Flares of systemic disease in primary Sjögren's syndrome.
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Biomedical subjects
Publications and source records attributed to G Holmes.
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OBJECTIVE: To establish the prevalence among women of primary Sjögren's syndrome (PSS) in Birmingham, UK. METHODS: Eight hundred and forty-six female Caucasians from two general practitioner lists were invited to complete a questionnaire that included a screening question on dry eyes and mouth. Individuals who responded positively were evaluated further. RESULTS: Overall, 65/% of individuals who were sent a questionnaire responded. Two had possible PSS, but were negative for anti-Ro/La antibodies. Our estimates of the prevalence of PSS ranged from < 0.1% up to 0.4%, depending on the assumptions used. CONCLUSION: Our data support previous studies suggesting a prevalence of PSS in the community of 0.1-0.6% rather than those suggesting a higher figure.
Waikato Environment for Knowledge Analysis (WEKA) is a comprehensive suite of Java class libraries that implement many state-of-the-art machine learning/data mining algorithms. Non-programmers interact with the software via a user interface component called the Knowledge Explorer. Applications constructed from the WEKA class libraries can be run on any computer with a web-browsing capability, allowing users to apply machine learning techniques to their own data regardless of computer platform. This paper describes the user interface component of the WEKA system in reference to previous applications in the predictive modelling of foods.
Previous studies have shown that the major metabolic resistance locus in the insecticide-resistant Drosophila line Rst(2)DDT(Wisconsin) maps between the markers cn and vg on chromosome 2. Six cytochrome P450 genes exist in this region. We investigated the expression levels of these P450 genes in DDT-resistant and -susceptible fly lines. We report: (i) DDT resistance is significant (> 30-fold) and dominant, (ii) resistance is reduced by the cytochrome P450 inhibitor PBO, (iii) there is constitutive over-expression relative to susceptible flies of two genes encoding cytochrome P450 enzymes within the cn-vg region (CYP6G1 = 4.3-fold; CYP12D1 = 6.0-fold), and (iv) exposure to DDT results in an increased expression of only one of these two P450 genes (CYP12D1 > or = 6-fold above constitutive resistant fly baselines).
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The Drosophila and vertebrate slit proteins have been characterized as secreted chemorepellents recognized by the robo receptor proteins that function principally for the guidance of neuronal axons and neurons. slit genes are also expressed in the limb. To provide a basis for the determination of slit functions in the limb we have isolated and characterized the expression of chick slit-2 and slit-3 in the developing limb and other tissues of the chick embryo. Both genes share similar expression profiles in the chick embryo when compared to that of their mammalian homologues, particularly in the neural tube. In the limb, their expression patterns suggest their involvement in many aspects of limb development. In the early limb bud, slit-2 is expressed in the peripheral mesenchyme and invading muscle precursors, while slit-3 expression is restricted to the future chondrogenic core of the limb bud. At later stages, both slit genes are expressed in interdigital mesenchyme, in inner periosteal cells, and in mesenchyme immediately radial to the periosteum and under the epidermis. slit-3 is also expressed in proliferating chondrocytes during cartilage development, while slit-2 is expressed in later muscle masses and peripherally to joints in the autopod.
A 26-year-old woman presented with a 12-month history of persistent dermatitis of the lips. She had failed to respond to cosmetic avoidance and therapeutic measures. Patch testing was negative, including her toothpaste and toothpaste flavours. She defied diagnosis until an acute flare followed immediately after dental treatment with a mint flavoured tooth cleaning powder. This led us to prick test her to mint leaves and this was positive. Her cheilitis settled after changing from her mint-flavoured toothpaste. A diagnosis of contact urticaria should be considered in cases of cheilitis of unknown cause.
A 43-year-old female with multiple congenital naevi presented with a 5-year history of right upper quadrant pain. Magnetic resonance imaging demonstrated a large epidural thoracic arachnoid cyst. This case highlights the need to consider that the management of patients with giant congenital melanocytic naevus is variable depending on the age of the patient, the location of lesions and the presence of complications such as neurocutaneous melanosis. The value of magnetic resonance scanning as a screening device is discussed.
When positionally cloned in late 1989, it was anticipated that mutations within the Wilms' tumour suppressor gene (WT1) would prove responsible for this common solid kidney cancer of childhood. Characterisation of the WT1 expression pattern and of the structure of the encoded protein isoforms and their mode of action has now spanned almost a decade. WT1 proteins act as nucleic acid-binding zinc finger-containing transcription factors involved in both transactivation and repression. These activities are facilitated and constrained by interactions with other proteins. Expression analyses and knockout mice indicate that WT1 protein plays a critical role in normal kidney and gonad development. Specific constitutional WT1 mutations results in several urogenital anomaly syndromes. While only 10% of sporadic Wilms' tumours do display WT1 mutation, WT1 is mutated in other cancers, including acute myeloid leukaemia. Much is still to be determined in WT1 biology. The next decade will see at least three streams of attention. The first two, elucidation of the role of WT1 in RNA metabolism and the characterisation of further protein partners, may together explain the distinct tissue-specific functions of WT1. Finally, further research into the role of WT1 in haematopoiesis will improve our understanding of WT1 in leukaemia.
