Search PubMed⌕ Search

Biomedical subjects

S Murray

Publications and source records attributed to S Murray.

At least 181 records · Page 10Linked to original sources

Detection and measurement of MeIQx in human urine after ingestion of a cooked meat meal.

A gas chromatographic-mass spectrometric assay has been developed for the measurement of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) in urine. The method employs capillary column gas chromatography, electron capture negative-ion chemical ionization mass spectrometry, a stable isotope-labelled analogue of MeIQx as internal standard and has a limit of detection of 5 pg MeIQx/ml urine. Six subjects consumed a fried beef meal and urine was collected before and after this event. While no MeIQx could be detected in urine collections made prior to meat consumption, the 12-h urine collections of all six subjects made after the meal contained the amine. When the amounts of MeIQx measured in the urine collections were compared to the quantities of amine ingested in the fried beef, it was found that 1.8-4.9% of the oral dose was excreted unchanged in urine. Metabolic studies in animals lead us to believe that MeIQx in the diet is efficiently absorbed and extensively biotransformed.

Gas Chromatography-Mass Spectrometry↗

Action spectrum of vascular specific injury using pulsed irradiation.

It has been clearly demonstrated that cutaneous blood vessels will be selectively damaged by a laser whose wavelength matches one of the three absorption spectral peaks of the chromophore, oxyhemoglobin, for example, 577 nm. A restriction in the application of this wavelength for the treatment of benign cutaneous vascular tumors, such as portwine stains, has been the penetration depth of 577 nm irradiation of approximately 0.5 mm from the dermal epidermal junction (DEJ). This study was undertaken to establish whether it was possible to increase the penetration depth from 0.5 mm by changing the wavelength to beyond 577 nm in albino pig skin. Results from this study confirm that penetration depth increases from 0.5 to 1.2 mm by changing the wavelength from 577 to 585 nm at 4 J/cm2, while maintaining the same degree of vascular selectivity as that previously described after 577 nm irradiation. This occurred in spite of a mismatch in the wavelength between 585 nm and the oxyhemoglobin absorption peak of 577 nm. Unlike 585 nm irradiation and in contrast with theoretical predictions, 590 nm laser light did not penetrate as deeply as 585 nm. Not only was there a reduction in the penetration depth of the laser beam from 1.2 mm at 585 nm to 0.8 mm at 590 nm, at 4 J/cm2, but there was also a decrease in vascular selectivity in albino pig skin exposed to 590 nm irradiation.

Animals↗

Effect of wavelength on cutaneous pigment using pulsed irradiation.

Several reports have been published over the last two decades describing the successful removal of benign cutaneous pigmented lesions such as lentigines, café au lait macules' nevi, nevus of Ota, and lentigo maligna by a variety of lasers such as the excimer (351 nm), argon (488,514 nm), ruby (694 nm), Nd:YAG (1060 nm), and CO2 (10,600 nm). Laser treatment has been applied to lesions with a range of pigment depths from superficial lentigines in the epidermis to the nevus of Ota in the reticular dermis. Widely divergent laser parameters of wavelength, pulse duration, energy density, and spotsizes have been used, but the laser parameters used to treat this range of lesions have been arbitrary, with little effort focused on defining optimal laser parameters for removal of each type. In this study, miniature black pig skin was exposed to five wavelengths (504, 590, 694, 720, and 750 nm) covering the absorption spectrum of melanin. At each wavelength, a range of energy densities was examined. Skin biopsies taken from laser-exposed sites were examined histologically in an attempt to establish whether optimal laser parameters exist for destroying pigment cells in skin. Of the five wavelengths examined, 504 nm produced the most pigment specific injury; this specificity being maintained even at the highest energy density of 7.0 J/cm2. Thus, for the destruction of melanin-containing cells in the epidermal compartment, 504 nm wavelength appears optimal.

Animals↗

The chief scientist reports ... hyperbaric oxygen for multiple sclerosis patients.

