Biomedical subjects

Jeffrey A Gornbein

Publications and source records attributed to Jeffrey A Gornbein.

9 recordsLinked to original sources

PubMed2006

Risk factors for fractures in older men and women: The Leisure World Cohort Study.

BACKGROUND: Osteoporosis results in >1.5 million fractures in the United States each year, leading to substantial health care costs and loss of quality of life. One major gap in our knowledge is how to effectively identify individuals at risk of developing a fracture. OBJECTIVE: We examined a population-based cohort for risk factors for fractures of the hip, wrist, and spine in men and women. METHODS: The Leisure World Cohort Study was established between 1981 and 1985 when residents of a southern California retirement community completed a postal health survey. Multiple lifestyle, medical, attitudinal, and anthropomorphic factors were self-reported. Fractures were identified from 4 follow-up surveys, hospital discharge records, and death certificates. Fracture rates were determined separately for men and women. Cox proportional hazards regression was used to identify predictors of fracture. RESULTS: Incident fractures of the hip (n = 1,227), wrist (n = 445), and spine (n = 729) incurred over the course of 2 decades were identified in the 13,978 residents surveyed. Mean (SD) age at entry was 74.9 (7.2) years for men and 73.7 (7.4) years for women. The most important risk factors for fracture were the same in men and women: age increased risk of hip and spine fractures (hazard ratio [HR] = 2.3-3.2 per 10 years) and history of fracture increased fracture risk at all 3 sites (HR = 1.4-3.2). In both men and women, glaucoma was a significant risk factor for hip fracture (HR = 1.9 and 1.3, respectively), and smoking was a risk factor for hip and spine fractures. Men and women with a positive mental attitude had fewer hip and spine fractures (HR = 0.7-0.9). High body mass index was protective at all 3 fracture sites in women (HR = 0.7-0.8), but those who used vitamin A supplements had increased rates of hip and wrist fracture (HR = 1.1 per 10,000 IU per day). CONCLUSIONS: Attitude, lifestyle choices, and the presence of medical conditions may influence the rate of osteoporotic fracture in older women and men and may help identify individuals at high risk.

Aged↗

PubMed2005

Loss of annexin A1 expression in human breast cancer detected by multiple high-throughput analyses.

To test the efficacy of combined high-throughput analyses (HTA) in target gene identification, screening criteria were set using >fivefold difference by microarray and statistically significant changes (p<0.01) in SAGE and EST. Microarray analysis of two normal and seven breast cancer samples found 129 genes with >fivefold changes. Further SAGE and EST analyses of these genes identified four qualified genes, ERBB2, GATA3, AGR2, and ANXA1. Their expression pattern was validated by RT-PCR in both breast cell lines and tissue samples. Loss of ANXA1 in breast cancer was further confirmed at mRNA level by Human Breast Cancer Tissue Profiling Array and at protein level by immunohistochemical staining. This study demonstrated that combined HTA effectively narrowed the number of genes for further study, while retaining the sensitivity in identifying biologically important genes such as ERBB2 and ANXA1. A distinctive loss of ANXA1 in breast cancer suggests its involvement in maintaining normal breast biology.

Algorithms↗

PubMed2005

Rethinking the cesarean rate: how pregnancy complications may affect interhospital comparisons.

