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Biomedical subjects

C Murphy

Publications and source records attributed to C Murphy.

At least 55 records · Page 3Linked to original sources

Phosphofructokinase activity in the brain in Alzheimer's disease.

The activity of phosphofructokinase, a key regulatory enzyme of glycolysis, was determined in neurosurgical samples of neocortex obtained from 6 patients with primary degenerative dementia, including 4 with Alzheimer's disease. No consistent reductions were seen compared with samples from nondemented controls. These results contrast with the greatly reduced activity reported previously for postmortem brain specimens from patients with Alzheimer's disease.

Adult

Continuous non-invasive beat-by-beat blood pressure (B.P.) measurement in the newborn.

Intermittent measurement of blood pressure (BP) is frequently performed in newborn babies under intensive care using an inflatable cuff encircling either the arm or leg. This paper describes work aimed at achieving continuous beat-by-beat measurement of the arterial pressure waveform by means of a finger cuff, the pressure of which is controlled by a feedback arrangement utilising a photoplethysmograph. Preliminary results are encouraging, but improvements to cuff design are still needed.

Blood Pressure Determination

Analysis of tamoxifen and its metabolites in human plasma by gas chromatography-mass spectrometry (GC-MS) using selected ion monitoring (SIM).

A method for the analysis of tamoxifen and its metabolites in plasma from tamoxifen treated breast cancer patients, by capillary GC-MS using selected ion monitoring has been developed. Metabolite extraction was carried out on a Sep-pak C18 cartridge and metabolite purification by selective ion exchange chromatographic steps. Satisfactory recovery of radioactive standards through the extraction and purification steps was obtained. The method was shown to be accurate and precise with precision coefficient of variation values ranging from 4.3-11% for tamoxifen and its metabolites. Tamoxifen, 4-hydroxytamoxifen, metabolite Y and N-desmethyltamoxifen were identified with certainty in patient plasma on the basis of GC relative retention times and mass spectral comparison with authentic standards; because of their low abundance in plasma cis-metabolite E and 3,4-dihydroxytamoxifen could only be tentatively identified but identical GC behaviour and a satisfactory comparison of the abundance of key fragment ions was achieved. The tamoxifen and metabolite concentration ranges (ng X ml-1) in the group of patients who received 40 or 80 ng tamoxifen for 14 days were tamoxifen, 307-745; N-desmethyltamoxifen, 185-491; 4-hydroxytamoxifen, 1.4-2.5; 3,4-dihydroxytamoxifen, 0.7-2.0; metabolite Y, 19.0-112; and metabolite E1, 0.9-2.0.

Aged

Analysis of tamoxifen, N-desmethyltamoxifen and 4-hydroxytamoxifen levels in cytosol and KCl-nuclear extracts of breast tumours from tamoxifen treated patients by gas chromatography-mass spectrometry (GC-MS) using selected ion monitoring (SIM).

Tamoxifen, 4-hydroxytamoxifen and desmethyltamoxifen levels were measured in cytosolic and 0.5 M KCl extracted nuclear fractions from a small series of breast tumours from tamoxifen treated patients by gas chromatography-mass spectrometry (GC-MS) using selected ion monitoring (SIM). Tamoxifen and desmethyltamoxifen were the most abundant metabolites. There was a small increment in the relative abundance of 4-hydroxytamoxifen in the nuclear extract over cytosol relative to both tamoxifen and desmethyltamoxifen. Further, there was a selective retention of tamoxifen relative to desmethyltamoxifen in the nuclear extract relative to the cytosol. It is concluded that all three compounds could potentially contribute to estrogen receptor mediated antiestrogenic effects in this target tissue.

Breast Neoplasms

Analysis of tamoxifen and 4-hydroxytamoxifen levels in immature rat uterine cytoplasm and KCl-nuclear extracts by gas chromatography-mass spectrometry (GC-MS) using selected ion monitoring (SIM).

