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Biomedical subjects

R Willoughby

Publications and source records attributed to R Willoughby.

At least 19 recordsLinked to original sources
PubMed2005

Dynamic hip screw in the management of reverse obliquity intertrochanteric neck of femur fractures.

AIM: To assess the results of treatment of reverse obliquity intertrochanteric fractures at Middlemore hospital and to compare this to the results in the literature. METHOD: This was a retrospective review of X-rays and clinical notes followed by phone conversations with the patients. RESULTS: Forty-two patients with reverse obliquity intertrochanteric neck of femur fractures were included. They were treated with one of three different implants (dynamic hip screw (DHS), reconstruction nail (RCN) or proximal femoral nail (PFN)). The revision rate for the DHS was 11% (4/35), RCN 40% (2/5) and PFN 0% (0/2). Of the 35 DHS implants, one was below a hip fusion. Of the remaining 34, 25 had the screws placed within 25 mm of the subchondral bone at the centre of the femoral head and nine did not. None of the implants placed within 25 mm of the femoral head failed while three of the others did. CONCLUSION: The results for treating this type of fracture with the DHS in this series are significantly better than that documented in the literature for the same fracture type, the reasons for this are unclear. There seems to be a trend towards better results with more accurate placement of the lag screw with this device. In this series, the RCN was less successful than the DHS and the PFN was used too infrequently to draw useful conclusions about its effectiveness.

Aged↗
PubMed2003

Anti-transglutaminase antibodies and the serological diagnosis of coeliac disease.

Tissue transglutaminase (tTG) has recently been identified as the antigenic target recognised by anti-endomysial antibodies in patients with coeliac disease. In this study, an enzyme-linked immunosorbent assay (ELISA) is used to measure IgA, IgG and IgM antibodies to tTG in patients with coeliac disease and a variety of other inflammatory disorders; and is compared to the standard immunofluorescence test used to detect endomysial antibodies (EMA). In the samples tested, 3% control sera (n=146), 83% EMA-positive sera (n=29), 9% patients with Graves' disease (n=94), 12% antimitochondrial antibody-positive sera (n=53), 11% rheumatoid arthritis patients (n=53) and 22% systemic lupus erythematosus (SLE) patients (n=46) were positive for anti-tTG antibodies. In contrast, none of the controls, 1% of patients with Graves' disease, 2% antimitochondrial antibody-positive sera, 2% rheumatoid arthritis patients and none of the SLE patients were positive for EMA. Measurement of IgG or IgM antibodies to tTG was much less reliable than IgA anti-tTG antibody for the serological diagnosis of coeliac disease. The addition of calcium to the coating buffer improved the assay characteristics of the anti-tTG ELISA. However, the IgA anti-tTG ELISA, with and without calcium, performed less well than the standard EMA test used for the serological diagnosis of coeliac disease. In particular, the anti-tTG ELISA gave a higher rate of non-specific positive reactions.

Antibodies↗
PubMed2001

'The dungeon of thyself': the claustrum as pathological container.

The author discusses the claustrum as an aspect of pathological containment within inner space and its relation to Bion's (1962a, b) container-contained concept. Having outlined the early psychoanalytic conceptual foundations of claustrophobia and the claustrum, the author charts the term from its introduction by Erikson in 1937 through its divergent developmental trajectories within the conceptual vocabulary of the classical, Independent and Kleinian schools up to Meltzer's (1992) contemporary reworking. The vicissitudes of the transmission of ideas within and between these groups is stressed, Esther Bick's work being particularly highlighted as an example of a nodal intellectual influence. The claustral space within the physical or internal object body, its internal structuralization, and the impairments in quality of psychic life of the selves that seek to inhabit such spaces, entered through intrusive projective identification, are highlighted. Developmental and psychopathological claustrum manifestations are discussed, particularly fear, separation, problems mourning and claustrophobia. A reciprocal and hierarchical avatar relation between the claustrum and the container is proposed.

Anxiety, Separation↗
PubMed2000

Single-dose pharmacokinetics and safety of the oral antiviral compound adefovir dipivoxil in children infected with human immunodeficiency virus type 1. The Pediatrics AIDS Clinical Trials Group.

