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Biomedical subjects

S Parker

Publications and source records attributed to S Parker.

At least 19 recordsLinked to original sources

Effective treatment of hyperhomocysteinemia in heart transplant recipients with and without renal failure.

BACKGROUND: Elevated total plasma homocysteine (tHcy) levels have been associated with vascular disease and higher mortality in patients with coronary artery disease. Graft coronary disease is a major cause of mortality in long-term survivors of heart transplantation, and hyperhomocysteinemia may be one of its causes. The objectives of our study were to establish the effectiveness of a 3 stage homocysteine-lowering algorithm in a group of 84 heart transplant (HTx) patients and to evaluate the effect of renal function on the response to homocysteine-lowering therapy. METHODS: Prospective treatment of 84 Htx patients (64 male; mean age, 48 +/- 13 years) with tHcy > 75th percentile consisted of a 3-stage treatment algorithm: Stage 1, folic acid (FA) 2 mg + vitamin (vit) B(12) 500 mcg daily; Stage 2, addition of vit B(6) 100 mg daily; Stage 3, increase FA to 15 mg daily. Serum creatinine (Cr) and tHcy levels were measured before treatment and 21 +/- 19 weeks after each stage of treatment. RESULTS: All 3 stages of treatment significantly lowered mean tHcy from 22.4 +/- 16.3 (mean +/- SD) micromol/liter to 16.3 +/- 6.7 micromol/liter (p < 0.00001), from 17.6 +/- 6.1 micromol/liter to 15.2 +/- 5.3 micromol/liter (p < 0.0001), and from 16.8 +/- 5.2 micromol/liter to 15.6 +/- 5.3 micromol/liter (p < 0.05), respectively. The average reduction from baseline was 38%. Creatinine levels did not change significantly during the study period. Total plasma homocysteine levels decreased below the 75th percentile in 55% of patients, with Cr levels significantly lower in this group of patients (126 +/- 36 micromol/liter vs 182 +/- 65 micromol/liter, p < 0.00001). However, we found no significant relationship between % change in tHcy and baseline Cr. CONCLUSIONS: In a group of 84 heart transplant patients with tHcy levels >75th percentile, treatment with FA and vit B(6) and B(12) according to a 3-stage algorithm resulted in statistically significant declines in mean tHcy levels. Overall, tHcy levels decreased 38%, with target tHcy levels <75th percentile achieved in 55% of the patients. The % change in tHcy was not related to Cr. Further studies are needed to correlate treatment of hyperhomocysteinemia with clinical endpoints, such as the time to development of transplant vasculopathy and long-term survival, and to define the most appropriate targets for therapy.

Adult↗

Efficient factorization with a single pure qubit and logN mixed qubits.

It is commonly assumed that Shor's quantum algorithm for the efficient factorization of a large number N requires a pure initial state. Here we demonstrate that a single pure qubit, together with a collection of log 2N qubits in an arbitrary mixed state, is sufficient to implement Shor's factorization algorithm efficiently.

Journal Article↗

Fusion of H4/D10S170 to the platelet-derived growth factor receptor beta in BCR-ABL-negative myeloproliferative disorders with a t(5;10)(q33;q21).

We have studied a patient who presented with clinical features suggestive of chronic myeloid leukemia in accelerated phase. BCR-ABL transcripts were undetectable by reverse transcription-PCR, but a novel reciprocal translocation, t(5;10)(q33;q21.2), was seen by standard cytogenetic analysis. Chromosome band 5q33 contains the gene encoding the platelet-derived growth factor beta receptor (PDGFbetaR), the receptor tyrosine kinase that is disrupted by the t(5;7), t(5;12), and t(5;14) in myeloid disorders, resulting in the fusion of PDGFbetaR to HIP1, TEL/ETV6, and CEV14, respectively. Southern analysis with PDGFbetaR cDNA revealed novel bands in patient but not control DNA after digestion with several restriction enzymes, indicating that this gene is also targeted by the t(5;10). Fluorescence in situ hybridization analysis of chromosome 5 indicated that a small inversion at 5q33 had taken place in addition to the interchromosomal translocation. The site of the chromosome 10 breakpoint fell within YAC 940e4. Because all PDGFbetaR fusions described thus far result in splicing to a common exon of this gene, we performed 5'-rapid amplification of cDNA ends PCR on patient RNA. Several clones were isolated in which PDGFbetaR fused in frame to H4/D10S170, a previously described ubiquitously expressed gene that is fused to the ret protein tyrosine kinase to form the PTC-1 oncogene in approximately 20% of papillary thyroid carcinomas. The presence of H4-PDGFbetaR chimeric mRNA in the patient was confirmed by reverse transcription-PCR; reciprocal PDGFbeta1R-H4 transcripts were not detected. We conclude that t(5;10)(q33;q21.2) is a novel translocation in BCR-ABL-negative chronic myeloid leukemia and that this abnormality results in an H4-PDGFbetaR fusion gene. This finding further strengthens the association between myeloproliferative disorders and deregulated tyrosine kinases.

