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Biomedical subjects

B Young

Publications and source records attributed to B Young.

At least 181 records · Page 10Linked to original sources
PubMed1986

Serum and urine zinc response in head-injured patients.

A prospective longitudinal evaluation of serum zinc concentrations was performed in 26 head-trauma patients, and 24-hour urine zinc excretion was determined in 15 of these subjects. Patients had markedly depressed admission serum zinc concentrations (mean +/- standard error of the mean: 40.2 +/- 3.2 micrograms/dl; normal values: 70 to 120 micrograms/dl), which gradually increased during the 16-day study period. All subjects demonstrated increased urinary zinc losses throughout the study period. Urinary zinc excretion was greater in patients with more severe head injuries. Indeed, patients with more severe head trauma had mean peak urinary zinc losses of greater than 7000 micrograms/day (normal less than 500 (micrograms/day). The implications of this altered zinc metabolism for protein metabolism, wound healing, and immune function, and the specific role of zinc in brain function and recovery from injury are discussed.

Adolescent↗
PubMed1986

A clinical study with brain brachytherapy for malignant gliomas.

A clinical trial with neutron brachytherapy for malignant glioma is now in progress at the University of Kentucky Medical Center. In the initial three year period, 32 patients entered the study. There were 24 males and eight females, and the peak incidence was seen in the seventh decade. All patients underwent surgical resection of tumor followed by Cf-252 implantation and external radiotherapy. The implantation procedure was well tolerated by the patients and demonstrated a short-term benefit in survival of patients who were able to complete planned radiotherapy. Older patients had less tolerance to radiotherapy. The evaluation of the beneficial effects of Cf-252 brachytherapy will require patients who are able to tolerate the whole course of therapy.

Adult↗
PubMed1986

Genetic analysis of cystic fibrosis: linkage of DNA and classical markers in multiplex families.

Linkage of cystic fibrosis (CF) to DNA and classical markers was studied in 36 families of two or three generations with at least two living affected children. Among the 79 affected children, no recombinants were detected between the disease and the markers MET and pJ3.11, previously shown to be linked to CF. No linkage between the human trypsin gene family (which appears to include at least 10 members) and CF was found, although not all genes of the trypsin family have been screened yet. In one of the CF families, recombination between MET and pJ3.11 was detected in an unaffected sib. Data from our families suggest that the gene order of markers among chromosome 7q is: (7cen;p8.33)collagen(COL1A2);DOCR1-917;paraoxonase+ ++(PON);(MET-cf-J3.11);T-cell receptor beta chain (TCRB);qter. There was no evidence for (or against) either postzygotic selection or meiotic drive to explain the high frequency of CF in Caucasian populations.

Cystic Fibrosis↗
PubMed1985

Identification of the cytochrome P-450 induced by macrolide antibiotics in rat liver as the glucocorticoid responsive cytochrome P-450p.

We administered triacetyloleandomycin (TAO) to rats and found that this macrolide antibiotic is the most efficacious inducer of liver microsomal cytochrome P-450 (P-450) examined to date. Liver microsomes prepared from TAO-treated rats contained greater than 5.0 nmol of P-450/mg of protein and a single induced protein as judged by analysis on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. This protein comigrated with P-450p, the major form of P-450 induced in liver microsomes of rats treated with pregnenolone-16 alpha-carbonitrile (PCN) or dexamethasone (DEX). On immunoblots of such gels developed with antibodies to P-450p, the TAO-induced protein reacted strongly as a single band. There was strict parallelism between the amount of immunoreactive P-450p in liver microsomes prepared from untreated rats or from rats treated with phenobarbital, TAO, DEX, or PCN, the ability of these microsomes to catalyze conversion of TAO to a metabolite which forms a spectral complex, and the ethylmorphine and erythromycin demethylase activities. Antibodies to P-450p specifically blocked microsomal TAO metabolite complex formation and ethylmorphine and erythromycin demethylase activities. Moreover, anti-P-450p antibodies completely immunoprecipitated solubilized TAO metabolite complexes prepared by detergent treatment of liver microsomes obtained from TAO-treated rats. Finally, we found that the major form of P-450 isolated from liver microsomes of TAO-treated rats and purified to homogeneity was indistinguishable from purified P-450p as judged by molecular weights, spectral characteristics, enzymatic activities, ability to bind TAO, peptide maps, and amino-terminal amino acid sequences. We concluded that, in addition to glucocorticoids, macrolide antibiotics are specific inducers of P-450p.

