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Biomedical subjects

G Brown

Publications and source records attributed to G Brown.

At least 271 records · Page 15Linked to original sources
PubMed1992

The economic impact of clinical pharmacists' unsolicited recommendations.

Clinical pharmacists in a 580-bed teaching hospital reported all targeted recommendations that occurred during a 5-month evaluation period. Five types of clinical recommendations were identified: (1) to start drug therapy, (2) to stop drug therapy, (3) to increase drug dose, (4) to decrease drug dose, and (5) to suggest alternative drug therapy. Two thousand sixty-four unsolicited, accepted recommendations were submitted to the investigator by approximately eight holders of full-time equivalent positions dedicated to clinical pharmacy services during the evaluation period. Three hundred forty-four recommendations were selected (every sixth submitted recommendation) and evaluated for their economic impact. The costs of drugs, monitoring, and treatment for the drug regimens were compared before and after each recommendation. Three classes of drugs (antineoplastics, anti-infectives, and gastrointestinal agents) contributed more than 90% of the economic impact. The net economic impact of the evaluated recommendations was a cost saving of $4636.06; this extrapolated to a net cost saving of $34.10 per pharmacist-day.

British Columbia↗
PubMed1992

Criteria for the definition of Epstein-Barr virus association in Hodgkin's disease.

There is a clear association between the Epstein-Barr virus (EBV) and Hodgkin's disease (HD). EBV is not, however, detectable within the affected tissues of all cases. The proportion of positive cases varies from 15-79% depending on the assay used to detect EBV. The techniques utilised vary not only in sensitivity but in their ability to detect viral DNA, RNA, or protein and in their ability to demonstrate the cellular localisation of the virus. Thus, the biological significance of a positive result will vary depending on the method of analysis. In the present study, four different methods of detecting EBV were compared. RNA in situ hybridization was found to be the most practical method of detecting EBV in tumour cells. Using this assay EBV was detected in the Reed-Sternberg cells of 33% and 45% of the two series of HD cases examined in this study. We believe that these cases should be considered EBV-associated.

Adolescent↗
PubMed1992

Autism and developmental abnormalities in children with perinatal cocaine exposure.

Cocaine in all forms is the number one illicit drug of choice among pregnant women. Records of 70 children with cocaine exposure in utero who were referred for developmental evaluation at a large inner-city hospital were reviewed in an effort to determine whether a specific pattern of abnormalities could be discerned. Patients received physical examinations, neurological screenings, and behavioral and developmental assessments based on the Gesell Developmental Inventory, and the Denver Developmental Screening Test. Documentation of specified drug use was obtained by history. Mean age (SEM) at referral was 19.2 (1.7) months. All mothers used cocaine in one of its forms, although polydrug use was common. Growth parameters were low (median = 15th percentile). Significant neurodevelopmental abnormalities were observed, including language delay in 94% of the children and an extremely high frequency of autism (11.4%). The high rate of autistic disorders not known to occur in children exposed to alcohol or opiates alone suggests specific cocaine effects.

Adolescent↗
PubMed1991

Identification and characterization of receptors for tumor necrosis factor-alpha in the brain.

Specific receptors for murine TNF have been identified in homogenates of rodent brain. These receptors are saturable and bind TNF with sufficient affinity to ensure occupancy by cytokine elaborated during infection. 125I-mTNF was detected in four specific complexes of Mr 130,000, 90,000, 66,000 and 60,000 after affinity labeling. Solubilization of brain membranes into detergent increased binding capacity 4-fold which indicates the presence of latent receptors for mTNF in the brain. Specific binding was greatest in the brainstem, least in the cerebellum and was also detected in the cortex, thalamus and basal ganglia.

Animals↗
PubMed1991

Changes in the levels of inositol lipids and phosphates during the differentiation of HL60 promyelocytic cells towards neutrophils or monocytes.

