Looking back and looking forward.
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Biomedical subjects
Publications and source records attributed to G Gallagher.
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Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterized by dermal, mucosal, and visceral telangiectases as well as pulmonary and cerebral arteriovenous malformations. Recurrent epistaxis occurs in the majority of patients, and by the very nature of the thin walled vessels involved it is often refractory to conventional forms of treatment. We present the case of an 82-year-old lady with intractable epistaxis secondary to HHT, that was successfully controlled by the application of fibrin glue.
Twenty-four properly functioning and six high carbon monoxide emission light-duty gasoline vehicles were emission tested in Denver, CO, using the Federal Test Procedure (FTP), a hot start Unified Cycle (UC), and the REP05 driving cycles at 35 degrees F. All were 1990-1997 model year vehicles tested on both an oxygenated and a nonoxygenated fuel. PM10 emission rates for the properly functioning vehicles using oxygenated fuel averaged 6.1, 3.6, and 12.7 mg/mi for the FTP, UC, and REP05, respectively. The corresponding values for the high emitters were 52, 28, and 24 mg/mi. Use of oxygenated fuel significantly reduces PM10 on the FTP, with all the reduction occurring during the cold start. MOUDI impactor samples showed that 33 and 69% of the PM mass was smaller than 0.1 microm for the FTP and REP05 cycles, respectively, when collected under standard laboratory conditions. Particle number counts were much higher on the REP05 than the FTP. Counts were obtained using secondary dilution of samples drawn from the standard dilution tunnel. FTP PM10 was mostly carbonaceous material, 36% of which was classified as organic. For the REP05, as much as 20% of the PM10 was sulfate and associated water. Forty-five percent of the REP05 PM carbon emissions was classified as organic. Driving cycle had a significant impact on the distribution of the emitted polynuclear aromatic hydrocarbons.
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Interleukin-10 (IL-10) is an important immunoregulatory cytokine. The recent characterisation of the proximal 5' flanking region of IL-10 led to the identification of the promoter region. Two polymorphic dinucleotide repeats and 10 single nucleotide polymorphisms (SNPs) have been identified and suggested to be useful genetic markers in several diseases. We have sequenced a further 5275 bp from -9296 to -4021 of the distal part of the 5' flanking region of the human IL-10 gene from the cosmid clone pWE15-4/11. Our sequence analysis reveals a high density of Alu-repeats within the IL-10 gene locus, including three novel, related structures which we term Alu-IL10 (A-C). Using three overlapping PCR products spanning 5110 bp of this distal part of the IL-10 gene the following single base pair substitutions were identified: at -8571 C/T, -8531 G/A, -6752 A/T, -6208 G/C, -5402 C/G. In addition a heterozygous three base pair deletion at -7400 was observed. The SNPs at -8571 C/T and -8531 G/A are contained within an Alu-repeat. These data should further the understanding of how the IL-10 gene is controlled in man and how its function may vary between individuals.
Beneficial effects of interleukin-10 therapy and lower endogenous interleukin-10 formation compared with atopic dermatitis and cutaneous T cell lymphomas indicated that interleukin-10 is a key cytokine in psoriasis. The interleukin-10 promoter is highly polymorphic, with two informative microsatellites, interleukin-10.G and interleukin-10.R. In order to understand whether interleukin-10 itself is a predisposing gene for the psoriasis susceptibility we analyzed interleukin-10 promotor polymorphism in patients. The distribution of interleukin-10.G and interleukin10.R microsatellite alleles did not vary between patients (n = 78) and healthy controls (n = 80). In addition, when the psoriasis patients were stratified according to age of onset (younger than 40 y of age, or age 40 and older), no difference in allele distribution was observed; however, a clear differential distribution was revealed at the interleukin10.G locus when patients were stratified according to whether they had a positive family history of psoriasis (p = 0.04). This difference was due to an over-representation of the interleukin10.G13 allele in those patients with familial disease (40.4% vs 19.6%, Chi-square = 7.292, p = 0.007). The positive association of allele interleukin10.G13 with familial psoriasis was especially true when patients with an early onset (< 40 y of age) of the disease were compared with those patients with early onset against a nonfamilial background (39.6% vs 14.5%, Chi-square = 8.959, p = 0.003). Patients with age-of-onset of less than 40 were 4-fold [odds ratio = 3.85 (1.55--9.62)] more likely to have a psoriatic family background if they carried this interleukin10.G13 allele. These data suggest that the interleukin-10 locus contributes to the heritability of psoriasis susceptibility.
