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D Brown

Publications and source records attributed to D Brown.

At least 235 records · Page 13Linked to original sources
PubMed1999

Caesarean myomectomy--a safe procedure. A retrospective case controlled study.

Sixteen women, with uterine fibroids in pregnancy, who were treated by caesarean myomectomy, were compared retrospectively with 16 women, without uterine fibroids who had caesarean section during the same period. Myomectomy was performed at caesarean section after delivery of the baby and the placenta, with the administration of intravenous oxytocin. The fibroid defects were occluded with continuous interlocking and fixed sutures. Routine caesarean section was performed on the subjects in the control group. The comparative efficacy of the procedure was measured by comparing pre- and post-operative haemoglobin levels, measured blood loss, need for blood transfusion, post-operative febrile morbidity and length of hospital stay in both groups. Caesarean myomectomy resulted in a mean blood loss of 495 ml (range 200-1000 ml) compared with 355 ml (range 150-900 ml) in the control group (P =0.907). The caesarean myomectomy group had a mean fall in haemoglobin level of 1.7 g/dl compared with a fall of 1.4 g/dl in the control group. There were no significant differences between the groups in the need for blood transfusion, post-operative febrile morbidity or length of hospital stay. The results indicate that caesarean myomectomy is safe and offers no significant increased risk to the patient over caesarean section alone. This is beneficial to the health sector by the avoidance of an interval myomectomy hence justifying the cost effectiveness of the procedure.

Journal Article↗
PubMed1999

Development of a patient information packet for veterans with cancer receiving chemotherapy.

BACKGROUND: Patient education is an important part of caring for cancer patients. Providing educational materials suitable to the particular patient population is crucial. Veterans with cancer represent a population that requires special educational materials. METHODS: A patient information packet (PIP) was developed for veteran cancer patients receiving chemotherapy. The PIP contains information about chemotherapy side effects, when to call for help, available resources, and information about support groups. RESULTS: The PIP was distributed by the oncology pharmacist to 96 newly diagnosed cancer patients. One-month evaluation of 85 patients revealed that 83 had utilized the materials. Thirty-four patients had read the PIP once; 32, twice; ten, three times; and six, four or more times. The PIP had helped 13 patients decide to call the VA Hospital and had helped 16 patients decide whom to call. CONCLUSION: The PIP, developed to meet the specific needs of this patient population, was well received and utilized.

Adult↗
PubMed1999

Short-term inflammatory responses following intratracheal instillation of fine and ultrafine carbon black in rats.

Ultrafine carbon black (ufCB) 14 nm in diameter and fine carbon black (CB) 260 nm in diameter were instilled intratracheally in rats at mass of 125 microg, and the bronchoalveolar lavage (BAL) profile at 6 h was assessed. UfCB generated a 50% neutrophil alveolitis 6 h after intratracheal instillation compared to CB, which showed similar activity to the phosphate-buffered saline (PBS) vehicle control. UfCB instillation also produced a marked increase in lactate dehydrogenase (LDH) levels in BAL fluid, which was associated with increased epithelial permeability measured as total protein. In contrast, CB had much less of an effect in increasing BAL protein. Although both particle types caused a decrease in glutathione (GSH) in lung tissue compared to control, the greatest depletion was seen in ufCB-treated animals. To investigate time response, bronchoalveolar lavage was carried out at 6 h, 24 h, and 7 days after a single 125-microg instillation of ufCB. Neutrophil influx was relatively persistent and was still maintained 7 days later. Tumor necrosis factor (TNF) production by BAL leukocytes increased gradually postinstillation, whereas NO production became significantly higher at 24 h after instillation and remained at raised levels up to 7 days. Higher doses of CB caused more inflammation than the ufCB. Thus, in the instillation model, a localized dose of particle over a certain level causes the particle mass to dominate the response, rather than the surface area. In contrast to the effect of CB, which showed a dose-related increasing inflammatory response, ufCB at the highest dose caused less of a neutrophil influx than at the lower dose. Six hours after intratracheal instillation, the threshold dose for neutrophil influx occurred at 50 microg. Calculation of surface area of particles instilled suggested that this was likely to be an overload-inducing dose of particles, as gauged from recent experiments with inhaled particles. In summary, this study provides evidence in a rat instillation model that ufCB has greater ability than CB to produce lung inflammation and oxidant stress at a relatively low dose of 125 microg. At high doses, however, BAL is not a reliable indicator of pulmonary response, since the overall response seems to scale to mass or volume of instilled particulate without an influence of surface area.