HL60 cells were adapted to grow in a serum-free medium containing 1 mg l-1 inositol, in which they differentiated normally towards neutrophils (in 0.9% by volume dimethylsulphoxide) and towards monocytes (in 10 nM phorbol myristate acetate). Cells that had been equilibrium-labelled with [2-3H]myo-inositol contained a complex pattern of inositol metabolites, several of which were at relatively high concentrations. These included InsP5 and InsP6, which were present at concentrations of about 25 microM and 60 microM, respectively. Striking and different changes occurred in the levels of some of the inositol polyphosphates as the cells differentiated towards either neutrophils or monocytes. Most notable were a large but gradual accumulation of Ins(1,3,4,5,6)P5 as HL60 cells decreased in size and acquired neutrophil characteristics, and much more rapid and sequential declines in InsP4, InsP5 and InsP6 as the cells started to take on monocyte character. There was a marked accumulation of free inositol and of phosphatidylinositol in the cells during neutrophil differentiation, probably caused at least in part by an increased rate of inositol uptake providing an increased intracellular inositol supply. The same accumulation of Ins(1,3,4,5,6)P5 occurred during neutrophil differentiation, whether it was induced by dimethylsulphoxide or by a combination of retinoic acid and a T-lymphocyte cell line-derived differentiation factor. Ins(1,4,5)P3, a physiological intracellular mediator of Ca2+ release from membrane stores, did not change in concentration during these differentiation processes. These observations suggest that some of the more abundant cellular inositol polyphosphates play some important, but not yet understood, role either in the processes of haemopoietic differentiation or in the expression of differentiated cell character in myeloid cells.

Cell Differentiation↗
PubMed1991

Changes in the kinetics of inositol transport during TPA-induced differentiation of HL60 cells towards monocytes.

When exposed to the phorbol ester TPA, HL60 cells undergo growth arrest and differentiate towards monocytes. During TPA-induced differentiation there was a 2.6-fold increase in the rate of inositol transport (Vmax), a 2.1-fold increase in intracellular inositol and a 1.5-fold increase in inositol lipid. An increase in the Vmax of inositol transport did not occur when the variant cell line HL60Ast3 was exposed to TPA, which has been shown in this cell line to induce growth arrest but not differentiation. This observation suggests that the change in inositol transport during HL60 monocyte differentiation is specifically associated with the process of cell differentiation as opposed to growth arrest.

Biological Transport↗
PubMed1991

Carnitine in dried blood spots: a method suitable for neonatal screening.

A method is described which enables the quantitative determination of both free and total carnitine levels in dried blood spots. This method is suitable for neonatal screening for either primary or secondary carnitine deficiency. The 95% confidence interval for free carnitine was 26-76 mumol/l (median = 44) and for total carnitine was 35-102 mumol/l (median = 60).

Carnitine↗
PubMed1991

Energy status of cells lacking dystrophin: an in vivo/in vitro study of mdx mouse skeletal muscle.

Although great strides have been made in understanding the genetics of Duchenne muscular dystrophy (DMD), uncertainty still remains as to the metabolic changes which are associated with the disease. We have used the recently discovered animal model of DMD, the mdx mouse, to study aspects of high energy phosphate metabolism and metabolic control indices in dystrophic muscle. This model of DMD has the dual advantage of having a genetic defect which is homologous to that in human DMD, and it lacks the fatty infiltration and necrosis which makes biochemical analysis of DMD so difficult. We have used nuclear magnetic resonance spectroscopy (NMR) to monitor developmental changes in high energy phosphates and pH. No differences were observed between young (less than 40-50 days old) control and mdx mice. The pH increase and alterations in phosphate ratios (i.e., a decline in PCr/ATP) observed in adult mdx vs. control mice are qualitatively similar to those observed in humans. Biochemical analysis showed a small decline in ATP and PCr content and a decline in some indices of energy status in adult mdx mice. As young mdx mice appeared to be normal, the lack of dystrophin does not correlate with metabolic changes. The changes which were observed were small enough that alterations in fibre composition could be the major contributory factor.

