Biomedical subjects
J Hampson
Publications and source records attributed to J Hampson.
The potential role of serum CA 125 in an ultrasound-based screening program for familial ovarian cancer.
We have assessed the potential role of a test based upon the measurement of serum CA 125 in an ultrasound-based screening program for familial ovarian cancer. A sample of peripheral blood was taken from 1502 self-referred, asymptomatic women whose pedigree showed that at least one close relative had developed the disease. All women in the study underwent one screening by transvaginal ultrasonography (consisting of one or more scans) to detect any persistent lesion and a change in ovarian volume. Women with a positive result were referred for surgery. The concentration of serum CA 125 was measured in all samples at the end of the study. Seven ovarian cancers (4 invasive and 3 of borderline malignancy; 5 FIGO stage Ia, 1 stage IIa, 1 stage III) and 55 benign lesions were detected. We calculated the effect that a prescreening test (based on different threshold values for serum CA 125) would have had on the number of women entering the ultrasound-based screening program, and on the detection rate and false-positive rate of the overall procedure. There was a direct relationship between the number of women referred for ultrasound screening and the detection rate. The use of a threshold value for serum CA 125 > or = 20 U/ml would have meant that 380 women (25.3%) were referred for ultrasonography and 5 out of 7 cancers (71%) would have been detected with a false-positive rate of 1.1%. The odds of a woman with a positive screening result having cancer at surgery would have been about 1:3 (which would improve to about 1:1 if observational indices of color Doppler imaging and a morphological score had been used throughout). We concluded that a prescreening immunochemical test based on the measurement of serum CA 125 (with a threshold value of > or = 20 U/ml) would increase the prior odds for familial ovarian cancer by 2.8, but would lower the overall detection rate by 29% at the prevalence screening.
Screening for early familial ovarian cancer with transvaginal ultrasonography and colour blood flow imaging.
OBJECTIVE: To assess the value of transvaginal ultrasonography with colour blood flow imaging in detecting early ovarian cancer in women with a family history of the disease. DESIGN: Study of self referred symptomless women with a close relative who had developed the disease. Each woman was screened to detect persistent lesions and defined changes in ovarian volume. Morphological score and pulsatility index were recorded. SETTING: Ovarian screening clinic. SUBJECTS: 1601 self referred women. INTERVENTIONS: Women with a positive screening result were recommended to have further investigations. MAIN OUTCOME MEASURES: Findings at surgery and histology of abnormal ovaries. Morphological score > or = 5 and pulsatility index < 1.0 at last scan. RESULTS: Women were aged 17 to 79 (mean 47) years; 959 (60%) were premenopausal, 469 (29%) were naturally postmenopausal, and 173 (11%) had had a hysterectomy. 157 women had a pedigree suggestive of the site specific ovarian cancer syndrome and 288 of multiple site cancers. 61 women had a positive screening result (3.8%, 95% confidence interval 2.9 to 4.9%), six of whom had primary ovarian cancer detected at surgery (five stage Ia, one stage III). Use of a high morphological score or a low pulsatility index increased the odds of finding ovarian cancer from 1:9 to about 2:5 (1:1 in the highest risk groups). Five interval cancers were reported (three ovarian and two peritoneal). Eight of the 11 cancers developed in women with pedigrees suggestive of inherited cancer. CONCLUSIONS: Transvaginal ultrasonography with colour flow imaging can effectively detect early ovarian cancer in women with a family history of the disease. The screening interval should be less than two years.
The relation of maternal language to variation in rate and style of language acquisition.
The main thrust of this paper is to question whether in earlier studies the 'motherese hypothesis' has been adequately tested. The present study first explores concurrent relations between maternal and child language at an early age, using the Snyder, Bates & Bretherton (1981) questionnaire to assess vocabulary at 1;1. With a large sample of 45 subjects, videotaped at 1;1 and 1;8, it was possible to analyse earlier talkers separately from later talkers. The results indicate pre-existing differences between the mothers of earlier and later talkers as early as 1;1--some 5 months before other studies have examined the possible facilitative effects of 'motherese'. Secondly, and perhaps more importantly, when the sample was divided according to stylistic preference at 1;8, several associations between maternal language at 1;1 and MLU at 1;8 emerged for the non-expressive group which were non-existent for the expressive group. These results imply that earlier studies may have been looking for the effectiveness of maternal input too late. Moreover, it may continue to be difficult to demonstrate consistent effects of child-directed speech as long as researchers continue to ignore individual differences in style of language acquisition.
