Implications of ejection fraction value for trastuzumab.
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Biomedical subjects
Publications and source records attributed to C Dickinson.
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Polarization observations of the cosmic microwave background with the Cosmic Background Imager from September 2002 to May 2004 provide a significant detection of the E-mode polarization and reveal an angular power spectrum of polarized emission showing peaks and valleys that are shifted in phase by half a cycle relative to those of the total intensity spectrum. This key agreement between the phase of the observed polarization spectrum and that predicted on the basis of the total intensity spectrum provides support for the standard model of cosmology, in which dark matter and dark energy are the dominant constituents, the geometry is close to flat, and primordial density fluctuations are predominantly adiabatic with a matter power spectrum commensurate with inflationary cosmological models.
For clients who receive medical treatment for a severe and enduring mental health problem, antipsychotic medication is the first line of treatment. The adverse effects of these medications are well documented and can lead to discontinuation of therapy. The newer atypical antipsychotics would seem to have distinct advantages over more traditional substances but significant weight gain can be experienced. This group is an attempt to capitalize upon psychosocial approaches to this such that outcome may be enhanced. The following is a description of an attempt to implement such a group and to explore the outcome. The group has been devised by one of the manufacturers of atypical antipsychotic medication concerned by the side-effect to their product. The group is formatted on a computer disc ready to use by any mental health professional and freely available.
UNLABELLED: The gagging reflex is a physiological reaction which safeguards the airway from foreign bodies. In some people this response is exaggerated to the extent that the acceptance/provision of dental treatment is not possible. The aim of this paper is to review the role of acupuncture in controlling gagging as a safe, cheap, quick and relatively non-invasive technique. METHOD: Ten people agreed to try ear acupuncture to control gagging during dental treatment. Prior to treatment the severity of gagging was assessed. Acupuncture needles were inserted into a specific anti-gagging point on each ear, manipulated briefly and left in situ. Dental treatment was then carried out and the effectiveness of the acupuncture in preventing gagging was assessed. After treatment, the needles were removed and the patient discharged. All acupuncture was carried out by a dentist trained in its use. RESULTS: Four people had a severe gag reflex which made treatment impossible and six had a very severe reflex which made treatment impossible and affected their dental attendance. Ear acupuncture completely controlled the gag reflex in eight cases (23 treatment episodes) and partially controlled the reflex in two cases (two treatment episodes). Dental treatment could be carried out in all cases and at all visits. The cost of materials was 0.2 pounds per person per visit. Additional clinical time was in the order of 2-3 minutes. There were no adverse reactions to the technique and, on all occasions, patients were fit to leave the surgery and travel home unaccompanied. CONCLUSIONS: Ear acupuncture was successful in controlling the gag reflex. It is a safe, quick, inexpensive and relatively noninvasive technique. A controlled clinical trial is required to investigate any placebo effect.
The aim of this study was to identify useful patterns of abnormal fluorine-18 fluorodeoxyglucose (FDG) uptake by different types of non-small cell (NSC) lung cancer and to assess their clinical implications. One hundred and three sequential patients with newly diagnosed, pathology-proven NSC lung cancer were included. FDG positron emission tomography (PET) images were acquired using a dedicated PET scanner. There were 35 squamous cell carcinomas (SQC), 17 large cell cancers (LGC), 38 adenocarcinomas (ADC), 1 bronchioloalveolar carcinoma (BAC) and 12 non-classified NSC cancers. PET images were categorized into detectable patterns of necrotic center in the primary tumor, satellite lesions (T4), hilar lymph nodes (N1), and N2, N3, and M1 lesions by visual interpretation of PET images for SQC, LGC, and ADC (n=90; BAC and non-classified NSC cancers were excluded). The PET lesions were correlated with surgical pathology and with CT findings in inoperable cases. Necrosis was more commonly present in the primary tumors of LGC (53%) and SQC (43%) than in those of ADC (26%) (P<0.0001 and <0.01, respectively). The frequencies of nodal uptake in ADC, SQC and LGC were similar (71%, 60%, and 59%, respectively). However, M1 lesions were present significantly more often in LGC (41%) and ADC (34%) than in SQC (3%) (both P<0.0001). Significantly more surgically inoperable cases were found by PET (T4, N3, M1) in ADC (50%) and LGC (41%) than in SQC (26%) (P<0.001 and <0.02, respectively). Our results suggest a wide variation of PET findings for different types of NSC lung cancer. Identification of these patterns is useful in clinical PET interpretation, in that knowledge of the most probable association between the PET patterns and the histological types will facilitate initial staging and planning of management.