Amino Acid Sequence↗

Human T cell leukaemia/lymphoma virus infection in pregnant women in the United Kingdom: population study.

OBJECTIVE: To assess the prevalence of human T cell leukaemia/lymphoma virus (HTLV) infection in pregnant women in the United Kingdom. DESIGN: Population study. SUBJECTS: Guthrie card samples from babies born in 1997-8. Samples were linked to data on mother's age and ethnic status and parents' country of birth and then anonymised. SETTING: North Thames Regional Health Authority. MAIN OUTCOME MEASURES: Presence of antibodies against HTLV in eluates tested by gelatin particle agglutination assay and results confirmed by immunoblot. RESULTS: Of 126 010 samples tested, 67 had confirmed antibodies to HTLV (59 HTLV-I, 2 HTLV-II, 6 untyped) and six had indeterminate results. Seroprevalence was 17.0 per 1000 (95% confidence interval 9.2 to 28.3) in infants whose mothers were born in the Caribbean, 3.2/1000 (1.5 to 5.9) with mothers born in west and central Africa, and 6.8/1000 (3.1 to 12.9) in infants of black Caribbean mothers born in non-endemic regions. In infants with no known risk (both parents born in non-endemic regions and mother not black Caribbean) seroprevalence was 0.06-0.12 per 1000. Mother's country of birth, father's country of birth, and mother's ethnic status were all independently associated with neonatal seroprevalence. An estimated 223 (95% confidence interval 110 to 350) of the 720 000 pregnant women each year in the United Kingdom are infected with HTLV. CONCLUSIONS: The prevalence of HTLV and HIV infections in pregnant women in the United Kingdom are comparable. The cost effectiveness of antenatal HTLV screening should be evaluated, and screening of blood donations should be considered.

Adult↗

Comparison of growth rates of Tritrichomonas foetus isolates from various geographic regions using three different culture media.

The growth rates of 16 isolates of Tritrichomonas foetus from three distinct geographic regions were investigated in modified Diamond's medium, liver infusion broth medium and a commercially available culture kit. While some differences in growth characteristics were detected for different isolates and in the three different media, all isolates grew. Trichomonads reached peak concentrations from an initial concentration of 10(4) trichomonads/ml on Days 2, 3 and 4 in modified Diamond's medium, on Days 2-6 (excluding CAPTF102) in the commercial culture kit and on Days 2-7 in liver infusion broth medium. Viable parasites were detectable for longer periods in liver infusion broth medium and the commercial culture kit than in Diamond's medium. Peak concentrations for isolates tended to be higher in modified Diamond's medium than in liver infusion broth medium or the commercial culture kit. Results show that these three media are suitable for the growth of all 16 T. foetus isolates from three continents and suggest that these media could be used effectively throughout the world.

Animals↗

HCV prevalence in pregnant women in the UK.

