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Biomedical subjects

E Hilton

Publications and source records attributed to E Hilton.

At least 19 recordsLinked to original sources
PubMed2002

Predictors of outcome of mammography in the National Health Service Breast Screening Programme.

BACKGROUND: Little is known about the factors influencing the risk of recall for assessment, invasive diagnostic procedures, and early rescreening after screening mammography. METHODS: From June 1996 to March 1998 women attending screening at 10 National Health Service Breast Screening Programme (NHSBSP) centres completed a self administered questionnaire and were followed up for their screening outcome. RESULTS: 1969 (3.3%) out of 60 443 women aged 50-64 who had never used hormone replacement therapy (HRT) were recalled for assessment but were not diagnosed with breast cancer (defined here as false positive recall). After adjustment for the variation between centres, false positive recall was decreased significantly among women who were likely to have had a previous NHSBSP mammogram (odds ratio (OR) 0.49, 95% confidence interval (95% CI) 0.38 to 0.63 for likely versus unlikely), who were postmenopausal (OR 0.65, 95% CI 0.56 to 0.76 for postmenopausal v premenopausal) and increased significantly for women reporting previous breast surgery (OR 1.64, 95% CI 1.42 to 1.89). Although false positive recall decreased significantly with parity and increasing body mass index, these effects were not large and no significant variation was found with age, education, family history of breast cancer, oral contraceptive use, sterilisation, exercise, smoking, or alcohol consumption. Altogether 655 (1.1%) women had an invasive diagnostic procedure; no personal characteristics were predictive of this outcome, 286(0.5%) were referred for early rescreening, and this was increased significantly by nulliparity and a family history of breast cancer. INTERPRETATION: Premenopausal women, those without a previous NHSBSP mammogram, and women with previous breast surgery have an increased risk of false positive recall by the NHSBSP.

Age Factors↗
PubMed2001

Contribution of HLA alleles in the regulation of antibody production in Lyme disease.

A small subset of patients infected with Borrelia burgdorferi (Bb) does not produce Bb specific antibody. Our research provides additional evidence of a genetic predisposition for seronegativity in some individuals with Lyme disease. Because human leukocyte antigen (HLA) class II, a heterodimeric glycoprotein, plays an essential role in the regulation of antibody production, we investigated the difference in HLA genes between seropositive and seronegative patients with Lyme disease (LD). Our results show that HLA-DR7 was associated with anti-Bb antibody production. Nine out of the 22 seropositive LD patients (40.9%) had HLA-DRB1*0701, *0703, *0704 (HLA-DR7); only 1 out of the 18 seronegative LD patients (5.6%) had HLA-DR7 (odds ratio (OR)=11.8, P=0.0126). HLA-DRB1*01021 and HLA-DRB1*0101, *0104, *0105 (HLA-DR1) contributed negatively to anti-Bb antibody production. Seven of 18 seronegative LD patients had HLA-DR1, only 1 of 22 seropositive LD patients had HLA-DR1 (38.9% vs. 4.5%, OR=13.4, P=0.0138). These results suggest that the presence and or lack of production of specific antibody to Bb infection may be associated with particular HLA specificities of the Class II.

Adult↗
PubMed2001

Influence of phenylalanine-481 substitutions on the catalytic activity of cytochrome P450 2D6.

