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Biomedical subjects

P Cook

Publications and source records attributed to P Cook.

At least 91 records · Page 5Linked to original sources

Amsacrine is safe and effective therapy for patients with myocardial dysfunction and acute leukemia.

The role of amsacrine in inducing remission in patients with cardiac disease and acute leukemia was evaluated. There were 17 patients with acute myelogenous leukemia (AML), six with acute lymphocytic leukemia (ALL), and one with biphenotypic leukemia. In this series of 24 patients whose disease had relapsed and who had reduced left ventricular ejection fraction, nine had a complete remission, seven with AML and two with ALL. In addition, four of six with newly diagnosed acute leukemia and reduced left ventricular ejection fraction also responded. Among nine patients who underwent endomyocardial biopsy, none had morphologic changes of sufficient degree to account for drug-induced heart failure. Patients with preexisting arrhythmias received amsacrine without incident if their serum potassium level was higher than 4.0 mEq/l at the time of drug administration. Amsacrine is safe and effective therapy for patients with acute leukemia and cardiac disease.

Amsacrine↗

Effect of phorbol esters on cytosolic protein kinase C content and activity in the human monoblastoid U937 cell.

12-O-Tetradecanoylphorbol-13-acetate (TPA) stimulates the human monoblastoid U937 cell to differentiate into a mature monocyte/macrophage-like cell. Since TPA may produce cellular responses by activating protein kinase C, the effects of TPA on kinase activity in the U937 cell were investigated. Brief exposures (less than or equal to 60 min) to TPA dramatically diminished protein kinase C-dependent phosphorylation of histone and endogenous substrates. However, using a peptide substrate corresponding to residues 720-737 of protein kinase C-epsilon, Ca2(+)-, phospholipid-, and diacylglycerol-dependent kinase activity was reduced only modestly after exposure to TPA. This phospholipid-dependent kinase activity coeluted on DEAE chromatography with protein kinase C. Examination of cytosolic protein kinase C content by Western blot analysis demonstrated a moderate decline in kinase content after TPA treatment. The decline was due primarily to loss of an 80-kDa species with preservation of a 76-kDa protein. The immunoreactive 76-kDa protein observed after TPA treatment comigrated on DEAE chromatography with the kinase activity phosphorylating the protein kinase C-epsilon peptide and had an elution profile similar to protein kinase C derived from untreated cells. Using antisera recognizing the catalytic and regulatory domains of the kinase, no evidence for proteolytic degradation of protein kinase C was observed. Although incubation of extracts from vehicle and TPA-treated cells inhibited the activity of partially purified protein kinase C, the degree of inhibition was similar in the two extracts. These findings suggest that TPA markedly diminishes protein kinase C-dependent phosphorylation of histone and endogenous substrates in part by altering kinase substrate specificity. These observations provide evidence for a novel post-translational process that can modulate protein kinase C-dependent phosphorylation.

Autoradiography↗

Role changes at the pharmacy-nursing interface: Kimball Medical Center.

The original goals and objectives of the CST program have been realized. Medication safety, control, accountability, and utilization efforts of decentralized satellite pharmacists have been brought to fruition. A career ladder has been created for the pharmacy technician. This has enabled the Department of Pharmaceutical Services to recruit, retain, and develop an exceptionally competent and proficient technical staff. The pharmacy has earned a new found respect from the nursing division. A greater awareness of its staff's positions as drug experts and information resources has evolved. Credibility has been established for additional pharmacy programs and proposed clinical activities. Pharmacists and technicians have gained an in-depth understanding of the procedures, problems, and challenges of the nursing services, which has enabled a bridge of understanding and a common bond of team effort to be built between the two departments.

Hospital Bed Capacity, 300 to 499↗

Short course high dose mitoxantrone with high dose cytarabine is effective therapy for adult lymphoblastic leukemia.

