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Biomedical subjects

Kevin Fox

Publications and source records attributed to Kevin Fox.

At least 19 recordsLinked to original sources
PubMed2006

EAE laboratory standards and accreditation.

Laboratory standards have been set by the European Association of Echocardiography of the European Society of Cardiology, in order to homogenize the practice of echocardiography in Europe and therefore ultimately, to protect patients. These standards have been developed for transthoracic, transesophageal and stress Echocardiography into two levels; the basic level, set to provide basic laboratory standards for an optimal clinical service and the advanced level, which is set to establish a fewer number of advanced laboratories in each country, where by in addition to basic standards, they may be providing extensive teaching and research.

Accreditation↗
PubMed2006

The role of nitric oxide and GluR1 in presynaptic and postsynaptic components of neocortical potentiation.

In this study, we investigated the mechanisms underlying synaptic plasticity at the layer IV to II/III pathway in barrel cortex of mice aged 6-13 weeks. This pathway is one of the likely candidates for expression of experience-dependent plasticity in the barrel cortex and may serve as a model for other IV to II/III synapses in the neocortex. We found that postsynaptic autocamtide-2-inhibitory peptide is sufficient to block long-term potentiation (LTP) (IC50 of 500 nm), implicating postsynaptic calcium/calmodulin-dependent kinase II in LTP induction. AMPA receptor subunit 1 (GluR1) knock-out mice also showed LTP in this pathway, but potentiation was predominantly presynaptic in origin as determined by paired-pulse analysis, coefficient of variation analysis, and quantal analysis, whereas wild types showed a mixed presynaptic and postsynaptic locus. Quantal analysis at this synapse was validated by measuring uniquantal events in the presence of strontium. The predominantly presynaptic LTP in the GluR1 knock-outs was blocked by postsynaptic antagonism of nitric oxide synthase (NOS), either with intracellular N-omega-nitro-L-arginine methyl ester or N-nitro-L-arginine, providing the first evidence for a retrograde transmitter role for NO at this synapse. Antagonism of NOS in wild types significantly reduced but did not eliminate LTP (group average reduction of 50%). The residual LTP formed a variable proportion of the total LTP in each cell and was found to be postsynaptic in origin. We found no evidence for silent synapses in this pathway at this age. Finally, application of NO via a donor induced potentiation in layer II/III cells and caused an increase in frequency but not amplitude of miniature EPSPs, again implicating NO in presynaptic plasticity.

Action Potentials↗
PubMed2006

Cancer-related relationship communication in couples coping with early stage breast cancer.

This longitudinal study examined the association between three types of communication strategies couples may use to handle stressors they experience during and after breast cancer treatment and psychological distress and relationship satisfaction of women with early stage breast cancer and their partners. Mutual constructive communication, mutual avoidance, and demand-withdraw communication strategies as well as psychological distress and marital satisfaction were rated by 147 patients and 127 partners during cancer treatment and 9 months later. Mutual constructive communication was associated with less distress and more relationship satisfaction for both patient and partner. Demand-withdraw communication was associated with higher distress and lower relationship satisfaction for both patient and partner. Mutual avoidance was associated with more distress for patient and partner but was not associated with relationship satisfaction. The negative association between mutual constructive communication and patient distress was stronger for patients with more physical impairment. Patients' perceptions of mutual constructive communication and mutual avoidance were associated with partners' distress, and patients' perceptions of mutual constructive and demand/withdraw communication were associated with partners' marital satisfaction. Clinical implications for couple-focused communication skills training for cancer patients and their partners are discussed.

Adaptation, Psychological↗
PubMed2006

Preservation of fertility and the impact of subsequent pregnancy in patients with premenopausal breast cancer.

