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Biomedical subjects

M L Anthony

Publications and source records attributed to M L Anthony.

At least 19 recordsLinked to original sources
PubMed2000

Surgical treatment of nonmelanoma skin cancer.

Nonmelanoma skin cancer is the most common human malignancy. An estimated 2.75 million patients worldwide are diagnosed with skin cancer each year, with more than one million in the United States alone. Treatment for skin cancer includes methods such as cryosurgery, curettage and electrodessication, local excision, and Mohs micrographic surgery. Regardless of the method used, the goal is to provide the patient with the safest, most cost-effective and curative treatment.

Ambulatory Surgical Procedures↗
PubMed2000

Extracorporeal membrane oxygenation. Saving tiny lives.

Infants with CDH require a dedicated nursing team that often comes from three different critical care areas: neonatal ICU, the ECMO unit, and the operating room. The team works together to directly affect the outcome of these infants through their preoperative, intraoperative, and postoperative care. The physiologic status of the patient and the psychosocial aspects of the family unit are of prime concern to the nursing team involved. Controversy still surrounds the use of ECMO because long-term effects on its survivors are unknown. It will be important for members of the team that manages the infant diagnosed with CDH to understand the benefits and limitations of ECMO. Even with its controversial aspects, ECMO offers the infant with CDH an alternative when conventional therapy fails. The collaborative efforts of the multidisciplinary team that manages these neonates must continue to evaluate treatment modalities and update techniques to maintain quality of care for this challenging population.

Critical Care↗
PubMed1999

Inhibition of phosphatidylcholine biosynthesis following induction of apoptosis in HL-60 cells.

Induction of apoptosis in HL-60 cells, using a variety of cytotoxic drugs, resulted, in all cases, in inhibition of CDP-choline:1, 2-diacylglycerol choline phosphotransferase, leading to an accumulation of its substrate, CDP-choline, and inhibition of phosphatidylcholine biosynthesis. Incubation of the cells with phosphatidylcholine reduced the number displaying an apoptotic morphology following drug treatment, and this was inversely related to the degree to which the drugs inhibited phosphatidylcholine biosynthesis. Inhibition of choline phosphotransferase by two of the drugs, farnesol and chelerythrine, was shown to be due to direct inhibition of the enzyme, while inhibition by the other drugs, etoposide and camptothecin, could be explained by the intracellular acidification that followed induction of apoptosis.

Alkaloids↗
PubMed1999

Laparoscopic splenectomy in children with sickle cell disease.

Sickle cell disease is a group of genetic disorders that are characterized by the production of hemoglobin S, anemia, and acute and chronic tissue damage secondary to blockages caused by abnormally shaped (i.e., sickle-shaped) red blood cells. In children, complications of sickle cell disease (e.g., splenic sequestration and splenomegaly) increase the risks for postoperative complications due to the physical stress of the large incisions previously require for splenectomy. An intracorporeal splenic fragmentation technique is now being used to avoid these complications and will be discussed in this article.

Anemia, Sickle Cell↗
PubMed1998

Induction of apoptosis in two mammalian cell lines results in increased levels of fructose-1,6-bisphosphate and CDP-choline as determined by 31P MRS.

Programmed cell death or apoptosis was induced in human promyelocytic leukemia (HL-60) and Chinese hamster ovary (CHO-K1) cells using several cytotoxic drugs that have different modes of action, including camptothecin, ceramide, chelerythrine, etoposide, farnesol, geranyl geraniol, and hexadecylphosphocholine. The consequent changes in cellular metabolism were monitored using 31P MRS measurements on intact cells and cell extracts. Cells undergoing programmed cell death exhibited characteristic changes in the levels of glycolytic and phospholipid metabolites. The most significant changes were increases in the concentration of the glycolytic intermediate, fructose-1,6-bisphosphate and in the concentration of CDP-choline, which is an intermediate in phosphatidylcholine biosynthesis. In HL-60 cells, the increase in fructose-1,6-bisphosphate levels could be explained by depletion of cellular NAD(H) levels. All of the agents used to induce apoptosis caused the accumulation of CDP-choline. Since the resonances of this compound occur in a relatively well resolved region of tissue spectra, it could provide a marker for apoptosis that would allow the noninvasive detection of the process in vivo using 31P MRS measurements.

Animals↗
PubMed1997

A cultural values assessment tool.