Amino Acid Sequence↗
PubMed1985

Metabolic and nutritional sequelae in the non-steroid treated head injury patient.

Energy production, substrate oxidation, serum protein levels, and weight change were studied in 16 non-steroid treated patients with severe head injury. Patients were evaluated during an average of 31.3 days from hospital admission to discharge. The mean measured energy expenditure (MEE) was 1.40 +/- 0.5 times predicted energy expenditure. Caloric balance [calories received = calories expended] was achieved by the 2nd week. Despite caloric balance and the administration of at least 1.5 g of protein per kg of body weight per day, the mean nitrogen balance was negative. There was a positive nitrogen balance in only 2 patients. These patients received a mean of 1.43 times the MEE in total kilocalories and 2.3 g of protein per kg of body weight. Fat and protein oxidation exceeded protein and fat administration for 3 weeks postinjury. Albumin levels dropped from a mean of 3.09 +/- 0.2 on admission to 1.98 +/- 0.4 within 2 weeks. The initial retinol binding protein levels were within the normal range, and the levels increased over time. There was marked weight loss (mean, 15.6 +/- 5.9 lb). Head injury induces a profound traumatic response identified by increased energy expenditure, a negative nitrogen balance, weight loss, hypoalbuminemia, and altered substrate oxidation. This response seems to be caused by the head injury alone and is not due to the administration of corticosteroids.

Adolescent↗
PubMed1985

Modulation of the activity of PALA by dipyridamole.

PALA is thought to inhibit an early step in de novo pyrimidine synthesis, causing depletion of intracellular pyrimidine nucleotides. Dipyridamole, a nucleoside transport inhibitor which can block restoration of nucleotide levels via the salvage pathway, was tested for its ability to augment the cytotoxicity of PALA against normal and malignant human cells in vitro. At the clinically relevant concentration of 1 microM, dipyridamole increased the cytotoxicity of PALA against a melanoma, a colon carcinoma, a promyelocytic leukemia (HL-60), and normal marrow (CFU-GM) in clonogenic assays. Dipyridamole produced 50% inhibition of uridine uptake in these cells at concentrations of less than 0.1 microM and reduced the LD50 of PALA by approximately 50% in mice. These results indicate that dipyridamole can markedly potentiate the activity of PALA in vitro and in vivo.

Animals↗
PubMed1985

Demonstration in multiple species of inducible hepatic cytochromes P-450 and their mRNAs related to the glucocorticoid-inducible cytochrome P-450 of the rat.

We have recently demonstrated that P-450p, a form of rat liver cytochrome P-450 inducible by steroids such as dexamethasone and pregnenolone-16 alpha-carbonitrile, by the macrolide antibiotic triacetyloleandomycin, and by phenobarbital, is immunochemically related to and shares 73% NH2-terminal amino acid sequence homology with rabbit cytochrome LM3c. Extending this interspecies comparison we now report that liver microsomes prepared from the rabbit, hamster, gerbil, and mouse contain inducible cytochromes P-450 that resemble P-450p in: (a) converting triacetyloleandomycin to a metabolite that forms a distinct spectral complex with cytochrome P-450 heme, (b) catalyzing the demethylation of erythromycin, and (c) reacting on immunoblots with antibodies directed against P-450p or LM3c. These three characteristics changed in parallel within treatment groups of a given species receiving different inducers of cytochrome P-450. However, there were striking qualitative and quantitative interspecies differences in the responses to inducers. For example, rifampicin was the most efficacious inducer of LM3c in the rabbit and yet was not at all an inducer of P-450p in the rat whereas pregnenolone-16 alpha-carbonitrile, an inducer in the rat, failed to induce LM3c in the rabbit. Immunoblot analysis of these microsomes revealed in each species except the rabbit a single immunochemically related protein. A second immunoreactive protein was present in microsomes from male and female and rifampicin- and dexamethasone-treated female rabbits. Two cloned cDNAs, which hybridized to a species of liver mRNA directing the synthesis of P-450p in a cell-free translation system, were used to probe Northern blots of liver RNAs. These revealed a single band of hybridizable mRNA in each species (except RNA from the rabbit which gave no signal even under conditions of reduced stringency) that was induced in qualitative proportions to that of the accumulated immunoreactive protein. We conclude that P-450p appears to be conserved in evolution and is represented in each of the species tested by one or more immunochemically related proteins which exhibit similar catalytic activities to those of P-450p.