Homology models of the active site of cytochrome P450 2D6 (CYP2D6) have identified phenylalanine 481 (Phe(481)) as a putative ligand-binding residue, its aromatic side chain being potentially capable of participating in pi-pi interactions with the benzene ring of ligands. We have tested this hypothesis by replacing Phe(481) with tyrosine (Phe(481)-->Tyr), a conservative substitution, and with leucine (Phe(481)-->Leu) or glycine (Phe(481)-->Gly), two non-aromatic residues, and have compared the properties of the wild-type and mutant enzymes in microsomes prepared from yeast cells expressing the appropriate cDNA-derived protein. The Phe(481)-->Tyr substitution did not alter the kinetics [K(m) (microM) and V(max) (pmol/min per pmol) respectively] of oxidation of S-metoprolol (27; 4.60), debrisoquine (46; 2.46) or dextromethorphan (2; 8.43) relative to the respective wild-type values [S-metoprolol (26; 3.48), debrisoquine (51; 3.20) and dextromethorphan (2; 8.16)]. The binding capacities [K(s) (microM)] of a range of CYP2D6 ligands to the Phe(481)-->Tyr enzyme (S-metoprolol, 22.8; debrisoquine, 12.5; dextromethorphan, 2.3; quinidine, 0.13) were also similar to those for the wild-type enzyme (S-metoprolol, 10.9; debrisoquine, 8.9; dextromethorphan, 3.1; quinidine, 0.10). In contrast, the Phe(481)-->Leu and Phe(481)-->Gly substitutions increased significantly (3-16-fold) the K(m) values of oxidation of the three substrates [S-metoprolol (120-124 microM), debrisoquine (152-184 microM) and dextromethorphan (20-31 microM)]. Similarly, the K(s) values of the ligands to Phe(481)-->Leu and Phe(481)-->Gly mutants were also increased 3 to 10-fold (S-metoprolol, 33.2-41.9 microM; debrisoquine, 85-90 microM; dextromethorphan, 15.7-18.8 microM; quinidine 0.35-0.53 microM). However, contrary to a recent proposal that Phe(481) has the dominant role in the binding of substrates that undergo CYP2D6-mediated N-dealkylation routes of metabolism, the Phe(481)-->Gly substitution did not substantially decrease the capacity of the enzyme to N-deisopropylate metoprolol (wild-type, 1.12 pmol/min per pmol of P450; Phe(481)-->Gly, 0.71), whereas an Asp(301)-->Gly substitution decreased the N-dealkylation reaction by 95% of the wild-type rate. Overall, our results are consistent with the proposal that Phe(481) is a ligand-binding residue in the active site of CYP2D6 and that the residue interacts with ligands via a pi-pi interaction between its phenyl ring and the aromatic moiety of the ligand. However, the relative importance of Phe(481) in binding is ligand-dependent; furthermore, its importance is secondary to that of Asp(301). Finally, contrary to predictions of a recent homology model, Phe(481) does not seem to have a primary role in CYP2D6-mediated N-dealkylation.

Alkylation↗
PubMed1999

Seroprevalence and seroconversion for tick-borne diseases in a high-risk population in the northeast United States.

PURPOSE: To determine the prevalence of serologic reactivity, the 1-year incidence of seroconversion, and the frequency of multiple infections, and their associations with symptoms in a group of volunteers at high risk for tick-borne infections in New York state. METHODS: We performed a seroepidemiologic study of Lyme borreliosis, 2 of the ehrlichioses, Rocky Mountain spotted fever, and babesiosis among 671 participants who lived or worked in a high-risk area (mainly in eastern Long Island, New York) for tick-borne diseases. Sera were collected in the winters of 1994 and 1995. Signs and symptoms of tick-borne disease were monitored monthly by mail and telephone. Lyme borreliosis serologies were done by enzyme-linked immunosorbent assay and Western blot. Rocky Mountain spotted fever serologies were initially screened using Dip-S-Ticks, followed by specific indirect immunofluorescence. Ehrlichiosis serologies were determined by epifluorescent microscopy, as were antibodies to Babesia microti. RESULTS: Of the 671 participants, 88 (13%) had antibodies to > or = 1 tick-borne organisms, including 34 (5% of the total) with antibodies to Borrelia burgdorferi. Twenty-seven participants had evidence of exposure to B. burgdorferi at baseline. Seven participants (1%) seroconverted during the course of the study, 5 of whom were symptomatic for Lyme borreliosis. Antibodies to spotted fever group rickettsiae were seen in 28 participants (4%), 22 of whom were positive at baseline and 6 of whom seroconverted during the observation period. None of the seropositive patients had any symptoms or signs of infection. Twenty-four participants (3%) had serologic evidence of exposure to Ehrlichia (all but one to Ehrlichia equi); 5 (0.7%) seroconverted during the observation period, including 3 subjects who were asymptomatic. Antibodies to B. microti were seen in 7 participants (1%), including one asymptomatic seroconversion during the year of observation. There was evidence of possible dual infection in 5 patients. CONCLUSION: In a high-risk population, there was evidence of exposure to 5 tick-borne pathogens; however, many infections were asymptomatic, and coinfections were rare.

