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F Lewis

Publications and source records attributed to F Lewis.

At least 19 recordsLinked to original sources
PubMed2005

Vulval Crohn's disease-- a multi-specialty approach.

We report a case of Crohn's disease where the patient initially presented with vulval ulceration to the gynaecology unit. Initial investigations were planned jointly by both the gynaecology and genitourinary medicine staff. An examination under general anaesthetic by both teams was performed and biopsies taken. These showed a chronic inflammatory process with epithelioid granulomas. The teams then referred the case to the dermatology team who made the diagnosis of vulval Crohn's disease and initiated treatment with prednisolone and azathioprine. The case illustrates the need for a multi-speciality approach when dealing with such cases.

Adult↗
PubMed2004

Testing for HER2 in breast cancer.

HER2 is a paradigm of a molecular target whose appropriate assessment is pivotal in the targeting of novel therapies for breast cancer, notably including Herceptin/Trastuzumab. Determining the correct levels requires immunohistochemical and molecular biological skills that are reproducible and measurable, coupled with a knowledge of the appropriate morphological and pathobiological context. Attaining these goals is not easy and laboratories testing for HER2 should maintain a high level of throughput of tests and engage in a recognized external quality assurance scheme. Fluorescence in-situ hybridization testing remains a particular challenge and there is a range of testing strategies. This testing forms the model for the identification of other novel molecular targets. In the future rapid throughput techniques such as real-time quantitative polymerase chain reaction (rqPCR), tissue microarrays or both should bring significant economies of cost and scale.

Breast Neoplasms↗
PubMed2003

Trial of heparin in viper bites.

AIMS OF THE STUDY: Viper bites produce hematotoxicity and coagulopathy which may be either true disseminated intravascular coagulation (DIC) or DIC-like syndrome. Role of heparin is studied in the present study of viper bite cases as use of heparin provides a rational therapy for defibrination caused by viper envenomation. METHODOLOGY: One hundred and twenty two patients with viper bite and incoagulable blood were randomised into test group and control group. Test group received heparin in addition to antisnake venom (ASV). Efficacy was assessed by monitoring bleeding time (BT), clotting time (CT), prothrombin time (PT), platelets, fibrinogen, blood urea (BU), serum creatinine, development of complications and overall outcome. RESULTS: Heparin group showed favourable outcome in all parameters studied. But many of them were not statistically significant. CONCLUSION: Heparin seems to be having a beneficial role which needs to be confirmed by larger trials and longer duration of heparin administration.

Adult↗
PubMed2001

Unlocking the archive--gene expression in paraffin-embedded tissue.

The histopathology archive represents a vast, well-characterized source of specimens covering virtually every disease and is available for molecular biological investigation. The archive has in recent years become widely used for molecular genetic analysis and DNA can be routinely extracted from formalin-fixed, paraffin-embedded tissue. More recently, archival specimens have become a source of material for extensive analysis of mRNA expression utilizing DNA microarrays, real-time quantitative reverse transcriptase polymerase chain reaction (PCR), and in situ hybridization and amplification techniques. These techniques will enable a greater understanding of the changes that occur in gene function during every stage of the development of disease and will lead to better diagnosis, better evaluation of prognosis, and better treatment through targeted therapeutic regimes.

Biological Specimen Banks↗
PubMed2001

Three stage AIDS incubation period: a worst case scenario using addict-needle interaction assumptions.

In this paper we develop and analyse a model for the spread of HIV/AIDS amongst a population of injecting drug users. We start off with a brief literature survey and review; this is followed by the derivation of a model which allows addicts to progress through three distinct stages of variable infectivity prior to the onset of full blown AIDS and where the class of infectious needles is split into three according to the different levels of infectivity in addicts. Given the structure of this model we are required to make assumptions regarding the interaction of addicts and needles of different infectivity levels. We deliberately choose these assumptions so that our model serves as an upper bound for the prevalence of HIV under the assumption of a three stage AIDS incubation period. We then perform an equilibrium and stability analysis on this model. We find that there is a critical threshold parameter R(0) which determines the behaviour of the model. If R(0)< or =1, then irrespective of the initial conditions of the system HIV will die out in all addicts and all needles. If R(0)>1, then there is a unique endemic equilibrium which is locally stable if, as is realistic, the time scale on which addicts inject is much shorter than that of the other epidemiological and demographic processes. Simulations indicate that if R(0)>1, then provided that disease is initially present in at least one addict or needle it will tend to the endemic equilibrium. In addition we derive conditions which guarantee this. We also find that under calibration the long term prevalence of disease in our variable infectivity model is always greater than in an equivalent constant infectivity model. These results are confirmed and explored further by simulation. We conclude with a short discussion.

