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Biomedical subjects

J Henderson

Publications and source records attributed to J Henderson.

At least 163 records · Page 9Linked to original sources

Time spent in hospital by the elderly in the final year of life as a health care indicator: inter-district comparisons.

We have studied the amount of time spent in hospital by elderly people in their final year of life in 1976, 1981 and 1986 in six districts covered by the Oxford record linkage study to determine the extent of differences between districts. There was consistent but insubstantial variation between the districts. Variation declined over time, suggesting that the use of hospital care for the elderly may, in this respect, be nearing consensus. We conclude that the measure of total time spent in hospital by the elderly in their last year of life was not a powerful discriminator between districts in this region. When record linkage is implemented elsewhere in England, it will be possible to make wider geographical comparisons to determine whether important variations exist elsewhere.

Aged↗

Dysregulation of parathyroid hormone-like peptide expression and secretion in a keratinocyte model of tumor progression.

Using a human keratinocyte model of tumor progression, we have examined the regulation of gene expression and secretion of a parathyroid hormone-like peptide (PLP) that has been implicated in the pathogenesis of hypercalcemia in cancer. A rapid and transient induction of PLP mRNA in response to serum stimulation was demonstrated in both established (HPK1A) and malignant (HPK1A-ras) cells; however the dose dependent increases were greater in HPK1A than in HPK1A-ras. Significant inhibition of this induction was noted with the addition of 1,25-dihydroxyvitamin D3 at a lower concentration in HPK1A than in HPK1A-ras. Amino-terminal PLP immunoreactivity and bioactivity correlated well (r = 0.98) when measured in conditioned medium. In the absence of mitogenic stimuli, malignant keratinocytes (HPK1A-ras) secreted significantly more PLP than established (HPK1A) keratinocytes. However, in response to increasing concentrations of epidermal growth factor and fetal bovine serum, PLP release was far greater from HPK1A (maximum 13 x basal) than from HPK1A-ras (maximum 3 x basal) cells. In addition, 1,25-dihydroxyvitamin D3 was more effective in inhibiting both basal and stimulated PLP secretion in HPK1A than in HPK1A-ras cultures. Reduction of extracellular Ca2+ from 2.0 mM to 0.5 mM appeared to be more effective at an early time point in reducing PLP secretion from the established cells compared with the malignant cells. These studies therefore demonstrate a progressive dysregulation of PLP expression and secretion in human keratinocytes in the transformation from established to malignant phenotype and may have important implications for understanding the pathogenetic mechanisms involved in vivo in the development of hypercalcemia in cancer.

Blotting, Northern↗

Accelerated silicosis in Scottish stonemasons.

A small group of stonemasons working with sandstone was exposed to levels of respirable quartz up to 130 times the workplace standard over a period of up to 6 years. Two died of accelerated silicosis, a disease that caused serious diagnostic difficulties and was initially not recognised by the doctors of the then Department of Health and Social Security Medical Boarding Centre (respiratory diseases). Previous descriptions of this disease in the UK date back to the years of the industrial revolution (late 18th century). One other mason on the site proved to have an earlier stage of accelerated silicosis and two had radiographic changes of early classic silicosis. Regulations intended to prevent silicosis have been in place in the UK for many decades and were strengthened by the Health and Safety at Work Act in 1974. Although the workers had been aware of a health risk from quartz, they had not been able to persuade management to take effective preventive action until serious illness had occurred. Current pressures on management to cut overheads and to achieve maximum productivity could, as in this instance, lead to neglect of health and safety standards.

Adult↗

Characterisation of virulent and benign strains of Bacteroides nodosus.

The extracellular proteases of 395 isolates of B. nodosus from ovine, bovine and caprine foot lesions were classified as either thermostable or thermolabile. Stable protease was associated with one and unstable protease with four distinctive isoenzyme patterns, each pattern differentiated by the relative mobility of paired isoenzymes. Pathogenicity tests on 64 isolates showed a correlation between the production of stable protease and the production of virulent ovine footrot lesions. The mean values for total protease activity, twitching motility and colony diameter were significantly higher for virulent compared to benign isolates, but the range of values overlapped. SDS-PAGE whole-cell electrophoretic profiles of virulent isolates were similar to the profiles of some benign isolates.

Analysis of Variance↗

Ophthalmology in the Oxford region: analysis of time trends from linked statistics.