Mitoxantrone is effective in the treatment of acute myelogenous leukemia and, in combination with either vincristine-prednisone or cytarabine (HiDAc), it is also effective in acute lymphoblastic leukemia (ALL). As mitoxantrone exhibits a steep dose-response curve against ovarian cancer cells and acute myeloid leukemia cells in vitro, we evaluated the safety and efficacy of high dose mitoxantrone with HiDAc in the treatment of ALL. Patients received mitoxantrone 20-37.5 mg/m2 daily for 2 days or 1 dose of 40-80 mg/m2 and HiDAc 3 g/m2 over 3 h once daily for five doses. All eight of the patients with previously untreated disease and eight of ten patients with ALL in relapse achieved complete remission (CR). The untreated patients included two with Philadelphia positive ALL who also achieved CR (one after one course of mitoxantrone-HiDAc, and one after one course of mitoxantrone-HiDAc followed by one additional dose of vincristine and daily prednisone). Seven of the eight previously untreated patients who achieved CR are still in remission. The one T-cell ALL has relapsed at 2 months after CR. The toxicity was acceptable. The regimen thus induces a remission rate equivalent to that of traditional vincristine-prednisone. The 'quality of remission' may be superior, and this therapy should be explored as a primary induction therapy in patients with ALL.

Antineoplastic Combined Chemotherapy Protocols↗

Percutaneous nucleotomy. An anatomic study of the risks of root injury.

Fifteen cadaveric dissections have been performed to determine the anatomic relationships of nucleotomy guide wires. All the 44 guide wires inserted were found to be in contact with at least one nerve root (eight transfixed a root). Guide wires passing anterior to the nerve roots always passed anterior to the center of the disc. Lateral displacement of the skin entry point made safe entry to the center of the disc impossible. Nerve root transfixion is likely to be a significant complication in percutaneous nucleotomy. Entry to the center of the disc avoiding the nerve roots is simplest if the skin entry is as near to the midline as possible.

Cadaver↗

Ecdysteroids affect in vivo protein metabolism of the flight muscle of the tobacco hornworm (Manduca sexta).

Ecdysteroid growth promotion of the dorsolongitudinal flight muscle of Manduca sexta was studied by measuring in vivo protein metabolism using both "flooding-dose" and "non-carrier" techniques. These procedures differ in that the former method includes injection of non-labelled phenylalanine (30 micromoles/insect) together with the [3H]amino acid. Injected radioactivity plateaued in the haemolymph within 7 min. With the flooding-dose method, haemolymph and intramuscular specific radioactivities were similar between 15 min and 2 h. Incorporation of [3H]phenylalanine into muscle protein was linear with either method between 30 and 120 min. Fractional rates (%/12 h) of synthesis with the flooding-dose technique were best measured after 1 h because of the initial delay in radioactivity equilibration. Estimation of body phenylalanine turnover with the non-carrier method showed 24-53%/h which was negligible with the flooding-dose method. Since the two methods yielded similar rates of protein synthesis, the large injection of non-labelled amino acid did not alter the rate of synthesis. Because the flooding-dose technique requires only a single time point measurement, it is the preferred method. The decline and eventual cessation of flight-muscle growth was mostly a consequence of declining protein synthesis though degradation increased between 76-86 h before eclosion and was relatively rapid. This decline in muscle growth could be prevented by treating pupae with 20-hydroxyecdysone (10 micrograms/insect). Protein accretion was promoted by a decline of up to 80% in protein breakdown, which was offset in part by a concurrent though much smaller decrease in protein synthesis. Therefore, ecdysteroids may increase flight-muscle growth by inhibiting proteolysis.

Animals↗

Pituitary microadenomas: a PET study.

Twenty cases of surgically verified pituitary microadenoma (17 with Cushing disease and three with acromegaly) were studied with positron emission tomography (PET) with use of fluorine-18-2-fluorodeoxyglucose (FDG). The diagnostic results were compared with those of other modalities, namely, computed tomography (CT), magnetic resonance (MR) imaging, and, in the cases of Cushing disease, simultaneous bilateral inferior petrosal sinus sampling (SIPS). The PET results showed 12 positive readings and one questionable reading, compared with seven positive readings and one questionable reading for CT (18 cases studied) and 13 positive and two questionable MR imaging readings. PET complemented MR imaging, in the sense that five of the positive PET readings were negative or questionable at MR imaging. PET studies of 20 healthy control subjects showed no false-positive cases, whereas other studies of healthy subjects with contrast material-enhanced CT and MR imaging have yielded, respectively, 20% and 15% positive readings, with findings suggestive of silent or occult adenomas.

