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1.
Can Fam Physician ; 55(10): e41-6, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19826141

ABSTRACT

OBJECTIVE: To evaluate the current patient care practices that address the predisposing and precipitating factors contributing to the prevention of hospital-acquired delirium in the elderly. DESIGN: Prospective cohort (observational) study. PARTICIPANTS: Patients 65 years of age and older who were admitted to medical teaching units at the University of Alberta Hospital in Edmonton over a period of 7 months and who were at risk of delirium. SETTING: Medical teaching units at the University of Alberta. MAIN OUTCOME MEASURES: Demographic data and information on predisposing factors for hospital-acquired delirium were obtained for all patients. Documented clinical practices that likely prevent common precipitants of delirium were also recorded. RESULTS: Of the 132 patients enrolled, 20 (15.2%) developed hospital-acquired delirium. At the time of admission several predisposing factors were not documented (eg, possible cognitive impairment 16 [12%], visual impairment 52 [39.4%], and functional status of activities of daily living 99 [75.0%]). Recorded precipitating factors included catheter use, screening for dehydration, and medications. Catheters were used in 35 (26.5%) patients, and fluid intake-and-output charting assessed dehydration in 57 (43.2%) patients. At the time of admission there was no documentation of hearing status in 69 (52.3%) patients and aspiration risk in 104 (78.8%) patients. After admission, reorientation measures were documented in only 16 (12.1%) patients. Although all patients had brief mental status evaluations performed once daily, this was not noted to occur twice daily (which would provide important information about fluctuation of mental status) and there was no formal attention span testing. In this study, hospital-acquired delirium was also associated with increased mortality (P < .004), increased length of stay (P < .007), and increased institutionalization (P < .027). CONCLUSION: Gaps were noted in patient care practices that might contribute to hospital-acquired delirium and also in measures to identify the development of delirium at an earlier stage. Effort should be made to educate health professionals to identify the predisposing and precipitating factors, and to screen for delirium. This might improve the prevention of delirium.


Subject(s)
Delirium/prevention & control , Aged , Alberta , Delirium/etiology , Diagnostic and Statistical Manual of Mental Disorders , Disease Susceptibility , Female , Hospitalization , Hospitals, General/statistics & numerical data , Humans , Male
2.
Leuk Lymphoma ; 50(10): 1606-17, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19626540

ABSTRACT

Recombinant interferon alpha-2b (IFN-alpha2) has direct and indirect antiproliferative effects in lymphoma, and may augment cytotoxicity when combined with chemotherapy. CALGB 8691 is a randomized study of daily oral cyclophosphamide (CPA) at 100 mg/m2 with or without IFN-alpha2 at 2 x 106 IU/m2 three times per week, followed by a second randomization between IFN-alpha2 maintenance (2 x 106 IU/m2 three times weekly) versus observation in treatment-naïve patients with follicular lymphoma (FL). Five hundred eighty-one patients were randomized to either CPA (n = 293) or CPA plus IFN-alpha2 (n = 288). One hundred five responding patients were randomized to observation and 99 to maintenance IFN-alpha2. With a median follow-up of 11.5 years, the median event-free and overall survival (OS) for CPA induction alone were 2.5 years (95% CI 2.2, 3.0) and 9 years (95% CI 7.7, 10.2), compared to 2.4 years (95% CI 2.1, 3.1) and 8.4 years (95% CI 7.5, 11.1) for the combination arm (p = NS). Patients with a partial response (PR) and randomized to observation had the worst outcome (event-free survival (EFS) 1.8 years versus 3.9 years; p = 0.002). Patients with a PR randomized to IFN-alpha2 had a similar EFS to compared to patients with complete response (CR), but this did not translate into a survival advantage. Myelosuppression was increased in IFN-alpha2-containing arms. Despite the small benefit in EFS in patients with PR randomized to IFN-alpha2 maintenance, we conclude that the addition of low dose IFN-alpha2 did not significantly improve the response rate, duration of response, event-free, or OS obtained with single-agent daily oral CPA in patients with previously untreated FL.


