Randomized phase II trial of the clinical and biological effects of two dose levels of gefitinib in patients with recurrent colorectal adenocarcinoma.

PURPOSE: The clinical objective of this trial was to evaluate gefitinib in patients with metastatic colorectal cancer that had progressed despite prior treatment. Serial tumor biopsies were performed when possible and analyzed for activation of the epidermal growth factor receptor (EGFR) signaling pathway. Serial serum samples were measured for amphiregulin and transforming growth factor-alpha (TGFalpha). PATIENTS AND METHODS: One hundred fifteen patients were randomly assigned to receive gefitinib 250 or 500 mg orally once a day. One hundred ten patients were assessable for clinical efficacy. Biologic evaluation was performed on paired tumor samples from 28 patients and correlated with clinical outcome. RESULTS: Median progression-free survival was 1.9 months (95% CI, 1.8 to 2.1 months) and 4-month progression-free survival rate was 13% +/- 5%. One patient achieved a radiographic partial response (RR = 1%; 95% CI, 0.01% to 5%). Median survival was 6.3 months (95% CI, 5.1 to 8.2 months). The most common adverse events were skin rash, diarrhea, and fatigue. In the biopsy cohort, expression of total or activated EGFR, activated Akt, activated MAP-kinase, or Ki67 did not decrease following 1 week of gefitinib. However, a trend toward decreased post-treatment levels of activated Akt and Ki67 was observed in patients with a PFS higher than the median, although these did not reach the .05 level of significance. CONCLUSION: Gefitinib is inactive as a single agent in patients with previously treated colorectal cancer. In tumor samples, gefitinib did not inhibit activation of its proximal target, EGFR. Trends were observed for inhibition of downstream regulators of cellular survival and proliferation in patients achieving longer progression-free survival.     

Normative Data on the Boston Naming Test and Two Equivalent 30-Item Short Forms

Because of the significance of the Boston Naming Test (BNT) in the differential diagnosis of the dementias, especially Alzheimer's disease, adequate norms from community-dwelling elderly individuals are essential. The present study describes the development of two new empirically derived equivalent short forms (30 items each) of the test. Normative data for the total BNT and the two equivalent 30-item halves based on item difficulty are presented using the performance of 314 community-dwelling individuals aged 65 and over. Age and education norms are presented using an overlapping midpoint interval strategy.     

Two cases of dermatoses koebnerizing within fields of previous radiotherapy

We describe two patients with newly diagnosed dermatoses localizing to the radiotherapy field following treatment for breast cancer. Patient 1 was a 53‐year‐old woman who developed bullous morphoea on her left breast two years after radiotherapy. Patient 2 was a 43‐year‐old woman who developed urticaria pigmentosa on her right breast eight months after radiotherapy and similar lesions gradually developed beyond the radiotherapy field. Both patients experienced a significant delay in diagnosis due to diagnostic confusion and concern over breast cancer recurrence. Irradiated skin demonstrates gradual and sustained alterations in fibrosis due to the production of long‐lived cytokines and chemokines. These changes can induce a koebnerizing response in conditions such as morphoea and urticaria pigmentosa. We explore the mechanisms behind radiotherapy‐induced skin changes, and highlight the potential for radiotherapy to exacerbate or unmask underlying dermatoses and systemic disease in the months and years following treatment.     

Social vulnerability and reactions to caregiving in daughters and daughters‐in‐law caring for disabled aging parents

Variables that have been conceptually linked with social vulnerability—income, educational level, employment, cessation of work to provide care, marital status, social support, and health—were used to predict four categories of reaction to caregiving in 159 daughters and daughters‐in‐law caring for their disabled aging parents. Social support, income, and health best predicted negative reactions to caregiving; social support alone best predicted feelings of family abandonment, impact on health, and impact on schedule. Compared with daughters and daughters‐in‐law who had not quit work to provide care, those who had quit work were significantly older, had lower incomes and fewer social supports, and were more involved in care. The results suggest that quitting work may be a precursor to social isolation that places the caregiver at increased risk for social vulnerability and negative reaction to caregiving. The implications of the findings for health care policy are discussed.     

