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Biomedical subjects

R Anderson

Publications and source records attributed to R Anderson.

At least 109 records · Page 6Linked to original sources

Out-of-hours dental services: a survey of current provision in the United Kingdom.

OBJECTIVE: To describe the variety of arrangements for providing out-of-hours dental care in the UK. DESIGN: A telephone interview survey of health authorities and health boards. SETTING: United Kingdom. SUBJECTS: 104 health authority contacts, usually consultants in dental public health, dental advisers or others in a position to describe the local dental service arrangements. RESULTS: At weekends, 25 authorities have no formal dental care arrangements for unregistered patients, 55 have separate arrangements for registered and unregistered patients, and 44 have 'universal access' arrangements--for anyone in an area, regardless of their registration status. On weekday nights over two-thirds (82/124) of UK health authorities have no formal arrangements for unregistered patients. Where there are separate 'safety-net' services intended for unregistered patients only they are usually (in 48 of 55 authorities) emergency treatment sessions. A fifth of authorities reported planned changes to their local out-of-hours arrangements, including the introduction of telephone triage, and moves to make care available at more times, to more people or from centralised premises. CONCLUSIONS: There is extremely wide geographical variation in the organisation of out-of-hours dental services provided in the United Kingdom. In many parts of the UK there are no formal out-of-hours care arrangements for unregistered patients, even at weekends. This unequal provision will mean inequitable access for many unregistered patients. With increasing demands from a growing unregistered population, and various government initiatives to make primary care services more integrated and accessible, the highly fragmented pattern of provision in many areas may no longer be acceptable.

Catchment Area, Health↗

The onset of germ cell migration in the mouse embryo.

Mouse primordial germ cells (PGCs) are specified between embryonic day 6.5 (E6.5) and E7.5, when they have been visualized as an alkaline phosphatase-positive (AP+) cell population in the developing allantois. By E8.5, they are embedded in the hind-gut epithelium. Previous experiments have suggested different sites for PGCs' origin, and it is unclear how they reach the gut epithelium. We have used transgenic mice expressing GFP under a truncated Oct4 promoter to visualize living PGCs. We find GFP+/AP+ cells in the posterior end of the primitive streak as a dispersed population of cells actively migrating into the allantois, and directly into the adjacent embryonic endoderm. Time-lapse analysis shows these cells to be actively migratory from the time they exit the primitive streak.

Alkaline Phosphatase↗

The role of cadherins during primordial germ cell migration and early gonad formation in the mouse.

Primordial germ cells (PGCs) are the founder cells of the gametes. In mammals, PGCs migrate from the hindgut to the genital ridges, where they coalesce with each other and with somatic cells to form the primary sex cords. We show here that, in both sexes, PGCs express P- and E-cadherins during and after migration, and N-cadherin at post-migratory stages. E-Cadherin is not expressed by PGCs whilst in the hindgut, but is upregulated as they leave. Blocking antibodies against E-, but not P-cadherin cause defective PGC-PGC coalescence, and in some cases, ectopic PGCs.

Animals↗

Phase II placebo-controlled trial of fozivudine tidoxil for HIV infection: pharmacokinetics, tolerability, and efficacy.

Fozivudine tidoxil (FZD) is a thioether lipid-zidovudine (ZDV) conjugate with anti-HIV activity demonstrated in vitro and in pilot phase I studies. To assess its safety, efficacy and pharmacokinetics, we conducted a multicenter, randomized, double-blind, placebo-controlled trial of FZD monotherapy in 72 HIV-infected patients who had not previously received antiretroviral therapy. In each dosage group (200 mg daily, 400 mg daily, 200 mg twice daily, 800 mg daily, 400 mg twice daily, and 600 mg twice daily), 12 patients were randomized to receive in a 10:2 ratio either FZD or a placebo for 4 weeks. Overall, FZD was well tolerated in all dosage groups; only 1 patient discontinued the drug, because of a moderate rise in aminotransaminase activity. HIV viral load fell in all the patients who were receiving FZD, except in the 200 mg daily group. The largest decrease (-0.67 log10) was observed in the 600 mg twice daily group. The plasma half-life was significantly longer (approximately 3.8 hours) than that of the parent drug ZDV. Exposure to ZDV, as reflected by the area under the time-concentration curve, was much lower after FZD than after ZDV administration. FZD thus appears to be as effective as and potentially better tolerated than ZDV during short-term administration and has the advantage of once daily intake.

