Successful treatment of a refractory verruca in a child with acute lymphoblastic leukaemia with topical cidofovir.
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Antiviral Agents↗
Biomedical subjects
M Cotter
Publications and source records attributed to M Cotter.
Odour management plans: a risk-based approach using stakeholder data.
Annoyance is a familiar reaction to odours arising from wastewater treatment sites, a reaction which can result in complaints and prosecutions. Odour management plans can be used to assess the extent of nuisance caused and prioritise mitigation measures. Often, these plans have been developed purely on the basis of technical assessments of emission and dispersion, with the general aim of limiting odour concentrations to a specific threshold at some distance from the works. They have often been prepared with inconsistent communication between the site staff and consultant during the development process, and may not directly refer to the affected population. This paper describes a risk-based approach to developing odour management plans, in which mitigation measures are assessed and prioritised on the basis of the likely frequency and intensity of odour exposure. A key element of the approach is the use of knowledge from data gained from key stakeholder groups: customers, staff, and regulators. Emphasis is placed on the development of clear communications between these groups, which helps both in terms of raising awareness amongst operators as to the significance of odour problems, and also in managing the expectations of customers and regulators. The practical application of this approach is demonstrated by the development of odour management plans for wastewater treatment sites by Yorkshire Water Services Ltd. These have used data from staff, customers and regulators to develop risk grids, which are then used to prioritise remediation measures. Involving staff in the data collection operations has been successful in raising awareness of the significance of odours, and has in turn led to low-cost emission reductions through improved housekeeping. Improved communications between operators, customers and regulators has led to more realistic expectations with regard to odour problems, a situation which can reduce conflict and prevent the imposition of stringent and sometimes unrealistic odour standards.
Communication↗
A novel t(15;17) translocation in acute myeloid leukaemia not associated with PML/RARalpha rearrangement.
We report a novel t(15;17)(q15;q11) translocation in acute myeloid leukaemia (AML M4) which was not associated with PML/RARalpha rearrangement or with acute promyelocytic leukaemia (APL) morphology. The leukaemia behaved in refractory fashion, with 70% blasts in the bone marrow after the first course of chemotherapy. In view of the refractory behaviour of the leukaemia, the patient was treated with high dose chemotherapy and autologous stem cell rescue. The patient is alive and well 22 months post-autologous stem cell transplant. This case demonstrates that while cytogenetic analysis provides important diagnostic and prognostic information, the precise location of the chromosomal breakpoints is critical in the interpretation of cytogenetic results.
Adult↗
High responding factor VIII inhibitors in mild haemophilia - is there a link with recent changes in clinical practice?
The development of high responding inhibitors is an increasingly recognized complication of mild Haemophilia. Inhibitors tend to develop in adolescence and adulthood and this is frequently preceded by high-intensity factor replacement therapy. We report two patients with mild Haemophilia who developed high responding inhibitors after continuous infusion with recombinant factor VIII (Kogenate) as prophylaxis for surgery. We discuss whether recent changes in clinical practice could be responsible for the apparent increase in high responding inhibitors in mild Haemophilia.
Adult↗
Intracellular forms of human NOTCH1 functionally activate essential Epstein-Barr virus major latent promoters in the Burkitt's lymphoma BJAB cell line but repress these promoters in Jurkat cells.
