Molecular determinants of cetuximab efficacy.

PURPOSE: To investigate whether mRNA expression levels of cyclin D1 (CCND1), cyclooxygenase 2 (Cox-2), epidermal growth factor receptor (EGFR), interleukin 8 (IL-8), and vascular endothelial growth factor (VEGF), all members of the EGFR signaling pathway, are associated with clinical outcome in patients with EGFR-expressing metastatic colorectal cancer (CRC) treated with cetuximab. PATIENTS AND METHODS: Thirty-nine patients with metastatic CRC, refractory to both irinotecan and oxaliplatin, were enrolled on IMCL-0144 and treated with single-agent cetuximab. The intratumoral mRNA levels of CCND1, Cox-2, EGFR, IL-8, and VEGF were assessed from paraffin-embedded tissue samples using laser-capture microdissection and quantitative real-time polymerase chain reaction. RESULTS: There were 21 women and 18 men with a median age of 64 years (range, 35 to 83 years). Higher gene expression levels of VEGF were associated with resistance to cetuximab (P = .038; Kruskal-Wallis test). The combination of low gene expression levels of Cox-2, EGFR, and IL-8 was significantly associated with overall survival (13.5 v 2.3 months; P = .028; log-rank test). Both findings were independent of skin toxicity that was itself significantly correlated to survival. Patients with a lower mRNA amount of EGFR had a longer overall survival compared with patients that had a higher mRNA amount (7.3 v 2.2 months; P = .09; log-rank test). Patients with lower expression of Cox-2 had a significantly higher rate of grade 2 to 3 skin reactions under cetuximab treatment. CONCLUSION: This pilot study suggests that gene expression levels of Cox-2, EGFR, IL-8, and VEGF in patients with metastatic CRC may be useful markers of clinical outcome in single-agent cetuximab treatment.     

Rotational chair (ROTO) instead of electronystagmography (ENG) as the primary vestibular test.

OBJECTIVES: To compare the sensitivity of rotational chair (ROTO) versus electronystagmography (ENG) in peripheral vestibular pathology. METHODS: Retrospective chart review. RESULTS: One thousand consecutive patients undergoing evaluation for dizziness and imbalance at a tertiary care referral balance center were reviewed. ROTO was the primary vestibular study used in all patients with ENG used as a confirmatory test at the discretion of the treating physician. A subgroup of 478 patients underwent both ROTO and ENG. Among the patients diagnosed with peripheral vestibulopathy, sensitivity for peripheral vestibulopathy was 71% for ROTO and 31% for ENG. However, specificity was 54% for ROTO and 86% for ENG. CONCLUSIONS: We conclude that in this retrospective cohort with the authors' clinical diagnoses, ROTO is a more sensitive diagnostic study of peripheral vestibular pathology. The higher sensitivity of ROTO and the higher specificity of ENG may support the use of ROTO as the primary vestibular study and ENG as a supplemental vestibular study. Prospective analysis with distinct diagnostic criteria and defined inclusion criteria are necessary before these results can be widely extrapolated.     

Satellite cells express distinct patterns of myogenic proteins in immature skeletal muscle.

Satellite cells are the myogenic cells lying between the myofiber sarcolemma and basal lamina. The objective of this study was to determine the expression patterns of MyoD, myogenin, and Pax7 within the satellite cell population in the growing rat soleus and extensor digitorum longus (EDL) muscles. Secondly, the expression of the myogenic markers was also studied within the interstitial cell compartment and myonuclei. It was discovered that the soleus contained a higher number of Pax7, MyoD, or myogenin-positive nuclei compared with the EDL. Similarly, myogenin was expressed at a lower level in the myonuclei of the soleus compared with the EDL, and myogenin was expressed at a higher level in the interstitial compartment of the soleus compared with the EDL. When interstitial nuclei, myonuclei, and double-labeled nuclei were used in the estimate of the satellite cell population, it was discovered that approximately of 13% of the myofibers in a transverse section of the soleus muscle and 4.1% of EDL myofibers exhibit a labeled satellite cell nucleus. Overall, results from this study suggest that expression patterns of these markers vary predictably among muscles with different growth dynamics and phenotypic characteristics.     

The influence of stimulus size on measured visual field extent in infants.

PURPOSE: To compare measured visual field extent for a 6 degrees stimulus (typical size used in studies of infants) with a 1.5 degrees stimulus (similar to the largest size used in Goldmann perimetry) in young infants. METHODS: A total of 120 infants (60 each at 3.5 months and 7 months of age) and 24 adults were tested monocularly with a kinetic perimetry procedure using a black double-arc perimeter. Each subject was tested with either a 6 degrees or 1.5 degrees white sphere, which was mounted on a black wand and moved smoothly toward the intersection of the perimeter arms at 3.4 degrees /s. Visual field extent along each perimeter arm was defined as the median of 2 to 3 measurements of the position of the leading edge of the stimulus when the subject made an eye movement toward the stimulus. RESULTS: The 6 degrees stimulus produced larger measured visual field extent than the 1.5 degrees stimulus in 3.5-month olds (temporal field only) and in 7-month olds (nasal and temporal field), but not in adults. CONCLUSIONS: Using the testing conditions of the present study, increasing stimulus size beyond the largest used in a Goldmann perimeter (approximately 2 degrees) increases measured visual field extent in young infants, but not in adults. This may relate to differences in peripheral summation areas or to differences in attentional factors between infants and adults.     

