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Biomedical subjects

D Brown

Publications and source records attributed to D Brown.

At least 271 records · Page 15Linked to original sources
PubMed1998

Biodistribution, stability, and antiviral efficacy of liposome-entrapped phosphorothioate antisense oligodeoxynucleotides in ducks for the treatment of chronic duck hepatitis B virus infection.

This study investigated the feasibility of using liposomes to increase the hepatic delivery and antiviral efficacy of phosphorothioate antisense oligodeoxynucleotides (PS-ODN) for the in vivo treatment of hepatitis B virus (HBV) infection. Ducks infected with duck hepatitis B virus (DHBV) were used as the model. We studied the stability of an antisense PS-ODN in duck plasma, its integrity during the process of liposome entrapment, its in vivo biodistribution, plasma clearance, and excretion. In addition, the intrahepatic distribution of a labeled free and liposome-entrapped ODN was also investigated. The results of our studies show that: 1) phosphorothioate ODN remain stable during the process of liposome entrapment; 2) are stable in duck plasma for many hours; 3) are rapidly cleared from the plasma when injected intravenously; 4) intravenous injection of antisense ODNs entrapped within liposomes enhances delivery of the ODN to the liver; and 5) inhibit DHBV replication. Serum DHBV DNA levels fell rapidly, with a corresponding decrease in intrahepatic viral replicative intermediates at the end of the 5-day study period. Although inhibition of viral replication and a fall in the target protein was observed, a marked inhibition of viral replication was also observed with high doses of a random-sequence ODN. Thus, it is not certain that inhibition of viral replication was entirely through an antisense mechanism. Therefore, liposomes may be effective vehicles to improve the delivery of antisense oligonucleotides to the liver for the therapy of hepatotropic viruses.

Animals↗
PubMed1998

New aspects of firing pattern autocontrol in oxytocin and vasopressin neurones.

In the rat, oxytocin (OT) and vasopressin (AVP) neurones exhibit specific electrical activities which are controlled by OT and AVP released from soma and dendrites within the magnocellular hypothalamic nuclei. OT enhances amplitude and frequency of suckling-induced bursts, and changes basal firing characteristics: spike patterning becomes very irregular (spike clusters separated by long silences), firing rate is highly variable, oscillating before facilitated bursts. This unstable behaviour which markedly decreases during hyperosmotic stimulation (interrupting bursting) could be a prerequisite for bursting. The effects of AVP depend on the initial phasic pattern of AVP neurones: AVP excites weakly active neurones (increasing burst duration, decreasing silences) and inhibits highly active neurones; neurones with intermediate phasic activity are unaffected. Thus, AVP ensures all AVP neurones discharge with moderate phasic activity (bursts and silences lasting 20-40 s), known to optimise systemic AVP release. V1a-type receptors are involved in AVP actions. In conclusion, OT and AVP control their respective neurones in a complex manner to favour the patterns of activity which are the best suited for an efficient systemic hormone release.

Animals↗
PubMed1998

Vasopressin regulated trafficking of a green fluorescent protein-aquaporin 2 chimera in LLC-PK1 cells.

Aquaporin 2 (AQP2) transfected into LLC-PK1 cells functions as a vasopressin-regulated water channel that recycles between intracellular vesicles and the plasma membrane upon vasopressin stimulation. The green fluorescent protein (GFP) of the jellyfish, Aequorea victoria, was used as an autofluorescent tag to monitor AQP2 trafficking in transfected LLC-PK1 cells. Two chimeras were constructed, one in which GFP was fused to the amino-terminus of AQP2 [GFP-AQP2(NT)] and the second in which it was fused to the carboxyl-terminus [AQP2-GFP(CT)]. The GFP-AQP2(NT) chimera trafficked in a regulated pathway from intracellular vesicles to the basolateral plasma membrane in response to vasopressin or forskolin stimulation of cells. In contrast, the AQP2-GFP(CT) chimera expressed in LLC-PK1 cells was localized constitutively on both apical and basolateral plasma membranes. The cellular location of this chimera was not modified by vasopressin or forskolin. Thus, while the GFP-AQP2(NT) chimera will be useful to study AQP2 trafficking in vitro, the abnormal, constitutive membrane localization of the AQP2-GFP(CT) chimera suggests that one or more trafficking signals exist on the carboxyl-terminus of the AQP2 protein.

Amino Acid Sequence↗
PubMed1998

Impact of temporal variation and the balance between excitation and inhibition on the output of the perfect integrate-and-fire model.

