Inheriting an ethical dilemma.
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Education, Nursing, Continuing↗
Biomedical subjects
J Denton
Publications and source records attributed to J Denton.
Quantification of vitamin D receptor mRNA in tissue sections demonstrates the relative limitations of in situ-reverse transcriptase-polymerase chain reaction.
In situ-reverse transcriptase-polymerase chain reaction (IS-RT-PCR) is a recently described technique that is used to localize low levels of mRNA within cells and tissue sections. One of the major criticisms levelled at this technique is that positive results may be meaningless, as amplification is required to demonstrate the transcripts of interest. The use of IS-RT-PCR to demonstrate mRNA for receptors for 1,25-dihydroxyvitamin D3 (VDR) in sections of human kidney and bone has previously been described. To ascertain whether the levels of VDR mRNA detected following IS-RT-PCR were transcriptionally significant, computerized image analysis was used to determine the mean silver grain density in human kidney and bone cells following conventional in situ hybridization and after various cycles of IS-RT-PCR. Only a few cycles of PCR were needed to produce an optimum signal, but amplification of signal following IS-RT-PCR was found to be relatively inefficient. Following the optimum number of cycles of IS-RT-PCR in kidney sections, there was a less than four-fold increase in signal. Similarly, in bone, the optimum signal detected was only approximately five times greater than that found with conventional in situ hybridization. These results clearly demonstrate that the increase in signal following IS-RT-PCR follows a more linear pattern and is relatively inefficient, compared with the usual exponential increase with conventional solution phase RT-PCR.
Bone and Bones↗
Differential patterns of osteoblast dysfunction in trabecular bone in patients with established osteoporosis.
AIMS: To analyse osteoblast function in 153 cases of established osteoporosis as previous work has indicated that osteoporosis is a heterogeneous condition characterised by different patterns of osteoclast and osteoblast dysfunction. METHODS: Histomorphometric data from 153 cases with established osteoporosis was used to analyse osteoblast function, using the following parameters: osteoblast number was assessed using the ratio of osteoblast surface to bone surface (ObS:BS); the percentage of active osteoblasts was assessed by using mineralising surface as a proportion of osteoid surface (sLS + dLS/OS); and the efficiency of active osteoblasts was assessed using the ratio of double to total labelled surface (dLS:tLS). The values of each parameter were standardised using age and sex matched control data and a three dimensional matrix was used to identify groups of patients with similar patterns of altered function. RESULTS: The largest group (60 cases) showed a reduction in all three parameters, while a small group (9 cases) had normal osteoblast function. However, one group showed reduction in osteoblast number only (23 cases), while another group showed a normal number of osteoblasts but both reduced percentage and efficiency of activity (14 cases). The results also suggest that efficiency of activity falls first and that this eventually leads to exit from the active pool. CONCLUSIONS: These results demonstrate the presence of heterogeneity of osteoblast dysfunction in osteoporosis, indicating that the disease is caused by interference at a variety of target sites along the pathway of osteoblast proliferation, differentiation, and activation. Greater understanding of this pathway and of the variety of alterations in the pathway that can occur in osteoporosis may allow more focused therapy for different patient groups identified on the basis of histomorphometric analysis.
Cell Count↗
Overuse foot and ankle injuries in ballet.
Incorrect techniques repeated daily by a dancer can lead to overuse injuries. This article discusses the causes and treatment of foot and ankle injuries in the ballet dancer. The author also addresses skin lesions that are common in dancers who wear pointe shoes.
Ankle Injuries↗
Educating nurses--the assisted conception nursing care course of the RCN Institute.
The Assisted Conception Nursing Care course of the Royal College of Nursing Institute is approaching its 5 yearly review. This professionally and academically validated course was designed in collaboration with the Fertility Nurses Group to meet the needs of those in specialist practice who are taking an increasingly significant role in the care of those needing support and treatment for fertility problems. The 6 month part-time course addresses areas as diverse as physiology and pharmacology, behavioural sciences and ethical, legal and cultural issues. There is also an emphasis on research awareness and the analysis of nursing and social policy. The course draws nurses from a wide area within the UK who particularly value the opportunity to share ideas and construct ongoing networks.
