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.     

Duration of spinal anaesthesia is determined by the partition coefficient of local anaesthetic

We have compared the duration of motor block produced by four local anaesthetics administered into a chronically implanted subarachnoid catheter in rabbits. Each group (n = 6) received four different doses of amethocaine, bupivacaine, lignocaine or procaine, and the duration of the resulting motor block was assessed. Dose-response curves were plotted for each drug. As a measure of activity of the anaesthetics, we used the dose of each drug required to produce block of 60-min duration (D60 min) and the correlation between D60 min and different drug properties was examined. An inverse linear correlation (r = 0.995; P < 0.01) was observed between log D60 min and the log of the partition coefficient of the local anaesthetics. No correlation was found between the effect and degree of protein binding, pKa or molecular weight. These results suggest that, in spinal anaesthesia, the partition coefficient could be used as a predictor of the duration of anaesthetic action.     

Hippocampal atrophy in normal aging. An association with recent memory impairment

OBJECTIVE: To estimate the prevalence of radiographically detectable hippocampal atrophy (HA) in a normal aging sample and to test whether such atrophy is associated with memory dysfunction. DESIGN: One hundred fifty-four medically healthy and cognitively normal elderly persons (aged 55 to 88 years) received magnetic resonance imaging and/or computed tomographic scans designed to identify HA. One hundred forty-five of these subjects also underwent psychometric tests of memory function. Multivariate analyses of variance were used to evaluate differences in memory performance between subjects with and without HA. SETTING: This study was conducted at a research clinic for the investigation of age-associated neuropsychological and neuroradiologic changes. PARTICIPANTS: Based on the following criteria, 154 subjects were consecutively selected from a larger group of elderly research volunteers participating in a study of normal aging: age of 55 years or greater; Global Deterioration Scale score of 2 or less; and Mini-Mental State examination score of 28 or greater. Subjects with evidence for significant medical, psychiatric, or neurologic disease were excluded. MAIN OUTCOME MEASURES: Outcome measurements included individual psychometric test scores and computed tomographic-magnetic resonance imaging hippocampal atrophy ratings. RESULTS: Nearly 33% of the subjects had radiographic evidence for HA. The prevalence of HA increased significantly with age and was more common in male than female subjects. After controlling for age, level of education, and vocabulary, subjects with HA were found to perform more poorly on tests of recent (secondary) verbal memory when compared with subjects without HA (P < .01). No significant differences were found for tests of immediate (primary) memory. CONCLUSION: We conclude that HA is a common accompaniment of normal aging and is associated with mild memory impairment. Additional research is needed to determine whether HA constitutes a significant risk for future dementia.     

Effects of delay on the type and velocity of travelling pulses in neuronal networks with spatially decaying connectivity

We study a one-dimensional model of integrate-and-fire neurons that are allowed to fire only one spike, and are coupled by excitatory synapses with delay. At small delay values, this model describes a disinhibited cortical slice. At large delay values, the model is a reduction of a model of thalamic networks composed of excitatory and inhibitory neurons, in which the excitatory neurons show the post-inhibitory rebound mechanism. The velocity and stability of propagating continuous pulses are calculated analytically. Two pulses with different velocities exist if the synaptic coupling is larger than a minimal value; the pulse with the lower velocity is always unstable. Above a certain critical value of the constant delay, continuous pulses lose stability via a Hopf bifurcation, and lurching pulses emerge. The parameter regime for which lurching occurs is strongly affected by the synaptic footprint (connectivity) shape. A bistable regime, in which both continuous and lurching pulses can propagate. may occur with square or Gaussian footprint shapes but not with an exponential footprint shape. A perturbation calculation is used in order to calculate the spatial lurching period and the velocity of lurching pulses at large delay values. For strong synaptic coupling, the velocity of the lurching pulse is governed by the tail of the synaptic footprint shape. Moreover, the velocities of continuous and lurching pulses have the same functional dependencies on the strength of the synaptic coupling strength gsyn: they increase logarithmically with gsyn for an exponential footprint shape, they scale like (In gsyn)1/2 for a Gaussian footprint shape, and they are bounded for a square footprint shape or any shape with a finite support. We find analytically how the axonal propagation velocity reduces the velocity of continuous pulses; it does not affect the critical delay. We conclude that the differences in velocity and shape between the front of thalamic spindle waves in vitro and cortical paroxysmal discharges stem from their different effective delays.     

An approach to general oncology: principles and procedures

53 patients clinically suspected of having a cerebellopontine angle (CPA) lesion were examined by computer tomography (CT) with 160 X 160 matrix EMI scanner. 17 cases (32%) had tumour positive CT, of which 12 were neurinomas and 1 meningioma. 1 CT suggestive of a CPA lesion was false positive and 1 unoperated case is probably a false negative CT. Three of the eleven verified neurinomas (27%) were of the medial type originating in the angle cistern. One neurinoma protruding 1 cm into the cistern showed no contrast enhancement. 2 CT scans (3.8%) were unsatisfactory due to movements and the large size of the head. CT is valuable for the investigation of CPA pathology and the diagnostic efficiency compares favourably to other neuroradiological procedures.     

Binary sequences with two-level autocorrelation

We derive the values of the Fourier spectrum, a decomposition, and an achievable upper bound on the linear span, for binary sequences with two-level autocorrelation     

Make believe and reality: Explorations of the imaginary realm.

Preschool children's ability to distinguish between pretense and reality was examined in 2 studies that adopted a modified version of the design used by P. L. Harris, E. Brown, M. Marriott, S. Whittall, and S. Harmer (1991) in which a pretend creature is assumed to hide inside a box. In Study 1, 19 4-year-olds participated in test conditions that closely followed Harris et al.'s procedures. In Study 2, 75 3- and 4-year-olds were randomly assigned to 1 of 4 emotionally colored pretense play scenarios that included 4 test conditions: an imaginary creature, invented by the adult or the child, whose affective value was either positive or negative. The results of both studies do not support Harris et al.'s interpretation of their data in terms of a breakdown of the distinction between pretense and reality. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A note on the equivalence between strict optical orthogonal codes and difference triangle sets

Zhang (see IEEE Trans. Commun., vol.47, p.967-973, July 1999) proposed a special family of optical address codes, called strict optical orthogonal codes (S-OOCs), was proposed for fiber-optic code-division multiple-access (FO-CDMA) networks. Such codes can strictly guarantee both cross-correlation and autocorrelation functions constrained to have the value one in fully asynchronous data communications and ultra fast switching. In Zhang's work the theory and designs of S-OOC, plus several examples, comparison tables, and performance analyses were presented. In this article, we set up the equivalence between S-OOC and so-called difference triangle sets (DTS), which have been extensively studied previously. Thus, all the known constructions, bounds, and analyses for DTS can be directly applied to S-OOC.     

7200-phase generalized Barker sequences

We present 7200-phase generalized Barker sequences with lengths from 19 to 31. Also, we show the number of known M-phase generalized Barker sequences (M=7200), inequivalent under the group of “Barker-preserving transformations”. The autocorrelation values of Barker sequences are also presented     

Conservative treatment of a vesicocervical fistula resulting from Shirodkar cervical cerclage

A case of a vesicocervical fistula caused by Shirodkar cervical cerclage and presenting as total urinary incontinence is reported. The patient was managed conservatively by bladder drainage alone with complete resolution of the fistulous tract. This rare complication is avoidable if the bladder is adequately dissected from the cervix during placement of the cerclage suture.