Diagnostic and therapeutic approaches for nonmetastatic breast cancer in Canada, and their associated costs. (65/42270)

In an era of fiscal restraint, it is important to evaluate the resources required to diagnose and treat serious illnesses. As breast cancer is the major malignancy affecting Canadian women, Statistics Canada has analysed the resources required to manage this disease in Canada, and the associated costs. Here we report the cost of initial diagnosis and treatment of nonmetastatic breast cancer, including adjuvant therapies. Treatment algorithms for Stages I, II, and III of the disease were derived by age group (< 50 or > or = 50 years old), principally from Canadian cancer registry data, supplemented, where necessary, by the results of surveys of Canadian oncologists. Data were obtained on breast cancer incidence by age, diagnostic work-up, stage at diagnosis, initial treatment, follow-up practice, duration of hospitalization and direct care costs. The direct health care costs associated with 'standard' diagnostic and therapeutic approaches were calculated for a cohort of 17,700 Canadian women diagnosed in 1995. Early stage (Stages I and II) breast cancer represented 87% of all incident cases, with 77% of cases occurring in women > or = 50 years. Variations were noted in the rate of partial vs total mastectomy, according to stage and age group. Direct costs for diagnosis and initial treatment ranged from $8014 for Stage II women > or = 50 years old, to $10,897 for Stage III women < 50 years old. Except for Stage III women < 50 years old, the largest expenditure was for hospitalization for surgery, followed by radiotherapy costs. Chemotherapy was the largest cost component for Stage III women < 50 years old. This report describes the cost of diagnosis and initial treatment of nonmetastatic breast cancer in Canada, assuming current practice patterns. A second report will describe the lifetime costs of treating all stages of breast cancer. These data will then be incorporated into Statistics Canada's Population Health Model (POHEM) to perform cost-effectiveness studies of new therapeutic interventions for breast cancer, such as the cost-effectiveness of day surgery, or of radiotherapy to all breast cancer patients undergoing breast surgery.  (+info)

Mound-cell movement and morphogenesis in Dictyostelium. (66/42270)

To examine the mechanisms of cell locomotion within a three-dimensional (3-D) cell mass, we have undertaken a systematic 3-D analysis of individual cell movements in the Dictyostelium mound, the first 3-D structure to form during development of the fruiting body. We used time-lapse deconvolution microscopy to examine two strains whose motion represents endpoints on the spectrum of motile behaviors that we have observed in mounds. In AX-2 mounds, cell motion is slow and trajectories are a combination of random and radial, compared to KAX-3, in which motion is fivefold faster and most trajectories are rotational. Although radial or rotational motion was correlated with the optical-density wave patterns present in each strain, we also found small but significant subpopulations of cells that moved differently from the majority, demonstrating that optical-density waves are at best insufficient to explain all motile behavior in mounds. In examining morphogenesis in these strains, we noted that AX-2 mounds tended to culminate directly to a fruiting body, whereas KAX-3 mounds first formed a migratory slug. By altering buffering conditions we could interchange these behaviors and then found that mound-cell motions also changed accordingly. This demonstrates a correlation between mound-cell motion and subsequent development, but it is not obligatory. Chimeric mounds composed of only 10% KAX-3 cells and 90% AX-2 cells exhibited rotational motion, suggesting that a diffusible molecule induces rotation, but many of these mounds still culminated directly, demonstrating that rotational motion does not always lead to slug migration. Our observations provide a detailed analysis of cell motion for two distinct modes of mound and slug formation in Dictyostelium.  (+info)

Management of the impalpable testis: the role of laparoscopy. (67/42270)

PURPOSE: To evaluate the use of laparoscopy in the management of the impalpable testis. DESIGN: A retrospective analysis of the clinical findings, interventions, and outcome in 87 consecutive boys undergoing laparoscopy for 97 impalpable testes. RESULTS: Fifty seven testes were either absent (n = 35) or present as a small remnant (n = 22), which was removed at contemporaneous groin exploration. There were 27 intra-abdominal testes, including four hypoplastic testes, which were removed laparoscopically. The 13 remaining viable testes were located in the groin. Conventional orchidopexy followed laparoscopy for 21 testes, and was successful in 17 cases. Two stage laparoscopically assisted Fowler Stevens orchidopexies were performed for 13 intra-abdominal testes, with eight satisfactory results. Ultrasound evaluation significantly reduced the number of conventional orchidopexies following laparoscopy. IMPLICATIONS: Laparoscopy is a rational and safe approach for precise localisation of the impalpable testis. Laparoscopically assisted two stage orchidopexy is a successful treatment procedure for intra-abdominal testes.  (+info)

Primary prevention of CHD: nine ways to reduce risk. (68/42270)

