Gas spectroscopy through multimode self-mixing in a double-metal terahertz quantum cascade laser.

A multimode self-mixing terahertz-frequency gas absorption spectroscopy is demonstrated based on a quantum cascade laser. A double-metal device configuration is used to expand the laser's frequency tuning range, and a precision-micromachined external waveguide module is used to enhance the optical feedback. Methanol spectra are measured using two laser modes at 3.362 and 3.428 THz, simultaneously, with more than eight absorption peaks resolved over a 17 GHz bandwidth, which provide the noise-equivalent absorption sensitivity of 1.20×10-3 cm-1 Hz-1/2 and 2.08×10-3 cm-1 Hz-1/2, respectively. In contrast to all previous self-mixing spectroscopy, our multimode technique expands the sensing bandwidth and duty cycle significantly.

Human pharmacokinetics and toxicity of high-dose metronidazole administered orally and intravenously.

This study is part of a clinical program to assess the use of nitroimidazoles as radiosensitizers of hypoxic tumor cells. A total of 37 patients with malignant tumors have been entered into the study to receive oral high-dose metronidazole in conjunction with radiation. Twenty-eight patients with malignant brain tumors received 6 gm/m2 three times a week for 3 weeks (a mean total dose of 5.3 gm/m2). Maximum mean plasma drug concentration of 1 mM was obtained at 4 hours after drug ingestion with a mean half-life of 13 hours. Tissue and cerebrospinal fluid levels of 80% to 90% of the plasma levels were obtained at 4 to 6 hours. A linear relationship between increased drug dose and increased plasma concentration was observed at doses of 2.5 gm/m2 up to 6 gm/m2. Acute gastrointestinal and central nervous system toxicity was the dose-limiting factor (50% and 25%, respectively, at total doses of 5.3 gm/m2). Pharmacokinetic studies of intravenous metronidazole were performed in eight consenting patients. Single doses of 0.5, 1, 1.5, and 2 gm were administered intravenously by zero-order infusion pump. Seven of the eight patients received a second identical dose orally 1 week later and the results were compared. Open two-compartment kinetic characteristics of metronidazole were computed from simultaneous plasma infusion and urine excretion rate equations, by use of a nonlinear least-squares regression analysis program (NONLIN). The mean (+/- SD) for alpha half-life was 1.2 +/- 1.3 hours, and that for the beta half-life was 9.8 +/- 5.9 hours. The absolute oral bioavailability was estimated to approximate 100%.

Purification of polyphenol oxidase free of the storage protein patatin from potato tuber.

Routine protein purification to homogeneity from potato tuber, as from other storage tissues and seeds, is often hindered due to the large amounts of storage protein present. In potato, patatin, the major storage protein of the tuber, often contaminates preparations. The present work describes the purification of polyphenol oxidase (PPO) from the potato tuber (Solanum tuberosum cv Cara) to homogeneity including the critical step of hydrophobic chromatography on Octyl-Sepharose which was sufficient to completely remove patatin. The purified PPO was found to be a doublet of M(r) 60,000 and 69,000 when analysed by SDS-PAGE with a Km 4.3 +/- 0.3 mM for L-dihydroxyphenylalanine. Both bands were found to have similar N-terminal corresponding to PPO isoforms when sequenced.

Creutzfeldt-Jakob disease probably acquired from a cadaveric dura mater graft. Case report.

A case of Creutzfeldt-Jakob disease (CJD) is reported in a 28-year-old woman who had received a cadaveric dural graft 19 months earlier after resection of a cholesteatoma. The circumstances of the case point to the graft as the most likely source of the disease. Cadaveric dura should be added to the list of materials that may transmit CJD, and it must be very carefully screened if it is used at all for grafting. Autologous tissue should be considered whenever possible.

Overcoming an autistic child's failure to acquire a tact repertoire.