Subject(s)
Antineoplastic Agents, Alkylating/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cyclophosphamide/therapeutic use , Lymphoma, Follicular/drug therapy , Adult , Aged , Aged, 80 and over , Antigens, CD20/biosynthesis , Antigens, CD20/immunology , Antineoplastic Agents, Alkylating/administration & dosage , Antineoplastic Agents, Alkylating/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Combined Modality Therapy , Cyclophosphamide/administration & dosage , Cyclophosphamide/adverse effects , Drug Synergism , Female , Follow-Up Studies , Humans , Immunologic Factors/administration & dosage , Immunologic Factors/adverse effects , Interferon alpha-2 , Interferon-alpha/administration & dosage , Interferon-alpha/adverse effects , Male , Middle Aged , Neoplasms, Second Primary/chemically induced , Recombinant Proteins , Survival Analysis , Treatment Failure , Young Adult
3.
Lymphology ; 42(4): 152-60, 2009 Dec.
Article in English | MEDLINE | ID: mdl-20218083

ABSTRACT

A patient with the classical phenotype of Lymphedema-Distichiasis syndrome (OMIM 153400) is described who showed no mutations in the sequence of FOXC2. Accordingly, a Gene Chip 250k array analysis was undertaken with dense SNP genotyping of the genomic region surrounding the FOXC2 locus on Chromosome 16 followed by copy number evaluation by real time PCR. The latter assay showed evidence of a duplicated region 5' of FOXC2 that could be causative for the patient's striking phenotype, which included both distichiasis and a hyperplastic refluxing lymphatic vascular and lymph node phenotype associated with pubertal onset lymphedema, scoliosis and strabismus.


Subject(s)
5' Untranslated Regions/genetics , Chromosomes, Human, Pair 16/genetics , Eyelashes/abnormalities , Forkhead Transcription Factors/genetics , Gene Duplication , Lymphedema/genetics , Mutation/genetics , Adult , Eyelashes/pathology , Female , Humans , Lymphedema/diagnosis , Oligonucleotide Array Sequence Analysis , Phenotype , Polymorphism, Single Nucleotide/genetics , Syndrome
4.
Breast Cancer Res Treat ; 113(3): 479-90, 2009 Feb.
Article in English | MEDLINE | ID: mdl-18306034

ABSTRACT

PURPOSE: To describe long-term results of a multimodality strategy for stage III breast cancer utilizing neoadjuvant doxorubicin followed by mastectomy, CMF, and radiotherapy. PATIENTS AND METHODS: Women with biopsy-proven, clinical stage III breast cancer and adequate organ function were eligible. Neoadjuvant doxorubicin (30 mg/m(2) days 1-3, every 28 days for 4 cycles) was followed by mastectomy, in stable or responding patients. Sixteen weeks of postoperative CMF followed (continuous oral cyclophosphamide (2 mg/kg/day); methotrexate (0.7 mg/kg IV) and fluorouracil (12 mg/kg IV) weekly, weeks 1-8, and than biweekly, weeks 9-16). Radiation therapy followed adjuvant chemotherapy. RESULTS: Clinical response rate was 71% (79/111, 95% CI = 62-79%), with 19% complete clinical response. Pathologic complete response was 5% (95% CI = 2-11%). Median follow-up is 15.6 years. Half of the patients progressed by 2.2 years; half died by 5.4 years (range 6 months-15 years). The hazard of dying was greatest in the first 5 years after diagnosis and declined thereafter. Time to progression and overall survival were predicted by number of pathologically involved lymph nodes (TTP: HR [10 vs. 1 node] 2.40, 95% CI = 1.63-3.53, P < 0.0001; OS: HR 2.50, 95% CI = 1.74-3.58, P < 0.0001). CONCLUSIONS: After multimodality treatment for locally advanced breast cancer, long-term survival was correlated with the number of pathologically positive lymph nodes, but not to clinical response. The hazard of death was highest during the first 5 years after diagnosis and declined thereafter, indicating a possible intermediate endpoint for future trials of neoadjuvant treatment.


Subject(s)
Adenocarcinoma/therapy , Breast Neoplasms/therapy , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adult , Aged , Antineoplastic Agents/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Combined Modality Therapy , Cyclophosphamide/administration & dosage , Disease Progression , Doxorubicin/administration & dosage , Female , Fluorouracil/administration & dosage , Follow-Up Studies , Humans , Mastectomy , Methotrexate/administration & dosage , Middle Aged , Neoadjuvant Therapy , Neoplasm Staging , Radiotherapy, Adjuvant , Survival Analysis
5.
J Affect Disord ; 107(1-3): 275-9, 2008 Apr.
Article in English | MEDLINE | ID: mdl-17884176