BACKGROUND: The cesarean rate has served an integral role in the monitoring of obstetrical care, and in 2002, the national rate reached 26.1%, the highest ever reported. OBJECTIVE: We sought to describe the effect of clinical complications on hospital cesarean rates. RESEARCH DESIGN: This was a population-based cohort study. SUBJECTS: All laboring women without a previous cesarean who delivered in California in 1995 as reported through public-use hospital discharge data were included. MEASURES: Women with and without maternal, fetal, or placental complications were compared with respect to cesarean use. Using recursive partitioning algorithms, women with complications were stratified into clinically homogeneous categories, which were analyzed separately with respect to cesarean use. RESULTS: The 443,532 women delivered at 288 hospitals and included 116,170 women (26.2%) in the complicated group (cesarean rate 22.6%); and 327,362 women (73.8%) in the uncomplicated group (cesarean rate 6.7%). At the hospital level, the cesarean rates among the complicated and uncomplicated patients respectively were: median 23.5% (range, 2.2-9.9%); and median 6.5% (range, 1.8-18.2%). Recursive partitioning algorithms suggested 16 distinct clinical categories, with cesarean rates varying from 8.9% for women with asthma to 84.5% for women with an unengaged fetal head. CONCLUSIONS: Cesarean rates varied widely across complication types, and complication-specific rates varied widely among hospitals. Although the presence of pregnancy complications upon hospital admission comprised the strongest factor affecting first-time cesarean use among laboring women, the importance and interdependence of these clinical conditions has yet to be incorporated into commonly used models for cesarean rate comparisons.

Adult↗

PubMed2004

Elective primary caesarean delivery: accuracy of administrative data.

The caesarean delivery rate has become a commonly used measure intended to reflect the quality of obstetric care. At least 25% of all primary caesarean deliveries occur electively, i.e. to women who are not in labour. This study is intended to validate a previously published model designed to use ICD-9-CM codes to identify and categorise cases of elective primary caesarean delivery by their indication. ICD-9-CM codes were compared with diagnoses written in the medical record for all women without a prior caesarean who delivered in the same month in a single hospital to examine the accuracy of the codes for 12 potential elective primary caesarean indications derived by the published model: malpresentation; bleeding; genital herpes; severe hypertension; uterine scar; multiple gestation; macrosomia; unengaged fetus; maternal soft tissue conditions; other hypertensive conditions; prematurity; and chromosomal anomalies. Of 440 eligible women, a total of 26 (5.9%) had an elective primary caesarean by medical record review vs. [27] (6.1%) by administrative data. Using medical record data as the gold standard, the sensitivity, specificity, and accuracy of administrative data for the identification of elective primary caesarean delivery were 73.1%, 98.1%, and 96.6%, respectively. Administrative coding for all of the 12 conditions was highly specific, although wide variability existed in its sensitivity; its accuracy ranged between 83.9% and 100%. These results suggest that, despite widespread use of caesarean delivery rates obtained through administrative data, more experience is needed to determine which obstetric codes may be sufficiently specific, sensitive, or prevalent to serve a monitoring or surveillance function reflecting the quality of obstetrical care. The results support continued efforts to use administrative data to monitor elective primary caesarean delivery.

Adult↗

PubMed2003

Proteomic profiling of cancer biomarkers.

Early detection and correct diagnosis are essential for effective treatment of cancer and patient survival. Complete sequencing of the human genome, and the genomes of other species, provides valuable tools for discerning the genetic abnormalities in cancer. However, differences between cancerous and normal cells reflect more than variations in genetic sequences and abundance of transcribed RNA. Many cancer biomarkers are manifestation of differences in post-transcriptional splicing and/or post-translational modifications. Thus, proteomic tools are being increasingly utilised in the post-genomic era for discovery of new cancer biomarkers. In this paper we will provide an overview of the biomarker discovery process from the proteomic profiling point of view, with emphasis given to the principles that are involved in the process, including the protein identification strategies, and how surface enhanced laser desorption ionisation mass spectrometry fits into the picture. The aim is to provide a resource for the experimental practitioner seeking awareness of the analytical tools that are now available in contemporary cancer research.

Biomarkers, Tumor↗

PubMed2002

New era of liver transplantation for hepatitis B: a 17-year single-center experience.