An 18-month uncontrolled study of the effects of hyperbaric oxygen therapy was conducted in 97 individuals with multiple sclerosis. Two-thirds of the patients were classified as progressive and one-third as stable. Assessment was based mainly on three aspects of activities of daily living: bladder function, mobility and communication. Bladder function showed a tendency to improve over the 12 month period of treatment but there was no evidence that treatment led to an improvement of mobility or communication. There are several reports of immediate improvement in bladder function, objectively and subjectively determined, in response to hyperbaric oxygen. In one study similar to that reported here, lack of deterioration in bladder function amongst progressive patients over two years, was related to continued hyperbaric oxygen treatment.

Activities of Daily Living↗

The expression of high molecular weight kininogen on human umbilical vein endothelial cells.

High molecular weight kininogen (HMWK) functions as a cofactor for activation of plasma serine zymogens and as an inhibitor of tissue cysteine proteases. Cell surfaces to which HMWK binds may provide sites for regulation of these systems. Localization of these HMWK-dependent processes at sites of vascular injury may depend on its binding to specific receptors on endothelial cells. In culture, passaged human umbilical vein endothelial cells (HUVEC) bind anti-HMWK antibody to the cell surface and contain 171 +/- 75 ng of HMWK/10(8) cells. [35S]Methionine-labeled HUVEC in culture synthesize a 120-kDa protein immunoisolated using an anti-kininogen antibody, and a 3500-nucleotide message for human HMWK was detected by Northern blot in RNA extracted from HUVEC. HUVEC also express unoccupied binding sites for HMWK on their surface. 125I-HMWK specifically binds to HUVEC in a reaction requiring Zn2+. 125I-HMWK binding to HUVEC is saturable at 4 degrees C but not at 23 degrees C. 125I-HMWK binds to HUVEC with equal affinity as unlabeled HMWK. Kallikrein, factor XII, fibrinogen, fibronectin, and thrombin do not inhibit 125I-HMWK binding to HUVEC. 125I-HMWK-HUVEC binding remains fully reversible at 60 min following the addition of a 50-fold molar excess HMWK. HUVEC express 9.3 +/- 2.0 X 10(5) (mean +/- S.E.) HMWK binding sites/cell (Kd = 52 +/- 13 nM). Both added and cell-bound 125I-HMWK migrate at 120 kDa on sodium dodecyl sulfate gel electrophoresis, suggesting that the protein remains uncleaved upon binding to the HUVEC surface. These studies indicate that HUVEC synthesize HMWK and the HUVEC surface has a site for its expression. By synthesizing and localizing HMWK to the cell surface, endothelial cells may contribute to the activation of plasma's contact serine zymogens and regulation of tissue cysteine proteases.

Blotting, Northern↗

An assay for 2-amino-3,8-dimethylimidazo[4,5-f]-quinoxaline and 2-amino-3,4,8-trimethylimidazo-[4,5-f]quinoxaline in fried beef using capillary column gas chromatography electron capture negative ion chemical ionization mass spectrometry.

A gas chromatographic/mass spectrometric assay has been developed for the simultaneous measurement of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) in fried beef. The method employs capillary column gas chromatography, electron capture negative ion chemical ionization mass spectrometry and a stable isotope labelled analogue of MeIQx as common internal standard. Two patties of lean minced beef which had been cooked separately were analysed and found to contain both compounds (patty 1:2.4 ng MeIQx g-1 meat, 1.2 ng DiMeIQx g-1 meat; patty 2:1.3 ng MeIQx g-1 meat, 0.5 ng DiMeIQx g-1 meat). Neither compound was present in the meat prior to cooking.

Animals↗

Effect of pulse duration on selective ablation of atherosclerotic plaque by 480- to 490-nanometer laser radiation.

