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Biomedical subjects

S Frankel

Publications and source records attributed to S Frankel.

At least 19 recordsLinked to original sources
PubMed1999

Population requirement for primary hip-replacement surgery: a cross-sectional study.

BACKGROUND: There has been a long-standing failure in many countries to satisfy the demand for several elective surgical treatments, including total hip replacement. We set out to estimate the population requirement for primary total hip replacement in England. METHODS: We undertook a cross-sectional study of a stratified random sample of 28,080 individuals aged 35 and over from 40 general practices in inner-city, urban, and rural areas of Avon and Somerset, UK. Prevalent disease was identified through a two-stage process: a self-report screening questionnaire (22,978 of 26,046 responded) and subsequent clinical examination. Incident disease was estimated from the point prevalence by statistical modelling. The requirement for total hip replacement surgery was estimated on the basis of pain and loss of functional ability, with adjustment for evidence of comorbidity and patients' treatment preferences. FINDINGS: 3169 people reported hip pain on the screening questionnaire. 2018 were invited for clinical examination, and 1405 attended. The prevalence of self-reported hip pain was 107 per 1000 (95% CI 101-113) for men and 173 per 1000 (166-180) for women. The prevalence of hip disease severe enough to require surgery was 15.2 (12.7-17.8) per 1000 aged 35-85 years. The corresponding annual incidence of hip disease requiring surgery was estimated as 2.23 (1.56-2.90), which suggests an overall requirement in England of 46,600 operations per year for patients who expressed a preference for, and were suitable for, surgery; the recent actual provision in England was about 43,500. INTERPRETATION: This research suggests that the satisfaction of demand for total hip replacement, given agreed criteria for surgery, is a realistic objective.

Adult↗
PubMed1999

A phase I study of recombinant human soluble interleukin-1 receptor (rhu IL-1R) in patients with relapsed and refractory acute myeloid leukemia.

PURPOSE: The recombinant human interleukin-1 receptor (rhu IL-1R) is a soluble truncated form of the type 1 full-length membrane-bound receptor that binds IL-1 with identical affinity to that of the membrane form. As such, it may have clinical potential by sequestering IL-1, thereby preventing it from binding to its membrane-bound receptor and eliciting a biological effect. As IL-1 has been shown to regulate leukemic cell proliferation in an autocrine fashion, a phase I trial of rhu IL-1R was conducted in patients with relapsed and refractory acute myeloid leukemia (AML). METHODS: The study group comprised 11 patients who were sequentially treated on one of three dose levels, receiving a single intravenous (i.v.) bolus dose on day 1 followed by 13 days of daily subcutaneous (s.c.) injections with the option of an additional 14 days of treatment if a response of stable disease or better was achieved. Dose level 1 i.v. bolus 500 microg/m2, s.c. dose 250 microg/m2 per day (five patients); dose level 2 i.v. bolus 1000 microg/m2, s.c. dose 500 microg/m2 per day (three patients); dose level 3 i.v. bolus 2000 microg/m2, s.c. dose 1000 microg/m2 per day (three patients). Owing to limited drug availability, the study was designed to only examine these three dose levels. RESULTS: rhu IL-IR was well tolerated. There was no grade 3 or 4 non-hematological toxicity related to the study drug and the maximum tolerated dose was not reached. No IL-1R-blocking antibodies developed during the course of the study. Serum levels of IL-1beta, IL-6 and TNF were undetectable before, during and after rhu IL-IR administration. The terminal half-life after i.v. dosing was at least 7-12 h, and after s.c. dosing 2-4 days. Serum levels of rhu IL-1R up to 360- and 25-fold those of pretreatment levels were achieved after i.v. and s.c. dosing respectively. No patient had a complete, partial or minor response to treatment; four had stable disease and seven had progressive disease. CONCLUSIONS: rhu IL-1R therapy was safe but did not have any apparent antileukemic effect at the doses administered.

Aged↗
PubMed1999

The effect of commencing combination antiretroviral therapy soon after human immunodeficiency virus type 1 infection on viral replication and antiviral immune responses.