The acyclic phosphonate analog adefovir is a potent inhibitor of retroviruses, including human immunodeficiency virus (HIV) type 1, and, unlike some antiviral nucleosides, does not require the initial phosphorylation step for its activity. Two oral dosages of the adefovir prodrug adefovir dipivoxil were evaluated in a phase I study with children with HIV infection. A total of 14 patients were stratified into age groups ranging from 6 months to 18 years of age. Eight patients received 1.5 mg of adefovir dipivoxil per kg of body weight, and six patients received 3.0 mg of adefovir dipivoxil per kg. Serum samples were obtained at intervals during the 8 h postdosing and were analyzed for adefovir concentrations. Patients were monitored for adverse effects. All samples collected resulted in quantifiable levels of adefovir (lower limit of quantitation, 25 ng/ml) from each patient. The areas under the concentration-versus-time curves (AUCs) were similar (P = 0.85) for the 1.5- and 3.0-mg/kg doses, while the apparent oral clearance (CL/F) was significantly higher (P = 0.05) for the 3-mg/kg dose. Pharmacokinetic parameters differed by patient age. In comparing those children older and younger than the median age of 5.1 years, AUC (P = 0.03), maximum concentration of drug in serum (P = 0.004), and the concentration at 8 h postdosing (P = 0.02) were significantly lower for the younger children. There were no significant differences for apparent volume of distribution and CL/F normalized to body surface area, but there was a suggestive difference in half-life (P = 0.07) among the subjects in the older and younger age groups. No significant adverse events were encountered. These data provide the basis for a multidose phase II study of adefovir dipivoxil in HIV-infected infants and children.

Adenine↗
PubMed2000

Quantitative assessment of marine sponge cells in vitro: development of improved growth medium.

As sources of natural products with potential human therapeutic value, marine sponges are important subjects for cell culture studies. A critical component of any cell culture system is its growth medium. Proceeding from the hypotheses that the thawed, cryopreserved, primary cells would display detectable differential responses and that those responses could be comparatively quantified, this study has established that multiwell screening assays are useful tools for improving medium formulations in cell cultures of the marine sponge, Teichaxinella morchella. Fluorescent probe signals were correlated with known cell densities and viabilities in a 96-well format. Analysis of variance and post-test methods were applied to judge the significance of signal differences seen in a variety of medium formulations. Results from a series of experiments suggested that reducing glutamine and selenium concentrations in the standard medium would result in greater DNA, protein, and esterase activity signals. This was confirmed by the direct comparison of the standard and improved medium formulations. Significantly higher protein content and esterase activity were associated with the improved medium. DNA content was also higher, though not significantly. The result is a new medium formulation that may be more able to support cell growth and division, providing an improved cell culture system for marine sponge cell studies. The assays can be used in additional studies to further improve the in vitro conditions for marine sponge cell culture.

Animals↗
PubMed1998

Diagnosis of gluten-sensitive enteropathy: is exclusive reliance on histology appropriate?

OBJECTIVE: Coeliac disease is a prevalent disorder but frequently remains undiagnosed because of varied modes of clinical presentation. In this study, methods for the detection of coeliac disease were evaluated in a clinical practice setting. METHODS: Small intestinal histology, IgA anti-endomysial and IgG anti-gliadin antibody tests were performed on 441 unselected, consecutive patients under investigation for small intestinal disease. Response to treatment and other clinical events were monitored over the ensuing years. RESULTS: Untreated coeliac disease was diagnosed in 97 patients and was excluded in 344. At clinical presentation, the endomysial antibody test was positive in 84 of the 97 untreated coeliac patients (sensitivity 87%) and negative in 340 of the 344 non-coeliac patients (specificity 99%). A typical histological lesion was found in 83 of the 97 coeliac patients (sensitivity 86%) but was absent in all 344 non-coeliacs (specificity 100%). The sensitivity of the gliadin antibody test was 69% and the specificity was 71%. CONCLUSIONS: In unselected patients attending a gastroenterology clinic, small bowel histology and endomysial antibody serology show similar predictive value in the diagnosis of coeliac disease. These results emphasize that a combination of clinical, histological and serological criteria are required for effective diagnosis of this disorder. Exclusive reliance on histology or serology will result in failure to make a diagnosis in a significant proportion of patients.

Adolescent↗
PubMed1996

Human umbilical vein endothelial cells: a new easily available source of endomysial antigens.