OBJECTIVES: to report on trends in ophthalmology workload using linked statistical data; DESIGN: analysis of linked abstracts of hospital inpatient and day case records for ophthalmology; SETTING: six districts in Southern England covered by the Oxford record linkage study; SUBJECTS: records for hospital admissions to ophthalmology from 1975 to 1985; MEASUREMENTS AND MAIN RESULTS: Over the period of study, the number of episodes of inpatient and day case care increased by 16.3%. Notable increases in age-specific admission rates were seen among the elderly. An increase in the number of individuals treated contributed about 67% and an increase in multiple admissions per individual contributed about 33% to the increase in admission rates. Both average length of stay per episode and total time in hospital per individual decreased consistently during the 11 years; and there was no increase in emergency readmissions over time. No significant changes over time were found in admission rates for retinal detachments and defects or for glaucoma. There was a statistically significant increase averaging 4.8% per annum in admission rates for cataract, and a significant decrease averaging 5.2% per annum in admission rates for strabismus and other disorders of binocular eye movement between 1975 and 1985. CONCLUSIONS: Age-specific admission rates in ophthalmology are much higher in the very young and old than in other age groups. Patterns of work in the specialty are therefore particularly affected by variation in the age distribution of the population. The increase in cataract surgery reflected both the increase in numbers of old people in the population and an increase in age-specific operation rates for cataract. Attempts to alter attitudes and behaviour of the elderly regarding eye diseases, disability, and facilities for treatment may have had a positive impact on the use of services. The decrease in admissions for children probably reflects the impact made by child health surveillance programmes. As the child screening programme has expanded, the admission rates for strabismus have decreased.

Adolescent↗

Familial chondrocalcinosis due to calcium pyrophosphate dihydrate crystal deposition in English families.

Familial predisposition to chondrocalcinosis (CC) due to calcium pyrophosphate dihydrate (CPPD) crystal deposition is described in five English kindreds. Two families were characterized by premature-onset polyarticular CC with little associated structural arthropathy. In one of these families, recurrent childhood fits were strongly associated with subsequent development of CC. Affected members of the other three families resembled sporadic disease in showing predominantly late-onset, oligoarticular CC with mild arthritis and destructive change in only one case. Knee synovial fluid levels of inorganic pyrophosphate (PPi) and nucleoside triphosphate pyrophosphate (NTPP) did not differ from those of 59 sporadic cases of CC due to CPPD, although PPi and NTPP levels in both groups were higher than in normal knee synovial fluid (P less than 0.0001). Urinary PPi levels were not different from normal controls. Screening for other metabolic abnormality was negative in all cases. This is the first report of familial CC in the UK, and the first to associate this condition with childhood fits. Absence of overt primary abnormality of PPi metabolism suggests that other factors relating to crystal nucleation/growth may be more relevant to predisposition in these cases.

Calcium Pyrophosphate↗

Workload trends in otolaryngology: some statistical observations from medical record linkage.

Trends in admission rates, lengths of stay, and clinical case mix (adjusted for multiple admissions per person) for Otolaryngology from 1975 to 1985 are described using the Oxford Record Linkage Study. Person-based admission rates increased generally, most strikingly amongst children and adolescents. Both length of stay per episode and total number of days an individual stayed in hospital each year decreased. Operations on tonsils and adenoids decreased averaging 2.2% per annum; admissions for diagnoses for otitis media with effusion increased averaging 8.2% per annum; for the operations of myringotomy and tympanostomy tube insertion increased averaging 9.2% per annum; for other diagnoses related to the ear increased averaging 5.7% per annum; and admissions for malignant neoplasms decreased averaging 2.0% per annum. Clearly more people are being treated for a changing case mix. The largest increases are occurring with children and adolescents.

Adolescent↗

Audit of workload in gynaecology: analysis of time trends from linked statistics.