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Agouti signaling protein (ASIP), the human (h) homolog of agouti, is an endogenous melanocortin peptide antagonist. To date, characterization of this protein has been performed with recombinant protein only and without the availability of an ASIP/agouti radioligand. In this report we describe the functional characteristics of a chemically synthesized truncated ASIP variant, ASIP-[90-132 (L89Y)], and the binding characteristics of its cognate radioligand, (125)I-ASIP-[90-132 (L89Y)]. Similar to full-length recombinant ASIP/agouti, ASIP-[90-132 (L89Y)] was a potent inhibitor of alpha-melanocyte-stimulating hormone cAMP generation at the cloned human melanocortin receptor (hMCR) subtypes hMC1R and hMC4R. It also displayed a lesser degree of inhibition at the hMC3R and hMC5R. However, ASIP-[90-132 (L89Y)] was found to be less potent than full-length recombinant ASIP and, surprisingly, only exhibited weak inhibitory activity at the hMC2R. In competition binding assays with the radioligand (125)I-ASIP-[90-132 (L89Y)], ASIP-[90-132 (L89Y)] displayed a hierarchy of binding affinity that roughly paralleled its rank order of inhibitory potency at the various MCR subtypes, i.e., hMC1R approximately hMC4R > hMC3R approximately hMC5R > hMC2R. Structure-activity studies revealed that ASIP-[90-132 (L89Y)] possessed greater pharmacological potency than either the further truncated ASIP variants ASIP-(116-132) or cyclo(CRFFRSAC). Interestingly, the latter molecules were both weak agonists at the hMC1R. These studies further support the concept that ASIP/agouti inhibits melanocortin action by directly binding to target MCRs and provide additional insight into the structural requirements for maximal inhibitory potency.
We begin by defining the concept of a 'CareMap', before briefly examining the context in which CareMaps emerged, as well as both their potential applications and the benefits arising from their implementation in health care services. We identify and discuss the history of, and critical aspects involved in, the development of the Antenatal Ward Care Delivery Map for the Mater Mothers' Hospital, Brisbane. We will address the multiple applications of, and specific benefits arising from, the formulation and implementation of the Antenatal Ward Care Delivery Map. Additionally, the relationship between the Care Delivery Map and other projects aimed at enhancing and maintaining high quality service delivery for patients across the continuum of care, will be explored. We examine the benefits of utilising the Care Delivery Map in professional education for clinical staff, as well as for health care consumers and their families. In conclusion, future projects enabled through the development of the Care Delivery Map are identified, as well as areas requiring further research.
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A novel RIA was used to examine the release of agouti-related protein-like immunoreactivity (AGRP-LI) from perfused rat hypothalamic tissue slices and to characterize AGRP-LI in rat serum. A continuous low level basal AGRP-LI release was observed from hypothalami of rats fed ad libitum before the rats were killed. Basal AGRP-LI release was 3-fold greater in rats fasted 48 h. In fasted animals leptin dose-dependently suppressed basal AGRP-LI release. In fed animals no change in basal AGRP-LI release was detected in response to 10(-6) M alpha-MSH, orexin B, melanin-concentrating hormone, or serotonin. HPLC analysis of AGRP-LI in rat serum identified a single peak that eluted in close proximity to synthetic AGRP (87-132) and mouse [Leu127Pro]AGRP and that was identical to the peak seen in hypothalamic and adrenal tissue extracts. The serum concentration of AGRP-LI in rats fed ad libitum was 0.865+/-0.323 nmol/liter (mean +/- SE). Food deprivation resulted in a slow, but statistically significant rise in serum immunoreactivity at 48 h [1.174+/-0.118 nmol/liter (mean +/- SE)]. Bilateral adrenalectomy did not change serum levels of AGRP-LI. These studies demonstrate that in the rat there are different levels of basal hypothalamic AGRP-LI release in fed and fasted states and that in the fasted rat this release can be profoundly suppressed by leptin. These studies also suggest that AGRP is present in the systemic circulation of rats.
