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Biomedical subjects

E Brown

Publications and source records attributed to E Brown.

At least 19 recordsLinked to original sources

Compact and trabecular components of the spine using quantitative computed tomography.

A computer algorithm was employed to quantify separately cortical and trabecular bone mineral density (BMD) from single energy computed tomography (CT) scans of 139 vertebrae (L1-L3) of 50 normal female subjects. In addition, the trabecular-to-integral and cortical-to-integral mass ratios were determined using digital image segmentation techniques. They showed that for the central 8-mm vertebral slice, the mass of integral bone consists of about one-fifth trabecular and four-fifth cortical bone. The trabecular-to-integral volume ratios were 0.37 +/- 0.08 and 0.63 +/- 0.08, respectively. Based on cross-sectional data from this subject group, the average annual loss was -2.21 +/- 0.15 mg/cm3 or -1.84 +/- 0.12% for trabecular bone, -3.15 +/- 0.25 mg/cm3 or -1.01 +/- 0.08% for cortical bone, and -2.60 +/- 0.20 mg/cm3 or -1.09 +/- 0.09% for the integral bone. The proportions of the age-related loss of BMD from the integral bone which originated from trabecular and cortical bone were 29.5 and 70.5%, respectively.

Adult

Circulating immune complexes may play a regulatory and pathogenic role in experimental autoimmune uveoretinitis.

We compared the time course of changes in serum levels of circulating immune complexes (CICs) and of IgG antibody after sensitization of albino Lewis and pigmented Lister strain rats with uveitogenic (retinal S-antigen) and non-uveitogenic (ovalbumin) protein antigens of comparable molecular weight. Normal levels of CICs were far lower in Lewis rats in which experimental autoimmune uveoretinitis (EAU) takes the form of a severe panuveitis, than in Lister rats, in which the disease is mild, focal, confined to the posterior segment, and of lower incidence. After sensitization with either S-antigen or ovalbumin, polyethylene-glycol-precipitable CIC (PEG-CIC) peaked and fell as IgG antibody levels rose in both rat strains. However, peak levels of PEG-CIC were lower and subsequent IgG antibody levels were higher in the Lewis strain than in the less susceptible Lister strain. In both strains of rat these linked PEG-CIC/IgG antibody responses occurred earlier after sensitization with uveitogenic (S-) antigen than with ovalbumin, whether or not individual S-antigen-sensitized Lister rats developed EAU. In contrast, complement-binding CIC rose substantially only in those rats of both strains displaying EAU in response to S-antigen and not in response to ovalbumin. We suggest that immune complex (idiotypic) regulation of IgG antibody responses may be more readily perturbed by a pathogenic autoantigen (S-antigen) than by a bland antigen (ovalbumin). We also suggest that differences between the balance of regulatory and pathogenic CIC responses to uveitogenic retinal antigen may underlie or reflect strain differences in susceptibility to and severity of EAU.

Animals

Formation and clearance of interstitial metabolites of dopamine and serotonin in the rat striatum: an in vivo microdialysis study.

In vivo microdialysis was employed in order to characterize the steady-state kinetics of the turnover of specific dopamine and serotonin metabolites in the rat striatum 48 h after surgery. Inhibitors of monoamine oxidase (MAO; pargyline) and catechol-O-methyltransferase (COMT; Ro 40-7592) were administered, either separately or in conjunction, at doses sufficient to block these enzymes in the CNS. In some experiments, the acid metabolite carrier was blocked with probenecid. Temporal changes were then observed in the efflux of interstitial dopamine, 3-methoxytyramine (3-MT), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA). The fractional rate constants for the accumulation or disappearance of the metabolites could be determined after pharmacological blockade of catabolic enzymes or the acid metabolite carrier. Interstitial 5-HIAA was found to be cleared with a half-life of approximately 2 h. After blockade of either MAO or COMT, HVA disappeared with a half-life of 17 min. Experiments employing probenecid suggested that some of the interstitial HVA was cleared by the acid metabolite carrier, the remainder being cleared by a probenecid-insensitive process, possibly conjugation. After MAO inhibition, DOPAC disappeared with an apparent half-life of 11.3 min. The rate of 3-MT accumulation after pargyline indicated that the majority of interstitial HVA (> 95%) is formed from DOPAC rather than 3-MT. The formation of 3-MT from interstitial dopamine, calculated from the accumulation rate of 3-MT after pargyline, appeared to follow first-order kinetics (k = 0.1 min-1).