Synovial sarcoma (SS) is a relatively rare sarcoma, which may be confused with several other mesenchymal and nonmesenchymal lesions. It bears the t(X;18) (SYT;SSX) translocation, which seems to be specific for this tumor type and can be detected in paraffin-embedded tissue, using reverse transcriptase-polymerase chain reaction (RT-PCR). However, the specificity and sensitivity of this detection method have rarely been examined in a large series. Using RT-PCR, we examined 250 mesenchymal and nonmesenchymal, benign and malignant, paraffin-embedded lesions for the SS t(X;18) (SYT-SSX) translocation. PCR products were obtained from 221 tumors (88.5%). There were 135 non-SS tumors, 22 biphasic, and 64 monophasic spindle/round cell SS, of which 10 were cytogenetically confirmed as t(X;18)-positive. SYT-SSX gene fusion transcripts were detected in the SS tumor category only (100% specificity), including 100% of the biphasic SS and 86% of monophasic spindle/round cell SS. Nine tumors originally diagnosed as SS were t(X;18) (SYT-SSX)-negative. Following reassessment, only 3 of these tumors showed clinicopathologic, immunohistochemical, and/or ultrastructural features consistent with that diagnosis, thus raising the overall detection sensitivity to 96%. With regard to the potential adverse effect of the fixatives used, PCR products were obtained in 100%, 91.5%, 90.5%, and 0% of tumors fixed with AFA, buffered formalin, Holland Bouin, and conventional Bouin's fluid, respectively. This study shows that the detection of the SS t(X;18) (SYT-SSX) in paraffin-embedded tissue is feasible with a 100% specificity and an overall 96% sensitivity, provided non-Bouin's fluid fixation is used.
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We provide characterization of a highly polymorphic dinucleotide repeat in the human TNF-receptor 1 gene (TNFR1, TNFRp55, CD120a). We have observed 11 alleles at this locus in individuals from the West of Scotland. In a panel of healthy, unrelated individuals from the West of Scotland (n = 143), the overall heterozygosity was 68%, indicating the potential usefulness of these markers in immunogenetic studies.
We have examined four polymorphic elements in the human interleukin-6 (IL-6) locus and described their allele distribution in 73 unrelated, healthy individuals from the West-of-Scotland. These comprised three single nucleotide polymorphisms (SNP) in the 5' promoter region of the gene and one VNTR in the 3' region of IL-6. A statistical consideration of the relationship between alleles at each locus was carried out. Of a total of 12 possible haplotypes observed in the population, the analysis suggested that four were prominent. These accounted for 41.1%, 28.1%, 14.4% and 3.4% respectively; in total, 87% of the haplotypes present. Frequently, these proposed haplotypes were supported by homozygosity across all four loci within individuals. We propose that these haplotypes be identified as IL6.0103, IL6.0204, IL6.0207 and IL6.0307, in recognition of their frequency in this population and the alleles that they contain.