Animals↗
PubMed1999

Fibrinogen-impregnated collagen as a combined haemostatic agent and antibiotic delivery system in a porcine model of splenic trauma.

OBJECTIVE: To assess the effect of rifampicin on the haemostatic function of a fibrinogen-impregnated collagen fleece. DESIGN: Laboratory experiment. SETTING: Government research establishment, UK. MATERIAL: Six Large White pigs. INTERVENTIONS: Four 5 cm incisions were made in the spleen of each animal. Three of the wounds were each covered with a sheet of either dry, saline-soaked or rifampicin-soaked fibrinogen-impregnated collagen. MAIN OUTCOME MEASURES: The bleeding time and blood loss from each wound was recorded. Systemic serum rifampicin concentrations were measured using a Staphylococcus aureus inhibition assay. RESULTS: Dry fibrinogen-impregnated collagen resulted in significantly less blood loss (112 (21) compared with 39 (13)ml, p < 0.05) and shorter bleeding time (16 (2) compared with 9 (1) min, p < 0.01) than in untreated control wounds. Pre-soaking in saline or rifampicin solution had no significant effect on its haemostatic function. Rifampicin concentrations above the minimum inhibitory concentration were recorded in the systemic circulation 45 minutes after injury and persisted for the duration of the experiment. CONCLUSIONS: Fibrinogen-impregnated collagen is an effective haemostatic agent in splenic trauma that may be of use for both the local and systemic delivery of antibiotics.

Animals↗
PubMed1999

Antibody to herpes simplex virus type 2 as a marker of sexual risk behavior in rural Tanzania.

A serosurvey was conducted in a random sample of 259 women and 231 men in 12 rural communities in Mwanza Region, Tanzania, using a type-specific ELISA for Herpes simplex virus type 2 (HSV-2) infection. Seroprevalence rose steeply with age to approximately 75% in women >=25 years old and 60% in men >=30. After adjusting for age and residence, HSV-2 prevalence was higher in women who were married, in a polygamous marriage, Treponema pallidum hemagglutination assay (TPHA)-positive, had more lifetime sex partners, or who had not traveled. Prevalence was higher in men who were married, had lived elsewhere, had more lifetime partners, had used condoms, or were TPHA-positive. HSV-2 infection was significantly associated with recent history of genital ulcer. The association between HSV-2 infection and lifetime sex partners was strongest in those <25 years old in both sexes. This association supports the use of HSV-2 serology as a marker of risk behavior in this population, particularly among young people.

Adolescent↗
PubMed1999

Localization of sodium bicarbonate cotransporter (NBC) protein and messenger ribonucleic acid in rat epididymis.

An acidic environment is important for sperm maturation in the epididymis and also helps to maintain mature sperm in an immotile state during storage in this organ. Both an Na+/H+ exchanger and an H+ATPase have been implicated in this process. The H+ATPase is concentrated in specialized apical (and/or narrow) and clear cells of the epididymis, while the Na+/H+ exchanger has not yet been localized in situ. As in other proton-secreting epithelia, bicarbonate transport occurs in the epididymis, where it is implicated in luminal acidification. In this study we used an antibody raised against a fusion protein (maltose-binding protein: MBP-NBC-5) from the C-terminus of the recently cloned rat kidney Na+/HCO3- cotransporter (NBC) to localize this protein in the epididymis and vas deferens of the rat. The distribution of the respective mRNA was mapped by in situ hybridization. NBC message was strongly expressed in the initial segment and the intermediate zone of the epididymis, and the NBC-5 antibody gave a strong basolateral staining in both principal cells and apical/narrow cells in this region. Western blotting revealed a single band at about 160 kDa in the epididymis. The intensity of staining as well as mRNA levels decreased in the cauda epididymidis and in the vas deferens, where only weak staining was seen. Basolateral NBC may function in parallel with apical proton secretion to regulate luminal acidification and/or bicarbonate reabsorption in the excurrent duct system.