ABSTRACT

BACKGROUND: Bipolar disorder is highly recurrent and rates of comorbidity are high. Studies have pointed to anxiety comorbidity as one factor associated with risk of suicide attempts and poor overall outcome. This study aimed to explore the feasibility and potential benefits of a new psychological treatment (Mindfulness-based Cognitive Therapy: MBCT) for people with bipolar disorder focusing on between-episode anxiety and depressive symptoms. METHODS: The study used data from a pilot randomized trial of MBCT for people with bipolar disorder in remission, focusing on between-episode anxiety and depressive symptoms. Immediate effects of MBCT versus waitlist on levels of anxiety and depression were compared between unipolar and bipolar participants. RESULTS: The results suggest that MBCT led to improved immediate outcomes in terms of anxiety which were specific to the bipolar group. Both bipolar and unipolar participants allocated to MBCT showed reductions in residual depressive symptoms relative to those allocated to the waitlist condition. LIMITATIONS: Analyses were based on a small sample, limiting power. Additionally the study recruited participants with suicidal ideation or behaviour so the findings cannot immediately be generalized to individuals without these symptoms. CONCLUSIONS: The study, although preliminary, suggests an immediate effect of MBCT on anxiety and depressive symptoms among bipolar participants with suicidal ideation or behaviour, and indicates that further research into the use of MBCT with bipolar patients may be warranted.


Subject(s)
Bipolar Disorder/therapy , Cognitive Behavioral Therapy/methods , Adolescent , Adult , Aged , Ambulatory Care , Anxiety Disorders/diagnosis , Anxiety Disorders/psychology , Anxiety Disorders/therapy , Bipolar Disorder/diagnosis , Bipolar Disorder/psychology , Depressive Disorder/diagnosis , Depressive Disorder/psychology , Depressive Disorder/therapy , Female , Humans , Male , Meditation/methods , Middle Aged , Personality Inventory , Pilot Projects , Psychotherapy, Group/methods , Suicide/psychology , Treatment Outcome , Waiting Lists
7.
Gut ; 53(7): 944-51, 2004 Jul.
Article in English | MEDLINE | ID: mdl-15194641

ABSTRACT

BACKGROUND AND AIMS: The causative molecular pathways underlying the pathogenesis of coeliac disease are poorly understood. To unravel novel aspects of disease pathogenesis, we used microarrays to determine changes in gene expression of duodenal biopsies. METHODS: cDNA microarrays representing 19 200 genes were used to compare gene expression profiles of duodenal biopsies from 15 coeliac disease patients with villous atrophy (Marsh III) and seven control individuals with normal biopsies (Marsh 0). In addition, the specific effect of gluten was studied by comparing the expression profiles of Marsh III lesions of seven patients exposed to gluten with four patients on a gluten free diet. RESULTS: Comparing Marsh III with Marsh 0 lesions identified 109 genes that differed significantly (p<0.001) in expression levels between patients and controls. A large number of these genes have functions in proliferation and differentiation pathways and might be important for correct development of crypt-villous units. Alterations in these pathways may lead to the characteristic hyperplasia and villous atrophy seen in coeliac disease. The analyses also revealed 120 differentially expressed genes (p<0.005) when comparing patients on a gluten free diet with those exposed to gluten. These genes further strengthen our observation of increased cell proliferation in the presence of gluten. CONCLUSIONS: Our study provides new candidate genes in the pathogenesis of coeliac disease. Based on our results, we hypothesise that villous atrophy in coeliac disease patients is due to failure in cell differentiation. These genes are involved in pathways not previously implicated in coeliac disease pathogenesis and they may provide new targets for therapy.


Subject(s)
Celiac Disease/genetics , Gene Expression Profiling/methods , Genetic Predisposition to Disease , Oligonucleotide Array Sequence Analysis/methods , Adult , Aged , Aged, 80 and over , Biopsy , Celiac Disease/diet therapy , Celiac Disease/pathology , Child, Preschool , Duodenum/pathology , Female , Gene Expression Regulation , Glutens/administration & dosage , Humans , Intestinal Mucosa/pathology , Male , Middle Aged , Reverse Transcriptase Polymerase Chain Reaction
8.
J Clin Oncol ; 21(9): 1819-24, 2003 May 01.
Article in English | MEDLINE | ID: mdl-12721259

