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Biomedical subjects

G L Hall

Publications and source records attributed to G L Hall.

35 records · Page 2Linked to original sources

beta-Interferon regulates the immunomodulatory activity of neonatal rodent microglia.

beta-interferon (beta-IFN) has both pro and anti-inflammatory properties, the balance of which leads to some suppression of disease activity in multiple sclerosis patients. Here, we examine the immunomodulation of neonatal rodent microglia, the principal CNS accessory cell, by beta-IFN and consider the interaction of beta-IFN and gamma-interferon (gamma-IFN). beta-IFN and gamma-IFN inhibit microglial proliferation. beta-IFN antagonises both gamma-IFN-induced upregulation of class II expression and the ability of gamma-IFN primed cells to mount a respiratory burst. In contrast, beta-IFN upregulates microglial Fc receptor expression and augments tumour necrosis factor alpha secretion from suboptimally stimulated microglia.

Adjuvants, Immunologic↗

Beta-interferon and multiple sclerosis.

Interferon-beta (IFN-beta) is the first therapeutic intervention shown to alter the natural history of multiple sclerosis (MS), a relapsing then progressive inflammatory degenerative disease of the CNS. Since publication of the first randomized placebo-controlled trial of IFN-beta, and subsequent acquisition of US and European product licences for use in relapsing-remitting MS, the hopes and expectations of patients have been elevated greatly only to be dampened as more critical analysis of the trial results, in conjunction with the cost of treatment, led to marked limitations on prescription in several countries. IFN-beta is not a cure. Here we review what is known about the mechanisms of action of IFN-beta in demyelinating disease, and propose a possible model of action of IFN-beta in the treatment of MS.

Humans↗

Continuous physiological monitoring: an integrated system for use in neonatal intensive care.

A general purpose, multi-channel digital data acquisition and analysis system (Amlab, Associative Measurements, Sydney) configured to collect and process physiological signals including electroencephalograph and blood pressure is described. Its advantages over analog and single-purpose instrumentation are discussed as is its potential, by the addition of transducers, to replace single-purpose instruments.

Electroencephalography↗

Intrathecal narcotics for obstetric analgesia in a community hospital.

OBJECTIVE: Our objective was to establish whether intrathecal narcotics for obstetric analgesia offer an adequate and cost-effective alternative to epidural analgesia with minimal side effects in our small, semirural community hospital with limited anesthesia coverage. STUDY DESIGN: Low-risk patients at > or = 35 gestational weeks in active labor were offered intrathecal narcotics. A retroactive chart review of every patient receiving an intrathecal injection was compared with a chart review of the next consecutive low-risk patient who did not receive an intrathecal narcotic. Age, parity, and status of labor at the time of application were noted, as was the subsequent rate of labor and the type of delivery. Side effects such as changes in vital signs, headache, vomiting, pruritus, urinary retention, and/or respiratory depression were noted. All study patients received fentanyl, 25 to 35 micrograms, plus 0.25 to 0.3 mg of preservative-free morphine combined with 6 to 8 mg of lidocaine. Within 15 minutes of delivery intravenous nalbuphine (Nubain), 5 mg, and oral naltrexone, 12.5 mg, were administered. Pain relief was recorded as excellent, satisfactory, or unsatisfactory (requiring additional medication). RESULTS: During the 30-month review period, 90 patients (3% of total deliveries) received intrathecal narcotics. There were three sets of twins, for a total of 93 live births. Ten patients (11%) required primary cesarean section, and of the 83 vaginal births 35 (38%) were spontaneous, two (2%) required forceps deliveries, and 46 (49%) were delivered by vacuum extraction, which was significantly higher than the 28 (31%) for controls. The rate of labor was not affected, with both groups requiring a similar rate of oxytocin (Pitocin) augmentation. Significantly more patients receiving intrathecal narcotics experienced pruritus and urinary retention compared with controls. There was no incidence of respiratory depression. Eighty-four (93%) of the 90 patients reported excellent pain relief, five patients had satisfactory relief lasting 2.5 to 6 hours, and one was unsatisfactory. CONCLUSIONS: In our hospital with limited anesthesia services intrathecal narcotics offer excellent labor pain relief with manageable side effects and without adverse obstetric outcome.

Adolescent↗

Predictive value of liver slices for metabolism and toxicity in vivo: use of acetaminophen as a model hepatotoxicant.

To establish the usefulness of liver slices as predictive models for in vivo metabolism and toxicity, acetaminophen was used as a model hepatotoxicant for which the role of metabolism in toxicity is well documented. Acetaminophen was incubated with liver slices prepared from the rat and hamster since these species differ in susceptibility to acetaminophen-induced hepatotoxicity. Formation of acetaminophen metabolites (sulfate, glucuronide, and glutathione conjugate), slice glutathione levels, and slice histopathology were assessed. Acetaminophen (0.5, 1, and 2 mM) induced a dose-dependent depletion of glutathione in hamster slices (sensitive species) but not rat slices (insensitive species). Formation of the acetaminophen toxic metabolite, as measured by glutathione conjugate formation, was much lower in rat slices compared with hamster slices. Rat slices also showed greater activity of the nontoxic sulfation and glucuronidation pathways. These data predicted an 11-fold greater susceptibility to toxicity in the hamster based on the proportion of the dose metabolized to the reactive species. In vivo data, using hepatic glutathione depletion as an indicator of toxic metabolite formation, would predict a similar difference (13.3-fold) between the hamster and the rat. To ascertain if the characteristic centrilobular lesion induced by acetaminophen in vivo could be reproduced in vitro, liver slice histopathology was assessed 6 and 12 hr after a 2-hr treatment with acetaminophen (2 mM). Discrete damage to the centrilobular regions of the liver were noted in hamster but not rat slices. Overall, based on metabolite formation, glutathione depletion, and slice histopathology, the liver slices were excellent predictors of acetaminophen hepatotoxicity in vivo.