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Some patients suffer from conditions that make holding toothbrushes difficult, if not impossible. This article describes a quick, simple and flexible method of adapting toothbrush handles to allow patients the best possible chance of performing adequate oral care.
Objective: The search for quality, cost-effective health care programs in the United States is now a major focus in the era of health care reform. New programs need to be evaluated as alternatives are developed in the health care system. The BirthPlace program provides comprehensive perinatal services with certified nurse-midwives and obstetricians working together in an integrated collaborative practice serving a primarily low-income population. Low-risk women are delivered by nurse-midwives in a freestanding birth center (The BirthPlace), which is one component of a larger integrated health network. All others are delivered by team obstetricians at the affiliated tertiary hospital. Wellness, preventive measures, early intervention, and family involvement are emphasized. The San Diego Birth Center Study is a 4-year research project funded by the U.S. Federal Agency for Health Care Policy and Research (#R01-HS07161) to evaluate this program. The National Birth Center Study (NEJM, 1989; 321(26): 1801-11) described the advantages and safety of freestanding birth centers. However, a prospective cohort study with a concurrent comparison group of comparable risk had not been conducted on a collaborative practice-freestanding birth center model to address questions of safety, cost, and patient satisfaction.Methods: The specific aims of this study are to compare this collaborative practice model to the traditional model of perinatal health care (physician providers and hospital delivery). A prospective cohort study comparing these two health care models was conducted with a final expected sample size of approximately 2,000 birth center and 1,350 traditional care subjects. Women were recruited from both the birth center and traditional care programs (private physicians offices and hospital based clinics) at the beginning of prenatal care and followed through the end of the perinatal period. Prenatal, intrapartum, postpartum and infant morbidity and mortality are being compared along with cost-effectiveness and acceptance of the model by patients. Data collection occurred primarily through medical record abstraction with the addition of two patient questionnaires. Comparability of the cohorts was established by using a validated methodology to determine medical/perinatal risk and birth center eligibility, which included assessment by two CNMs and an independent blind review by a perinatologist. The cost analysis uses a resource-utilization approach and new methodologies such as activity-based-costing to compare costs from both the perspective of the payor and the health care provider. Patient satisfaction was measured using a self-administered patient questionnaire.Results: Current preliminary results from approximately 38% of the final expected study sample are available. Crude and adjusted analysis have been conducted. Overall, the preliminary results suggest similar morbidity and mortality in the two groups. Fetal deaths are 0.75% in the index and 0.64% in the comparison group, with early neonatal deaths at 0.26% and 0.23%, respectively. The traditional care group showed adjusted rate differences of 5.83% more major maternal intrapartum complications and 9% more NICU admissions. While the birth center group showed adjusted rate differences of 5.5% more low birth weight and 0.95% more preterm birth. For other outcomes, the birth center group showed an adjusted rate difference of 22.34% more exclusive breastfeeding at discharge. Also, there was less utilization of cesarean section and assisted delivery in the birth center group as compared to the traditional care group. The adjusted rate difference for normal spontaneous vaginal deliveries in nulliparas was 10.23% more in the birth center group, with similar results in multiparas with and without history of cesarean (28.88% and 7.84%, respectively). Preliminary results also show that the average total cost for pregnancy-related services paid by California Medicaid was $4,550 for the birth center and $5,535 for the traditional care group. Final results based on the full study sample (full data available February 1998) details of payor costs such as provider, facility, NICU, and ancillary along with costs from the health care system perspective and patient satisfaction results will be presented.Conclusion: Current results suggest similar morbidity and mortality between the birth center program and traditional care groups, with less resource utilization translating to lower costs in the collaborative practice model. Results suggest that collaborative practice using a freestanding birth center as an adjunct to an integrated perinatal health care system may provide a quality, lower-cost alternative for the provision of perinatal services.