OBJECTIVE: To evaluate the variables affecting orthotopic liver transplantation (OLT) outcome for hepatitis B virus (HBV) in a large patient cohort over a 17-year period. SUMMARY BACKGROUND DATA: Historically, OLT for chronic HBV infection has been associated with aggressive reinfection and poor survival results. More recently, OLT outcome has been improved with the routine use of antiviral therapy with either hepatitis B immune globulin (HBIg) or lamivudine; however, HBV recurrence remains common. The authors studied the factors affecting HBV recurrence and outcome of transplantation, including the effects of combination viral prophylaxis with HBIg and lamivudine. METHODS: A retrospective review of 166 OLT recipients for chronic HBV over a 17-year period at a single center was performed. Median follow-up was 29 months. HBV recurrence was defined by HBsAg seropositivity after OLT. HBIg monotherapy was used in 28 (17%) patients, lamivudine monotherapy in 20 (12%), and HBIg and lamivudine combination in 89 (54%); 29 (17%) did not receive any HBV prophylaxis. Hepatocellular carcinoma (HCC) was present in 43 patients (26%) and urgent United Network for Organ Sharing (UNOS) status was assigned to 27 patients (16%). Univariate and multivariate analyses were performed to identify factors that affected OLT outcome. RESULTS: Overall 1-, 3-, and 5-year patient survival rates were 85.8%, 73.6%, and 71.8%, respectively. As expected, HBV recurrence-free survival rates were significantly lower than overall survival rates (76.4%, 58.7%, and 48.3%). When compared with a nontreated cohort, OLT recipients receiving combination viral prophylaxis with HBIg and lamivudine showed markedly reduced HBV recurrence rates and significantly improved 1- and 3-year recurrence-free survival rates. By univariate estimates, patient survival was reduced in the presence of HCC, in the Asian population, and urgent candidates by UNOS classification. Graft loss rates were significantly increased in urgent OLT candidates, Asians, patients with pretransplant positive DNA, and in the presence of HCC. Factors that were significant by univariate analysis or thought to be clinically relevant were subjected to multivariate analysis. By multivariate estimates, urgent UNOS or presence of HCC adversely affected patient and graft survival rates, whereas combination prophylactic therapy strongly predicted improved patient and graft survival rates as well as recurrence-free survival rates. CONCLUSIONS: Orthotopic liver transplantation for HBV under combination viral prophylaxis results in survival rates equivalent to other indications. Pretransplant viral replication, UNOS status, and the presence of HCC are all sensitive markers for posttransplantation outcome. Viral prophylactic therapy has effectively reduced HBV recurrence and prolonged survival outcomes. The combination of HBIg and lamivudine is the prophylactic regimen of choice.

Antiviral Agents↗

PubMed2002

Cyclin D1 amplification and p16(MTS1/CDK4I) deletion correlate with poor prognosis in head and neck tumors.

OBJECTIVES/HYPOTHESIS: Cyclin D1, a cell cycle regulator localized to chromosome 11q13, is amplified in several human tumors including head and neck squamous cell carcinoma (HNSCC). Amplification and/or overexpression of cyclin D1 have been correlated to a poor prognosis. Deletion of the p16 gene, localized to 9p21, has also been observed in a significant proportion of HNSCC. The p16 gene regulates cyclin D1-CDK4 activity and prevents retinoblastoma tumor suppressor gene phosphorylation, thereby downregulating cellular proliferation. Detection of cyclin D1 amplification and p16 deletion using a simple and sensitive method will be valuable for the development of effective treatment modalities for head and neck cancer. STUDY DESIGN: We have used fluorescence in situ hybridization (FISH) to study cyclin D1 amplification and p16 gene deletion in head and neck tumors. Both single- and dual-color FISH were performed. METHODS: Paraffin-embedded tissues from 103 patients with HNSCC were analyzed using genomic DNA probes for cyclin D1 and p16. Dual-color FISH was performed with chromosome 11 or 9 centromeric probes as a control. Twenty-eight of these samples were analyzed for p16 expression by immunohistochemistry. RESULTS: Cyclin D1 amplification was observed in 30% (31/103) of patients, and p16 deletion in 52% (54/103). Lack of p16 expression was observed in 64% (18/28) of patients. There was a good correlation between the deletion of p16 sequences and the loss of p16 expression (P = .008). Amplification of cyclin D1 had a statistically significant association with recurrence, distant metastasis, and survival at 36 months. There was a significant association between p16 deletion and the development of distant metastases. Cyclin D1 amplification and p16 deletion together correlated with recurrence, distant metastasis, and survival. CONCLUSIONS: We demonstrate that FISH is a simple and sensitive method for detecting cyclin D1 amplification and p16 deletion in head and neck cancer. Our results suggest that these two genetic aberrations together portend a poorer outcome than either of the abnormalities alone in head and neck cancer.

