Organ preservation in anal and rectal cancers

For the past 10 to 15 years, radiation therapy and chemotherapy have played an increasingly important role in the treatment of various gastrointestinal malignancies, most prominently in anal and rectal cancer. Critical issues in the care of patients with anal and rectal cancer include not only local control and survival but organ preservation as well. For patients with carcinoma of the anal canal, external-beam irradiation with 5-fluorouracil and chemotherapy with mitomycin C have replaced surgery as primary therapy. Current studies are optimizing this therapy. In contrast, the management of distal rectal cancer is in evolution. Although the abdominoperineal resection has been long regarded as the definitive treatment of distal rectal cancer, it is associated with substantial morbidity (loss of anorectal function with a permanent colostomy and a high incidence of sexual and genitourinary dysfunction). As an alternative, treatment programs utilizing sphincter-preserving procedures with radiation therapy and chemotherapy are under active investigation. In selected patients, these strategies appear promising, and there have been reports of satisfactory local control and survival, as well as preservation of sphincter integrity.     

A predictive model for matrix and analyte effects in electrospray ionization of singly-charged ionic analytes

In electrospray ionization (ESI), droplets with a surface excess charge are created. The rate of production of surface excess charge is a constant and is equal to the rate of ion production. The ions appearing in the mass spectrum are postulated to be those that formed the surface excess charge at the time of droplet formation (or their collision products). An equilibrium model based on competition among the ions in the solution for the limited number of excess charge sites has been developed. This model accurately predicts the response curves of singly-charged ionic analytes as a function of the concentration of electrolyte and other analytes and provides an explanation for the selective effectiveness of ESI. At low concentrations of total analyte (micromolar and less), the response curves are linear, indifferent to the presence of other low concentration analytes, and suppressed by electrolyte concentrations in excess of the minimum required. At higher analyte concentrations, the response becomes independent of analyte concentration but highly affected by the presence of other analytes.     

Response of Plasmodium falciparum to chloroquine and Fansidar in vivo and chloroquine and amodiaquine in vitro in Uganda

The response of P. falciparum to chloroquine and pyrimethamine-sulfadoxine in vivo and chloroquine and amodiaquine in vitro was investigated in parasitaemic school children from six locations. Mean parasite sensitivity to chloroquine at day 7 was 74% (range 61-97) with parasite clearance rates between 2-3 days and complete defervescence in 85% of febrile children. Sensitivity declined in the four sites followed up to day 14 to 45% (range 37-53). Parasites were significantly more sensitive to pyrimethamine/sulfadoxine at 5/6 sites (100% day 7) but 5% of subjects became parasitaemic by day 14. In vitro isolates were significantly less sensitive to chloroquine than to amodiaquine with a mean 99% effective concentration of 348 mumol/L compared to 6.44 mumol/L. Clearly the role of chloroquine as the primary therapy for uncomplicated P. falciparum malaria should be reconsidered especially in the light of increasing disease severity and resurgence. Amodiaquine may be suitable alternative with pyrimethamine/sulfadoxine as second line and for more severe malaria prior to referral. The cost of alternative antimalarials and the dynamic and deteriorating pattern of resistance are powerful arguments for more objective slide diagnosis to minimise drug pressure and a regular drug sensitivity surveillance system. We believe that the latter should concentrate on measuring clinical drug efficacy in symptomatic outpatients rather than in asymptomatic children while the former needs more pragmatic and economical strategies possibly centred on seasonality and risk.     

Apoptosis in the rostral migratory stream of the developing rat

The rostral migratory stream consists of a large number of cells migrating from the lateral ventricles to the rostral telencephalon, primarily the olfactory bulb. The pathway continually provides neuro- and glioblasts throughout life. The present paper indicates that a considerable number of cells undergo apoptotic cell death en route, even in young (day 3) rats when presumably many vacant sites are still available in the developing brain.     

PMMA tacticity and alumina powder dispersion stability

Summary Sedimentation experiments and X-ray photoelectron spectroscopy (XPS or ESCA) analyses have been used to study the effect of poly(methylmethacrylate) (PMMA) tacticity on aluminum oxide powder dispersion stability in a common solvent medium. The relative trends from sedimentation densities, and from surface analyses after solvent washing show that (PMMA) adsorption is greatest with isotactic polymer, where isotactic>atactic>syndiotactic adsorption. These results suggest that surface adsorption and hence dispersion stability can be influenced by polymer chain configuration as well as by chain conformation.     