A 6-year-old nonvocal autistic girl who had acquired over 30 signs as mands (requests), simple intraverbals (English-sign translations), and imitative responses repeatedly failed to acquire a tact (labeling) repertoire. It was speculated that the verbal stimulus "What is that?" blocked the establishment of stimulus control by nonverbal stimuli. When procedures to transfer stimulus control from verbal to nonverbal stimuli were implemented, the subject quickly learned to tact all 18 target stimuli.

Teaching intraverbal behavior to preschool children.

Four preschool children who were taught to tact a set of Peabody picture cards were unable to emit those same responses under intraverbal conditions. A transfer of stimulus control procedure was used to bring the responses under intraverbal control. A multiple probe design was used to demonstrate experimental control. The results indicate that the transfer procedure was effective in developing the responses as intraverbals, and in increasing the subjects' scores on the Verbal Fluency subtest of the McCarthy Scales. A second study demonstrated that teaching four additional subjects to tact both the items and the class of which the items were members resulted in the untrained emergence of a few intraverbal responses for two of four subjects. For the other subjects and classes, it was still necessary to teach each of the responses as intraverbals, further demonstrating that tacts and intraverbals are separate verbal operants. The implications of these results for the use of Skinner's (1957) analysis of verbal behavior for studying typical language development are discussed.

Skinner's verbal behavior: A reference list.

The language literature contains many citations to Skinner's book Verbal Behavior (1957), however, most of them are negative and generally unsupportive. The current list of references was assembled to bring readers in contact with the growing body of literature which supports Skinner's work. A total of 136 references were found and divided into two categories, (1) conceptual, and (2) experimental and applied. These references are presented in an effort to stimulate additional research in this important aspect of behavior analysis.

Correlates of compliance among chiropractic patients treated for low back pain.

To test Becker's revision of the Health Belief Model in predicting adherence to a chiropractic regimen, 50 patients diagnosed with recurrent acute lumbago were interviewed regarding health beliefs. All subjects had initiated treatment 12 months before the onset of research. This enabled the calculation of a compliance score for each patient, expressed as the percentage of appointments kept to appointments recommended over a 1-yr period. Posttreatment health beliefs were correlated with the compliance measure. From the four dimensions of the model tested, two categories showed variables having significant associations with appointment keeping. Intention to comply was strongly correlated with compliance (P less than 0.01). However, contrary to the model, subjects' estimates of disability were negatively related with adherence to the program (P less than 0.05). It was suggested that patients reporting high levels of disability showed forced compliance. Clinical applications derived from these results are included to aid chiropractors in the prediction and management of compliance.

Changes in the location of polyphenol oxidase in potato (Solanum tuberosum L.) tuber during cell death in response to impact injury: comparison with wound tissue.

In order to elucidate the nature of the response of potato to impact injury at the biochemical level, changes in the location of the enzyme responsible for the discoloration, polyphenol oxidase, were determined using immunogold location with an antibody specific for potato tuber polyphenol oxidase. Tissue printing revealed that the enzyme was distributed throughout the tuber. Following impact injury, both tissue printing and quantitative electron microscopy indicated that there was no increase in the level of the enzyme although there was subcellular redistribution of polyphenol oxidase. This redistribution was first apparent at 12 h after impact, as determined by the use of confocal immunolocation, and coincided with loss of membrane integrity. These changes were examined in parallel with a number of stress-related parameters in both impact and wound responses. Wounding was accompanied by active gene expression and protein synthesis, leading to metabolic activity and tissue repair. In contrast, the bruising response was characterised by a limited active response and vital-staining methods indicated that after 16 h the tissue undergoes cell death.

High-dose metronidazole: pharmacokinetics and bioavailability using an iv preparation and application of its use as a radiosensitizer.

