A phase I-II study of paclitaxel, ifosfamide, and vinorelbine with filgrastim (rhG-CSF) support in advanced non-small-cell lung cancer

PURPOSE: We designed a phase I-II trial of three active agents, paclitaxel, ifosfamide, and vinorelbine, in advanced non-small-cell lung cancer (NSCLC) to: 1) define the dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) of paclitaxel with filgrastim (G-CSF) support; and 2) determine the overall response rate and median survival of patients treated on this regimen. PATIENTS AND METHODS: We treated cohorts of patients with stage IIIB or IV NSCLC with ifosfamide 1.2-1.6 g/m2/day x 3 and vinorelbine 20-25 mg/m2/day x 3 and escalating doses of paclitaxel at 100-175 mg/m2 on day 2 with G-CSF support on a 21-day cycle. One prior experimental single-agent chemotherapy regimen was allowed. RESULTS: Fifty-six patients, were enrolled on this trial: 27 on the phase I portion of the study and an additional 29 at the recommended phase II dose (RPTD). Thirteen patients had received prior chemotherapy. Paclitaxel doses of 175 mg/m2 and 150 mg/m2 produced dose-limiting myelosuppression, and the RPTD was determined to be paclitaxel 135 mg/m2 with ifosfamide 1.2 g/m2/day on days 1-3 and vinorelbine 20 mg/m2/ day on days 1-3 with G-CSF support. The overall response rate was 18%, with a median survival of 6.1 months. Six of 35 patients (17%) treated at the RPTD achieved a partial response to therapy. Grade IV neutropenia was observed in 19 of 35 patients at this dose, with eight patients suffering febrile neutropenia. CONCLUSIONS: This non-cisplatin-containing three-drug regimen has substantial toxicity and low activity in advanced NSCLC, and does not seem to improve on prior regimens. It is unclear whether the lack of efficacy relates to an antagonistic reaction between the specific drugs, administration schedule, or to subtherapeutic doses of the individual agents.     

Sacrospinous colpopexy in the management of uterovaginal prolapse

The tet(M) genes were characterized from 84 isolates of 10 different bacterial species isolated from the periodontal pockets of 16 patients with periodontal disease. A 740 bp polymerase chain reaction product from the hypervariable region of the tet(M) structural gene was cleaved with the restriction enzymes AluI and HinfI. Three different restriction patterns were identified for each of the two enzymes. By DNA sequencing, using a direct solid-phase automated sequencing method, the isolates could be grouped into 3 different clusters of tet(M) subtypes. The internal DNA homology within each subtype was 98-100%; the homology between clusters was 89-94%. Two different subtypes were identified in 9 of 10 bacterial species, and the remaining species had 3 different subtypes. One of the subtypes (M3) was seen mainly in the anaerobic isolates. This subtype was different from all earlier sequenced structural tet(M) genes present in the Genbank. Most patients had two different subtypes of tet(M), and a third subtype was seen in the 3 patients who exhibited the greatest variety of tetracycline-resistant bacterial species. It appears that the presence of one subtype of the tet(M) gene within a patient or bacterial species does not prevent the acquisition of another subtype of the same gene. This study identified a new subtype of the tet(M) gene and grouped it into 3 distinct yet highly homologous genetic subtypes.     

Concordant but different: Cognitive function, cerebral anatomy, and metabolism in monozygotic twins with Alzheimer's disease.

To illustrate the utility of the twin method in Alzheimer's disease (AD) research, a pair of monozygotic twins, concordant for the disease but markedly different in their clinical presentations, was studied in detail. Neuropsychological evaluation, magnetic resonance imaging (MRI), and cerebral glucose metabolic studies revealed a typical behavioral presentation for AD in Twin A. In contrast, Twin B showed prominent visuospatial impairments. Although there was no identified cause for the disparate presentations, a close correspondence was observed between the neuropsychological findings and the regional brain measures. The results suggest that the trajectory of AD may vary widely even in genetically identical individuals. Factors accounting for the variability include potential intrauterine, early developmental, and environmental differences. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Transthyretin amyloidosis: a new mutation associated with dementia