Adenoma↗

Regional brain metabolism during auditory hallucinations in chronic schizophrenia.

Regions of the brain involved in language and attention were studied using [18F]-fluorodeoxy-glucose in PET. In nine chronic DSM-III schizophrenic patients who had persistent auditory hallucinations, ten who had recovered from hallucinations and ten normal controls. In none of the regions examined was metabolic activity significantly different in hallucinating patients compared with that in other groups. However, a pattern of seven significant correlations of metabolic activity between language regions and between frontal and parietal cortex characterised the hallucinating but not the other groups. Three of the seven correlations were significantly greater in hallucinating patients than in the two other groups, and six were greater in hallucinating patients than controls. Metabolism in Broca's region and its right-hemisphere homologue correlated positively and significantly in the hallucinating group, as it did in anterior cingulate and left superior temporal areas, and in right frontal and parietal areas. Hallucination ratings correlated with metabolism in the anterior cingulate region.

Adult↗

Haemorrhage during minitracheotomy: reduction of risk by altered incision.

A 46-year-old male was admitted to an intensive care unit: for 11 days he waa ventilated via a naso-tracheal tube. Because of excess tracheal secretions, a mini tracheotomy was attempted on the unit which resulted in profuse arterial haemorrhage, necessitating immediate reintubation and subsequent formal tracheostomy. The authors feel that this complication was due to a mid-line vertical incision and that this could have been avoided by a horizontal incision across the lower part of the cricothyroid membrane, as close to the cricoid cartilage as possible. They describe their recommended technique.

Hemorrhage↗

Training residents to care for the mentally ill.

Recent changes in Royal College training requirements have highlighted the need for residency programs to be able to offer challenging and worthwhile experiences to their trainees in caring for the chronically mentally ill. This training should bring them into contact with patients at each stage of their illness and recovery and expose them to the different settings in which treatment or management takes place. Postgraduate programs face many problems in organizing this teaching that arise from the nature and course of long-term psychiatric illnesses, the organization of residency training programs, attitudes and preconceptions of residents and teachers and competing time demands. The authors review these problems, identify specific goals for the training and suggest strategies for achieving these goals. Expectations of postgraduate programs, clinical placements, supervisors and residents themselves are outlined.

Attitude of Health Personnel↗

Problems in analysis of data from muscles of rats flown in space.

Comparison of hindlimb muscles of rats flown on Spacelab-3 or tail-traction-suspended showed that 11-17 h reloading post-flight might have altered the results. Soleus atrophied, plantaris, gastrocnemius and extensor digitorum longus grew slower, and tibialis anterior grew normally. In both flight and simulated soleus and plantaris, higher tyrosine and greater glutamine/glutamate ratio indicated negative protein balance and increased glutamine production, respectively, relative to controls. Aspartate was lower in these muscles. Reloading generally decreased tyrosine, but increased aspartate and glutamine/glutamate. These data showed that at 12 h of reloading after flight is characterized by reversal to varying extents of effects of unloading.

Adaptation, Physiological↗

Rat muscle protein turnover and redox state in progressive diabetes.

Protein synthesis and degradation, and redox state were measured in soleus and extensor digitorum longus muscles of rats up to 12 days after injection of streptozotocin. Muscle growth was slower in these animals apparently due to slower protein synthesis throughout the duration of diabetes. Up to day 4 after injection of streptozotocin or withdrawal of insulin from treated, diabetic animals, the muscle ratio of lactate/pyruvate, an indicator of the cytoplasmic NAD+ redox couple, was lower and protein degradation was faster than in control muscles. Thereafter, the ratio of lactate/pyruvate was greater and protein degradation was slower than in size- or age-matched control muscles. Insulin treatment in vitro or in vivo increased lactate/pyruvate and decreased proteolysis. Therefore, in muscles of streptozotocin-diabetic rats, the initial increase and later fall in proteolysis, and the inhibition of proteolysis by insulin, may correlate with opposite changes in NADH/NAD+.

Animals↗