The melanocortin-1 receptor (MC1R) is a seven-transmembrane (TM) G-protein-coupled receptor whose natural ligands are the melanocortin peptides, adrenocorticotropic hormone, and alpha-, beta-, and gamma- melanocyte stimulating hormone (MSH). To test a previously constructed three-dimensional model of the molecular interaction between the long-acting, superpotent alpha-MSH analog [Nle4,D-Phe7]MSH (NDP-MSH) and the human MC1R we examined the effects of site-directed receptor mutagenesis on the binding affinity and potency of NDP-MSH. In addition, we also examined the effects of these same mutations on the binding affinity and potency of the structurally related agonists alpha-MSH, gamma-MSH, and Ac-Nle4-cyclic-[Asp5,His6,D-Phe7,Arg8,Trp9,Lys10]NH2 (MT-II). Mutagenesis of acidic receptor residues Glu94 in TM2 and Asp117 or Asp121 in TM3 significantly altered the binding affinity and potency of all four agonists suggesting that these receptor residues are important to the ligand-receptor interactions of all. A disproportionate change in agonist potency versus affinity observed with simultaneous mutation of these acidic residues (mutant constructs D117A/D121A or E94A/D117A/D121A) or introduction of a single positive charge (mutant construct D121K) also implicates these residues in receptor activation. In addition, results from the individual mutation of aromatic receptor residues Phe175, Phe196, and Phe257, and simultaneous mutation of multiple TM4, -5, and -6 tyrosine and phenylalanine residues suggests that aromatic-aromatic ligand-receptor interactions also participate in binding these melanocortins to the MC1R. These experiments appear to have identified some of the critical receptor residues involved in the ligand-receptor interactions between these melanocortins and the hMC1R.
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[Nle4, DPhe7]-alpha-MSH (NDP-MSH), a highly potent analogue of alpha-melanocyte-stimulating hormone (alpha-MSH), possesses nanomolar efficacies at all the melanocortin receptor subtypes except the MC2R. Evaluation of the melanocortin "message" sequence of [Nle4, DPhe7]-alpha-MSH was performed on the human melanocortin receptor subtypes designated hMC1, hMC3R, hMC4R, and hMC5R. Tetrapeptides and tripeptides were stereochemically modified to explore topochemical preferences at these receptors and to identify lead peptides possessing agonist activity and subtype selectivity. Four peptides were discovered to only bind to the hMC1 and hMC4 receptor subtypes. The tetrapeptide Ac-His-DPhe-Arg-Trp-NH2 (1) possessed 0.6 microM binding affinity at the hMC1R, 1.2 microM binding affinity at the hMC4R, and agonist activity at both receptors. The tripeptides Ac-DPhe-Arg-Trp-NH2 (6) and Ac-DPhe-Arg-DTrp-NH2 (7) possessed 2.0 and 9.1 microM binding affinities, respectively, only at the hMC4R, and both compounds effected agonist activity. The tetrapeptide Ac-His-Phe-Arg-DTrp-NH2 (4) possessed 6.3 microM affinity and full agonist activity at the hMC1R, while only binding 7% at the hMC3R, 36% at the hMC4R, and 11% at the hMC5R at a maximal concentration of 10 microM. These data demonstrate that the His-Phe-Arg-Trp message sequence of the melanocortin peptides does not bind and stimulate each melanocortin receptor in a similar fashion, as previously hypothesized. Additionally, this study identified the simplest structural agonists for the hMC1R and hMC4R receptors reported to date.