Twelve subjects were treated with zidovudine, lamivudine, and ritonavir within 90 days of onset of symptoms of acute infection to determine whether human immunodeficiency virus type 1 (HIV-1) infection could be eradicated from an infected host. In adherent subjects, with or without modifications due to intolerance, viral replication was suppressed during the 24-month treatment period. Durable suppression reduced levels of HIV-1-specific antibodies and cytotoxic T lymphocyte responses in selected subjects. Proviral DNA in mononuclear cells uniformly persisted. The persistence of HIV-1 RNA expression in lymphoid tissues and peripheral blood mononuclear cells suggests that elimination of this residual pool of virus should be achieved before considering adjustments in antiretroviral therapeutic regimens. In addition, given the reduction in levels of virus-specific immune responses, it would seem prudent to consider enhancing these responses using vaccine strategies prior to the withdrawal of antiviral therapy.

Acquired Immunodeficiency Syndrome↗
PubMed1999

The dementia dilemma.

Explore the source record for details and available documents.

Advance Directive Adherence↗
PubMed1998

Reporting on quality of life in randomised controlled trials: bibliographic study.

OBJECTIVES: To examine the frequency and quality of reporting on quality of life in randomised controlled trials. DESIGN: Search of the Cochrane Controlled Trials Register 1980 to 1997 to identify trials from all disciplines, from oncology, and from cardiovascular medicine that reported on quality of life. Assessment of abstracts from articles published from 1993 to 1996. Assessment of a sample of full reports with a standardised instrument. MAIN OUTCOME MEASURES: Prevalence of reporting on quality of life. Conditions and interventions studied in trials reporting on quality of life. Quality of reporting on quality of life. RESULTS: During 1980-97 reporting on quality of life increased from 0.63% to 4.2% for trials from all disciplines, from 1.5% to 8.2% for cancer trials, and from 0.34% to 3.6% for cardiovascular trials. Of 364 abstracts, 65% reported on drug interventions. Of a sample of 67 full reports, authors of 48 (72%) used 62 established quality of life instruments. In 15 reports (22%) authors developed their own measures, and in 2 (3%) methods were unclear. Response rates were given in 38 (57%), and complete reporting on all items and scales occurred in 31 (46%). CONCLUSIONS: Less than 5% of all randomised controlled trials reported on quality of life, and this proportion was below 10% even for cancer trials. A plethora of instruments was used in different studies, and the reporting of methods and results was often inadequate. Standards for the measurement and reporting of quality of life in clinical trials research need to be developed.

Data Collection↗
PubMed1998

Childhood energy intake and adult mortality from cancer: the Boyd Orr Cohort Study.

OBJECTIVE: To examine the relation between energy intake in childhood and adult mortality from cancer. STUDY DESIGN: Cohort study. SETTING: 16 rural and urban centres in England and Scotland. SUBJECTS: 3834 people who took part in Lord Boyd Orr's Carnegie survey of family diet and health in prewar Britain between 1937 and 1939 who were followed up with the NHS, central register. Standardised methods were used to measure household dietary intake during a one week period. MAIN OUTCOME MEASURES: Cancer mortality. RESULTS: Significant associations between childhood energy intake and cancer mortality were seen when the confounding effects of social variables were taken into account in proportional hazards models (relative hazard for all cancer mortality 1.15 (95% confidence interval 1.06 to 1.24), P = 0.001, for every MJ increase in adult equivalent daily intake in fully adjusted models). This effect was essentially limited to cancers not related to smoking (relative hazard 1.20; 1.07 to 1.34; P = 0.001), with similar effects seen in men and women. CONCLUSION: This positive association between childhood energy intake and later cancer is consistent with animal evidence linking energy restriction with reduced incidence of cancer and the association between height and human cancer, implying that higher levels of energy intake in childhood increase the risk of later development of cancer. This evidence for long term effects of early diet confirm the importance of optimal nutrition in childhood and suggest that the unfavourable trends seen in the incidence of some cancers may have their origins in early life.

Adolescent↗
PubMed1998

Childhood leg length and adult mortality: follow up of the Carnegie (Boyd Orr) Survey of Diet and Health in Pre-war Britain.