Ultrasound evaluation of the fetal heart can be performed. Knowledge of the embryology, anatomy, and function of the heart have led us to understand the pathophysiology of congenital heart disease. In this review we discuss the indications as well as some basic principles of fetal echocardiography.
IgA pemphigus is rare but may be underdiagnosed. We describe two cases, a 50-year-old female with a pustular eruption resembling subcorneal pustular dermatosis and a 55-year-old male with a pruritic vesiculopustular eruption simulating dermatitis herpetiformis. They illustrate the clinical heterogeneity of IgA pemphigus which is likely to reflect differences in autoantigens, analogous to pemphigus vulgaris and pemphigus foliaceus. There is now evidence that IgA pemphigus encompasses at least two subgroups: a subcorneal pustular dermatosis (SPD)-type, (see case 1) characterized by subcorneal pustules and autoantibodies to desmocollin 1; and intra-epidermal neutrophilic dermatosis (IEN)-type cases (see case 2) which show intra-epidermal pustules and in whom the autoantigen may be desmoglein 3, the pemphigus vulgaris antigen.
Susceptibility to coeliac disease is genetically determined by possession of specific HLA-DQ alleles, acting in concert with one or more non-HLA linked genes. The pattern of risk seen in sibs and twins in coeliac disease is most parsimonious with a multiplicative model for the interaction between the two classes of genes. Based on a sib recurrence risk for coeliac disease of 10% and a population prevalence of 0.0033, the sib relative risk is 30. To evaluate the contribution of the MHC region to the familial risk of coeliac disease, we have examined haplotype sharing probabilities across this region in 55 coeliac disease families. Based on these probabilities the sib relative risk of coeliac disease associated with the MHC region is 3.7. Combining these results with published data on allele sharing at HLA, the estimated sib relative risk associated with the MHC region is 3.3. Therefore, the MHC genes contribute no more than 40% of the sib familial risk of coeliac disease and the non-HLA linked gene (or genes) are likely to be the stronger determinant of coeliac disease susceptibility.
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OBJECTIVES: Drug use review is used by both the public and private sector to influence prescribing behavior and patient drug use. Past interventions mailed to prescribers have had mixed results. The objective was to evaluate the effect of a one-time, mailed intervention on subsequent use of sedative hypnotic medication. METHODS: An experimental design was used. The intervention contained guidelines for the use of sedative hypnotics, a prescriber profile detailing sedative hypnotic prescribing, and a patient profile. Clustering of patients and their shared prescribers was done to avoid contamination bias and statistical problems associated with a lack of independence of observations. Subjects were 189 Washington State Medicaid recipients who had received at least one tablet per day of a sedative hypnotic medication for 1 year and their prescribing physicians or (when information about the physician was lacking) the dispensing pharmacy. RESULTS: A significant reduction in the use of targeted sedative hypnotic medications was measured in the intervention group (-27.6%) versus the control group (-8.5%). In the intervention group, 9.4% of patients began a new prescription for a benzodiazepine not targeted by the drug use review, whereas no control patients had new use of nontarget benzodiazepines. CONCLUSIONS: The intervention achieved a statistically significant decrease in targeted drug use, and the amount of reduction is likely to have decreased the risk of fractures associated with benzodiazepine use. This study adds to the recent evidence that mailed drug use review interventions can have a desirable impact on patient drug use.
Twenty-six children with intellectual disability and six normal children, all suffering from refractory partial seizures, received open-label gabapentin (range = 10-50 mg kg(-1) day(-1); mean = 26.7 mg kg(-1) day(-1) as an add-on medication to their antiepileptic drug regimen. Mean seizure frequency during baseline was 9.5 seizures per week. Both groups had a significant reduction in seizure frequency. Response scores and response ratios did not differ between the intellectually disabled and normal groups (1.67+/-0.67 and 1.25+/-0.69, P = 0.697, and -0.400+/-0.089 and -0.283+/-0.159, P = 0.961, respectively). Behavioural side-effects were more likely to occur in patients with intellectual disability in comparison with the mentally normal group (P = 0.0107). In the present patient population, patients younger than 10 years of age, all of whom had intellectual disability, were more likely to have side-effects than those older than 10 years of age. Observed adverse effects, which were generally mild, occurred in patients with baseline intellectual disability, attention deficit disorder and behavioural problems. Behavioural adverse effects warranted discontinuation of the medication in only three patients. The severity of intellectual disability (mild versus moderate or severe) did not affect the extent of the response or the occurrence of side-effects. It is concluded that gabapentin is equally effective as an add-on medication against partial seizures in patients with or without intellectual disability. However, children with intellectual disability who also are less than 10 years of age with baseline attention deficit appear to be at a higher risk of behavioural side-effects.
In addition to dispensing, pharmacists are ideally positioned to provide cognitive services that are targeted at optimizing drug therapy through identification and resolution of drug therapy problems. The Washington Cognitive Activities and Reimbursement Effectiveness project sought to determine: (1) if pharmacists would respond to a financial incentive by performing more cognitive services, and (2) the effect on drug cost of cognitive services they performed.