Acetaminophen↗

Species differences in membrane susceptibility to lipid peroxidation.

The susceptibility of liver microsomes to lipid peroxidation was evaluated in seven species: rat, rabbit, trout, mouse, pig, cow, and horse. Lipid peroxidation was measured as thiobarbituric acid reactive substances formed in the presence of either FeCl3-ADP/ascorbate or FeCl2/H2O2 initiating systems. For rat, rabbit, and trout microsomes, the order of susceptibility to peroxidation was rat greater than rabbit much greater than trout. The lack of peroxidation in trout microsomes could be explained by high microsomal vitamin E levels. Membrane fatty acid levels differed between species. Docosahexaenoic acid predominated in the trout, arachidonic acid in the rat, and linoleic acid in the rabbit. The contribution of individual fatty acids to lipid peroxidation reflected the degree of unsaturation with docosahexaenoic greater than arachidonic much much greater than linoleic. For all species except trout, the predicted susceptibility to peroxidation, based on the response of individual fatty acids, agreed well with directly measured microsomal peroxidation. With the exception of the trout, vitamin E content ranged from 0.083-0.311 nmol/mg microsomal protein between species, and low levels did not influence susceptibility to peroxidation. Trout microsomes peroxidized only after vitamin E depletion by prolonged incubation. The data indicate that below a vitamin E threshold, species differences in membrane susceptibility to peroxidation can be reasonably predicted based only on content of individual peroxidizable fatty acids.

Animals↗

Interleukin 1 beta is localized in the cytoplasmic ground substance but is largely absent from the Golgi apparatus and plasma membranes of stimulated human monocytes.

The subcellular location of IL-1 beta was determined using a postsectioning immunoelectron microscopic method on ultrathin frozen sections of human monocytes stimulated with LPS. This methodology permits access of antibody probes to all sectioned intracellular compartments, and their visualization at high resolution. Staining was performed with a rabbit antibody that specifically recognized amino acids 197-215 in the 33-kD IL-1 beta precursor molecule, followed by affinity-purified goat anti-rabbit IgG conjugated to 10 nm colloidal gold particles. Approximately 90% of the IL-1 beta antigens were localized in the ground substance of the cytoplasm at 4 or 20 h after activation, when both intracellular and extracellular accumulation of IL-1 beta was well underway. No significant IL-1 beta staining was observed on the outer cell membrane, nor within the lumens of the endoplasmic reticulum (ER), the Golgi apparatus, or secretory vesicles. In contrast, lysozyme was localized in the ER and dense secretory granules using these methods. Our results suggest that IL-1 beta is not anchored on the plasma membrane, and that its secretion occurs by a novel mechanism that does not use a secretory leader sequence, nor the classical secretory pathway involving the ER and Golgi apparatus.

Antigens↗

Education in early detection of oral squamous cell carcinoma: a community outreach program.

An educational program consisting of a slide presentation and lecture, a demonstration of how to examine the oral soft tissues, and handout materials was presented to practitioners, hygienists, assistants, and other personnel in their office. A pretest, a critique by the participants, and a follow-up questionnaire were used to determine the value of the program.

Audiovisual Aids↗

Use of an inclined footrest for panoramic dental radiography.

An inclined footrest was evaluated as a positioning aid for dental panoramic radiography. Experimental and control groups of students were examined by a conventional panoramic technique, with and without the addition of an inclined footrest. All radiographs obtained were evaluated for six parameters in a single-blind fashion by three dentists. Results indicated that the inclined footrest reduced spinal-shadow artifacts and improved over-all image quality.

Adult↗

Chromatographic determination of dicofol and metabolites in egg yolks.

Egg yolk was spiked with p,p'-dicofol (p,p'-DCF) (0.1-2.0 micrograms/gm), p,p'-dichlorobenzophenone (p,p'-DCBP) (0.1-2.0 micrograms/gm), and 1,1-bis(4-chlorophenyl)-2,2-dichloroethylene (p,p'-DDE) (0.05-1.0 micrograms/gm). The fortified egg yolk (2-5 g) was mixed with acetonitrile to extract non-fat organic materials. After removal of acetonitrile, the spiked chemicals were separated with a column chromatograph packed with acid alumina. Recovery efficiencies for p,p'-DCBP and p,p'-DDE were determined by gas chromatography, and for p,p'-dicofol by high performance liquid chromatography. The recovery efficiencies for p,p'-dicofol, p,p'-DCBP and p,p'-DDE were 77.2-93.8%, 84.1-101.1%, and 88.5-96.0%, respectively.

Animals↗

Gas chromatographic method for determination of chlorpyrifos and its metabolite 3,5,6-trichloro-2-pyridinol (TCP) in dates.

A method is described for the determination of the insecticide chlorpyrifos and its metabolite TCP in green, unprocessed, and processed dates with the seeds incorporated. After extraction, chloropyrifos is cleaned up using Florisil and analyzed using a gas chromatography (GC) equipped with a nitrogen/phosphorus detector. TCP is derivatized using bis-(trimethylsilyl)-acetamide (BSA) to form the TCP-derivative and analyzed by a gas chromatograph equipped with a Hall electrolytic conductivity detector. Recoveries of chlorpyrifos from all fortified dates (0.05 and 0.1 ppm) ranged from 86 to 110% with an average of 94.5%. Recoveries of TCP from all fortified dates (0.1 and 0.2 ppm) ranged from 79 to 99% with an average of 86%. Limits of detection for chlorpyrifos and TCP in green, unprocessed, and processed dates were 0.02 and 0.05 ppm, respectively.

Chlorpyrifos↗