Animals↗
PubMed1999

The organizational context of non-lethal workplace violence: its interpersonal, temporal, and spatial correlates.

This article examines 993 violent incidents involving faculty, students, and staff that occurred at a highly ranked teaching and research university and its affiliated medical center. Violent incidents were included in the sample if they involved faculty, students, or staff, regardless of their specific location or context (i.e., whether they occurred on campus and/or off-campus and whether they occurred within the context of work or some other activity). The theoretical goal of the project was to compare work-related incidents with non-work-related incidents of interpersonal violence occurring in a single, multifunctioning, and professionally hierarchical organization. Data were collected over a 7-year period from three police departments (city, county, and university), university records, and criminal history records obtained from the state police. The coding protocol was developed to capture crime-scene information pertinent to each of the incidents. This included information about the victim, the perpetrator, the relationship between the victim and perpetrator, and the violent incident. The data were examined using nonparametric statistics and logistic regression to model predictive differences between the workplace and non-workplace incidents. The results suggest that the workplace incidents of violence differ from the non-workplace incidents according to their time, victim age, degree of victim injury, and whether the workplace is a medical location. The authors conclude that these differences are better explained by the movement of people in and out of the workplace who bring societal violence with them, rather than by a category or type of workplace violence.

Adult↗
PubMed1999

Seasonality and diversity of Group A rotaviruses in Europe.

Group A rotaviruses are a major cause of severe gastroenteritis in children under 4 y of age worldwide. Group A rotaviruses have been identified in many animal and bird species, they are antigenically complex, and multiple serotypes infect humans. Re-assortant rotavirus vaccines are now available which confer protection against severe illness due to rotavirus serotypes G1-4. Before vaccines are introduced it is necessary to establish the diversity of rotavirus in the target population to ensure efficacy and to establish a baseline for future surveillance strategies. The purpose of this review is to describe our current knowledge of the diversity of rotaviruses across Europe. Since multinational studies with standardized methodology have not been performed, this review is based on the available published studies. In Europe, more than 90% of Group A rotavirus strains that have been typed are of serotypes G1-4, with an average 8% of non-G1-4 strains in published studies. The percentage of non-typeable strains may fluctuate from one year to another, and has been as high as 18% in one study in Great Britain, indicating the need for a more systematic study. Group A rotavirus infection typically occurs as a winter peak in the European countries studied. Comparison of seasonality data from national laboratory surveillance systems showed seasonal differences, with the annual rotavirus peak occurring first in Spain, usually in December, followed by France in February, and ending in Northern Europe in England and Wales in February or March, and the Netherlands and Finland in March.

Child↗
PubMed1999

Role of iron in Nramp1-mediated inhibition of mycobacterial growth.

Innate resistance to mycobacterial growth is mediated by a gene, Nramp1. We have previously reported that Nramp1 mRNA from macrophages of Mycobacterium bovis BCG-resistant (Bcgr) mice is more stable than Nramp1 mRNA from macrophages of BCG-susceptible (Bcgs) mice. Based on these observations and on reports that show that the closely related Nramp2 gene is a metal ion transporter, we evaluated the effect of iron on the growth of Mycobacterium avium within macrophages as well as on the stability of Nramp1 mRNA. The addition of iron to macrophages from Bcgs mice resulted in a stimulation of mycobacterial growth. In contrast, iron increased the capacity of macrophages from Bcgr mice to control the growth of M. avium. When we treated recombinant gamma interferon (IFN-gamma)-activated macrophages with iron, we found that iron abrogated the growth inhibitory effect of IFN-gamma-activated macrophages from Bcgs mice but that it did not affect the capacity of macrophages from Bcgr mice to control microbial growth. A more detailed examination of the effect of iron on microbial growth showed that the addition of small quantities of iron to resident macrophages from Bcgr mice stimulated antimicrobial activity within a very narrow dose range. The effect of iron on the growth inhibitory activity of macrophages from Bcgr mice was abrogated by the addition of catalase or mannitol to the culture medium. These results are consistent with an Fe(II)-mediated stimulation of the Fenton/Haber-Weiss reaction and hydroxyl radical-mediated inhibition of mycobacterial growth.

Animals↗
PubMed1999

Application of a low cost telemedicine link to the diagnosis of neonatal congenital heart defects by remote consultation.

