Scoping Review of Textbooks for Medical Spanish Education.

Despite medical Spanish program proliferation to teach clinicians the language skills to communicate effectively with Spanish-speaking patients, course material selection remains a challenge. We conducted a scoping review to systematically identify medical Spanish textbooks, evaluate utility, and identify gaps. On average, language reviewers scored books lower than medical reviewers. Medical and language professionals present complementary perspectives to evaluating medical Spanish educational materials. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40670-021-01333-8.

The Toronto outcome measure for craniofacial prosthetics: reliability and validity of a condition-specific quality-of-life instrument.

PURPOSE: The purpose of this study was to refine the Toronto Outcome Measure for Craniofacial Prosthetics (TOMCP), present evidence for its reliability and validity, and use the instrument to explore differences in quality of life between prostheses made with chlorinated polyethylene (CPE) (experimental) and silicone (control). MATERIALS AND METHODS: As part of a multicenter prospective controlled randomized double-blind single-crossover clinical trial of the two materials, the TOMCP was administered at the start and end of two 4-month study arms, during which 42 patients wore prostheses made from one material then the other. Reliability was assessed at the crossover. To determine validity of the TOMCP, the Linear Analogue Self-Assessment (LASA-12) and the Short-Form 8 (SF-8) were also administered with the TOMCP. The TOMCP was reduced by removing items that were unreliable, had poorly distributed answers, showed increased internal consistency after their removal, or were too highly correlated with more than one other item. The tests of reliability and validity were then repeated. Finally, the reduced instrument was used to test for differences in quality of life between prostheses made of the two materials. RESULTS: The item reduction tactics pared the 52-item instrument down to 27 items. The correlations of both TOMCP versions with the LASA-12 and the SF-8 were found to be statistically significant, providing evidence of the validity of the TOMCP. The instrument revealed significantly better quality of life with silicone rather than CPE prostheses. CONCLUSIONS: Both versions of the TOMCP were found to be reliable and valid. The instrument was able to show differences in quality of life between two materials.

P53 genotype as a determinant of ER expression and tamoxifen response in the MMTV-Wnt-1 model of mammary carcinogenesis.

Clinical studies show that estrogen receptor-α (ER) expressing tumors tend to have better prognosis, respond to antiestrogen therapy and have wild-type p53. Conversely, tumors with inactivating mutations in p53 tend to have worse outcomes and to be ER-negative and unresponsive to antihormone treatment. Previous studies from our laboratory have shown that p53 regulates ER expression transcriptionally, by binding the ER promoter and forming a complex with CARM1, CBP, c-Jun, RNA polymerase II and Sp1. In this study, the MMTV-Wnt-1 transgenic mouse model was used to demonstrate that p53 regulation of ER expression and function is not solely an in vitro phenomenon, but it is also operational in mammary tumorigenesis in vivo. The expression of ER and the ability to respond to tamoxifen were determined in mammary tumors arising in p53 wild type (WT) or p53 heterozygous (HT) animals carrying the Wnt-1 transgene. In p53 WT mice, development of ER-positive tumors was delayed by tamoxifen treatment, while tumors arising in p53 HT mice had significantly reduced levels of ER and were not affected by tamoxifen. P53 null tumors were also found in the p53 HT mice and these tumors were ER-negative. ER expression was upregulated in mouse mammary tumor cell lines following transfection with WT p53 or treatment with doxorubicin. These data demonstrate that p53 regulates ER expression in vivo, and affects response to tamoxifen. Results also provide an explanation for the concordant relationship between these prognostic proteins in human breast tumors.

Clinical trial of chlorinated polyethylene for facial prosthetics.

PURPOSE: Extraoral maxillofacial prostheses have been fabricated with silicone elastomer for 50 years with few improvements. The objective of this controlled, randomized, prospective, double-blind, single-crossover, multicenter, phase III clinical trial was to determine the noninferiority of chlorinated polyethylene elastomer (CPE) to silicone elastomer for fabricating prostheses. MATERIALS AND METHODS: Forty-two patients were randomly assigned to wear a custom-made prosthesis fabricated from both materials for 4 months and asked to rate their satisfaction (0 = not satisfied, 10 = completely satisfied). Many other measures of prosthesis performance were investigated (see online appendices). RESULTS: Of the 28 patients who completed the study, 68% had used silicone prostheses previously. Overall, patients rated the silicone prosthesis higher than CPE (difference: 2.2, 95% confidence interval [CI]: 0.9 to 3.6, P = .017). Previous users had a stronger preference for silicone (difference: 3.3, 95% CI: 1.7 to 4.9, P = .001), while the 9 new users rated the two materials similarly (difference: 0.0, 95% CI: -2.1 to 2.1, P = 1.00). CONCLUSIONS: The noninferiority of CPE could not be established because of the early termination of the trial. Previous users of silicone prostheses preferred those made of silicone. However, new users expressed no preference between prostheses fabricated with the low-cost CPE or silicone. The authors have developed original clinical trial methodology for assessing extraoral maxillofacial prostheses.