Concentration-response relationships for adenosine agonists during preconditioning of rabbit cardiomyocytes

Although adenosine receptors have been implicated in the induction of preconditioning in a variety of experimental models, there is controversy concerning the specific adenosine receptor subtypes mediating this effect. Concentration-protection relationships for adenosine and adenosine agonists in rabbit cardiomyocytes were used to characterize the role of adenosine receptor subtypes in preconditioning. Isolated cells were ischemically preconditioned or pre-incubated for 10 min with increasing concentrations of adenosine, CCPA (2-chloro-N6-cyclopentyladenosine), APNEA (N6-2-(4-aminophenyl)ethyladenosine), or BNECA (N6-benzyl-5'-N-ethyl-carboxamidoadenosine) in the presence or absence of 1 or 10 microM of the selective A1-adenosine antagonist DPCPX (8-Cyclopentyl-1,3-dipropylxanthine). Following a 30-min post-incubation period, cells were pelleted, layered with oil and ischemically incubated for 180 min. Injury was assessed by osmotic swelling and trypan blue exclusion of sequential samples, and determination of the areas beneath the mortality curves. Adenosine produced a broad concentration-protection curve which was displaced to the right by DPCPX. The curve for A1-selective agonist CCPA was biphasic, with an initial response below 1 nM and a second above 1 microM. DPCPX abolished the early response leaving a steep monophasic curve between 0.1 and 10 microM CCPA. The APNEA curve appeared moriophasic, the major slope occurring between 1-100 nM; DPCPX (1 microM) shifted the concentration-response curve approximately 30-fold and decreased the slope. Adenosine receptor agonist BNECA produced preconditioning characterized by a shallow monophasic concentration-protection curve with a maximal effect of 49% and an EC50 of approximately 5 nM; DPCPX shifted the BNECA concentration-protection relationship approximately 40-fold with only a modest increase in slope. Analysis of the data suggests that induction of preconditioning results from interaction of agonists with the A1 receptor and a second adenosine receptor having properties consistent with the A3 receptor. Adenosine, CCPA, APNEA, BNECA and DPCPX each appear to be selective for the A1 adenosine receptor subtype in isolated rabbit cardiomyocytes.     

The Second Canadian Gastroesophageal Reflux Disease Consensus: moving forward to new concepts

Gastroesophageal reflux disease (GERD) is a disease with serious consequences that may result in significant impairment in quality of life and disease morbidity. Across all grades of severity of symptoms and severity of underlying esophageal disease, proton pump inhibitors (PPIs) provide therapeutic gains over prokinetics (PKs) or H2 receptor antagonists (H2RAs). The potential cost effectiveness of using medications with higher acquisition costs that may lower health care costs overall is often disregarded when conducting cost comparisons with medications having lower 'up-front' costs. Limiting therapy to less effective agents condemns many patients to protracted suffering, repeated physician visits and needless reinvestigation of symptoms that could have been resolved by appropriate initial therapy. Based on current data, use of any classification of symptom severity as a basis for selecting one class of therapeutic agents over another for first line therapy (i.e. PKs, H2RAs for 'mild' GERD, versus a PPI for 'severe' disease) is unwarranted.     

A greedy algorithm to determine the number of transporters in a cyclic electroplating process

This paper presents a local optimization algorithm for minimizing the number of transporters required for material handling in a cyclic processing line. Within a cycle, a given set of transportation operations must be performed. Each operation consists of picking up a work-in-process job at a stage and delivering it to the next stage. The length of time that a job can remain at a particular stage is restricted by a time window. The transporters that perform the operations move on a shared track, and traffic collisions must be avoided during their movements. To avoid traffic collisions, the operations are partitioned into groups, where each group is served by a single transporter. A local optimal solution is obtained when the group sizes are maximized. We show that the duals of the linear programming subproblems formulated in the process of maximizing the group sizes are specially structured shortest-path problems. This leads to an effective search method for the maximization problem. Conditions when die proposed algorithm achieves die global optimal solution are discussed. The algorithm's performance is evaluated on both randomly generated test problems and benchmark problems.