OBJECTIVE: To evaluate human umbilical vein endothelial cells (HUVEC) as an alternative source of endomysial antigen (EmAg) and to assess their suitability for the detection of endomysial antibodies (EmA) in coeliac disease (CD). METHODS: HUVEC were reacted on glass slides with patient sera and examined by fluorescent microscopy. Flow cytometry was used to determine whether the EmAg was expressed on the surface of the cells or was intracellular. Absorption studies were used to confirm the specificity of results. RESULTS: The data presented here show that HUVEC contain an intracellular antigen that binds to immunoglobulin A (IgA) from patients with active CD. Correlation studies showed that HUVEC antibodies were present in the sera of all patients that contained EmA and reticulin IgA antibodies whereas reticulin antibodies were only present in 24 of the 31 patients who were either EmA or HUVEC positive. All of the sera tested which were negative for EmA were also negative for HUVEC antibodies. Ten patients with Crohn's disease and 10 patients with ulcerative colitis were negative for HUVEC or EmA reactivity, as were 16 control subjects attending the gastroenterology clinic with non-specific symptoms and normal small intestinal biopsies. CONCLUSIONS: These findings suggest that the antigen found in HUVEC is antigenically similar to that found in reticulin and endomysium and that all three antigens may be the same. In contrast to the monkey oesophagus, HUVEC offer an easily available antigen for the serological diagnosis of coeliac disease.

Antibodies, Anti-Idiotypic↗
PubMed1993

Identification and expression of the outer capsid protein (VP4) of the IDIR strain of group B rotavirus.

The polypeptide encoded by gene 3 of the IDIR strain of group B rotavirus (GBR) was synthesized by means of a baculovirus expression system. Immunoblot analysis identified the IDIR virus gene 3 product as analogous to the outer capsid protein, VP4, encoded by gene 4 of group A rotaviruses (GAR). This coding assignment had previously been difficult to establish by sequence comparisons, since IDIR virus gene 3 shared < 20% identical amino acid sequences with any GAR protein. Trypsin digestion of the gene 3 protein resulted in the appearance of a product indistinguishable in size from the VP5* outer capsid protein of IDIR agent virions. The recombinant IDIR virus VP4 maintained at least some antigenic epitopes of the native virion protein, as evidenced by reactivity with convalescent antibody obtained following infection of infant rat pups with the IDIR agent. Reactivity was also demonstrated with antisera directed against bovine and porcine isolates of GBR as well as with ADRV, a human strain of GBR.

Amino Acid Sequence↗
PubMed1992

The effects of equine rhinovirus, influenza virus and herpesvirus infection on tracheal clearance rate in horses.

The response of horses exposed to three common respiratory viruses was studied by measuring tracheal mucociliary clearance rates in the trachea. Tracheal clearance rates (TCR) were determined before, during illness and following recovery in horses exposed to equine rhinovirus (ERhV-2), equine influenza virus (EIV) and equine herpesvirus (EHV-4) by means of lateral scintigraphs made following an injection of technetium-99m sulphide colloid into the tracheal lumen. In six horses exposed to ERhV-2, TCR remained within normal limits. Exposure to EIV resulted in reduced TCR in six of seven horses, with TCR remaining below the 95% confidence limits of normal values for each horse for up to 32 days despite the resolution of clinical signs. Moderate changes were observed in six horses exposed to EHV-4, but significant reductions in TCR were evident in three animals. Measurement of TCR was a useful, minimally-invasive technique which demonstrated that respiratory viruses may cause persistent changes in TCR, even though clinical signs are not evident.

Animals↗
PubMed1991

Improved detection of rotavirus shedding by polymerase chain reaction.

To improve identification of children excreting rotavirus a method for the amplification of rotavirus RNA by the polymerase chain reaction (PCR) was developed. The assay was compared with a solid-phase enzyme immunoassay in the detection of rotavirus shedding by infants in hospital during the winter peak of rotavirus infections. Forty children were studied in an intermediate care unit after transfer from intensive care units. Only two were admitted primarily because of diarrhoea; the other thirty-eight were admitted for management of various other disorders. Rotavirus shedding was detected by enzyme immunoassay in twenty of the infants, and nine of these (aged 1 week to 8 months) remained in hospital for more than 5 days after the initial detection of rotavirus and could be studied long term. Of 103 faecal samples from the nine infants, 60 (58%) contained rotavirus RNA detected by reverse-transcriptase (RT)/PCR, whereas only 37 (36%) were positive for rotavirus antigen by the immunoassay (chi 2 = 10.3, p less than 0.002). The geometric mean time of rotavirus shedding was 9.5 (range 1-19) days as detected by RT/PCR and 5.7 (range 1-17) days by the immunoassay (p less than 0.018). In five of the nine children, RT/PCR detected rotavirus shedding for 2-7 days longer than the immunoassay and in four children RT/PCR was positive 1 or more days before rotavirus antigen was detected. Further studies should attempt to find out whether infected infants are capable of spreading wild-type virus during periods when they are not shedding antigen as detectable by enzyme immunoassay.

