Signal transduction. A taste of things to come.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to A Mitchell.
Explore the source record for details and available documents.
There is considerable concern about the adverse effects on the skeleton of loss of menstrual function as a result of athletic activity, as well as uncertainty as to how it should be managed clinically. In a pilot intervention study 34 elite middle and long-distance runners, aged 18-35 years, with menstrual irregularity due to their athletic activity were randomized to three groups: (A) to receive hormone replacement therapy (HRT) and 1000 mg calcium per day (n = 10), (B) to receive 1000 mg calcium per day (n = 14), (C) a control group who received no treatment (n = 10). Bone mineral density (BMD) was measured in the left hip and lumbar spine (L2-4) using dual-energy X-ray absorptiometry. Results were first analyzed according to whether menstruation returned, either naturally or secondary to HRT (EU), and compared with those from subjects who remained amenorrheic (AM). During the first year BMD increased in the EU group in Ward's triangle (3.8%) and the lumbar spine (4.1%; both P < 0.05). BMD fell in the AM group in all regions and the between-group differences were 5.6% (p < 0.02) in Ward's triangle, 5.8% (p < 0.02) in L2-4 and 3.9% in the trochanter (p < 0.05). An 'intention to treat' analysis was then performed. It was found that the mean relative improvement at 1 year in spinal BMD was only 1.5%, due to return of menses in some of the controls and withdrawals from treatment in the treatment group. In consequence, a trial designed to show, with 80% power and 5% significance, a measurable benefit in lumbar spine BMD resulting from allocation to HRT treatment would require about 1150 athletes with amenorrhea or oligomenorrhea. These numbers could be reduced substantially to 380 subjects by confining the trial to completely amenorrheic athletes, who in this study were less likely to regain menses. For these and other logistical reasons, an HRT trial in amenorrheic athletes could only be successfully organized through international collaboration. This study illustrates the major effects of treatment withdrawals and instability of menstrual status on the design of longitudinal studies on the bony effects of menstrual dysfunction prior to menopause.
OBJECTIVES: Allografts offer many advantages over prosthetic valves, but allograft durability varies considerably. METHODS: From 1969 through 1993, 618 patients aged 15 to 84 years underwent their first aortic valve replacement with an aortic allograft. Concomitant surgery included aortic root tailoring (n = 58), replacement or tailoring of the ascending aorta (n = 56), and coronary artery bypass grafting (n = 87). Allograft implantation was done by means of a "freehand" subcoronary technique (n = 551) or total root replacement (n = 67). The allografts were antibiotic sterilized (n = 479), cryopreserved (n = 12), or viable (unprocessed, harvested from brain-dead multiorgan donors or heart transplant recipients, n = 127). Maximum follow-up was 27.1 years. RESULTS: Thirty-day mortality was 5.0%, and crude survival was 67% and 35% at 10 and 20 years. Ten- and 20-year rates of freedom from complications were as follows: endocarditis, 93% and 89%; primary tissue failure, 62% and 18%; and redo aortic valve replacement, 81% and 35%. Multivariable Cox analyses identified several valve- and procedure-related determinants: rising allograft donor age and antibiotic-sterilized allograft for mortality; donor more than 10 years older than patient for endocarditis; rising donor age minus patient age, rising implantation time (from harvest to aortic valve replacement), and donor age more than 65 years for tissue failure; and rising donor age minus patient age, young patient age, rising implantation time, and subcoronary implantation preceded by aortic root tailoring for redo aortic valve replacement. Estimated 10- and 20-year rates of freedom from tissue failure for a 70-year-old patient with a viable valve from a 30-year-old donor and no other risk factors were 91% and 64%; the figures were 71% and 20% if the donor age was 65 years. The rates of freedom from tissue failure for a 30-year-old patient with a 30-year-old donor were 82% and 39%; the figures were 49% and 3% with a 65-year-old donor. Beneficial influences of a viable valve were largely covered by short harvest time (no delay for allografts from brain dead organ donors or heart transplant recipients) and short implantation time. CONCLUSIONS: Primary allograft aortic valve replacement can give acceptable results for up to 25 years. The late results can be improved by the use of a viable allograft, by matching patient and donor age, and by more liberal use of free root replacement with re-implantation of the coronary arteries rather than tailoring the root to accommodate a subcoronary implantation.