OBJECTIVE: To report on trends in workload patterns in gynaecology using linked statistical data. DESIGN: Retrospective analysis of linked abstracts of hospital inpatient and day case records for patients treated in the National Health Service in gynaecology. SETTING: Six health districts in the south of England covered by the Oxford record linkage study. SUBJECTS: Records for hospital admissions to gynaecology (excluding obstetric admissions) from 1975 to 1985. MEASUREMENT AND MAIN RESULTS: Inpatient episodes increased by 23.5% and day case episodes increased by 13.1%. More people treated contributed about 90% and increased readmissions contributed about 10% to the increase in workload. The workload was decreased by strike action in 1975 and 1981-2. Average length of stay decreased substantially and consistently over the 11 years. Emergency readmissions increased annually by an average of 2.7%. Admission rates in 11 groups of surgical procedures accounting for 85% of all gynaecological inpatients are reported, and increases occurred in 10 of the 11 groups. For example, average increases in annual admission rates were 1.0% for sterilization, 1.9% for legal abortion and 8.2% for biopsy of the cervix, the rate for dilatation and curettage decreased by 1.4%. CONCLUSIONS: The increase in admission rates in gynaecology was almost entirely due to increases in numbers of people treated. The rise would have been even greater if the increase in private patients had been considered. The increase may reflect increased expectations on the part of patients and their doctors, advances in technology and increased bed availability due to declining lengths of stay.

England↗

Regulation of parathyroid hormone-like peptide in cultured normal human keratinocytes. Effect of growth factors and 1,25 dihydroxyvitamin D3 on gene expression and secretion.

We have examined the expression and secretion of endogenous parathyroid hormone-like peptide (PLP) in primary cultures of normal human keratinocytes. In response to growth factors and fetal bovine serum, PLP mRNA expression and immunoreactive PLP release into conditioned medium was rapidly increased (within hours) whereas these effects were inhibited by 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. These early responses were not influenced by raising the medium calcium concentration from 0.15 to 1.0 mM. In contrast, increasing the medium calcium concentration to 1.0 mM, addition of 1,25(OH)2D3, or a combination of both, resulted in a delayed augmentation (after several days) in PLP production which was associated with an increase in cellular differentiation as assessed by production of high molecular weight keratin. To investigate whether these factors were acting at the level of transcription of the PLP gene, a series of vectors were prepared by fusing segments of the 5' flanking region of the rat PLP gene to a growth hormone reporter gene. Transient transfection of these constructs into cultured keratinocytes and measurement of immunoreactive growth hormone in the medium showed that a region stimulated by growth factors is located in a 1.9-kb fragment of the 5' flanking region and that a PLP gene promoter region less than 1.2 kb and greater than 0.3 kb upstream of the cap site contains cis-acting elements which respond positively to serum, and negatively to 1,25(OH)2D3. These combined studies demonstrate that, in normal human keratinocytes, growth factors may acutely stimulate PLP mRNA levels and PLP release, whereas 1,25(OH)2D3 inhibits these responses. At least part of these effects are at the level of gene transcription. Additionally, PLP synthesis and release are enhanced under conditions in which keratinocyte differentiation is induced.

Animals↗

Tendering care.

The Northlake Cancer Treatment Center places high-tech medicine in a soothing environment.

Cancer Care Facilities↗

A comparison of interpretation of screening mammograms by a radiographer, a doctor and a radiologist: results and implications.

In 1986, a project began to assess the feasibility of mobile breast screening, using oblique view mammography, in rural areas near Edinburgh. One of the aims of the project was to determine the feasibility, in terms of accuracy and cost, of non-radiologist prescreeners. The sensitivity and specificity of each reader was calculated (using 12-month interval cancer rates). Sensitivities of 80%, 80% and 83% were found for a radiographer, a non-radiologist doctor and a radiologist respectively, with corresponding specificities of 78%, 84% and 86%. When each reader was costed, prescreening was no cheaper than the radiologist reading all the films himself (79.10 pounds for the radiologist reading 1,000 pairs of films alone, against 84.97 pounds with the radiographer prescreening and 163.93 pounds with the non-radiologist doctor prescreening). We were unable to demonstrate any advantages of prescreening, but found that double reading of the films, though costly, would have increased the sensitivity of the programme.

Adult↗

Parathyroid hormone-like peptide in normal and neoplastic mesothelial cells.

Mesothelioma has not been commonly reported as a cause of hypercalcemia of malignancy. We have studied a patient with malignant mesothelioma and hypercalcemia in association with elevated plasma concentrations of parathyroid hormone-like peptide (PLP). Immunohistochemical analysis of the tumor and seven of eight other mesotheliomas that were not associated with hypercalcemia revealed the presence of PLP cytoplasmic immunopositivity. PLP immunopositivity was also detected in normal and reactive mesothelial cells. The results of these studies suggest that PLP immunoreactivity is common in normal and neoplastic mesothelial cells and raises the possibility that PLP production may play a role in the pathogenesis of hypercalcemia associated with mesothelioma.

