Disruption and reacquisition of binocular vision in childhood and in adulthood

PURPOSE OF REVIEW: This article reviews the most recent studies that address the loss of and restoration of binocular vision in childhood and adulthood and summarizes recent changes in treatment approaches. RECENT FINDINGS: Studies during the last two years support the idea of continued plasticity of the binocular visual system throughout life. Children and adults with strabismus onset following binocular vision maturation are susceptibility to a permanent disruption of stereopsis and sensory fusion. Plasticity of the binocular visual system, however, also means continued restorability of function. Despite a rather short critical time interval for restoration of normal function (three months in children and 12 months in adults), peripheral or extramacular binocular visual function can be restored in most patients whose onset of disruption follows binocular maturation. SUMMARY: Stereoacuity loss can occur in the visually mature patient who develops strabismus later in life and delay of treatment can be deleterious to the restoration of normal macular binocular vision. However, despite any delay of treatment, most patients with strabismus acquired following binocular vision maturation will manifest some stereoacuity or sensory fusion following eye realignment. These findings suggest all patients with strabismus need to have their eyes aligned, either surgically or optically, to maximize their binocular vision outcome.     

In Vitro penetration of a novel oxaborole antifungal (AN2690) into the human nail plate

Onychomycosis is a challenging fungal infection to treat topically, likely due to the unique properties of the nail plate. This seemingly impenetrable barrier has high resistance to the passage of antifungal drugs in sufficient concentrations to kill the causative fungi deep in the nail bed. Recently, a new class of antifungal agent was described, termed oxaboroles, which have broad-spectrum activity. These oxaboroles were designed with properties believed to be required to allow for easier transit through the nail plate. Herein, we report (i) the nail penetration results of four oxaboroles that led to the selection of AN2690, (ii) the results of the nail penetration of AN2690 from four vehicles, and (iii) the nail penetration of AN2690 in its chosen vehicle compared to a commercial control, ciclopirox. AN2690 has superior penetration compared to ciclopirox, and achieves levels within and under the nail plate that suggest it has the potential to be an effective topical treatment for onychomycosis.     

平贝碱乙的分离和鉴定

本文报道了自东北平贝母(Fritillaria ussuriensis Maxim)中分得一种新的甾体生物碱,经光谱(IR,MS,¹HNMR及¹³CNMR)解析和衍生物制备,推定其结构为5α,17β,22α-cevanine-3 β,6α,12α,14α,16β,20β-hexol,定名为平贝碱乙。     

Psychosocial factors associated with the uptake of contralateral prophylactic mastectomy among <Emphasis Type="Italic">BRCA1/2</Emphasis> mutation noncarriers with newly diagnosed breast cancer

Purpose

Women who are newly diagnosed with breast cancer may consider contralateral prophylactic mastectomy (CPM) to reduce their future risk of cancer in their unaffected breast. Pre-surgical BRCA1/2 genetic testing can provide valuable risk information to guide this choice. However, little is understood about why BRCA1/2 mutation noncarriers, who are generally not at substantially elevated risk of contralateral disease, select CPM.

Methods

We examined the uptake of CPM among breast cancer patients identified as BRCA1/2 mutation noncarriers (n = 92) as part of a larger prospective study of the impact of pre-surgical BRCA1/2 testing. Data obtained from self-report questionnaires and patient medical records were used to examine associations between theoretically relevant background and psychosocial factors and BRCA1/2 mutation noncarriers’ decisions to undergo CPM.

Results

Among BRCA1/2 mutation noncarriers, 25% (n = 23) elected to undergo CPM. Psychosocial factors including a self-reported physician recommendation for CPM, greater perceived contralateral breast cancer risk, and greater perceived benefits of CPM were all significantly associated with the uptake of CPM.

Conclusions

A sizeable minority of BRCA1/2 mutation noncarriers choose to undergo CPM after learning their mutation status through pre-surgical genetic testing. BRCA1/2 mutation noncarriers’ cognitive perceptions and social influences appear to be important in shaping their decisions regarding CPM. This work highlights the importance of several psychosocial factors in influencing patients’ surgical decisions. Future research is needed that examines the formation of BRCA1/2 mutation noncarriers’ beliefs regarding their disease and available treatment options, and that characterizes the physician-patient communication that occurs in this complex decision-making context.

     

A phase II trial of gemcitabine, 5-fluorouracil and leucovorin in advanced esophageal carcinoma

BACKGROUND: The aim of this study was to evaluate the overall response rate, toxicity and overall survival in patients with locally advanced or metastatic esophageal cancer treated with gemcitabine, 5-fluorouracil (5-FU) and leucovorin. PATIENTS AND METHODS: Patients with either adenocarcinoma or squamous cell carcinoma of the esophagus could enroll; however, patients could not have received prior chemotherapy for metastatic disease. Treatment cycles consisted of infusions of all three agents at days 1, 8 and 15, repeated every 28 days. Patients received gemcitabine 1,000, leucovorin 25 and 5-FU 600 mg/m(2). Tumor assessment was performed every 2 cycles. Responses were assessed using the Eastern Cooperative Oncology Group solid tumor response criteria. RESULTS: Thirty-five patients with metastatic or locally advanced esophageal cancer enrolled. One complete response and ten partial responses were observed for an overall response rate of 31.4%. An additional 11 patients had stable disease as their best response. The median survival was 9.8 months with a 1-year survival rate of 37.1%. Toxicity was predominately hematologic, with 58% of patients experiencing grade 3 or 4 neutropenia. CONCLUSION: The combination of gemcitabine, 5-FU and leucovorin had activity in advanced esophageal cancer. Patients tolerated the regimen well, with myelosuppression occurring most commonly. The combination merits further investigation as a treatment for esophageal cancer.     