Babesiosis↗
PubMed1999

Motor feedback physiological control for a continuous flow ventricular assist device.

The response of a continuous flow magnetic bearing supported ventricular assist device, the CFVAD3 (CF3) to human physiologic pressure and flow needs is varied by adjustment of the motor speed. This paper discusses a model of the automatic feedback controller designed to develop the required pump performance. The major human circulatory, mechanical, and electrical systems were evaluated using experimental data from the CF3 and linearized models developed. An open-loop model of the human circulatory system was constructed with a human heart and a VAD included. A feedback loop was then closed to maintain a desired reference differential pressure across the system. A proportional-integral (PI) controller was developed to adjust the motor speed and maintain the system reference differential pressure when changes occur in the natural heart. The effects of natural heart pulsatility on the control system show that the reference blood differential pressure is maintained without requiring CF3 motor pulsatility.

Algorithms↗
PubMed1999

Relations among indexes of memory disturbance and depression in patients with Lyme borreliosis.

This study examined the relation between complaints of memory disturbance and measures of mood and memory functioning in 55 patients with serological evidence of late-stage Lyme Borreliosis (LB). Patients completed the Self-Ratings of Memory Questionnaire (SRMQ) and the Beck Depression Inventory. Memory functioning was assessed with the California Verbal Learning Test. Depressed patients exhibited more frequent complaints of memory disturbance on the SRMQ, although their pattern of responses did not differ from nondepressed patients. There was a significant correlation between subjective memory ratings and self-reported depression (Spearman rho = -.57, p < .001). No relation was observed between subjective memory ratings and objective memory performance. The results indicate subjective complaints of more severe memory disturbance in patients with LB and depression. Particular attention should be paid to the assessment of depression and subjective symptoms of memory disturbance when administering neuropsychological tests of memory functioning in patients with LB.

Adult↗
PubMed1999

The neuropsychological examination of naming in Lyme borreliosis.

Although subjective complaints of word finding and naming deficits are commonly reported by patients with Lyme Borreliosis (LB), the existence of these disturbances has not been thoroughly investigated. Forty-four patients with LB and 43 healthy controls were administered a symptom questionnaire, the Boston Naming Test (BNT), the Controlled Oral Word Association Test (COWAT), and a series of category naming tasks. LB patients had a higher rate of complaints of word-finding disturbance (55% vs. 14%). Lower mean scores were observed on the BNT, but not on the COWAT, nor on category naming tasks. Thirty-six percent of the LB sample exhibited BNT scores in the impaired range. BNT scores in this group were correlated with a measure of memory retrieval, but not with verbal fluency indexes. There was no relation between naming scores and depression. LB patients exhibit impairments in word finding that appear to be secondary to a generalized retrieval deficit.

Adult↗
PubMed1998

A vaccine consisting of recombinant Borrelia burgdorferi outer-surface protein A to prevent Lyme disease. Recombinant Outer-Surface Protein A Lyme Disease Vaccine Study Consortium.

BACKGROUND: Lyme disease is a multisystem inflammatory disease caused by infection with the tick-borne spirochete Borrelia burgdorferi and is the most common vector-borne infection in the United States. We assessed the efficacy of a recombinant vaccine consisting of outer-surface protein A (OspA) without adjuvant in subjects at risk for Lyme disease. METHODS: For this double-blind trial, 10,305 subjects 18 years of age or older were recruited at 14 sites in areas of the United States where Lyme disease was endemic; the subjects were randomly assigned to receive either placebo (5149 subjects) or 30 microg of OspA vaccine (5156 subjects). The first two injections were administered 1 month apart, and 7515 subjects also received a booster dose at 12 months. The subjects were observed for two seasons during which the risk of transmission of Lyme disease was high. The primary end point was the number of new clinically and serologically confirmed cases of Lyme disease. RESULTS: The efficacy of the vaccine was 68 percent in the first year of the study in the entire population and 92 percent in the second year among the 3745 subjects who received the third injection. The vaccine was well tolerated. There was a higher incidence of mild, self-limited local and systemic reactions in the vaccine group, but only during the seven days after vaccination. There was no significant increase in the frequency of arthritis or neurologic events in vaccine recipients. CONCLUSIONS: In this study, OspA vaccine was safe and effective in the prevention of Lyme disease.