BACKGROUND: For many years the central focus of research into gastrointestinal hypersensitivity reactions has been the mast cell population of the intestinal lamina propria. Since bile is known to deliver immunological mediators to the gastrointestinal tract, the possibility arises that extra-intestinal populations of mast cells may also contribute to IgE-mediated intestinal damage. OBJECTIVES: To characterize hepatic mast cells in the rat and to investigate the role of the hepatobiliary system in a model of IgE-mediated reactivity to dietary antigen. METHODS: Wistar rats were passively sensitized with monoclonal antidinitrophenyl (DNP) IgE antibodies, and were later challenged orogastrically with DNP-HSA. Additional animals were sensitized, then bile duct-cannulated prior to antigen challenge. At various time points, liver and intestinal samples were collected for histological examination, and bile was collected and assayed for histamine and TNFalpha. RESULTS: Hepatic mast cells display a mucosal mast cell-like phenotype, and are closely associated with the vessels of the portal triads. Orogastric antigen challenge led to a rapid and significant decline (P<0.0001) in detectable mast cells as a result of anaphylactic degranulation. The median number of granulated mast cells associated with each portal triad in liver sections declined from six per portal triad to one per portal triad post-antigen challenge. After 15 min, biliary histamine concentrations rose above background levels (P<0.01). TNFalpha was also detectable in the majority (4/6) of bile samples within 15 min of challenge. Histological examination of the gastrointestinal mucosa revealed disruption to the villous epithelium ranging from oedematous changes to gross destruction. Such damage was not seen in animals in which bile had been externally drained. CONCLUSION: The data indicate that biliary products are major contributors to the gastrointestinal damage arising from IgE-mediated hypersensitivity reactions in the rat, and such hypersensitivity reactions may involve a population of mast cells which reside in the liver.
BACKGROUND: Increasing pressure on limited NHS resources has led to the introduction in primary care of a skill mix which seeks to match clinical presentation to an intervention based on skills and training. There has also been increasing emphasis on the use of telephone consultations. However, outcomes on the benefits of these different approaches may be difficult to obtain and process variables such as the views of patients may be important. OBJECTIVE: The objective of the study was to answer the following questions (i) how many existing GP consultations do doctors and patients assess as being suitable for consultation with a specially trained nurse or for telephone advice from a doctor?; (ii) do doctors and patients share similar views on the suitability of individual cases?; and (iii) do these assessments differ between acute, chronic and urgent cases? METHOD: A sample of 750 patients comprising of 150 patients attending for booked consultation with each of five doctors were interviewed prior to the consultation and asked whether they would be happy to see a specially trained practice nurse or if their problem could be dealt with by a doctor on the telephone. For each case the GP gave his response. A similar study was undertaken with 150 'extras' patients who needed to be seen urgently and who could not wait for an appointment the following day. The viewpoint of the GP was compared with that of the patient. RESULTS: GPs felt that 20% of all booked cases could be seen by a nurse compared with the patients' assessment of 29%. These figures were higher for acute booked cases (30 and 34%) and for urgent extras (44 and 58%). There was a poor agreement between the viewpoints of doctor and patient especially for chronic booked cases although this agreement increased with the more acute presentations. The number of cases that could be dealt with on the telephone ranged from 5 to 9% with poor agreement between doctor and patient. CONCLUSION: This study extends the findings of a number of others which indicate that patients can be seen satisfactorily by nurses, and that both doctors and patients see scope for increasing the number of consultations dealt with by nurses. Booked patients with chronic presentations and urgent extras are more likely than their doctors to think that they could be dealt with by the nurse. This may be due to a difference in perspective between doctors and patients about the outcome they hope to achieve in the consultation. Further qualitative work is needed to explore these differences and to clarify the best approach to this expanding area.