Interleukin-10 (IL-10) is a pleiotropic cytokine with important immunoregulatory functions whose actions influence activities of many of the cell-types in the immune system. We report here identification and cloning of a gene and corresponding cDNAs encoding a novel homologue of IL-10, designated IL-19. IL-19 shares 21% amino acid identity with IL-10. The exon/intron structure of IL-19 is similar to that of the human IL-10 gene, comprising five exons and four introns within the coding region of the IL-19 cDNA. There are at least two distinct IL-19 mRNA species that differ in their 5'-sequences, suggesting the existence of an intron in the 5'-sequences of coding portion of the IL-19 gene. The longer 5'-sequence contains an alternative initiating ATG codon that is in-frame with the rest of the coding sequence. The expression of IL-19 mRNA can be induced in monocytes by LPS-treatment. The appearance of IL-19 mRNA in LPS-stimulated monocytes was slightly delayed compared to expression of IL-10 mRNA: significant levels of IL-10 mRNA were detectable at 2 h post-stimulation, whereas IL-19 mRNA was not detectable until 4 h. Treatment of monocytes with IL-4 or IL-13 did not induce de novo expression of IL-19, but these cytokines did potentiate IL-19 gene expression in LPS-stimulated monocytes. In addition, GM-CSF was capable of directly inducing IL-19 gene expression in monocytes. IL-19 does not bind or signal through the canonical IL-10 receptor complex, suggesting existence of an IL-19 specific receptor complex, the identity of which remains to be discovered.
Burn dressing changes require profound analgesia for a short duration. This study aimed to determine whether an operator-adjusted target-controlled infusion of alfentanil could provide effective analgesia for burn dressing changes. Ten patients with a burn of between 5 and 50% of body surface area were studied. Pain scoring was performed before, during and following the dressing change. Target and effect site concentrations of alfentanil were recorded during and for 15 min after the dressing change. Median baseline visual analogue pain score (VAS) was 22 mm. Median (range) duration of dressing change was 35 (20-75) min. Median (range) VAS during the dressing change was 30 (14-66) mm. All patients were satisfied with their pain relief. There was no respiratory depression or cardiovascular instability. No patient became sedated and there were no episodes of nausea or vomiting. Median (range) total dose of alfentanil was 2.6 (1-10.7) mg. This study supports the efficacy of an operator-adjusted target-controlled infusion of alfentanil to provide analgesia for burn dressing changes.
In order to prescribe appropriate analgesia for burns dressing changes the pain experienced by 30 burned patients during this procedure was recorded. Patients received analgesia prior to their dressing changes according to the current protocol in the burns unit. During the same period the medical and nursing staff in the unit who were involved in prescribing and administering the analgesia for the dressing change, were asked to assess the severity of pain that they thought patients experienced during dressing changes. Patients recorded their worst pain as none or mild in 64% of procedures. In contrast, no surgeon and only one nurse, rated pain as none or mild. The discrepancy between severity of pain recorded by patients and the pain predicted by staff prescribing and administering analgesia has clinical implications.
OBJECTIVES: To determine the frequency of use of irrigation amongst head and neck surgeons in the U.K. and Ireland, the range of fluids in use; to identify differences in practice in benign and malignant surgery, and ascertain common theories about irrigation, wound infection and tumour recurrence. METHOD: A postal survey of 695 members of the B.A.O.L. Head and Neck Surgeons (348/695 returned). Eight questions with tick box replies and space for free text. Members were asked about their practice of wound irrigation and opinions on its effect(s). Of 348 returned questionnaires 301 were used, 47 discarded as members had retired. RESULTS: 203 of 301 carried out head and neck tumour surgery (67.44%). 67.98% routinely perform wound irrigation. A variety of fluids are used, the most common being sterile water, then saline (table II). Reducing wound infection and tumour recurrence were reasons for irrigating by 47.1%, reducing infection alone, 15.22%, and reducing tumour recurrence alone, 31.16%. 59.42% believe that irrigation prevents wound seeding by benign tumour cells, 70.29% by malignant cells. Irrigation was performed by 70% of surgeons who did more than 5 head and neck tumour procedures per year and by 56% of surgeons who did less than five. CONCLUSIONS: There is little evidence for the putative effects of wound irrigation as noted from literature. Most studies have been performed on animals. There is a need for further research into wound irrigation, types of fluid used and its effects on head and neck cancer patients.