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Biomedical subjects

R Stone

Publications and source records attributed to R Stone.

At least 37 records · Page 2Linked to original sources

Medicare: challenges and future directions in a changing health care environment.

In this GSA-sponsored Congressional Briefing Seminar, authorities from several disciplines summarize the history, rationale, strengths, weaknesses, and future challenges of the Medicare program. In the current arena of health care reform, the role of Medicare is far from certain, and it is crucial to understand and confront a multitude of issues, many of which are raised in this briefing.

Aged

Serum alpha-fetoprotein and neural tube defects in the first trimester of pregnancy. MRC Vitamin Study Research Group.

As part of the Medical Research Council randomized trial of vitamin supplementation in the prevention of neural tube defects (NTDs), maternal serum alpha-fetoprotein (AFP) was available for 19 NTD pregnancies. Each of these was matched with four unaffected controls, by maternal age, participating centre, and duration of sample storage. The samples came from women whose gestational age ranged from 6 to 14 completed weeks. The median AFP level in the affected pregnancies was 1.2 multiples of the median value in unaffected pregnancies of the same gestational age (95 per cent confidence interval (CI) 0.83-1.59). This confirmed the view that serum AFP measurement is of no practical value in the detection of NTDs in the first trimester of pregnancy. The study also showed that folic acid supplementation, used as a method of preventing NTDs, had no effect on the concentrations of maternal serum AFP up to 14 weeks of pregnancy.

Female

T-lymphocyte recognition of a portion of myelin basic protein encoded by an exon expressed during myelination.

The major isoform of myelin basic protein (MBP) in the healthy adult central nervous system is the 18.5-kDa protein which is produced by mRNA derived from exons 1, 3, 4, 5, 6 and 7 of the MBP gene. Since isoforms containing exon 2-encoded protein (X2MBP) are expressed during myelin formation, we examined T cell reactivity specific for X2MBP in a disease characterized by remyelination subsequent to demyelination, multiple sclerosis (MS). T cell lines specific for X2MBP were derived from three MS patients as well as one healthy control. This suggests that candidate autoantigens in demyelinating/remyelinating diseases should include not only the major isoforms of myelin proteins, but also isoforms expressed aberrantly during a disease process since they too may be the target of a T cell-mediated autoimmune process.

Adult

A novel candidate autoantigen in a multiplex family with multiple sclerosis: prevalence of T-lymphocytes specific for an MBP epitope unique to myelination.

Although the major isoform of myelin basic protein (MBP) in the healthy adult CNS is the 18.5-kDa protein, other isoforms containing exon 2 encoded protein (21.5 kDa and 20.2 kDa) exist and are expressed primarily during myelin formation. Since remyelination is a prominent feature in MS lesions, we examined the frequencies of T cell lines (TCLs) specific for epitopes within exon 2 encoded MBP (X2MBP), and also within 18.5-kDa MBP, in members of a multiplex family with MS. TCLs specific for X2MBP were as prevalent as TCLs specific for immunodominant epitopes within 18.5-kDa MBP. In addition, while frequencies of TCLs specific for 18.5-kDa MBP were no different between the affected and unaffected, the frequency of X2MBP-specific TCLs correlated with disease.

Aged

The use of free beta-hCG in antenatal screening for Down's syndrome.

OBJECTIVE: To investigate the value of the measurement of free beta human chorionic gonadotrophin (hCG) as a serum marker of Down's syndrome in the second trimester of pregnancy. DESIGN: A prospective observational study using stored antenatal serum samples. SETTING: Serum samples collected from women receiving routine antenatal care in Oxford. SUBJECTS: Seventy-five singleton pregnancies with fetal Down's syndrome and 367 unaffected singleton pregnancies. Each affected pregnancy was matched with five control pregnancies for maternal age, gestational age, and duration of storage of the serum sample. None of the pregnancies were associated with neural tube defects. MAIN STUDY MEASURES: Maternal serum free beta-hCG levels. These were compared with total hCG levels in the same pregnancies. The performance of screening using free beta-hCG was compared with that using the principal markers, namely alpha-fetoprotein (AFP), unconjugated oestriol (uE3), and total hCG together with maternal age. RESULTS: The median free beta-hCG level in the affected pregnancies was 2.22 multiples of the normal median (MoM), significantly higher than in the unaffected pregnancies (95% confidence interval, 1.84-2.68 MoM). The discriminatory performances of free beta-hCG and total hCG, each considered separately, were similar; with a cut-off level of 2.5 MoM the detection rate was 43% and 5.7 of unaffected pregnancies had raised free beta-hCG levels (likelihood ratio of 7.5 (43/5.7)), somewhat better discrimination than the 32% and 4.6% respectively using total hCG (likelihood ratio of 7.0 (32/4.6)). With a higher cut-off level of 3.5 MoM, the rates were 19% and 2.7% respectively (likelihood ratio of 7.0), using free beta-hCG, worse than the 19% and 1.4% using total hCG (likelihood ratio of 13.6). Screening using maternal age, AFP, uE3 and free beta-hCG (instead of total hCG) yielded a detection rate of 62% (instead of 58%) at a screening risk cut-off level corresponding to a 5% false-positive rated). CONCLUSION: The main advantage in using free beta-hCG instead of total hCG is that there is a small increase in the detection rate (4%) for a given false-positive rate when used with maternal age, AFP and uE3. The main disadvantage is that there is less practical experience with free beta-hCG measurement and insufficient data to screen in certain categories of pregnancy (e.g. twins). The best practical advice is to use total hCG for the present but consider changing to free beta-hCG either (i) after further data are available that will permit the interpretation of screening results in the same way as is currently available with total hCG, or (ii) if its use with another marker confers a worthwhile increase in the detection rate for a given false-positive rate.

Adult

Hexamethylene bisacetamide in myelodysplastic syndrome and acute myelogenous leukemia: a phase II clinical trial with a differentiation-inducing agent.

Hexamethylene bisacetamide (HMBA) is a potent inducer of differentiation of a number of transformed cell lines in vitro. We report results of a phase II clinical trial in 41 patients with myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML) to whom HMBA was administered by continuous infusion for 10 days and repeated after an interval of 18 to 75 days. HMBA induced a complete remission (CR) in three patients and a partial remission (PR) in six patients. The median duration of CR was 6.8 months (range 1.3 to 16 months) and 3.7 months for PR (range 1 to 7 months). No significant difference was observed between responders and nonresponders with respect to the mean HMBA plasma levels, which were 0.86 +/- 0.04 mmol/L and 0.87 +/- 0.12 mmol/L, respectively. In certain patients morphologic and chromosome analyses provided evidence that HMBA induced differentiation of transformed hematopoietic precursors. The most prominent toxicity was thrombocytopenia, generally reversible on cessation of administration of HMBA.

Acetamides