Understanding social policy in Europe.
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Biomedical subjects
Publications and source records attributed to S Jackson.
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Necrotizing granulomatous nodules are a common feature in patients with rheumatoid disease, affecting 20 per cent of seropositive patients. Although most commonly found subcutaneously at points of pressure, these nodules may occur in the connective tissues elsewhere in the body. In the upper aerodigestive tract, nodules have been described in diverse locations, but commonly in the trachea, larynx and the ear. We present the first reported case of a rheumatoid nodule affecting the nasal septum.
Mortality in treated squamous cell carcinoma of the oral cavity is most often owing to locoregional failure. In an attempt to improve survival, an aggressive approach to surgical management is often favoured. Although it is generally accepted that the N0 neck should be treated if the risk of micrometastatic disease exceeds 20%, there is little direct support in the literature for this position. A retrospective review of all patients presenting with T1-2, N0 squamous cell carcinoma of the oral cavity treated at the Cancer Control Agency of British Columbia from 1985 to 1994 was conducted. Patients were followed for a minimum of 5 years with documentation of patterns of recurrence and disease-specific survival relative to initial management. The decision regarding management of the neck was frequently made to accommodate treatment of the primary site or reconstructive strategies. Thirteen percent of patients with T1, N0 disease underwent prophylactic neck dissection. No significant difference in outcome was noted in this group. Thirty-three percent of patients with T2, N0 disease underwent prophylactic neck dissection. There was a trend toward improved 5-year survival and lower recurrence rates in the group whose necks were treated, but the difference was not found to be statistically significant. In conclusion, this review showed a trend toward increased survival with prophylactic treatment of the neck in T2, N0 squamous cell carcinoma of the oral cavity, but a larger study would be needed to show a statistically significant benefit.
Compared with nondiabetic subjects, type 2 diabetic individuals are at an increased risk for coronary artery disease and coronary restenosis after angioplasty or stenting. Increased proliferation and migration of vascular smooth muscle cells (VSMCs) contribute importantly to the formation of both atherosclerotic and restenotic lesions. Therefore, pharmaceutical interventions targeting proteins that regulate VSMC growth or movement are a promising new approach to treat diabetes-associated cardiovascular disease. Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a member of the nuclear receptor superfamily that, when activated by thiazolidinedione (TZD) insulin sensitizers, regulates a host of target genes. All of the major cells in the vasculature express PPAR-gamma, including endothelial cells, VSMCs, and monocytes/macrophages. PPAR-gamma is present in intimal macrophages and VSMCs in early human atheromas. In an animal model of vascular injury; PPAR-gamma levels are substantially elevated in the neointima that forms after mechanical injury of the endothelium. Recent experimental studies provide evidence that PPAR-gamma may function to protect the vasculature from injury. Cell culture studies have shown that TZD PPAR-gamma ligands inhibit both the proliferation and migration of VSMCs. These antiatherogenic activities of PPAR-gamma may also occur in vivo, because TZDs inhibit lesion formation in several animal models. PPAR-gamma ligands may also protect the vasculature indirectly by normalizing metabolic abnormalities of the diabetic milieu that increase cardiovascular risk. Activation of PPAR-gamma, newly defined in vascular cells, may be a useful approach to protect the vasculature in diabetes.
Expiratory only resistive loaded breathing (RL) reduces high energy electromyogram (EMG) power (EH) during an isometric contraction of a leg extensor muscle, but not an arm flexor. An interaction between afferent activity during expiratory RL and inspiratory non-loaded phases of breathing, which the contraction spanned, could have accounted for the reduced EH in these long contractions. Therefore this study tested the hypothesis that brief arm extensor muscle contractions (70% of maximal force), performed during a single phase of expiratory RL, would also exhibit reduced EH. Surprisingly, EH in triceps, but not biceps brachii was reduced significantly when the contraction was performed during inspiratory RL rather than expiratory RL. The results suggest that either (a) short and prolonged contractions or (b) motor drive to arm and leg extensors are affected differently by RL.
Ultraviolet B (UVB) damage is recognized as the most important etiological factor in the development of skin cancer. Human papillomaviruses (HPV) have also been implicated in the disease, although the mechanism of action of these viruses remains unknown. We present evidence here that Bak protein is involved in signaling apoptosis in the skin in response to UVB damage, and that cutaneous HPV E6 proteins target and abrogate Bak function by promoting its proteolytic degradation both in vitro and in regenerated epithelium. Additionally, HPV positive skin cancers had undetectable levels of Bak in contrast to HPV negative cancers, which expressed Bak. This study supports a link between the virus and UVB in the induction of HPV-associated skin cancer and reveals a survival mechanism of virally infected cells.