ABSTRACT

PURPOSE: To determine whether biochemical modulation with LV (leucovorin) enhances the efficacy of CAF (cyclophosphamide, doxorubicin, and fluorouracil) against metastatic breast cancer. PATIENTS AND METHODS: Women with histologically confirmed stage IV breast cancer, Cancer and Leukemia Group B (CALGB) performance status 0 to 2, and no prior chemotherapy for metastatic disease were randomly assigned to receive CAF (cyclophosphamide 500 mg/m2 day 1, doxorubicin 40 mg/m2 day 1, and fluorouracil [FU] 200 mg/m2 intravenous bolus days 1 to 5) with or without LV (LV 200 mg/m2 over 30 minutes days 1 to 5 given 1 hour before FU). RESULTS: Two hundred forty-two patients were randomly assigned to treatment; 124 patients had visceral crisis and 40 patients had a CALGB performance status score of 2. The median follow-up was 6 years. The two study arms were similar with regard to serious adverse events; four patients died from treatment-related causes, two patients on each study arm. Predictive variables for time to treatment failure and survival were visceral disease and performance status. The overall response rate was 29% for CAF versus 28% for CAF plus LV. The median time to treatment failure (9 months) and median survival (1.7 years) did not differ by treatment arm. CONCLUSION: Modulation of CAF with LV improved neither response rates nor survival among women with metastatic breast cancer, compared with CAF alone. Multivariate analyses confirmed the prognostic importance of performance status and visceral crisis. However, the overall and complete response rates, response durations, time to treatment failure, and survival were the same in the two treatment arms.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Aged , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Breast Neoplasms/pathology , Cyclophosphamide/administration & dosage , Disease Progression , Doxorubicin/administration & dosage , Female , Fluorouracil/administration & dosage , Health Status , Humans , Leucovorin/administration & dosage , Middle Aged , Neoplasm Metastasis , Prognosis , Survival , Treatment Outcome , Viscera/pathology
9.
Appl Radiat Isot ; 57(6): 875-82, 2002 Dec.
Article in English | MEDLINE | ID: mdl-12406632

ABSTRACT

Imaging plates (IPs) are a reusable media, which when exposed to ionizing radiation, store a latent image that can be read out with a red laser as photostimulated luminescence (PSL). They are widely used as a substitute for X-ray films for diagnostic studies. In diagnostic radiology this technology is known as computed radiography. In this work, the energy response of a commercial IP to beta-particle reference radiation fields used for calibrations at the National Institute of Standards and Technology was investigated. The absorbed dose in the active storage phosphor layer was calculated following the scaling procedure for depth dose for high Z materials with reference to water. It was found that the beta particles from Pm-147 and Kr-85 gave 68% and 24% higher PSL responses than that induced by Sr-90, respectively, which was caused by the different PSL detection efficiencies. In addition, normalized response curves of the IPs as a function of depth in polystyrene were measured and compared with the data measured using extrapolation chamber techniques. The difference between both sets of data resulted from the continuous energy change as the beta particle travels across the material, which leads to a different PSL response.


Subject(s)
Brachytherapy/instrumentation , X-Ray Film , Luminescent Measurements
10.
Seizure ; 10(6): 442-6, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11701000

ABSTRACT

The successful surgical treatment of medically refractory epilepsy is based on one of three different principles: (1) elimination of the epileptic focus, (2) interruption of the pathways of neural propagation, and (3) increasing the seizure threshold through cerebral lesions or electrical stimulation. Temporal lobe epilepsy, being the most common focal epilepsy, may ultimately require temporal lobectomy. This is a case report of a 36-year-old male with drug-resistant right mesial temporal lobe epilepsy who failed to obtain seizure control after stereotactic radiosurgery to the seizure focus. Complex-partial seizures occurred 6-7 times monthly, and consisted of a loss of awareness followed by involuntary movements of the right arm. EEG/CC TV monitoring indicated a right mesial temporal lobe focus, which was corroborated by decreased uptake in the right temporal lobe by FDG-PET and by MRI findings of right hippocampal sclerosis. Stereotactic radiosurgery was performed with a 4MV linac, utilizing three isocenters with collimator sizes of 10, 10, and 7 mm respectively. A dose of 1500 cGy (max dose 2535 cGy) was delivered in a single fraction to the patient's right amygdala and hippocampus. There were no acute complications. Following radiosurgery the patient's seizures were improved in both frequency and intensity for approximately 3 months. Antiepileptic medications were continued. Thereafter, seizures increased in both frequency and intensity, occurring 10-20 times monthly. At 1 year post radiosurgery, standard right temporal lobectomy including amygdalohippocampectomy was performed with subsequent resolution of complex-partial seizures. Histopathology of the resected temporal lobe revealed hippocampal cell loss and fibrillary astrocytosis, consistent with hippocampal sclerosis. No radiation-induced histopathologic changes were seen. We conclude that low-dose radiosurgery doses temporarily changed the intensity and character of seizure activity, but actually increased seizure activity long-term. If radiosurgery is to be an effective alternative to temporal lobectomy for medically intractable temporal lobe epilepsy, higher radiosurgery doses will be required. The toxicity and efficacy of higher-dose radiosurgery is currently under investigation.