The effect of varying pulse duration on selective ablation of human arterial plaque was evaluated by measuring ablation thresholds and ablation efficiencies on fresh human fibrofatty plaque, calcified plaque, normal intima, deep media, and adventitia using 480- to 490-nm laser radiation at 1, 8, and 50-microseconds pulse durations. For all tissues examined, the ablation threshold energy increased with increasing pulse duration, but the threshold for normal tissue ablation was approximately twice that of plaque at all pulse durations. Ablation efficiency was studied at a fluence that was twice the ablation threshold for plaque. For those fluences, normal intima had detectable ablation only at 50 microseconds. The ablation efficiency of fibrofatty plaque was minimally reduced with prolongation of pulse duration; however, there was a substantial decrease in the ablation efficiency of calcified plaque when the pulse duration was lengthened from 8 to 50 microseconds. These data show significant selective ablation of fibrofatty and calcified plaque at 1, 8, and 50 microseconds and suggest that the optimal pulse width for selective ablation of all plaque in the 480- to 490-waveband is less than 50 microseconds.

Aortic Diseases↗

Measurement of MeIQx and DiMeIQx in fried beef by capillary column gas chromatography electron capture negative ion chemical ionisation mass spectrometry.

A gas chromatographic-mass spectrometric assay has been developed for the simultaneous measurement of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) in fried beef. The method employs capillary column gas chromatography, electron capture negative ion chemical ionisation mass spectrometry and a stable isotope labelled analogue of MeIQx (the synthesis of which is described) as common internal standard. Two patties of lean minced beef which had been cooked separately were analysed and found to contain both compounds (patty 1-2.4 ng MeIQx/g meat, 1.2 ng DiMeIQx/g meat; patty 2-1.3 ng MeIQx/g meat, 0.5 ng DiMeIQx/g meat). Neither compound was present in the meat prior to cooking.

Animals↗

Enhancement by cyclosporin A of daunorubicin efficacy in Ehrlich ascites carcinoma and murine hepatoma 129.

Cyclosporin A abrogates pleiotropic drug resistance in certain experimental tumors. Its impact on drug-sensitive tumors has not been investigated. Our studies show that in drug-sensitive Ehrlich ascites carcinoma and hepatoma 129 cyclosporin A enhances daunorubicin inhibition of DNA synthesis in vitro and prolongs survival of host mice in vivo. Of particular interest is that cyclosporin A converts ineffective daunorubicin regimens into those which result in prolongation of host mice survival. Other agents known to reverse pleiotropic drug resistance are reported to exert their effects by increasing intracellular drug accumulation. In contrast, our studies of drug transport in drug-sensitive Ehrlich ascites carcinoma and hepatoma 129 show that cyclosporin A causes minimal enhancement of [3H]daunorubicin uptake without inhibition of [3H]daunorubicin efflux in both the presence and absence of interrupted active daunorubicin efflux. This suggests that the mechanism of action of daunorubicin enhancement by cyclosporin A in drug-sensitive tumors is not simply the result of increased intracellular daunorubicin accumulation. In vivo dosages of cyclosporin A in the current study are comparable to those which can be used with reasonable safety in humans. We conclude that cyclosporin A may be useful in the potentiation of anthracycline antibiotic therapy directed against drug-sensitive as well as drug-resistant tumors.

Animals↗

Metabolism of the mutagen MeIQx in vivo: metabolite screening by liquid chromatography-thermospray mass spectrometry.

2-Amino-3,8-dimethylimidazo(4,5-f)quinoxaline (MeIQx) is a potent mutagen found in cooked food. MeIQx and its isotopically labelled (13C, 15N2 and 14C) analogues were synthesised and used for metabolic studies in vivo. An equimolar mixture of MeIQx and its 13C, 15N2 stable isotope labelled analogue (containing tracer amounts of 14C-MeIQx) was given intraperitoneally to mice. Some 67% of the radioactivity was eliminated in urine and faeces within 24h. Four radiolabelled species were observed when urine was analysed by HPLC, corresponding to unchanged MeIQx and three more polar metabolites. Urine was analysed directly by HPLC-thermospray mass spectrometry. Four signals were observed containing the characteristic 1:1 isotopic doublet, corresponding to unchanged MeIQx, an MeIQx glucuronide, and two uncharacterized metabolites.

Animals↗

Significant bacteremia associated with replacement of intrauterine contraceptive device.