Adult↗

PubMed2002

Using administrative data to identify indications for elective primary cesarean delivery.

OBJECTIVE: To develop a methodology to identify indications and normative rates for elective primary cesarean delivery using administrative data. DATA SOURCES/STUDY SETTING: All delivery discharges in 1995, as reported to the California Office of Statewide Health Planning and Development (secondary data). STUDY DESIGN: Retrospective population based study. DATA COLLECTION/EXTRACTION: Data were entered into a recursive partitioning algorithm to develop a hierarchy of conditions by which patients with multiple conditions could be sorted with respect to the binary outcome of labor or elective primary cesarean without labor. This hierarchy was examined for its clinical consistency, validated on a second sample, and compared with results obtained from logistic regression. PRINCIPAL FINDINGS: Four percent (19,664) of delivery discharges in 1995 underwent elective primary cesarean. Twelve clinical conditions contributed to the hierarchy, and accounted for 92.9 percent of all women experiencing elective primary cesarean delivery. The remaining 7.1 percent of the elective primary cesarean cases were classified as "unspecified." CONCLUSIONS: A standardized methodology (utilizing recursive partitioning algorithms) for assigning indications for elective primary cesarean is presented. This methodology relies on administrative data, classifies women with complex comorbidity patterns into clinically relevant subpopulations, and can be used to establish normative rates for benchmarking specific indications for cesarean delivery.

Algorithms↗

PubMedDate not supplied

Histopathologic characteristics predicting HER-2/neu amplification in breast cancer.

The HER-2/neu gene is a proto-oncogene that is amplified in 10-30% of breast cancers. New drugs for targeted therapy, such as Herceptin, are effective for patients with HER-2/neu-positive tumors, making it necessary to have a noncostly and accurate method to assess HER-2/neu status. We studied the correlation of findings made by fluorescent in situ hybridization (FISH) and immunohistochemistry (IHC) staining and the possibility of combining IHC and other clinicopathologic characteristics of breast tumors to predict FISH-determined HER-2/neu status. The clinicopathologic characteristics analyzed were the size of the tumor, p53, lymph-vascular invasion, estrogen/progesterone receptors (ER/PR), tumor grade, axillary lymph node status, and patient age. A total of 199 cases of invasive breast cancer studied at the UCLA Pathology Laboratory during 2003 were included in this study. Tumors with IHC 0, 1+, 2+, and 3+ scores were found to be FISH positive in 3.5%, 6.4%, 25.7%, and 81.5% of the respective groups. Our study showed a strong association between the FISH-negative and IHC scored 0 and 1+ tumors, suggesting that the FISH test may not be necessary in these cases (p<0.0001). Although the concordance between IHC 3+ and FISH positive is high, 18% of the patients with overexpression of HER-2/neu fail to show gene amplification by FISH. HER-2/neu positivity was found to be proportionally associated with increasing grade in infiltrating ductal carcinoma (p<0.0001). p53-positive tumors are more likely to be HER-2/neu amplified (p=0.0003). Tumors that are negative for ER/PR are also associated with HER-2/neu positivity by FISH (31.15%, p=0.0016). FISH-determined HER-2/neu status is not associated with histologic type, tumor size, nodal status, lymph-vascular invasion, or patient age.

Age Factors↗