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Biomedical subjects

T Dougherty

Publications and source records attributed to T Dougherty.

9 recordsLinked to original sources
PubMed2000

Fatal nifedipine ingestions in children.

Nifedipine is a prototypical dihydropyridine calcium channel "blocker" that can cause hypotension and cardiac conduction abnormalities. When compared to other calcium channel antagonists, overdoses have been reported to be relatively benign with treatment consisting mainly of supportive care. We report two pediatric cases of death secondary to accidental ingestion of long acting nifedipine (Adalat). Both cases did not respond to aggressive supportive care that included calcium, atropine, epinephrine, glucagon, sodium bicarbonate, and transthoracic pacing.

Accidents, Home↗
PubMed2000

100th American society for microbiology annual meeting.

The 100th ASM Annual Meeting, attended by approximately 10,000 delegates, continued the trend of concentrating on bacteria and antibacterial therapy, mixed with genomics and a diverse number of additional topics. Of the various marketable drug classes, the quinolones received attention with respect to susceptibility studies and several drug comparison studies. New marketable drugs were also of interest, especially given the reservoirs of resistance presented by several speakers. Drugs in development include the antibacterial daptomycin and protegrins and the antifungal lipodepsinonapeptides and echinocandins, to name a few. It is still unclear whether or not antibiotic treatment regimens for Chlamydia pneumonia will he necessary, as association of this bacteria with several chronic diseases, such as atherosclerosis and asthma, was discussed. The development of novel antibiotics was highlighted and the potential role that microbial genomics technology could play was a recurring theme. In fact, a number of symposia treated the increasingly popular topic of genomics in a variety of themes, including phenotyping arrays, transcriptional profiling, proteomics, expression profiling, genome sequencing, target areas or essentiality of genes via gene knockout systems, the role of genomics in pharmaceutical development and fungal genomics. Similarly, genomics plays a role in developing a deeper appreciation for classical areas of interest in microbial physiology, such as gene regulation, cell division, fatty acid biosynthesis, DNA replication and cell signalling. Even in the bio-inorganic field of study in microbial metabolite activation, genomics plays a role. The sequencing of the large gene clusters of the auxiliary proteins necessary to synthesise or activate the metallo-proteins provided insights into the mechanisms of activation of these microbial enzymes, including the genes for the nif gene cluster in Azotobacter vinelandii, the urease from Kiebsiella aerogenes and the three hydrogenases in Ralstonia eutropha.

Anti-Bacterial Agents↗
PubMed1994

Naltrexone, serotonin receptor subtype antagonists, and carbohydrate intake in rats.

Functional interactions between serotonergic (5-HT) and opioid drugs have been observed with 5-HT3 receptor antagonism enhancing the inhibitory actions of naloxone and naltrexone in both food-deprived and glucoprivic rats; 5-HT2A/C receptor antagonism enhanced naltrexone's inhibition of insulin hyperphagia. The present study examined whether pretreatment with either general 5-HT (methysergide: 0.5-5 mg/kg), 5-HT2A/C (ritanserin: 0.25-2.5 mg/kg), or 5-HT3 (ICS 205930: 0.5-5 mg/kg) antagonists altered the pattern and magnitude of ad lib intake of simple (sucrose: 10%) or more complex (maltose dextrin: MD, 10%) carbohydrate solutions, or naltrexone's (0.25-2.5 mg/kg) inhibition of these forms of intake. Methysergide significantly increased the pattern and magnitude of sucrose intake at low (0.5-2.5 mg/kg) doses, and transiently delayed the pattern of MD intake at high (5 mg/kg) doses. Ritanserin significantly accelerated the pattern, but not the magnitude of sucrose intake at low (0.25-1.25 mg/kg) doses without affecting MD intake. ICS 205930 reduced the magnitude of sucrose intake at the highest (5 mg/kg) dose, and transiently reduced MD intake. Naltrexone dose dependently altered the pattern and magnitude of both sucrose and MD intake. Coadministration of ritanserin and naltrexone either eliminated or delayed the pattern of opioid antagonist inhibition of both sucrose and MD intake. Methysergide and ICS 205930 pretreatment produced minor changes in the pattern of naltrexone-induced inhibition. These data indicate that 5-HT receptor differentially modulate the pattern of carbohydrate intake, and indicate differential ingestive interactions between 5-HT and opioid antagonists under challenge and palatable conditions.

Animals↗
PubMed1991

Hepatic arterial infusion chemotherapy with complete hepatic venous isolation and extracorporeal chemofiltration: a feasibility study of a novel system.