Statins have beneficial effects on platelet free radical activity and intracellular distribution of GTPases in hyperlipidaemia.

In addition to lowering cholesterol, statins may alter endothelial release of the vasodilator NO and harmful superoxide free radicals. Statins also reduce cholesterol intermediates including isoprenoids. These are important for post-translational modification of substances including the GTPases Rho and Rac. By altering the membrane association of these molecules, statins affect intracellular positioning and hence activity of a multitude of substances. These include eNOS(endothelial NO synthase), which produces NO (inhibited by Rho), and NADPH oxidase, which produces superoxide (dependent on Rac). Statins may improve endothelial function by enhancing production of NO while decreasing superoxide production. A total of 40 hypercholesterolaemic patients were randomized to treatment with either atorvastatin or placebo; 20 normolipidaemic patients were also studied. Platelet nitrite, NO and superoxide were examined as was the cellular distribution of the GTPases Rho and Rac at baseline and after 8 weeks of treatment.Following atorvastatin therapy, platelet NO was increased (3.2 pmol/10(8) platelets) and superoxide output was attenuated [-3.4 pmol min(-1) (10(8) platelets)(-1)] when compared with placebo. The detection of both Rho and Rac was significantly reduced in the membranes of platelets, implying reduced activity. In conclusion, the results of the present study show altered NO/superoxide production following statin therapy. A potential mechanism for this is the change in the distribution of intracellular GTPases, which was considered to be secondary to decreases in isoprenoid intermediates, suggesting that the activity of the former had been affected by atorvastatin.

Paracrine overexpression of insulin-like growth factor-1 enhances mammary tumorigenesis in vivo.

Insulin-like growth factor-1 (IGF-1) stimulates proliferation, regulates tissue development, protects against apoptosis, and promotes the malignant phenotype in the breast and other organs. Some epidemiological studies have linked high circulating levels of IGF-1 with an increased risk of breast cancer. To study the role of IGF-1 in mammary tumorigenesis in vivo, we used transgenic mice in which overexpression of IGF-1 is under the control of the bovine keratin 5 (BK5) promoter and is directed to either the myoepithelial or basal cells in a variety of organs, including the mammary gland. This model closely recapitulates the paracrine exposure of breast epithelium to stromal IGF-1 seen in women. Histologically, mammary glands from transgenic mice were hyperplastic and highly vascularized. Mammary glands from prepubertal transgenic mice had significantly increased ductal proliferation compared with wild-type tissues, although this difference was not maintained after puberty. Transgenic mice also had increased susceptibility to mammary carcinogenesis, and 74% of the BK5.IGF-1 mice treated with 7,12-dimethylbenz[a]anthracene (20 microg/day) developed mammary tumors compared with 29% of the wild-type mice. Interestingly, 31% of the vehicle-treated BK5.IGF-1 animals, but none of the wild-type animals, spontaneously developed mammary cancer. The mammary tumors were moderately differentiated adenocarcinomas that expressed functional, nuclear estrogen receptor at both the protein and mRNA levels. These data support the hypothesis that tissue overexpression of IGF-1 stimulates mammary tumorigenesis.

Understanding the development of human bladder cancer by using a whole-organ genomic mapping strategy.