Subject(s)
Epilepsy, Temporal Lobe/surgery , Radiosurgery/methods , Temporal Lobe/surgery , Adult , Dose-Response Relationship, Radiation , Epilepsy, Temporal Lobe/diagnosis , Humans , Male , Radiography , Temporal Lobe/diagnostic imaging , Temporal Lobe/pathology , Treatment Failure
11.
Clin Cancer Res ; 7(9): 2703-11, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11555582

ABSTRACT

PURPOSE: The HER-2/erbB-2/c-neu (HER-2) proto-oncogene is a M(r) 185,000 transmembrane tyrosine kinase that is amplified and/or overexpressed by 20-40% of breast cancers. HER-2 has been associated with worse prognosis and resistance or sensitivity to specific treatment. We evaluated circulating levels of extracellular domain of HER-2 (ECD/HER-2) in metastatic breast cancer patients and investigated the prognostic and predictive significance of circulating HER-2 levels regarding endocrine therapy or chemotherapy. EXPERIMENTAL DESIGN: Plasma samples from 242 patients were assayed for circulating ECD/HER-2 levels, using a sandwich enzyme immunoassay. ECD/HER-2 was correlated with clinical data gathered from these patients while they were participating in prospective Cancer and Leukemia Group B (CALGB) therapeutic protocols for metastatic breast cancer. RESULTS: Eighty-nine (37%) of 242 patients had elevated ECD/HER-2 levels (> or =10.5 ng/ml). ECD/HER-2 was significantly associated with tumor burden, progesterone receptor levels, and presence of visceral metastases. Patients with elevated pretreatment levels had a significantly shorter OS but not time-to-progression than did those with ECD/HER-2 levels <10.5 ng/ml in univariate analysis. In univariate but not multivariate subset analyses, among patients treated with endocrine therapy (megestrol acetate), elevated initial ECD/HER-2 was associated with worse OS compared with nonelevated patients. However, among patients treated with chemotherapy (mainly anthracycline-containing regimens), OS did not differ significantly. Rates of response to either endocrine therapy or chemotherapy were similar for patients with elevated and nonelevated ECD/HER-2 levels. CONCLUSIONS: ECD/HER-2 levels are elevated in 35-40% of patients with metastatic breast cancer. Elevated ECD/HER-2 levels are associated with a poorer prognosis in these patients. However, no predictive role for ECD/HER-2 was identified, either for endocrine therapy or for anthracycline-based chemotherapy in the metastatic setting.


Subject(s)
Breast Neoplasms/blood , Receptor, ErbB-2/blood , Adult , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Female , Humans , Middle Aged , Multivariate Analysis , Neoplasm Metastasis , Prognosis , Proto-Oncogene Mas , Randomized Controlled Trials as Topic , Survival Analysis , Time Factors , Treatment Outcome
12.
Med Phys ; 28(7): 1397-405, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11488570

ABSTRACT

A computer dose model for a low energy gamma-emitting stent in a heterogeneous medium is described. The method is based on the Sievert model which is adapted to the dose-point-kernel (DPK) model to compute the dose distribution about filtered gamma sources (Sievert-DPK model). The new gamma stent model can take into account effects such as the metallic wire attenuation and the presence of dense calcified plaque in a stented artery. The Sievert-DPK model is tested against numerical simulations around cylindrical shell sources with dimensions comparable to those of a stent using a Monte Carlo transport code. For low energy gamma sources (Cs-131 and Pd-103), it is shown that the Sievert-DPK model is consistent with the Monte Carlo results to about 5%-10% for distances up to 5 mm from the cylindrical surface and 2.5 mm beyond the cylinder edges. These results indicate that the Sievert-DPK model may be useful to predict the dose in intravascular therapy applications for heterogeneous systems consisting of soft tissue, metal and dense plaque.


Subject(s)
Angioplasty, Balloon, Coronary/methods , Radiometry/methods , Calibration , Cesium Radioisotopes/therapeutic use , Gamma Rays , Models, Statistical , Monte Carlo Method , Palladium/therapeutic use , Phantoms, Imaging , Radioisotopes/therapeutic use , Reproducibility of Results , Software , Water
13.
Am J Hematol ; 66(1): 32-8, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11426489