Acquired Immunodeficiency Syndrome↗
PubMed2001

The distribution of Biomphalaria spp. in different habitats in relation to physical, biological, water contact and cognitive factors in a rural area in Minas Gerais, Brazil.

A total of 256 sites in 11 habitats were surveyed for Biomphalaria in Melquiades rural area (State of Minas Gerais) in August and November 1999 and in March 2000. Of the 1,780 Biomphalaria collected, 1,721 (96.7%) were B. glabrata and 59 (3.3%) B. straminea. Snails were found in all habitats except in wells, with the largest mean numbers in tanks, seepage ponds and canals, and the smallest numbers in springs, rice fields and fishponds. People's knowledge of the occurrence of Biomphalaria at the collection sites and the presence of Biomphalaria ova were strongly correlated with the occurrence of snails, and distance between houses and collection sites, as well as water velocity were inversely correlated with Biomphalaria occurrence (p < 0.001). The strongest predictor o f Biomphalaria occurrence was the presence of tilapia fish in fishponds. Fourteen Biomphalaria (0.8% of all snails) found at 6 sites were infected with Schistosoma mansoni. Suggestions are made for the utilization of local people's knowledge in snail surveys and further studies are recommended on the possible use of tilapia for biological control of Biomphalaria in fishponds, as well as modeling of S. mansoni transmission and reinfection.

Animals↗
PubMed2001

A mathematical treatment of AIDS and condom use.

In this paper we examine the impact of condom use on the sexual transmission of human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) amongst a homogeneously mixing male homosexual population. We first derive a multi-group SIR-type model of HIV/AIDS transmission where the homosexual population is split into subgroups according to frequency of condom use. Both susceptible and infected individuals can transfer between the different groups. We then discuss in detail an important special case of this model which includes two risk groups and perform an equilibrium and stability analysis for this special case. Our analysis shows that this model can exhibit unusual behaviour. As normal, if the basic reproduction number, R0, is greater than unity then there is a unique disease-free equilibrium which is locally unstable and a unique endemic equilibrium. However, when R0 is less than unity two endemic equilibrium solutions can also co-exist simultaneously with the disease-free solution which is locally stable. Numerical simulations using realistic parameter values confirm this and we find that in certain circumstances the disease-free solution and one of the endemic solutions are both locally asymptotically stable, while the other endemic solution is unstable. This unusual behaviour has important implications for control of the disease as reducing R0 to less than unity no longer guarantees eradication of the disease. For a restricted special case of this two-group model we show that there is only the disease-free equilibrium for R0 < or = 1 which is globally stable. For R0 > 1 the disease-free equilibrium is unstable and there is a unique endemic equilibrium which is locally stable. We then attempt to fit the model to HIV and AIDS incidence data from San Francisco, USA. The paper concludes with a brief discussion.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Three-stage AIDS incubation period: a best case scenario using addict-needle interaction assumptions.

In this paper we extend the 'needles that kill' model discussed in Kaplan & O'Keefe (1993) to allow addicts to progress through three-stages of variable infectivity prior to the onset of full-blown AIDS, and where the class of infectious needles is split into three according to the different levels of infectivity in addicts. Given the structure of this model we are required to make assumptions regarding the interaction of addicts and needles of different infectivity levels. We deliberately choose these assumptions so that our model serves as a lower bound for the prevalence of HIV under the assumption of a three-stage AIDS incubation period. We find that there is a critical threshold parameter R0 which determines the behaviour of the model. If R0 > 1 then there is a unique endemic equilibrium which is locally stable if, as is realistic, the timescale on which addicts inject is much shorter than that of the other epidemiological and demographic processes. Simulations indicate that if R0 > 1, then provided that disease is initially present in at least one addict or needle then it will tend to the endemic equilibrium. In addition, we derive conditions which guarantee this. We also find that under calibration the long-term prevalence of disease in the 'needles that kill' model is the same as in our three-stage model.

Behavior, Addictive↗
PubMed1996

Schistosoma mansoni: use of a subtractive cloning strategy to search for RFLPs in parasite-resistant Biomphalaria glabrata.

A subtractive cloning strategy has been applied for the identification of two cDNA clones whose corresponding transcripts were elevated in Schistosoma mansoni-resistant (BS-90) compared to susceptible (M-line) snails. Clone pBS11 encoded a 1.9-kb transcript that was more elevated compared to a 500-bp transcript encoded by clone pBS12. Consequently, more attention was focused on the molecular characterization of clone pBS11. Results showed that the transcript encoded by this clone was expressed in the albumen gland and was developmentally regulated. Sequence analysis of pBS11 demonstrated the presence of an open reading frame that corresponded to a novel Biomphalaria glabrata albumen gland gene product. Comparative Southern analysis of the resistant and susceptible snail lines using pBS11 as probe indicated the presence of a BamHI and EcoRI RFLP between the two strains.