The search for the genomic sequences involved in human cancers can be greatly facilitated by maps of genomic imbalances identifying the involved chromosomal regions, particularly those that participate in the development of occult preneoplastic conditions that progress to clinically aggressive invasive cancer. The integration of such regions with human genome sequence variation may provide valuable clues about their overall structure and gene content. By extension, such knowledge may help us understand the underlying genetic components involved in the initiation and progression of these cancers. We describe the development of a genome-wide map of human bladder cancer that tracks its progression from in situ precursor conditions to invasive disease. Testing for allelic losses using a genome-wide panel of 787 microsatellite markers was performed on multiple DNA samples, extracted from the entire mucosal surface of the bladder and corresponding to normal urothelium, in situ preneoplastic lesions, and invasive carcinoma. Using this approach, we matched the clonal allelic losses in distinct chromosomal regions to specific phases of bladder neoplasia and produced a detailed genetic map of bladder cancer development. These analyses revealed three major waves of genetic changes associated with growth advantages of successive clones and reflecting a stepwise conversion of normal urothelial cells into cancer cells. The genetic changes map to six regions at 3q22-q24, 5q22-q31, 9q21-q22, 10q26, 13q14, and 17p13, which may represent critical hits driving the development of bladder cancer. Finally, we performed high-resolution mapping using single nucleotide polymorphism markers within one region on chromosome 13q14, containing the model tumor suppressor gene RB1, and defined a minimal deleted region associated with clonal expansion of in situ neoplasia. These analyses provided new insights on the involvement of several non-coding sequences mapping to the region and identified novel target genes, termed forerunner (FR) genes, involved in early phases of cancer development.

Anxiety and prenatal testing: do women with soft ultrasound findings have increased anxiety compared to women with other indications for testing?

OBJECTIVE: To determine whether there is a difference in anxiety levels in women referred for soft ultrasound findings, AMA, and abnormal serum marker screens, all of whom have a similar risk for chromosome abnormalities, in order to provide an understanding of patients' anxiety, which may enhance the genetic counseling process. METHODS: Two self-administered questionnaires were completed after the genetic counseling session. Participants were recruited from multiple prenatal clinics throughout Houston, Texas. The State-Trait Anxiety Inventory Form Y was used to measure anxiety in study participants. Both state and trait anxiety were assessed. Differences between groups were examined using one-way analysis of variance, crosstabulation, chi-square, and Tukey multiple comparisons analysis. A p-value of < 0.05 was considered significant. RESULTS: Two hundred fifteen women participated in the study: 124 AMA, 55 abnormal maternal serum screens, and 36 soft ultrasound findings. Our findings revealed that women with soft ultrasound findings and abnormal maternal serum screens had significantly higher state anxiety than women who are AMA. State anxiety in women with soft ultrasound findings was not significantly different from women with abnormal maternal serum screens. No significant difference was found between the three groups for trait anxiety. Perceived risk, decision to undergo amniocentesis, education level, and income were factors that significantly affected the women's anxiety scores. However, none of these factors proved to be successful indicators of state or trait anxiety. CONCLUSION: A woman's referral indication is associated with different levels of anxiety as compared to the actual numerical risk for chromosome abnormalities presented during a genetic counseling session.

Prognostic significance of cytogenetically detected chromosome 21 anomalies in childhood acute lymphoblastic leukemia: a Pediatric Oncology Group study.

Chromosome anomalies have been shown to have prognostic significance in children with acute lymphoblastic leukemia (ALL). Chromosome 21 was evaluated for its ability to predict outcome when found in either a single copy (the Mono21 group) or when involved in a structural aberration (the Misc21 group). Both anomalies were associated with an increased risk of failure for patients with standard-risk ALL, rather than higher-risk ALL. Event-free survival was 50.0% at 5 years and 48.4% at 8 years for standard-risk patients with Mono21+Misc21, compared with 77.8 and 75.5%, respectively, for standard-risk patients without these anomalies of chromosome 21. There was no significant difference in outcome between the Mono21 and the Misc21 group (P = 0.10). Mono21 and Misc21 were determined to be independently prognostic whether or not the primary leukemic clone had fewer than 45 chromosomes. The frequency of an adverse outcome was comparable to other poor prognosis subgroups such as hypodiploidy (<45 chromosomes), t(9;22), or t(4;11), all of which have been targeted for aggressive therapy even if the case is otherwise standard risk.

Subclinical impairment of arterial mechanics in systemic lupus erythematosus identified by arterial waveform analysis.