The occurrence of early-stage breast cancer in premenopausal women who desire children is a considerable clinical challenge. The frequent use of adjuvant cytotoxic chemotherapy can induce ovarian failure and infertility, while the frequent use of adjuvant hormonal therapy is a contraindication to conception. A variety of techniques to preserve fertility in spite of adjuvant chemotherapy are under investigation, with promising early results. Ovarian stimulation with retrieval of eggs for in vitro fertilization and cryopreservation prior to the commencement of chemotherapy seems to hold the greatest promise for patients. There is no evidence that patients treated with curative intent for early-stage breast cancer who subsequently become pregnant have a compromised survival, but patients should be counseled regarding their risk of recurrence in general and whether a high recurrence risk might make subsequent pregnancy and motherhood an unwise choice. The offspring of breast cancer survivors do not appear to suffer deleterious consequences as a result of the diagnosis or treatment of the mother.

Antineoplastic Agents, Hormonal↗
PubMed2006

Cancer-specific self-efficacy and psychosocial and functional adaptation to early stage breast cancer.

BACKGROUND: Although self-efficacy is considered a key psychological resource in adapting to chronic physical illness, this construct has received less attention among individuals coping with cancer. PURPOSE: To examine changes in cancer self-efficacy over time among women with early stage breast cancer and associations between task-specific domains of self-efficacy and specific psychological, relationship, and functional outcomes. METHODS: Ninety-five women diagnosed with early stage breast cancer completed surveys postsurgery and 1 year later. RESULTS: Cancer-related self-efficacy was relatively stable over 1 year, with only 2 domains of efficacy-(a) Activity Management and (b) Self-Satisfaction-evidencing significant increases over the 1-year time period. Cross-sectional findings were relatively consistent with predictions and suggested that specific domains of self-efficacy were more strongly related to relevant domains of adaptation. Longitudinal findings were not as consistent with the domain-specificity hypothesis but did suggest several predictive associations between self-efficacy and outcomes. Personal Management self-efficacy was associated with higher relationship satisfaction, higher Communication Self-Efficacy was associated with less functional impairment, and higher Affective Management self-efficacy was associated with higher self-esteem 1 year later. CONCLUSIONS: Specific domains of cancer-related self-efficacy are most closely related to relevant areas of adaptation when considered cross-sectionally, but further study is needed to clarify the nature of these relationships over time.

Activities of Daily Living↗
PubMed2005

A comparison of experience-dependent plasticity in the visual and somatosensory systems.

In the visual and somatosensory systems, maturation of neuronal circuits continues for days to weeks after sensory stimulation occurs. Deprivation of sensory input at various stages of development can induce physiological, and often structural, changes that modify the circuitry of these sensory systems. Recent studies also reveal a surprising degree of plasticity in the mature visual and somatosensory pathways. Here, we compare and contrast the effects of sensory experience on the connectivity and function of these pathways and discuss what is known to date concerning the structural, physiological, and molecular mechanisms underlying their plasticity.

Action Potentials↗
PubMed2005

The diagnostic accuracy of plasma BNP and NTproBNP in patients referred from primary care with suspected heart failure: results of the UK natriuretic peptide study.

OBJECTIVES: To determine the diagnostic accuracy of the measurement of plasma B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NTproBNP) in patients referred by their general practitioners (GPs) with symptoms suggestive of heart failure. Additionally, to compare the diagnostic accuracy of the resting 12-lead electrocardiogram (ECG) with that of the peptides. DESIGN: A diagnostic accuracy study. SETTING: Rapid-access heart failure clinics in five hospitals. PARTICIPANTS: 306 patients referred by their GPs with suspected heart failure. MAIN OUTCOME MEASURES: Sensitivity, specificity, positive and negative predictive values (PPV and NPV) and positive and negative likelihood ratios for BNP, NTproBNP and the ECG for the diagnosis of heart failure. Area under the receiver operating characteristics (ROC) curves for the two natriuretic peptides. RESULTS: The diagnosis of heart failure was confirmed in 104 (34%) patients. The area under the ROC curve was 0.84 [95% CI 0.79-0.89] for BNP and 0.85 [0.81-0.90] for NTproBNP. At the manufacturers' recommended decision cut-points, NTproBNP provided a higher NPV (0.97) than BNP (0.87), but at lower PPV (0.44 versus 0.59). An abnormal ECG did not add any further predictive value to that of NTproBNP. CONCLUSIONS: We have confirmed the value of the measurement of plasma BNP or NTproBNP as a 'rule-out' test for heart failure in patients currently referred by GPs to rapid access diagnostic clinics. A simple classification of the 12-lead ECG into 'normal' or 'abnormal' adds little value to ruling out heart failure in these circumstances. Further work is necessary to establish the best decision cut-points for use in clinical practice.