Adult↗

Liposome encapsulation of a soluble recombinant fragment of the respiratory syncytial virus (RSV) G protein enhances immune protection and reduces lung eosinophilia associated with virus challenge.

Respiratory syncytial virus (RSV) is a leading cause of bronchiolitis and pneumonia in young children and infants. Previous animal studies have shown that immunizing intramuscularly or intraperitoneally with the RSV G protein has elicited protective as well as harmful immune responses upon RSV challenge. In an RSV immunization strategy designed to target the respiratory tract directly (the site of RSV replication), we immunized BALB/c mice intranasally with a liposome-encapsulated, prokaryotically expressed thioredoxin fusion protein consisting of amino acids 128-229 of the RSV G protein (Trx-G(128-229)). Upon intranasal challenge with RSV, a 100 to 500-fold reduction in lung RSV replication was observed in mice immunized with liposome-encapsulated Trx-G(128-229) compared to a sham-immunized control group. Analysis of bronchoalveolar lavage fluids revealed an influx of eosinophils (18% of total cells) in mice immunized with Trx-G(128-229) alone. Such eosinophilic infiltration was diminished (to 4.5% of total cells), however, in mice immunized with liposome-encapsulated Trx-G(128-229). Histological analysis of lung tissue revealed an accumulation of cells around the bronchioles and vessels in mice immunized with Trx-G(128-229) alone followed by RSV challenge which was not increased further in mice immunized with liposome-encapsulated Trx-G(128-229). These results show that intranasal immunization of BALB/c mice with Trx-G(128-229), when encapsulated in liposomes, can reduce the level of RSV replication in the lung as well as specifically reduce the degree of eosinophilic infiltration compared to mice immunized with Trx-G(128-229) alone. This demonstrates the potential of liposomes and particular recombinant fragments of the RSV G protein as an effective combination in RSV vaccine studies.

Animals↗

CGS 21680, dibutyryl cyclic AMP and rolipram attenuate the pro-inflammatory interactions of the Pseudomonas aeruginosa -derived pigment, 1-hydroxyphenazine, with human neutrophils.

The effects of the intracellular adenosine 3':5' cyclic monophosphate (cAMP)-elevating agents, CGS 21680 (0.01- 1 microM) and rolipram (0.01-1 microM), as well as those of dibutyryl cAMP (0. 05-4 mM) on the pro-inflammatory interactions of the P. aeruginosa -derived pigment, 1-hydroxyphenazine (1-hp, 3.1 and 12.5 microM), with human neutrophils have been investigated in vitro. Ca(2+)fluxes in FMLP-activated neutrophils were measured using a fura-2/AM spectrofluorimetric procedure, while a colourimetric method was used to measure release of the primary granule enzyme, elastase, from the cells. Treatment with 1-hp resulted in delayed clearance of Ca(2+)from the cytosol of N -formyl- L -methionyl- L -leucyl- L -phenylalanine (FMLP, 1 microM)-activated neutrophils and increased release of elastase. All 3 test agents caused dose-related antagonism of 1-hp-mediated potentiation of elastase release from activated neutrophils, which was associated with restoration of Ca(2+)homeostasis. These observations demonstrate the potential of cAMP-elevating agents, acting on Ca(2+)clearance mechanisms in activated neutrophils, to attenuate the potentially harmful pro-inflammatory effects of 1-hp.

Adenosine↗

Electrical impedance scanning for classifying suspicious breast lesions: first results.

It has long been established that cancer cells exhibit altered local dielectric properties compared with normal cells. Consequently, different electrical conductivity and capacitance are measurable in malignant vs normal tissues. In this study we evaluated the reliability of electrical impedance scanning (EIS), a new technology, for the classification of suspicious lesions: differentiating benign from malignant, and as a primary means of detection of breast cancer. Fifty-two women with 58 sonographically and/or mammographically suspicious findings were examined using electrical impedance scanning. Two different examination modes of TransScan TS2000 (Siemens, Erlangen, Germany), the standard-resolution mode for a routine overview examination, and the targeted high-resolution mode for a local examination of the suspicious lesion were used. All patients were additionally imaged by MR mammography (MRM) and underwent core-biopsy and/or surgical treatment after the EIS examination. With respect to the histopathological findings (29 malignant and 29 benign lesions) 27 of 29 (93.1%) malignant lesions were correctly identified using the high-resolution mode of EIS, whereas 19 of 29 (65.5%) benign lesions were correctly identified as benign (10 of 29 benign lesions showed as false-positive findings). Negative and positive predictive values of 90.5 and 73.0% were observed, respectively. Using the standard-resolution mode 22 of 29 malignancies were correctly detected (sensitivity 75.9%), whereas 22 of 29 were correctly identified as benign (specificity 72.4%). Electrical impedance scanning appears to be a promising new technology providing a relatively high sensitivity for the verification of suspicious mammographic and/or sonographic lesions especially using the high-resolution mode for local examinations. Artifacts, such as signals from superficial skin lesions, poor contact, and air bubbles, are currently a limitation.