The objective of the study was to assess the prevalence and epidemiology of hepatitis C virus (HCV) infection in pregnant women in the North Thames region, and in the UK in general. Demographic data were linked to neonatal samples prior to anonymization and testing by anti-HCV EIA, and with RIBA 3 confirmation. Risk factors for maternal infection were explored. Area-specific seroprevalence rates were multiplied into population sizes to estimate HCV prevalence in pregnant women in the UK. A total of 241/126,009 samples were confirmed anti-HCV positive, and a further 40 were indeterminate, representing a seroprevalence of 0.19-0.22%; 51% of maternal HCV infections were in UK-born women (71% of the population), and 22% in women from continental Europe (5% of the population). Among European-born women, HCV prevalence was associated with birth in continental Europe, partner not being notified at birth registration, partner born in a different region to the mother, and inner city residence. Four of the 241 anti-HCV positive samples (1.7%) were also anti-HIV-1 positive. It was estimated that each year an estimated 1150 out of 730,000 pregnancies in the UK would involve a woman infected with HCV (uncertainty range 660-1850), a prevalence of 0.16% (0.09-0.25%). On the basis of reported rates of mother-to-child transmission of HCV, this would represent approximately 70 paediatric HCV infections per year.

Adolescent↗

The general practice perspective on cancer services in Lothian.

OBJECTIVES: The aim of the present study was to obtain views from general practices about current and potential improvements to services for patients with suspected lung, large bowel, non-melanoma skin and breast cancer. METHOD: A questionnaire study was carried out of 134 general practices within the Lothian Health Board boundary. Information was sought about referral choices, communication, quality of care, liaison between community and hospital, health promotion, treatment outcomes and palliative care. Main outcome measures were determinants of primary care referral behaviour and clinical investigation strategies, and perception of quality in secondary care and health promotion services. RESULTS: Seventy-nine general practices (59%) returned completed questionnaires. One-fifth of practices maintained a cancer register, and 85% provide patient information about cancer prevention. Initial management was disease dependent. Most cases of suspected lung cancer, about half of suspected colorectal cancer cases and very few cases of suspected breast cancer were investigated in primary care before referral to hospital. Hospital referral depended on knowledge of local services. A minority of practices wanted referral guidelines. It was estimated that 92% of lung and breast cancer cases, 68% of colorectal cancers and 35% of skin cancers are seen within 4 weeks. Breast cancer care was rated more highly than that for other cancers. One-third ranked community nursing support as 'excellent' and 10-15% described it as 'fair' or 'poor'; 77% describe palliative care as 'excellent' or 'good'. Fifty-one percent believe that communication with hospital is 'excellent' or 'good'. Practices were sometimes unaware of the hospital's post-diagnosis management plan; communication was often too slow and practices often received 'poor' advice about symptom control. Eighty percent thought that hospital follow-up for breast, colorectal and lung cancer should be routine; 20% thought that it was indicated for non-melanomatous skin cancer. CONCLUSIONS: Communication problems between primary and secondary sectors need to be tackled innovatively and the perceived quality variation in services addressed-perhaps by developing local guidelines. Practices would welcome further education about health promotion resources and cancer epidemiology.

Attitude of Health Personnel↗

A high diagnostic rate in older patients attending an integrated syncope clinic.

OBJECTIVES: To describe the findings in the first year of an integrated syncope clinic for older patients and to review the published literature on "integrated" syncope clinics investigating older people. DESIGN: Review of syncope clinic database and Medline search for relevant literature. SETTING: Outpatient syncope clinics in two district hospitals in the same city. PARTICIPANTS: Secondary referrals from the in- and outpatient population with recurrent unexplained presyncopal and syncopal symptoms. RESULTS: The results of testing in 76 patients over the age of 60 years were available for analysis. A diagnosis was achieved in 67 (88%) of the patients with 76% of the diagnoses being cardiovascular in origin. The prevalence rates of neurocardiogenic syncope (32%) and carotid sinus syndrome (17%), however, differed from previously reported rates. CONCLUSIONS: Evaluation of presyncopal and syncopal events in an "integrated syncope clinic" achieves a high diagnostic yield in older subjects.

