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Biomedical subjects

J E Murphy

Publications and source records attributed to J E Murphy.

At least 91 records · Page 5Linked to original sources

Stable transformation of soybean by electroporation and root formation from transformed callus.

Soybean protoplasts from a number of commercially important cultivars have been genetically engineered by way of electroporation using chimeric genes coding for resistance to the aminoglycoside antibiotics kanamycin and G418. Effective electroporation conditions were determined by monitoring transient expression from aminoglycoside 3'-phosphotransferase II (APHII) expression plasmids. Electroporation of protoplasts with a chimeric APHII gene and subsequent selection on media supplemented with kanamycin resulted in the recovery of calli resistant to the antibiotic. Enzyme assays for APHII activity and Southern blot hybridization confirmed the expression of the foreign DNA and its stable integration into the soybean genome. Root formation was induced from transformed calli, and these roots maintained expression of the APHII gene.

Journal Article↗

Aminoglycoside monitoring: use of a pharmacokinetic service versus physician recommendations.

Two patient populations were evaluated regarding the monitoring of aminoglycoside serum concentrations by either a pharmacokinetic service (PKS) or staff physicians. Both groups were evenly matched by demographic characteristics, underlying disease state(s), and indication for aminoglycoside therapy. Patients in the PKS group showed increased incidence of clinical improvement after therapy when compared with the physicians' group; a decreased length of stay and duration of treatment were also observed in this group. Aminoglycoside dosing and monitoring by the PKS provided an estimated average cost savings of $491,00 per patient. The results indicate that the PKS may provide cost savings and benefit in aminoglycoside monitoring for the patient and/or the hospital.

Adolescent↗

Hypothyroxinemia in cardiac arrest.

Thyroid function was evaluated in cardiac arrest (CA), a condition associated with marked activation of the pituitary-adrenal axis. Blood samples were obtained in 24 patients immediately after diagnosis of CA and again ten minutes later. Samples were also obtained from 22 patients admitted consecutively to the intensive care unit (ICU). Abnormalities of thyroid indexes among patients on the ICU who had not experienced CA were low triiodothyronine (T3) in 45%, low thyroxine (T4) in 32%, low free T4 (equilibrium dialysis) in 21%, and elevated reverse T3 levels in 36%. The alterations of thyroid values were both more common and marked in patients with CA, with abnormally low T3 in 84% of the patients, low T4 in 65%, low free T4 in 65%, and high reverse T3 in 80%. Thyroxine-binding globulin and prealbumin concentrations were below the normal range in 40% and 21% of patients with CA. A thyroid hormone-binding inhibitor was detected in 38% of patients with CA. Thyroglobulin level was slightly high in patients with CA but not significantly different from controls on the ICU. The abnormalities present at zero minutes were further exaggerated ten minutes after CA. We conclude that abnormalities on tests measuring thyroid function are extremely common during the cardiovascular emergency of CA.

Adult↗

Correlation of pharmacokinetic indices with therapeutic outcome in patients receiving aminoglycosides.

The influence of five pharmacokinetic indices on therapeutic response was retrospectively studied in 45 adult patients treated with aminoglycosides for bacterial infections. Subjects were treated for a minimum of five days, had culture and sensitivity reports, and had at least one set of steady-state peak and trough serum aminoglycoside concentrations. Serum drug concentrations were determined by enzyme-multiplied immunoassay or by fluorescence polarization assay. Minimum inhibitory concentrations (MICs) for the drugs were determined by microdilution assays. Cure was determined by negative cultures or absence of clinical evidence of infection. Values for five pharmacokinetic indices were determined for each patient: ratio of steady-state peak serum concentration to MIC (Cssmax/MIC); time that the serum concentration remained above the MIC during a 72-hour period (tsupra-MIC(72)); the intensity index for a 72-hour period (II(72)), which is related but not identical to the area under the curve (AUC), reflecting the contributions of Cssmax/MIC and tsupra-MIC(72); time that the serum concentration was greater than four times the MIC during a 72-hour period (tsupra-(4 X MIC)(72)), and the intensity index related but not identical to AUC greater than four times the MIC (II4 X MIC(72)), which reflects the contribution of Cssmax/(4 X MIC) and tsupra-(4 X MIC)(72). Statistical analysis revealed significant correlations between each of the five indices and the patients' therapeutic responses. The following index values were associated with cures: Cssmax/MIC greater than 4 (and ideally greater than 8); tsupra-MIC(72) of at least 40 hours; tsupra-(4 X MIC)(72) of at least 10 hours; (4) II(72) greater than 400; and II4 X MIC(72) greater than 50. All five pharmacokinetic indices were good predictors of patient outcome. The ratio of maximum steady-state serum aminoglycoside concentration to minimum inhibitory concentration is the index most easily monitored and interpreted.

Adult↗

gamma 3-Melanocyte-stimulating hormone immunoreactivity is a component of the neuroendocrine response to maximal stress (cardiac arrest).

