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Biomedical subjects

J G Collins

Publications and source records attributed to J G Collins.

139 records · Page 8Linked to original sources

Effects of halothane on spinal neuronal responses to graded noxious heat stimulation in the cat.

This study was undertaken to examine the dose-response effects of clinical concentrations of halothane on activity of wide-dynamic-range (WDR) neurons in the dorsal horn of the spinal cord of the decerebrate, spinal cord-transected cat. All cells (n = 40) responded maximally to high-intensity (greater than 45 C) noxious heat stimulation. Following administration of halothane, 0.5, 1.0, and 1.5 per cent, the mean spontaneous discharge frequency was significantly decreased (P < 0.01) by 44, 74, and 87 per cent, respectively. The mean evoked discharge frequencies were also significantly decreased at all temperatures (46, 48.5 51 C) by all concentrations of halothane. The slope of the regression line relating heat intensity and evoked neuronal discharge frequency was significantly decreased (P < 0.01) with both 1.0 and 1.5 per cent halothane by 46 and 75 per cent, respectively. Since the spinal cord was transected, these results indicate that these effects were the result of a direct action at the level of the spinal cord. The neuronal activity that was suppressed was evoked by stimuli that were exclusively noxious. This substantiates the ability of halothane to modify the transmission of noxious information at the spinal cord level, and thus explains a mechanism by which halothane may induce analgesia.

Animals↗

Halothane-induced changes in neuronal activity of cells of the nucleus reticularis gigantocellularis of the cat.

The ability of 0.5% and 1.0% halothane to suppress neuronal activity of cells in the nucleus reticularis gigantocellularis (NRGC) was studied in decerebrate cats. These drug effects were examined in order to substantiate further the potential involvement of the NRGC in the modulation of transmission of pain information. Only cells of the NRGC, which were excited exclusively by electrical stimulation of A-delta fibers in the superficial radial nerve, were studied. Both concentrations of halothane caused a significant, dose-dependent reduction of spontaneous and evoked activity of all cells studied. These findings correlate well with previous reports of other anesthetics suppressing NRGC activity. In light of the selective depression by anesthetics and narcotic analgesics of spinal cord dorsal horn cells associated with noxious stimuli, these findings, when combined with anatomic, physiologic, and behavioral studies of NRGC, provide further evidence of the involvement of NRGC in the signaling of noxious stimuli and the analgesic effects of halothane exerted at this site.

Animals↗

Methotrexate-induced sudden fatal pulmonary reaction.

A teenage girl in bone marrow remission with acute lymphocytic leukemia died suddenly from pulmonary edema. She had taken her first oral dose of methotrexate and cyclophosphamide 10 hours previously when she was feeling well and was asymptomatic. One week previously she had received the last of four intrathecal injections of methotrexate. Autopsy showed marked pulmonary edema as well as chronic lung changes, as previously described in patients with methotrexate pneumonitis. There is usually at least a 12-day interval from the onset of administration of methotrexate to the onset of the lung toxicity. The authors suggest the patient was sensitized by the intrathecal methotrexate and then reacted with angioneurotic edema of the lung when given the first oral dose of methotrexate. Careful examination for infectious agents, including electron microscopy, was negative.

Adolescent↗

Aldose reductase and sorbitol dehydrogenase distribution in rat kidney.

The sorbitol pathway catalyzes the conversion of glucose to fructose via the intermediate sorbitol. It consists of aldose reductase (AR) and sorbitol dehydrogenase (SDH). In adult (44 day) kidney zones, AR was highest in the outer medulla. In substructures AR was highest in distal convoluted tubule. The AR was greatest in newborn and 8-day zones of developing rat kidney. Acute alloxan diabetes was associated with decreased AR in small arteries, but not glomeruli. The SDH was lowest in outer medulla. It was most active in glomeruli and distal convoluted tubules. The diabetic state leads to no change of SDH in arteries but an increase in glomeruli. SDH increased with development. This study demonstrates AR and SDH in substructures of the kidney. The pathway is present in developing kidney. In diabetes the enzymatic changes would tend to decrease accumulation of sorbitol.

