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Biomedical subjects

S K Miller

Publications and source records attributed to S K Miller.

35 records · Page 2Linked to original sources
PubMed1992

Effect of the radioprotector WR2721 on irradiation-induced injury to ciliated cells of eustachian tube.

Our previous studies revealed that injury to the ciliated cells of the eustachian tube may be the primary cause of irradiation-induced serous otitis media. The purpose of this study was to investigate the effects of the radioprotector WR2721 on irradiation-induced injury to ciliated cells of the eustachian tube (ET) in chinchillas. Twelve chinchillas were divided into two groups: the control group and the experimental group, which was pretreated with a single intraperitoneal dose of the radioprotector S-2-[3-aminopropylamino]ethylphosphorothioic acid (WR2721) 400 mg/kg. The two groups were exposed to 30 Gy of 13-MeV electrons in a single fraction to the area of the bullae and nasopharynx. Ciliary dysfunction was tested and ciliated cells of the ET were examined by scanning and transmission electron microscopy. Pretreatment with WR2721 was found to protect ciliated cells of the ET from irradiation injury.

Amifostine↗
PubMed1992

Permeability of arachidonic acid metabolites through the round window membrane in chinchillas.

Our previous studies showed that samples of middle ear effusion contain high concentrations of arachidonic acid metabolites (AAMs); both prostaglandins (PGs) and leukotrienes (LTs). Since abnormal levels of AAMs in the perilymph seem to be associated with salicylate ototoxicity and the round window membrane (RWM) is the most likely route of entry from the middle ear to the inner ear, it would be important to know the permeability of AAMs through the RWM. Permeability of AAMs was determined by applying labeled and standard representatives AAMs on the RWM and counting radioactivity or measuring concentrations of AAMs in perilymph at different time intervals. Using chinchillas as experimental animals, samples of perilymph were obtained through a fenestration made at the helicotrema of the cochlea after 0.5, 1, 2, and 4, hours from placing tritiated or standard PGE2, 6-keto-PGF1 alpha, LTB4, LTC4 and 15-hydroxyeicosatetraenoic acid (HETE) over RWMs. Radioactivity in the perilymph was determined by a scintillation counter and concentrations of AAMs were measured by reverse phase high performance liquid chromatography (RP-HPLC) and radioimmunoassay. AAMs, which are twenty carbon fatty acids, were found to cross the RWM readily. Radioactivity and concentrations of AAMs in perilymph were detected in 30 minutes and peaked by one hour from the application of AAMs on the RWM. The results of this study suggest that AAMs such as PGs and LTs present in the middle ear fluid can cross the RWM readily and enter into the perilymphatic space of the cochlea. Sensorineural hearing loss observed in chronic otitis media could be mediated by PGs and LTs in the middle ear effusion crossing over to the inner ear through the RWM.

Adrenal Cortex Hormones↗
PubMed1992

Effect of exogenous arachidonic acid metabolites applied on round window membrane on hearing and their levels in the perilymph.

Our previous studies revealed that treatment with sodium salicylate or indomethacin caused hearing loss, a decrease in prostaglandin (PG) levels, and an increase in leukotriene (LT) levels of the arachidonic acid (AA) cascade in the perilymph. We suspected that decreased PG-levels and/or elevated LT-levels in the inner ear may be responsible for the salicylate ototoxicity. In order to test this hypothesis, effects of exogenous treatments with PGs, PG-analog, LTs, and other lipoxygenase products on hearing and levels of AA metabolites in the perilymph were studied in chinchillas. Cyclooxygenase products, PGI2, 6-keto-PGF1 alpha, Iloprost (PGI2 analog), PGE2, and LTB4, LTC4, and 15-hydroxyeicosatetraenoic acid (15-HETE) in the lipoxygenase products in the dose of 150 ng were applied on the round window membrane (RWM); cochlear function tested by auditory brainstem response (ABR) and samples of perilymph were collected at 0.5, 1, 2, and 4 hours after the application. Samples of perilymph were assayed for all spectra of AA metabolites by high performance liquid chromatography (HPLC) and radioimmunoassay (RIA). PG-treated animals developed minimal or no hearing loss. LT-treated animals exhibited hearing loss of 20 to 40 dB, peaking at one hour after the treatment. Elevated levels of arachidonic acid metabolites were measured in the perilymph of the ears treated with respective AA metabolites, with peak levels at one hour from the application. The findings of this study indicate that hearing loss can be induced by altered levels of PGs or LTs in the perilymph. This is another strong evidence that salicylate induced ototoxicity can be mediated by abnormal arachidonic acid metabolism in the inner ear.

Animals↗
PubMed1992

Effect of round window membrane application of salicylate and indomethacin on hearing and levels of arachidonic acid metabolites in perilymph.