Faculty members at a small liberal arts college teaching in a course entitled "Contemporary Cultures: China, Guatemala and Nigeria" found that using a cultural values assessment tool strengthened the course. This assessment tool was developed by a faculty member teaching in the course when no standardized tool of this type could be found. Students and faculty involved with this senior core course found the cultural values assessment tool to be effective in introducing the course, in stimulating some critical thinking throughout the course and in concluding the course.

Cultural Characteristics↗
PubMed1995

Classification of toxin-induced changes in 1H NMR spectra of urine using an artificial neural network.

NMR spectra of urine from rats treated with a range of liver, kidney and testicular toxins at various doses were measured and classified using neural network methods. Toxin-induced changes in the levels of 18 low molecular weight endogenous urinary metabolites were assessed using a simple semi-quantitative scoring system. These scores were used as input to an artificial neural network, the use of which has been explored as a means of predicting the class of toxin. With this limited data set, based only the level of the maximal changes of these 18 metabolites, the network was able to predict the class and hence target organ of the toxins. Renal cortical toxicity was well predicted as was liver toxicity. The few examples of renal medullary toxins in the data set resulted in relatively poor training of the network although correct classification was still possible.

Chemical and Drug Induced Liver Injury↗
PubMed1995

1H NMR spectroscopic studies on the reactions of haloalkylamines with bicarbonate ions: formation of N-carbamates and 2-oxazolidones in cell culture media and blood plasma.

1H NMR spectroscopic methods have been applied to compare the in vitro reactivity of the renal papillary nephrotoxin 2-bromoethanamine (BEA) with those of selected halide-substituted nephrotoxic analogues, 2-chloroethanamine (CEA), 2-fluoroethanamine (FEA), and 1-phenyl-2-iodoethanamine (PIEA). The primary 1H NMR-detectable transformation during a 24 h incubation of confluent Madin Darby canine kidney (MDCK) cells with BEA, CEA, and FEA (at concentrations up to the IC50 determined by neutral red uptake) was the appearance in cell culture media of 2-oxazolidone (OX). Additional novel signals assigned as FEA carbamate (N-carbamoyl-2-fluoroethanamine) were observed in media collected following incubation of cells with FEA. We propose that N-carbamate intermediates are formed from the spontaneous reaction of these haloalkylamines with HCO(3-)-buffered growth media and that OX is formed from the carbamate via elimination of the hydrogen halide. Further 1H NMR experiments, conducted for up to 8 h at 25 degrees C on 5 mM solutions of BEA, CEA, and FEA in 2H2O containing a 20-fold excess of HCO3- at pH 7.6, demonstrated a time-dependent decrease in the concentration of the free haloalkylamines accompanied by the production of N-carbamate intermediates and OX. Under these pseudo-first-order reaction conditions, the formation of OX from BEA was complete within approximately 6 h. In similar reaction conditions OX formation from CEA (24 h after initiation) had reached 54% of its final equilibrium concentration. Equivalent experiments demonstrated that PIEA was almost completely converted to 4-phenyl-2-oxazolidinone (PHOX) within 2 h. These observations reveal the strong disposition of this series of haloalkylamines toward reaction with HCO3- and indicate that the compounds in this family may exist only transiently as free amines in vivo, where there will virtually always be excess HCO3-. The physiological relevance of the in vitro findings is further indicated by the NMR-detectable conversion of BEA to OX and also an alkylating aziridine (AZ) moiety in rat plasma containing BEA. The ability to form carbamoylated species and OX (or PHOX) may mediate the toxicity of this series of haloalkylamines and hence is potentially of considerable significance.

Animals↗
PubMed1994

Studies on the comparative toxicity of S-(1,2-dichlorovinyl)-L-cysteine, S-(1,2-dichlorovinyl)-L-homocysteine and 1,1,2-trichloro-3,3,3-trifluoro-1-propene in the Fischer 344 rat.

