Phase II trial of paclitaxel and granulocyte colony-stimulating factor in patients with pancreatic carcinoma: a Southwest Oncology Group study

PURPOSE: Pancreatic cancer is difficult to treat, with most patients surgically unresectable at the time of diagnosis. Radiotherapy and chemotherapy can offer palliation, but more effective therapy is needed. This trial evaluated the effects of an aggressive schedule of paclitaxel given with granulocyte colony-stimulating factor (G-CSF) to patients with advanced pancreatic cancer. PATIENTS AND METHODS: All patients were required to have a histologic diagnosis of pancreatic adenocarcinoma with measurable disease and no prior chemotherapy or radiation therapy. Patients had to have performance status of 0 to 2, pretreatment absolute granulocyte count > or = 1,500/microL, and platelet count greater than or equal to the institutional lower limit of normal. Following pretreatment with dexamethasone, diphenhydramine, and cimetidine, patients received paclitaxel at a dose of 250 mg/m2 by 24-hour infusion on day 1, repeated every 21 days. G-CSF was given at a dose of 5 microg/kg/d on days 3 to 18 or until two consecutive absolute neutrophil counts (ANCs) > or = 10,000/microL were obtained. Doses of paclitaxel were modified depending on nadir counts. RESULTS: Forty-five patients were entered onto this study, with six ineligible. For the 39 eligible patients, there was one complete response (CR) and two partial responses (PRs), five stable/no responses, 23 increasing disease, two early deaths, and six patients whose assessment was inadequate to determine response. The response rate was therefore three of 39 or 8% (95% confidence interval [CI], 2% to 21%). The median survival time for the 39 eligible patients was 5 months. The most common toxicities were anemia, leukopenia/granulocytopenia, malaise/fatigue, nausea/vomiting, alopecia, thrombocytopenia, paresthesias, and liver function abnormalities. There was one death due to sepsis. CONCLUSION: Single-agent paclitaxel in this dose and schedule has minimal activity in pancreatic adenocarcinoma patients.     

Analysis of multilayered dielectric waveguides: variationaltreatment

A fast and near exact modal analysis is presented to obtain the propagation constants and electric field profiles for dielectric multilayered channel (rib) waveguides. Calculations are performed for a particular channel configuration and found to be in excellent agreement with those obtained using the finite difference method     

Restoration of squamous mucosa after ablation of Barrett's esophageal epithelium

BACKGROUND: Antireflux therapy has generally failed to induce regression of Barrett's epithelium. It was hypothesized that squamous epithelium could be restored if the columnar tissue was ablated while gastric acid secretion was suppressed. METHODS: Ten white men with Barrett's esophagus received 40 mg of omeprazole daily. Thereafter, every 2-5 weeks they underwent videotaped endoscopies to argon laser photoablate columnar tissue, obtain biopsy specimens, and assess results. Squamous re-epithelialization was assessed by correlation of videotapes and directed biopsies. RESULTS: Patients had one to eight areas ablated, totaling 0.5-12.0 cm2. Videotape assessments were corroborated by biopsy in all but one instance. Thirty-eight of 40 treatment locations partially or completely re-epithelialized with squamous tissue. Squamous regrowth appeared to occur by spread from contiguous squamous borders and de novo from glandular tissue. Regrowth was influenced by the extent of squamous borders and completeness of ablations. Nonablated glandular tissue persisted beneath squamous epithelium. CONCLUSIONS: Ablation of Barrett's epithelium and suppression of acid secretion facilitated squamous re-epithelialization. A progenitor cell within the metaplastic tissue has the potential to differentiate normally.     

In vitro studies on the use of clay, clay minerals and charcoal to adsorb bovine rotavirus and bovine coronavirus

Rotaviruses are the leading cause and coronaviruses are the major contributors of acute gastroenteritis in the young of various mammalian and avian species. Despite numerous trials and decades of research, vaccines have limited efficacy particularly for calves. As an alternative method of controlling infection, we have investigated broad spectrum antiviral agents that are not discriminatory among various viruses. This report involves testing a variety of adsorbent agents including charcoal, clay, and clay minerals to adsorb rotavirus and coronavirus in vitro. Results revealed that all the adsorbent agents had good to excellent capability of adsorbing rotavirus and excellent capability of adsorbing coronavirus. Percent adsorptions ranged from 78.74% to 99.89% for rotavirus and 99.99% for coronavirus; while sand (negative control) was < 0.01%. A high affinity binding was present as determined by a low percent desorption (0.06-3.09%). However, the adsorbent bound virus complex retained, and may have actually enhanced, infectivity.     

