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Biomedical subjects

A Mitchell

Publications and source records attributed to A Mitchell.

At least 145 records · Page 8Linked to original sources

Radial cortical and trabecular bone densities of men and women standardized with the European Forearm Phantom.

We previously showed that it is possible to cross-calibrate peripheral bone densitometers using the European Spine Phantom (ESP). We have now performed a multinational study of cross-calibrated radius bone density based on normal subjects of both sexes in eight European centers. Six centers were equipped with machines made by Scanco or Stratec for determining distal radial trabecular bone density by quantitative computed tomography (QCT) and two were equipped with Lunar SP2 single photon absorptiometry (SPA) equipment for measuring midshaft cortical bone density. Subjects recruited ranged from 20 to over 80 years of age. Over one hundred and fifteen men were studied by QCT and a different cohort of 104 men were studied with SPA; the equivalent figures for women were 235 and 123. Reference ranges were derived for bone density against age for each of the four groups, and their applicability is discussed in relation to between-center differences in the results obtained. There were insignificant differences (P > 0.05 with Bonferroni correction) between centers in the values obtained by QCT in the different populations. However, there were considerably larger and highly statistically significant differences between midshaft cortical bone density values of about 10% of overall means between subjects from eastern Finland and central Belgium (P < 0.001), with higher Finnish values. Women had considerably lower radial trabecular bone density values than men at all ages, a result that differentiates the radius from the spine. This sex difference widened after menopause. These results have important implications for understanding the contribution of bone density to the differential risk of Colles' fracture in the two sexes and suggest that further work is needed to establish young normal reference ranges for radial bone density in Europe.

Absorptiometry, Photon↗

Determination of apolipoprotein mRNA levels by ribonuclease protection assay.

The ribonuclease protection assay procedure described enables the relative quantitation of either single mRNAs or multiple mRNA species simultaneously in a sample of total RNA and demonstrates its applicability to two systems of relevance to the study of apolipoproteins, namely, liver tissue and liver-derived cell lines in culture. The main requirements of the method are the availability of cDNA cloned into a vector that directs the transcription of antisense RNA for the preparation of radioactive probes, and choice of suitable restriction endonuclease sites for linearizing the cDNA so that the final protected products of the various mRNA species are sufficiently different in size to allow their separation. For moderately abundant apolipoprotein mRNAs in rat liver, the method is sensitive down to 1 microgram total RNA. Other experimental sources of RNA or the assay of less abundant mRNA species may require a larger amount of starting material. These aspects of the assay need to be determined for each probe/ tissue system to be studied. The need for adjustments to the specific radioactivity of the probes will depend on the relative abundance of the target mRNA molecules and can be readily determined empirically. The rationale for varying the specific radioactivities to facilitate multiple assays as suggested here is both simple and effective. A preliminary assay provides information on the relative levels of the mRNA species of interest, and the step of preparing, in parallel, a sample of unlabeled antisense RNA provides the means for quantitative dilution of specific radioactivity of the 32P-labeled RNA probe where required.

Animals↗

Familiarization with complementary medicine: report of a new course for primary care physicians.

A course entitled "Familiarization in Complementary Medicine" has been established at Exeter University. The syllabus of the course is presented, together with significant issues for debate that were raised by the attending primary care physicians. The delegates started with a positive but questioning attitude toward complementary medicine (CM) and acknowledge that they gained useful information, leading to increased confidence in discussing CM with patients. The course to a large extent met their needs and expectations. Benefits and draw-backs of integrating CM within general practice were explored. The main advantage of CM, apart from the potential intrinsic value of the techniques themselves, was identified as the time to establish a good therapeutic relationship with the patient. The particular concerns about CM that were expressed by the doctors included poor dialogue with CM practitioners, doubts about competence, and lack of readily identifiable and recognized qualifications. The risk of holding out unrealistic hope of cure was their greatest concern, however, especially if patients were thereby denied an effective orthodox treatment. The course was popular and will be repeated on a regular basis; similar courses for other health professionals including nurses are being planned.

Attitude of Health Personnel↗

Striving to prevent falls in an acute care setting--action to enhance quality.