Breast Neoplasms↗

A method for the preparation of highly purified adeno-associated virus using affinity column chromatography, protease digestion and solvent extraction.

Recombinant adeno-associated virus (AAV) is becoming the vector of choice for many gene therapy protocols. There has been much recent progress made toward increasing AAV titres but a continuing problem in using AAV has been that it is relatively difficult to concentrate and purify. Traditional methods, such as caesium chloride (CsCl) gradients, have drawbacks, notably extended purification times and the ability to process only limited volumes. Where the target cells of interest require a high multiplicity of infection (MOI), or to complete in vivo experiments, there is a requirement for both the production of high titre and a large volume of virus. This is laborious to obtain using traditional methods. A simple technique is described here for purifying AAV, involving affinity chromatography, protease digestion and solvent extraction that retains both the high yields and titres obtained using CsCl gradients. In addition, this technique displays a fast throughput and may be used to purify AAV from larger volumes than CsCl gradients. The high yield and purity of these virus preparations has allowed us to achieve good levels of expression in the target cell types tested. The purification technique described here will be applicable to any protocol that requires high titre, high purity recombinant AAV (rAAV).

Blotting, Western↗

Early outcomes after allogeneic stem cell transplantation for leukemia and myelodysplasia without protective isolation: a 10-year experience.

Although it is common practice to use some form of isolation to protect allogeneic stem cell transplant patients from infection, the necessity for these practices in all environments has not been demonstrated. The current study evaluated patterns of infection and 100-day transplant-related mortality in 288 patients with myelodysplasia and leukemia transplanted without isolation. Patients were allowed out of hospital at any time within constraints of the medication schedule. Fever, foci of infection, and positive cultures within 28 days and death within 100 days because of the transplant procedure were recorded. Fever occurred in 57% of patients, and 10% had a clinical or radiographic focus of infection. Most infections were apparently endogenous; blood cultures from 24% of recipients grew organisms, 87% of which were gram-positive bacteria. Four patients (1%) died with aspergillus infection in circumstances indicating that isolation would not have been helpful. Twenty percent of patients remained without evidence of infection throughout. Transplant-related mortality at 100 days was 1% for 108 patients with early leukemia receiving transplants from matched siblings. For patients at higher risk, by virtue of donor and/or disease status, mortality was 21%. These figures compare favorably with those reported to the International Bone Marrow Transplant Registry, the majority of patients having been subjected to some form of isolation. We conclude that allogeneic stem cell transplantation can be safely performed in some environments without confining patients continuously to the hospital.

Adolescent↗

Activation of human neutrophils with chemotactic peptide, opsonized zymosan and the calcium ionophore A23187, but not with a phorbol ester, is accompanied by efflux and store-operated influx of calcium.

The objective of this study was to monitor alterations in cellular Ca2+ metabolism following activation of neutrophils with receptor- (chemotactic peptide, FMLP, 1 microM; opsonized zymosan, OZ, 0.5 mg/ml) and non-receptor (calcium ionophore, A23187, 1 microM; phorbol 12-myristate 13-acetate, PMA, 25 ng/ml)-mediated stimuli of the pro-inflammatory functions of these cells. Ca2+ fluxes in activated neutrophils were measured using a fura-2-based spectrofluorimetric method in combination with radiometric (45Ca) procedures which facilitate distinction between net efflux and net influx of the cation. Exposure of neutrophils to receptor-mediated stimuli and to A23187 was associated with an abrupt increase in cytosolic Ca2+ coincident with a rapid efflux of the cation which terminated at around 30 s. In the case of FMLP and OZ, this was followed by a delayed (30-60 s), store-operated influx of Ca2+, which was complete at around 5 min after addition of the stimulus. With A23187, however, influx of Ca2+ occurred immediately following activation of the cells. There were no detectable alterations in cytosolic Ca2+ or measurable net efflux or influx of the cation above control levels in PMA-activated neutrophils. These data demonstrate that FMLP, OZ- and A23187-mediated alterations in neutrophil cytosolic Ca2+ are due to mobilization of both intracellular and extracellular cation, while activation of neutrophils by PMA is independent of alterations in cytosolic Ca2+.