Alcohol Oxidoreductases↗

Aldose reductase and sorbitol dehydrogenase distribution in substructures of normal and diabetic rat lens.

Aldose reductase (AR) and sorbitol dehydrogenase (SDH) make up the sorbitol pathway, which has been implicated in the pathogenesis of sugar cataracts. The levels of the two enzymes were determined with quantitative histochemical techniques in the epithelium, cortex, and nucleus of normal and diabetic rat lenses. The ratio of activity of AR to SDH was found to be nearly 50 to 1 in all substructures. This would strongly favor sorbitol accumulation and subsequent cataract formation.

Alcohol Oxidoreductases↗

Synthesis, cytotoxicity, cell uptake and DNA interstrand cross-linking of 4,4'-dipyrazolylmethane-linked multinuclear platinum anti-cancer complexes.

Two cationic multinuclear platinum complexes linked with the 4,4'-dipyrazolylmethane (dpzm) ligand, trans-[[Pt(NH3)2Cl]2-mu-dpzm]Cl2 (di-Pt) and trans-[trans-[Pt(NH3)2Cl]2[trans-[Pt(NH3)2(mu-dpzm)2]]]Cl4 (tri-Pt), have been synthesized. Both complexes show activity in the murine leukaemia cell line L1210 (IC50 = 3.8 and 2.5 microm, respectively) and the cisplatin-resistant subline L1210/DDP (8.8 and 3.6 microM), and in the human ovarian carcinoma 2008 (2.5 and 17.8 microM) and its cisplatin-resistant subline C13*5 (20.9 and 37.7 microM). Both complexes show high levels of uptake into 2008 cells, when administered at 100 microM, but significantly reduced uptake in the cisplatin-resistant cell line C13*5 (di-Pt, 66% decrease; tri-Pt, 42%; cisplatin, 86%). Both complexes form very high levels of DNA interstrand cross-links in vitro, with 50% interstrand cross-linking observed at far lower concentrations (di-Pt, 12 nM; tri-Pt, 22 nM) than cisplatin (450 nM). It is proposed that the higher extent of interstrand cross-linking may be due to the rigid nature of the dpzm linking ligand, which prevents the complexes from forming short-range intrastrand adducts, like the GpG adduct formed by cisplatin. The results of this study indicate the importance of the flexibility of the linking ligand for the cytotoxicity of di- and trinuclear platinum anti-cancer complexes.

Animals↗

Toxicity of new spinal agents.

The clinical success of perispinal administration of opiates for pain relief has demonstrated the power of manipulating the neurochemistry of the spinal cord. This article briefly discussed reasons for increased interest in new spinal agents and some of the issues associated with determining their clinical safety.

Analgesics, Opioid↗

The clinical, microbial, and host response characteristics of the failing implant.

The goal of this study was to provide new data regarding levels of inflammatory and growth factor mediators and bacterial pathogens associated with failing implants, as compared to healthy implants. Twenty-one patients with failing implant sites (group 1) and 8 patients with only healthy implants (group 2) were included. Fifteen of the 21 failing implant patients (group 1) also presented with at least one stable nondiseased implant. Plaque samples were examined, using DNA oligonucleotide probes for 40 different microbes. Gingival crevicular fluid samples were collected for the analyses of catabolic bone resorbing agonists prostaglandin E2 (PGE2), interleukin-1 beta (IL-1 beta) and IL-6 and anabolic bone-forming growth factors transforming growth factor beta (TGF-beta) and platelet-derived growth factor (PDGF). Although positive trends were noted, there were no significant differences in any of the microbial, inflammatory, or growth factors mediators comparing failing to stable implants in group 1. This study found greater detection frequencies of P. nigrescens, P. micros, F. nucleatum ss vincentii, and F. nucleatum ss nucleatum, as well as significant elevations in GCF levels of PGE2, IL-1 beta, and PDGF in mouths with failing implant sites as compared to mouths with healthy control implants. Risk appears to be primarily at a patient level and secondarily at a site or implant level from a clinical, microbial (P. micros and P. nigrescens), and biochemical (PGE2 and IL-1 beta) perspective. Furthermore, the counts of P. nigrescens and P. micros were found to correlate with concentrations of PGE2 at a site level.

Adult↗