A GC-MS (SIM) method has been developed which allows the measurement of tamoxifen and its metabolites in uterine cytosol and 0.5 M KCl-extracts of uterine nuclei from groups of immature rats. The method was shown to be specific, precise and accurate. Using this procedure tamoxifen and 4-hydroxytamoxifen were tentatively identified and measured in uterine extracts after tamoxifen administration. When tamoxifen and 4-hydroxytamoxifen levels in uterine cytosol and 0.5 M KCl nuclear extracts were compared a relative enrichment in the nuclear fraction of 4-hydroxytamoxifen (relative to tamoxifen) was consistently seen. These observations are supportive of a role for 4-hydroxytamoxifen in mediating the antiestrogenic actions of tamoxifen in the immature rat uterus. In some of the uterine cytosolic fractions desmethyltamoxifen and metabolite Y could also be detected.

Animals

Intravenous phenobarbital for alcohol withdrawal and convulsions.

In a prospective, uncontrolled study, 62 alcoholic patients received IV phenobarbital (IV-PB) to treat the alcohol withdrawal (AW) syndrome. Initially 260 mg of IV-PB were administered followed by 130 mg every 30 minutes to an end point of light sedation. A mean loading dose of 598 (+/- 192) mg of IV-PB resulted in a mean increase in the serum PB level of 13.9 (+/- 4.7) microgram/mL. Thus, the serum PB level rose 1.65 micrograms/mL for each mg/kg of IV-PB administered to these adult patients in AW. Forty-six of 48 tremulous patients (96%) showed improvement in their AW tremors. None of the 38 patients who presented with AW seizures had another convulsion during a mean observation period of three hours and 47 minutes. Transient ataxia or over-sedation occurred in three of 62 patients (5%) and was exacerbated by concurrent ethanol, diazepam, or phenytoin (six of 17), who were excluded from the study. We conclude that IV-PB is a safe and efficacious therapy for mild to moderate AWS, and IV-PB may prevent AW seizures.

Acute Disease

Age and biochemical status predict preference for casein hydrolysate.

Two studies investigated relationships between chemosensory preference, age, and biochemical status. In the first study, 10 young and 16 elderly participants rated the relative pleasantness of several concentrations of casein hydrolysate, a nutritionally significant stimulus, prepared in an amino acid deficient soup base. Blood assays were performed to assess total protein, albumin, and blood urea nitrogen (BUN). Elderly persons and those whose blood values indicated lower biochemical status preferred higher concentrations than young persons and those with blood values indicative of higher biochemical status. In a second study 20 young and 20 elderly participants performed the same pleasantness task and then rated the stimuli for intensity using the method of magnitude matching. For each person a single index of biochemical status was produced using measures of protein, albumin, and BUN. As in the first study, age and biochemical index predicted preferred concentration of casein hydrolysate, but intensity ratings did not.

Adult

Evaluation and treatment of smell dysfunction.

We gave 63 patients with symptoms of smell dysfunction a full evaluation by age-adjusted olfactory threshold and odor identification testing, rhinomanometry, nasal cytology, nasal endoscopy, computed tomographic (CT) scan and a trial of medical treatment. CT scans were valuable for identifying ethmoid sinus disease and nasal endoscopy for inspecting olfactory epithelium. A trial of prednisone served as a diagnostic modality to identify correctable causes of smell dysfunction. Given that there are 2 million people in the United States with a smell dysfunction, that the average physician knows little about its diagnosis and treatment and that the psychosocial impact to an afflicted person is great, we urge a greater awareness of smell dysfunction, its diagnosis and its treatment.

Adult

A transcribed satellite DNA from the bullfrog Rana catesbeiana.

We have cloned and sequenced a 360 bp repeated sequence from genomic DNA of the bullfrog Rana catesbeiana. This sequence, which we call satellite 1, makes up 0.7% of the genome (1.6 X 10(5) repeats) and is scattered throughout the length of all the chromosomes. In situ hybridization with strand-specific probes demonstrated that transcripts from both strands of satellite 1 occur on lamp-brush chromosome loops. We suggest that these transcripts arise by readthrough from upstream structural gene promoters. Sequences that cross-react with satellite 1 were found in genomic DNA of four out of five other Rana species that we tested, but were absent from the DNA of Xenopus, Bombina, and Acris.

Animals

Odor identification: the blind are better.

Twenty sighted and twenty blind adults, 19 to 66 years of age, participated in tests of olfactory sensitivity to n-butyl alcohol and of identification of 80 everyday odors. The blind had poorer absolute sensitivity, but outperformed the sighted at identification. Age proved an important factor in the comparison; more than half the variance in identification within each group was ascribable to an age-related decline.