We consider how the output of the perfect integrate-and-fire (I&F) model of a single neuron is affected by the properties of the input, first of all by the distribution of afferent excitatory and inhibitory postsynaptic potential (EPSP, IPSP) inter-arrival times, discriminating particularly between short- and long-tailed forms, and by the degree of balance between excitation and inhibition (as measured by the ratio, r, between the numbers of inhibitory and excitatory inputs). We find that the coefficient of variation (CV; standard deviation divided by mean) of efferent interspike interval (ISI) is an increasing function of the length of the tail of the distribution of EPSP inter-arrival times and the ratio r. There is a range of values of r in which the CV of output ISIs is between 0.5 and 1. Too tight a balance between EPSPs and IPSPs will cause the model to produce a CV outside the interval considered to correspond to the physiological range. Going to the extreme, an exact balance between EPSPs and IPSPs as considered in [24] ensures a long-tailed ISI output distribution for which the moments such as mean and variance cannot be defined. In this case it is meaningless to consider quantities like output jitter, CV, etc. of the efferent ISIs. The longer the tail of the input inter-arrival time distribution, the less is the requirement for balance between EPSPs and IPSPs in order to evoke output spike trains with a CV between 0.5 and 1. For a given short-tailed input distribution, the range of values of r in which the CV of efferent ISIs is between 0.5 and 1 is almost completely inside the range in which output jitter (standard deviation of efferent ISI) is greater than input jitter. Only when the CV is smaller than 0.5 or the input distribution is a long-tailed one is output less than input jitter [21]. The I&F model tends to enlarge low input jitter and reduce high input jitter. We also provide a novel theoretical framework, based upon extreme value theory in statistics, for estimating output jitter, CV and mean firing time.

Action Potentials↗
PubMed1998

Influence of GB virus C viraemia on the clinical, virological and histological features of early hepatitis C-related hepatic disease.

BACKGROUND/AIMS: GB virus C is a newly described RNA virus. The aims of this study were to determine the prevalence of GB virus C infection in patients with chronic type C hepatitis and to examine the clinical, virological and histological features in hepatitis C and GB virus C co-infected patients. METHODS/RESULTS: One hundred and sixty patients with hepatitis C infection were studied. GBV-C RNA was detected in 33/160 (20.6%) patients; co-infected patients with hepatitis C and GB virus C infection were significantly younger (p=0.04). No difference was found between the two groups according to gender and biochemical parameters. Seventy-two of the 160 patients, for whom a liver tissue specimen taken simultaneously with the serum was available and who had compensated liver disease, were studied separately. The source of infection, duration of infection, HCV genotype and HCV RNA concentrations did not differ between 15/72 patients with dual infection and 57/72 with hepatitis C infection alone. Patients with co-infection had significantly higher degrees of portal and periportal inflammation (p=0.0006 and 0.01, respectively). No difference was observed in parenchymal activity score or extent of fibrosis. CONCLUSIONS: These results indicate a relatively high prevalence of GB virus C infection in younger patients with chronic hepatitis C, suggesting a common route of transmission. Although GB virus C co-infection does not alter the biochemical and virological profile of patients with HCV hepatitis, there is an association between GB virus C and hepatitis C viraemia and portal and periportal inflammation.

Adult↗
PubMed1998

Dental materials: 1996 literature review.

This critical review of the published literature on dental materials for the year 1996 has been compiled by the Dental Materials Panel of the UK. It continues the series of annual reviews started in 1973 and published in the Journal of Dentistry. Emphasis has been placed upon publications which report upon the materials science or clinical performance of the materials. The review has been divided by accepted materials classifications (fissure sealants, glass polyalkenoate cements, dentine bonding, dental amalgam, endodontic materials, casting alloys, resin-bonded bridges and ceramo-metallic restorations, ceramics, denture base resins and soft lining materials, impression materials, implants materials, orthodontic materials, biomechanics and image processing, resin composites and casting investment materials and waxes). Three hundred and thirteen articles have been reviewed.

Dental Alloys↗
PubMed1998

Dental materials: 1996 literature review. Part 2.

This critical review of the published literature on dental materials for the year 1996 has been compiled by the Dental Materials Panel of the UK. It continues the series of annual reviews started in 1973 and published in the Journal of Dentistry. Emphasis has been placed upon publications which report upon the materials science or clinical performance of the materials. The review has been divided by accepted materials classifications (fissure sealants, glass polyalkenoate cements, dentine bonding, dental amalgam, endodontic materials, casting alloys, resin-bonded bridges and ceramo-metallic restorations, ceramics, denture base resins and soft lining materials, impression materials, implants materials, orthodontic materials, biomechanics and image processing, resin composites and casting investment materials and waxes). Three hundred and thirteen articles have been reviewed.