Adolescent↗
PubMed1998

Psychological factors in the prediction of Lyme disease course.

OBJECTIVE: To determine whether history of severe, long-term, premorbid, psychological stress is associated with increased incidence of chronic physical symptoms in presumed Lyme disease patients. METHODS: Fifty-seven patients presenting at Lyme Disease Clinic of Long Island Jewish-Hillside Medical Center were studied for presenting symptoms, presence or absence of Lyme disease, and past history of psychological trauma. They were restudied 1 to 1.5 years later for presence or absence of physical symptoms. Statistical analyses compared symptom course for patients with and without Lyme disease, antibiotic and nonantibiotic treatments, and past history of psychological trauma. RESULTS: There was correlation between history of past traumatic psychological events and chronicity of physical symptoms whether or not the patient had presumed Lyme disease or had received antibiotic treatment. CONCLUSION: Traumatic psychological experiences predating onset of Lyme disease symptoms may play an important etiologic role in the chronicity of these symptoms.

Adult↗
PubMed1998

Performance of a continuous flow ventricular assist device: magnetic bearing design, construction, and testing.

A new centrifugal continuous flow ventricular assist device, the CFVAD III, which is fully magnetic bearing suspended, has been developed. It has only one moving part (the impeller), has no contact (magnetic suspension), is compact, and has minimal heating. A centrifugal impeller of 2 inch outer diameter is driven by a permanent magnet brushless DC motor. This paper discusses the design, construction, testing, and performance of the magnetic bearings in the unit. The magnetic suspension consists of an inlet side magnetic bearing and an outlet side magnetic bearing, each divided into 8 pole segments to control axial and radial displacements as well as angular displacements. The magnetic actuators are composed of several different materials to minimize size and weight while having sufficient load capacity to support the forces on the impeller. Flux levels in the range of 0.1 T are employed in the magnetic bearings. Self sensing electronic circuits (without physical sensors) are employed to determine the impellar position and provide the feedback control signal needed for the magnetic bearing control loops. The sensors provide position sensitivity of approximately 0.025 mm. A decentralized 5 axis controller has been developed using modal control techniques. Proportional integral derivative controls are used for each axis to levitate the magnetically supported impeller.

Algorithms↗
PubMed1998

Effect on attendance at breast cancer screening of adding a self administered questionnaire to the usual invitation to breast screening in southern England.

STUDY OBJECTIVE: The primary aim of the research described in this paper was to ascertain whether inclusion of a self administered questionnaire with the usual invitation to routine breast screening affected screening uptake. Secondary aims included establishing appropriate questionnaire distribution and collection methods within the framework of the National Health Service Breast Screening Programme and optimisation of questionnaire design. DESIGN: Randomised study. SETTING: Oxfordshire and West of London Breast Screening Units. PARTICIPANTS/METHODS: 6400 women invited for routine screening mammography were individually randomised to receive either the usual breast screening invitation alone, or to receive the usual invitation accompanied by a self administered questionnaire, to be returned at the time of screening. Participants were then followed up and attendance rates at screening were compared between groups. MAIN RESULTS: Screening attendance rates were similar in women who did and did not receive a questionnaire (71% in each group). Of those who were sent a questionnaire and attended for screening, 77% returned a completed questionnaire. Screening uptake was not affected by the way in which the questionnaire was returned or by whether or not personal details and signed permission for follow up were requested. CONCLUSIONS: The inclusion of a self administered questionnaire accompanying the invitation to breast screening did not adversely affect screening uptake. A high proportion of women completed the questionnaire.

Breast Neoplasms↗
PubMed1997

Efficacy of Lactobacillus GG as a Diarrheal Preventive in Travelers.