Education, Nursing↗
Mycobacterium xenopi--an unusual presentation as tenosynovitis of the wrist in an immunocompetent patient.
Mycobacterium xenopi is an atypical acid-fast bacillus which may colonize tap water supplies. It typically causes pulmonary infection, particularly in patients with pre-existing lung damage, and non-pulmonary involvement is rare. We describe the first reported case of tenosynovitis due to this organism in an immunocompetent male patient.
Aged↗
Histomorphometric classification of postmenopausal osteoporosis: implications for the management of osteoporosis.
AIMS: To define and group static and dynamic iliac crest histomorphometric parameters in women with established osteoporosis. METHODS: Iliac crest biopsy specimens from 146 white women were sectioned undecalcified and examined using image analysis. RESULTS: Five distinct groups were defined on the basis of histomorphometric changes in cell function: group 1, decreased osteoblastic and osteoclastic activity; group 2, decreased osteoblastic and increased osteoclastic activity; group 3, increased osteoblastic and osteoclastic activity; group 4, no bone surface cell activity; and group 5, apparently normal osteoblastic and osteoclastic activity. CONCLUSIONS: Five distinct subgroups of patients with postmenopausal osteoporosis can be defined based on changes in bone cell function. Defining cellular dysfunction in this way may be important for tailoring treatment regimens to the needs of individual patients.
Age Factors↗
Managing multiple births. Part 2: Conception and beyond.
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Female↗
Intravenous pamidronate: evolution of an effective treatment strategy.
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Aged↗
Age related histomorphometric changes in bone in normal British men and women.
AIMS: To define the iliac crest histomorphometry of static variables in 234 individuals aged 16-100 years (91 men, 143 women) and of dynamic variables in 84 individuals aged 19-94 years (33 men, 51 women) from the North West of England. METHODS: Iliac crest biopsy specimens were sectioned, undecalcified, and examined using image analysis. RESULTS: The decrease in the quantity of cortical and trabecular bone and the connectivity of trabecular bone was more pronounced in women than men. This was associated with a reduction in bone formation and increased bone resorption which was greater in women at both the tissue and cellular level. Some of these histomorphometric differences first became evident at the natural menopause, and therefore provide clues as to the cause of the high prevalence of osteoporosis in postmenopausal women. CONCLUSIONS: These results show an age and sex dependent variation both in static and dynamic parameters, which differ, in some respects, from other studies and confirm the need for large regional studies to provide a database of normal morphometric results for a specific population.
Adolescent↗
Mast cells in the synovium and synovial fluid in osteoarthritis.
SF and synovium from normal individuals and patients with OA, RA and traumatic arthritis (TA) were studied for the presence of mast cells (MC). When compared with normals, patients with OA had large numbers of intact and degranulated MC in the synovium and SF of diseased joints. The numbers of MC are comparable with those in RA where they have been implicated in the pathogenesis of joint damage. These data raise the possibility that in OA too MC may participate in the pathological processes in articular and periarticular tissues.
Adult↗
Possible clearance of effete polymorphonuclear leucocytes from synovial fluid by cytophagocytic mononuclear cells: implications for pathogenesis and chronicity in inflammatory arthritis.
A feature common to all forms of chronic inflammatory arthritis, irrespective of the possible underlying cause, is the persistent exudation of large numbers of polymorphonuclear leucocytes (PMNL) into synovial fluid. These cells possess potent degradative enzymes and proinflammatory mediators, and their removal is vital to normal inflammatory resolution. A major route of disposal of extravasated PMNL appears to be programmed cell death (apoptosis), followed by their rapid recognition, and intact phagocytosis, by mature tissue macrophages. Such macrophages, containing PMNL (cytophagocytic mononuclear cells (CPM)), long recognised in synovial fluid as Reiter cells, are commonly found in reactive arthritis, spondyloarthritis, and crystal arthritides, but only rarely in rheumatoid disease. In a retrospective analysis of 187 knee synovial fluid cytospins, the relation between the formation of CPM and the presence of apoptotic (pyknotic) PMNL was investigated. As long as the synovial fluid examined was fresh there was a high correlation between numbers of CPM (as a percentage of macrophages) and pyknotic numbers of PMNL in fluids containing CPM. This suggests that the formation of CPM occurs in vivo and is involved in the disposal of PMNL. Numbers of pyknotic PMNL increased rapidly in stored synovial fluid without a significant change in numbers of CPM, and were highest in synovial fluid which did not contain CPM. The presence or absence of CPM, or their disease associations, could not be explained simply by limiting numbers of macrophages, or apoptotic PMNL in synovial fluid. These findings are consistent with a regulatory role for CPM in synovial fluid, where they may be important in preventing autolysis of PMNL, and thus local tissue damage.