Lowering cholesterol can reduce the incidence of coronary heart disease. Treating hypertension reduces overall mortality and is most effective in reducing the risk of coronary heart disease in older patients. Smoking cessation reduces the level of risk to that of nonsmokers within about three years of cessation. Aspirin is likely to be an effective means of primary prevention, but a group in whom treatment is appropriate has yet to be defined. Evidence that supplementation with vitamin A or C reduces the risk of coronary heart disease is inadequate; the data for use of vitamin E are inconclusive. Epidemiologic evidence is sufficient to recommend that most persons increase their levels of physical activity. Lowering homocysteine levels through increased folate intake is a promising but unproven primary prevention strategy. Hormone replacement therapy was associated with reduced incidence of coronary heart disease in epidemiologic studies but was not effective in a secondary prevention trial.  (+info)

Protein subcellular location prediction. (69/42270)

The function of a protein is closely correlated with its subcellular location. With the rapid increase in new protein sequences entering into data banks, we are confronted with a challenge: is it possible to utilize a bioinformatic approach to help expedite the determination of protein subcellular locations? To explore this problem, proteins were classified, according to their subcellular locations, into the following 12 groups: (1) chloroplast, (2) cytoplasm, (3) cytoskeleton, (4) endoplasmic reticulum, (5) extracell, (6) Golgi apparatus, (7) lysosome, (8) mitochondria, (9) nucleus, (10) peroxisome, (11) plasma membrane and (12) vacuole. Based on the classification scheme that has covered almost all the organelles and subcellular compartments in an animal or plant cell, a covariant discriminant algorithm was proposed to predict the subcellular location of a query protein according to its amino acid composition. Results obtained through self-consistency, jackknife and independent dataset tests indicated that the rates of correct prediction by the current algorithm are significantly higher than those by the existing methods. It is anticipated that the classification scheme and concept and also the prediction algorithm can expedite the functionality determination of new proteins, which can also be of use in the prioritization of genes and proteins identified by genomic efforts as potential molecular targets for drug design.  (+info)

Nanoelectrospray--more than just a minimized-flow electrospray ionization source. (70/42270)

The comparison between electrospray ionization (ESI) mass spectra from NaCl solutions with and without analyte obtained under ionspray and nanospray conditions reveals different mass spectral behavior of the two ESI techniques. This can be attributed to the different initial droplet sizes which are in the microns range for ionspray, while in nanospray they are believed to be about one order of magnitude smaller. In the context of the widely accepted uneven-fission model, nanospray would then enter one fission generation later; in addition, a higher initial droplet surface charge density in nanospray results in early fissions without extensive evaporation and thus increase in sample and salt concentration. This rationalizes that ionspray spectra closely resemble nanospray spectra from solutions with about one order of magnitude higher salt concentrations, showing a higher tolerance of nanospray towards salt contamination. When the analyte is a peptide (in a solution containing a high molar surplus of salt), molecule ion formation effectively competes with salt cluster ion formation; when the analyte is a sugar, it is detectable beside a high salt concentration only with nanospray, indicating the supporting effect of surface activity on ion release in the case of peptides. A model is presented which explains the different mass spectral behaviour of ionspray and nanospray by suggesting different "predominant fission pathways" depending on the size of the initial droplets.  (+info)

Theoretical calculations of glycine and alanine gas-phase acidities. (71/42270)

The gas-phase acidities of glycine and alanine were determined by using a variety of high level theoretical methods to establish which of these would give the best results with accessible computational efforts. MP2, MP4, QCISD, G2 ab initio procedures, hybrid Becke3-LYP (B3LYP) and gradient corrected Becke-Perdew (BP) and Perdew-Wang and Perdew (PWP) nonlocal density functionals were used for the calculations. A maximum deviation of approximately 13 and 18 kJ/mol from experimental data was observed for the computed delta Hacid and delta Gacid values, respectively. The best result was obtained at G2 level, but comparable reliability was reached when the considerably less time consuming B3LYP, BP, and PWP density functional approaches were employed.  (+info)

Differentiation of isomeric photomodified oligodeoxynucleotides by fragmentation of ions produced by matrix-assisted laser desorption ionization and electrospray ionization. (72/42270)

UV irradiation of oligodeoxynucleotides at 254 nm generates several different types of DNA photoproducts, including cis-syn cyclobutane pyrimidine dimers, pyrimidine[6-4] pyrimidone photoproducts and their Dewar valence isomers, and thymine-adenine photoproducts (TA*). Studies of photoproducts in oligodeoxynucleotides require the development of suitable structure determination methods such as mass spectrometry. In an earlier study (Vollmer et al. Int. J. Mass Spectrom. Ion Processes 1997, 165/166, 487-496), we showed that fast atom bombardment and tandem sector mass spectrometry can be used to locate the site of photomodification and identify most of the photoproducts of d(TATTAT). One goal of the present research was to expand the method to the more sensitive electrospray ionization (ESI) and matrix-assisted laser desorption/ionization (MALDI) methods. A second goal was to test the generality of the methods by investigating not only the photoproducts of d(TATTAT) but also those of three other oligodeoxynucleotides, d(GTATTAT), d(GGCTATAA), and d(AATTAA). The photoproducts of these sequences were separated by HPLC and gave characteristic fragment ions in postsource decompositions of MALDI-produced ions and collisionally activated decompositions of ESI-produced ions.  (+info)