Traveler's diarrhea can be a debilitating problem for individuals on international trips. Retrospective and prospective studies have shown the incidence of traveler's diarrhea to range from 15-56%. 1,2A placebo-controlled, double-blinded study in Finnish travelers found that the probiotic Lactobacillus GG decreases the incidence of traveler's diarrhea.3 Lactobacillus GG, initially isolated from healthy humans, is remarkable in its ability to resist acid and bile degradation and to adhere to the intestinal mucosa.4 To assess the efficacy of Lactobacillus GG in preventing diarrhea in American tourists, a study was conducted at the Travel and Immunization Center of the Long Island Jewish Medical Center (LIJMC).

Journal Article↗
PubMed1997

Duration of tick attachment as a predictor of the risk of Lyme disease in an area in which Lyme disease is endemic.

Animal studies have shown an exponential increase in the risk of Borrelia burgdorferi infection after 48-72 h of deer tick attachment. Persons with tick bites were prospectively studied to determine if those with prolonged tick attachment constitute a high-risk group for infection. Ticks were identified, measured for engorgement, and assayed by polymerase chain reaction (PCR) for B. burgdorferi DNA. Duration of attachment was determined from the scutal index of engorgement. Of 316 submissions, 229 were deer ticks; 14% were positive by PCR. Paired sera and an intact tick for determination of duration of attachment were available for 105 subjects (109 bites). There were 4 human cases (3.7% of bites) of B. burgdorferi infection. The incidence was significantly higher for duration of attachment > or =72 h than for <72 h: 3 (20%) of 15 vs. 1 (1.1%) of 94 (P = .008; odds ratio, 23.3; 95% confidence interval, 2.2-242). PCR was an unreliable predictor of infection. Tick identification and measurement of engorgement can be used to identify a small, high-risk subset of persons who may benefit from antibiotic prophylaxis.

Animals↗
PubMed1997

Temporal study of immunoglobin M seroreactivity to Borrelia burgdorferi in patients treated for Lyme borreliosis.

Forty-six patients with late Lyme disease who were considered improved or cured following treatment were monitored by immunoglobin M (IgM) immunoblotting (mean monitoring period, 27.6 months). There was a persistent IgM response in 32 (97%) of 33 initially positive patients. All but three showed a consistent number, type, and intensity of IgM bands over the entire follow-up period. IgM immunoblotting may not be useful for monitoring the response to treatment of Lyme borreliosis.

Adult↗
PubMed1996

Recommendation to include OspA and OspB in the new immunoblotting criteria for serodiagnosis of Lyme disease.

In October 1994, the Second National Conference on the Serologic Diagnosis of Lyme Disease recommended a two-step approach to serological testing. The first step was the performance of an enzyme-linked immunosorbent assay (ELISA); the second step was a confirmatory immunoblot. New criteria for the interpretation of a positive immunoblot were also recommended. The committee decided to omit the 31- and 34-kDa bands (OspA and OspB, respectively) from the choice of bands considered diagnostic for a positive immunoblot. Since we had previously included these in our diagnostic criteria for Lyme disease-positive immunoblots, we reviewed data for all patients attending a Lyme disease center with positive ELISAs and immunoblot assays for Lyme disease from 1 September 1992 to 31 December 1993. The criteria for a positive Western blot (immunoblot) were the presence of 5 or 12 bands, including the 10 recommended by the conference, and the presence of the 31- and 34-kDa protein bands. Of the 136 patients evaluated, 50 were considered to have Lyme disease. Of these 50, 4 (8%) would not have met immunoblot criteria for the diagnosis if the new recommendations were used. Had the 31- and 34-kDa bands been included as part of the diagnostic requirements for immunoblot, these patients would have been included. Although overdiagnosis of Lyme disease appears to be the more frequent problem, our concern is that the exclusion of the 31- and 34-kDa protein bands from the diagnostic criteria may result in the underdiagnosis of Lyme disease by those who would rely too heavily on serological confirmation. The addition of the 31- and 34-kDa bands to those recommended for confirmatory immunoblot should be reconsidered.

Adult↗