ABSTRACT

In order to assess the prevalence rate of HTLV-1-associated T-cell lymphomas and human retrovirus infection in general, approximately 21,000 individuals representing various patient populations, retroviral risk groups, and blood donors were examined for HTLV-I, HTLV-II, HIV-1, or HIV-2 infection using serologic and PCR assays. The prevalence rates among volunteer blood donors were 0.02% and 0% for HTLV and HIV, respectively. Significantly increased HTLV prevalence rates were observed among paid blood donors, African American health care clinic patients, Amerindians, recipients of HTLV-positive cellular blood products, intravenous drug users, sexual contacts and family members of HTLV-positive people, and patients with primary thrombocytosis and other-than-low-grade non-Hodgkin's lymphoma (NHL). Among some of these groups there were significant differences in the prevalence of HTLV-I versus HTLV-II. The eight HTLV-positive NHL patients all had mature, high-grade, CD4+ T-cell lymphomas with clonally integrated HTLV-I, for a prevalence of 4% among other-than-low-grade NHL patients. Seven of the eight died from their disease within 2 years despite treatment. Interestingly, two groups at risk for HTLV infection, namely needle stick victims and recipients of HTLV-infected and/or pooled plasma products, showed no evidence for infection. Significantly increased HIV-1 prevalence was observed among paid blood donors, African Americans, homosexuals, female prostitutes, hemophiliacs, and other-than-low-grade NHL patients. Only one patient was infected with HIV-2. Of the nine HIV-positive, other-than-low-grade NHL patients, seven HIV-1 positives had B-cell lymphomas, one HIV-1 positive had an HTLV-I-positive CD4+ T-cell lymphoma, and one infected with HIV-2 had a CD4+ T-cell lymphoma that was HTLV negative. The data indicate that HTLV-I lymphoma, while uncommon, is not necessarily rare among other-than-low-grade NHL cases in the United States and, given its poor prognosis, should probably be studied separately in clinical trials.


Subject(s)
Leukemia-Lymphoma, Adult T-Cell/epidemiology , Retroviridae Infections/epidemiology , Black or African American , Agammaglobulinemia/epidemiology , Blood Donors , Comorbidity , DNA, Neoplasm/analysis , DNA, Viral/analysis , Family Health , HIV Infections/epidemiology , HIV Infections/virology , HIV-1/isolation & purification , HIV-2/isolation & purification , HTLV-I Infections/epidemiology , HTLV-II Infections/epidemiology , Hemophilia A/epidemiology , Indians, North American , Leukemia/epidemiology , Leukemia-Lymphoma, Adult T-Cell/ethnology , Lymphoma/classification , Lymphoma/epidemiology , Lymphoma/ethnology , Lymphoma/virology , Lymphoma, AIDS-Related/epidemiology , Lymphoma, AIDS-Related/ethnology , Lymphoma, AIDS-Related/virology , Needlestick Injuries/complications , Prevalence , Retroviridae Infections/ethnology , Retroviridae Infections/virology , Rheumatic Diseases/epidemiology , Risk Factors , Seroepidemiologic Studies , Sexual Behavior , Substance Abuse, Intravenous , Thrombocytosis/epidemiology , Transfusion Reaction , United States/epidemiology
14.
Cancer Res ; 61(12): 4683-8, 2001 Jun 15.
Article in English | MEDLINE | ID: mdl-11406537

ABSTRACT

Critical aspects of the biology and molecular basis for prostate malignancy remain poorly understood. To reveal fundamental differences between benign and malignant growth of prostate cells, we performed gene expression profiling of primary human prostate cancer and benign prostatic hyperplasia (BPH) using cDNA microarrays consisting of 6500 human genes. Frozen prostate specimens were processed to facilitate extraction of RNA from regions of tissue enriched in either benign or malignant epithelial cell growth within a given specimen. Gene expression in each of the 16 prostate cancer and nine BPH specimens was compared with a common reference to generate normalized measures for each gene across all of the samples. Using an analysis of complete pairwise comparisons of expression profiles among all of the samples, we observed clearly discernable patterns of overall gene expression that differentiated prostate cancer from BPH. Further analysis of the data identified 210 genes with statistically significant differences in expression between prostate cancer and BPH. These genes include many not recognized previously as differentially expressed in prostate cancer and BPH, including hepsin, which codes for a transmembrane serine protease. This study reveals for the first time that significant and widespread differences in gene expression patterns exist between benign and malignant growth of the prostate gland. Gene expression analysis of prostate tissues should help to disclose the molecular mechanisms underlying prostate malignant growth and identify molecular markers for diagnostic, prognostic, and therapeutic use.


Subject(s)
Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Humans , Male , Multigene Family , Prostatic Hyperplasia/genetics , Prostatic Hyperplasia/metabolism , Prostatic Hyperplasia/pathology , Prostatic Neoplasms/genetics , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/pathology
15.
Med Phys ; 28(4): 661-70, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11339764

ABSTRACT

125I brachytherapy sources have been widely used for interstitial implants for a number of years in several tumor sites, especially the prostate. The design of the new I-Plant Model 3500 iodine source is novel, yet its characteristics are similar to those of two existing designs, Model 6711 and the Symmetra. Dosimetry parameters (including dose rate constant, radial dose function, and anisotropy function, as defined by AAPM Task Group 43) were measured with LiF thermoluminescent dosimeters in water-equivalent plastic phantoms. The dose rate constant was found by direct comparison of calibrated I-Plant Model 3500 and Model 6711 seeds in a solid water phantom, to be 1.01 (cGy/h)/U. The radial dose function and anisotropy function are similar to those of the Model 6711 and Symmetra seeds.