Aged↗

Randomized controlled trial of supported discharge in patients with exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: A randomised trial was performed on patients presenting to hospital with an exacerbation of chronic obstructive pulmonary disease (COPD) to compare outcomes in those managed at home with support with those admitted to hospital in the standard manner. METHODS: Over an 18 month period all patients presenting to the Royal Infirmary of Edinburgh on weekdays (n=718) with a diagnosis of an exacerbation of COPD were assessed for inclusion in the trial. Patients with impaired level of consciousness, acute confusion, acute changes on radiography, or an arterial pH of <7.35 or with other serious medical or social reasons for admission were excluded. Patients randomised to home support were discharged with an appropriate treatment package (antibiotics, corticosteroids, nebulised bronchodilators and, if necessary, home oxygen). They were visited by a nurse the following day and thereafter at intervals of 2-3 days until recovery when they were discharged from follow up. Parallel observations were made on patients allocated to normal hospital admission up to the point of discharge. Patients in both groups were assessed at home eight weeks after the initial assessment. RESULTS: Among weekday patients 353 (50%) were considered obligatory admissions, 140 (19%) were admitted because of co-morbidity, 17 (2%) because of poor social circumstances, and 24 (3%) did not consent to the trial. The remaining 184 (26%) were randomised (2:1) either to home support or to a standard hospital admission. The median time to discharge was 7 days for the home support group and 5 days for the admitted group (p<0.01); 25% of the home support group and 34% of the admitted group were readmitted before the final assessment at eight weeks (p>0.05). There were no significant differences between the groups in attendances by GPs and carers or in health status measured eight weeks after the initial assessment. Satisfaction with the service was good. The mean total health service cost per patient was estimated as 877 pounds sterling for the home support group and 1753 pounds sterling for the admitted group. CONCLUSIONS: This study shows that home supported discharge is a well tolerated, safe, and economic alternative to hospital admission for a proportion of patients referred to hospital for admission for an exacerbation of COPD.

Adult↗

Incidental treatment of nipple discharge caused by benign intraductal papilloma through diagnostic Mammotome biopsy.

OBJECTIVE: The purpose of this study was to evaluate imaging-guided vacuum-assisted mammotome biopsy as a minimally invasive method of obtaining a satisfactory diagnosis and eliminating the bothersome symptoms in patients presenting with nipple discharge. MATERIALS AND METHODS: Forty-nine women who presented with nipple discharge and who had final pathologic diagnoses of papillary lesions were retrospectively identified. Fifty-six lesions were biopsied in this group. The examinations included mammography, ductography, sonography, and, if possible, percutaneous biopsy. All lesions were centrally located and most were superficial. Of this study group, four patients with five lesions proceeded to sonographically guided automated core biopsy, and 38 patients with 44 intraductal lesions identified by sonography advanced to sonographically guided biopsy with an 11-gauge mammotome probe. One patient underwent stereotactic 11-gauge mammotome biopsy. Patients not advancing to sonographically guided biopsy were those with masses either in the nipple or nipple-areolar complex (five patients), one patient with no identifiable lesion at sonography, and one directly referred for open surgical biopsy. RESULTS: In all biopsied patients, satisfactory tissue for diagnosis was obtained. In patients biopsied with the mammotome probe, follow-up at a mean time of 13 months revealed resolution of the presenting problematic discharge in 97.2% of patients. Complications were mild and infrequent. Only one of 50 percutaneously biopsied lesions was not benign and required subsequent surgery. CONCLUSION: Papilloma excision with percutaneous biopsy allows safe and accurate tissue analysis and a high probability of terminating the symptomatic nipple discharge.

Adult↗

Collection of Ph-negative progenitor cells from interferon responsive patients with chronic myeloid leukemia: effect of granulocyte-colony-stimulating factor mobilization.

BACKGROUND AND OBJECTIVE: The observation that patients with chronic myeloid leukemia (CML) may relapse following stem cell transplantation because of Philadelphia positive cells contaminating the graft have led to a variety of strategies to reduce this contamination. This study investigate the feasibility of collective, Ph-re cells from patients with CML in chronic phase. DESIGN AND METHODS: A total of 18 patients with chronic myeloid leukemia in chronic phase who had responded to varying degrees to treatment with interferon-a (IFN) were subjected to mobilization with granulocyte colony-stimulating factors and peripheral blood progenitor cell collection. Nine patients were in complete cytogenetic remission (CCR) and nine were partial responders. IFN was stopped 2 to 4 weeks before the procedure. G-CSF was given by subcutaneous injection once daily at a dose of 10 microg/kg. RESULTS: Five patients underwent one collection procedure only, 10 underwent two procedures and 3 patients had three collections. The median number of nucleated cells (NC) per patient collected was 10.2 x 10(8)/kg (4.4-19.7) and the median number of CD34(+) cells was 2.5 x 10(6)/kg (0.4-9.4). Analyzable cytogenetic data were available for 26/34 (76%) leukapheresis procedures. The median percentage of Ph- negative metaphases for patients in CCR was 100% (73-100). Patients not in CCR had a higher level of Ph-positive cells in their collections (median 23%, range 0-79%, p=0.01). Of the nine patients in CCR, 8 had at least one apheresis from which progenitor cells were 100% Ph-negative; conversely, patients not in CCR had detectable Ph-positive cells in every collection. Four patients have undergone autologous stem cell transplantation. INTERPRETATION AND CONCLUSIONS: It was possible to collect sufficient Ph negative progenitor cells from patients in CCR but collections from other patients contained significant numbers of Ph-positive cells.