Our previous studies revealed that systemic salicylate-induced ototoxicity is associated with altered levels of arachidonic acid metabolites (AAMs) in the perilymph. In order to eliminate the possibility of systemic toxic effects of salicylate when it is given parenterally, an animal model of salicylate-induced ototoxicity was developed by applying it on the round window membrane (RWM). Using chinchillas as experimental animals, sodium salicylate (150 micrograms) or another nonsteroidal anti-inflammatory drug (NSAID), indomethacin (20 micrograms) was applied on the RWM, cochlear function was determined by auditory brainstem response (ABR) and perilymph assayed for AAMs both prostaglandins (PGs) and leukotrienes (LTs) by high performance liquid chromatography (HPLC) and radioimmunoassay (RIA) at different time intervals. When salicylate or indomethacin was applied on the RWM, dose-dependent ABR threshold losses of 20 to 50 dB was observed in 1 to 2 hours associated with decreased concentrations of 6-keto-PGF1 alpha and elevated levels of LTs. The hearing loss recovered to normal threshold over a period of 8 hours. The control group showed no hearing loss or any change in PG or LT-levels in the prilymph. The results of this study suggest that the method of inducing ototoxicity by applying salicylate or indomethacin on the RWM seems to be a reliable method for avoiding systemic toxicity of the parenteral treatment method and that ototoxicity induced by salicylate or indomethacin may be mediated by decreased PGs and elevated LTs.

Animals↗
PubMed1991

Improvement of spectral resolution in shift-reagent-aided 23Na NMR spectroscopy in the isolated perfused rat heart system.

The level of intracellular sodium (Nai) is maintained at approximately 14 mM in healthy myocytes. When myocytes are damaged, Nai increases and therefore the level of Nai may be a means of evaluating myocardial cell integrity. A particularly useful method to monitor Nai levels is 23Na NMR spectroscopy. However, because of the isochronous nature of the extracellular sodium (Nao) and Nai NMR signals, paramagnetic lanthanide shift reagents (LSR), such as dysprosium triphosphate, Dy(PPP)7-(2), have been used to shift the Nao signal. This reveals the unshifted Nai signal and allows the NMR monitoring of Nai in isolated perfused hearts and other systems. A major shortcoming of this method (the "shift-only" method) is in the need to minimize the Nao signal by not submerging the perfused hearts in Na(+)-containing buffer. An equally undesirable alternative is the utilization of relatively high concentrations of LSR to shift a large Nao signal sufficiently to enable reasonable resolution and quantitation of Nai. We present here a method, the "shift-relaxation" method, which is a combination of using a mixture of Dy(PPP)7-(2), a shift reagent, and gadolinium triphosphate, Gd(PPP)7-(2), a relaxation agent, with data acquisition using an inversion-recovery (IR) pulse sequence. This combination allows differentiation between Nao and Nai by the difference in their respective T1 values in addition to the shift between them. With this technique we can selectively minimize the extracellular signal and therefore minimize the need for a large Dy-induced shift, as well as allow data acquisition on a heart submerged in Na(+)-containing perfusate. The resulting improved discrimination between Nai and Nao at relatively low levels of LSR should be helpful for ultimate in vivo applications and potential clinical applications, where a lower dose of LSR also means a decreased possibility of physiologically deleterious effects. Also included in this paper is a method for the quick determination of an accurate 180 degrees pulse which is required for the optimization of the IR method.

Animals↗
PubMed1990

Detection of intramyocardial hemorrhage using high-field proton (1H) nuclear magnetic resonance imaging.

Proton (1H) nuclear magnetic resonance (NMR) imaging has been used to define zones of myocardial infarction (MI), which appear as areas of relatively increased signal intensity (SI). However, zones of decreased SI have been observed within the areas of infarction and have been postulated to result from intramyocardial hemorrhage. To explore this phenomenon further, ex vivo spin-echo 1H NMR imaging at 1.5 Tesla was performed in 17 dogs after 24 hr (n = 9) and after 72 hr (n = 8) of coronary artery occlusion. In all dogs, a zone of increased SI (118 +/- 9% compared with normal myocardium) was observed in the distribution of the occluded coronary artery. In 12 of the 17 dogs, zones of decreased SI (92 +/- 8% compared with normal) were seen within or around the central zone of increased SI. Gross inspection and histological assessment of sliced myocardium usually disclosed hemorrhage in the regions of decreased SI. In three of the five dogs with no apparent zones of decreased SI on NMR, the infarct was small, and only minor hemorrhage was observed by gross inspection, whereas in the remaining two dogs no hemorrhage was seen. Myocardial flow in the hemorrhagic regions was significantly higher than in the necrotic core (59 +/- 29% vs. 31 +/- 24% compared with control, P less than 0.05). Image-derived calculation of T2 relaxation times in the different infarcted regions revealed a significant shortening of T2 in the infarcted hemorrhagic zones with decreased SI compared with the infarct zones with increased SI (49 +/- 8 msec vs. 66 +/- 8 msec, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Development of a delayed-type hypersensitivity granuloma model in the mouse for the study of chronic immune-mediated inflammatory disease.

