Diseases of the lips

Heath care providers should be comfortable with normal as well as pathologic findings in the lips, because the lips are highly visible and may display clinical manifestations of local, as well as systemic inflammatory, allergic, irritant, and neoplastic alterations. Fortunately, the lips are easily accessible. The evaluation should include a careful history and physical examination, including visual inspection, as well as palpation of the lips and an examination of associated cervical, submandibular, and submental nodes. Pathologic and microscopic studies, as well as a review of medications, allergies, and habits, may further highlight possible etiologies. Many lip conditions, including premalignant changes, are relatively easy to treat, when the abnormalities are detected early; however, advanced disease and malignancies are challenging for both the patient and clinician. Treatment should be focused on eliminating potential irritants or allergens and treatment of the primary dermatosis. In this paper we review physiologic variants as well as pathologic conditions of the lips

Characterisation of immune responses to varicella vaccination in relation to clinical outcome

PhDThis thesis examines both humoral and cellular adaptive immune responses to varicella vaccination (up to 18 months post immunisation), in an ethnically diverse population of healthcare workers. Using two parameters of humoral immunity at six weeks post first vaccination; (avidity readings 60%, and a TRFIA reading 400mIU/mL) a cut-off of 130mIU/mL was defined for a more sensitive in house immuno assay (TRFIA), in this vaccinated adult population. Using these cut-offs, three patterns of antibody responses were identified; primary responders who seroconverted following vaccination, secondary responders who had pre-existing immunity and subjects who responded poorly to vaccination. Demographic and immunological characteristics of each subset were examined. An association between black ethnicity and lower antibody titre to vaccination in primary responders was identified, whilst Caucasians were more likely to have a history and pre-existing immunity, in keeping with the epidemiology of chickenpox in temperate climates. The follow-up study revealed that affinity maturation to VZV can take longer than 18 months in response to vaccination. At follow-up, 25% of subjects recruited at this time point were seronegative by TRFIA. Seroconversion after two doses of vaccine and a TRFIA titre of <500mIU/ml after two doses were significantly associated with waning antibody titre over time. Positive IFN- ELISPOT responses at 18 months did not necessarily correspond with TRFIA seropositive status.

Мікрофлора ротової порожнини. Навчальний посібник для студентів стоматологічних факультетів вищих медичних навчальних закладів ІІІ-ІV рівнів акредитації

The aim of this manual is to provide an accurate comprehensive and up to date coverage of Microbiology, Virology and Immunology of human oral cavity. It includes a review of the oral flora composition, methods of the microflora study and oral infection diagnostics. Special attention has been directed to the aetiology of caries and parodontitis. Wide-spread bacterial, fungal and viral infections of the oral mucosa have been described in the 4-7 parts of the manual.The book is principally intended for dental students, but practicing dentists will find it useful

Serological array for the diagnosis of viral infection of the central nervous system

Encephalitis caused by the alphaherpes viruses HSV 1, HSV 2 and VZV can be devastating and rapid, accurate diagnosis is required. Whilst existing molecular techniques are invaluable in diagnosing acute disease, detection of antibody is needed to confirm infection and to make a diagnosis after the acute stage or during post-infectious encephalitis. Current immunoassays are limited by the volume of sample required. The aim of this project was to develop a rapid, accurate, low sample volume assay to improve diagnosis using Luminex technology.The immunodominant proteins of HSV and VZV, glycoprotein D (gD) and glycoprotein E (gE), were expressed in insect cells using a baculovirus expression vector. Expressed proteins were purified, characterised and used to develop in-house enzyme-linked immunosorbent assays (ELISA) to detect HSV and VZV type-specific antibodies. The performance of each newly developed in-house ELISA was compared with commercial ELISA assays using well characterised serum panels. An excellent correlation between the in-house ELISAs and the commercial ELISA assays (100% for HSV gD and 99% for VZV gE) was observed. To differentiate between HSV-1 and HSV-2 a new commercial ELISA assay (Omega) utilising a branched chain peptide (peptide 55 which provides immune selection of HSV-2 specific antibody) was evaluated against two commercially available HSV-2 ELISA assays. The Omega assay showed an overall agreement of 97.6% with Western blot and other ELISA assays. The two expressed proteins, together with peptide 55, were used to develop a triplex fluorescent microbead immunoassay for the simultaneous detection and quantitation of anti-viral antibody in human sera. Initially a monoplex assay for each analyte was developed and optimised individually and then the three assays were mixed together in a triplex assay. Results for HSV-1 gD and VZV gE obtained from the triplex assay showed a 100% agreement with HSV-1 and VZV in-house ELISA results. In the case of peptide 55, the triplex assay results showed better sensitivity than the Omega ELISA assay with an overall agreement with Western blot and other assays of 98.4%. In addition, in order to facilitate the diagnosis of alphaherpesviruses CNS infections the triplex assay was joined together with a biplex fluorescent microbead immunoassay designed for detecting and measuring human IgG and albumin in CSF and serum samples. The sensitivity and reproducibility of the resultant five-analyte multiplex immunoassay and the previous triplex assays were compared and found to have equivalent sensitivity and specificity. The sensitivity and minimal sample requirements of the new assay suggests that it will be a powerful tool for the diagnosis and study of both acute and post-infectious viral encephalitis.EThOS - Electronic Theses Online ServiceThe government of Suadi ArabiaGBUnited Kingdo