Calcimycin↗

Accelerated resequestration of cytosolic calcium and suppression of the pro-inflammatory activities of human neutrophils by CGS 21680 in vitro.

We have investigated the effects of the adenosine A(2A) receptor agonist CGS 21680 (0.01 - 1 microM) on reactive oxidant production by, and elastase release from FMLP-activated human neutrophils, as well as on cytosolic Ca(2+) fluxes and intracellular concentrations of cyclic AMP. Oxidant production, elastase release and cyclic AMP were assayed using lucigenin-enhanced chemiluminescence, colourimetric and radioimmunoassay procedures respectively, while cytosolic Ca(2+) fluxes were measured by fura-2 spectrofluorimetry in combination with radiometric procedures which distinguish between net efflux and influx of the cation. Treatment of neutrophils with CGS 21680 did not affect the FMLP-activated release of Ca(2+) from intracellular stores, but resulted in dose-related acceleration of the rate of decline in fura-2 fluorescence, as well as decreases in both efflux and store-operated influx of Ca(2+), compatible with enhancement of resequestration of the cation by the endo-membrane Ca(2+)-ATPase. These effects on neutrophil Ca(2+) handling were associated with increased intracellular cyclic AMP and with inhibition of oxidant production and release of elastase. In contrast, treatment of neutrophils with the selective A(2A) receptor antagonist, ZM 241385 (2.5 microM), prevented the transient increase in cyclic AMP in FMLP-activated neutrophils which was associated with delayed sequestration of incoming Ca(2+) during store-operated influx. The CGS 21680-mediated reduction of Ca(2+) efflux from FMLP-activated neutrophils was also antagonized by pretreatment of the cells with ZM 241385 (2.5 microM), as well as by thapsigargin (1 microM), an inhibitor of the endo-membrane Ca(2+)-ATPase. ZM 241385 also neutralized the cyclic AMP-elevating and anti-inflammatory interactions of CGS 21680 with neutrophils. We conclude that A(2A) receptors regulate the pro-inflammatory activities of human neutrophils by promoting cyclic AMP-dependent sequestration of cytosolic Ca(2+).

Adenosine↗

Wolman disease successfully treated by bone marrow transplantation.

Wolman disease is characterized by severe diarrhea and malnutrition leading to death during infancy. Lysosomal acid lipase deficiency is the cause of the symptoms and signs. It is inherited in an autosomal recessive manner. All Wolman disease patients have adrenal gland calcification. Previous therapeutic attempts have failed to provide remission. We report successful long-term bone marrow engraftment in a patient with Wolman disease resulting in continued normalization of peripheral leukocyte lysosomal acid lipase enzyme activity. Diarrhea is no longer present. Now, at 4 years of age, this patient is gaining developmental milestones. Cholesterol and triglyceride levels are normal. Liver function is normal. This is the first long-term continued remission reported for Wolman disease.

Bone Marrow Transplantation↗

Enteric colonisation following natural exposure to Campylobacter in pigs.

A survey was conducted to establish the prevalence of Campylobacter in pigs from an integrated commercial hog farm. This study was carried out in four different groups of pigs: 1) adult gilts (50); 2) pregnant sows (9); 3) piglets at day-of-birth (73); 4) weaned piglets (20). Rectal and/or caecal samples were collected from each pig. Campylobacter was cultured and enumerated from such samples using Bolton enrichment broth and Campy-Cephex agar plates. Both biochemical and serological tests were used to determine Campylobacter species. Gilts had a 76 per cent incidence of Campylobacter with a mean of 76.3 per cent for C. jejuni, 21 per cent for C. coli and 2.6 per cent for C. lari. Pregnant sows had a 100 per cent incidence of Campylobacter with a mean of 87 per cent for C. jejuni and 13 per cent for C. coli. Newborn piglets had a 57. 8 per cent incidence of Campylobacter, rising to 100 per cent by the time of weaning. Thus it appears that pigs, from the day of birth, are highly susceptible to colonisation by Campylobacter.