OBJECTIVE: To determine whether accurate remote echocardiographic diagnosis of congenital heart disease could be achieved using a low cost telemedicine system. DESIGN: Echocardiographic images obtained by a paediatrician from neonates suspected of having congenital heart disease were transmitted by a telemedicine link across two integrated service digital network (ISDN) lines to a regional paediatric cardiology unit for interpretation by a consultant paediatric cardiologist. The "tele-echo" diagnosis was verified by the paediatric cardiologist on direct consultation and echocardiography. SETTING: Neonatal unit of Altnagelvin Hospital, Londonderry (a district general hospital) and the regional paediatric cardiology department, Royal Belfast Hospital for Sick Children. MAIN OUTCOME MEASURES: Accuracy of the diagnosis made using the telemedicine link; impact on patient management. RESULTS: Between September 1995 and September 1997 echocardiographic images were transmitted on 63 patients. A diagnosis was made in 61 (97%) (transmitted images were unsatisfactory in two). Congenital heart disease was diagnosed in 42 patients. Fourteen patients with major congenital heart disease were accurately diagnosed within 24 hours of admission using the telemedicine link and were transferred to the regional paediatric cardiology unit. A further 28 with less serious congenital heart disease continued to be managed at the district general hospital. Congenital heart disease was excluded in 19. Follow up consultation confirmed accurate diagnosis or exclusion of congenital heart disease in 57 (93%). There were four inaccurate diagnoses (6.3%; three undetected small ventricular septal defects and one pulmonary stenosis). CONCLUSIONS: Transmitted images were of sufficient quality to allow confirmation or exclusion of major congenital heart disease. The telemedicine link facilitated early diagnosis and initiation of appropriate management in patients with complex congenital heart disease and avoided the need for transfer in those where significant congenital heart disease was excluded.

Costs and Cost Analysis↗
PubMed1999

GAIP, a Galphai-3-binding protein, is associated with Golgi-derived vesicles and protein trafficking.

Proteins of the regulators of G protein signaling (RGS) family bind to Galpha subunits to downregulate their signaling in a variety of systems. Galpha-interacting protein (GAIP) is a mammalian RGS protein that shows high affinity for the activated state of Galphai-3, a protein known to regulate post-Golgi trafficking of secreted proteins in kidney epithelial cells. This study aimed to localize GAIP in epithelial cells and to investigate its potential role in the regulation of membrane trafficking. LLC-PK1 cells were stably transfected with a c-myc-tagged GAIP cDNA. In the transfected and untransfected cells, GAIP was found in the cytosol and on cell membranes. Immunogold labeling showed that membrane-bound GAIP was localized on budding vesicles around Golgi stacks. When an in vitro assay was used to generate vesicles from isolated rat liver and Madin-Darby canine kidney cell Golgi membranes, GAIP was found to be concentrated in fractions of newly budded Golgi vesicles. Finally, the constitutive trafficking and secretion of sulfated proteoglycans was measured in cell lines overexpressing GAIP. We show evidence for GAIP regulation of secretory trafficking before the level of the trans-Golgi network but not in post-Golgi secretion. The location and functional effects of GAIP overlap only partially with those of Galphai-3 and suggest multiple roles for GAIP in epithelial cells.

Animals↗
PubMed1999

Effect of acidification on the location of H+-ATPase in cultured inner medullary collecting duct cells.

In previous studies, our laboratory has utilized a cell line derived from the rat inner medullary collecting duct (IMCD) as a model system for mammalian renal epithelial cell acid secretion. We have provided evidence, from a physiological perspective, that acute cellular acidification stimulates apical exocytosis and elicits a rapid increase in proton secretion that is mediated by an H+-ATPase. The purpose of these experiments was to examine the effect of acute cellular acidification on the distribution of the vacuolar H+-ATPase in IMCD cells in vitro. We utilized the 31-kDa subunit of the H+-ATPase as a marker of the complete enzyme. The distribution of this subunit of the H+-ATPase was evaluated by immunohistochemical techniques (confocal and electron microscopy), and we found that there is a redistribution of these pumps from vesicles to the apical membrane. Immunoblot evaluation of isolated apical membrane revealed a 237 +/- 34% (P < 0.05, n = 9) increase in the 31-kDa subunit present in the membrane fraction 20 min after the induction of cellular acidification. Thus our results demonstrate the presence of this pump subunit in the IMCD cell line in vitro and that cell acidification regulates the shuttling of cytosolic vesicles containing the 31-kDa subunit into the apical membrane.

