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Biomedical subjects

D Pearson

Publications and source records attributed to D Pearson.

At least 127 records · Page 7Linked to original sources

An assessment of a double-isotope method for the detection of transferrin accumulation in the lungs of patients with widespread pulmonary infiltrates.

1. The accumulation in the lung of the plasma protein transferrin was determined in 44 patients with widespread pulmonary infiltrates of various causes and in 11 healthy volunteers using a double-isotope method based on labelling in vivo of circulating transferrin with indium and erythrocytes with technetium. 2. In 22 patients meeting criteria for the adult respiratory distress syndrome (ARDS) the mean transferrin accumulation rate was threefold greater (P less than 0.005) than in 22 patients not meeting these criteria, although most possessed an appropriate risk factor for ARDS, in addition to extensive radiographic changes. 3. The double-isotope method did not completely separate patients with ARDS from those not meeting the criteria or from control subjects and cannot be considered a diagnostic test for the condition. Statistically significant rates of transferrin accumulation, however, occurred more frequently in patients with ARDS (82%) than in controls (64%) or in those without ARDS (59%).

Adolescent↗

The use of serum carcinoembryonic antigen to assess therapeutic response in locally advanced and metastatic breast cancer: a prospective study with external review.

Serum carcinoembryonic antigen (CEA) has been measured throughout initial systemic endocrine treatment in 87 patients with stage III and 179 patients with stage IV breast cancer. Clinical response has been assessed after six months according to UICC criteria with external review of clinical and radiological data. Pretreatment CEA concentrations have been compared with those found in 55 'disease free' women attending a diagnostic breast clinic. A strong correlation exists between therapeutic response and alterations in CEA concentration (above 6 ng/ml) in patients presenting with stage IV disease. More than 50% of such patients either present with or develop CEA concentration greater than 6 ng/ml during the first six months of treatment.

Adult↗

A comparison of two methods of measuring gamma camera uniformity.

Two quantitative methods of measuring intrinsic uniformity of gamma cameras have been compared. One is a modified NEMA protocol, and the other a simpler method of data acquisition and processing that can be carried out in departments with restricted data-processing facilities. Both methods show the same trend in uniformity and lead to action being taken to rectify deterioration in performance at the same time. The use of cusum plots to monitor trends in performance and set action levels is discussed and compared with a simple plot of the data as a time series.

Methods↗

Inhibition of protein synthesis in LLC-PK1 cells increases calcitonin-induced plasminogen-activator gene transcription and mRNA stability.

The peptide hormone calcitonin induces the accumulation of urokinase-type plasminogen activator (uPA) mRNA in pig kidney LLC-PK1 cells. By itself, inhibition of protein synthesis had a negligible effect on uPA mRNA accumulation. Inhibition of protein synthesis led to two superinductive effects: an increase in calcitonin-induced uPA mRNA accumulation over time, and a shift in the dose-response curve so that lower calcitonin doses became more potent. To explain these two superinductive effects of protein-synthesis inhibition on calcitonin treatment, we demonstrated that the inhibition of protein synthesis increased both calcitonin-induced uPA-gene transcription and uPA-mRNA stability. Different protein-synthesis inhibitors had similar actions, arguing against the possibility that the results were attributable to an anomalous action of a particular inhibitor. The superinductive effects of protein-synthesis inhibition could not be mimicked when a tumour promoter, 12-O-tetradecanoylphorbol 13-acetate (TPA), was used instead of calcitonin as an inducer. Calcitonin and TPA exert their effects through different pathways, suggesting a clue to the mechanism of superinduction. Although inhibition of protein synthesis has been reported to increase transcription and mRNA stability in a number of other systems, the one described here appeared unique in combining both effects in the context of hormonal regulation.

Animals↗

Dexamethasone coordinately inhibits plasminogen activator gene expression and enzyme activity in porcine kidney cells.

The peptide hormone, calcitonin, induces urokinase-type plasminogen activator (uPA) enzyme activity in cultured LLC-PK1 pig kidney cells. This induction occurs as a consequence of transcriptional activation of the uPA gene. Treatment with the synthetic glucocorticoid hormone, dexamethasone, was found to inhibit calcitonin induction of uPA enzyme activity by as much as 80%. The inhibitory effect of dexamethasone was attributed to at least two mechanisms: induction of an inhibitor of uPA enzyme activity, and reduction in uPA mRNA levels. Study on reduction of uPA mRNA levels showed that dexamethasone significantly reduced the transcription rate of the calcitonin-induced uPA gene, without affecting the half-life of uPA mRNA. Although dexamethasone has been reported to induce inhibitors of plasminogen activator enzyme activity and to inhibit transcription of various genes, the system described here appears novel in that both actions are coordinated.