NaCl-tolerant lactic acid bacteria (LAB) strains LC-10 (Lactobacillus casei) and LP-15 (Lact. plantarum) and NaCl were used as additives to sorghun (Sorghum bicolor). Numbers of LAB were significantly (P < 0.05) higher in all the additive-treated silages than in the control silage at an early stage of ensiling. During the fermentation process, addition of NaCl or LAB effectively inhibited the growth of aerobic bacteria and clostridia, but not yeasts. All the additive-treated silages had significantly (P < 0.05) lower pH, ammonia nitrogen content, dry matter loss and gas production but significantly (P < 0.05) higher lactic acid content and residual water soluble carbohydrates compared with the control silage. The improvement in silage quality was in the order: LAB > NaCl > control. Yeast counts were high in all additive-based silages and they increased during the exposure of the silages to air. As a result, these silages suffered aerobic deterioration, whereas the control silage was stable. The results confirmed that the NaCl or LAB improved fermentation quality but did not prevent aerobic deterioration of the silage.     

Granulation tissue polyposis associated with carcinoid tumours of the small intestine

We report two patients with ileal carcinoid tumours which were associated with polyps due to mucosal granulation tissue proliferation. In both cases the tumours had extensively infiltrated the small bowel wall and mesentery, and one had hepatic metastases. The mucosal surface of each specimen showed numerous, pale brown, sessile polyps which were restricted to the intestinal segment involved by carcinoid tumour, although not always closely related to neoplastic cells. The polyps were formed by the proliferation of capillaries, smooth muscle cells and myofibroblasts as demonstrated by immunohistochemistry and electronmicroscopy.     

High-temperature sensible-heat storage options

Alkali-metal carbonate salts meet the requirements for high-temperature solar central receiver systems, but because of their corrosiveness they present special problems in the design of storage tanks. In order to reduce corrosion and temperature sufficiently to retain strength in the storage containing wall, internal and thermal insulation is required. We present design options and operation criteria for sensible-heat, molten-salt storage with internal insulation.     

A 16-Mbit/s adapter chip for the IBM token-ring local area network

The authors describe a 9.02×9.02-mm chip built in 1-μm CMOS with two levels of metal and an additional mask level for fabricating capacitors. It contains both analog and digital circuits and has provisions for self-test. The function includes the transmitter, receiver, protocol handler, an microprocessor, as well as interfaces for RAM/ROM storage, IBM PC bus, IBM PS/2 bus, IBM 3174 bus, and Motorola 68000 bus. The physical design terrains are formed by 24K circuits of standard cell gates, a 10K-circuit equivalent hand-honed custom microprocessor, and an analog macro. The chip operates from a single 5-V supply, and the power consumption is 0.8 W nominal at 16 Mb/s. The chip can also be operated at 4 Mb/s     

A Low-Complexity Circuit for On-Sensor Concurrent A/D Conversion and Compression

A low-complexity circuit for on-sensor compression is presented. The proposed circuit achieves complexity savings by combining a single-slope analog-to-digital converter with a Golomb-Rice entropy encoder and by implementing a low-complexity adaptation rule. The adaptation rule monitors the output codewords and minimizes their length by incrementing or decrementing the value of the Golomb-Rice coding parameter k. Its hardware implementation is one order of magnitude lower than existing adaptive algorithms. The compression circuit has been fabricated using a 0.35 muM CMOS technology and occupies an area of 0.0918 . Test measurements confirm the validity of the design.     

High Throughput Primer Walking of cDNA Clones

Primer walking of cloned DNA is a standard research tool. It has been used in the past to determine the sequence of individual clones of interest. With the expansion of DNA sequencing capacity the need to be able to walk larger numbers of clones has become necessary. Our laboratory is a mid-sized genomics facility. In conjunction with the Advanced Biomedical Computing Center (ABCC) we have developed methods for automating the primer selection, DNA sequencing, contig assembly and sequence analysis for clones arrayed in microtiter format. This approach has allowed us to walk 475 clones (five microtiter plates) selected from a cDNA library.