Animals↗
PubMed1984

Evidence for the activation of the endogenous opiate system in hamsters infected with human blood flukes, Schistosoma mansoni.

Nociceptive thresholds were investigated in golden hamsters infected with the human blood fluke, Schistosoma mansoni. Increases in thermal thresholds suggestive of analgesia were evident by 20-25 days of infection. These increased further during a 40-42 day period. The altered responses were suppressed by the opioid antagonist naloxone. Non-invasive inhibition of the activity of the pineal gland by exposure to light also reduced nocturnal analgesia in schistosome infected animals. Naloxone antagonism and pineal inhibition of morphine- induced analgesia was obtained similarly in control, uninfected animals. Taken together, these findings suggest strongly that infection with S. mansoni results in a chronic activation of the endogenous opiate system.

Analgesia↗
PubMed1984

Cerebellar glioblastoma in childhood.

Cerebellar glioblastoma multiforme in childhood is extremely rare. Only ten such cases have been reported to date. Although treatment results are reported to be extremely poor, complete tumor clearance was achieved in a patient treated with superfractionated radiotherapy. She received high dose postoperative radiotherapy using a three times per day technique and is disease-free for more than three years posttherapy. This suggests that improved tumor response can be obtained by high dose postoperative radiotherapy using a modified fractionation technique.

Adolescent↗
PubMed1984

Intracerebral neutron brachytherapy for hemispheric glioblastoma multiforme. A pilot study.

The University of Kentucky Brain Tumor Study and Research Group has developed a new treatment protocol of interstitial brain brachytherapy using Californium-252 neutron source implantation in 1980. Only patients with malignant gliomas were eligible for this pilot study. Nine patients entered the Phase I trial of the protocol study between November 1980 and October 1981. According to the design of the protocol, all patients who had a verified histologic diagnosis of glioblastoma multiforme underwent postoperative intracerebral Cf-252 neutron source implantation, followed by 6 000 cGy of external photon beam irradiation. The purpose of this pilot study was to test the feasibility of interstitial Cf-252 neutron source implantation and only one implant afterloading applicator was used for brachytherapy. The implant applicator was placed in the center of tumor and the procedure was performed under CT guidance. In the assessment of the procedure, Karnofsky functional performance status, intellectual status, neurological examination, CT scans, and complications were used. All patients tolerated the procedure well and no serious complications were encountered. Despite the quality of these early treatments, there was some evidence of short-term benefit in duration of survival of the patients. We believe that further technical improvement to achieve an adequate isodose distribution to cover the tumor volume might result in longer duration improvement in survival.

Aged↗
PubMed1984

The development of hospital wide patient-education director competencies.

Members of the patient-education divisions of the Michigan Society of Healthcare Education and Training and the Great Lakes Chapter of the Society of Public Health Education drafted a model job description and related competencies, using representative position descriptions and a role delineation project as a basis. The product of this effort can serve as a model for hospital administrators hiring patient educators, professional organizations supporting patient education, universities and colleges training such specialists, and patient-education specialists pursuing continuing education.

Education Department, Hospital↗
PubMed1984

Modulation of cytarabine uptake and toxicity by dipyridamole.

The effect of dipyridamole, an inhibitor of membrane nucleoside transport, on the uptake and toxicity of cytarabine was examined in normal and malignant tissues. Preliminary pharmacokinetic data were obtained in mice and humans to determine appropriate dipyridamole dosage ranges for in vitro testing. At concentrations achievable in man, dipyridamole produced 75% and 94% reductions in cytarabine uptake in freshly harvested normal mouse and human bone marrow cells, respectively. Under the same conditions, greater than 90% reductions in cytarabine uptake were also seen in both L1210 murine leukemia and HL-60 human leukemia cells. In addition, treatment with dipyridamole also reduced the growth inhibitory effects of cytarabine on HL-60 cells in culture and protected mice from toxic doses of this antimetabolite. These results demonstrate the ability of dipyridamole to modulate the activity of cytarabine in both murine and human cells.

Animals↗
PubMed1983

Cutaneous stimulation of the bladder in multiple sclerosis: a case report.

We report on the use of transcutaneous electrical nerve stimulation to improve bladder emptying in a multiple sclerosis patient with a hypotonic bladder. Urodynamic testing demonstrated decreased bladder capacity, earlier first sensation and increased bladder pressure during trials of stimulation.

Adult↗