Structural and functional changes in wall and endothelial components of arterial blood vessels underlie the accelerated vascular disease progression in systemic lupus erythematosus (SLE). Using pulse contour analysis we sought to determine if subclinical vascular abnormalities could be identified in a well-characterised cohort of patients with SLE who had no increase in traditional cardiovascular risk factors. Radial artery pressure waveforms were obtained by applanation tonometry and pressure envelopes were analysed by descriptive and model-based approaches. Waveshape morphology was quantified by a novel eigenvector approach and model-based compliance indices of the large arteries (C1, capacitative arterial compliance) and small arteries (C2, reflective arterial compliance) were derived using a third-order four-element modified Windkessel model. Data were recorded from 30 patients with SLE (mean age 44 +/- 7 years and mean SLAM-R 10 +/- 4) and 19 age-matched control subjects. Significant differences in the lower frequency sinusoidal components of the pressure waveforms were evident between groups (P < 0.05). Both C1 and C2 were significantly reduced in patients with SLE: C1 mean +/- SD 13.5 +/- 4.0 ml/mmHg x 10 versus C1 17.5 +/- 4.8 ml/mmHg x 10 (P = 0.003 in patients vs. controls, respectively) and C2 5.2 +/- 3.4 ml/mmHg x 100 versus C2 9.4 +/- 2.8 ml/mmHg x 100 (P < 0.001 in patients vs. controls, respectively). In this group of SLE patients, without an excess of traditional cardiovascular risk factors and SLAM-R scores indicating mild disease, descriptive and model-based analysis of arterial waveforms identified vascular abnormalities at a preclinical stage.

Comparison of full-field digital mammography and screen-film mammography for detection and characterization of simulated small masses.

OBJECTIVE: The two objectives of this study were to create an ex vivo phantom model that closely mimics human breast cancer for detection tasks and to compare the performance of full-field digital mammography with screen-film mammography in detecting and characterizing small breast masses in a phantom with a spectrum of complex tissue backgrounds. MATERIALS AND METHODS: Sixteen phantom breast masses of varying sizes (0.3-1.2 cm), shapes (round and irregular), and densities (high and low) were created from shaved tumor specimens and imaged using both full-field digital and screen-film mammography techniques. We created 408 detection tasks that were captured on 68 films. On each radiograph, six detection tasks were partially obscured by areas of varying breast-pattern complexity, including low (predominantly fatty), mixed (scattered fibroglandular densities and heterogeneously dense), and high (extremely dense) density patterns. Each detection task was scored using a five-point confidence scale by three mammographers. Receiver operating characteristic (ROC) curve analysis was performed to analyze differences in detection of masses between the two imaging systems, and sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were computed. RESULTS: Full-field digital mammography showed higher area under the ROC curve than screen-film mammography for detecting masses in each breast background and performed significantly better than screen-film mammography in mixed (p = 0.010), dense (p = 0.029), and all breast backgrounds combined (p = 0.004). Full-field digital mammography was superior to screen-film mammography for characterizing round and irregular masses and low- and high-density masses. CONCLUSION: Full-field digital mammography was significantly superior to screen-film technique for detecting and characterizing small masses in mixed and dense breast backgrounds in a phantom model.

Dendritic cells loaded with killed allogeneic melanoma cells can induce objective clinical responses and MART-1 specific CD8+ T-cell immunity.

Dendritic cells (DCs) loaded with killed allogeneic tumors can cross-prime tumor-specific naive CD8 T cells in vitro, thereby providing an option to overcome human leukocyte antigen restriction inherent to loading DC vaccines with peptides. We have vaccinated 20 patients with stage IV melanoma with autologous monocyte-derived DCs loaded with killed allogeneic Colo829 melanoma cell line. DCs were generated by culturing monocytes with granulocyte macrophage-colony stimulating factor (granulocyte macrophage-colony stimulating factor) and interleukin (IL-4) and activated by additional culture with tumor necrosis factor and CD40 ligand. A total of 8 vaccines were administered at monthly intervals. The first patient was accrued December 2002 and the last November 2003. Fourteen patients were alive at 12 months, 9 patients were alive at 24 months, and 8 patients are alive as of January 2006. The estimated median overall survival is 22.5 months with a range of 2 to 35.5 months. Vaccinations were safe and tolerable. They induced, in 2 patients who failed previous therapy, durable objective clinical responses, 1 complete regression (CR) and 1 partial regression (PR) lasting 18 and 23 months, respectively. Three out of 13 analyzed patients showed T-cell immunity to melanoma antigen recognized by autologous T cells (MART-1) tissue differentiation antigen. Two of 3 patients showed improved immune function after vaccinations demonstrated by improved secretion of interferon (IFN)-gamma or T-cell proliferation in response to MART-1 derived peptides. In one of these patients, vaccination led to elicitation of CD8 T-cell immunity specific to a novel peptide-derived from MART-1 antigen, suggesting that cross-priming/presentation of melanoma antigens by DC vaccine had occurred. Thus, the present results justify the design of larger follow-up studies to assess the clinical response to DC vaccines loaded with killed allogeneic tumor cells in patients with metastatic melanoma.

