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.     

Apoptosis occurs in granulosa cells but not cumulus cells in the atretic antral follicles in pig ovaries

The porcine antral follicles, 3-6 mm in diameter, were dissected from the ovaries of mature pigs, and then granulosa and cumulus cells were isolated from each follicle. In atretic follicles, high activity of neutral Ca2+/Mg2+-dependent endonuclease and DNA ladder formation, estimated by electrophoresis, were noted in granulosa cells but not in cumulus cells. Extremely low activity of the endonuclease and no DNA ladder formation were observed in both types of cells obtained from healthy follicles. Moreover, apoptotic cells were observed histochemically among granulosa cells only. A good correlation (r = 0.987) between the endonuclease activity of granulosa cells and the progesterone/estradiol ratio of follicular fluid in each follicle was found. These results suggest that apoptosis occurs in granulosa cells but not cumulus cells in the atretic antral follicles in pigs.     

The pharmacokinetics of pancuronium bromide in infants, children and adults

Laparoscopic retroperitoneal lymph node dissection is a new surgical procedure used to enhance staging in men with clinical stage I nonseminomatous germ cell tumors of the testis. The procedure has been performed in a limited number of patients at several centers with extensive laparoscopic experience. Laparoscopic retroperitoneal lymphadenectomy is a technically demanding procedure which can be successfully completed in the majority of patients. However, the risk of complications is greater than in patients who undergo standard open retroperitoneal lymph node dissection. The primary advantage of a laparoscopic approach is shortened hospitalization and rapid return to normal activity. The role of laparoscopy in the management of patients with testis malignancy has not been defined. The use of this staging procedure may help minimize the need for surveillance studies following surgery and may be best utilized in men with a lower likelihood of nodal metastases. Ultimately, prospective study in large groups of patients will be necessary to determine the role of laparoscopic retroperitoneal lymph node dissection in patients with testis cancer.     

Polymeric prodrugs of mitomycin C designed for tumour tropism and sustained activation

Prodrugs of mitomycin C (MMC) based on soluble poly-[N-(2-hydroxyethyl)-L-glutamine] (pHEG) polymers have been evaluated as tumour-targeted drugs. These materials are designed to exploit the enhanced permeability of tumour vasculature, combining a passive tumour tropism with decreased systemic liberation of free MMC. A tri- or tetrapeptide linkage (e.g. Gly-Phe-Ala-Leu) between pHEG and the aziridine nitrogen of MMC can combine good hydrolytic stability with rapid cleavage by lysosomal enzymes, releasing free MMC. The conjugates showed decreased systemic toxicity and could be administered to mice at a total MMC dose of 15 mg/kg i.v., compared with just 6 mg/kg for free MMC. Conjugates also showed better activity against animal models of established tumours, achieving up to 77% increased life span (ILS) against solid P388 leukaemia, compared with only 23% for free MMC, and up to 121% ILS against solid C26 colorectal carcinoma, compared with no activity for the free drug. Improving the therapeutic index of anticancer drugs by combining tumour tropism with decreased systemic toxicity is a versatile approach that should produce a new generation of improved anticancer agents.     

Drift hole mobility in strained and unstrained doped Si1-xGex alloys

Results of the drift hole mobility in strained and unstrained SiGe alloys are reported for Ge fractions varying from 0 to 30% and doping levels of 10¹⁵-10¹⁹ cm^-3. The mobilities are calculated taking into account acoustic, optical, alloy, and ionized-impurity scattering. The mobilities are then compared with experimental results for a boron doping concentration of 2×10¹⁹ cm^-3. Good agreement between experimental and theoretical values is obtained. The results show an increase in the mobility relative to that of silicon     

Efficient diode-pumped single-frequency erbium:ytterbium fiberlaser

We report a 7.6-mW single-frequency fiber laser operating at 1545 nm, using for the first time an Er³⁺:Yb³⁺ doped fiber and a fiber grating output coupler. The laser did not exhibit self-pulsation, which is a typical problem in short three-level fiber lasers, and had a relative intensity noise (RIN) level below -145.5 dB/Hz at frequencies above 10 MHz. The linewidth of the laser was limited by the relaxation oscillation sidebands in the optical spectrum and was typically less than 1 MHz     

Effect of postoperative mydriatics on the iris

PURPOSE: To assess the role postoperative mydriatics play after extracapsular cataract extraction (ECCE) and posterior chamber intraocular lens (IOL) implantation in causing iris modifications and in controlling inflammation. SETTING: Outpatients Department, Ninewells Hospital, Dundee, Scotland. METHODS: The prospective study comprised 136 patients who had standardized ECCE. Half the patients used a mydriatic for 2 weeks postoperatively. Anterior chamber activity, pain, and eye redness were evaluated at 2 weeks postoperatively; pupil shape, peripheral anterior synechias, IOL position, and iris adhesions, at 6 weeks. RESULTS: Iris-lens adhesions were significantly more common in the group using a mydriatic. There was no difference between the two groups in postoperative inflammation. CONCLUSION: Mydriatics should not be used routinely after ECCE with posterior chamber IOL implantation.     

The effects of cholecystokinin A and B receptor antagonists, devazepide and L 365260, on citalopram-induced decrease of exploratory behaviour in rat

The present study has been divided into two sets. In the first set, the aim of the experiments was to investigate the dose-response effect of selective serotonin re-uptake inhibitor (SSRI) citalopram on rat exploratory behaviour in the elevated plus-maze. In the second set of experiments, the effect of cholecystokinin (CCK) CCKA and CCKB receptor antagonists, devazepide and L 365260, on citalopram-induced decrease of exploratory behaviour in the elevated plus-maze was studied. Citalopram (5 and 10 mg/kg) decreased the number of open and total arm entries, line crossings on open arms, and percentage of time spent exploring in open arm. Dose 15 mg/kg was without any effect on rat exploratory behaviour. Devazepide (0.01 and 1.0 mg/kg) failed to modify any of the citalopram-induced changes observed. L 365260 (1.0 mg/kg) reversed most of the effects of citalopram: the numbers of open and total arm entries, the number of line crossings, and the percentage of time spent exploring in open arms. L 365260 at dose level 0.01 mg/kg was ineffective. These results support the involvement of the CCKB receptor subtype in SSRI-induced anxiogenic-like effects in rodents.