Aged↗
PubMed2005

Couple-focused group intervention for women with early stage breast cancer.

This study examined the efficacy of a couple-focused group intervention on psychological adaptation of women with early stage breast cancer and evaluated whether perceived partner unsupportive behavior or patient functional impairment moderated intervention effects. Two hundred thirty-eight women were randomly assigned to receive either 6 sessions of a couple-focused group intervention or usual care. Intent-to-treat growth curve analyses indicated that participants assigned to the couples' group reported lower depressive symptoms. Women rating their partners as more unsupportive benefited more from the intervention than did women with less unsupportive partners, and women with more physical impairment benefited more from the intervention group than did women with less impairment. Subgroup analyses comparing women attending the couple-focused group intervention with women not attending groups and with usual care participants indicated that women attending sessions reported significantly less distress than did women receiving usual care and women who dropped out of the intervention.

Adult↗
PubMed2005

Partner unsupportive responses, avoidant coping, and distress among women with early stage breast cancer: patient and partner perspectives.

This 18-month longitudinal study examined the associations among partner unsupportive behavior, avoidant coping, and distress experienced by 219 women with early stage breast cancer. The role of patient and partner ratings of unsupportive behavior were evaluated. Results indicated that patient and partner ratings of unsupportive behavior were highly correlated. Growth curve modeling suggested that unsupportive behavior, from both patient and partner perspectives, predicted more avoidant coping and distress. When partner and patient perceptions were placed in the same model, patient perceptions mediated the association between partners' ratings of their unsupportive behavior and patient distress. Avoidance also mediated the association between unsupportive behavior and distress, extending prior cross-sectional findings. Results highlight the long-term detrimental effects of partners' unsupportive behavior on the quality of life of women with early stage breast cancer.

Adaptation, Psychological↗
PubMed2005

Ethnic disparities in adjuvant chemotherapy for breast cancer are not caused by excess toxicity in black patients.

BACKGROUND: Black patients with breast cancer may be at greater risk for chemotherapy-related hematologic toxicity than white patients because of lower baseline blood cell counts. We hypothesize that these baseline differences could lead to excess hematologic toxicity and greater modification of chemotherapy dosing in black patients and that this may contribute to the poorer survival observed in black patients with breast cancer compared with white patients with breast cancer. PATIENTS AND METHODS: We performed a retrospective cohort study of black and white patients with breast cancer treated with adjuvant chemotherapy at an academic medical center over an 18-month period. Clinical chart review and pharmacy records were used to collect data on the following: modification of chemotherapy dose or administration; hematologic toxicity; blood cell counts before, during, and after therapy; occurrence of febrile neutropenia; use of prophylactic antibiotics; and use of granulocyte colony-stimulating factor in order to determine whether ethnicity was an independent predictor of these outcomes. RESULTS: Among 23 black patients and 98 white patients with breast cancer treated with adjuvant chemotherapy, modification of chemotherapy administration occurred in 56 patients (46%). Modification was more common among black patients (65.2% vs. 41.8%; relative risk [RR], 1.56; P = 0.04). Black patients were more likely to receive reduced cumulative doses of adjuvant chemotherapy (RR, 2.49; P = 0.03). CONCLUSION: Our findings suggest that hematologic tolerability of adjuvant chemotherapy is similar in black and white patients. Strategies aimed at improving psychosocial barriers to adjuvant therapy and at reducing surgical complications in black patients may improve overall breast cancer outcomes in this group.

Black or African American↗
PubMed2004

Impact of concurrent versus sequential tamoxifen with radiation therapy in early-stage breast cancer patients undergoing breast conservation treatment.