Ceramics↗
PubMed1998

Occupational stress and community mental health nursing: what CPNs really said.

The Claybury Nursing Stress Study assessed the levels of occupational stress experienced by both ward-based and community nurses. This paper presents the results obtained from a qualitative analysis of statements made by community psychiatric nurses during a questionnaire based interview. Key areas identified by CPNs as relevant to stress and coping are reported and suggestions for further, qualitative research in this area are made.

Adaptation, Psychological↗
PubMed1998

The need for nursing leadership in uncertain times.

BACKGROUND: The world today is changing and being affected by advances in technology and communication, as well as changes in the political, economic, demographic and social environment. These changes also effect the delivery of health care services. AIM: A review of the literature was conducted to examine how the profession of nursing can ensure that it is involved in shaping the health care system of the future. KEY ISSUES TO EMERGE: The nursing profession requires leadership which empowers nurses, enabling them to lead the profession into the next millennium. Pressures for change in health care delivery make the move from bureaucratic management to effective leadership essential. Development of an appropriate model of leadership will ensure that nurses play a pivotal role in the process of change. CONCLUSION: Transformational leadership is the model that will assist nursing to develop into an empowered profession with the potential to be a dominant voice in reshaping the health care system of the future.

Ethics, Nursing↗
PubMed1998

A comparison of oral fluid and serum for the detection of rubella-specific antibodies in a community study in Addis Ababa, Ethiopia.

OBJECTIVE: To assess the utility of oral fluid compared with serum for the determination of age-prevalence of rubella-specific antibodies in an urban African community setting. METHOD: Paired serum and oral fluid samples were collected from 439 individuals aged 0-49 years in Addis Ababa, Ethiopia, as part of a larger seroepidemiological survey in 1994. Oral fluid was sampled using a simple sponge device that was well accepted by subjects of all ages; venous blood was collected by Vacutainer system. We measured rubella-specific antibodies in serum by the Radial Haemolysis (RH) test, supported by two confirmatory assays, and in oral fluid by IgG antibody-capture radioimmunoassay (GACRIA). RESULTS: Sensitivity and specificity of oral fluid results compared to serum were 89% and 76%, respectively. Sensitivity declined from 96% in age group 0-19 years to 90% in age group 20-29 and 78% in age group 30-49. Specificity was 86% in 0-9 year olds contrasting with 61% in older groups (10-49 years). The positive predictive value of an oral fluid sample was high in all age groups (range 92-100%), while the negative predictive value declined from > or =80% in those aged <10 years to <10% in those aged > or =30 years. Serum confirmatory tests suggested a proportion of false serum RH negatives, increasing with age, indicating a need to standardize serum as well as oral fluid tests. CONCLUSION: In the community setting of a developing country, oral fluid surveys could be useful to estimate age-prevalence of rubella immunity and identify rubella-susceptible children for follow-up. Further work is required to simplify assays and sample processing, improve assay sensitivity and estimate assay specificity more precisely, and compare and standardise collection methods suitable for surveillance of a variety of childhood viral infections.

Adolescent↗
PubMed1998

Young people with spina bifida: transfer from paediatric to adult health care.

An expectation of health care for young people with disability is that quality coordinated care continues to be available as they pass from the paediatric to the adult health care system. While individual clinicians provide this service well, the widespread absence of coordinated multidisciplinary care for young people with spina bifida in the adult health care system is a major deficiency. This paper describes the planning and implementation that underpinned the transfer of 10 young people with spina bifida from a paediatric to an adult service. The range of structural, financial and 'cultural' barriers that need to be overcome before patients can be successfully transferred is highlighted; lessons learned from this model may serve to facilitate the development of other transfer services.

Adolescent↗
PubMed1998

Cadmium inhibits vacuolar H(+)-ATPase and endocytosis in rat kidney cortex.