We have demonstrated that intracellular forms of NOTCH1 transactivate two major Epstein-Barr virus (EBV) latent promoters, the LMP1 and Cp1 promoters in an EBV-negative B-cell line, BJAB. Truncated intracellular NOTCH1 associated with the nuclear membrane (DeltaE) transactivates the LMP1 promoter fivefold; however, the intranucleus localized form of NOTCH1 (ICN) transactivates this promoter approximately twofold in chloroamphenicol acetyltransferase (CAT) reporter assays in BJAB cells. Additionally, DeltaE activated the major Cp1 promoter 12-fold, whereas the ICN form of NOTCH1 activates at only about half that level when compared to that of DeltaE membrane-bound NOTCH1. This result differs from previously observed data, where intracellular NOTCH1 bound to the nuclear membrane, DeltaE, and nucleus-localized NOTCH1, ICN, all had similar levels of activation in 293 cells. This suggests distinct transcriptional activities in different cell types. Moreover, in Jurkat cells, a T-cell line, intranucleus localized NOTCH1 molecules demonstrated a repressive activity against the two EBV major latent promoters. Only DeltaE activated the Cp1 and LMP1 promoters at a level slightly above background, whereas intranucleus localized NOTCH1 ICN, or the form of NOTCH1 lacking the ankyrin repeats, DeltaE(TAR), surprisingly resulted in the repression of these promoters in Jurkat cells. Similarly, another truncated form of NOTCH1, referred to as ICNW, which contains the tryptophan residue W(1767) within one of the RBP-Jkappa interacting domains, repressed the LMP1 promoter approximately twofold. Further analysis of the truncated NOTCH1 molecules on the LMP1 promoter element, lacking the two RBP-Jkappa binding sites, suggests that repression in Jurkat cells may be affected by the presence of the two RBP-Jkappa binding sites. These studies indicate that intracellular NOTCH1 can activate the EBV major latent promoters in BJAB cells. However, in Jurkat cells, intracellular truncated forms of NOTCH1 lacking the RBP-Jkappa binding sites repress these EBV latent promoters. Only the membrane-bound form of NOTCH1, DeltaE, activated the EBV major latent promoters in Jurkat cells, albeit at a lower level than that seen in BJAB cells. Our data suggest that EBNA2 and truncated intracellular nuclear localized forms of NOTCH1 may be functionally similar in their interactions with RBP-Jkappa; however, these molecules may have distinctly different transcriptional partners in BJAB and Jurkat cells. Moreover, these truncated NOTCH1 molecules may not represent the normal processed forms of NOTCH1 in cells and may exhibit dominant negative phenotypes in the absence of the required posttranslational modifications. Further investigations are necessary to determine the similarity and differences occurring with intracellular NOTCH1 in other B- and T-cell lines.
Adaptor Proteins, Signal Transducing↗
Consistency in the observation of features used to classify duct carcinoma in situ (DCIS) of the breast.
AIM: To determine interobserver and intra-observer agreement in the assessment of cytological grade and intraduct necrosis in pure duct carcinoma in situ (DCIS) of the breast. METHODS: Sixty unselected cases with illustrated diagnostic criteria were circulated to 19 practising histopathologists. RESULTS: Overall agreement was moderate for cytological grade in three categories: 71% agreement; weighted kappa (kappa w), 0.36; intraduct necrosis in three categories (absent, present, extensive): 76% agreement; kappa w, 0.57; and the Van Nuys classification system: 73% agreement; kappa w, 0.48. Agreement was no better among observers participating in the National External Quality Assurance Programme. Intra-observer agreement for cytological assessment (69.6% agreement; kappa w, 0.52) and intraduct necrosis (68.3% agreement; kappa w, 0.48) was moderate, suggesting that individual variation rather than precision of criteria contributes to the lack of agreement. CONCLUSIONS: Moderate agreement on observations can be achieved by non-specialist pathologists, with better agreement on necrosis than cytological grade. There was evidence of consistent individual bias towards over or under scoring cytological grade, which could be corrected with adequate and prompt feedback.
Breast Neoplasms↗
Distinct patterns of viral antigen expression in Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus coinfected body-cavity-based lymphoma cell lines: potential switches in latent gene expression due to coinfection.
Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV), also referred to as human herpesvirus 8 (HHV-8), are human gammaherpesviruses associated with numerous lymphomas and proliferative diseases in humans. We were interested in the protein expression patterns of specific latent and lytic proteins from the EBV genome in two body-cavity-based lymphoma cell lines, BC-1 and BC-2, which are coinfected with EBV and KSHV. BC-1 and BC-2 were analyzed using specific antibodies to latent proteins known to be essential for EBV immortalization of human primary B-lymphocytes in vitro and lytic antigens important for EBV replication and production of viral progeny. The coinfected cell lines are compared with two singly infected KSHV cell lines to determine whether antibodies against EBV-specific proteins cross-reacted against KSHV antigens. All the KSHV-infected cell lines express the KSHV-specific latency-associated nuclear antigen (LANA) with a specific pattern in the nucleus. This staining was distinct from that seen for EBNA1 in the EBV coinfected lines BC-1 and BC-2 staining the nucleus as a diffused pattern throughout the nucleus with denser staining in some regions. The coinfected cell lines all express EBNA1 and LMP1 at lower levels compared with singly infected EBV lymphoblastoid cell lines (LCLs). However, the essential latent antigens EBNA2, EBNA3A, and EBNA3C are not expressed in BC-1 and BC-2. This indicates potential regulation of EBV latent gene expression by KSHV-encoded viral or KSHV-induced cellular gene products. Additionally, lytic gene expression analysis demonstrated that BZLF1 and BMRF1 are expressed along with other early antigens (EA-D). A specific protein is detected in a singly infected KSHV cell line with cross-reactivity to antibodies that detected the EA-D complex. Moreover, in all the cell lines infected with EBV, KSHV, or EBV and KSHV, human serum with antibodies against KSHV antigens recognizes specific viral antigens approximately 110 and 41-42 kDa, suggesting that human antibodies against KSHV-specific antigens can cross-react with similar EBV antigens. Therefore these data suggest that the EBV pattern of gene expression in the coinfected cell lines is a type II pattern of latency also seen in other human tumors including nasopharyngeal carcinoma and Hodgkin's lymphoma. This distinct pattern of latent and lytic gene expression in these cell lines may provide clues as to the selection for coinfection in these body cavity based lymphomas in immunocompromised hosts.