Animals

Populations of larvae of anopheles spp. in natural breeding sites in western Venezuela, an area of refractory malaria.

Studies have been undertaken into on the diversity and relative abundance of larvae of Anopheles (Nyssorhynchus) spp. in 22 permanent or temporary pools in an area of 70 km2 in the eastern piedmont of the Venezuela Andes, between the mountains and the plains, an area in which malaria is refractory and A. nuñeztovari is present. Twelve species were identified, the most frequent, abundant and sympatric being A. triannulatus, A. albitarsis, A. nuñeztovari, A. oswaldoi and A. strodei. The samples from the permanent pools showed greater diversity of species and greater numbers of larvae than the samples from the temporary pools. The existence of the same larval associations in pools of other localities in the eastern piedmont of the Venezuelan Andes suggests the possibility of the making an ecological map of the breeding sites of A. nuñeztovari and for these anophelines in a region extending for 430 km.

Animals

CNS complications of cocaine abuse: prevalence, pathophysiology, and neuroradiology.

The United States is facing an epidemic of cocaine use by adolescents and young adults from all socioeconomic backgrounds. Epidemiologic data suggest that the use of the drug continues to increase on a year-by-year basis. This is a serious public health problem because cocaine is highly addictive and is associated with a variety of serious complications. In the CNS, these include stroke, intracerebral hemorrhage, vascular spasm, and possibly vasculitis. Seizures and sudden death have been reported. Cocaine use during pregnancy may be associated with fetal hypoxia, intracerebral hemorrhage, and possibly congenital malformations in the neonate. Many of these complications have been recognized only in the last 5-10 years. For example, ischemic changes in the brains of chronic cocaine abusers have been reported only recently. Because even further increases in cocaine use are predicted by drug enforcement officials, it is expected that radiologists will encounter its complications more frequently in the future. Therefore, radiologists should become familiar with the radiologic manifestations of the drug's effects. This article describes the drug's pathophysiology and complications and discusses the evolving role of imaging procedures.

Brain

Computed tomography of the calves. A screening procedure in the diagnosis of unilateral thrombosis of the deep veins of the lower limbs.

A prospective study of twelve patients, referred to the Department of Radiology of the University Hospital of the West Indies between March, 1990 and November, 1991 with a clinical diagnosis of deep vein thrombosis, was undertaken. All patients had computed tomography of the calves, as well as venography of the affected limb. Six patients (50%) had positive venograms. Of these, five had a difference of greater than 10% between the areas of the muscular compartments of the two limbs. Six patients had negative venograms but only three demonstrated a difference of a similar magnitude. The ratios of the area of the muscular compartment to the total limb area were also compared. Two of the six patients with positive venograms showed a greater ratio in the affected limb. One of the six patients with negative venograms showed a greater ratio in the affected limb. In this study, 83.3% of patients who did not have thrombosis of the deep veins of the calves had a ratio of muscular area to total limb area that was less than or equal to that of the unaffected side. This latter finding provides a potentially useful means of screening patients referred for venograms.

Humans

Endocervical glandular atypia in Papanicolaou smears.