When chemotherapeutic drugs with low liver extraction are used for hepatic arterial infusion (HAI), dosage limits are usually determined by systemic rather than hepatic toxicity. If such agents could be administered by HAI at dosages limited by hepatic toxicity, regional drug exposure and therapeutic efficacy might be significantly enhanced. We report herein a novel system that achieves complete hepatic venous isolation using a dual-balloon vena cava catheter that can be inserted percutaneously. This catheter is connected to a carbon filter in an extracorporeal venous bypass circuit to recover drug that is not absorbed by the liver after HAI. The hemodynamic response to this system was evaluated in six pigs. When the animals were placed on the extracorporeal circuit, we observed a 22% decrease in cardiac output that was well tolerated without significant change in blood pressure. When the filter was incorporated into the circuit, cardiac output was significantly reduced (50%); however, continuous infusion of phenylephrine rapidly normalized blood pressure, heart rate, cardiac output, and left ventricular filling pressures. Initial testing of chemofiltration efficacy was performed in four of the six animals, the remaining two animals being used only to assess hemodynamic response. One each of the four tested animals received either doxorubicin (3 or 9 mg/kg), mitomycin C (1 mg/kg), or cisplatin (1 mg/kg) by HAI. The filter removed over 90% of hepatic venous doxorubicin and mitomycin C and 65% of hepatic venous cisplatin. This feasibility study confirms that hepatic venous isolation with chemofiltration can significantly reduce systemic exposure to high-dose chemotherapeutic agents given by HAI.

Animals↗
PubMed1988

Picture memory: recognizing added and deleted details.

When people are presented simple and complex pictures and then tested in a same-changed recognition test with a simple or complex form of each, d' is greater for the simple than the complex picture (Pezdek & Chen, 1982). The results of three experiments confirm the robustness of this "asymmetric confusability effect" and test a model of the processes underlying this effect. According to the model, pictures are schematically encoded such that the memory representation of both simple and complex pictures is similar to the simple form of each. In Experiment 1, a sentence was presented that described the central schema in the picture prior to subjects' viewing each picture. This manipulation exaggerated the asymmetric confusability effect; schematic processing thus underlies the effect. Results of Experiment 2 refute the hypothesis that the effect results from subjects erroneously anticipating a recall test rather than a recognition test. Furthermore, although some of the nonschematic elaborative information in complex pictures is stored in memory, it is difficult to retrieve to verify that something is missing when complex presentation pictures are changed to simple test pictures (Experiment 3). Thus, although people are able to distinguish large sets of old pictures from new distractor pictures, their ability to detect missing elaborative visual details is more limited.

Attention↗
PubMed1987

Effects of flicker-induced depth on chromatic subjective contours.

Two experiments examined the dependence of illusory colors on boundary salience and depth stratification by using flicker-induced depth. The first used a subjective-contour stimulus that appeared as a translucent colored rectangle covering a set of inducing circles and a dark background. The circles were then flickered so as to be perceived as background, and the previously dark background moved forward and appeared as foreground. Simultaneously, the chromatic subjective contour was eliminated. In the second experiment, a subjective-contour (faces/vase-concentric squares) figure was tinted with the McCollough effect, which produced a strong subjective color edge. This edge was visible only with the faces/vase percept and not in the squares percept. Flickering the target locked it into the square configuration because in this case the flicker held the entire pattern in the same depth plane. This eliminated the subjective color edge. Depth stratification and subjective color blockage were maximal at a flicker rate of 6 Hz.

Color Perception↗
PubMed1986

Molecular cloning of human ornithine aminotransferase mRNA.

The isolation and characterization of a cDNA clone for the mRNA of human ornithine aminotransferase (OATase; ornithine-oxo-acid aminotransferase; L-ornithine:2-oxo-acid aminotransferase, EC 2.6.1.13), a nonabundant mitochondrial matrix enzyme that is severely deficient in a hereditary chorioretinal degenerative disease (gyrate atrophy), is described. Human liver, retina, and retinoblastoma (Y79) mRNAs were prepared and tested for the OATase mRNA content by in vitro translation, immunoprecipitation, and NaDodSO4/PAGE. The retinoblastoma cells were found to be expressing this enzyme at a relatively high level. The primary translation product of the OATase mRNA is larger than the pure OATase protein on NaDodSO4/PAGE by approximately equal to 4 kDa, suggesting a precursor protein. lambda gt11 cDNA libraries were prepared from the human mRNAs, and the recombinant clones were immunoscreened as plaques with two different preparations of rabbit anti-human OATase antibodies. A clone (lambda gtRB315) was isolated from the retinoblastoma library that reacts with both of the antibody preparations, and the DNA sequence of its 2.1-kilobase-pair cDNA insert was obtained. An open reading frame consisting of 1371 nucleotides is present in the sequence, and a putative translational initiation methionine codon is identified at position 55. A putative leader sequence consisting of 32 amino acid residues is identified, resulting in a precursor protein of 439 amino acid residues and a molecular mass of 48,534 Da and a mature protein of 407 residues and 45,136 Da. The amino acid sequences of seven tryptic peptides (115 amino acid residues) of the pure human OATase were obtained by microsequencing. When the tryptic peptide and cDNA-derived amino acid sequences were compared, homologies in 111 of 115 residues, including a match of 20 consecutive residues, were observed. An RNA blot hybridization of 32P-labeled OATase cDNA to normal human retina and retinoblastoma mRNAs demonstrated an OATase mRNA species of approximately equal to 2.2 kilobases. The level of OATase mRNA in the normal human retina is approximately equal to 1/100th the level of rhodopsin mRNA and 1/5th to 1/10th the level present in the retinoblastoma cells.

Amino Acid Sequence↗