PURPOSE: To assess the impact of sequencing of tamoxifen and radiation therapy (RT) on outcomes in early-stage breast cancer. PATIENTS AND METHODS: This retrospective study evaluates the effect of the sequence of tamoxifen with RT on outcomes in stage I to II breast cancer patients who underwent breast-conservation treatment (BCT) and received adjuvant tamoxifen, with or without adjuvant chemotherapy. Patients were grouped as concurrent (tamoxifen given during RT followed by continued tamoxifen; 174 patients) and sequential (RT followed by tamoxifen; 104 patients). RESULTS: Median follow-up after RT was 8.6 years for both groups. The pathologic T and N stage, race, estrogen and progesterone status, number of positive nodes, and RT were comparable between the two groups (all P >/= .08). More women age 49 years or younger and women who received chemotherapy were in the sequential group than the concurrent group (6% and 25%, respectively; P < .0001). The sequence of tamoxifen therapy did not influence 10-year local recurrence rates (sequential, 7%; concurrent, 3%; P = .52), overall survival (sequential, 86%; concurrent, 81%; P = .64), or relapse-free survival (sequential, 76%; concurrent, 85%; P = .35). When adjusting age and chemotherapy use in the multivariable Cox model, hazard ratios comparing sequential versus concurrent tamoxifen therapy were 1.56 (95% CI, 0.87 to 2.79), 1.23 (95% CI, 0.63 to 2.41), and 1.22 (95% CI, 0.33 to 4.49) for the overall survival, relapse-free survival, and local recurrence, respectively. CONCLUSION: The therapeutic regimens of tamoxifen given concurrently or sequentially with RT both appear to be reasonable options for patients treated with BCT.

Adult↗
PubMed2004

Fifteen-year results of breast-conserving surgery and definitive irradiation for Stage I and II breast carcinoma: the University of Pennsylvania experience.

PURPOSE: To determine the 15-year outcomes for women with early stage breast cancer after breast conservation therapy. METHODS AND MATERIALS: Between 1977 and 1990, 937 women with Stage I and II breast carcinoma (55% T1N0, 16% T2N0, 18% T1N1, and 11% T2N1) underwent lumpectomy, axillary lymphadenectomy, and definitive irradiation. The median patient age was 52 years. Of the 937 patients, 375 (40%) received adjuvant chemotherapy and/or hormonal therapy, including 249 (92%) of the 270 women with pathologically positive nodes. The median follow-up was 10.1 years. RESULTS: For the overall group, the 15-year overall survival rate was 71%, and the rate of freedom from distant metastases was 76%. The 15-year local failure rate was 19%. The 15-year contralateral breast cancer rate was 12%. The most common first events were distant failure (13%), local failure (10%), contralateral breast cancer (7%), and second malignant neoplasms (6%). The local failure rate at 10 years for favorable subsets of tumors characterized by mammographic detection, resection with negative margins, treatment with chemotherapy, and treatment with hormones was 8%, 10%, 10%, and 7%, respectively. Local failures were most commonly observed within (true recurrence), or just outside (marginal miss), the primary tumor bed (66%, 85 of 128). The rate of true recurrence or marginal miss at 5, 10, and 15 years was 5%, 10%, and 12%, respectively. CONCLUSION: These high rates of survival and local control confirm that breast conservation therapy yields favorable results in women with early breast cancer into the second decade after treatment.

Adult↗
PubMed2004

Couples' support-related communication, psychological distress, and relationship satisfaction among women with early stage breast cancer.

This study examined associations between couple communication about cancer and psychological distress and relationship satisfaction of women diagnosed with early stage breast cancer. One hundred forty-eight couples completed a videotaped discussion of a cancer-related issue and a general issue. Patients completed measures of psychological distress and relationship satisfaction. Videotapes were coded with the Rapid Marital Interaction Coding System. Analyses focused on partner responses to patient self-disclosures. During cancer-issue discussions, patients reported less distress when partners responded to disclosures with reciprocal self-disclosure and humor and when partners were less likely to propose solutions. Fewer links between partner responses to patient self-disclosures and distress were found in general-issue discussions. Results suggest partner responses play a role in women's adaptation to breast cancer.