OBJECTIVE: To investigate the relation between childhood height, its components--leg length and trunk length--and mortality in adulthood. DESIGN: Cohort study based on the Carnegie (Boyd Orr) Survey of diet and health in pre-war Britain, 1937-9. SETTING: The 14 centres in England and Scotland that participated in the Carnegie Survey and where children were examined. Scottish centres: Aberdeen, Dundee, West Wemyss, Coaltown of Wemyss, Hopeman, Methlick, Tarves, Barthol Chapel. English Centres: Liverpool, York-shire, Barrow in Furness, Wisbech, Fulham, and Bethnal Green. SUBJECTS: 2990 boys and girls aged between 2 years and 14 years 9 months when they were examined in 1937-9. These children were drawn from 1134 families who underwent a one week assessment of family diet and home circumstances. Of these, 2547 (85%) have been traced and flagged using the NHS Central Register. MAIN OUTCOME MEASURES: Age adjusted overall, coronary heart disease, and cancer mortality in men and women in relation to age and sex specific z scores for height, leg length, and trunk length. All analyses were adjusted for the possible confounding effects of childhood and adult socioeconomic circumstances and childhood diet. RESULTS: Leg length was the component of childhood height most strongly associated with socioeconomic and dietary exposures. There was no significant relation between childhood height and overall mortality. Height-mortality relations were observed in relation to both coronary heart disease (CHD) and cancer. Leg length was the component of height most strongly related to cause specific mortality. In men and women CHD mortality increased with decreasing childhood leg length. Men in the lowest leg length quintile had a relative risk (RR) of 2.5 (95% CI 1.0 to 6.2) compared to those with the longest legs (linear trend p = 0.14). Similarly, women in the lowest leg length quintile had a RR of 3.9 (95% CI 0.8 to 19.0; linear trend p < 0.01). Adjustment for childhood and adult socioeconomic circumstances had little effect on these trends. In men, but not women, those who as children had long legs experienced increased cancer mortality. The significant relations between anthropometry and both CHD and cancer mortality were restricted to those aged < 8 years when measured. CONCLUSIONS: These findings suggest that adverse diet and living conditions in childhood, for which leg length seems to be a particularly sensitive indicator, are associated with increased risk of CHD in adulthood and possibly reduced cancer risk. It is likely that these influences operate after birth, during the first few years of life.

Adolescent↗
PubMed1997

Measures of Proscar, Hytrin, and Cardura side effects.

The importance of reporting correlations among side effects is examined using studies of BPH drugs as examples. The special relation of placebo effects in studying side-effects of drugs, as opposed to their efficacies, is introduced, and the need for special new controls is presented.

Adrenergic alpha-Antagonists↗
PubMed1997

Cutaneous dendritic cells promote replication of immunodeficiency viruses.

The cutaneous or mucosal DC-T cell environments seem extremely supportive of immunodeficiency virus replication. Apart from very early after SIV infection, similar virus producing cells have been difficult to detect in the lymphoid tissues where DCs and T cells are also known to interact. Large amounts of virus can be visualized in the germinal centers of the lymph nodes, much of which represents immune complexed virus that is trapped on the follicular dendritic cell surface. However, whether these virus-carrying cells actually make virus or even virus proteins requires further investigation. We believe that once an individual is systemically infected, free virus and/or virus-infected cells will seed peripheral tissues and when encountering similar DC-T cell environments as described in the oral mucosae, can set up sites of chronic virus replication. For instance, a virus-carrying T cell that migrates to the periphery would, on entering this milieu, interact with the mature DCs and activate virus production. This likely occurs at similar sites around the body, such as the mucosal associated lymphoid tissue of the gut, and is probably independent of the route of infection.

Animals↗
PubMed1997

Interleukin-2-activated hematopoietic stem cell transplantation for breast cancer: investigation of dose level with clinical correlates.