Gene expression patterns and profile changes pre- and post-erlotinib treatment in patients with metastatic breast cancer.

PURPOSE: To delineate gene expression patterns and profile changes in metastatic tumor biopsies at baseline and 1 month after treatment with the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib in patients with metastatic breast cancer. EXPERIMENTAL DESIGN: Patients were treated with 150 mg of oral erlotinib daily. Gene expression profiles were measured with Affymetrix U133A GeneChip and immunohistochemistry was used to validate microarray findings. RESULTS: Estrogen receptor (ER) status by immunohistochemistry is nearly coincided with the two major expression clusters determined by expression of genes using unsupervised hierarchical clustering analysis. One of 10 patients had an EGFR-positive tumor detected by both microarray and immunohistochemistry. In this tumor, tissue inhibitor of metalloproteinases-3 and collagen type 1 alpha 2, which are the EGF-down-regulated growth repressors, were significantly increased by erlotinib. Gene changes in EGFR-negative tumors are those of G-protein-linked and cell surface receptor-linked signaling. Gene ontology comparison analysis pretreatment and posttreatment in EGFR-negative tumors revealed biological process categories that have more genes differentially expressed than expected by chance. Among 495 gene ontology categories, the significant differed gene ontology groups include G-protein-coupled receptor protein signaling (34 genes, P = 0.002) and cell surface receptor-linked signal transduction (74 genes, P = 0.007). CONCLUSIONS: ER status reflects the major difference in gene expression pattern in metastatic breast cancer. Erlotinib had effects on genes of EGFR signaling pathway in the EGFR-positive tumor and on gene ontology biological process categories or genes that have function in signal transduction in EGFR-negative tumors.     

Superior outcome with hypomethylating therapy in patients with acute myeloid leukemia and high‐risk myelodysplastic syndrome and chromosome 5 and 7 abnormalities

BACKGROUND:

Outcome of patients with acute myeloid leukemia (AML) and high‐risk myelodysplastic syndrome (MDS) with chromosome 5 and 7 abnormalities (excluding del 5[q]) has been poor, with <10% of patients alive at 2 years.

METHODS:

The authors investigated whether treatment with hypomethylating agents (5‐azacytidine/decitabine) leads to an improved outcome. Between January 2004 and December 2007, 81 patients (37 [46%] with AML [≥20% blasts]; 44 [54%] with high‐risk MDS) with chromosome 5 and 7 abnormalities were treated with hypomethylating agents as their initial therapy. These included 68 patients with complex (≥3) abnormalities and 13 with <3 aberrations. During the same period, 151 patients (126 with AML, 25 with MDS) with chromosome 5 and 7 abnormalities (128 complex, 23 noncomplex) were treated with intensive chemotherapy (including cytarabine‐based regimens in 72% and other regimes in 28%).

RESULTS:

The median ages for the 2 groups were 66 years and 61 years, respectively (ranges, 37‐85 years and 19‐89 years). Thirty‐three (41%) patients in the hypomethylating group achieved complete remission (CR) versus 53 (35%) in the chemotherapy group (P = .395). With a median follow‐up of 51 weeks (range, 12‐101 weeks) and 40 weeks (range, 5–128 weeks), 22 of 33 patients in the hypomethylating group and 33 of 53 patients in the chemotherapy group had developed disease recurrence. The median CR duration was 45 weeks and 23 weeks, respectively (P = .153). The overall survival was superior for the hypomethylating group compared with the chemotherapy group (P = .019).

CONCLUSIONS:

Treatment with hypomethylating agents may be superior to chemotherapy in patients with chromosome 5 and 7 abnormalities. Cancer 2009. © 2009 American Cancer Society.     

Results of the hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone regimen in elderly patients with acute lymphocytic leukemia

BACKGROUND.

Understanding the causes of failure in older patients with acute lymphocytic leukemia (ALL) may help improve treatment strategies for patients in this particular age group.

METHODS.

The objectives of the current study were to define the causes of death in older patients (aged ≥60 years) with ALL during induction and consolidation‐maintenance with a dose‐intensive regimen of alternating 8 courses of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper‐CVAD) with high doses of methotrexate and cytarabine followed by maintenance with 6‐mercaptopurine, vincristine, methotrexate, and prednisone and to compare their outcomes with the outcomes of older patients who received earlier, less intensive regimens and younger patients who received hyper‐CVAD. One hundred twenty‐two older patients who received hyper‐CVAD were compared with 34 older patients who received less intensive regimens and with 409 younger patients who received hyper‐CVAD.

RESULTS.

The complete response (CR) rates in older patients receiving hyper‐CVAD, older patients receiving other regimens, and younger patients receiving hyper‐CVAD were 84%, 59%, and 92%, respectively (P < .001); and the respective induction mortality rates were 10%, 12%, and 2% (P not significant in older patients). The incidence of disease resistance during induction was 5%, 27%, and 2%, respectively (P < .001). The majority of deaths were related to infections. Among patients who achieved a CR, death in CR was noted in 34%, 15%, and 7% of older patients receiving hyper‐CVAD, older patients receiving other regimens, and younger patients, respectively (P < .001); and the respective rates of recurrence were 40%, 80%, and 48% (P = .004). The estimated 5‐year survival rates were 20%, 9%, and 48%, respectively (P < .001).

CONCLUSIONS.

The results of the current study suggested that intensifying the chemotherapy in older patients with ALL reduced the incidence of leukemia resistance but increased the incidence of death in CR from myelosuppression‐associated infections. The overall benefit:risk ratio was favorable. Identifying novel, low‐intensity agents/regimens for older patients with ALL may improve the results further. Cancer 2008. © 2008 American Cancer Society.