This study documented bone loss at three different sites in the early postmenopausal period, and examined potential predictors. Forty-three women underwent repeated measurements of bone density at the lumbar spine, proximal femur and distal radius for up to 14 years. Individual rates of bone loss were calculated for the spine and hip; for radial trabecular bone, rates were calculated separately for two time periods, earlier and later after menopause. In the spine and radius, initially high rates of loss diminished with time after menopause. No positive correlations for bone loss were found between the three sites, suggesting that faster than average bone loss was specific to individual bones. High body mass index (BMI) was significantly protective against fast bone loss at the spine and radius; in the spine, each unit increase in BMI was associated with a approximately 5% reduction in the rate of bone loss. Of the other variables measured (maximum oxygen consumption, lean body mass, fat mass, mean psoas muscle area at the L3 level, hand grip strength as well as anthropometry) only bone densitometry was sufficiently predictive to help guidance on hormone replacement or other prophylactic therapy. The data suggest that the known relationship between excessive leanness and risk of osteoporosis and vertebral fracture after menopause might in part be due to fast post-menopausal bone loss. Because bulk of psoas muscle was associated with low spine loss rates, the data also support a role for applied muscular loading in local maintenance of bone density.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The pattern of histone H4 acetylation in different genomic regions has been investigated by immunoprecipitating oligonucleosomes from a human lymphoblastoid cell line with antibodies to H4 acetylated at lysines 5, 8, 12 or 16. DNA from antibody-bound or unbound chromatin was assayed by slot blotting. Pol I and pol II transcribed genes located in euchromatin were shown to have levels of H4 acetylation at lysines 5, 8 and 12 equivalent to those in input chromatin, but to be slightly enriched in H4 acetylated at lysine 16. In no case did the acetylation level correlate with actual or potential transcriptional activity. All acetylated histone H4 isoforms were depleted in non-coding, simple repeat DNA in heterochromatin, though the extent of depletion varied with the type of heterochromatin and with the isoform. Two single copy genes that map within or adjacent to blocks of paracentric heterochromatin are depleted in H4 acetylated at lysines 5, 8 and 12, but not 16. Consensus sequences of repetitive elements of the Alu family (SINES, enriched in R bands) were associated with H4 that was more highly acetylated at all four lysines than input chromatin, while H4 associated with Kpn I elements (LINES, enriched in G bands) was significantly underacetylated.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
BACKGROUND: Strokes that occur during coronary artery bypass grafting are often caused by embolism. Intraoperative transcranial Doppler monitoring can detect cerebral microemboli. The aims of this study were to identify the pattern of microembolic phenomena during various stages of coronary artery bypass grafting, to verify whether numbers of high-intensity transient signals correlated with early neuropsychologic deficits, and to identify, using magnetic resonance imaging scans, whether radiologic evidence of cerebral infarction correlated with microembolic numbers during the bypass period. METHODS: Forty-one consecutive patients undergoing coronary bypass grafting with transcranial Doppler monitoring were enrolled in this study. All had preoperative and postoperative magnetic resonance imaging brain scans. A subgroup of 32 patients were studied by comparing microembolic load and early neuropsychological outcomes. RESULTS: Transcranial Doppler monitoring confirmed that most microemboli occurred during cardiopulmonary bypass. A significant early neuropsychological deficit after coronary artery bypass grafting did correspond to the total microembolic load during bypass (p = 0.008). However, patients with cerebral infarction on magnetic resonance imaging had significantly more microembolic signal during the preincision phases and not during the bypass period. CONCLUSIONS: Microembolic load during bypass is associated with early neuropsychologic deficits. In contrast, patients who show evidence of strokes during coronary artery bypass grafting have a higher microembolic load during the preincision phase than those without cerebral infarction. Differing mechanisms may be responsible for these different outcomes.