Animals↗
PubMed1996

Fluorescent polymerase chain reaction of a panel of CA repeats on chromosome 6 in the indolent phase of follicular centre cell lymphoma.

Twenty-four cases of histologically defined follicle centre cell (FCC) lymphoma have been examined for allele imbalance at 19 microsatellite loci spanning the length of chromosome 6, including six markers within the major histocompatibility complex (MHC), using fluorescent polymerase chain reaction (PCR) to amplify microsatellites. Nineteen cases were observed in which imbalance of one or more markers on chromosome 6 had occurred (79%). The frequency of allele imbalance was significantly higher on 6p than 6q, and two regions of deletions, 6p24-25 and 6p21.3-23, were identified in which the loci showed a significantly high allele imbalance frequency.

Chromosomes, Human, Pair 6↗
PubMed1996

Microsatellite instability in follicle centre cell lymphoma.

Fluorescent polymerase chain reaction (PCR) was used to assay 12 microsatellite markers (APC x 2, DCC, P53 x 2, RB1, NM23, WT1, D6S260, D6S262, D6S281 and TNFa) to look for evidence of microsatellite instability in 40 cases of follicle centre cell lymphoma (FCC). Evidence of novel alleles seen in the tumour tissue but not the normal uninvolved tissue was seen in seven cases (17%). In only two of these cases (5%) was more than one locus involved but in these cases multiple affected loci were seen (4/12 and 7/12 respectively). The detection of microsatellite instability indicates a DNA repair defect such as that which would be predicted to occur in cells with mutated mismatch repair genes, a novel finding in FCC lymphoma.

Chromosomes, Human, Pair 14↗
PubMed1996

Antenatal screening for cystic fibrosis.

OBJECTIVE: To assess the practicality of implementing antenatal screening for cystic fibrosis in Yorkshire. DESIGN: Prospective study in which all pregnant women were offered testing for the delta F508 mutation which accounts for about 85% of carriers in Yorkshire. The reproductive partners of those found to be cystic fibrosis carriers were then tested and any carrier referred for genetic counselling. SETTING: Antenatal clinics in two hospitals and eight general practices. POPULATION: Six thousand and seventy-one pregnant women. RESULTS: A total of 3773 women (62%) accepted the screening offer. This was a lower uptake rate than in other published UK studies: Aberdeen (85-91%), Manchester (85%), Edinburgh (76-84%) and Oxford (67%). Nonetheless there were large and statistically significant differences in the uptake rate between centres within the study: 78% and 60% for the two hospitals and 67% for the general practices. One hundred and thirty women (3.4%) were found to be carriers and three carrier couples were identified. The median time interval for the laboratory to produce a result was five days and the cost was pounds 16 on average. CONCLUSIONS: Antenatal screening for cystic fibrosis does not pose any special practical difficulties. It would be feasible to introduce it into routine practice in Yorkshire.

Attitude to Health↗
PubMed1996

Serum and gastric luminal epidermal growth factor in Helicobacter pylori-associated gastritis and peptic ulcer disease.

BACKGROUND: Helicobacter pylori is the cause of chronic (type B) gastritis, duodenal ulceration (DU), and gastric ulceration (GU). Smoking is associated with delayed ulcer healing. Epidermal growth factor (EGF) is produced in the salivary and Brunner's glands of the upper gastrointestinal tract, inhibits gastric acid secretion, and is a powerful mitogen. MATERIALS AND METHODS: We sought to determine gastric luminal EGF (GL-EGF) in smokers and patients with Hp-associated DU and the effects of Hp eradication. Our aim was to determine GL-EGF in patients with GU and the effect of ulcer healing and to measure serum EGF in patients with Hp gastritis with or without DU disease. RESULTS: GL-EGF was reduced in smokers compared to controls (p = .008). Subjects with HP gastritis had reduced GL-EGF compared to controls (p = .0002). There was no difference in GL-EGF between Hp-positive subjects who had DU and those with chronic gastritis alone. Eradication of Hp from those patients with DU had no effect on the low levels of GL-EGF. There was no difference between GL-EGF in Hp gastritis alone and in Hp-associated active GU. GL-EGF fell after ulcer healing (p = .04), a difference confirmed by analysis of paired samples from patients before and after ulcer healing (p = .03). There was no difference in serum EGF between controls and subjects with Hp infection. There was no difference in serum EGF in subjects with DU associated and non-ulcer-associated gastritis. CONCLUSIONS: Subjects with Hp gastritis, or those who smoke, had low concentrations of GL-EGF regardless of whether DU was present. Eradication of Hp did not return the concentrations of GL-EGF to normal in DU subjects. Individuals and Hp gastritis and inactive GU had low levels of GL-EGF compared to non-ulcer Hp infection. The relative increase in GL-EGF that occurred with ulceration of the gastric mucosa may have resulted from the development of an ulcer-associated cell lineage. Serum EGF did not play a role in the pathogenesis of Hp gastritis or of associated DU ulcer disease.