The mechanism of cadmium (Cd)-induced damage in the mammalian proximal tubule that is manifested by defects in reabsorption of various compounds, is poorly understood. A vacuolar H(+)-ATPase (V-ATPase) in proximal tubule (PT) brush border and intracellular vesicles may be affected by Cd, and this may influence intracellular vesicle trafficking and reabsorption of the filtered proteins. We studied the effects of Cd on V-ATPase and endocytosis in rat renal PT in vivo and on acidification mechanisms in isolated renal cortical organelles in vitro. The V-ATPase activity in brush border membrane (BBM) from Cd-intoxicated rats was 40% lower compared to that in control animals. Immunofluorescence studies in cortical tissue sections and Western blot studies in BBM from Cd-treated rats showed a strongly decreased abundance of the 31 kDa and 70 kDa V-ATPase subunits. Functional studies in vivo showed a dramatically diminished endocytosis of fluorescein-labeled dextran in PT cells from Cd-treated animals, whereas morphological studies revealed a loss of endocytic invaginations and subapical vesicles in the same cells. In studies in vitro, Cd inhibited V-ATPase activity in a concentration- and time-dependent manner in both BBM and endocytic vesicles, whereas in endocytic vesicles, Cd inhibited ATP-driven intravesicular acidification and accelerated the dissipation of transmembrane pH gradients. We conclude that Cd may impair acidification in cell organelles by (a) causing a loss of V-ATPase protein in their limiting membranes, (b) inhibiting the intrinsic V-ATPase activity, and (c) dissipating the transmembrane pH gradient. This may inhibit endocytosis of filtered proteins and impair vesicle-mediated recycling of some membrane transporters, thus contributing to the loss of reabsorptive capacity of the PT.

Acid-Base Equilibrium↗
PubMed1998

Comparison of several equations and derivation of a new equation for calculating basal metabolic rate in obese children.

OBJECTIVES: To compare basal metabolic rate (BMR) calculated by the Harris-Benedict, Ravussin, Cunningham, World Health Organization (WHO) and Schofield equations to BMR determined in an obese pediatric population. The second objective is to derive a new equation, based on measured BMR in obese children, for calculating BMR in obese pediatric patients. METHODS: The study included 110 (50 male/60 female) healthy obese subjects (BMI > 28) (11.7 +/- 2.8 years, 73 +/- 27 kg, 152 +/- 14 cm and 38 +/- 6% fat) who had preprandial BMR determined by indirect calorimetry. These results were compared to BMR calculated with the five above mentioned equations. Fat-free mass was determined by bioelectrical impedance and body composition was calculated using the appropriate equation. The age groups analyzed were as follows: males 3 to 10 and 11 to 18 years old; females 3 to 10 and 11 to 18 years old. A new equation was derived by stepwise multiple regression analysis using 100 randomly selected subjects from our test group and tested using the remaining 10 subjects. RESULTS: Basal metabolic rate calculated by the Ravussin and Cunningham equations in all subgroups was lower (p < 0.05) than measured BMR. Basal metabolic rate calculated by the Harris-Benedict equation was lower (p < 0.05) than measured BMR in male populations ages 3 to 10, 11 to 18, and in the entire cohort. Measured BMR was overestimated by the Harris-Benedict equation (p < 0.05) in females 11 to 18 years old; by the WHO equation (p < 0.05) in both male and females 3 to 10 years old and by the Schofield equation (p < 0.05) in males 11 to 18 years old. In comparison to measured BMR, the WHO equation appeared to be the most accurate for estimating BMR in males and females 11 to 18 years old. However, BMR calculating using our new equation in the 10 test subjects was similar to measured BMR. CONCLUSIONS: The WHO equation was the most accurate of the prediction equations studied. However, our new prediction equation may be more appropriate for calculating BMR in an obese pediatric population.

Adolescent↗
PubMed1998

GB virus C infection in patients with primary antibody deficiency.

Sera from 77 patients with common variable immunodeficiency (CVID) were tested for GB virus C (GBV-C) RNA, because they are prone to unexplained chronic hepatitis, and from 28 patients with X-linked agammaglobulinemia (XLA) who have a similar primary antibody deficiency but are not prone to hepatitis. Eight CVID and 8 XLA patients were positive; 6 positive CVID and 3 XLA patients had abnormal liver enzymes, explained in 3 by either hepatitis B or C virus infection. Most patients tested had antibodies to the E2 antigen of GBV-C, apparently passively acquired from their immunoglobulin therapy. The high prevalence of GBV-C viremia in CVID and XLA patients is probably explained by their long-term exposure to blood products. Our data indicate that GBV-C does not cause chronic hepatitis in immunocompromised XLA patients and is not the cause of chronic non-B or -C hepatitis in the majority of CVID patients.

Adult↗
PubMed1998

Nutritional utilization by rats of chickpea (Cicer arietinum) meal and its isolated globulin proteins is poorer than that of defatted soybean or lactalbumin.