The importance of endocervical glandular atypia in a cervicovaginal Papanicolaou smear has not been fully investigated. Between July 1988 and June 1989, 21,930 cervicovaginal smears were reviewed by the Massachusetts General Hospital Cytopathology Laboratory. One hundred smears with endocervical atypia were identified, an incidence of 0.46%. Follow-up was available on 63 cases: Seven had negative follow-up smears for at least 2 years, 15 had negative biopsies, seven had endocervical polyps, two had endometrial hyperplasia, eight had mild dysplasia, five had moderate dysplasia, six had severe dysplasia, six had squamous carcinoma in situ, five had adenocarcinoma in situ, and two had invasive adenocarcinoma. Twelve women's smears showed endocervical atypia with features suggestive of reactive atypia; three of these had dysplasia. Twenty-six (41%) of the Papanicolaou smears with endocervical atypia had coexisting squamous atypia or dysplasia. We conclude that endocervical atypia may be associated with substantial cervical disease in as many as half of cases.

Adult

Analysis of the genes involved in the insulin transmembrane mitogenic signal in Chinese hamster ovary cells, CHO-K1, utilizing insulin-independent mutants.

CHO-K1 cells, wild type (WT), grow in a defined medium with insulin as the only essential hormone. When starved for insulin, these cells accumulate in G0/G1 stage. Insulin binding to its receptor stimulates DNA synthesis and cell division and induces an increase in abundance of mRNA for c-fos, c-jun, Krox-20, Krox-24 (zif/268), fra-1, jun-B, c-myc, and JE. The kinetics of induction of these genes are similar to that shown with serum induction of 3T3. These genes show maximum stimulation at insulin concentrations of 20, 160, or 320 ng/ml and their expression is inhibited at higher concentrations. The addition of cycloheximide results in superinduction. The WT and insulin-independent mutants show no detectable signal for KC, fos-b, or nur77 and no increase over the basal level of pI-15, probably eliminating these genes as participants in the insulin mitogenic signal. These mutants synthesize DNA in the absence of insulin at rates that vary from 4 to 12 times that of the quiescent (insulin unstimulated) WT and are further inducible by insulin. The mutants have "constitutive" levels of Krox-24 (zif/268), fra-1, jun-B, c-myc, and JE (INS-type 2 genes) mRNAs that vary from mutant to mutant, reaching a maximum of an 8-fold increase for fra-1 and JE over the quiescent WT levels. There were no detectable levels of mRNA for genes c-fos and Krox-20 and no increase in level of mRNA for c-jun (INS-type 1 genes) as compared to the quiescent WT. Thus, although these INS-type 1 and type 2 genes may be involved in the full insulin mitogenic signal, the constitutive up-regulation of only genes in INS-type 2 is sufficient for insulin-independent DNA synthesis and cell division. Analysis of hybrids constructed between WT and mutant 27 indicate that the mutant phenotype is recessive, pointing to the existence of a regulatory gene producing a negative regulator.

Animals

Randomized trial of one-dose versus six-dose cefazolin prophylaxis in elective general thoracic surgery.

The objective of this study was to compare the efficacy of one to six doses of cefazolin as prophylaxis in general thoracic surgery using a randomized, double-blind design. Two-hundred eight consecutive patients admitted to a regional thoracic surgery unit for elective thoracotomy and lung resection were eligible for the trial. There were no wound infections in the one-dose group and two in the six-dose group (95% confidence intervals [CI]: -0.008, +0.048 [The positive number refers to the largest possible difference in favor of the one-dose group and the negative number, the largest possible difference in favor of the six-dose group]). Each group had eight postoperative chest infections (CI: -0.075, +0.077) and three empyemas (CI: -0.004, +0.050). Thirty-day mortality was 5% in the one-dose group and 4% in the six-dose group (CI: -0.053, +0.069). Postoperative duration of hospital stay, requirement for antibiotics, and the need for reoperation were comparable. These results suggest that six doses of cefazolin do not confer clinically important benefit beyond that obtained from a single dose for prophylaxis of wound infection in elective general thoracic surgery.

Cefazolin

Is antibiotic prophylaxis necessary for internal fixation of low-energy fractures?