Microcirculatory hemodynamics and endothelial dysfunction in systemic lupus erythematosus.

OBJECTIVE: Impaired flow-mediated dilation (FMD) occurs in disease states associated with atherosclerosis, including SLE. The primary hemodynamic determinant of FMD is wall shear stress, which is critically dependent on the forearm microcirculation. We explored the relationship between FMD, diastolic shear stress (DSS), and the forearm microcirculation in 32 patients with SLE and 19 controls. METHODS AND RESULTS: DSS was calculated using (mean diastolic velocity x 8 x blood viscosity)/baseline brachial artery diameter. Doppler velocity envelopes from the first 15 seconds of reactive hyperemia were analyzed for resistive index (RI), and interrogated in the frequency domain to assess forearm microvascular hemodynamics. FMD was significantly impaired in SLE patients (median, 2.4%; range, -2.1% to 10.7% versus median 5.8%; range, 1.9% to 14%; P<0.001). DSS (dyne/cm2) was significantly reduced in SLE patients (median, 18.5; range, 3.9 to 34.0 versus median 21.8; range, 14.1 to 58.7; P=0.037). A strong correlation between FMD and DSS, r(s)=0.65, P=0.01 was found. Postischemic RI was not significantly different between the 2 groups; however, there were significant differences in the power-frequency spectrums of the Doppler velocity envelopes (P<0.05). CONCLUSIONS: These data suggest that in SLE, altered structure and function of the forearm microcirculation contributes to impaired FMD through a reduction in shear stress stimulus.

African-American men with nonpalpable prostate cancer exhibit greater tumor volume than matched white men.

BACKGROUND: Although prostate cancer (PC) mortality disproportionately affects African-American (AA) men, limited data exist comparing the pathologic characteristics of white and AA patients with nonpalpable PC (clinical stage T1c). METHODS: The authors reviewed the radical prostatectomy (RP) specimens from 37 consecutive AA men with clinical stage T1c PC and 35 white men who were matched for age, clinical stage, serum prostate-specific antigen (PSA) level, year of surgery, prostate weight, and prostate biopsy strategy. Pathologic characteristics were compared after mapping tumor foci and calculating tumor volumes by using computer software. RESULTS: For AA men, the median age (57.7 years), mean serum PSA level (9.3 ng/mL), mean prostate weight (43 g), and biopsy strategy (73% sextant) were matched with the cohort of 35 white men (median age, 57.1 years; mean PSA, 9.3 ng/mL;, mean prostate weight, 43 g; biopsy strategy, 66% sextant). Despite similar biopsy characteristics between the 2 groups (Gleason score > or =7 in 43% of AA men vs. 37% of white men), AA men exhibited significantly higher prostatectomy Gleason scores (> or =7 in 76% of AA men vs. 34% of white men; P = .01). AA men also had a higher mean tumor volume (1.82 cm3 vs. 0.72 cm3; P = .001) and had 2.8 times more tumor per ng/mL of serum PSA (0.22 cm3 per ng/mL vs. 0.079 cm3 per ng/mL; P = .001). CONCLUSIONS: Compared with a cohort of white men with similar clinical features at the time of biopsy, AA men with nonpalpable PC had higher prostatectomy Gleason scores, greater cancer volume, and greater tumor volume per ng/mL of serum PSA. These data provide additional support for the concept of early PC detection using a serum PSA threshold of 2.5 ng/mL for biopsy among AA men.

Evidence for alternative candidate genes near RB1 involved in clonal expansion of in situ urothelial neoplasia.