Adult↗
PubMed1996

Promoter region polymorphism in the human TNF-alpha gene is not associated with lichen sclerosus.

The pathogenesis of lichen sclerosus remains unknown. However, it has been frequently associated clinically with autoimmunity. The MHC haplotype A1, B8, DR3 is associated with many autoimmune conditions and has also been associated with the uncommon allele of the tumour necrosis factor (TNF-alpha) promoter polymorphism. This allele is also associated with higher production of TNF in vivo and in vitro, and thus it has been speculated that it is the TNF-alpha gene which underlies the genetic association of many diseases with the autoimmune haplotype. There have been many reports of HLA associations with lichen scleroses, but these have not been concordant. We therefore decided to analyse the TNF-alpha polymorphism in patients with lichen scleroses to determine if TNF-alpha was likely to play a role in susceptibility or severity of lichen scleroses. No association between alleles of the TNF-alpha polymorphism and lichen scleroses was found.

Alleles↗
PubMed1996

Allele imbalance at tumour suppressor loci during the indolent phase of follicle centre cell lymphoma.

We have examined 41 cases of follicle centre cell lymphoma with fluorescent PCR of microsatellite repeats closely linked to or within six tumour suppressor gene loci (APC, DCC, P53, RB1, WT1 and NM23). These probes are highly informative with heterozygousity rates in the range of 57%-90%. In addition we have used four loci from chromosome 6 (D6S260, TNFa, D6S281 and D6S262) as control loci which are unlikely to be involved in the pathogenesis of lymphoma. Of 369 informative PCR reactions allele imbalance was identified in 38 (10%) and this was seen in 23 of the 41 cases. Looking at individual loci allele imbalance was seen in APC(1) 11%, APC(2) 12%, P53(1) 5%, P53 (2) 7%, WT1 5%, RB1 13%, DCC 18% and NM23 0%. This frequency of change was no different from that seen at the control loci D6S260 16%, TNFa 20%, D6S281 4% and D6S262 9%. In the indolent phase of germinal centre cell lymphoma there is therefore quite a high rate of allele imbalance at all loci but this is no higher in those loci linked to tumour suppressor genes.

Alleles↗
PubMed1995

Genetic abnormalities during transition from Helicobacter-pylori-associated gastritis to low-grade MALToma.

The helicobacter-associated transition from chronic gastritis to MALToma (lymphoma of mucosa-associated lymphoid tissue) may require genetic change in the host. We have studied gastrectomy specimens from twelve cases of primary B-cell gastric lymphoma showing evidence of chronic gastritis and low-grade or high-grade MALToma to look for allele imbalance at microsatellites for six tumour-suppressor genes. We detected allelic imbalance at two of these loci (DCC in three, APC in two). In two DCC cases allele imbalance was seen in the transition from chronic gastritis to low-grade MALToma and in the third between low-grade and high-grade. Allele imbalance between chronic gastritis and low-grade MALToma is not necessarily causal in the transition. Rather, genetic change has occurred in the process of transformation.

Alleles↗
PubMed1995

Some selected psychological and social characteristics of veteran psychiatric inpatients without stable housing.

In this study were compared scores on selected MMPI subscales and demographic variables from 58 veterans with stable housing and 54 veterans without stable housing. Both groups were selected from the same inpatient psychiatric treatment program at the Houston VA Medical Center. The MMPI was administered and a number of demographic variables were collected from patients' archival computerized records. Comparison of MMPI scores indicated that patients without housing had marginally significantly higher scores on the clinical research subscale PD4A (Social Alienation). They were also significantly less likely to be married or employed. Logistic regression analysis indicated that, when multiple predictors were considered, marital status was the only significant risk factor for absence of stable housing. Results underscore the relevance of social services to treatment, discharge, and rehabilitation planning when working with veterans without stable housing.

Adult↗