Adult

Age-related differences in the pleasantness of chemosensory stimuli.

Modest decrements in both taste threshold sensitivity and, more recently, suprathreshold sensitivity have been associated with the aging process. The present study was designed to investigate the existence of changes in preference for various concentrations of single tastes and of the same single tastes in more complex chemosensory mixtures. In this study, 300 participants from three different age groups (18-26, 32-45, over 65) rated for pleasantness four concentrations of sodium chloride, sucrose, and citric acid presented in both aqueous and beverage bases. Results showed significant effects of age, stimulus background, stimulus, concentration, and of several interactions, and they suggest that elderly subjects find salt and sugar pleasanter at higher concentrations than younger subjects do.

Adolescent

Recovery of acetylcholinesterase activity after acute organophosphate treatment of CNS reaggregate cultures.

The effect of a single dose of diisopropylfluorophosphate on acetylcholinesterase (AChE) activity was examined in mouse CNS reaggregate cultures. At 17-24 days in culture, reaggregates were treated with 0.6 mg/liter DFP for 15 min. The recovery of AChE activity was examined in culture. After treatment, 5.4 +/- 1.19% of control AChE activity remained. By 24 hr, 31.6 +/- 6.4% of control activity had returned and the recovery of activity was essentially complete by 7 days after treatment. Recovery of AChE activity after DFP treatment required protein synthesis, since there was no recovery in the presence of cycloheximide. After treatment with the reversible inhibitor, physostigmine at 0.5 mg/ml, recovery of AChE activity was complete within 24 hr after treatment. These results indicate that CNS reaggregate cultures not only express differentiated functions of the CNS, but also have the capacity to turn over proteins, and thus may provide a good model system in which to examine mechanisms of toxicity.

Acetylcholinesterase

Cognitive and chemosensory influences on age-related changes in the ability to identify blended foods.

Two experiments explored the effects of age, sex, and chemosensory function on the ability of blindfolded participants to identify a series of 12 blended foods. In the first experiment 40 persons aged 18 to 26 and 40 persons over 65 years of age attempted to identify the pureed foods using both taste and odor cues. Half the participants in each group were female, half were male. The average percentage correct on first attempt to identify was significantly higher in young than in old individuals. An Age X Sex interaction revealed a female superiority over men in the elderly group only. With feedback and practice, participants improved, but the age effect remained significant. In the second experiment, 20 young and 17 elderly women who had their nostrils occluded attempted the same identification task. When deprived of olfaction, the performance of young women fell to the same level as that of the old women on first exposure. The relative contributions of cognitive, gustatory, and olfactory/trigeminal factors to the age-related decline in chemosensory function are discussed.

Adolescent

Treatment of fractures of the femur with the Grosse-Kempf rod.

Intramedullary rod placement provides excellent fixation for many fractures of the femur. It also carries a high union rate, a low infection rate, and a shortened hospital stay for the patient. Certain fractures of the femur are not suitable for fixation with a standard intramedullary and alone. Use of the Grosse-Kempf rod, with interlocking screws, allows for stable fixation for long oblique fractures, spiral fractures, comminuted fractures, segmental fractures, fractures with a butterfly fragment, and fractures located in the proximal or distal shaft of the femur. The Louisiana State University (LSU) Orthopedic experience in the use of the Grosse-Kempf rod is presented in this article. We have treated a total of 60 fractures of the femur in 58 patients with this fixation system. This series consists of 58 acute fractures, one established nonunion, and one established infected nonunion. All patients in the group of acute fractures and who have had adequate follow up and time have healed. This group consists of 29 healed fractures and four fractures which are healing, but have recently had the static screw removed. Eight patients were lost to follow up, two died of causes unrelated to the treatment, and 17 have been placed recently and have not had time to heal. There was one instance of wound infection in the acute fracture group, associated with the distal screws, but this has not required rod removal. The Grosse-Kempf rod provides the treating physician with another option in the treatment of fractures of the femur not suitable for use by the standard intramedullary rod. The procedure is difficult, but we have found it to be reliable in treatment of difficult fractures.

Adolescent