Nouns in early lexicons: evidence, explanations and implications.
Many theories of grammatical and lexical acquisition assume that children learn predominantly nouns, and specifically names of objects, when they first begin to acquire words in the second year. We show that the noun bias in early vocabularies is far from universal, and that it rests only in part on the acquisition of object names. An analysis of vocabulary composition from 45 children at 1;8 indicates that more nouns are acquired than all other word classes, but that of the nouns acquired only about half are the names of basic level object classes (BLOCs). An examination of the use of nouns in mother-child discourse shows that non-object words referencing locations, actions and events, for example, are used in distinctive pragmatic and grammatical contexts which might enable a child to grasp the word's use and eventually its meaning. It is concluded that a theory of lexical acquisition in discourse context is required to explain word learning at all levels and for all word types. Implications for semantic bootstrapping theories are considered.
Long-term bone marrow cultures established from bone marrow transplant recipients.
Following bone marrow transplantation (BMT), the stroma remains host-derived, and has therefore been exposed to the high doses of chemoradiotherapy used in BMT conditioning. We have used long term bone marrow culture (LTBMC) to study the effect of this conditioning therapy on the stroma. Twenty-five BMT recipients were studied, comprising 13 allografts and 12 autografts. Marrow was aspirated prior to transplant (6 cases) and at 3, 6 or 12 months post-BMT. Fifteen haematologically normal subjects were studied in parallel. The stromal layer of LTBMC was visually assessed at weekly intervals and supernatant cells counted and assayed for colony forming unit-granulocyte/macrophage (CFU-GM). Five of the six cases studied both before and after BMT formed less confluent stroma following the procedure. A successive improvement in the proportion of patients forming good stroma was observed with increasing time from BMT. Supernatant cell and CFU-GM counts were not significantly different from normal following BMT. No clear relationship was observed between stromal confluence and any of the following: supernatant cell and CFU-GM counts, transplant type, underlying disease, conditioning regime or time to engraftment. These data support the view that BMT conditioning regimes cause stromal damage, and that this damage gradually improves with time.
Low-affinity receptors for tumour necrosis factor-alpha, interferon-gamma and granulocyte-macrophage colony-stimulating factor are expressed on human placental syncytiotrophoblast.
Scatchard binding analysis has been employed to characterize expression of low-affinity receptors for tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and granulocyte-macrophage colony-stimulating factor (GM-CSF) by isolated human placental syncytiotrophoblast microvillous plasma membrane (StMPM) vesicles. Trophoblastic receptors for the c-kit ligand (stem cell factor) could not be identified using the same methods. No high-affinity receptors could be detected for GM-CSF or IFN-gamma, but a minority of high-affinity TNF-alpha receptors were identified. Cross-inhibition studies indicated the low-affinity receptors to be specific for each cytokine rather than to be non-specific cytokine-binding factors. Only relatively high-affinity receptors for TNF-alpha and IFN-gamma could be detected on the BeWo human choriocarcinoma cytotrophoblast cell line, whereas receptor affinity for GM-CSF was similar to that on syncytiotrophoblast. Immunohistochemical staining has confirmed expression of IFN-gamma receptor by syncytiotrophoblast: in contrast, staining for the established TNF-R1 and TNF-R2 receptors was associated mainly with placental vascular endothelium. These low-affinity cytokine receptors could reflect unique biological responses of foetal syncytiotrophoblast in the presence of local concentrations of maternal cytokine.
Correlation in ages at death from familial ovarian cancer among sisters.
The analysis of pedigrees taken from 97 of 1466 women attending a screening clinic for early familial ovarian cancer showed that there was a strong correlation in the ages at death from the disease among sisters (r = 0.68, confidence limits 0.51-0.82, P < 0.001), but not between mothers and daughters. This information can be used to help counsel women who are considering the appropriate time for more intensive screening or prophylactic oophorectomy.
Nodular regenerative hyperplasia of the liver in Behçet's disease.
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A study of well-being of elderly people in three communities in Zimbabwe.
The purpose of this research was to assess the well-being of elderly people in three different community types in Zimbabwe. Well-being was defined as general health, health resource access, nutrition, habits, and physical function. Major health problems, hygiene, nutrition and access to health care did vary between communities, but there was a low level of physical dependency throughout. The findings suggest that once a critical decline in fitness occurs, elderly people may rapidly die as a result of diminished medical and physical support. These findings are relevant to future plans for elderly care services in Zimbabwe.
Elderly support and intergenerational transfer in Zimbabwe: an analysis by gender, marital status, and place of residence.