Temporal Pattern of Cocaine Intake Determines Tolerance vs Sensitization of Cocaine Effects at the Dopamine Transporter

The dopamine transporter (DAT) is responsible for terminating dopamine (DA) signaling and is the primary site of cocaine''s reinforcing actions. Cocaine self-administration has been shown previously to result in changes in cocaine potency at the DAT. To determine whether the DAT changes associated with self-administration are due to differences in intake levels or temporal patterns of cocaine-induced DAT inhibition, we manipulated cocaine access to produce either continuous or intermittent elevations in cocaine brain levels. Long-access (LgA, 6 h) and short-access (ShA, 2 h) continuous self-administration produced similar temporal profiles of cocaine intake that were sustained throughout the session; however, LgA had greater intake. ShA and intermittent-access (IntA, 6 h) produced the same intake, but different temporal profiles, with ‘spiking'' brain levels in IntA compared with constant levels in ShA. IntA consisted of 5-min access periods alternating with 25-min timeouts, which resulted in bursts of high responding followed by periods of no responding. DA release and uptake, as well as the potency of cocaine for DAT inhibition, were assessed by voltammetry in the nucleus accumbens slices following control, IntA, ShA, and LgA self-administration. Continuous-access protocols (LgA and ShA) did not change DA parameters, but the ‘spiking'' protocol (IntA) increased both release and uptake of DA. In addition, high continuous intake (LgA) produced tolerance to cocaine, while ‘spiking'' (IntA) produced sensitization, relative to ShA and naive controls. Thus, intake and pattern can both influence cocaine potency, and tolerance seems to be produced by high intake, while sensitization is produced by intermittent temporal patterns of intake.     

Influences of the colonic microbiome on the mucous gel layer in ulcerative colitis

The colonic mucus gel layer (MGL) is a critical component of the innate immune system acting as a physical barrier to microbes, luminal insults, and toxins. Mucins are the major component of the MGL. Selected microbes have the potential to interact with, bind to, and metabolize mucins. The tolerance of the host to the presence of these microbes is critical to maintaining MGL homeostasis. In disease states such as ulcerative colitis (UC), both the mucosa associated microbes and the constituent MGL mucins have been shown to be altered. Evidence is accumulating that implicates the potential for mucin degrading bacteria to negatively impact the MGL and its stasis. These effects appear more pronounced in UC.   This review is focused on the host-microbiome interactions within the setting of the MGL. Special focus is given to the mucolytic potential of microbes and their interactions in the setting of the colitic colon.     

Communication,collaboration and contagion: “Virtualisation” of anatomy during COVID‐19

COVID‐19 has generated a global need for technologies that enable communication, collaboration, education and scientific discourse whilst maintaining physical distance. University closures due to COVID‐19 and physical distancing measures disrupt academic activities that previously occurred face‐to‐face. Restrictions placed on universities due to COVID‐19 have precluded most conventional forms of education, assessment, research and scientific discourse. Anatomists now require valid, robust and easy‐to‐use communication tools to facilitate remote teaching, learning and research. Recent advances in communication, video conferencing and digital technologies may facilitate continuity of teaching and research activities. Examples include highly‐interactive video conferencing technology, collaborative tools, social media and networking platforms. In this narrative review, we examine the utility of these technologies in supporting effective communication and professional activities of anatomists during COVID‐19 and after.     

Sex role identity and depression in nurses

The relationship between sex role identity and depression in nurses was explored. It was posited that nurses tend to be high in feminine traits and have traditional attitudes and that these traits and attitudes will be correlated with depressive symptoms. The sample consisted of 203 nurses employed at a 350‐bed metropolitan hospital. The research questionnaire included: (a) the Maferr Inventory of Feminine Values, (b) the Bem Sex Role Inventory, (c) the Zung Self‐Rating Depression Scale, and (d) demographic data. It was found that a strong and positive association existed between traditional attitudes toward feminine sex roles and depressive symptoms. However, relationships between feminine traits and depressive symptoms were not found. Data analysis also indicated statistically significant relationships between both androgenous traits, masculine traits, and lack of depressive symptoms. Limitations in scope and sampling procedures were discussed. In addition, the significance to nursing was discussed.