Learning to Observe Relationships and Coping

Milieu relationships provide the critical background presence to staff's attempts to motivate, regulate, and teach patients how to cope with stress. Forging a connection with hospitalized children and adolescents demands attention to how they respond to adults and engage with staff around milieu expectations. Assessment guides that deal with these issues are presented. Important aspects of children's relatedness are presented in the context of their working models of adults and the influence of these representations on their response to staff. Coping skills are explained with particular emphasis on behavioral coping strategies. Tied to the assessment process are interventions that emphasize staff's role in helping patients manage strong affects and avoid the use of nonproductive behavior regulation strategies.     

Nonemergent ED patients referred to community resources after medical screening examination: characteristics, medical condition after 72 hours, and use of follow-up services.

INTRODUCTION: Limited access to medical care has resulted in large numbers of patients seeking primary care for non-emergent emergency conditions in emergency departments. This influx of patients is contributing to overcrowding and delays in care for patients with emergencies. In response, a system was implemented in which persons with non-emergent medical conditions, following a medical screening examination, did not receive further ED assessment or treatment and instead were referred to community resources. The purpose of this study was to describe the characteristics of individuals who were referred to community-based services, their condition after 72 hours, and their use of follow-up health care services. METHODS: All referred cases (n=225) were reviewed for chief complaint and demographics. Phone contact was attempted after 72 hours to determine the person's condition and if community resources were utilized. RESULTS: Of the 225 cases, 52% were female, with a mean age of 33 years. Their most common chief complaints were extremity problems (16%), toothache (9%), and medication refill (8%). Follow-up phone contact was successful with 82 people (37%) an average of 14 days after their ED visit. The majority (55%) reported their condition had improved; 39%were unchanged, and 6% were worse. Thirty-one people(40%) accessed community resources and 8 (26%) returned to another emergency department. No clinically significant associations were found between patient demographics and use of community resources. DISCUSSION: Most people who were successfully contacted for follow-up and who had come to the emergency department with non-emergent chief complaints did not access community resources and their condition frequently improved. Additional studies, with improved follow-up, are needed before suggesting that referring individuals to community resources is an acceptable practice.     

Addressing quality of life issues in adolescents: social skills interventions.

OBJECTIVE: The purpose of this study was to determine whether social skills training can improve the social interaction skills of adolescents with craniofacial conditions (CFCs) in a natural environment (school lunchroom). DESIGN: This study used a pre-post between-group comparison design. Differences between treatment and control subjects were analyzed via a repeated measures analysis of variance. SETTING: The observations were conducted in the respective school lunch-rooms of the adolescents. Social skills groups were conducted in an outpatient clinic setting. MAIN OUTCOME MEASURES: Structured data based on 45 minutes of observation was coded for type, frequency, and duration of social contact. Specific measures included subject initiations and responses, peer initiations and responses, conversation events, total positive communication, and frequency of nondirected comments. RESULTS: Both target and peer-controlled total communication improved across time with adolescents receiving social skills intervention showing significantly more improvement than those adolescents not receiving direct social skills interventions. Adolescents receiving treatment participated in significantly more target initiated conversations lasting at least three interchanges and showed a trend toward a greater frequency of target initiations and positive responses to peer initiations. Peers were more likely to respond to treatment subject initiations after intervention. Fewer treatment subjects used nondirected communication, whereas control subjects continued to use nondirected communication at a slightly increased frequency. CONCLUSIONS: This study provides preliminary evidence that social skills training can increase the frequency of positive social interactions with peers for adolescents with CFCs.     

Trends in Folic Acid Awareness and Behavior in the United States: The Gallup Organization for the March of Dimes Foundation Surveys, 1995–2005

Objective: To summarize changes in folic acid awareness, knowledge, and behavior among women of childbearing age in the United States since the U.S. Public Health Service (USPHS) 1992 folic acid recommendation and later fortification. Methods: Random-digit dialed telephone surveys were conducted of approximately 2000 women (per survey year) aged 18–45 years from 1995–2005 in the United States. Results: The percentage of women reporting having heard or read about folic acid steadily increased from 52% in 1995 to 84% in 2005. Of all women surveyed in 2005, 19% knew folic acid prevented birth defects, an increase from 4% in 1995. The proportion of women who reported learning about folic acid from health care providers increased from 13% in 1995 to 26% in 2005. The proportion of all women who reported taking a vitamin supplement containing folic acid increased slightly from 28% in 1995 to 33% in 2005. Among women who were not pregnant at the time of the survey in 2005, 31% reported taking a vitamin containing folic acid daily compared with 25% in 1995. Conclusions: The percentage of women taking folic acid daily has increased modestly since 1995. Despite this increase, the data show that the majority of women of childbearing age still do not take a vitamin containing folic acid daily. Health care providers and maternal child health professionals must continue to promote preconceptional health among all women of childbearing age, and encourage them to take a vitamin containing folic acid daily.