The renal tubular toxicity of various halogenated xenobiotics has been attributed to their enzymatic bioactivation to reactive intermediates by S-conjugation. A combination of high resolution proton nuclear magnetic resonance (1H NMR) spectroscopy of urine, renal histopathology and more routinely used clinical chemistry methods has been used to explore the acute toxic and biochemical effects of S-(1,2-dichlorovinyl)-L-cysteine (DCVC), S-(1,2-dichlorovinyl)-L-homocysteine (DCVHC) and 1,1,2-trichloro-3,3,3-trifluoro-1-propene (TCTFP) up to 48 h following their administration to male Fischer 344 (F344) rats. In the absence of gross renal pathology, 1H NMR urinalysis revealed increased excretion of the tricarboxylic acid cycle intermediates citrate and succinate following DCVC administration. In contrast, both DCVHC and TCTFP produced functional defects in the S2 and S3 segments of the proximal tubule that were confirmed histologically. In these cases, 1H NMR urinalysis revealed increased excretion of glucose, L-lactate, acetate and 3-D-hydroxybutyrate (HB) as well as selective amino aciduria (alanine, valine, glutamate and glutamine). The significance of the proximal nephropathies induced by DCVHC and TCTFP is discussed in relation to biochemical observations on other xenobiotics that are toxic by similar mechanisms.

Animals↗
PubMed1994

Pattern recognition classification of the site of nephrotoxicity based on metabolic data derived from proton nuclear magnetic resonance spectra of urine.

The computer-based pattern recognition procedures of nonlinear mapping and principal-component analysis have been applied to analyze 1H NMR-generated metabolic data on the biochemical effects of 15 acute nephrotoxin treatments affecting the renal cortex and/or renal medulla in rats. The 1H NMR signal intensities for 16 urinary metabolites representative of several major intermediary biochemical pathways were estimated using either a simple semiquantitative scoring system or complete peak intensity quantitation. NMR-derived data were treated as input coordinates in a multidimensional metabolic space and were analyzed by pattern recognition methods through which the dimensionality was reduced for display and categorization purposes. Different nephrotoxin treatments were initially classified using semiquantitative metabolite scores on the basis of their 1H NMR-detectable biochemical effects, and a good separation of renal cortical toxin treatments from renal medullary toxin treatments was achieved. The refinement of using exact peak heights rather than metabolic data scores utilized the available metabolic information more fully and provided a unique classification of each type of toxin according to its pattern of biochemical effects and site of toxic action. Principal-component analysis provided consistently better results than did nonlinear mapping in terms of discrimination between different sites of toxicity, and maps generated from correlation matrices gave improved discrimination, compared with those based directly on the original metabolic data. A comparison between the use of an added internal quantitation standard (3-trimethylsilyl-[2,2,3,3-2H4]-1-propionate) and independently determined glucose excretion rates for scaling to the NMR-detected urinary glucose levels demonstrated that the consistent classification of site-specific nephrotoxicity was independent of the quantitation standard used. This study has provided a rigorous assessment of data processing, relative quantitation, and pattern recognition methods, and the utility of applying these methods to the classification of NMR-derived toxicological data. The considerable potential of the NMR-pattern recognition approach in the assessment of nephrotoxicity has also been confirmed with the discovery of new combinations of molecular markers of renal cellular damage.

Animals↗
PubMed1994

Studies of the biochemical toxicology of uranyl nitrate in the rat.

High resolution 1H NMR spectroscopy of urine and plasma, conventional clinical chemical methods and histopathology have been applied to investigate the effects of uranyl nitrate (UN) on renal function and biochemistry in the Fischer 344 (F344) rat. Administration of UN (5-20 mg/kg) to male F344 rats resulted in a dose-related proximal nephropathy assessed conventionally by histopathology and urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG), and related to changes in the patterns of low MW metabolites observed in 400 MHz 1H NMR spectra of urine. The changes in urinary metabolite profiles included elevations in glucose accompanied by minor elevations in certain amino acids (alanine, valine and glutamate). 1H NMR urinalysis also revealed altered excretion of low MW metabolites which are not routinely measured, such as L-lactate, acetate, citrate, succinate and 2-oxoglutarate (2-OG). In addition, the striking appearance of high concentrations of 3-D-hydroxybutyrate (HB) in the urine was noted, in the absence of acetoacetate or acetone, and it is suggested that this may provide a new marker of proximal tubular damage for certain types of nephrotoxic mechanism. Broadening of the 1H NMR signals of citrate following 10 mg/kg UN was shown to be due to a dynamic exchange process involving chelation with urinary Ca2+ and Mg2+ ions. Conventional biochemical analysis of plasma from UN-treated rats revealed dose-related increases in creatinine, urea and HB concentrations. 1H NMR-detected evidence of raised alanine amino-transferase (ALT) levels in rats administered the highest dose of UN was indicated by the partial deuteration of alanine in lyophilised plasma reconstituted in 2H2O. The degree of 1H NMR-detected abnormalities agreed well with histopathological observations and conventional biochemical indices of nephrotoxicity and more fully characterised the renal changes produced by UN. The significance of HB-uria in UN-induced proximal nephropathy is discussed in relation to biochemical observations on other proximal nephrotoxins.