As an extension of studies on the clinical use of nitroimidazoles as radiosensitizers, single-dose pharmacokinetic studies of iv metronidazole (500 mg/100-ml vials) were performed in eight consenting patients. Single doses of 0.5, 1.0, 1.5, and 2.0 g (0.29-1.21 g/m2) were administered iv by a zero-order infusion pump. Serial timed blood and urine samples were assayed for metronidazole and its two metabolites (acetic acid and ethoxy compounds) using a high-pressure liquid chromatographic assay. Open two-compartment kinetic characteristics of metronidazole were computed from simultaneous plasma infusion and urine excretion-rate equations using a nonlinear least-squares regression analysis program (NONLIN). Means of the four kinetic parameters were (h-1): k12, 1.18; k21, 0.86; k10, 0.22; and k'e, 0.46 x 10(-4). Means of the apparent volumes of distribution were (liters/kg): Vc, 0.41; VB, 1.02; and Vss, 0.75. The mean (+/- SD) for alpha-half-life was 1.2 +/- 1.3 hours, and that for beta-half-life was 9.8 +/- 5.9 hours. Seven of the eight patients received a second identical dose orally 1 week later, and the absolute bioavailability was estimated to approximate 100%. Unless the oral route is not feasible and if immediate high peak blood levels are not necessary, oral metronidazole is the preferred route of administration of metronidazole for its radiosensitizing effects.

Effect of misonidazole therapy on human granulopoietic stem cells.

Misonidazole is a 2-nitroimidazole compound currently being assessed as a radiosensitizing agent. The effects of misonidazole on human bone marrow hematopoiesis were assayed by culture of committed granulocyte-macrophage progenitor cells (CFU-C). Three groups of patients with nonhematologic malignancies were selected for study. The first group of patients received a single, large dose of misonidazole; the second group received smaller, multiple doses of misonidazole; and the third group who did not receive any misonidazole served as irradiation controls. In 14 of 16 patients who received single or multiple doses of misonidazole, there was a significant decrease in the number of CFU-C present in the bone marrow after misonidazole therapy. In five patients who received irradiation only, there was no difference in the number of pre- and post-treatment bone marrow CFU-C. In misonidazole treated patients, extensive washing of post-treatment bone marrow samples failed to return CFU-C growth to control values. Suppression of CFU-C growth persisted for 3 weeks and returned to control values by 8 weeks. This reduction in the proliferative capacity of human bone marrow progenitor cells suggests that misonidazole may add to the myelotoxicity already associated with radiotherapy, systemic chemotherapy, or as combination of the two.

The role of automatic reinforcement in early language acquisition.

The vocal behavior of five children was recorded and analyzed during pre- and post-pairing conditions. Between these conditions there was a pairing condition where a target sound, word, or phrase was paired with an established form of reinforcement (e.g., tickling). In the first experiment all of the children emitted the targeted responses during the post-pairing condition. The results showed that the children acquired new vocal and verbal responses by pairing neutral stimuli with established forms of conditioned or unconditioned reinforcement. Perhaps the most significant aspect of these results was that new vocal responses were acquired by the children without the use of direct reinforcement, echoic training, or prompts. In the second experiment several parameters of the pairing procedure were examined. The results of the two experiments have implications for the analysis of native language acquisition, and for the development of language intervention procedures for individuals who fail to acquire language.

New side effect of the hypoxic cell sensitizer, misonidazole.

As part of a phase II study with the hypoxic cell radiosensitizer, misonidazole, we have encountered two cases of dermatitis. When all drugs were withdrawn and the patients were challenged with a small single dose of misonidazole, identical adverse reactions reappeared demonstrating a drug-related skin hypersensitivity.

Radiation and nitroimidazoles in supratentorial high grade gliomas: a second clinical trial.

As a continuation of a previous controlled trial using "high-dose" metronidazole as a specific sensitizer of hypoxic cells, we used a more efficient nitroimidazole derivative (misonidazole, MISO) in combination with higher doses of radiation in patients with supratentorial high-grade astrocytomas. Sixty-six patients were stratified according to functional level and histological grading, and randomly allocated within 2 weeks of operation of 1 of 3 therapeutic groups: 1, conventional radiation alone; 2, large fractions of radiation with high-dose metronidazole; and 3, radiation as in Group 2 but with equitoxic doses of MISO. We examined survival as the principal end-point of the study. Neither by increasing the dose of radiation over the previous study, nor by using a more efficient sensitizer, were we able to improve survival over the current conventional daily fractionated radiation.