Subject(s)
Brachytherapy/instrumentation , Brachytherapy/methods , Iodine Radioisotopes , Radiometry , Models, Statistical , Monte Carlo Method , Phantoms, Imaging , Photons , Temperature , Water
16.
N Engl J Med ; 344(8): 539-48, 2001 Feb 22.
Article in English | MEDLINE | ID: mdl-11207349

ABSTRACT

BACKGROUND: Many cases of hereditary breast cancer are due to mutations in either the BRCA1 or the BRCA2 gene. The histopathological changes in these cancers are often characteristic of the mutant gene. We hypothesized that the genes expressed by these two types of tumors are also distinctive, perhaps allowing us to identify cases of hereditary breast cancer on the basis of gene-expression profiles. METHODS: RNA from samples of primary tumor from seven carriers of the BRCA1 mutation, seven carriers of the BRCA2 mutation, and seven patients with sporadic cases of breast cancer was compared with a microarray of 6512 complementary DNA clones of 5361 genes. Statistical analyses were used to identify a set of genes that could distinguish the BRCA1 genotype from the BRCA2 genotype. RESULTS: Permutation analysis of multivariate classification functions established that the gene-expression profiles of tumors with BRCA1 mutations, tumors with BRCA2 mutations, and sporadic tumors differed significantly from each other. An analysis of variance between the levels of gene expression and the genotype of the samples identified 176 genes that were differentially expressed in tumors with BRCA1 mutations and tumors with BRCA2 mutations. Given the known properties of some of the genes in this panel, our findings indicate that there are functional differences between breast tumors with BRCA1 mutations and those with BRCA2 mutations. CONCLUSIONS: Significantly different groups of genes are expressed by breast cancers with BRCA1 mutations and breast cancers with BRCA2 mutations. Our results suggest that a heritable mutation influences the gene-expression profile of the cancer.


Subject(s)
Breast Neoplasms/genetics , Gene Expression , Genes, BRCA1 , Germ-Line Mutation , Neoplasm Proteins/genetics , Transcription Factors/genetics , Algorithms , BRCA2 Protein , Breast Neoplasms/pathology , DNA Methylation , DNA, Complementary/analysis , DNA, Complementary/genetics , DNA, Neoplasm/analysis , DNA, Neoplasm/genetics , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Genotype , Heterozygote , Humans , Neoplasm Proteins/biosynthesis , Oligonucleotide Array Sequence Analysis , RNA, Messenger/analysis , RNA, Messenger/genetics , RNA, Neoplasm/analysis , Transcription Factors/biosynthesis
17.
Cancer Res ; 60(19): 5323-8, 2000 Oct 01.
Article in English | MEDLINE | ID: mdl-11034064

ABSTRACT

Comparative genomic hybridization analysis has demonstrated that breast tumors from BRCA1 and BRCA2 germ-line mutation carriers contain a large number of chromosomal copy number gains and losses. A high regional copy number gain at 6q22-q24 was observed in one BRCA1 tumor, and fluorescence in situ hybridization analysis indicated a strong amplification of the MYB oncogene (15 copies of MYB compared with 1 copy of chromosome 6 centromere). Fluorescence in situ hybridization analysis revealed amplification of MYB in 5 (29%) of 17 BRCA1 breast tumors, whereas none of 8 BRCA2 tumors and 13 breast cancer cell lines, and only 2 of 100 sporadic breast tumors exhibited altered MYB copy numbers. Gene amplification resulted in mRNA overexpression as determined by Northern blot and cDNA microarray analysis, and protein overexpression by immunohistochemical staining. We conclude that MYB amplification is infrequent in sporadic breast cancer but common in breast tumors from BRCA1 mutation carriers, suggesting a role of this cell cycle regulator and transcription factor in the progression of some BRCA1 tumors. However, we cannot rule out the significance of other genes in the 6q22-q24 amplicon.