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In this study we measured the levels of plasma and salivary IgG subclasses in 81 HIV-1-infected individuals and 30 uninfected controls. Salivary IgG1 was increased in HIV-1-infected patients, while salivary IgG2 and IgG4 were decreased. Patients with high levels of plasma anti-HIV-1 IgG antibodies presented a higher CD4+ cell count and lower viral load. High levels of anti-HIV-1 IgG antibodies in plasma were also associated with high levels of anti-HIV-1 IgG antibodies in parotid saliva. In comparing the HIV-1 recognition patterns of salivary IgG with plasma IgG, we determined that plasma and salivary IgG antibodies had similarities as well as differences in their reactivity to HIV-1 antigens. The present study demonstrates that HIV-1 infection affects both plasma and salivary IgG and provides evidence that the origin of HIV-1-specific IgG antibodies in parotid saliva is primarily transudated from plasma; however, some local synthesis of IgG in parotid saliva also occurs.
Wilms' tumor (WT) is associated with loss of heterozygosity at chromosome 11p13, the site of the Wilms' tumor suppressor gene, WT1. Although the preferential loss of maternal alleles suggested that differential allelic expression of WT1 might occur, this has not been evident in normal fetal tissues or WTs. In this study, we show that the WT1 antisense regulatory region is differentially methylated, with Southern blot analysis of four loss of heterozygosity-negative WTs and their corresponding normal kidneys indicating that allelic methylation is lost in WTs. Reverse transcription-PCR expression analysis correlates methylation with monoallelic expression of the antisense WT1 transcript (WT1-AS) in normal kidney. However, WTs display hypomethylation and biallelic expression of WT1-AS. Our findings are consistent with imprinting of WT1-AS in normal kidney and the relaxation of imprinting in Wilms' tumorigenesis. This identifies the WT1 antisense regulatory region in intron 1 as a primary site for epigenetic deregulation at chromosome 11p13 in WTs.
We have determined that polymeric IgA in saliva of HIV-1-uninfected individuals binds in varying degrees to components of culture supernatants containing HIV-1 recombinant proteins when ELISA is used for the determination. This finding did not extend to salivary IgG antibodies. Further, such problems were not encountered in Western blot. Binding did not appear to be mediated by salivary proteins known to bind to IgA, including secretory component, amylase, lactoferrin, lysozyme, galactosyl transferase, or secretory leukocyte protease inhibitor, and was not influenced by blocking reagents or by changes in secondary anti-IgA antibodies. Although these findings will not likely impact on the use of saliva as a diagnostic fluid for HIV-1 infection (the HIV-1 response in saliva is mostly of the IgG isotype), they indicate that assessments of this secretion as an indicator of IgA mucosal immune responses to HIV-1 vaccines should be undertaken with caution.
BACKGROUND: Peroxisome proliferator-activated receptor-gamma (PPARgamma) is activated by fatty acids, eicosanoids, and insulin-sensitizing thiazolidinediones (TZDs). The TZD troglitazone (TRO) inhibits vascular smooth muscle cell (VSMC) proliferation and migration in vitro and in postinjury intimal hyperplasia. METHODS AND RESULTS: Rat and human VSMCs express mRNA and nuclear receptors for PPARgamma1. Three PPARgamma ligands, the TZDs TRO and rosiglitazone and the prostanoid 15-deoxy-Delta(12,14)-prostaglandin J2 (15d-PGJ2), all inhibited VSMC proliferation and migration. PPARgamma is upregulated in rat neointima at 7 days and 14 days after balloon injury and is also present in early human atheroma and precursor lesions. CONCLUSIONS: Pharmacological activation of PPARgamma expressed in VSMCs inhibits their proliferation and migration, potentially limiting restenosis and atherosclerosis. These receptors are upregulated during vascular injury.
AIM: To determine how many individuals with haemochromatosis undergoing therapeutic venesections in our department might be eligible for blood donation. METHODS: Patients with genetic haemochromatosis were assessed with respect to complications of their disorder, the presence of other medical conditions and their suitability to be blood donors. RESULTS: Of 74 patients, 53 have been tested and shown to be homozygous for the Cys282Tyr mutation, and 30 of these (40%) fulfilled criteria for blood donation. This group is having 409 units of blood removed annually or 13-units per individual that is currently discarded. Of these 30 patients, all (100%) were keen to be blood donors. CONCLUSION: It is timely to review the policy regarding use of this wasted blood for transfusion.