Although most falls do not result in serious physical injury, they can contribute to a loss of confidence and mobility which can culminate in a significant reduction in quality of life. Furthermore, the potential to fall is often increased when an individual is institutionalized because of frailty or confusion. The purpose of the study was, therefore, to establish whether a structured intervention would assist in preventing falls in an acute setting. This pre-test/post-test study was carried out over a 12-month period. Interventions included risk assessment, an alert system, reinforcing preventive actions, staff education and ongoing audits and feedback. Initial analysis of the data and comparison of fall rates indicated a significant reduction in the rate of falls between the pre- and post-intervention phases, although subsequent statistical analysis did not identify any significant relationships. It must be noted that no controls existed for extraneous variables, although patient profiles varied minimally during the period of the study. Outcomes include: a reduction in fall numbers and rates, enhanced staff morale with ownership of the programme, provision of a learning experience for staff (on which to build), and the fostering of a professional approach to improving the quality of patient care.

Accidental Falls↗

The one-stop coronary cholesterol clinic: a multidisciplinary approach to implementing evidence-based treatment.

We describe a 'one-stop' cholesterol clinic implementing a regime based on the Scandinavian Simvastatin Survival Study (4S) in patients with established coronary heart disease in a district general hospital. The clinic has been established in collaboration with the cardiac rehabilitation centre. It was commissioned as an audit project by the purchasing authority, Walsall Health, a need having been shown in a previous audit. In the new clinic, audit is inbuilt, rather than being carried out as a separate retrospective exercise, and undertaken prospectively for all patients. Central to this is a database, used for routine correspondence and administration, as well as monitoring outcome. This application of information technology has improved clinical practice. Attendance at the clinic has been excellent. Half the consultations have resulted in therapeutic interventions, many of which may otherwise have been missed. Over 50% of patients were eligible for lipid-lowering medication under the protocol. Cholesterol targets based on 4S were achieved but with much lower drug doses, which may have major cost implications. Cholesterol levels measured within 24 hours of admission for myocardial infarction were poor predictors of results obtained after convalescence. After the clinic visit, most patients were taking aspirin plus one or two other secondary prevention treatments. Guidelines have been issued to primary care. Future plans for audit links with general practitioners, integration of the metabolic and cardiological assessment of survivors of myocardial infarction, and for long-term monitoring of clinical events in treated patients are discussed.

Aged↗

Juxtacortical dedifferentiated chondrosarcoma from a primary periosteal chondrosarcoma.

In this report, we describe dedifferentiation in a primary periosteal chondrosarcoma in the proximal tibia of a 73-year-old man. The diagnosis of primary periosteal chondrosarcoma was made by the characteristic radiographic, gross, and microscopic features of the tumor. The presence of dedifferentiation, however, in the form of malignant fibrous histiocytoma, was an unexpected histologic finding. Although rare, dedifferentiation is a well-recognized occurrence in secondary chondrosarcomas arising from precursor osteochondromas. This event has not been previously documented in the setting of primary periosteal chondrosarcoma.

Aged↗

Direct and continuous assessment by cells of their position in a morphogen gradient.

According to the morphogen gradient concept, cells in one part of an embryo secrete diffusible molecules (morphogens) that spread to other nearby cells and activate genes at different threshold concentrations. Strong support for the operation of a morphogen gradient mechanism in vertebrate development has come from the biochemical experiments of Green and Smith, who induced different kinds of gene expression in amphibian blastula cells exposed to small changes in activin concentration. But the interpretation of these experiments has been complicated by recent reports that cells tested for gene expression 3 hours after exposure to activin fail to show the graded response previously reported at 15 hours, a result suggesting that cells recognize their position in a gradient by an indirect mechanism. Here we conclude from the in situ analysis of blastula tissue containing activin-loaded beads that cells respond directly to changing morphogen concentrations in a way that resembles a ratchet-like process.

Activins↗

Evolution of spinal bone loss and biochemical markers of bone remodeling after menopause in normal women.