Apoptosis↗
Refrigeration preserves synovial fluid cytology.
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Arthritis↗
Camelford water poisoning accident: serial neuropsychological assessments and further observations on bone aluminium.
The serial cognitive assessment of ten individuals made between 8 and 26 months after the water at Camelford in Cornwall was accidentally contaminated with aluminium sulphate, showed consistent evidence of impairment of information processing and memory. There was no obvious relationship between these impairments and measurements of anxiety and depression. Serial bone biopsies in two individuals showed that the aluminium which was present 6 and 7 months after the accident had disappeared by 19 months. In the eight individuals biopsied 12-17 months after the accident the bone showed no stainable aluminium. Thus, aluminium deposited in the bone of normal individuals can disappear within 18 months. After an accident such as that at Camelford important evidence of toxicity is likely to be missed if an investigation is delayed. The abnormal neuropsychological findings indicate cognitive impairment, but whether this was caused by an acute episode of brain damage, or other causes such as the psychological effects of stress resulting from the accident, is uncertain.
Accidents↗
Cytokine inter-relationships and their association with disease activity in arthritis.
In order to investigate the relationships between cytokine production and arthritic disease we have determined the concentrations of immunoreactive interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-6, tumour necrosis factor-alpha (TNF-alpha), interferon-alpha (IFN-alpha), IFN-gamma, and soluble IL-2-receptor (sIL-2R), as well as bioactive IL-1 and IL-6, in synovial fluids (SF) and plasma of patients with a variety of arthritides. Careful assay revealed only minimal concentrations of IL-1, particularly its biologically active form, in SF. No IL-1 was detectable in the plasma of patients that had IL-1 in their SF. Concentrations of both immunoreactive IL-1 beta and TNF-alpha in SF of rheumatoid arthritis (RA) patients were significantly higher than those in SF from patients with other inflammatory arthritides or osteoarthritis (OA). IL-6 and sIL-2R concentrations in both SF and plasma were higher in RA patients than in OA patients, and were significantly correlated. Approximately half of the SF from patients with all arthropathies contained detectable IFN-alpha, whilst IFN-Y was present in less than 10%. There were significant associations between IL-6, sIL-2R, IL-1 beta, TNF-alpha and IFN-alpha. The concentration of these cytokines, where detectable, was also related to leukocyte counts in the SF, as well as to parameters assessing local and systemic disease activity. Although IL-6 was the cytokine most clearly related to other cytokines, and to parameters assessing disease activity, the relationship between general articular disease activity and IL-6 was only evident in patients with arthropathies other than rheumatoid arthritis.
Arthritis↗
Differential metabolism of 25-hydroxyvitamin D3 by cultured synovial fluid macrophages and fibroblast-like cells from patients with arthritis.