Ocular monitoring in immunosuppressed patients and quantification of immunosuppression by assessment of intracellular cytokines.

Although laboratory indices, such as drug levels, are in routine use for monitoring immunosuppression, these do not always correlate well with an individual's risk of toxicity. In practice individual organs are monitored for toxicity with a combination of laboratory and clinical methods. These methods are limited by the fact that one has to await compromise before making therapeutic changes and there are often idiosyncrasies in the way individuals respond. Ocular complications can be sight threatening and many have proposed routine ocular monitoring in immunosuppressed patients. This study prospectively monitored a cohort of patients receiving high levels of immunosuppression for the prevention of rejection of heart, lung and heart-lung transplants for the development of ocular complications and to assess ocular morbidity. Specific surrogate markers that gave more information about the level of immunosuppression in a particular patient would improve patient care. Cytokines have the advantage of being directly generated by the immune response and offer promise as surrogate markers. Various, and not always consistent, cytokine profiles have been described for a number of conditions. Flow cytometry with intracellular cytokine staining allows quantification of the amount of cytokine present. These studies used this technique to describe the cytokine profile and changes in cytokine profile seen in patients during treatment for autoimmune uveitis and in patients with human immunodeficiency virus (HIV) receiving combination anti-retroviral therapy (ART). These studies emphasized the importance of prompt and careful clinical examination in the presence of clinical symptoms but did not support routine screening of patients on high levels of immunosuppression. Accurate measurements of interleukin-2 (IL-2) and interferon-gamma (IFNgamma) in patients with uveitis did not correlate well with disease activity. In contrast patients with different HIV profiles did show measurably different Thl cytokine expression providing information on the T cell deficits that persist despite treatment with ART

Understanding risk factors for herpes zoster and postherpetic neuralgia in UK primary care: investigations to inform vaccine policy.

Background: Herpes zoster affects millions of people worldwide each year and many go on to suffer long-term pain, called postherpetic neuralgia (PHN). As zoster is common and PHN is difficult to treat, preventing zoster through vaccination is important. This thesis aims to better understand risk factors for zoster and PHN, in order to inform vaccination policy. Methods: Three large observational studies were carried out using primary care data from the UK Clinical Practice Research Datalink and linked secondary care data from the Hospital Episodes Statistics. First, a matched case-control study quantified the effects of possible risk factors for zoster and explored whether their effects differed by age group. Second, a descriptive study looked at antiviral prescription patterns and patient characteristics associated with antiviral receipt after zoster diagnosis. Third, a cohort study assessed risk factors for PHN and investigated whether their effects were modified by antiviral use. Results: The case-control study of zoster risk factors included 144,959 zoster patients and 549,336 controls and found an increased risk of zoster among patients with rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, chronic obstructive pulmonary disease, asthma, chronic kidney disease, depression and type 1 diabetes; odds ratios ranged from 1.14 to 1.72. In general, the relative effects of these risk factors on zoster decreased with increasing age. In the descriptive study of antiviral use, of 142,216 zoster cases, only 58.1% received an antiviral prescription at zoster diagnosis. Antivirals were even under-prescribed among the immunosuppressed and older individuals, for whom guidelines recommend routine treatment. The cohort study of PHN risk factors identified 119,413 zoster patients, 5.8% of whom developed PHN. An increased risk of PHN was found among patients with rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, chronic obstructive pulmonary disease, asthma, depression, type 2 diabetes, lower socioeconomic status, smoking and under- or overweight; odds ratios ranged from 1.13-1.82. Antiviral use was not associated with PHN risk overall. The zoster case-control and PHN cohort study showed that patients with severely immunosuppressive conditions were at greatest risk of both zoster and PHN. Conclusions: A number of patient characteristics and comorbidities were associated with increased zoster and PHN risks. Patients at highest risk of zoster and PHN are those of older age and those with immunosuppression; currently, patients with immunosuppression are not eligible for vaccination, highlighting a need for alternative risk reduction strategies in this group. Low antiviral use at zoster diagnosis suggests treatment guidelines be revised to encourage greater use, especially among the immunosuppressed and older individuals who are recommended, but not routinely given, antivirals. Research on the cost-effectiveness of vaccinating patients with specific risk factors is needed