A series of 54 patients who had low-energy, closed fractures requiring internal fixation were entered into a randomized prospective study comparing prophylactic antibiotics with no treatment. In five patients who did not have antibiotics a superficial wound infection or fever was recorded. In those who received antibiotics, no infection or fever was detected. However, there was no statistical difference between the two groups, and it is concluded that there is no need for prophylactic antibiotics when internally fixing low-energy fractures.

Adolescent

Form perception at birth: Cohen and Younger (1984) revisited.

Cohen (1988; Cohen & Younger, 1984) has suggested that there is a shift in the perception of form sometime after 6 weeks of age. Prior to this age infants can remember the specific orientations of line segments, but cannot process and remember the angular relations that line segments can make. Experiment 1 used simple line stimuli with newborn infants to test this suggestion. Following habituation to a simple two-line angle the newborns dishabituated to a change of orientation but not to a change in angle, confirming Cohen and Younger's suggestion that orientation is a powerful cue in early shape perception. In Experiments 2 and 3 newborns were familiarized either to an acute or to an obtuse angle that changed its orientation over trials. On subsequent test trials the babies gave strong novelty preferences to a different angle. Alternative interpretations of the results are discussed, but these experimental findings are compatible with the suggestion that newborns can quickly learn to process angular relations, and that rudimentary form perception may not be dependent on a lengthy period of learning and/or maturation for its development.

Attention

A comparison of Collins and UW solutions for cold ischemic preservation of the rat liver.

A new solution which can extend successful preservation times for hepatic allografts was recently developed at the University of Wisconsin (UW). To examine the mechanism of improved viability using this solution, we developed a model of orthotopic hepatic transplantation in the rat. As a baseline study, we compared parameters of viability of allografts preserved in Collins solution to those preserved in UW, including survival, bile output, peak AST, and allograft weight change during storage. Seventy-four rats were transplanted following storage in Collins solution and 70 rats were transplanted after storage in UW. Cold-storage time varied between 2 and 24 hr. The survival with preservation in UW was significantly better than that with Collins when storage time was greater than 2 hr. The preservation time for a viable organ using UW was greater than double that using Collins. The peak AST using UW was lower than that with Collins for cold ischemic times (CIT) up to 10 hr, with significance demonstrated at 5-6 and 7-8 hr when compared with Collins. Prolonged CIT resulted in an increase in liver weight with Collins-preserved livers and a decrease in weight with UW-preserved livers. Using a model of orthotopic liver transplantation in the rat, we demonstrated a doubling of preservation time when UW solution was substituted for Collins. Similar improvements in recipient survival and biochemical parameters of injury have been demonstrated in the canine model and in human clinical trials.

Adenosine

Coliphage Q beta RNA replication: RNA catalytic for single-strand release.

We have generated 14 recombinant RNA templates for Q beta replicase, each having either an exogenous inverted repeat sequence or a sequence with no repeat. These templates were used to initiate in vitro replication by Q beta replicase in amounts that saturated the enzyme. We observed that replication rates for RNAs that putatively contained secondary structures in the recombinant sequences ranged from 33 to 69% that of a wild-type MDV-1 RNA control, regardless of the size of the inserted hairpin. Moreover, most of the newly synthesized RNA was present as single strands. Alternatively, RNAs that contained exogenous sequences not expected to form secondary structures exhibited replication rates less than 25% that of MDV-1. In each case, the reaction rate was correlated with the length of the insertion, and the majority of product RNA consisted of duplexed molecules (complementary plus and minus strands hybridized together). When these same recombinant RNAs were used in reactions in which the molar amount of RNA template was 10(6)-10(7) times lower than that of the replicase, only those that putatively contained secondary structures survived in the replication reaction. Our results are consistent with the theory that hairpin structure formation during RNA synthesis by Q beta replicase directly influences the regeneration of single-stranded RNA products.

Base Sequence