Acids↗
PubMed1999

Expression of NCAM recapitulates tubulogenic development in kidneys recovering from acute ischemia.

Recovery of the kidney from acute renal failure relies on a sequence of events including epithelial cell dedifferentiation and proliferation followed by differentiation and restoration of the functional integrity of the nephron. The factors responsible for, and the significance of, reversion to a less differentiated cell phenotype and its relationship to the proliferative response after ischemia are poorly understood. In an attempt to identify adhesion molecules that may be influential in the recovery process, the expression of neural cell adhesion molecule (NCAM) and markers of epithelial differentiation and proliferation were analyzed at various times after an ischemic insult. In maturing nephrons, NCAM is detectable by immunohistochemistry in renal vesicles, S-shaped bodies, and early tubules. There is minimal cellular NCAM expression in normal tubules of the adult kidney. In contrast, in postischemic kidneys, NCAM expression is abundant in S3 proximal tubule cells 5 days after reperfusion. As in developing tubules, NCAM is concentrated in basal and lateral aspects of cells that have no apical gp330 or dipeptidyl peptidase IV detectable on their brush border. The expression of NCAM is preceded by disassembly of the brush border and proliferation of surviving S3 cells, which is most prominent at 2 days postischemia. NCAM expression persists in some flattened and dedifferentiated cells for up to 7 wk after ischemia. Thus proximal tubule epithelial cells of the postischemic kidney express NCAM in a pattern that recapitulates the expression of NCAM in the developing kidney. Such reversion of phenotype extends at least back to the early stages of renal vesicle formation, and this reversion may represent a critical step in the reestablishment of a normal tubule. NCAM-matrix interactions may mediate the motogenic and mitogenic responses of the dedifferentiated epithelium that are critical to reestablishment of a functional proximal tubule.

Animals↗
PubMed1999

Reduced water permeability and altered ultrastructure in thin descending limb of Henle in aquaporin-1 null mice.

It has been controversial whether high water permeability in the thin descending limb of Henle (TDLH) is required for formation of a concentrated urine by the kidney. Freeze-fracture electron microscopy (FFEM) of rat TDLH has shown an exceptionally high density of intramembrane particles (IMPs), which were proposed to consist of tetramers of aquaporin-1 (AQP1) water channels. In this study, transepithelial osmotic water permeability (Pf) was measured in isolated perfused segments (0.5-1 mm) of TDLH in wild-type (+/+), AQP1 heterozygous (+/-), and AQP1 null (-/-) mice. Pf was measured at 37 degrees C using a 100 mM bath-to-lumen osmotic gradient of raffinose, and fluorescein isothiocyanate (FITC)-dextran as the luminal volume marker. Pf was (in cm/s): 0.26 +/- 0.02 ([+/+]; SE, n = 9 tubules), 0.21 +/- 0.01 ([+/-]; n = 12), and 0.031 +/- 0.007 ([-/-]; n = 6) (P < 0.02, [+/+] vs. [+/-]; P < 0.0001, [+/+] vs. [-/-]). FFEM of kidney medulla showed remarkably fewer IMPs in TDLH from (-/-) vs. (+/+) and (+/-) mice. IMP densities were (in microm-2, SD, 5-12 micrographs): 5,880 +/- 238 (+/+); 5,780 +/- 450 (+/-); and 877 +/- 420 (-/-). IMP size distribution analysis revealed mean IMP diameters of 8.4 nm ([+/+] and [+/-]) and 5.2 nm ([-/-]). These results demonstrate that AQP1 is the principal water channel in TDLH and support the view that osmotic equilibration along TDLH by water transport plays a key role in the renal countercurrent concentrating mechanism. The similar Pf and AQP1 expression in TDLH of (+/+) and (+/-) mice was an unexpected finding that probably accounts for the unimpaired urinary concentrating ability in (+/-) mice.