The levels of gamma 3-MSH immunoreactivity (gamma 3MSH-IR), beta-endorphin immunoreactivity (beta-endorphin-IR), ACTH, PRL, and cortisol were determined in 23 patients with cardiac arrest (CA) and in a group of 22 patients consecutively admitted to the Intensive Care Unit (ICU controls). Blood was obtained immediately after CA and at frequent intervals for the next 2 h. In ICU patients, blood was obtained the morning after admission. gamma 3MSH-IR was consistently elevated after CA; it was present in all 23 patients and was detectable in 113 of 114 samples. The mean peak gamma 3MSH-IR level was 162 +/- 20 (+/- SE) pg/ml in CA patients and the mean gamma 3MSH-IR level was 35 +/- 6 pg/ml in ICU controls (P less than 0.01). gamma 3MSH-IR was undetectable (less than 20 pg/ml) in normal subjects. CA also was associated with increases in ACTH, beta-endorphin-IR, cortisol, and PRL. The group of ICU controls had stress hormone levels that were generally within the normal range. Distribution of plasma beta-endorphin-IR by gel chromatography showed two peaks of immunoreactivity corresponding to the beta-endorphin and beta-lipotropin standards in both the CA and ICU control groups. Distribution of gamma 3MSH-IR in CA plasma showed a major peak of immunoreactivity with a mol wt of approximately 6,000 daltons and two minor components of approximately 4,000 and 11,000 dalton. No immunoreactivity coeluted with a gamma 3MSH standard. We conclude that gamma 3MSH-immunoreactive peptides are a consistent component of the massive release of pituitary and adrenal glandular products after CA.

Adrenocorticotropic Hormone↗

The Parodi-Irgens feline sarcoma virus and simian sarcoma virus have homologous oncogenes, but in different contexts of the viral genomes.

We have identified the oncogene and the putative transforming protein of the Parodi-Irgens feline sarcoma virus (PI-FeSV). The PI-FeSV is defective and needs a helper virus for its replication. The v-onc sequences in the PI-FeSV were found to be related to the v-sis sequences of the simian sarcoma virus (SSV). PI-FeSV nonproducer cells express two viral RNAs, a 6.8-and a 3.3-kilobase RNA. The 6.8-kilobase RNA contains gag, sis, and env sequences but lacks the pol gene. The 3.3-kilobase RNA, on the other hand, contains only env sequences. We have detected one feline leukemia virus-related protein product in these cells, namely, a 76-kilodalton protein which contains determinants of the feline leukemia virus gag proteins p15 and p30. The v-sis sequences in the PI-FeSV have been located near the 5' end of the viral genome. Taken together, these results imply that the p76 protein contains both feline leukemia virus gag and sis sequences and probably is the transforming protein of this virus. In contrast, in SSV the sis sequences are located towards the 3' end of the viral genome, and the sis protein is thought to be expressed via a subgenomic RNA. PI-FeSV and SSV therefore use different schemes to express their onc-related sequences. The v-sis sequences in the PI-FeSV contain restriction sites which reflect the different origin of the v-sis sequences in the PI-FeSV and SSV. The homologous oncogenes of the PI-FeSV and SSV thus were transduced by two different retroviruses, feline leukemia virus and the simian sarcoma-associated virus, apparently from the genomes of different species.

Base Sequence↗

In-vivo comparison of the adsorption capacity of "superactive charcoal" and fructose with activated charcoal and fructose.

This study was undertaken to assess the in-vivo capacity of two activated charcoal products to adsorb aspirin after its ingestion by seven healthy volunteers. The two products, Norit-A and Super-Sorb, were combined with fructose solution and administered after the subjects ingested 975 mg of aspirin. Urinary excretion of salicylates was measured during both charcoal administration phases and after ingestion of aspirin alone in all subjects. Results showed statistically significant differences in salicylate excretion between all phases. Super-Sorb ("superactive charcoal") adsorbed almost twice (1.7) as much as aspirin as the regular activated charcoal, Norit-A. Super-Sorb therefore has a greater in-vivo adsorption capacity for aspirin and should be a more effective antidote in poisonings with this drug.

Adjuvants, Pharmaceutic↗

Clinical utility of six methods of predicting phenytoin doses and plasma concentrations.

The usefulness of six reported methods of predicting phenytoin doses or plasma concentrations in epileptic patients is compared. Forty adult epileptic outpatients who were taking phenytoin sodium orally were followed prospectively for nine months; 16 met requirements for inclusion in the study. Six methods of predicting phenytoin dosage or plasma concentrations--one equation, two nomograms, and three graphs--were compared to actual phenytoin doses and corresponding steady-state serum levels. Criteria establishing good, high, and low predictions were specified for each method. No method produced consistently accurate results. Good dosage predictions occurred in 42-60% of the predictions with the six methods. Low predictions occurred in 0-50% of the estimates; 8-53% of the predictions were high. It is concluded that certain methods are clinically useful under some conditions if recommended cautions are observed.

Adult↗