Adult↗
PubMed2004

The interpersonal process model of intimacy: the role of self-disclosure, partner disclosure, and partner responsiveness in interactions between breast cancer patients and their partners.

This study evaluated H. Reis and P. Shaver's (1988) interpersonal process model of intimacy in a sample of 98 women with breast cancer and their partners. Couples engaged in two discussions and rated self- and partner disclosure, perceived partner responsiveness, and intimacy experienced. A mediational model was tested in which partner responsiveness mediated the association between disclosure and intimacy. For patients, perceived responsiveness partially mediated the association between partner disclosure and intimacy, but self-disclosure was not significantly associated with responsiveness or intimacy. For partners, perceived responsiveness mediated the association between self-disclosure and perceived partner disclosure and intimacy. For breast cancer patients, partner disclosure predicted patient feelings of intimacy, because this type of disclosure was associated with greater feelings of acceptance, understanding, and caring. These findings may have implications for interventions to improve relationship closeness among couples coping with breast cancer.

Adult↗
PubMed2004

Gemcitabine and trastuzumab combinations for patients with metastatic breast cancer overexpressing HER2/neu.

In HER2/neu-positive metastatic breast cancer, the combination of chemotherapy and trastuzumab has become a standard of care. This review discusses HER2/neu overexpression in breast cancer and the use of trastuzumab-based therapies. Specifically, the rationale for a gemcitabine/trastuzumab combination in this disease entity and the available clinical data on the use of the combination are discussed. Response rates of 12%-42% have been seen with single-agent gemcitabine and 37%-62% with trastuzumab/gemcitabine combinations. Further work is currently ongoing to examine this promising combination.

Antibodies, Monoclonal↗
PubMed2003

The origin of cortical surround receptive fields studied in the barrel cortex.

The neocortex is thought to be organized into functional columns of neurons, each of which processes an element of a larger representation. In the barrel cortex, the thalamic input to the column preferentially terminates in a barrel. To study the extent and nature of functional connections between columns, we measured the degree to which whisker responses are relayed between columns in the barrel cortex. Inactivating a single barrel by iontophoresis of the GABA(A) agonist muscimol abolished the representation of that barrel's whisker in neighboring barrels. Reactivating a single barrel by iontophoresis of the GABA(A) antagonist bicuculline while the rest of the cortex was blocked by muscimol led to single whisker receptive fields. Under the same conditions, septal cells tended to exhibit multiwhisker receptive fields. These studies demonstrate that the surround receptive fields of barrel cells are generated by intracortical transmission and that many septal cells derive a component of their surround receptive field from the thalamus.

Anesthetics↗
PubMed2003

Neocortical long-term potentiation and experience-dependent synaptic plasticity require alpha-calcium/calmodulin-dependent protein kinase II autophosphorylation.

Experience-dependent plasticity can be induced in the barrel cortex by removing all but one whisker, leading to potentiation of the neuronal response to the spared whisker. To determine whether this form of potentiation depends on synaptic plasticity, we studied long-term potentiation (LTP) and sensory-evoked potentials in the barrel cortex of alpha-calcium/calmodulin-dependent protein kinase II (alphaCaMKII)T286A mutant mice. We studied three different forms of LTP induction: theta-burst stimulation, spike pairing, and postsynaptic depolarization paired with low-frequency presynaptic stimulation. None of these protocols produced LTP in alphaCaMKIIT286A mutant mice, although all three were successful in wild-type mice. To study synaptic plasticity in vivo, we measured sensory-evoked potentials in the barrel cortex and found that single-whisker experience selectively potentiated synaptic responses evoked by sensory stimulation of the spared whisker in wild types but not in alphaCaMKIIT286A mice. These results demonstrate that alphaCaMKII autophosphorylation is required for synaptic plasticity in the neocortex, whether induced by a variety of LTP induction paradigms or by manipulation of sensory experience, thereby strengthening the case that the two forms of plasticity are related.

Animals↗