Blood culture samples were taken from 23 women at different stages when an intrauterine contraceptive device was replaced. Transient bacteremia resulting from vaginal organisms was found in 13% of women 4 to 6 minutes after insertion of the new device. Previous reports have failed to demonstrate bacteremia associated with either first insertion or removal of intrauterine contraceptive device. Our results show that replacement of an intrauterine contraceptive device, a more traumatic procedure, causes significant bacteremia, and chemoprophylaxis should be given to patients in the groups at risk.

Female↗

The pulsed dye laser for fragmenting urinary calculi.

The properties of a laser which effect stone fragmentation have been studied. The pulsed dye laser emitting at 504 nm. in one microsecond duration pulses appears to be the optimum out of a wide range of parameters tested. The laser is coupled to a 200 micron core fiber; this complete with its cladding has a total diameter of only 0.25 mm. Most calculi are fragmented by a series of pulses of up to 30 mJ. The system is used by firing bursts of pulses with the fiber actually in contact with the stone. The result is a very controlled fragmentation which is particularly suited to use in the confines of the ureter. This modality of treatment utilises less energy than ultrasound or electrohydraulic probes to fragment a stone and the very fine, flexible fiber represents a considerable miniaturization.

Calcium Oxalate↗

An assessment of the pulsed dye laser for fragmenting calculi in the pig ureter.

The pulsed dye laser was used to fragment ureteric calculi in 10 pig ureters, compared to electrohydraulic disintegration in six pig ureters. The stones were impacted in the proximal ureter and approached by rigid ureteroscopy. Four ureters did not have stones impacted but had ureteroscopes passed. The stones were fragmented and the particles left to pass spontaneously. The degree of inflammatory reaction was graded at the site of fragmentation as well as in the middle and lower ureter. The degree of inflammation seen at the site of fragmentation was significantly less in the laser group than in the electrohydraulic group (p = 0.0027). It was noted that the degree of inflammation seen in the lower ureter was significantly greater than that seen at the site of fragmentation (p = 0.01), and that this grade of inflammation correlated well with the size of ureteroscope used (p = 0.0026). Further, the degree of dilatation of the ureter and pelvicalyceal system was significantly greater when the larger calibre ureteroscope had been used (p = 0.0056) ranging up to hydronephrosis with flattening of the papillae. If there is any parallel which can be drawn between the pig ureter and the human ureter then it suggests that ureteroscopy is more significant than the modality of fragmentation used. The contribution of the laser may therefore be more by the miniaturization of instrumentation which will be made possible than by any advantage it may have as a fragmenter.

Animals↗

Pulsed dye laser fragmentation of ureteral calculi: initial clinical experience.

The pulsed dye laser, emitting at wavelengths of 504 nm. for 1 microsecond. at a frequency of 5 Hz. transmitted via a 250 mu in diameter silicon-coated quartz fiber, was passed into the ureter through the working channel of a 9.5F rigid ureteroscope. Seventeen patients with ureteral calculi too large to be extracted directly, who were unable to be treated by extracorporeal shock wave lithotripsy or who otherwise would have required transureteral or percutaneous ultrasonic stone removal, underwent attempted stone fragmentation by pulsed dye laser application. Of the 17 calculi 16 were fragmented to spontaneously passable or easily extractable fragments. There was no significant ureteral injury, thermal or otherwise, attributable to laser energy action. At 3-month followup 15 of the 17 ureters had improved and 2 showed evidence of ureterscopic injury. The mechanism of stone fragmentation by laser is small volume "shock wave" formation.

Coloring Agents↗

Trp-P-2 is not detectable in cooked meat and fish.

A gas chromatographic-mass spectrometric assay has been developed for the measurement of 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) in cooked meat and fish. The method employs capillary column gas chromatography, electron capture negative ion chemical ionisation mass spectrometry, a deuterated analogue of Trp-P-2 as internal standard and has a limit of detection of 0.1 ng Trp-P-2/g food. Four different meats and three types of fish, cooked either by frying on an electric hotplate or by charcoal broiling, were analysed for Trp-P-2. No Trp-P-2 was detected in any of the samples. The assay was modified to give an improved limit of detection of 25 pg Trp-P-2/g food and fried ground beef was re-examined. Once again, no Trp-P-2 was detected in this cooked meat.

Animals↗