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A Mitchell

Publications and source records attributed to A Mitchell.

At least 19 recordsLinked to original sources
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

Determination of the test performance of less costly methods of Helicobacter pylori detection.

Since Helicobacter pylori (Hp) has become so important in the management of peptic ulcers, it is imperative that noninvasive and inexpensive methods of diagnosis be available. The objective of this prospective, double-blind study was to determine the performance of the noninvasive 14C-urea breath test and the less expensive hematoxylin-phloxin-saffron (HPS) and Giemsa stains in the detection of this infection. As well, we set out to determine the minimal number of biopsies required to make an accurate diagnosis. Fifty consenting adults referred for gastroscopy underwent antral biopsies for HPS, Giemsa and Steiner silver staining and a 14C-urea breath test. The ability of HPS, Giemsa, and the breath test to differentiate between the presence or absence of Hp infection as defined by the silver stain was assessed using contingency table analysis. Hp was detected in 24 patients with the silver stain. Half of these patients had evidence of ulcer disease, compared to 3 of 26 patients who were negative for Hp on silver stain (p < 0.01). The Hp positive group were more frequently male (62% vs. 31%, p < 0.05) and more often had chronic active gastritis (96% vs. 7.7%, p < 0.001). The sensitivity of the breath test, HPS, and Giemsa stains were 95.8% (95% confidence interval: 79-100%), 75% (53-90%), and 95.8% (79-100%), respectively. Specificity was 100% (87-100%) for all 3 methods of detection. The breath test was also able to discriminate between heavily infected and moderately infected patients as defined by silver stain (p < 0.05), and could be shortened from 30 to 15 min without any loss of accuracy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Experience of an implantable central venous access system in a district general hospital.

Reliable access to a central vein is increasingly important in the treatment of major acute and chronic disease. The use of an implantable central venous access device in a district general hospital is reviewed. Fifty-four PortaCaths (Kabi Pharmacia, Milton Keynes, UK) were inserted in 51 patients over a 7-year period. Most patients had haematological disease, often with neutropenia and thrombocytopenia. There were a total of 22,515 catheter days experience. Twelve catheters were removed for complications with an overall complication rate of 0.93/1000 catheter days. There were four line infections and four episodes of periport sepsis. Occasional catheter thrombosis was usually cleared with urokinase. Neutropenic and immunocompromised patients had an increased complication rate. PortaCaths were well tolerated by patients and required minimum maintenance. An implantable central venous access device proved safe and reliable for use in a district general hospital.

Adolescent↗
PubMed1993

Chordoma and chondroid neoplasms of the spheno-occiput. An immunohistochemical study of 41 cases with prognostic and nosologic implications.

BACKGROUND: Chordomas are rare neoplasms that show a proclivity for the spheno-occiput and sacral regions. A "chondroid" variant involving the spheno-occiput has been associated with improved survival. "Classic" or nonchondroid chordomas are uniformly immunoreactive for keratins. Chondroid chordomas are said to be immunonegative for epithelial markers, a feature used to support the concept that they represent chondrosarcomas. METHODS: The authors performed immunohistochemical studies on 25 patients with chondroid chordoma (mean age, 40.0 years) and on 16 patients with classic chordomas (mean age, 44.2 years) to establish tumor subsets based upon immunophenotype, specifically reactivity for epithelial markers. Kaplan-Meier survival curves were then constructed for each group with age as an added variable. RESULTS: All classic chordomas reacted for keratins as did 8 (32%) of the 25 chondroid chordomas. Forty-four percent of classic and 85% of chondroid chordomas were positive for S-100 protein. At 5 years, all patients younger than 40 years of age were alive in both the classic and chondroid groups. In contrast, of patients older than 40 years of age, only 22% with classic chordomas and 38% with chondroid chordomas were alive. CONCLUSIONS: Regardless of tumor subtype, age is the single most important variable in determining survival; patients younger than 40 years of age do better than older patients. There are no significant survival differences between patients with cartilage-containing tumors that are keratin immunopositive ("true" chondroid chordoma) or negative (chondrosarcoma). Immunostaining for keratins is of no prognostic value in assessing chondroid lesions of the spheno-occiput.

Adult↗
PubMed1993

Cortical blindness and seizures possibly related to cisplatin, vinblastine, and bleomycin treatment of ovarian dysgerminoma.

Ovarian dysgerminoma is the most common ovarian malignancy in young women. Conservative treatment is indicated in the reproductive-age woman who wishes to preserve childbearing capacity. This case report describes a patient with ovarian dysgerminoma who underwent chemotherapy with a cisplatin-vinblastine-bleomycin regimen that resulted in serious toxic complications--including cortical blindness and seizures--that were transient in nature. Although current chemotherapy regimens have dramatically improved the overall survival of women with germ-cell tumors, there are toxic complications such as those demonstrated in this report, and toxicity must be balanced against presumed benefit.

Adult↗
PubMed1992

Maxepa versus bezafibrate in hyperlipidemic cardiac transplant recipients.