Animals↗
PubMed1993

Studies on the effects of L(alpha S,5S)-alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid (AT-125) on 4-aminophenol-induced nephrotoxicity in the Fischer 344 rat.

4-Aminophenol (para-aminophenol; PAP) causes selective necrosis to the S3 segment of the proximal tubule in experimental animals. The mechanism of PAP nephrotoxicity has not been fully elucidated, although it has been suggested to involve glutathione (GSH)-dependent S-conjugation followed by processing by the enzyme gamma-glutamyl transpeptidase (gamma GT) to the corresponding cysteine S-conjugate. This proposed toxicity mechanism was probed further by administering L-(alpha S,5S)-alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid (AT-125), a potent gamma GT inhibitor, to Fischer 344 (F344) rats before treatment with PAP (100 mg/kg). AT-125 pretreatment did not appear to protect against PAP-induced nephrotoxicity as assessed by renal histopathology, clinical chemistry and proton nuclear magnetic resonance (1H NMR) spectroscopy of urine. These data suggest that renal gamma GT activity is not a prerequisite for PAP nephrotoxicity and that the generation of a cysteine S-conjugate is not a unique requirement for the induction of PAP nephrotoxicity.

Aminophenols↗
PubMed1993

Raised transaminase activity of blood plasma from rats with experimentally-induced kidney damage detected by spin-echo 1H-NMR spectroscopy.

We report the application of spin-echo 1H-NMR spectroscopy to the detection of raised plasma transaminase activity in rats treated with the nephrotoxic cephalosporin antibiotic cephaloridine (CPH). Spin-echo 1H-NMR analysis of lyophilized plasma, reconstituted in H2O reveals a doublet at delta 1.48 for alanine. However when samples were reconstituted with 2H2O we noted that in samples from CPH-treated rats (but not in control samples) there was a variable degree of appearance of a singlet at delta 1.47 together with a reduction in the doublet at delta 1.48. We suggest that this is due to the release of transaminases from damaged tissue which, via a reversible conversion of alanine to pyruvate, causes selective deuteration of alanine at the alpha-hydrogen (alpha-CH) position. This observation suggests that these 1H-NMR spectral patterns are dependent on the level of plasma transaminases and this may provide a novel indicator of tissue damage.

Alanine↗
PubMed1992

Cephaloridine-induced nephrotoxicity in the Fischer 344 rat: proton NMR spectroscopic studies of urine and plasma in relation to conventional clinical chemical and histopathological assessments of nephronal damage.

The acute toxicological effects of the nephrotoxic antibiotic cephaloridine (CPH, 0-1500 mg/kg) in male Fischer 344 (F344) rats, have been investigated over 48 h using clinical chemistry, histopathology and proton nuclear magnetic resonance (1H NMR) spectroscopy of urine and plasma. High field (400 and 600 MHz)1H NMR urinalysis revealed increased excretion of lactic acid, acetoacetate, alanine, valine, lysine, glutamine and glutamate and a severe, time-dependent glycosuria. A major change observed in urine of CPH-treated animals was the dose-dependent increase in HB which may relate to altered energy metabolism. CPH also caused dose-dependent decreases in the urinary excretion of hippurate, allantoin and protein (conventional assay). This abnormal metabolic profile is consistent with a functional defect in the S1/S2 regions of the proximal tubule, and was confirmed by histology post mortem. Functional changes observed included elevations in blood urea nitrogen (BUN) and urine flow rate (UFR) and dose-related decreases in urine osmolality. Spin-echo 1H NMR spectroscopic analysis of lyophilised plasma, reconstituted with 2H2O revealed an abnormal phase modulation of the methyl signal from free alanine and it is postulated that this is due to the release of transaminases from damaged tissue which via a reversible conversion to pyruvate, cause variable deuteration of alanine at the alpha-CH position. This observation suggests that 1H NMR spectral patterns are also dependent on the level of plasma transaminases and this may provide a novel indicator of tissue damage.

Animals↗