New developments in analysis of ocular surface diseases|Nieuwe ontwikkelingen in analyse van ziekten van het oogoppervlak

The thesis is divided into three parts, each part investigates a different disease of the ocular surface. The first part describes a new animal model to follow allogenetic limbal transplants by enhanced green fluorescent protein (E-GFP). In this model E-GFP is able to reliably follow transplant survival, however E-GFP itself is immunogenic. Conjunctival melanoma is the topic of part II, where non-invasive diagnostic techniques are investigated. Both exfoliative cytology and the newer Biopore membrane cytology are described. Immunohistochemical staining for the S-100 protein family were performed. Furthermore a new conjunctival melanoma cell line has been developed. In part III several single nucleotide polymorphisms for lactoferrin and IL-10 have been investigated in patients with herpes simplex keratitis or a bacterial corneal ulcer.UBL - phd migration 201

Epidemiology and molecular biology of elephant endotheliotropic herpesvirus 1 in the Asian elephant Elephas maximus

Herpesviruses are ubiquitous and are found worldwide, most animal species can be infected with multiple herpesviruses. Some cause clinical disease and others remain symptomatic throughout life. Herpesviruses are found in both captive and wild animals including Asian elephants (Elephas maximus). Elephant Endothelioltropic Herpesvirus (EEHV) has been reported in both captive and wild Asian elephants, with a number of cases being reported in North America, Europe and Asia. It has been suggested that EEHV is associated with haemorrhagic disease, which has been attributed to a number of Asian elephant deaths, affecting mostly juveniles and calves. Clinical signs can vary from weight loss, lethargy, depression, cyanosis of the tongue and sudden death. Molecular testing using qPCR has enabled the detection of individual variants of EEHV, this thesis investigates the EEHV1 variant. EEHV1 has been highlighted as the variant that is more frequently associated with deaths. This thesis includes five studies investigating different aspects of EEHV. Including, the relationship between pregnancy and EEHV viral shedding, the use of an amended human protocol for culturing endothelial cells, EEHV tissue tropism, a potential genetic or familial link between EEHV associated deaths and the detection of potential co-pathogens. The main findings from this thesis include: 1) the use of a longitudinal study investigating a potential link between the physiological stress of pregnancy and EEHV viral shedding. This study suggested there was no link between pregnancy and EEHV viral shedding however other stressors may be involved. 2) Using an amended human umbilical vein endothelial cell protocol, the culture of Asian elephant endothelial cells was successful. The cells from this study may be used in subsequent drug testing and vaccine development. 3) Quantitative PCR was used to determine EEHV1 tropism in tissues from two deaths associated with the virus. Tropism appeared to be for the heart and liver. 4) This thesis provides results from a preliminary study into a potential link between EEHV associated deaths. The data from an Asian elephant genogram shows there is the possibility of a genetic or familial link, which requires further investigation. 5) A number of tissues from deaths associated with EEHV and or death from other causes were investigated for the presence of potential co-pathogens, including the presence of encephalomyocarditis virus (EMCV), using microarray technology. The results indicated there were no co-pathogens present in the tissues. This thesis adds to the current published data, and includes the first known preliminary study investigating a potential genetic link between elephant deaths due to EEHV