Antigens, Viral↗
Age-Related Disease Penetrance in a Large Medullary Thyroid Cancer Family With a Codon 609 RET Gene Mutation.
Background: Familial medullary thyroid cancer (MTC) is a form of type 2 multiple endocrine neoplasia in which individuals develop MTC as the sole phenotypic manifestation of their disease. A previous study has suggested that patients with familial MTC may have a later age of onset (and more indolent course) of MTC than is observed in individuals with multiple endocrine neoplasia type 2A. Methods and Results: The age-related penetrance of MRC, C-cell hyperlasia, and a positive pentagastrin test for carriers of a codon 609 mutation of the RET gene in a large MTC family was determined. Pentagastrin testing and surgical pathology findings for patients who had thyroidectomies were correlated with RET sequence analysis findings. The penetrance of this mutation for the development of MTC was 0% at age 20, 10% at age 20, 10% at age 30, 50% at age 45, and approximately 100% at age 60. The ages of onset of C-cell hyperplasia and a positive pentagastrin stimulation test were similar, and both preceded the age of onset of MTC. Carriers of the mutated gene in this family had a later age of onset of disease that has been reported for families with multiple endocrine neoplasia type 2A and 2B syndromes. Conclusions: These results may have implications for the clinical management of MTC families with a 609 mutation.
Journal Article↗
Examination of cytological smears and clot sections prepared from pleural fluids: a comparative study.
Between January 1989 and May 1990, the Department of Cytology of Llandough Hospital examined 784 pleural fluid cytological preparations, 99 of which were also examined as paraffin wax sections of clots that had formed. To assess whether this practice yields worthwhile information, we reviewed the cytology and clot sections of 99 patients with pleural effusions and correlated the results with subsequent histology and review of clinical case notes. The specificities of each method separately and when combined was high: 92% clot section, 85% smear cytology and 85% combined. The sensitivity using clot section alone was 49%, smear cytology alone 46% and in combination, 54%. Analysis showed no significant difference between sensitivities. When pleural fluid clot formation occurs, we recommend the continued examination of clot sections, since it yields an increase in positive diagnoses, albeit not statistically significant.
Cytodiagnosis↗
Keratin 18 is associated with a subset of older taste cells in the rat.
All or nearly all intragemmal (elongated) cells of rat taste buds were immunopositive for keratins 7, 8, and 19. In contrast, keratin 18 was detected in 19 +/- 5 cells per taste bud (mean +/- sd), or about 25% of the intragemmal cells. During taste bud development keratins 7, 8, and 19 were evident initially in polygonal cells and later in elongated taste cells. Keratin 8 appeared in vallate taste cells at P0 (postnatal day 0), followed by keratins 7 and 19 at P1, and keratin 18 at P2-P3. Keratin 18 was always limited to elongated cells. The assemblage of elongated taste cells comprising a taste bud began with a single elongated cell, rather than with the synchronous elongation of a cluster of cells. Developmental errors were observed at P2-P3, e.g., some vallate taste cells had a misoriented axis. In order to study the pace of keratin differentiation during cell turnover we injected bromodeoxyuridine (BrdU) into adult rats to monitor taste cell age. Keratin-19-positive intragemmal cells differentiated within 1 day. In contrast, keratin 18 was first detected in cells aged 3 days. Hence, both in taste cell development and replacement, keratin 18 was restricted to the older cells; it was the last taste cell keratin to become expressed during differentiation.