A cutaneous model of delayed-type hypersensitivity granuloma (DTH GRA) was developed, using methylated bovine serum albumin (mBSA) which could be easily quantified and represented chronic cellular immune-mediated inflammation characteristic of rheumatoid arthritis (RA). Quantitative kinetics showed maximal DTH GRA "wet" tissue weights at d.5 post-induction, diminishing between d.15-22; DTH GRA "dry" tissue weights peaked between d.8-22. Histological evaluation revealed early extensive fibrin deposition, edema, mixed PMN/mononuclear leucocyte infiltration and angiogenesis (d.2-5), followed by increased macrophage recruitment, lymphocyte infiltration, angiogenesis and vasculitis (d.10-15). Fibrin resorption and replacement by fibrous tissue resulted in resolution by d.35. It is suggested that the DTH GRA reaction represents a relevant model for probing pathogenic mechanisms and potential therapeutics for RA.

Animals↗
PubMed1989

Adolescent smoking. A review of prevalence and prevention.

This review critically evaluates the extensive literature on the epidemiology and prevention of adolescent smoking. Trends in adolescent smoking attitudes and behavior as well as the immediate and long-term health consequences of adolescent smoking are discussed. The factors associated with adolescent smoking and several smoking interventions are analyzed. Suggestions are made for improving the evaluation of future programs designed to prevent adolescent smoking.

Adolescent↗
PubMed1989

What is the role of carotid arterial resection in the management of advanced cervical cancer?

From 1977 through 1988, 16 patients underwent carotid artery resection and reconstruction or simple ligation in the treatment of advanced cervical carcinomas. Three patients underwent carotid artery ligation, with postoperative transient ischemic attacks, which resolved, in one patient. In the remaining 13 patients, interposition saphenous vein grafts were used to reconstruct the resected carotid arteries. In one of these 13 patients, the previously unresected carotid artery ruptured and was treated by carotid artery resection with interposition vein grafting and coverage by a myocutaneous flap. There were two immediate postoperative strokes, with excellent neurologic recovery in one, and one late postoperative stroke (6 months). There was one postoperative death. Adjunctive intraoperative irradiation (1500 to 2000 rad) was employed in 15 patients to decrease the risk of recurrent disease. Since 1982, pectoralis major muscle flaps have been constructed in all patients to cover the vein grafts, with no subsequent carotid artery blowouts. Seven patients are free of cancer more than 1 year after surgery. In conclusion, carotid artery resection for the treatment of advanced cervical carcinomas may be accomplished with acceptable morbidity and mortality rates in carefully selected cases. Coverage of the vein graft by a myocutaneous flap appears to protect against carotid artery blowout. Intraoperative irradiation appears to decrease significantly the local recurrence rate of these aggressive tumors.

Aged↗
PubMed1987

The effects of ammonium sulfate and acid on horse and human serum butyrylcholinesterase (EC 3.1.1.8).

1. Results of laboratory experiments which compared horse and human serum butyrylcholinesterase (EC 3.1.1.8) with respect to their acid inactivation and ammonium sulfate protection show: 2. Horse serum butyrylcholinesterase is more resistant to inactivation at pH 3.0 than human serum butyrylcholinesterase. 3. The loss of activity at pH 3.0 for both horse and human butyrylcholinesterase does not follow first order kinetics. 4. Both human and horse serum butyrylcholinesterase are protected from pH 3.0 inactivation by ammonium sulfate concentrations up to 33% saturation (1.37 M).

Ammonium Sulfate↗
PubMed1986

The effects of cyclosporin A on leucocyte infiltration and procoagulant activity in the mouse delayed hypersensitivity response in vivo.

A model of delayed type hypersensitivity (DTH) to methylated bovine serum albumin was established and characterised in the mouse pleural cavity. Fluid exudate formation was delayed, peaking around 24 h and diminishing by 48-72 h. Exudate leucocyte accumulation was also delayed, rising by 24 h and reaching maximal levels between 24-72 h. Significant PMN leucocyte infiltration was observed early on, although macrophages dominated the reaction from 24 h onwards. Small numbers of lymphoid cells were also observed. Treatment with cyclosporin A (CsA) at 100 mg/kg p.o. around the time of antigen challenge significantly reduced fluid exudate volume but consistently failed to reduce either leucocyte infiltration or the PMN: mononuclear cell ratio throughout the reaction. CsA treatment enhanced DTH exudate leucocyte procoagulant activity (PCA) although leucocyte morphology remained unaltered. The development of carrageenan edema in the hind paws of mice was unaffected by CsA treatment (50-200 mg/kg p.o.). These results suggest that (1) CsA selectively suppresses DTH vascular permeability responses without affecting leucocyte accumulation and (2) CsA does not affect the lymphokine-mediated induction of leucocyte PCA associated with DTH reactions in vivo.

Animals↗
PubMedDate not supplied

Implementing TQM.

Total quality management (TQM) is an organized, systematic approach to problem solving and continuous improvement. American corporations have found that TQM is an excellent way to improve competitiveness, lower operating costs, and improve productivity. Increasing numbers of laboratories are investigating the benefits of TQM. For this month's column, we asked our respondents: What steps has your laboratory taken to implement TQM?

Attitude of Health Personnel↗