Aging↗

Investigation of the anti-inflammatory and membrane-stabilizing potential of spiramycin in vitro.

The effects of the 16-member macrolide spiramycin (2.5-80 mg/L) and the 14-member agent clarithromycin on the production of superoxide by activated human neutrophils were compared in vitro and related to membrane-stabilizing activity. Superoxide production was measured by lucigenin-enhanced chemiluminescence with N-formyl-L-methionyl-L-leucyl-L-phenylalanine (1 microM) as the stimulus, and membrane-stabilizing activity was measured by a haemolytic procedure. Clarithromycin, but not spiramycin, caused dose-related inhibition of superoxide production by activated neutrophils and also protected erythrocytes against haemolysis, while spiramycin possessed only weak membrane-stabilizing activity. These observations underscore the apparent association between the anti-inflammatory and membrane-stabilizing properties of macrolides.

Adult↗

Psychiatric patients who desire aesthetic surgery: identifying the problem patient.

Plastic surgeons are often confronted with psychiatric patients seeking aesthetic surgery. It is imperative for surgeons to recognize underlying psychiatric illnesses and to acknowledge their influence over patient motives and judgment. It is the goal of this paper to present the defining characteristics of the major psychiatric disorders as illustrated in the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, in a manner that will allow plastic surgeons to incorporate and utilize this information in daily practice. It is the authors' hope that this paper will assist plastic surgeons in ultimately preventing patient dissatisfaction within the population of patients with psychiatric disorders.

Body Image↗

Release of vasoactive cytokines by antibody-enhanced dengue virus infection of a human mast cell/basophil line.

We report here the first demonstration of dengue virus infection and vasoactive cytokine response of a cell of the mast cell/basophil lineage. Infection of KU812 cells was dependent on dengue-specific antibody and gave rise to infectious virions. This antibody-enhanced dengue virus infection triggered a four- to fivefold increase in the release of interleukin-1beta (IL-1beta) and a modest increase for IL-6 but not for an alternate cytokine, granulocyte-macrophage colony-stimulating factor. The results suggest a potential role for mast cells/basophils in the pathogenesis of dengue virus-induced disease.

Animals↗

Urinary retention in patients with BPH treated with finasteride or placebo over 4 years. Characterization of patients and ultimate outcomes. The PLESS Study Group.

OBJECTIVES: Knowledge regarding the incidence and prevalence of acute urinary retention and the ultimate outcome is very limited. The purpose of the present analysis was to document the natural history and outcomes of acute urinary retention (AUR) further specified as being either precipitated or spontaneous, and to evaluate the potential benefit of finasteride therapy. MATERIALS AND METHODS: Three thousand and forty men with moderate to severe symptoms of BPH and enlarged prostate glands by digital rectal examination were enrolled into the 4-year placebo-controlled PLESS trial and were evaluated for occurrences of AUR and BPH-related surgery. Men in the study were seen every 4 months; discontinued patients were followed up 6 months after discontinuation and again at the end of the 4-year trial. Complete 4-year data on outcomes (occurrence of AUR or BPH-related surgery) was available for 92% of the enrolled subjects in each treatment group. An endpoint committee, blinded to treatment group and center, reviewed and categorized all study-related documentation relating to retention and surgery. RESULTS: Over the 4-year period, 99 of 1,503 placebo-treated patients (6.6%) experienced one or more episodes of AUR in comparison with 42 or 1,513 finasteride-treated patients (2.8%; p<0. 001). Approximately half of the episodes of retention were spontaneous and clearly BPH-related, while the other episodes were precipitated by another factor (PAUR). After spontaneous AUR, subsequent surgery was performed in 39 of 52 (75%) placebo-treated patients versus 8 of 20 (40%) finasteride-treated patients (p = 0. 01). BPH-related surgery was less common in men who had a prior episode of PAUR (26% in the placebo group and 14% in the finasteride group). CONCLUSION: There is a continual risk of spontaneous and precipitated acute urinary retention in men with moderate to severe lower urinary tract symptoms and an enlarged prostate gland. Fewer patients who developed precipitated AUR than spontaneous AUR go on to need subsequent BPH-related surgery. Significantly fewer finasteride-than placebo-treated patients developed AUR, and among those men, fewer ultimately needed BPH-related surgery.

Finasteride↗