Animals↗

A prospective study of spontaneous miscarriage in ultrasonically normal pregnancies and relevance to chorion villus sampling.

A total of 1,068 patients were examined by ultrasound to ensure normality of pregnancy and followed prospectively from booking until 28 weeks. The spontaneous miscarriage rate was 2.7 per cent occurring within the first 16 weeks. Threatened miscarriage was associated with a 38 per cent fetal loss. Miscarriage was less likely as pregnancy advanced. The reduction in subsequent miscarriage rate before 11 weeks and from 11 weeks onwards is statistically significant (p less than 0.001). Gravidity, maternal age and a history of previous fetal loss did not contribute significantly to the miscarriage rate. Patients with a history of fetal loss were more likely to experience a threatened miscarriage. The relevance of these findings to chorion villus sampling is discussed.

Abortion, Spontaneous↗

Adult nephroblastoma--five cases treated by surgery, radiotherapy and chemotherapy.

Nephroblastoma in adults is rare; consequently very little experience of treatment for adult cases has been reported. We report five cases of adult nephroblastoma managed by nephrectomy, radiotherapy and combination chemotherapy. The treatment schedules were derived from childhood nephroblastoma regimens. However, four of the five patients were dead within 12 months of nephrectomy and all five had progression of disease whilst on combination chemotherapy. A good prognosis should not be anticipated for adult nephroblastoma. The chemotherapy schedules which are so successful in childhood nephroblastoma may require modification to improve prognosis in adults.

Adult↗

Adrenal cortical carcinoma: survival after radiotherapy.

This study describes 15 patients with histologically proven adrenal cortical carcinoma seen at one radiotherapy centre between 1968 and 1981. Nine patients had radiotherapy following surgery and their 10 year uncorrected survival was 33%. Prognostic factors included age at diagnosis, hormone production and complete surgical removal. Two of the three long term survivors developed second malignancies.

Adrenal Cortex Hormones↗

A new genetic approach for studying hormonal regulation of urokinase-type plasminogen activator gene expression in LLC-PK1 cells.

In LLC-PK1 cells, a cyclic AMP (cAMP)-elevating peptide hormone, calcitonin, induces urokinase-type plasminogen activator (uPA) gene transcription without concomitant protein synthesis. To understand the molecular mechanism of the uPA gene regulation by cAMP, we developed a system which allows us to obtain mutant cells with modified regulatory proteins. A uPA-gpt hybrid gene was constructed, in which the regulatory region of the uPA gene was linked to a bacterial xanthine-guanine phosphoribosyltransferase gene (gpt), and it was transfected into LLC-PK1 cells. A stably transformed cell line, which expressed gpt only in the presence of calcitonin, was obtained, and then these cells were treated with a chemical mutagen, ethyl methanesulfonate. Cells were screened for constitutive gpt expression and, as mutations in regulatory proteins should affect the two genes at the same time, cells were further screened for an increased basal uPA mRNA level. Several such clones were obtained and none of them had modified cAMP-dependent protein kinase activity, suggesting that mutations were in the post-protein kinase step in the pathway of hormone action. Five clones were fused with the parent LLC-PK1 cells, and all of the fusion cells showed reduced basal uPA mRNA levels, indicating that they were recessive mutants. One clone was analyzed further for sensitivity to calcitonin in the induction of uPA mRNA, and it showed a significantly different dose-response pattern compared with parent cells. These results suggest that the uPA gene is regulated, at least partly, by a negatively regulating factor and that the action of cAMP is linked to this factor.

Animals↗

Effect of spinal irradiation on growth.

Standing height, sitting height, and leg length were measured in 79 patients (aged 16-30 years), who had been given craniospinal irradiation (n = 37) or cranial irradiation (n = 42) in childhood for a brain tumour and had completed their growth. Their measurements were compared with established standards for sitting height and leg length in British children (aged 16-18 years). To examine the effects of spinal irradiation on spinal growth independent of growth hormone deficiency we analysed the leg length (LL) minus sitting height (SH) standard deviation score (SDS) and used the cranial group as controls. There was an overall significant difference between the median craniospinal LL-SH SDS (1.98) and the median cranial LL-SH SDS (0.545). Within the craniospinal group there was a significant correlation with age at treatment, but there was no such correlation for the cranial group. After splitting age at treatment into three groups (0 less than 5, 5 less than 10, and 10-15 years) there was a significant difference between the LL-SH SDS of the craniospinal and cranial groups for each of the age ranges. In conclusion, spinal irradiation has a profound effect on spinal growth and the younger the child is when given irradiation the greater the subsequent skeletal disproportion. Our most conservative figures indicate that the eventual loss in height is 9 cm when irradiation is given at 1 year, 7 cm when given at 5 years, and 5.5 cm when given at 10 years.