Incubating hematopoietic stem cells with IL-2 in vitro for 24 h generates cytotoxic T cells. When infused into patients, these cells may stimulate a graft-versus-tumor (GVT) effect. This clinical trial was designed to assess the ability of IL-2 activated peripheral blood stem cells (PBSC) to reconstitute hematopoiesis, to investigate dose levels and dose-limiting toxicities of IL-2, and to evaluate clinical results and preliminary laboratory effects using a combination of IL-2-activated autologous PBSC followed by IL-2 after transplantation. Sixty-one women with stage II-IV breast cancer were treated. After the administration of carboplatin (200 mg/m2/day for 3 days) and cyclophosphamide (2 g/m2/day for 3 days), patients received autologous PBSC that were cultured in IL-2 for 24 h followed by parenteral administration of IL-2 beginning the day of transplantation. Three escalating doses of IL-2 were evaluated with increasing duration up to 4 weeks. Of the 57 patients receiving IL-2 after tranplantation, 19 patients (33.3%) were unable to complete the planned course of IL-2 therapy due to persistent fevers (n = 9), diarrhea (n = 2), pulmonary capillary leak syndrome (n = 3), development of a rash (n = 1), atrial fibrillation (n = 1), or patient's request (n = 3). One death occurred during hospitalization. Engraftment of neutrophils occurred on day 11.5 (mean; range 8-21 days) and platelets on day 11.7 (mean; range 7-33 days). The maximal tolerated dose of IL-2 was 6 x 10(5) IU/m2/day for 4 weeks. Disease-free survival rates for all stages were comparable to current reports in the literature. Preliminary laboratory evaluations include FACScan analysis of the IL-2 activated PBSC demonstrating an increased percentage of CD3+, CD25+, HLA-DR+ T cells. Phenotypically similar cells were present in peripheral blood samples of patients when tested 15 days after transplantation. This study demonstrates successful engraftment with IL-2-activated PBSC after high-dose chemotherapy for women with stage II-IV breast cancer. The regimen is feasible and, although toxicities are common, they are manageable and correlate with increasing dose and duration of IL-2.

Adult↗
PubMed1997

Purchasing evidence: the corollary of evidence-based purchasing.

The National Health Service (NHS) market led to problems in funding research and development (R&D). The current policy is to resolve these by funding R&D through a national levy on purchasers. The policy does not, however, address the underlying problem that evidence produced by R&D is largely irrelevant to purchasers. The consequences of this policy are likely to be that purchasing will have limited impact in securing health gain most effectively, the progress and impact of R&D will be impaired, and its funding will remain insecure. If R&D and purchasing were integrated each could become more effective. This integration can be fostered through developing the regulation of purchasers and providers within the NHS market.

Community Participation↗
PubMed1997

An actin-related protein in Drosophila colocalizes with heterochromatin protein 1 in pericentric heterochromatin.

The actin-related proteins have been identified by virtue of their sequence similarity to actin. While their structures are thought to be closely homologous to actin, they exhibit a far greater range of functional diversity. We have localized the Drosophila actin-related protein, Arp4, to the nucleus. It is most abundant during embryogenesis but is expressed at all developmental stages. Within the nucleus Arp4 is primarily localized to the centric heterochromatin. Polytene chromosome spreads indicate it is also present at much lower levels in numerous euchromatic bands. The only other protein in Drosophila reported to be primarily localized to centric heterochromatin in polytene nuclei is heterochromatin protein 1 (HP1), which genetic evidence has linked to heterochromatin-mediated gene silencing and alterations in chromatin structure. The relationship between Arp4 and heterochromatin protein 1 (HP1) was investigated by labeling embryos and larval tissues with antibodies to Arp4 and HP1. Arp4 and HP1 exhibit almost superimposable heterochromatin localization patterns, remain associated with the heterochromatin throughout prepupal development, and exhibit similar changes in localization during the cell cycle. Polytene chromosome spreads indicate that the set of euchromatic bands labeled by each antibody overlap but are not identical. Arp4 and HP1 in parallel undergo several shifts in their nuclear localization patterns during embryogenesis, shifts that correlate with developmental changes in nuclear functions. The significance of their colocalization was further tested by examining nuclei that express mutant forms of HP1. In these nuclei the localization patterns of HP1 and Arp4 are altered in parallel fashion. The morphological, developmental and genetic data suggest that, like HP1, Arp4 may have a role in heterochromatin functions.

Actins↗