Predicting the use of individualized risk assessment for breast cancer.

PURPOSE: The purpose of this study was to investigate the decision to obtain individualized risk assessment (IRA) after a breast cancer education session. METHODS: A sample of both African American and Caucasian women was used to determine if there were differences by race/ethnicity in uptake of the assessment and differences in the variables that were most predictive of uptake. The sample included 166 women between the ages of 18 and 80. Sixty-two percent of the sample were African American women. KEY FINDINGS: The results suggested that African American women and Caucasian women used different factors and used other factors differently to decide whether or not to obtain an IRA. CONCLUSIONS AND IMPLICATIONS: These results are discussed within the context of health disparities among ethnic minority and Caucasian women with implications for breast cancer control programs. The results of this study suggest that knowledge alone does not lead to opting for a personalized risk assessment, and that African American and Caucasian women use different pieces of information, or information differently to make decision about getting more personalized information about risk.     

A medical student-staffed outpatient oncology clinic: A 10-year Brazilian experience

BACKGROUND: This is an update of a 10-years student-staffed oncology clinic. METHODS: Students are divided into 4 teams; each sees 1 to 2 outpatients weekly. RESULTS: By April 2006, 95 medical students participated, 89% for 2 or more years; 70% reported activity contributed to ability to read medical papers, and 59% improved their scientific writing. Of 39 students currently involved, 33 (84%) improved clinical skills in taking history, 27 (69%) in physical examination, and 34 (87%) in physician-patient relation. A total of 21 (56%) reported increased knowledge in general internal medicine. Although only 11% of former students pursued a specialty in Medical Oncology, 77% rated this clinic as the best extracurricular activity. CONCLUSIONS: Attendance of outpatient clinic in medical oncology can contribute significantly to the general medical education.     

Impact of erythropoietin on the reduction of blood transfusions and on survival of lung cancer patients receiving first-line chemotherapy

INTRODUCTION: Anaemia is a common problem in patients with cancer who receive chemotherapy and is normally associated with a negative impact on patients' quality of life (QOL), poor cancer control and diminished survival. In clinical trials, recombinant human erythropoietin has been shown to correct and prevent anaemia, decrease the need for blood transfusions and improve cancer patients' QOL. METHODS: A retrospective study followed lung cancer patients who received first-line chemotherapy in our hospital in 1998 and in 2005. The incidence of anaemia was analysed, as was the impact of incorporating erythropoietin into the treatment. RESULTS: The incidence of anaemia was 68% (69% of which reported asthenia) in 1998 vs. 54% (60% with asthenia) in 2005. The comparison of anaemia rates (1998 vs. 2005) were grade 1 (16% vs. 32%), grade 2 (36% vs. 16%), grade 3 (16% vs. 5%) and grade 4 (none). Treatment for anaemia included transfusion 52%, intravenous iron 5% and epoetin 4% in 1998. In 2005 anaemia was treated with transfusion 9%, intravenous iron 41%, and epoetin 49%. Median survival (1998 vs. 2005) was 242 days [95% confidence interval (CI) 217-329) vs. 356 days (95% CI 322-382). CONCLUSIONS: Erythropoietin is a valid alternative for cancer patients with anaemia undergoing chemotherapy. It can possibly avoid the need for transfusions without negatively impacting survival.     