Animals↗
PubMed1999

Dual role of the basic helix-loop-helix transcription factor scleraxis in mesoderm formation and chondrogenesis during mouse embryogenesis.

Scleraxis is a basic helix-loop-helix (bHLH) transcription factor shown previously to be expressed in developing chondrogenic cell lineages during embryogenesis. To investigate its function in embryonic development, we produced scleraxis-null mice by gene targeting. Homozygous mutant embryos developed normally until the early egg cylinder stage (embryonic day 6.0), when they became growth-arrested and failed to gastrulate. Consistent with this early embryonic phenotype, scleraxis was found to be expressed throughout the embryo at the time of gastrulation before becoming restricted to chondrogenic precursor cells at embryonic day 9.5. At the time of developmental arrest, scleraxis-null embryos consisted of ectodermal and primitive endodermal cell layers, but lacked a primitive streak or recognizable mesoderm. Analysis of molecular markers of the three embryonic germ layers confirmed that scleraxis mutant embryos were unable to form mesoderm. By generating chimeric embryos, using lacZ-marked scleraxis-null and wild-type embryonic stem cells, we examined the ability of mutant cells to contribute to regions of the embryo beyond the time of lethality of homozygous mutants. Scleraxis-null cells were specifically excluded from the sclerotomal compartment of somites, which gives rise to the axial skeleton, and from developing ribs, but were able to contribute to most other regions of the embryo, including mesoderm-derived tissues. These results reveal an essential early role for scleraxis in mesoderm formation, as well as a later role in formation of somite-derived chondrogenic lineages, and suggest that scleraxis target genes mediate these processes.

Animals↗
PubMed1999

Effect of neonatal exposure to estrogenic compounds on development of the excurrent ducts of the rat testis through puberty to adulthood.

Neonatal exposure to diethylstilbestrol (DES) can alter the structure of the testicular excurrent ducts in rats. We characterized these changes according to dose and time posttreatment and established whether potent estrogens (ethinyl estradiol), environmental estrogens (genistein, octylphenol, bisphenol A, parabens), and tamoxifen induce such changes. Rats were administered these compounds neonatally and assessed at several time points during (day 10, or day 18 for some treatments) and after (days 18, 25, 35, and 75) the treatment period to detect any changes in testis weight, distension of the rete testis and efferent ducts, epithelial cell height in the efferent ducts, and immunoexpression of the water channel aquaporin-1 (AQP-1). Treatment with DES (10, 1, or 0.1 microg/injection; equivalent to 0.37, 0.037, or 0.0037 mg/kg/day, respectively) induced dose-dependent changes in testis weight and all parameters. These effects were most pronounced at days 18 and 25 and appeared to lessen with time, although some persisted into adulthood. Neonatal treatment with ethinyl estradiol (10 microg/injection; equivalent to 0.37 mg/kg/day) caused changes broadly similar to those induced by 10 mg DES. Administration of tamoxifen (2 mg/kg/day) caused changes at 18 days that were similar to those induced by 1 microg DES. Treatment with genistein (4 mg/kg/day), octylphenol (2 mg/injection; equivalent to 150 mg/kg/day), or bisphenol A (0.5 mg/injection; equivalent to 37 mg/kg/day) caused minor but significant (p<0.05) decreases in epithelial cell height of the efferent ducts at days 18 and/or 25. In animals that were followed through to 35 days and/or adulthood, these changes were no longer obvious; other parameters were either unaffected or were affected only marginally and transiently. Administration of parabens (2 mg/kg/day) had no detectable effect on any parameter at day 18. To establish whether these effects of estrogens were direct or indirect (i.e., resulting from reduced follicle-stimulating hormone/luteinizing hormone secretion), the above end points were assessed in animals in which gonadotropin secretion was suppressed neonatally by administration of a gonadotropin-releasing hormone antagonist. This treatment permanently reduced testis weight, but did not affect any of the other end points, apart from a minor transient reduction in efferent duct epithelial cell height at 18 days. This study suggests that structural and functional (expression of AQP-1) development of the excurrent ducts is susceptible to impairment by neonatal estrogen exposure, probably as a consequence of direct effects. The magnitude and duration of adverse changes induced by treatment with a range of estrogenic compounds was broadly comparable to their estrogenic potencies reported from in vitro assays.

Animals↗