GABAergic Interneurons at Supraspinal and Spinal Levels Differentially Modulate the Antinociceptive Effect of Nitrous Oxide in Fischer Rats

Background: The study hypothesizes that nitrous oxide (N2O) releases opioid peptide in the brain stem, which results in inhibition of [gamma]-aminobutyric acid-mediated (GABAergic) neurons that tonically inhibit the descending noradrenergic inhibitory neurons (DNIN), resulting in activation of DNIN. In the spinal cord, activation of DNIN leads to the release of norepinephrine, which inhibits nociceptive processing through direct activation of [alpha]2 adrenoceptor and indirect activation of GABAergic neurons through [alpha]1 adrenoceptor. Arising from this hypothesis, it follows that GABAergic neurons will modulate the antinociceptive effect of N2O in diametrically opposite directions at supraspinal and spinal levels. The authors have tested this tenet and further examined the effect of midazolam, a GABA-mimetic agent, on N2O-induced antinociceptive effect.

Methods: Adult male Fischer rats were administered muscimol (GABAA receptor agonist) intracerebroventricularly (icv), gabazine (GABAA receptor antagonist) intrathecally (intrathecal), or midazolam intraperitoneally (intraperitoneal). Fifteen minutes later, they were exposed to air or 75% N2O and were subjected to the plantar test after 30 min of gas exposure. In some animals administered with midazolam, gas exposure was continued for 90 min, and the brain and spinal cord were examined immunohistochemically.

Results: The N2O-induced antinociceptive effect, which was attenuated by icv muscimol, intrathecal gabazine, and intraperitoneal midazolam. Midazolam inhibited N2O-induced c-Fos expression (a marker of neuronal activation) in the pontine A7 and spinal cord.     

Human ovarian-carcinoma cell lines and companion xenografts: a disease-oriented approach to new platinum anticancer drug discovery

Summary A disease-oriented approach to the discovery of novel platinum anticancer drugs has been established through the setting up of parallel human ovarian-carcinoma cell lines and xenografts. The correlation between in vitro and in vivo antitumour activity was determined for four reference platinum agents (cisplatin, carboplatin, iproplatin and tetraplatin) in eight companion lines. Two methods of assessing antitumour effect were used in vitro (tritiated thymidine incorporation and sulforhodamine B staining) and three were applied in vivo [28-day treated/control (T/C) ratio, growth delay and specific growth delay]. In vitro, large differences in cytotoxicity across the cell lines were observed for each drug. This was also reflected in the xenografts for cisplatin and carboplatin and, to a lesser extent, for iproplatin. A correlation analysis of in vitro vs in vivo data revealed a high, statistically significant positive correlation for cisplatin and a strong positive correlation for carboplatin. However, for the two platinum(IV) drugs, the correlation was less good. In particular, tetraplatin was markedly less active in vivo (showing a general lack of activity against all of the tumour lines) than its in vitro potency against the cell lines predieted, resulting in poor correlation coefficients. These human tumour panels may be valuable for the elucidation of both cellular/molecular and corresponding in vivo pharmacological mechanisms of platinum drug resistance. Moreover, the HX/62 and SKOV-3 tumour lines, which exhibit a level of intrinsic resistance to the four reference agents both in vitro and in vivo (and which were derived from patients who had not received prior platinum therapy), represent particularly useful evaluation models for the discovery of novel broad-spectrum platinum drugs.This study was supported by grants to the Institute of Cancer Research from the Cancer Research Campaign and the Medical Research Council, the Johnson Matthey Technology Centre and Bristol Myers Squibb Oncology     

Initial experience with a radiology imaging network to newborn and intensive care units

A digital image network has been installed in the James Whitcomb Riley Hospital for Children on the Indiana University Medical Center to create a limited all digital imaging system. The system is composed of commercial components, Philips/AT&T CommView system, (Philips Medical Systems, Shelton, CT; AT&T Bell Laboratories, West Long Beach, NJ) and connects an existing Philips Computed Radiology (PCR) system to two remote workstations that reside in the intensive care unit and the newborn nursery. The purpose of the system is to display images obtained from the PCR system on the remote workstations for direct viewing by referring clinicians, and to reduce many of their visits to the radiology reading room three floors away. The design criteria includes the ability to centrally control all image management functions on the remote workstations to relieve the clinicians from any image management tasks except for recalling patient images. The principal components of the system are the Philips PCR system, the acquisition module (AM), and the PCR interface to the Data Management Module (DMM). Connected to the DMM are an Enhanced Graphics Display Workstation (EGDW), an optical disk drive, and a network gateway to an ethernet link. The ethernet network is the connection to the two Results Viewing Stations (RVS) and both RVSs are approximately 100 m from the gateway. The DMM acts as an image file server and an image archive device. The DMM manages the image data base and can load images to the EGDW and the two RVSs. The system has met the initial design specifications and can successfully capture images from the PCR and direct them to the RVSs.(ABSTRACT TRUNCATED AT 250 WORDS)     

Management of papillary carcinoma arising in thyroglossal-duct anlage.

Cysts of the thyroglossal duct are common congenital abnormalities. They present as asymptomatic midline cervical swellings. The risk of malignant change is low; only 103 cases have been reported in the world literature, 85% of which were papillary adenocarcinomas. The appropriate treatment for this condition remains controversial. The authors describe three patients who had papillary carcinoma contained within a thyroglossal-duct rest. All were treated by cyst resection and thyroid suppression, but without thyroidectomy and radioactive thyroid ablation. Postoperatively, all patients remained disease free, with no recurrence at follow-up ranging from 10 to 29 years. Isolated papillary carcinomas arising from primitive thyroid remnants, associated with a palpably normal thyroid gland at surgery and a negative thyroid scan, can be treated adequately by excising the thyroglossal mass.