Differential metabolism of 25-hydroxyvitamin D3 (25(OH)D3) has been shown for macrophages and fibroblast-like cells (possibly synoviocytes) cultured for two to 50 days after isolation from the synovial fluid of 12 patients with various forms of inflammatory arthritis. Macrophages synthesised the active metabolite of vitamin D3, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), the synthesis of which was increased by bacterial lipopolysaccharide, a known macrophage activating factor. In contrast, fibroblast-like cells formed 24, 25-dihydroxyvitamin D3 (24,25(OH)2D3), synthesis of which was stimulated by 1,25(OH)2D3 and inhibited by lipopolysaccharide. The synthesis of 1,25(OH)2D3 and 24,25(OH)2D3 by macrophages and fibroblast-like cells respectively was inhibited by ketoconazole, indicating that both hydroxylases are dependent on cytochrome P-450. Mean (SEM) synovial fluid and serum 25(OH)D3 concentrations were 16.7 (1.7) and 22.2 (2.6) ng/ml and those of 1,25(OH)2D3 were 29.4 (4.8) and 43.3 (4.0) pg/ml respectively. In most cases concentrations were lower in synovial fluid than in paired serum samples, but in two patients 1,25(OH)2D3 concentrations were greater in synovial fluid than in serum, suggesting local synthesis within the affected joints.
24,25-Dihydroxyvitamin D 3↗
Minimal access surgery for gastroesophageal reflux: laparoscopic placement of the Angelchik prosthesis in pigs.
Conventional surgery for gastroesophageal reflux is effective but requires laparotomy. Minimal access surgery for gastroesophageal reflux could provide a decrease in morbidity. The Angelchik antireflux prosthesis is an alternative to fundoplication for the treatment of this ailment. We evaluated the results of laparoscopic placement of the Angelchik prosthesis in 10 pigs. The duration of the procedure averaged 44 min. The mean lower esophageal sphincter pressure increased from 12.2 +/- 2.8 mmHg at baseline to 45.2 +/- 7.8 (P less than 0.05), 32.1 +/- 3.9 (P less than 0.05), and 25.1 +/- 6.5 mmHg (P greater than 0.05) as measured immediately postoperatively, at 1 week, and at 3 weeks, respectively, following placement of the prosthesis. There was no instance of prosthetic migration or esophageal perforation. One postoperative death due to distention and perforation of the colon occurred. Two animals developed distal esophageal impaction of food. We conclude that the antireflux prosthesis can be safely and effectively placed using laparoscopic methods in a porcine model. Further development of this technique is warranted.
Animals↗
Metabolism of 25-hydroxyvitamin D3 to 24,25-dihydroxyvitamin D3 by blood derived macrophages from a patient with alveolar rhabdomyosarcoma during short-term culture and 1 alpha,25-dihydroxyvitamin D3 after long-term culture.
We have examined the ability of blood-derived monocytes and macrophages isolated from a patient with alveolar rhabdomyosarcoma and hypercalcaemia, to form 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) or 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25(OH)2D3) from 25-hydroxyvitamin D3 (25(OH)D3). Adherent monocyte-macrophage cells incubated with 25(OH)D3 over the initial 2 days in culture synthesized 1.9 pmol 24,25(OH)2D3/h/incubation (representing 0.63 pmol/h/10(6) cells), whereas macrophages synthesized 1.03 and 1.15 pmol 1 alpha,25(OH)2D3/h/incubation after 1 and 4 weeks in culture respectively. In a further experiment synthesis of 1 alpha,25(OH)2D3 by long-term cultured macrophages fell from 2.25 to 0.04 pmol/h/incubation following exposure to 10 nM 1 alpha,25(OH)2D3 for 7 days, whereas 24,25(OH)2D3 synthesis was induced (0.46 pmol/h/incubation). The vitamin D3 metabolites were identified by co-chromatography with authentic 24,25(OH)2D3 or 1 alpha,25(OH)2D3 in three different high-performance liquid chromatography systems. Serum 1 alpha,25(OH)2D3 in the patient was markedly suppressed at 5 pg/ml (normal 20-50 pg/ml) indicating that raised 1 alpha,25(OH)2D3 was not the cause of the hypercalcaemia, but rather, that raised calcium may have suppressed renal 1 alpha,25(OH)2D3 synthesis. Administration of APD (3-amino-1-hydroxypropylidine-1,1-bisphosphonate) corrected the hypercalcaemia in the patient suggesting that increased bone resorption was responsible for the raised calcium. The results of this study show for the first time that immature blood derived monocyte-macrophage cells can synthesize 24,25(OH)2D3 before they mature into macrophages able to synthesize 1 alpha,25(OH)2D3.
24,25-Dihydroxyvitamin D 3↗