Adolescent↗

A controlled trial of nandrolone decanoate in the treatment of rheumatoid arthritis in postmenopausal women.

To determine whether an anabolic steroid had any benefit in the treatment of rheumatoid arthritis 47 patients entered a parallel group study. Twenty four received nandrolone decanoate 50 mg intramuscularly every third week for two years and 23 patients received no anabolic steroids. Other therapy was unaltered. Patients attended for clinical and biochemical assessments as well as the objective assessments of elementary body composition by in vivo neutron activation analysis and measurement of the mineral content of the distal femur by single photon absorptiometry on five occasions. A modest clinical deterioration (except for grip strength) was seen in both groups. No significant changes in calcium or alkaline phosphatase were seen. There was no significant change in total body calcium, total body phosphorus, body weight, or bone index/bone width measurements in either group. Significant increases occurred in total body nitrogen, total body potassium, haemoglobin, and packed cell volume (by six months) in the group treated with nandrolone decanoate. Comparison of 10 patients in the group treated with nandrolone decanoate also receiving oral steroid therapy with 14 patients in this group not receiving oral steroid therapy showed no significant differences. The main side effect of nandrolone decanoate was hoarseness. No radiological changes were seen. Nandrolone decanoate, in a dose that produces a significant anabolic effect, has no demonstrable action on bone metabolism in rheumatoid arthritis but may improve the chronic anaemia by six months.

Anabolic Agents↗

Pulmonary vascular permeability to transferrin in the pulmonary oedema of renal failure.

Thirteen patients with renal failure and pulmonary oedema were assessed for evidence of increased pulmonary vascular permeability to protein by a double isotope technique. Comparison was made with 10 patients with cardiogenic pulmonary oedema, 11 healthy volunteers, and 10 patients with the adult respiratory distress syndrome. There was no significant difference in the accumulation of a radiolabelled plasma protein (transferrin) in patients with renal or cardiogenic pulmonary oedema and normal volunteers. Patients with adult respiratory distress syndrome showed significantly greater protein permeability (p less than 0.001). In pulmonary oedema associated with renal failure managed by current regimens there was no evidence of increased permeability to transferrin.

Adult↗

The role of growth hormone in stunted head growth after cranial irradiation.

The head sizes of 38 patients, growth hormone (GH) deficient following craniospinal (n = 26) or cranial irradiation (n = 12), have been assessed before (n = 38) and on completion of GH therapy (n = 15) or at the end of a similar period of observation without GH (n = 7). These results were compared to the change in head size seen in idiopathic GH deficiency following GH therapy (n = 14). Before GH therapy, the latter had small heads [mean occipitofrontal circumference SD score (SDS) -1], which were relatively large compared to the height deficit [height SDS (CA) -4.7], and they exhibited catch-up growth with GH (delta occipitofrontal circumference SDS + 0.7, final occipitofrontal circumference SDS -0.2). In contrast, over a similar period all patients, who previously had received cranial irradiation in the dosage range 2700-4750 centi-Geigy, irrespective of the radiation schedule or GH treatment, showed a decrease in occipitofrontal circumference SDS (mean delta -0.9), a significant difference to the expected head growth of normal children over a similar period (p less than 0.01). We have noted that restricted head growth occurs in the years following cranial irradiation and is unaffected by GH therapy. Earlier work has shown that cranial irradiation may impair intelligence. The exact relationship between intellectual impairment and stunted head growth remains to be determined.

Adolescent↗

Children's return to school after treatment for solid tumours.

Great advances have been made in recent years in the treatment of children's cancers. Consequently, increasing numbers are now returning to school. The pilot study described in this paper looks at the problems experienced by some of these children, their teachers and parents, and some of the solutions which have been found, with a view to eventually taking some action to help the situation. The results are based on detailed studies of 16 children who had all been off treatment for two or more years and had therefore returned to school on a normal full-time basis. Parents and teachers were interviewed. The preparation for the return to school, reintegration problems including general physical, academic, psychological and behavioural ones, schoolmates' reactions, siblings' reactions, and the teachers, and parents, suggestions for how these might be alleviated are considered. Five important factors emerged especially clearly: Children whose treatment absence was right at the start of their schooling had particularly severe problems in integrating into school. Children at secondary schools had special anxieties about their school-work, especially Mathematics, which leads to consideration of the whole problem of teaching during absence from school. Some children are having severe problems in obtaining efficient prostheses. Whilst classmates were usually welcoming or unconcerned, much teasing was experienced from children in other classes, particularly in secondary schools. Whilst attention is focused on the sick child, siblings are developing severe problems of their own which need special attention. Most teachers and parents would have welcomed advice on or help with these problems and it is hoped that, when a larger scale study has clarified the finer points, some systems for helping will be devised.

Adaptation, Psychological↗