Adult↗

Hospital care for the elderly in the final year of life: a population based study.

OBJECTIVES: To determine whether among people aged 65 and over those who died at advanced old age spent more of their last year of life in hospital than those who died younger, and whether the increase in longevity in the elderly between 1976 and 1985 was accompanied by increased time spent in hospital in the last year of life. DESIGN: Linkage of death records to abstracts of records of hospital inpatient care in the preceding year of patients' lives. SETTING: Six health districts in England covered by the Oxford record linkage study. RESULTS: People who died at advanced ages (85 and over) were less likely than people who died at younger ages (65-84) to have been admitted to hospital in the last year of life. Once admitted the very old tended to spend longer in hospital than others. The mean total time spent in hospital by the elderly in the year before death (based on all deaths including those among people not admitted at all) showed no appreciable change over time. The median time in hospital based on all deaths increased by about three days between 1976 and 1985. During that time there was a gain in life expectancy in the population of about one year from the age of 65. CONCLUSION: The gain in life expectancy in this population was not at the expense of any substantial increase in time spent in hospital in the final year of life.

Age Factors↗

Structure and dynamics of M13mp19 circular single-strand DNA: effects of ionic strength.

Dynamic and static light scattering, CD, and optical melting experiments have been conducted on M13mp19 viral circular single-strand DNA as a function of NaCl concentration. Over the 10,000-fold range in concentration from 100 microM to 1.0 M NaCl, the melting curves and CD spectra indicate an increase in base stacking and stability of stacked regions with increased salt concentration. Analysis of dynamic light scattering measurements of the single-strand DNA solutions as a function of K2 from 1.56 to 20 X 10(10) cm-2 indicates the collected autocorrelation functions are biexponential, thus revealing the presence of two decaying dynamic components. These components are taken to correspond to (1) global translational motions of the molecular center of mass and (2) motions of the internal molecular subunits. From the evaluated relaxation rates of these components, diffusion coefficients D0 and Dplat are determined. The center of mass translational diffusion coefficient D0, varies in a nonmonotonic manner, by 10%, from 3.75 X 10(-8) to 3.39 X 10(-8) cm2/s over the NaCl concentration range from 100 microM to 1.0 M. Likewise, the radius of gyration RG, obtained from static light scattering experiments, varies by 15% from 699 to 830 A over the same NaCl range Dplat, the diffusion coefficient of the internal subunits, displays a different dependence on the NaCl concentration and decreases, by nearly 22% in a titratable fashion, from 12.46 X 10(-8) to 10.26 X 10(-8) cm2/s, when the salt is increased from 100 microM to 1.0 M. A semiquantitative interpretation of these results is provided by analysis of the light scattering data in terms of the circular Rouse-Zimm chain. Rouse-Zimm model parameters are estimated from the experimental results, assuming the circular chains are composed of a fixed number of Gaussian segments, N + 1 = 15. The rms displacement of the internal segments, b, is estimated to be the smallest (442 A) in 100 mM NaCl. Increases of b to 467 A in 100 microM and 524 A in 1.0 M NaCl are observed. Meanwhile, the hypothetical friction factor of the internal subunits, f, progressively increases as the NaCl concentration is raised. It is inferred from the evaluated Rouse-Zimm model parameters that both the static flexibility of the circular chain and diffusive displacements of the internal subunits decrease with increases in NaCl concentration from 100 mM to 1.0 M.(ABSTRACT TRUNCATED AT 400 WORDS)

Chemical Phenomena↗

Measurement of protease thermostability, twitching motility and colony size of Bacteroides nodosus.

Total extracellular protease activity of Bacteroides nodosus in TAS liquid culture varied directly with cell mass and buffer concentration between 20 and 50 mM HEPES, MOPS and TES buffers, but not with Tris which gave anomalous high cell counts, nor with Na2Co3 which showed a decline of protease activity and cell mass. The stability of HEPES-buffered crude protease preparations were estimated on the basis of temperature or Ca2+ activity. Variation of the estimates for cellular twitching was greater than that for colony diameter in benign and virulent strains of B. nodosus. Surface translocation, quantified on the basis of colony diameter, reached a limit after 72 h incubation on modified TAS agar, ranging from 0.04 to 0.14 mm per h for six isolates tested.

Animals↗