In this paper, we present whole-organ histologic and genetic mapping studies using hypervariable DNA markers on chromosome 13 and then integrate the recombination- and single-nucleotide polymorphic sites (SNPs)-based deletion maps with the annotated genome sequence. Using bladders resected from patients with invasive urothelial carcinoma, we studied allelic patterns of 40 microsatellite markers mapping to all regions of chromosome 13 and 79 SNPs located within the 13q14 region containing the RB1 gene. A whole-organ histologic and genetic mapping strategy was used to identify the evolution of allelic losses on chromosome 13 during the progression of bladder neoplasia. Markers mapping to chromosomal regions involved in clonal expansion of preneoplastic intraurothelial lesions were subsequently tested in 25 tumors and 21 voided urine samples of patients with bladder cancer. Four clusters of allelic losses mapping to distinct regions of chromosome 13 were identified. Markers mapping to the 13q14 region that is flanked by D13S263 and D13S276, which contains the RB1 gene, showed allelic losses associated with early clonal expansion of intraurothelial neoplasia. Such losses could be identified in approximately 32% bladder tumor tissue samples and 38% of voided urines from patients with bladder cancer. The integration of distribution patterns of clonal allelic losses revealed by the microsatellite markers with those obtained by genotyping of SNPs disclosed that the loss within an approximately 4-Mb segment centered around RB1 may represent an incipient event in bladder neoplasia. However, the inactivation of RB1 occurred later and was associated with the onset of severe dysplasia/carcinoma in situ. Our studies provide evidence for the presence of critical alternative candidate genes mapping to the 13q14 region that are involved in clonal expansion of neoplasia within the bladder antecedent to the inactivation of the RB1 gene.

Long-term outcomes in patients with metastatic melanoma vaccinated with melanoma peptide-pulsed CD34(+) progenitor-derived dendritic cells.

Between March 1999 and May 2000, 18 HLA-A*0201(+) patients with metastatic melanoma were enrolled in a phase I trial using a dendritic cell (DC) vaccine generated by culturing CD34(+) hematopoietic progenitors. This vaccine includes Langerhans cells. The DC vaccine was loaded with four melanoma peptides (MART-1/MelanA, tyrosinase, MAGE-3, and gp100), Influenza matrix peptide (Flu-MP), and keyhole limpet hemocyanin (KLH). Ten patients received eight vaccinations, one patient received six vaccinations, one patient received five vaccinations, and six patients received four vaccinations. Peptide-specific immunity was measured by IFN-gamma production and tetramer staining in blood mononuclear cells. The estimated median overall survival was 20 months (range: 2-83), and the median event-free survival was 7 months (range: 2-83). As of August 2005, four patients are alive (three patients had M1a disease and one patient had M1c disease). Three of them have had no additional therapy since trial completion; two of them had solitary lymph node metastasis, and one patient had liver metastasis. Patients who survived longer were those who mounted melanoma peptide-specific immunity to at least two melanoma peptides. The present results therefore justify the design of larger follow-up studies to assess the immunological and clinical outcomes in patients with metastatic melanoma vaccinated with peptide-pulsed CD34-derived DCs.

Surfactant protein A gene deletion and prognostics for patients with stage I non-small cell lung cancer.

PURPOSE: The present study was conducted to determine clinical relevance of surfactant protein A (SP-A) genetic aberrations in early-stage non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: To determine whether SP-A aberrations are lung cancer-specific and indicate smoking-related damage, tricolor fluorescence in situ hybridization with SP-A and PTEN probes was done on touch imprints from the lung tumors obtained prospectively from 28 patients with primary NSCLC. To further define the clinical relevance of SP-A aberrations, fluorescence in situ hybridization was done on both tumor cells and adjacent bronchial tissue cells from paraffin-embedded tissue blocks from 130 patients NSCLC for whom we had follow-up information. RESULTS: SP-A was deleted from 89% of cancer tissues and the deletion was related to the smoking status of patients (P < 0.001). PTEN was deleted from 16% in the cancer tissues and the deletion was not related to the smoking status of patients (P > 0.05). In the cells isolated from paraffin-embedded tissue blocks, SP-A was deleted from 87% of the carcinoma tissues and 32% of the adjacent normal-appearing bronchial tissues. SP-A deletions in tumors and adjacent normal-appearing bronchial tissues were associated with increases in the risk of disease relapse (P = 0.0035 and P < 0.001, respectively). SP-A deletions in the bronchial epithelium were the strongest prognostic indicators of disease-specific survival (P = 0.025). CONCLUSIONS: Deletions of the SP-A gene are specific genomic aberrations in bronchial epithelial cells adjacent to and within NSCLC, and are associated with tumor progression and a history of smoking. SP-A deletions might be a useful biomarker to identify poor prognoses in patients with NSCLC who might therefore benefit from adjuvant treatment.