Adult↗

Effect of the worldwide epidemic on HIV prevalence in the United Kingdom: record linkage in anonymous neonatal seroprevalence surveys.

OBJECTIVE: To assess the impact of the worldwide HIV/AIDS epidemic on the prevalence of HIV in women in the United Kingdom (UK), particularly in the large immigrant and ethnic minority communities. METHOD: Unlinked anonymous neonatal seroprevalence survey with electronic record linkage of data from child health computers (maternal age and ethnic status) and birth registration (parent's country of birth). RESULTS: Of a total 137456 samples collected in 1997-1998, 188 (0.14%) were anti-HIV-1 seropositive. Seroprevalence was highest in women born in East Africa (2.3%) and Central Africa (1.9%). 76.4% of seropositive newborns were delivered to mothers born in sub-Saharan Africa; a further 6.0% had fathers from sub-Saharan Africa. However, there was little evidence of HIV in women born in Southern Asia [prevalence 0.0081%; 95% confidence interval (CI) 0-0.04], and none within UK-born Asian communities. Prevalence among the UK-born Black African community was low (0.14%; 95% CI 0-0.6). Among infants with both parents known to be born in the UK, seroprevalence was 0.023% (95% CI 0.01-0.04) in London, and zero (95% CI 0-0.007) in non-Metropolitan areas. Irrespective of mother's region of birth, seroprevalence was 4.2 times higher (95% CI 3.0-5.8) in newborns whose father's details were not recorded at birth registration, a marker for single unsupported mothers. CONCLUSION: The risk of HIV among pregnant women from sub-Saharan Africa has been recognized. However, in southern England, HIV is very rare in women from Southern Asia and in UK-born women in ethnic minority communities, in spite of cultural and travel ties to high-prevalence countries. Data linkage in anonymous surveys assists in monitoring the impact of the worldwide epidemic on prevalence and incidence locally.

Adult↗

Comparison of two sampling tools for diagnosis of Tritrichomonas foetus in bulls and clinical interpretation of culture results.

OBJECTIVE: To compare sensitivity for diagnosing Tritrichomonas foetus infection in bulls using 2 sampling tools and to calculate negative predictive values for infection. DESIGN: Randomized clinical trial. ANIMALS: 30 Bos taurus bulls naturally or experimentally infected with T foetus. PROCEDURE: Preputial scrapings were obtained once/wk for 6 weeks using an artificial insemination pipette and a metal brush; which tool was used first for each bull was randomly determined. Samples were collected first from the left side of the prepuce and then from the right side and placed in commercially available transport media chi 2 Values and confidence limits were adjusted for effect of clustering of results by bull. RESULTS: Significant differences in sensitivity of results were not found between samples collected using the brush or pipette. Using the pipette, sensitivity was estimated to be 91.6% (95% confidence interval, 84.3 to 95.7%); negative predictive values ranged from 41 to 99% for prevalence of infection of 90 to 5%, respectively. Sensitivity was 88.8% for first sample obtained and 96.1% for second sample obtained. CONCLUSIONS AND CLINICAL RELEVANCE: Collection of preputial scrapings with an artificial insemination pipette or a metal brush and use of a commercially available culture system can provide a sensitive diagnostic test for T foetus infection in bulls. Calculated negative predictive values indicated that 1 or 2 tests would suffice in most clinical situations. For bulls from herds in which T foetus is endemic, 2 to 4 tests/bull may be required to ensure that each bull is not infected.

Animals↗