In addition to their role in anogenital cancer, human papillomaviruses (HPVs) are also involved in the development of a range of cutaneous lesions. HPV types 5 and 8 are associated with the development of skin cancers in individuals with Epidermodysplasia verruciformis (EV). A broad spectrum of HPV types are also commonly found in non-melanoma skin cancers in immunocompromised individuals, such as organ transplant recipients. The skin cancers in EV and immunocompromised patients occur predominantly at body sites exposed to ultra violet (UV) radiation, pointing to a key role for UV in their development. Here we show that the E6 protein from a range of cutaneous HPV types effectively inhibits apoptosis in response to UV damage. This occurs in both p53 null and wild type cells and does not require p53 degradation.
Little is known about the incidence of secondary insults, particularly cerebral perfusion pressure insults, in children. The objectives of this study were to assess the duration of CPP insults at three different thresholds in children and to relate CPP insults to outcome. Eighteen children (age < 16, median & mean 8 years) admitted to the Neurointensive Care Unit who had ICP, MAP and CPP continuously monitored were studied. Using the Edinburgh secondary insult analysis program, data was scanned for CPP insults at three different thresholds: CPP < 70 mmHg, < 60 mmHg and < 50 mmHg. Outcome was assessed using the Glasgow Outcome Scale. Thirty percent of the time CPP was between 60 and 70 mmHg, 21% of the time CPP was between 50 and 60 mmHg and 8% of the time the CPP was less than 50 mmHg. Compared with adults, there was more than twice the incidence of CPP insults in all threshold groups. BP remained relatively stable above 70 mmHg across all three CPP threshold groups. However, ICP increased slightly on average from about 13-->17 mmHg when CPP decreased from the < 70 to < 60 mmHg group (p < 0.001). There was a marked increase in ICP to greater than 30 mmHg on average in the CPP < 50 mmHg group (p < 0.001). CPP insults less than 70, 60 and 50 mmHg do occur commonly in children, a larger dataset and possibly longer term follow up measures will be needed to identify potentially treatable physiological factors most effecting the outcome of children.
This study examines possible differences and similarities between social behaviour problems in children with problems classified as pervasive developmental disorder not otherwise specified (PDD-NOS) and a group of children with problems classified as ADHD, as measured by parent questionnaires. The instruments involved were the CBCL (Child Behaviour Checklist), the ABC (Autism Behaviour Checklist) and a new instrument: the CSBQ (Children's Social Behaviour Questionnaire). In comparing the PDD-NOS group and the ADHD group, the results show that, according to parent reports, both groups have severe problems in executing appropriate social behaviour, but the PDD-NOS group can be distinguished from the ADHD group by the nature and the extent of these problems. The PDD-NOS group had significantly more social problems (as measured by the CBCL Social scale), withdrawn problems (as measured by the CBCL Withdrawn scale) and PDD-specific problems (as measured on the ABC Relating scale, the ABC Language scale, the CSBQ total score, the CSBQ Social Interaction scale and CBSQ Communication scale). In addition, although the descriptions of the social problems are global, i.e. on scale level, the results also show that the social problems of PDD-NOS children can be positively formulated and described as at least including severe social interaction problems, withdrawn behaviours and communication problems.
It is well known that African Americans are at low risk for one of the most serious diagnoses in dermatology--skin cancer. A consequence of this lower cancer risk has been an undervaluing of the importance of appropriate dermatologic care in this population. In fact, there are many other skin diseases and disorders that not only cause significant morbidity among this population but also emotional and psychological sequelae. This article examines barriers and challenges to providing dermatologic care among African Americans and provides recommendations and suggestions for improving care delivery in this population.
The Children's Social Behavior Questionnaire (CSBQ) contains items referring to behavior problems seen in children with milder variants of PDD. Data of large samples of children diagnosed as having high-functioning autism, PDDNOS, ADHD, and other child-psychiatric disorders were gathered. Besides the CSBQ, parents completed the Autism Behavior Checklist (ABC) and the Child Behavior Checklist (CBCL). The data provided the basis for scale construction of the CSBQ, a comparison of the CSBQ scales with other instruments and a comparison of groups on scores on the CSBQ. The 5 scales obtained referred to Acting-out behaviors, Social Contact problems, Social Insight problems, Anxious/Rigid behaviors and Stereotypical behaviors. Results show that the CSBQ has good psychometric qualities with respect to both reliability and validity. A comparison of the different groups showed that significant group differences were found on all scales. In general, the autism group received the highest scores, followed by the PDDNOS group and the ADHD group. Exceptions were on the Acting-out scale, where the ADHD group scored highest and on the Social Insight scale, where no significant difference was found between the PDDNOS group and the ADHD group. Implications of the results and suggestions for further research are discussed.