Chemotherapy for breast cancer during pregnancy: an 18-year experience from five London teaching hospitals.

Purpose: The rare association between breast cancer and pregnancy means that few oncologists gain an expertise in this area. In particular, there are few published data concerning the use of chemotherapy for breast cancer during pregnancy. In this retrospective case series, we describe the experiences of five hospitals in London, United Kingdom, and how they manage this condition.

Ability of static and statistical mechanics posturographic measures to distinguish between age and fall risk.

Traditional posturographic analysis and four statistical mechanics techniques were applied to center-of-pressure (COP) trajectories of young, older "low-fall-risk" and older "high-fall-risk" individuals. Low-fall-risk older adults were active 3 days per week in a cardiac rehabilitation program, while high-fall-risk older adults were diagnosed with perilymph fistula. Subjects diagnosed with perilymph fistula must have experienced two of the following vestibular findings: constant disequilibrium, positional vertigo and/or a positive fistula test.

How precise do precision tints have to be and how many are necessary?

Among those individuals who habitually wear precision tints, reading speed can vary as a function of the chromaticity of the illuminating light. The reading speed decreases as the chromaticity departs from optimum, whether in saturation or in hue. When the distance in the CIE 1976 UCS diagram between the chromaticity of the illuminating light and that optimal for reading exceeds about 0.

Extracellular matrix remodeling by human granzyme B via cleavage of vitronectin, fibronectin, and laminin.

Human granzyme B (GrB) released from cytotoxic lymphocytes plays a key role in the induction of target cell apoptosis when internalized in the presence of perforin. Here we demonstrate that GrB also possesses a potent extracellular matrix remodeling activity. Both native and recombinant GrB caused detachment of immortalized and transformed cell lines, primary endothelial cells, and chondrocytes.

Biomarker changes during neoadjuvant anastrozole, tamoxifen, or the combination: influence of hormonal status and HER-2 in breast cancer--a study from the IMPACT trialists.

Purpose: To investigate the relationships between biomarker changes in breast cancer during neoadjuvant (preoperative) endocrine therapy.

Patients And Methods: The IMPACT trial compared the preoperative use of tamoxifen with anastrozole alone or in combination in postmenopausal women (n = 330) with primary breast cancer. Biomarkers were measured in tumor biopsy specimens taken at baseline, and after 2 and 12 weeks of treatment.

The stability of lipidic analogues of GnRH in plasma and kidney preparations: the stereoselective release of the parent peptide.

The conjugation of a lipoamino acid to the N-terminus of Gonadotropin releasing hormone (GnRH) produces a lipophilic peptide from which the parent GnRH peptide is released into solution on treatment with plasma and kidney enzyme preparation. Our findings show that one stereoisomer of the Laa is cleaved very rapidly, providing a bolus dose of the peptide while the opposite stereoisomer is cleaved much more slowly, providing prolonged elevation of peptide concentration. The Laa-Glu linkage appears to act as a two phase prodrug system.

Aromatase inhibitors in early breast cancer therapy.

Third-generation aromatase inhibitors, letrozole, anastrozole, and exemestane, are active and well tolerated in postmenopausal patients with hormone-sensitive advanced or metastatic breast cancer, as either first- or second-line therapy. These agents are being investigated as neoadjuvant therapy of locally advanced breast cancer and as adjuvant therapy of early breast cancer. In a large neoadjuvant study, letrozole resulted in significantly more responses than tamoxifen, with significantly more patients becoming eligible for breast-conserving surgery.

Short-term changes in Ki-67 during neoadjuvant treatment of primary breast cancer with anastrozole or tamoxifen alone or combined correlate with recurrence-free survival.

Purpose: Neoadjuvant (preoperative) therapy for breast cancer may allow for the development of intermediate markers of treatment benefit, thereby circumventing the need for efficacy trials of adjuvant therapy, which require much larger patient numbers and longer follow-up. The aim of this study--as part of the Immediate Preoperative "Arimidex" (anastrozole), Tamoxifen, or Arimidex Combined with Tamoxifen (IMPACT) trial (n = 330)--was to test the hypotheses that changes in Ki-67 after 2 weeks and/or 12 weeks: (i) differed between treatments, (ii) predicted clinical tumor response, and/or (iii) may predict long-term outcome differences between treatments in adjuvant therapy.

Experimental Design: The Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial compared these same agents in the adjuvant setting.

Myocardial infarction increases ACE2 expression in rat and humans.

Aims: Angiotensin converting enzyme (ACE) 2 catalyses the cleavage of angiotensin (Ang) I to Ang 1-9 and of Ang II to Ang 1-7. ACE2 deficiency impairs cardiac contractility and upregulates hypoxia-induced genes, suggesting a link with myocardial ischaemia. We studied the expression of ACE2 after myocardial infarction (MI) in the rat as well as in human failing hearts.

Phase II studies of pemetrexed in metastatic breast and gynecologic cancers.

Pemetrexed (Alimta) is active in a variety of solid tumors, including breast and gynecologic cancers. Phase II trials of pemetrexed at a dose of 600 mg/m2 without vitamin B12 and folic acid supplementation in largely pretreated metastatic breast cancer patients demonstrated objective response rates of 21% and 28%, with generally manageable neutropenia constituting the primary toxicity. In phase II trials using 500 mg/m2 with or without vitamin supplementation in anthracycline- and taxane-pretreated patients, response rates were lower (approximately 9%) and treatment was generally well tolerated irrespective of vitamin supplementation status.

The high resolution crystal structure of a native thermostable serpin reveals the complex mechanism underpinning the stressed to relaxed transition.

Serpins fold into a native metastable state and utilize a complex conformational change to inhibit target proteases. An undesirable result of this conformational flexibility is that most inhibitory serpins are heat sensitive, forming inactive polymers at elevated temperatures. However, the prokaryote serpin, thermopin, from Thermobifida fusca is able to function in a heated environment.

