified interval. The proposed model allows the distributions of the transition times between states to depend on covariates and the time in the previous state. An estimation procedure for the underlying distributions and the model coefficients is suggested with the EM algorithm. The EMS algorithm (Smoothed EM algorithm) is also considered to obtain smooth estimates of the distributions. The proposed method is illustrated with data from an AIDS study and a study of patients with malignant melanoma.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Monitoring dietary change in a low-fat diet intervention study: advantages of using 24-hour dietary recalls vs food records.

OBJECTIVE: The purpose of the study was to evaluate two methods of dietary assessment for monitoring change in fat intake in a low-fat diet intervention study. DESIGN: The two dietary assessment methods were a 4-day food record (4DFR) and an unannounced 24-hour dietary recall conducted by telephone interview (referred to as a telephone recall [TR]). Subjects were assigned randomly to either a low-fat diet intervention group or a control group that received no counseling about fat intake. Dietary data were collected at baseline, 6 months, and 12 months. SUBJECTS: Two hundred ninety postmenopausal women with localized breast cancer were recruited at seven clinical centers in the United States. STATISTICAL ANALYSIS: Analysis of variance was used to test for significant differences in mean fat and energy intakes. RESULTS: Three sources of error were identified: (a) an instrument effect, suggesting underreporting at baseline of approximately 8% in mean energy intake and 11% in mean fat intake in the TR group compared with the 4DFR group (P = .0001); (b) a repeated measures effect observed for the 4DFR, suggesting underreporting of approximately 7% for energy intake and 14% for fat intake in the control group at 6 and 12 months compared with baseline values (P < .001); and (c) an adherence effect (or compliance bias), suggesting greater compliance to the low-fat intervention diet when subjects were keeping food records than when estimates were based on the unannounced TR. Compared with the TR, the 4DFR overestimated the extent of fat reduction in the low-fat diet intervention group by 41% (P = .08) and 25% (P = .62) at 6 and 12 months, respectively. APPLICATION: Multiple days of unannounced 24-hour recalls may be preferable to multiple-day food records for monitoring dietary change in diet intervention studies.

Aged↗
PubMed1996

Clinical detection of sarcopenic obesity by bioelectrical impedance analysis.

To assess whether bioelectrical impedance analysis (BIA) provides clinically useful information on body composition beyond that obtained from measuring height and weight, we clinically classified 306 obese patients (233 females and 73 males) into tertiles of increasing fat-free mass estimated by BIA. Because fat-free mass by BIA is an estimate of lean body mass, the lowest tertile was clinically defined as sarcopenic obesity (reduced lean body mass), as contrasted with proportionate or muscular obesity in the next two tertiles. Fat mass in patients in each of the above tertiles based on BIA was then compared with fat mass estimated by using the equations of Garrow and Webster with body mass index (weight/height2). BIA-estimated fat mass was 4.3 kg greater in the sarcopenic group (n = 102) than predicted from body mass index. Fat mass predicted by BIA in the proportionate (n = 102) and muscular (n = 102) groups differed by less than the SEE of fat mass predicted by BMI. In premenopausal women at increased risk of breast cancer BIA showed a high prevalence of sarcopenic obesity (28/30) in these women at normal body mass indexes. Thus, BIA may be clinically useful for demonstrating sarcopenic obesity, but additional studies are needed to determine the metabolic and clinical significance of sarcopenic obesity.

Adipose Tissue↗
PubMed1994

Efficient power computation for exact and mid-P tests for the common odds ratio in several 2 x 2 tables.

When designing a study that may generate a set of sparse 2 x 2 tables, or when confronted with 'negative' results upon exact analysis of such tables, we need to compute the power of exact tests. In this paper we provide an efficient approach for computing exact unconditional power for four exact tests on the common odds ratio in a series of 2 x 2 tables. These tests are the traditional exact test; a test based on a probability ordering of the sample space; and two tests based on ordering the sample space according to distance from the mean, or median. For each test, we consider both a conservative version and a mid-P adjusted version. We explore three computational options for power determination: exact power computation, calculation of exact upper and lower bounds for power, and Monte Carlo confidence bounds for power. We present an interactive program implementing these options. For study design, the program may be run several times to arrive at a sample configuration with adequate power.

Case-Control Studies↗
PubMed1994

Analysis of longitudinal data: random coefficient regression modelling.

We review random coefficient regression (RCR) models and methods for fitting these models from an applications perspective. Methods for data with exponential family distributions are presented with the Gaussian distribution as a special case. Attention is given to interpretation of fixed effects and the correlation structures implied by RCR models. Estimation methods are presented wtih computational approaches. Problems associated with testing fixed effects include accurate variance estimation and robustness to misspecification of the covariance structure. Methods for model selection and assessment are presented. An example is used to demonstrate recommended approaches.

Adult↗
PubMed1994

Application of multistage Markov modeling to malignant melanoma progression.

BACKGROUND: A fundamental research goal in clinical melanoma studies is to understand the natural history of melanoma and its relationship with prognostic factors. The current understanding of melanoma progression and the relationship of risk factors is based on two-stage modeling. METHODS: The authors propose a multistage Markov model for melanoma progression. This model is applied to a data set consisting of approximately 3900 follow-up staging visits of patients with melanoma. The approach takes into account the heavy censoring encountered in this data set and all chronic, subclinically progressive disease. The Markov transition parameters are expressed as Cox regression functions of the relevant prognostic variables. Parameter estimation is achieved by using a missing-data approach. RESULTS: Tumor thickness, level, and site and patient gender and age at diagnosis are independent risk factors in the transition from local to nodal disease. Tumor thickness and level of invasion and patient age are factors in the transition from local disease to dissemination (without intervening involvement of the nodes). Tumor thickness, patient age, primary site, and the number of involved lymph nodes are factors in the transition from nodal disease to dissemination. Transition from dissemination to death is affected by primary thickness, patient gender, number of nodes involved, and site of metastases. CONCLUSION: This multistage analysis contributes to a more accurate understanding of the progress of melanoma and is likely to be applicable to the study of other progressive diseases. Graphic goodness-of-fit results suggest satisfactory predictability of the model to other data sets.

Female↗
PubMed1994

Clinical evaluation of a minimal intervention meal replacement regimen for weight reduction.

OBJECTIVE: The purpose of this study was to evaluate a simplified weight loss program in which subjects were provided a widely available meal replacement product and its package insert information (Ultra Slim-Fast). METHOD: Weekly follow-up visits were carried out by non-physician personnel for weight measurement, distribution of product, and completion of a subjective questionnaire. No dietary counseling was provided. A total of 273 of 301 subjects (91%) completed 12 weeks of study. Men lost 50% (from 119 to 108% of ideal body weight) and women lost 35% (from 122 to 111% of ideal body weight) of excess body weight. Thirty-five patients who lost < 9 lbs in 12 weeks were considered non-adherent and were excluded from the next phase of the study during which 238 subjects were followed biweekly. RESULTS: Despite a $25/week payment for participation nearly 44% of subjects dropped out or were judged non-compliant prior to the end of the study. At 116 weeks, 133 (97 females, 36 males) of 238 subjects remained in the study (44% of the initial population), with average weight loss from baseline of 13.6 +/- 10.5 lb in females and 14.0 +/- 10.5 lb in males. DISCUSSION: The weight loss observed (approximately 10% of body weight) is significant and has been associated with important health benefits particularly for patients with hypertension and non-insulin dependent diabetes. The potential advantages of using meal replacements for mild obesity include wide availability to aid compliance, low cost and minimal professional intervention.

Adult↗