Subject(s)
Breast Neoplasms/genetics , Genes, BRCA1/genetics , Genes, myb/genetics , Blotting, Northern , Breast Neoplasms/metabolism , Chromosomes, Human, Pair 6/genetics , DNA, Complementary/genetics , DNA, Complementary/metabolism , DNA, Neoplasm/genetics , DNA, Neoplasm/metabolism , Gene Amplification , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Germ-Line Mutation , Humans , In Situ Hybridization, Fluorescence , Nucleic Acid Hybridization , Oncogene Proteins v-myb/biosynthesis , Oncogene Proteins v-myb/genetics , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , RNA, Messenger/metabolism , Receptors, Estrogen/physiology , Receptors, Progesterone/physiology
18.
Med Phys ; 26(11): 2451-60, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10587232

ABSTRACT

A model for the description of the near-field dose deposition from a 32p impregnated stent in an arterial system consisting of soft tissue and dense plaque is presented. The model is based on the scaling property of the dose-point-kernel (DPK) function which is extended to a heterogeneous medium consisting of a series of layers of different materials. It is shown that, for each point source originating from the stent surface, the DPK function for water can be scaled consistently along the path through the different layers of material to predict the dose at a given point in the heterogeneous medium. Radiochromic film dosimetry on actual 32p stents is used to test the new model. The experimental setup consists of a water-equivalent phantom in which a stent is deployed and on which a thin layer of polytetrafluoroethylene (PTFE) is deposited to simulate the presence of plaque. Layers of radiochromic films stacked over the phantom are used to measure the dose at distances varying from approximately 0.1 mm to approximately 3 mm from the stent surface with and without PTFE. It is shown that the proposed new DPK model for a heterogeneous medium agrees very well with the experimental data and that it compares favorably to the usual homogeneous DPK model. These results indicate that the new model can be used with confidence to predict the dose in a realistic artery in the presence of plaque.


Subject(s)
Brachytherapy/methods , Models, Cardiovascular , Stents , Angioplasty, Balloon, Coronary , Calibration , Coronary Disease/radiotherapy , Humans , Phantoms, Imaging , Radiotherapy Dosage/standards
19.
Med Phys ; 26(11): 2461-4, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10587233

ABSTRACT

Good clinical physics practice requires that dose rates of brachytherapy sources be checked by the institution using them, as recommended by American Association of Physicists in Medicine Task Group 56 and The American College of Radiology. For intravascular brachytherapy with catheter-based systems, AAPM Task Group 60 recommends that the dose rate be measured at a reference point located at a radial distance of 2 mm from the center of the catheter axis. AAPM Task Group 60 also recommends that the dose rate along the catheter axis at a radial distance of 2 mm should be uniform to within +/- 10% in the center two-thirds of the treated length, and the relative dose rate in the plane perpendicular to the catheter axis through the center of the source should be measured at distances from 0.5 mm to R90 (the distance from a point source within which 90% of the energy is deposited) at intervals of 0.5 mm. Radiochromic film dosimetry has been used to measure the dose distribution in a plane parallel to and at a radial distance of 2 mm from the axis of a novel, catheter-based, beta source for intravascular brachytherapy. The dose rate was averaged along a line parallel to the catheter axis at a radial distance of 2 mm, in the centered 24.5 mm of the treated length. This average dose rate agreed with the dose rate measured with a well ionization chamber by the replacement method using source trains calibrated with an extrapolation chamber at the National Institute of Standards and Technology. All of the dose rates in the centered 24.5 mm of a line parallel to the axis at a distance of 2 mm were within +/-10% of the average.


Subject(s)
Beta Particles/therapeutic use , Brachytherapy/instrumentation , Brachytherapy/standards , Calibration , Film Dosimetry , Radiotherapy Dosage , United States
20.
Muscle Nerve ; 22(4): 473-9, 1999 Apr.
Article in English | MEDLINE | ID: mdl-10204782

ABSTRACT

Mutations in the sarcoglycan genes cause autosomal-recessive muscular dystrophies. Because sarcoglycan genes and their protein products are highly expressed both in skeletal and cardiac muscle, patients with these mutations might be expected to be at risk to develop dilated cardiomyopathy. We therefore studied 13 patients with alpha-, beta-, gamma-sarcoglycan gene mutations by thorough cardiological assessment. Electrocardiographic or echocardiographic abnormalities were observed in about 30% of cases showing a severe course of muscular dystrophy. No correlation was found between the presence of cardiac abnormalities and the type of mutation or sarcoglycan gene involved. The cardiac involvement was never severe, but it may be detected in early stages of the muscle disease. The absence of overt cardiac dysfunction may be due to lower sarcoglycan protein expression in cardiac than skeletal muscle or to less sarcolemmal instability at the myocardial level, possibly related to the different distribution of forces generated by contraction of the myocardium with respect to proximal limb-girdle muscles.


Subject(s)
Cytoskeletal Proteins/genetics , Heart/physiology , Membrane Glycoproteins/genetics , Muscular Dystrophies/genetics , Adolescent , Adult , Blotting, Western , Child , Child, Preschool , Female , Genes, Recessive , Humans , Immunohistochemistry , Male , Middle Aged , Mutation , Phenotype
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