Watt-scale 50-MHz source of single-cycle waveform-stable pulses in the molecular fingerprint region.

We report a coherent mid-infrared (MIR) source with a combination of broad spectral coverage (6-18 µm), high repetition rate (50 MHz), and high average power (0.5 W). The waveform-stable pulses emerge via intrapulse difference-frequency generation (IPDFG) in a GaSe crystal, driven by a 30-W-average-power train of 32-fs pulses spectrally centered at 2 µm, delivered by a fiber-laser system. Electro-optic sampling (EOS) of the waveform-stable MIR waveforms reveals their single-cycle nature, confirming the excellent phase matching both of IPDFG and of EOS with 2-µm pulses in GaSe.

Experimental electric field visualisation of multi-mode dynamics in a short cavity swept laser designed for OCT applications.

An experimental study into the modal dynamics of a short cavity, fast frequency-swept laser is presented. This commercially available external cavity swept source is designed for use in optical coherence tomography (OCT) applications and displays a number of dynamic lasing regimes during the course of the wavelength sweep. Interferometric full electric field reconstruction is employed, allowing for measurement of the laser operation in a time-resolved, single-shot manner. Recovery of both the phase and intensity of the laser output across the entire sweep enables direct visualization of the laser instantaneous optical spectrum. The electric field reconstruction technique reveals the presence of multi-mode dynamics, including coherent mode-locked pulses. During the main part of the imaging sweep, the laser is found to operate in a second harmonic sliding frequency mode-locking regime. Examination of the modal evolution of this coherent regime reveals evidence of previously unobserved frequency switching dynamics.

High-power frequency comb at 2 µm wavelength emitted by a Tm-doped fiber laser system.

We report on the generation of a high-power frequency comb in the 2 µm wavelength regime featuring high amplitude and phase stability with unprecedented laser parameters, combining 60 W of average power with <30 fs pulse duration. The key components of the system are a mode-locked Er:fiber laser, a coherence-preserving nonlinear broadening stage, and a high-power Tm-doped fiber chirped-pulse amplifier with subsequent nonlinear self-compression of the pulses. Phase locking of the system resulted in a phase noise of less than 320 mrad measured within the 10 Hz-30 MHz band and 30 mrad in the band from 10 Hz to 1 MHz.

Direct experimental measurement of single-mode and mode-hopping dynamics in frequency swept lasers.

A time-resolved study is presented of the single-mode and mode-switching dynamics observed in swept source vertical cavity surfing emitting lasers and swept wavelength short external cavity lasers. A self-delayed interferometric technique is used to experimentally measure the phase and intensity of these frequency swept lasers, allowing direct examination of the modal dynamics. Visualisation of the instantaneous optical spectrum reveals mode-hop free single mode lasing in the case of the vertical cavity laser, with a tuning rate of 6.3 GHz/ns. More complex mode-switching behaviour occurs in the external cavity laser, with the mode-hopping dynamics found to be dominated by the deterministic movement of the spectral filter. Evidence of transient multi-mode operation and mode-pulling is also presented.

A comparison of efficacy of sargramostim (yeast-derived RhuGM-CSF) and filgrastim (bacteria-derived RhuG-CSF) in the therapeutic setting of chemotherapy-induced myelosuppression.

A randomized, double-blind, multicenter study in 181 afebrile cancer patients with ANC levels < 500/microL receiving myelosuppressive chemotherapy was undertaken to compare sargramostim (yeast-derived recombinant human granulocyte-macrophage colony-stimulating factor, RhuGM-CSF) and filgrastim (bacteria-derived recombinant human granulocyte colony-stimulating factor, RhuG-CSF) in the treatment of chemotherapy-induced myelosuppression. Patients received daily subcutaneous (SC) injections of either agent until ANC levels reached at least 1500/microL. There was no statistical difference between treatment groups in the mean number of days to reach an ANC of 500/microL, but the mean number of days to reach ANC levels of 1000/microL and 1500/microL was approximately one day less in patients receiving filgrastim. Fewer patients in the sargramostim arm were hospitalized, and they had a shorter mean length of hospitalization, mean duration of fever, and mean duration of i.v. antibiotic therapy compared with patients who received filgrastim. Both growth factors were well tolerated. No patient was readmitted to the hospital after growth factor was discontinued. Sargramostim and filgrastim have comparable efficacy and tolerability in the treatment of standard-dose chemotherapy-induced myelosuppression in community practice.

Randomized trial comparing the tolerability of sargramostim (yeast-derived RhuGM-CSF) and filgrastim (bacteria-derived RhuG-CSF) in cancer patients receiving myelosuppressive chemotherapy.

A prospective, randomized, double-blind, multicenter study in cancer patients receiving myelosuppressive chemotherapy was undertaken to evaluate and compare the tolerability of sargramostim (yeast-derived recombinant human granulocyte-macrophage colony-stimulating factor, RhuGM-CSF) and filgrastim (bacteria-derived recombinant human granulocyte colony-stimulating factor, RhuG-CSF) in the prophylaxis or treatment of chemotherapy-induced neutropenia. In all, 137 evaluable patients received sargramostim (300 micrograms; 193 mg/m2) or filgrastim (481 mg; 7 mg/kg) once daily by self-administered s.c. injection, usually beginning within 48 h after completion of chemotherapy. With the exception of a slightly higher incidence of grade 1 fever (< 38.1 degrees C) with sargramostim, there were no statistically significant differences in the incidence or severity of local or systemic adverse events possibly related to the growth factors. Although the study was not designed to evaluate efficacy directly, there also were no statistically significant differences between treatment groups in total days of growth factor therapy, days of hospitalization, or days of i.v. antibiotic therapy during the treatment period. Both sargramostim and filgrastim were comparably well tolerated when given by s.c. injection in this group of patients, and no clinically significant differences between the growth factors were demonstrated.