Adenine Nucleotides↗
PubMed1991

Changes in inositol transport during DMSO-induced differentiation of HL60 cells towards neutrophils.

[3H]Inositol uptake by HL60 cells was measured during DMSO-induced differentiation towards neutrophils. The values for Km (53.2 microM) and Vmax (5.3 pmol/min per 10(6) cells) obtained for control HL60 cells are in good agreement with previously published figures for this cell line. Inositol transport into HL60 cells was an active, saturable and specific process which was unaffected by extracellular glucose concentrations. Inositol transport rates changed during DMSO-induced differentiation of HL60 cells towards neutrophils. An increase in inositol transport rates occurred during the first 4 days of exposure to 0.9% DMSO and was concommitant with the period leading to growth arrest and prior to the acquisition of the differentiated phenotype. These changes preceded the rise in intracellular inositol concentration from 10.9 to 132.7 microM seen between day 1 and day 5. After 4 days exposure to DMSO the rate of inositol transport fell to a value of 3.2 +/- 0.3 pmol/min per 10(6) cells at day 7, this was accompanied by a small reduction in intracellular inositol from a peak value of 132.7 to 112 microM. The inositol transport rate, thus, appears to closely accompany changes in the intracellular concentration of inositol. Inositol transport in human peripheral blood neutrophils was an order of magnitude slower than the value for uninduced HL60 cells, but the Km for inositol transport was similar in both cell types and was unchanged during HL60 differentiation. This suggests that changes in inositol transport rate are achieved by the modulation of a commonly expressed inositol transporter, one consequence of which is the alteration of intracellular inositol concentrations.

Biological Transport, Active↗
PubMed1991

Vitreous surgery for retinal detachment associated with choroidal coloboma.

We report the results of vitreous surgery in seven eyes with retinal detachments caused by retinal breaks at the margin of, or within, a choroidal coloboma. All seven eyes (100%) were reattached; visual acuities in five (71%) of the seven eyes improved from preoperative levels. Vitrectomy was combined with air-fluid exchange and endodrainage through preexisting retinal breaks or planned retinotomies in all but one of the cases. Part or all of the rim of the choroidal coloboma in six eyes underwent endophotocoagulation. The two eyes that did not experience postoperative visual improvement underwent intraoperative endolaser treatment 360 degrees around the optic nerve. If peripapillary endophotocoagulation is performed, especially through the papillomacular bundle, nerve fiber damage may occur and prevent visual recovery, despite retinal reattachment. For eyes with retinal detachment associated with choroidal colobomas involving the optic nerve, postoperative laser treatment through the papillomacular bundle may be preferable.

Adolescent↗
PubMed1991

Defective erythropoiesis in primary myelofibrosis associated with a chromosome 11 abnormality.

A case of primary myelofibrosis was identified with a previously unreported complex karyotype with two abnormal clones in addition to a proportion of normal cells: 46,XY,-2,-11, + der(2)t(2;11) (q24/31;q13), + mar and 45,XY,-2,-11, + der(2)t(2;11)(q24/31;q13), + mar, -17, del(7q). Study of circulating committed progenitors from this patient consistently showed (1) an absence of erythroid progenitors which is uncommon and (2) greatly increased granulocyte-monocyte progenitors (CFU-GM) which is generally observed in myelofibrosis. Further study showed that peripheral blood mononuclear cells co-cultured with irradiated normal bone marrow stroma generated increased numbers of CFU-GM compared with controls but failed to generate erythroid progenitors, providing evidence for an intrinsic defect in erythropoiesis. Only once previously has the absence of erythroid progenitors in primary myelofibrosis been studied in relation to cytogenetic abnormalities. This case also revealed a complex karyotype which, however, shared with our case a defect on chromosome 11. The identification of two cases of primary myelofibrosis which lack committed erythroid progenitor cells and which show in common a chromosomal defect on chromosome 11 point to the existence of genes on this chromosome which play a key role during erythropoiesis.

Aged↗