Origin of renal cell carcinomas

Cancer is a heritable disorder of somatic cells: environment and heredity are both important in the carcinogenic process. The primal force is the “two hits” of Knudson’s hypothesis, which has proved true for many tumours, including renal cell carcinoma. Knudson et al. [1, 2] recognised that familial forms of cancer might hold the key to the identification of important regulatory elements known as tumour-suppressor genes. Their observations (i.e., that retinoblastoma tend to be multifocal in familial cases and unifocal in sporadic presentation) led them to propose a two-hit theory of carcinogenesis. Furthermore, Knudson postulated that patients with the familial form of the cancer would be born with one mutant allele and that all cells in that organ or tissue would be at risk, accounting for early onset and the multifocal nature of the disease. In contrast, sporadic tumours would develop only if a mutation occurred in both alleles within the same cell, and, as each event would be expected to occur with low frequency, most tumours would develop late in life and in a unifocal manner [3, 4]. The kidney is affected in a variety of inherited cancer syndromes. For most of them, both the oncogene/tumour-suppressor gene involved and the respective germline mutations have been identified. Each of the inherited syndromes predisposes to distinct types of renal carcinoma. Families with hereditary predisposition to cancer continue to provide a unique opportunity for the identification and characterisation of genes involved in carcinogenesis. A surprising number of genetic syndromes predispose to the development of renal cell carcinoma, and genes associated with five of these syndromes have been already identified: VHL, MET, FH, BHD and HRPT2. Few cancers have as many different types of genetic predisposition as renal cancer, although to date only a small proportion of renal cell cancers can be explained by genetic predisposition. Supported by an unrestricted educational grant from Pfizer.     

Hypoxia and fatigue-induced modification of function and proteins in intact and skinned murine diaphragm muscle

Fatigue studies of isolated, intact muscles typically utilize solutions saturated with O2. However, under in vivo fatiguing conditions, less oxygen is delivered to the muscles and they actually experience hypoxia. No studies to date have correlated the effects of acute hypoxia on the isometric contractile properties of intact muscles, skinned fibers isolated from the same muscles, and the cellular content of specific muscle proteins. Therefore, we have studied the effects of in vitro acute hypoxia on the fatigability of intact diaphragm muscle strips and on the isometric contractile properties of single Triton-skinned fibers isolated from control and hypoxic diaphragm muscles. We found that hypoxia and fatiguing stimulation per se affect the tetanic force of intact muscle strips without exhibiting any significant deleterious effects on the calcium-activated force of skinned muscle fibers dissected from the intact muscles. In contrast, fatiguing stimulation under hypoxic conditions decreased both the tetanic force of muscle strips and the calcium-activated force of skinned muscle fibers. Gel electrophoresis of muscles subjected to hypoxia and hypoxic-fatigue revealed that there is a significant reduction in three protein bands when compared to control muscles. Protein modification may be the underlying mechanism of muscle fatigue under physiologic conditions.     

Intranasal Tat Alters Gene Expression in the Mouse Brain

Intranasal (IN) delivery of HIV-1 Tat in aging mice was investigated as a possible model for HIV-1 infection in the brain. After IN administration, the distribution of [¹²⁵I]-labeled Tat in the brains of Swiss Webster mice was evaluated by autoradiography and gamma counting. [¹²⁵I]-labeled Tat was detected at the highest concentrations in the olfactory bulb, cervical nodes, and trigeminal nerve tract. In another experiment, APPSw transgenic mice were used to model chronic Tat exposure. The mice were treated intranasally with 6 μg Tat (n = 4) or vehicle (n = 4) three times per week for 4 weeks. Total RNA was isolated from the frontal cortex, and differential gene expression analysis was performed using gene microarrays. Gene ontology profiles indicated innate immunity, inflammatory and apoptotic responses. Five genes of interest in the Tat-treated mice that were significantly elevated in the microarrays were validated by RT-PCR. One gene, the Toll-like receptor 9 (Tlr9), has previously been shown to activate signaling cascades leading to innate immunity and enhanced HIV-1 gene expression. A second gene, Fas, plays a key role in neuroinflammation. Two cysteine-rich cytokines associated with chemotaxis were elevated: MCP-1 (Ccl2), which is chemotactic for monocytes, and Ccl17 (TARC), which is chemotactic for lymphocytes. Finally, the gene sestrin was significantly elevated and has been associated with oxidative stress, in particular amyloid beta-induced oxidative stress. This IN Tat model of neuroinflammation may be useful to study HIV-1-induced neurodegeneration. This paper was presented at an NIMH workshop “HIV Preclinical–Clinical Therapeutics Research Meeting”, May 5–16, 2006.     