Accelerated coronary artery disease is the most serious obstacle to long-term survival in cardiac transplant recipients. Lipid abnormalities are found frequently in these patients, and there is growing evidence that even minimally increased levels of cholesterol and triglycerides contribute to the development of accelerated coronary artery disease. However, the optimal lipid-lowering therapy after cardiac transplantation has not been defined. In an open, randomized study, the efficacy and safety of bezafibrate (400 mg/day) and fish oil (Maxepa) (10 g/day) for 3 months were compared in 87 cardiac transplant recipients with serum total cholesterol > 6.5 or triglycerides > 2.8 mmol/liter, or both. After 1 month, bezafibrate reduced total cholesterol by 13%, low-density lipoprotein cholesterol by 20% and apolipoprotein B by 13%. It also increased apolipoprotein A1 and high-density lipoprotein cholesterol by 12 and 20%, respectively, and significantly reduced fibrinogen at 3 months. Maxepa had no significant effect on these variables, but was as effective as bezafibrate in reducing triglycerides (36 and 31%, respectively). Both drugs increased lipoprotein (a) to a similar extent, and bezafibrate significantly increased serum creatinine. These results suggest that bezafibrate has better lipid-, apolipoprotein- and hemostatic modifying properties than does Maxepa, but its potentially adverse effect on renal function needs further investigation.

Apolipoprotein A-I↗
PubMed1992

Antibodies to defined histone epitopes reveal variations in chromatin conformation and underacetylation of centric heterochromatin in human metaphase chromosomes.

Unfixed metaphase chromosome preparations from human lymphocyte cultures were immunofluorescently labelled using antibodies to defined histone epitopes. Both mouse monoclonal antibody HBC-7, raised against the N-terminal region of H2B, and rabbit serum R5/12, which recognizes H4 acetylated at Lys-12, gave non-uniform labelling patterns, whereas control antibodies against total histone fractions H4 and H1 produced homogeneous fluorescence. HBC-7 bound approximately uniformly to the bulk of the chromosomes, but the major heterochromatic domains of chromosomes 1, 9, 15, 16 and the Y showed significantly brighter fluorescence. Serum R5/12 indicated an overall reduction in acetylation of H4 in metaphase chromosomes compared with interphase nuclei, although some specific chromosomal locations had considerably elevated acetylation levels. Acetylation levels in the major heterochromatic domains appeared extremely low. To investigate further the differences noted in heterochromatin labelling, metaphases from cultures grown in the presence of various agents known to induce undercondensation of the major heterochromatic domains were similarly immunolabelled. Decondensed heterochromatin no longer exhibited higher than normal immunofluorescence levels with HBC-7. The higher resolution afforded by "stretching" the centromeric heterochromatin of chromosomes 1, 9 and 16 confirmed the low level of H4 acetylation in these domains. We consider the implications of these observations in relation to chromatin conformation and activity.

Acetylation↗
PubMed1992

The organisation of repetitive DNA sequences on human chromosomes with respect to the kinetochore analysed using a combination of oligonucleotide primers and CREST anticentromere serum.

The spatial relationship between the families of repetitive DNAs present at the centromeres of human chromosomes and the position of the kinetochore was examined by combining immunocytochemistry with the PRINS oligonucleotide primer extension technique. Heterochromatic domains were decondensed with 5'-azacytidine to facilitate this study. Using this approach our results clearly show that the alphoid DNA sequences are closely associated with the kinetochore of human chromosomes. Simple-sequence satellite DNAs occupy separate, non-overlapping domains within the centromere. These two major families are separated by a third, relatively low-copy repetitive DNA family, SAU-3A. Pulse-field gel electrophoresis was employed to analyse the centromeric domain of human chromosome no. 9 in more detail and the results although preliminary support the conclusions drawn from the immunocytochemistry/PRINS approach.

Antibodies, Antinuclear↗
PubMed1992

Dipyridamole vasodilator response after human orthotopic heart transplantation: quantification by oxygen-15-labeled water and positron emission tomography.

To assess coronary vasodilator reserve after orthotopic heart transplantation, regional myocardial perfusion was measured with oxygen-15-labeled water and dynamic positron emission tomography in 14 cardiac allograft recipients who were not experiencing rejection and who had no angiographic evidence of epicardial coronary sclerosis 15 to 73 months (mean +/- SD 43 +/- 19) after transplantation (group I). Twelve normal men with an average age of 31 years (group II) served as a control group. Regional perfusion was measured at rest and after the intravenous administration of 0.6 mg/kg body weight of dipyridamole. Rest regional myocardial blood flow was homogeneously distributed throughout the left ventricle and was significantly higher in transplant recipients (mean 1.16 +/- 0.26 ml/g per min [range 0.8 to 1.73] than in normal subjects (mean 0.85 +/- 0.13 ml/g per min [range 0.57 to 0.99]; p = 0.001) as was rest heart rate-systolic blood pressure product (rate-pressure product 11,255 +/- 2,540 vs. 7,073 +/- 1,306; p less than 0.001). After dipyridamole, perfusion in the transplant recipients was homogeneous and slightly lower (2.73 +/- 1.03 vs. 3.40 +/- 1.09 ml/g per min; p = NS), whereas rate-pressure product was slightly higher (12,179 +/- 2,266 vs. 10,885 +/- 1,895; p = NS) than the value in normal subjects. Dipyridamole vasodilator response (dipyridamole/rest myocardial blood flow) ranged from 1.23 to 4.92 (mean 2.50 +/- 1.13) in group I and from 2.65 to 5.45 (3.97 +/- 0.89) in group II (p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