The main objective of this study was to describe longitudinal patterns of spinal bone loss in normal women who undergo a natural menopause. The second objective was to determine if a proportion of women suffer excessively rapid postmenopausal bone loss from the spine. If this was the case it was the aim to devise a means of predicting the woman at excess risk; but if all women lost bone at similar rates, the aim was to document changing loss rates over the first 5-8 postmenopausal years. Responding women in six suburban general practices recalled for cervical smears who had their last menstrual period 9- 36 months previously were invited to participate in a longitudinal study of bone loss and the biochemical markers plasma osteocalcin and urinary hydroxyproline. Sixty-four subjects agreed to participate, a response rate of 80%. In the ensuing 5 years, six received hormone replacement therapy and are not reported on. The main outcome measures were rates of spinal bone loss over 5 years, measured by dual photon absorptiometry, and radial bone loss over the first 2 years measured to quantitative computed tomography. Spinal bone loss was similar between individuals, with 94% of the variability in the data being accounted for by a statistical model that assumed parallel rates of bone loss. A less restrictive model allowing women to have different rates of spinal bone loss accounted for 12% more of the remaining variance in the data than the previous model. However, rates of radial bone loss were more dissimilar between women than rates of spinal loss. The results of the biochemical data collected serially showed that the plasma osteocalcin rose slowly to a plateau at 5 years postmenopause; in contrast, the hydroxyproline fell progressively with time over the whole period of study. These results were interpreted as being consistent with diminishing rates of bone destruction which gradually reequilibrated with bone formation as time passed after menopause.

Absorptiometry, Photon↗

Use of certainty of opinion data to enhance clinical decision making.

Clinical decision making and diagnostic testing procedures are frequently evaluated using indices such as sensitivity and specificity. These indices require an assumption that the underlying disease state or the diagnostic test result is binary, which may be an unreasonable assumption in many clinical situations. They also fail to recognise the potential for different degrees of diagnostic confidence. In this paper, we report some data from a clinical study of postpartum mothers in which, in addition to the diagnostic result, an expression of certainty or strength of belief was ascertained. We illustrate how the certainty of opinion data can be combined with the diagnostic opinion in order to enhance the interpretation of the study, and the implications for improving the accuracy of clinical decision making in general.

Decision Making↗

Measuring patient and relative satisfaction with level or aggressiveness of care and involvement in care decisions in the context of life threatening illness.

The objective of the study was to develop valid and reliable discriminative indices which measure patient and relative satisfaction with two closely related aspects of medical care: the level of care received and their involvement in decisions regarding care. We generated items by literature review and interviews with patients, relatives, and health care providers. In the final questionnaires, we included the items identified most frequently as sources of dissatisfaction and rated most important by 102 patients and 153 relatives. To measure reliability and validity we administered the instruments to 105 patients and 75 relatives of competent patients and 89 relatives of incompetent patients. We constructed three questionnaires: the Patient Satisfaction Index with 23 items, the Relative of Competent Patient Satisfaction Index with 34 items, and the Relative of Incompetent Patient Satisfaction Index with 29 items. We found mean scores of 75-80% of the maximum possible score, with a wide range of scores. The intraclass correlation for the instruments varied from 0.86 to 0.94. Correlations with global ratings were high (0.59-0.75) and similar to predictions. Correlations with caregiver ratings were lower than predicted (0.18-0.22). For both patients and relatives, our instruments discriminate between those with higher and lower satisfaction with the level of medical care and with their involvement with decision-making.

Aged↗

Fourteen-year experience with homovital homografts for aortic valve replacement.

Two hundred seventy-five unprocessed, viable homograft ("homovital") aortic valves were used for aortic valve replacement in patients aged 1.5 to 79 years (mean 45.8 +/- 19 years) with maximum follow-up of a 14-year period (mean 4.8 years). Ninety-two percent (252 patients) had New York Heart Association class III or IV functional status before operation and 25 underwent emergency operation. Valves were harvested under sterile conditions and kept in nutrient medium 199. Freehand (subcoronary) technique was used in 147 patients and freestanding root replacement was used in 128. Cumulative survival rates for the whole group were 92% +/- 2% at 5 years and 85% +/- 3% at 10 years, as compared with 96% +/- 2% and 94% +/- 4%, respectively, for the 98 patients who underwent isolated root replacement. Multivariate analysis determined that root replacement with associated procedures and operation for prosthetic endocarditis were risk factors for death, whereas previous xenograft valve, operation for endocarditis, and operation for aortic regurgitation were risk factors for reoperation. Actuarial rates for freedom from degenerative valve failure diagnosed at operation, by postmortem examination, or by routine echocardiography were 94% +/- 2% at 5 years and 89% +/- 3% at 10 years. Recipient age younger than 30 years and previous xenograft valve were risk factors for late degeneration. We conclude that homovital valves demonstrate good durability, particularly in patients older than 30 years, who had a 10-year freedom from degeneration rate of 97%.

Adolescent↗

Neuromuscular choristoma.