Response to treatment with antidepressants of patients with severe or moderate nonpsychotic depression and of patients with psychotic depression.

Hospitalized patients were divided into nonpsychotic severely depressed (N = 53), nonpsychotic moderately depressed (N = 54), and psychotic depressed (N = 25) groups and treated with either imipramine or amitriptyline, up to 250 mg/day, for 4 weeks. Good response occurred in 39% of the 38 severely depressed, 67% of the 49 moderately depressed, and 32% of the 19 psychotic depressed patients who completed treatment. The response of the patients with nonpsychotic severe depression did not differ significantly from the response of those with psychotic depression, and both groups fared worse than the group with nonpsychotic moderate depression.

Malignant melanoma with melanosis. Ultrastructural and histological studies.

Ultrastructural and histological investigations were performed on a case of generalized melanosis associated with superficial spreading melanoma. The hyperpigmentation of the general body surface, mucous membranes and nail beds was associated with deposition of melanin in macrophages in the dermis, together with some hyperactivity of epidermal melanocytes. Melanin granules were observed lying free in the stroma, suggesting pigment incontinence and phagocytosis by macrophages. Giant melanosomes were noted in melanocytes, keratinocytes and melanophages in the hyperpigmented skin. No evidence was found to suggest dissemination of individual malignant cells throughout the skin. Subcutaneous nodules of malignant melanoma were, however, present, as well as metastases to the iris, liver and to other organs.

5-Fluorouracil, adriamycin, and mitomycin-C (FAM) chemotherapy for adenocarcinoma of the lung.

Twenty-five patients with advanced measurable adenocarcinoma of the lung were treated with combination chemotherapy consisting of 5-fluorouracil, adriamycin, and mitomycin-C (FAM). Objective response (1CR, 8PR) was obtained in 36% of patients. The median duration of response was 7.0 months and the median survival for responders is greater than 8.5 months. Five responders are alive 5.5 to 23.5 months after starting therapy. Three of four patients evidencing stabilization of disease are alive at 10-23 months. Non-responding patients had a median survival of 2.5 months and none lived beyond seven months. Tumor response and survival suggested correlation with initial performance status and limited disease. The FAM regimen was tolerated well, with moderate bone marrow suppression and gastrointestinal symptoms being the only clinically significant toxicities. These results indicate that patients with advanced pulmonary adenocarcinoma can obtain objective tumor regression with FAM chemotherapy.

Sarcoidosis following adjuvant high-dose methotrexate therapy for osteosarcoma.

A patient who had undergone amputation and adjuvant chemotherapy with methotrexate doxorubicin hydrochloride for osteosarcoma of the femur later developed granulomatous hilar and paratracheal lymphadenopathy and multiple pulmonary nodules. Biopsy of the nodules showed noncaseating granulomas typical of sarcoidosis. Hilar adenopathy and granulomatous pneumonitis have been reported following methotrexate therapy, but a roentgenographic pattern of isolated, discrete pulmonary nodules has not been described. Treatment with immunosuppressive chemotherapy may have inhibited the development of sarcoidosis, which became manifest only after cessation of the chemotherapy.

Bulk transfer of fluid in the interstitial compartment of mammary tumors.

Venous blood leaving a solid tumor showed higher erythrocyte concentration than did aortic blood. Net fluid loss of efferent blood as calculated from hematocrit differences was 2.7 to 6.7% of flow volume, 4.5 to 10.2% of perfusing plasma volume, or 0.14 to 0.22 ml fluid per hr per g in 2 to 5 g transplanted MTW9 and Walker 256 mammary carcinomas, and primary N-nitrosomethylurea- and 7,12-dimethylbenz(alpha)anthracene-induced mammary carcinomas of rats. Net fluid loss was directly related to blood flow but inversely related to tumor size. Increased hydrostatic pressure in tumor interstitial space was a consistent finding. Micropore chambers embedded in transplanted tumors drained 4 to 5 times more interstitial fluid than did identical chambers in the s.c. tissue. It is concluded that: (a) convective currents are present within the interstitial spaces of tumors; (b) the magnitude of fluid transfer can be measured by the difference in hemoconcentration between afferent and efferent tumor blood; and (c) the volume of this fluid transfer is not altered by hormone-induced tumor regression. The increased hydrostatic pressure of tumor interstitial spaces is interpreted as being due to absence of an anatomically well-developed lymphatic network. The bulk transfer of fluid within interstitial spaces is comparable to lymphatic drainage and should be considered in assessing drug concentration and distribution in solid tumors.

Quantitation of cell shedding into efferent blood of mammary adenocarcinoma.

The rate of tumor cell shedding into efferent tumor blood was measured in growing and regressing MTW9 rat mammary carcinomas. The hormone-dependent tumor, grown as an 'isoession was induced by reduction of mammotropin level in the host. Tumor cells were differentiated from normal leukocytes by indirect immunofluorescence. Growing tumors shed 3.2 x 10-6 and regressing tumors shed 4.1 x 10-6 cells per 24 hr per g tissue. Cell shedding rates of growing versus regressing tumors were not siginificantly different over a tumor size range of 2 to 4 g. The number of tumor cells in the arterial blood was 12-fold smaller than in the efferent tumor blood. It is concluded that: (ay cell shedding via blod probably plays only a minor role in the total cell loss by gtowing MTW9 carinomas; (b) hormone-induced tumor regression does not depend on increased cell shedding; (c) tumor cells are rapidly cleared from circulating blood; and (d) a 2-g MTW9 carcinoma pours enough cells into the host circulation to transplant the tumor every 24 hr.