Immune and clinical outcomes in patients with stage IV melanoma vaccinated with peptide-pulsed dendritic cells derived from CD34+ progenitors and activated with type I interferon.

Twenty-two HLA A*0201 patients with stage IV melanoma were enrolled in a phase 1 safety and feasibility trial using a composite dendritic cell (DC) vaccine generated by culturing CD34 hematopoietic progenitors and activated with IFN-alpha. The DC vaccine was loaded with peptides derived from four melanoma tissue differentiation antigens (MART-1, tyrosinase, MAGE-3, and gp100) and influenza matrix peptide (Flu-MP). Twenty patients were evaluable, 14 of whom received vaccination with peptide-pulsed DCs without keyhole limpet hemocyanin (KLH) and 6 of whom received vaccination with KLH-loaded DCs. Patients were vaccinated until disease progression or until they had received eight vaccinations. None of the analyzed patients showed the expansion of melanoma-peptide-specific circulating effector memory T cells that secrete IFN-gamma in direct ELISPOT. Melanoma-peptide-specific recall memory CD8 T cells able to secrete IFN-gamma and to proliferate could be detected in six of the seven analyzed patients. There were no objective clinical responses. The estimated median overall survival was 12 months (range 2-38), and the median event-free survival was 4 months (range 1-12). There was no statistically significant survival advantage in patients who received KLH-loaded vaccines. As of March 2005, four patients remained alive, 26+, 28+, 28+, and 36+ months. Three of them had received KLH-loaded vaccines and all of them had had additional therapy. Overall, these results suggest that IFN-alpha-activated CD34-DCs are safe but elicit only limited immune responses, underscoring the need to test different DC maturation factors.

An assessment of risk understanding in Hispanic genetic counseling patients.

This study sought to identify if differences existed in risk comprehension and risk format understanding between genetic counseling patients of Hispanic and Caucasian ethnicity. A total of 107 questionnaires were collected, 56 from Hispanic patients, and 51 from Caucasian controls. Of the total population 41.1% (44/107) could not demonstrate sufficient risk understanding, which was 71.4% (40/56) of Hispanics and 7.8% (4/51) of Caucasians. Fractions were the best-understood format for all participants. However, both Hispanics and Caucasians had difficulties with the percentage risk format. Discrepancies were also noted in qualitative word format understanding. Awareness of differences in risk comprehension may affect the selection of counseling techniques and strategies utilized by genetic counselors when educating patients about risk related information.

Color stability of dry earth pigmented maxillofacial silicone A-2186 subjected to microwave energy exposure.

PURPOSE: The purpose of this study was to measure spectrophotometrically the color stability of pigmented A-2186 silicone maxillofacial elastomer with 10% by volume of titanium white dry earth opacifier before and after exposure to microwave energy over a simulated 1.5-year period of microwave sterilization. MATERIALS AND METHODS: A-2186 silicone elastomer opacified with titanium white dry earth pigment, pigmented with 5 cosmetic dry earth pigment colors [no pigment (control) group (Pc), red (Pr), yellow ochre (Py), burnt sienna (Po), and a mixture of Pr + Py + Po color group (P3)], was used in this study. Each of the 5 experimental groups consisted of 5 specimens. All specimens were placed in a 250 ml glass beaker filled with 150 ml of water (replenished for each microwave exposure). An exposure of 6 minutes was used 18 times (simulating 1.5 years of microwave sterilization with one 6 minute exposure monthly). Reflectance values were measured by spectrophotometer. Three- and two-way analyses of variance with repeated measures were performed for the color difference (DeltaE*) with the factors of group/color/months, and group/months, respectively. Means were compared by Tukey Honest Significant Difference (HSD) multiple range test calculated at the 0.05 level of significance using SPSS. RESULTS: The trained human eye can detect color changes (DeltaE*) greater than 1.0. Most DeltaE* values of the red pigment group at all intervals and the mixed pigment group at 15- and 18- month intervals increased significantly greater than 1.0 (p < 0.001) compared with the control group. Yellow and burnt sienna groups remained the most color stable over time with DeltaE* values below 0.35. CONCLUSIONS: Lack of color stability of red dry earth pigmented A-2186 silicone maxillofacial elastomers was clinically significant after 12-month exposure to microwave energy as compared with yellow, burnt sienna, and opacified A-2186 dry earth pigments.