The effects on performance, digestibility, N utilization and plasma amino acid concentrations of dietary chickpea (Cicer arietinum, var. Kabuli) seed meal, globulin proteins or buffer-insoluble residue [starch + non-starch polysaccharides (NSP) + lignin] were studied in growing rats. Chickpea meal, defatted soybean meal, chickpea globulins and lactalbumin were each incorporated into diets as the sole source of dietary protein (100 g/kg). In addition, chickpea insoluble residue was included in a control diet in the same proportion found in the chickpea meal. Rats were killed while under halothane anesthesia after 10 d of consuming the diets, and ileal contents were washed out and freeze-dried for digestibility measurements. Weight gains and gain:feed ratios of rats fed chickpea diets for 10 d did not differ from those of rats fed defatted soybean but were significantly lower than those of rats given the control (lactalbumin) diet. However, ileal and fecal N digestibilities and N retention by rats fed the chickpea diet were significantly lower than those obtained with the lactalbumin or soybean diet. The inclusion of both chickpea meal or its globulin proteins in the diet significantly increased the amount of N excreted, primarily as urea, through the urine. However, although ileal N digestibility values for chickpea meal were significantly lower, those for its constituent globulins did not differ from control values. Urea levels in plasma in rats fed diets containing chickpea meal, globulins or soybean meal were significantly higher than in those fed lactalbumin. Furthermore, the concentrations of glycine, phenylalanine, histidine, arginine and ornithine in the plasma of rats fed chickpea meal, its globulins or defatted soybean were significantly higher, whereas those of threonine, leucine, lysine and tryptophan were significantly lower than lactalbumin-fed controls. The chickpea insoluble residue had no adverse effects on performance or N utilization by rats. We conclude that the low nutritional value of chickpea meal is likely to be due mainly to adverse effects of its globulin proteins on growth and N metabolism rather than to the action of any known antinutritional factor present in the diet.

Amino Acids↗
PubMed1998

Clinical impact of abnormal gut flora in infants receiving parenteral nutrition.

OBJECTIVE: Illness is associated with the carriage of abnormal flora (aerobic Gram-bacilli except E. coli) in the oropharynx and rectum. The aim of this study was to investigate whether carriage of abnormal flora is associated with increased risk of sepsis and septicemia in surgical newborn infants. METHODS: A 2-year prospective study was carried out on 94 consecutive newborn infants requiring parenteral nutrition (PN) for gastrointestinal abnormalities. Throat and rectal swabs were taken on day 1 of PN and twice weekly. Patients were divided into two groups: abnormal flora (AF; n = 41) and normal flora (NF; n = 53). Sepsis was defined as clinical features of generalized inflammation requiring blood culture. Septicemia was the combination of sepsis and positive blood culture. RESULTS: Among the infants carrying abnormal flora Pseudomonas and Enterobacter spp. predominated. Duration of PN (AF median 30 days; NF median 9 days), incidence of sepsis (AF 29%; NF 6%), and septicemia (AF 22%; NF 2%) were significantly greater in the group of infants with abnormal flora. Surveillance cultures allow the detection of a subset of infants on PN at high risk of sepsis and septicemia. The degree of gut dysfunction related to the severity of underlying disease determines the duration of PN and the development of abnormal flora. The association between abnormal carriage and increased risk of sepsis and septicemia may be because of the intestinal endotoxin pool known to cause liver impairment and consequent suppression of systemic immunity.

Enterobacter↗
PubMed1998

Surgical salvage after failed radiation for paranasal sinus malignancy.

OBJECTIVE: To comment on the role of surgical salvage following failed initial treatment for paranasal sinus malignancy. DESIGN: A retrospective analysis of one hundred eighty patients treated at The Princess Margaret Hospital, Toronto, from 1976 to 1993. MATERIALS AND METHODS: Thirty-four of 95 patients (36%) who failed initial treatment underwent surgical salvage. Initial therapy in this group was radiation only (n = 27) and combined therapy (n = 7). Patient, tumor, and surgical data were recorded. There were 23 T4, three T3, six T2, and two T1 carcinomas. Survival, recurrence rates, and the influence of a variety of variables on outcome were analyzed. RESULTS: Two- and 5-year overall actuarial survival calculated from the date of diagnosis was 54% and 35%, respectively. Two- and 5-year overall actuarial survival calculated from the date of salvage surgery was 44% and 22%, respectively. Advanced age (P < .004), patients with T4 category disease (P < .04), and squamous cell carcinomas (P < .049) correlated with poorer outcome on univariate analysis. Local failure was the most common cause of death (n = 13; 65%). CONCLUSION: Salvage surgery has a limited role in the management of persistent or progressive disease following failure of initial treatment. Careful postradiation surveillance with endoscopic biopsy under general anesthesia and immediate surgical resection when appropriate may improve the salvage rate.

Actuarial Analysis↗