Neuromuscular choristomas are rare, with only 13 cases having been previously reported. They usually arise in association with large nerves, and most often occur in the first decade of life. A few have been congenital. Although resection is typically curative, in two instances partial resection alone appears to have been followed by spontaneous regression. The authors report an unusual example of an otherwise classic neuromuscular choristoma where the lesion appeared to grow after incomplete initial resection. Re-excision disclosed a fibromatosis unassociated with choristoma. Despite its wide excision, a recurrence of the fibromatosis required a forequarter amputation. Theories of histogenesis and the clinicopathologic features of the neuromuscular choristomas reported to date are reviewed. The term "benign Triton tumor," although incorrectly applied to this lesion, should be reserved for benign, true nerve sheath neoplasms exhibiting myogenic differentiation.

Axilla↗

A highly conserved nuclear gene for low-level phylogenetics: elongation factor-1 alpha recovers morphology-based tree for heliothine moths.

Molecular systematists need increased access to nuclear genes. Highly conserved, low copy number protein-encoding nuclear genes have attractive features for phylogenetic inference but have heretofore been applied mostly to very ancient divergences. By virtue of their synonymous substitutions, such genes should contain a wealth of information about lower-level taxonomic relationships as well, with the advantage that amino acid conservatism makes both alignment and primer definition straightforward. We tested this postulate for the elongation factor-1 alpha (EF-1 alpha) gene in the noctuid moth subfamily Heliothinae, which has probably diversified since the middle Tertiary. We sequenced 1,240 bp in 18 taxa representing heliothine groupings strongly supported by previous morphological and allozyme studies. The single most parsimonious gene tree and the neighbor-joining tree for all nucleotides show almost complete concordance with the morphological tree. Homoplasy and pairwise divergence levels are low, transition/transversion ratios are high, and phylogenetic information is spread evenly across gene regions. The EF-1 alpha gene and presumably other highly conserved genes hold much promise for phylogenetics of Tertiary age eukaryote groups.

Animals↗

Population pharmacodynamics of romazarit.

1. The response to romazarit, a disease modifying anti-rheumatoid agent, was observed in patients with rheumatoid arthritis (RA) in a double-blind placebo controlled study. 2. Two hundred and twenty-four patients were recruited from 11 centres and treated with placebo or romazarit at a dose of 200 mg or 450 mg every 12 h for up to 24 weeks. Disease activity was measured using the Ritchie Index (RI). Plasma concentrations of romazarit were measured at each of up to eight assessments of RI. 3. The effect of romazarit was examined using analysis of variance (ANOVA) in 164 patients who contributed 61% of observations of disease activity. Observations after 12 weeks of treatment were excluded from ANOVA. 4. A population pharmacokinetic-dynamic model for the time course of disease progress and the response to placebo and romazarit was used to describe observations from all patients. 5. The population model suggested that the effect of romazarit was on the rate of progress of the disease and was describable by an Emax model. Concentration was a better predictor of response than dose. 6. Romazarit was significantly better than placebo in improving the RI in patients with RA. The placebo efficacy of romazarit treatment was similar to that associated with placebo treatment. 7. The population model provided a more complete description and explanation of the clinical pharmacology and therapeutic potential of romazarit than ANOVA.

Administration, Oral↗

The value of sonography in the diagnosis of traumatic rupture of the anterior cruciate ligament of the knee.

OBJECTIVE: The purpose of this study was to test the efficacy of sonography in the diagnosis of rupture of the anterior cruciate ligament in the setting of a recent traumatic hemarthrosis. SUBJECTS AND METHODS: Sonography was prospectively performed in 37 patients with a recent traumatic hemarthrosis of the knee, no bone abnormality seen on plain radiographs, and no history of a previous knee injury. The presence of a hypoechoic collection along the lateral wall of the femoral intercondylar notch was interpreted as a hematoma at the femoral attachment of the anterior cruciate ligament. Arthroscopy was subsequently performed in 30 patients. The findings of three diagnostic techniques (sonography, MR imaging, and arthroscopy) were compared. RESULTS: The sonographic findings were confirmed by MR imaging and arthroscopy in 34 of the 37 patients. For the three false-negative results, sonographic findings were abnormal but equivocal in two cases and were reported as negative. The technique was therefore 91% sensitive and 100% specific. The positive predictive value was 100%. The negative predictive value was 63%. CONCLUSION: Sonography is a useful and inexpensive method of detecting the presence of rupture of the anterior cruciate ligament in the clinical setting of a traumatic hemarthrosis.

Adolescent↗