Reduced dosage of genes encoding ribosomal protein S18 suppresses a mitochondrial initiation codon mutation in Saccharomyces cerevisiae

A yeast mitochondrial translation initiation codon mutation affecting the gene for cytochrome oxidase subunit III (COX3) was partially suppressed by a spontaneous nuclear mutation. The suppressor mutation also caused cold-sensitive fermentative growth on glucose medium. Suppression and cold sensitivity resulted from inactivation of the gene product of RPS18A, one of two unlinked genes that code the essential cytoplasmic small subunit ribosomal protein termed S18 in yeast. The two S18 genes differ only by 21 silent substitutions in their exons; both are interrupted by a single intron after the 15th codon. Yeast S18 is homologous to the human S11 (70% identical) and the Escherichia coli S17 (35% identical) ribosomal proteins. This highly conserved family of ribosomal proteins has been implicated in maintenance of translational accuracy and is essential for assembly of the small ribosomal subunit. Characterization of the original rps18a-1 missense mutant and rps18a delta and rps18b delta null mutants revealed that levels of suppression, cold sensitivity and paromomycin sensitivity all varied directly with a limitation of small ribosomal subunits. The rps18a-1 mutant was most affected, followed by rps18a delta then rps18b delta. Mitochondrial mutations that decreased COX3 expression without altering the initiation codon were not suppressed. This allele specificity implicates mitochondrial translation in the mechanism of suppression. We could not detect an epitope-tagged variant of S18 in mitochondria. Thus, it appears that suppression of the mitochondrial translation initiation defect is caused indirectly by reduced levels of cytoplasmic small ribosomal subunits, leading to changes in either cytoplasmic translational accuracy or the relative levels of cytoplasmic translation products.     

Mechanical consequences of core drilling and bone-grafting on osteonecrosis of the femoral head

We employed an anatomically realistic three-dimensional finite-element model to explore several biomechanical variables involved in coring or bone-grafting of a segmentally necrotic femoral head. The mechanical efficacy of several variants of these procedures was indexed in terms of their alteration of the stress:strength ratio in at-risk necrotic cancellous bone. For coring alone, the associated structural compromise was generally modest, provided that the tract did not extend near the subchondral plate. Cortical bone-grafting was potentially of great structural benefit for femoral heads in which the graft penetrated deeply into the superocentral or lateral aspect of the lesion, ideally with abutment against the subchondral plate. By contrast, central or lateral grafts that stopped well short of the subchondral plate were contraindicated biomechanically because they caused marked elevations in stress on the necrotic cancellous bone. Calculated levels of stress were relatively insensitive to variations in the diameter of the graft.     

Effects of aging and schedules of knowledge of results on motor learning

Little research has been conducted on aging and the learning of motor skills. In this study, we examined the effects of different schedules of knowledge of results (KR) on the acquisition and retention of a movement timing task by young adults (20-23 years) and older adults (60-82 years). The results indicated that there were differences between young and older adults in the accuracy and consistency of motor performance when KR was provided. Accuracy effects persisted during a retention interval when KR was no longer provided, although there were no differences in variability. There were no interactions of age with any of the KR-related variables. These findings suggest that the ability to process KR, and the effects of KR on motor learning, are similar in young and older adults. These findings are discussed in terms of age-related issues in movement control and learning processes.     

Electron transfer by domain movement in cytochrome bc1

The cytochrome bc1 is one of the three major respiratory enzyme complexes residing in the inner mitochondrial membrane. Cytochrome bc1 transfers electrons from ubiquinol to cytochrome c and uses the energy thus released to form an electrochemical gradient across the inner membrane. Our X-ray crystal structures of the complex from chicken, cow and rabbit in both the presence and absence of inhibitors of quinone oxidation, reveal two different locations for the extrinsic domain of one component of the enzyme, an iron-sulphur protein. One location is close enough to the supposed quinol oxidation site to allow reduction of the Fe-S protein by ubiquinol. The other site is close enough to cytochrome c1 to allow oxidation of the Fe-S protein by the cytochrome. As neither location will allow both reactions to proceed at a suitable rate, the reaction mechanism must involve movement of the extrinsic domain of the Fe-S component in order to shuttle electrons from ubiquinol to cytochrome c1. Such a mechanism has not previously been observed in redox protein complexes.     

Spatial distribution of femoral bone mineral in dual energy X-ray absorptiometry images: a possible technique to improve discrimination between normal and osteoporotic patients

The measurement of bone mineral density (BMD) using dual energy X-ray absorptiometry (DXA) provides an indicator of subsequent risk of hip fracture, but because of the significant overlap of measurements obtained from osteoporotic and control groups its predictive power is limited. The radiographic technique of Singh grading for the assessment of femoral osteoporosis utilizes information about the distribution of trabecular bundles, but the morphological information available in the DXA image has not previously been analysed. In this study of DXA images from 64 individuals (32 controls and 32 classified as osteoporotic) a subjective grading technique analogous to Singh grading is proposed, and quantitative measurements are made of image features corresponding to two of the categories. Discrimination was assessed using receiver operating characteristic (ROC) curves: the best discrimination was by spinal BMD (Az = 0.85 +/- 0.05) a performance equalled by one of the new parameters; the subjective grading method (Az = 0.79 +/- 0.07) performed as well as measurements of BMD in the femur. These results suggest that although the alternative measures do not improve on the discrimination possible using spinal BMD, morphological information from the hip itself may in the future have a place in the assessment of bone quality.