This paper describes elderly support and intergenerational transfer by gender, marital status, and place of residence for 150 elderly persons in Zimbabwe. The survey was conducted in September 1988, and includes information on background characteristics, income, and cash support from all sources, noncash support, and the support of elders to others. Conclusions and implications are discussed.
Inhibition of hematopoietic colony-forming cells. Normal bone marrow extract versus transforming growth factor-beta 1.
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Development of multipotential haemopoietic stem cells to neutrophils is associated with increased expression of receptors for granulocyte macrophage colony-stimulating factor: altered biological responses to GM-CSF during development.
Interleukin-3 (IL-3) dependent multipotent haemopoietic stem cells FDCP-Mix A4 (A4) were induced to differentiate and develop into mature neutrophils in response to Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) plus granulocyte CSF (G-CSF). This resulted in an increase in cell number over seven days of culture, following which the cells lost the ability to undergo further proliferation. The effect of GM-CSF on these cells has been assessed at various stages of development. Clonogenic cells, able to respond to GM-CSF, were generated only at days 3, 4 post-induction. From day 5 onwards, mature post-mitotic neutrophils are produced and clonogenic cells are lost. Loss of proliferative potential, in response to GM-CSF, was confirmed using [3H]-thymidine incorporation. Receptors for GM-CSF, were also measured during development using [125I]-GM-CSF binding assays. Although the dissociation constant for GM-CSF binding sites did not vary considerably, the number of such sites increased dramatically from about 20 (day 0, when the cells have a primitive morphology) to about 1000 by day 6 (when the cells are predominantly mature neutrophils). GM-CSF-stimulated Na+/H+ antiport activation was also determined. Although few GM-CSF receptors are expressed at day 0, there is a significant response (63% of maximal) to GM-CSF in terms of intracellular alkalinisation: this response increased markedly until, by day 4 (700 GM-CSF binding sites/cell), there is a maximal activation of the antiport by GM-CSF. By day 7 (greater than 900 GM-CSF binding sites/cell), however, there is significant reduction in activation of the Na+/H+ antiport by GM-CSF. Nonetheless, increased viability of these mature cells is still seen in response to GM-CSF. These results suggest that not only does expression of GM-CSF receptors alter during development of multipotential cells to mature neutrophils, but that these receptors are coupled to different intracellular effector mechanisms as the cells progressively mature.
Selective inhibition of primitive hemopoietic colony-forming cells by an extract from normal marrow: comparison with transforming growth factor-beta.
An extract from normal bone marrow (NBME) which inhibits proliferation of spleen colony-forming units CFU-S selectively inhibits interleukin 3 (IL-3)-driven colony formation by primitive hemopoietic progenitors. This activity is distinct from transforming growth factor-beta (TGF beta), which also inhibits development of primitive progenitors. There is evidence that the two activities inhibit proliferation of target cells by different mechanisms and that the bone marrow extract has a direct effect on cell cycling, whereas the effect of TGF beta to suppress proliferation is probably indirect.
The effects of TGF beta on haemopoietic cells.
Transforming growth factor beta (TGF beta) suppresses the growth of differentiation inducible, murine IL-3-dependent multipotential cell lines but has no growth inhibitory effect upon an IL-3-independent (leukaemic) cell line arising from one of them, nor on IL-3-dependent cell lines that are unable to undergo differentiation. TGF beta inhibits in vitro colony formation by normal multipotential haemopoietic progenitor cells. Bipotential progenitors recruited by GM-CSF are, however, more resistant to the inhibitory effects of TGF beta, whereas progenitors recruited by the lineage restricted factor, M-CSF, are sensitive to the inhibitory effects. These data indicate that responsiveness to TGF beta is differentiation linked and studies with the cell lines suggest that response (or lack of response is not determined solely by levels of expression of TGF beta receptors. Furthermore, the effects of TGF beta 2 on haemopoietic progenitors are very similar to those induced by TGF beta.
Ethical assessments within legislative systems.
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Chronic Q fever endocarditis causing massive splenomegaly and hypersplenism.
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Screening for early ovarian cancer.
Transvaginal ultrasound scanning with colour Doppler imaging can be used to detect early ovarian cancer. About one in three women with a family history of the disease and a positive screening result (i.e. a persistent intraovarian mass with a characteristic blood supply) will have histological signs of primary cancer. A randomized controlled clinical trial should be undertaken to assess whether screening and immediate treatment of women from the general population will improve survival rates from the disease.