Antigens, Viral↗
PubMed1990

Immunoglobulins and other modalities for the prevention and treatment of enteric viral infections.

Viral infections of the gastrointestinal tract constitute a major health problem during the first years of life. In addition to causing acute diarrhea, rotaviruses and other enteric viruses may be involved in the pathogenesis of necrotizing enterocolitis and other neonatal enteric diseases. There are several potential methods for the prevention and treatment of gastrointestinal viral infections. Antiviral immune globulins, administered by the parenteral or oral route, might prove useful for the inhibition of intestinal viral replication. Alternatively, specific glycoprotein inhibitors of viral-cell binding might be used to prevent the productive infection of intestinal epithelial cells. In addition, since many enteric viruses require proteolytic enzymes for protein cleavage, protease inhibitors may prove to be effective agents for the inhibition of intestinal viral replication. At this point in time, these methods have proven useful for the inhibition of rotavirus infection in experimental animals. The successful application of these and other methods for the prevention of enteric infections in humans might substantially reduce the morbidity and mortality associated with enteric diseases.

Animals↗
PubMed1987

Sialic acid glycoproteins inhibit in vitro and in vivo replication of rotaviruses.

We investigated the interactions of rotaviruses with glycoproteins and cells that support rotaviral replication. We found that a wide range of naturally occurring glycoproteins, including ovalbumins and ovomucoids from chicken and turkey eggs, and mucin derived from bovine submaxillary glands, inhibit the replication of rotaviruses in MA-104 cells. Our studies further indicated that the glycoproteins bind directly to rotaviruses and that virus-glycoprotein binding is dependent largely upon interactions with sialic acid oligosaccharides. We found that accessible sialic acid oligosaccharides are required for efficient rotavirus infection of MA-104 cells, thus demonstrating that sialic acid oligosaccharides play an important role in the interactions of rotaviruses with both glycoproteins and cells that support rotaviral replication. Bovine submaxillary mucin and chicken ovoinhibitor can also prevent the shedding of rotavirus antigen and the development of rotavirus gastroenteritis in a mouse model of rotavirus infection. Our findings document that a range of glycoproteins inhibit the in vivo and in vitro replication of rotaviruses and suggest that the alteration in the quantity or chemical composition of intestinal glycoproteins is a potential means for the modulation of enteric infections.

Animals↗
PubMed1984

Multiple neoplasms in hairy cell leukaemia.

A patient who presented simultaneously with typical hairy cell leukaemia (HCL) and multiple myeloma (MM) is described. He was treated with melphalan and irradiation and 18 months later presented with an adenocarcinoma. The occurrence of multiple neoplasms in this patient may reflect an underlying predisposition to neoplasia secondary to the immunological defects common in B cell lymphoproliferative diseases.

Adenocarcinoma↗
PubMed1983

Relationship between immunoglobulin levels, lymphocyte subpopulations and Rai staging in patients with B-CLL.

27 patients with B-CLL were evaluated before treatment. All patients were staged according to the 'Rai' classification and the following cell populations were studied B cells, surface immunoglobulin characteristics, mouse red cell rosettes, T cells (E+) and T cell subsets (TG and TM). Serum immunoglobulins were measured in all patients. The relationship between the clinical stage and the above immunological parameters was studied and the possible role of splenic involvement in the finding of abnormal ratios of T cell subsets in the peripheral blood of patients with B-Cell is discussed.

Agammaglobulinemia↗
PubMed1982

Effects of intake of L-ascorbic acid on the incidence of dermal neoplasms induced in mice by ultraviolet light.

We have carried out a study of large malignant skin tumors (squamous cell carcinomas) and other lesions in hairless mice (groups of 38-45) intermittently exposed to ultraviolet light over a period of 15 weeks, beginning when the mice were about 10 weeks old. The several groups were given a standard diet with 0%, 0.3%, 5%, and 10% added L-ascorbic acid (vitamin C) throughout the study. No lesions developed in unirradiated control groups. The lesions were counted every 14 days for 4 months, beginning 4 weeks before the end of the period of irradiation. The observed incidence of lesions of several sizes during successive time periods was analyzed by the statistical method recommended by a committee of the International Agency for Research on Cancer. A pronounced effect of vitamin C in decreasing the incidence and delaying the onset of the malignant lesions was observed with high statistical significance.

Animals↗