Protective effects of Hibiscus tiliaceus L. methanolic extract to V79 cells against cytotoxicity and genotoxicity induced by hydrogen peroxide and tert-butyl-hydroperoxide

Plants of the genus Hibiscus thrives produce a diversity of molecules with bioactive properties. In a previous study of Hibiscus tiliaceus L. methanolic extract (HME) using bacteria and yeast, as test media, it has been shown that HME strongly inhibited the mutagenic action of H₂O₂ or tert-butyl-hydroperoxide (t-BHP). Here, our interest is to evaluate the genotoxicity and the antigenotoxic/antimutagenic properties of HME using oxidative challenge with H₂O₂ and t-BHP in V79 cells. We determined cytotoxicity using clonal survival assay; evaluated DNA damage using the comet assay and the micronucleus test in binucleated cells besides of the lipid peroxidation degree and the reduced glutathione content. We examined the ability of HME in quenching hydroxyl radical by means of a HPLC-based method utilizing the hypoxanthine/xanthine oxidase assay. At concentrations ranging from 0.001 to 0.1 mg/mL, HME was not cytotoxic, genotoxic or mutagenic. Treatment with non-cytotoxic concentrations of HME increased cell survival after H₂O₂ and t-BHP exposure and prevented DNA damage. The pre-treatment with HME also was able to decrease the mutagenic effect of these genotoxins, evaluated using the micronucleus test. HME prevented the increase in lipid peroxidation and decrease in GSH content in response to the oxidative challenge. Therefore, the ability in preventing against H₂O₂- and t-BHP-induced GSH depletion and lipid peroxidation was probably a major contribution to the cytoprotective effects. Moreover, HME acts as a hydroxyl radical scavenger. In summary, HME did not have a harmful or inhibitory effect on the growth of V79 cells and presented antioxidant activity, consequently, both antigenotoxic and antimutagenic effects against oxidative DNA damage.     

Mineral bone content in full-term infants. Effect of anthropometric characteristics

The clinical importance of the measurement of bone mineral content (BMC) in fullterm infants by photon absorptiometry relies on a comparatively narrow normative range that is necessary requisite to interpret the data from a single child. In the attempt to reduce the artifactual scattering of data, it was undertaken a normative study to control all variables that might affect BMC at birth. Thus, growth parameters and birth season (as an index of maternal vit. D status) were related to BMC, Bone Width (BW) and the considered growth parameters did not show any significant difference related to sex and birth season. Thus, all data were analyzed together. It appears that BMC at birth in fullterm infants averaged 92.2 +/- 14.6 mg/cm. BMC did not correlate with skeletal length, crown length and gestational age in the considered range. Conversely, significant correlation were found between BMC and BW and between BMC and body weight. We conclude that: a) birth season and sex do not affect bone mineralization in fullterm infants, b) any comparison among BMC should be established within populations homogeneous for weight and BW.     

Cordocentesis and evaluation of fetal wellbeing in a very high-risk population (a very reliable index)]

In a population of 57 very high-risk pregnant women (severe clinical history and/or compromised fetus). A total of 240 tests for antepartum fetal evaluation were performed: baseline cardiotocography (CTG), biophysical profile scoring (BPS), doppler-velocimetry of umbilical artery and determination of blood gas analysis in venous umbilical cord blood obtained by cordocentesis. The results of the CTG, BPS, and umbilical artery doppler velocimetry showed a significant relation with those of pH and pO2. The sensitivity, specificity, false-abnormal value, and false-normal value of the CTG, PBS, and doppler velocimetry, used for the diagnosis of fetal acidosis, hypoxia, and asphyxia were comparable. The rate of fetal (asphyxia) was high if present severe/terminal CTG (85.0%), abnormal (4) BPS (82.0%), or absent-end diastole in umbilical artery doppler velocimetry (74.0%). The immediate complication rate due to cordocentesis procedure was minimal.