Animals↗
Antisocial behavior, somatization, and sensation-seeking behavior in mothers of clinic-referred children.
OBJECTIVE: The relationship between antisocial behavior and somatization was studied in a sample of mothers of clinic-referred, school-age children. The goal was to overcome some of the methodological limitations of past research in this area and to provide a preliminary test of the theory that these disorders share a common substrate: a tendency toward behavioral disinhibition. METHOD: Structured diagnostic interviews and an objective personality measure were used to assess antisocial behavior and somatization in a sample of 90 biological mothers (mean age 34 years) of children referred to an outpatient mental health clinic. A rating scale measure of sensation-seeking behavior was used as a measure of behavioral disinhibition. Structured interviews were used to assess a history of antisocial behavior in the children and their biological fathers. RESULTS: Results indicated a link between somatization and antisocial behavior both within individuals and across generations. This intergenerational link could not be solely accounted for by assortative mating between women with somatization and antisocial men. Both somatization and antisocial behavior were correlated with scores on the sensation seeking scale. CONCLUSIONS: These findings are consistent with the theory that antisocial behavior and somatization are related syndromes and that behavioral disinhibition may be a common predisposition that underlies both.
Adolescent↗
Cancer and nuclear power stations.
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Humans↗
Bone cancer in Wales overestimated.
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Bone Neoplasms↗
Cause and effect of ischaemia in chronic experimental diabetic neuropathy.
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Aminoglutethimide↗
Effects of long-term streptozotocin diabetes on the contractile and histochemical properties of rat muscles.
Contractile and histochemical properties of soleus (a slow-twitch muscle) and extensor digitorum longus (EDL, a fast-twitch muscle) were studied in mature rats after 3 months of streptozotocin-induced diabetes. Results were compared with age- and weight-matched controls. Diabetes produced profound wasting of fast muscles and particularly of the fast glycolytic (FG) fibres. Slow muscle fibres, both within the mixed EDL and in soleus, were less atrophied. Strength performance of EDL was reduced by diabetes, but maintained in soleus. Diabetes was without effect on the time to peak tension (TTP) and half-relaxation time (HRT) of EDL. However it produced profound slowing of soleus muscles, particularly of the relaxation phase. Part of the slowing effect of diabetes may be related to a histochemically demonstrable loss of fast oxidative glycolytic (FOG) fibres in soleus. Histochemical staining for the oxidative marker succinic dehydrogenase (SDH) revealed marked disruption of reaction product distribution in soleus, indicating an impairment of oxidative capacity.
Animals↗
Gastric cancer: a continuing diagnostic challenge--a district general hospital's experience.
We present the results of 87 consecutively referred patients with malignant gastric tumours who presented to the North Middlesex Hospital between 1980 and 1984, inclusively. The results of this prospective study showed a high incidence of adenocarcinoma situated in the cardia (16 per cent of patients), and antral carcinomas presented more commonly with chronic blood loss. Delay in diagnosis was still a serious problem and weight loss remained an underestimated symptom, especially when combined with other upper gastrointestinal symptomology. The majority of tumours were adenocarcinomas. Six patients had unusual tumours which had special therapeutic and prognostic implications. The results of the above study are compared with the European experience of the management of malignant gastric tumours.
Adenocarcinoma↗
Fast to slow phenotypic changes in rabbit muscle can be induced without increases in neural activity.
Immobilization of rabbit tibialis anterior (fast) muscle in a lengthened position for 5 weeks led to a fivefold increase in the number of slow oxidative fibres. Unlike the situation in other models of phenotypic change in adult muscle, the increased expression of slow phenotype was not associated with an increase in the level of electrical activation, as monitored in the stretched muscles by chronic telemetric electromyography.
Animals↗
Recovery from immobilization-induced atrophy of rabbit soleus muscles can be accelerated by chronic low-frequency stimulation.
Immobilization of rabbit soleus muscles with an ankle joint angle of 90 degrees led to gross degeneration after 2 weeks. Natural recovery in the subsequent 2 weeks had little effect on the mean area of soleus fibres, although there were signs of regeneration. However chronic low-frequency activation of soleus muscles by nerve stimulation greatly accelerated recovery, producing muscle fibres of normal areas and with characteristics of maturity.
Animals↗