Aromatase inhibitors--extending the benefits of adjuvant therapy beyond tamoxifen.

Adjuvant tamoxifen is still considered standard care for postmenopausal women with early stage hormone receptor-positive breast cancer. However, efficacy and safety of tamoxifen are limited by its partially estrogenic properties. Aromatase inhibitors have proven highly effective in advanced breast cancer and are currently being investigated in the adjuvant setting, either as an alternative to or in sequence with tamoxifen, or as extended adjuvant therapy following tamoxifen.

Exostoses of the external auditory canal: a long-term follow-up study of surgical treatment.

To determine the postoperative incidence, extent and recurrence rate of exostoses of the external auditory canal in a cohort of patients involved in different water sports. A cross-sectional study of 31 patients (46 ears), with exostoses treated by surgery in the Royal Cornwall Hospital between 1980 and 1999. A questionnaire was used to obtain information about the type of water exposure pre- and postoperatively.

Maximizing clinical benefit with trastuzumab.

To optimize patient management in breast cancer a number of factors are considered, including hormone receptor and HER2 status. A feasible approach for women with less aggressive, estrogen receptor/HER2-positive metastatic breast cancer is to consider trastuzumab (Herceptin; F. Hoffmann-La Roche, Basel, Switzerland) combined with endocrine therapy.

Rotational energy transfer in collisions between CO(X 1Sigma+, v= 2 , J = 0, 1, 4, and 6) and He at temperatures from 294 to 15 K.

Infrared-vacuum ultraviolet double resonance experiments have been implemented in the ultracold environment provided by a Cinetique de Reaction en Ecoulement Supersonique Uniforme apparatus. With this technique rate coefficients of two kinds have been measured for rotational energy transfer in collisions between CO and He: (a) those for total removal from the selected rotational states J = 0, 1, 4, and 6 in the vibronic state X 1Sigma+, v = 2, and (b) those for transfer between selected initial and specific final states. Using different Laval nozzles, results have been obtained at several different temperatures: 294, 149, 63, 27, and 15 K.

In search of the good life: a cultural odyssey in the East and West.

In the first part of this article, the authors argue that any conception of well-being is culturally embedded and depends on how the notions of "well" and "being" are defined and practiced in different cultural communities. To support this argument, they conduct a comprehensive review of the empirical literature, which shows that members of individualistic and collectivistic cultures differ in their emotional experience of well-being. This difference has been traced to the indigenous psychology of selfhood in those cultures.

Efficacy and safety of trastuzumab.

The human epidermal growth factor receptor (HER) 2 is overexpressed in approximately 20-25% of human breast cancers and is an independent adverse prognostic factor. Targeted therapy directed against this receptor has been developed in the form of a humanised monoclonal antibody, trastuzumab. This antibody has shown activity as a single agent in metastatic breast cancer both prior to chemotherapy and in heavily pretreated patients.

Relaxation of H2O from its /04>- vibrational state in collisions with H2O, Ar, H2, N2, and O2.

We report rate coefficients at 293 K for the collisional relaxation of H2O molecules from the highly excited /04>(+/-) vibrational states in collisions with H2O, Ar, H2, N2, and O2. In our experiments, the mid R:04(-) state is populated by direct absorption of radiation from a pulsed dye laser tuned to approximately 719 nm. Evolution of the population in the (/04>(+/-)) levels is observed using the combination of a frequency-quadrupled Nd:YAG laser, which selectively photolyses H2O(/04>(+/-)), and a frequency-doubled dye laser, which observes the OH(v=0) produced by photodissociation via laser-induced fluorescence.

Identification of a novel apolipoprotein, ApoN, in ovarian follicular fluid.

A novel apolipoprotein, designated ApoN, has been identified in bovine ovarian follicular fluid using chromatographic purification methods, amino acid sequence analysis, molecular biology, and bioinformatics. The apolipoprotein is a hydrophobic 12-kDa protein processed from the C terminus of a 29-kDa precursor expressed in a number of tissues, including the ovary, testis, the anterior chamber of the eye, skeletal muscle, uterus, and liver. Bovine, porcine, and murine ApoN display significant homology at the amino acid level across the entire precursor sequence.

The novel angiotensin-converting enzyme (ACE) homolog, ACE2, is selectively expressed by adult Leydig cells of the testis.

The metallopeptidase angiotensin-converting enzyme (ACE) plays a pivotal role in the cardiovascular system by generating the vasoconstrictor peptide angiotensin II. A homolog of ACE with different substrate specificity, ACE2, has recently been cloned that shows an expression pattern restricted to endothelial cells of the heart and kidney, epithelial cells of the distal tubule of the kidney, and the testis. Although the importance of ACE2 to cardiac function is already evident, its role in the testis remains unknown.

Pharmacotherapies for obstructive sleep apnoea: where are we now?

Obstructive sleep apnoea (OSA) is common, causes considerable morbidity and probably contributes to mortality particularly through associated cardiovascular disease. The physical therapy of continuous positive airway pressure (CPAP) is extremely effective in the majority of patients but most patients would prefer an alternative. Intuitively, OSA should be amenable to pharmacotherapy.

Towards a comprehensive view of the primary structure of venom proteins from the parasitoid wasp Pimpla hypochondriaca.

Venom from the parasitoid wasp Pimpla hypochondriaca has potent in vivo activity against insect haemocytes and disrupts host immune responses. Using hybridisation techniques, and more recently random sequence analysis, we had previously identified cDNAs encoding 10 venom proteins from this wasp and deduced their primary structures. We have now extended the random sequence analysis and discovered a further nine cDNAs encoding proteins with predicted signal sequences.