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Biomedical subjects

E Williams

Publications and source records attributed to E Williams.

At least 73 records · Page 4Linked to original sources
PubMed1999

A null mutation in the inflammation-associated S100 protein S100A8 causes early resorption of the mouse embryo.

S100A8 (also known as CP10 or MRP8) was the first member of the S100 family of calcium-binding proteins shown to be chemotactic for myeloid cells. The gene is expressed together with its dimerization partner S100A9 during myelopoiesis in the fetal liver and in adult bone marrow as well as in mature granulocytes. In this paper we show that S100A8 mRNA is expressed without S100A9 mRNA between 6.5 and 8. 5 days postcoitum within fetal cells infiltrating the deciduum in the vicinity of the ectoplacental cone. Targeted disruption of the S100A8 gene caused rapid and synchronous embryo resorption by day 9. 5 of development in 100% of homozygous null embryos. Until this point there was no evidence of developmental delay in S100A8-/- embryos and decidualization was normal. The results of PCR genotyping around 7.5-8.5 days postcoitum suggest that the null embryos are infiltrated with maternal cells before overt signs of resorption. This work is the first evidence for nonredundant function of a member of the S100 gene family and implies a role in prevention of maternal rejection of the implanting embryo. The S100A8 null provides a new model for studying fetal-maternal interactions during implantation.

Animals↗
PubMed1999

A novel orthotopic model of breast cancer metastasis to bone.

Breast cancer affects approximately one woman in twelve and kills more women than any other cancer. If detected early, patients have a five year survival rate of 66%, but once metastatic disease has developed, there is no effective treatment. About 70% of patients with metastatic disease have bone involvement, while lungs and liver are the other common targets. Bone metastases cause severe pain, pathological fractures and hypercalcaemia and thus are a significant clinical problem. The development of new therapies for metastatic breast carcinoma depends on a better understanding of the mechanism of homing of the tumour cells to bone, liver and lungs and the factors required for their growth in these organs. Research on mechanisms of breast cancer metastasis, particularly to bone, has relied on in vitro studies or on tumour models in which the inoculation route is designed to promote delivery of tumour cells to a specific organ. Metastases in bone are achieved by inoculation into the right ventricle of the heart. To our knowledge there has been no report of a model of metastatic spread from the mammary gland to distant sites which reliably includes bone. In this paper, we describe our recent development of a novel murine model of metastatic breast carcinoma. The new model is unique in that the pattern of metastatic spread closely resembles that observed in human breast cancer. In particular, these murine breast tumours metastasise to bone from the primary breast site and cause hypercalcaemia, characteristics not normally found in murine tumours, but common in human disease. Furthermore, in a preliminary characterisation of this model, we show that secretion of parathyroid hormone-related protein, a role for which has been implicated in breast cancer spread to bone, correlates with metastasis to bone. This model therefore provides an excellent experimental system in which to investigate the factors that control metastatic spread of breast cancer to specific sites, particularly bone. The special advantage of this system is that it involves the whole metastasis process, beginning from the primary site. Existing models consider mechanisms that pertain to growth of tumour once the site has been reached. An understanding of the regulation of these factors by potential therapeutic agents could lead to improvement in therapies designed to combat metastatic disease. For the first time, this development will allow exploration of the molecular basis of site-specific metastasis of breast cancer to bone in a clinically relevant model.

Animals↗
PubMed1999

Children with autism experience problems with both objects and people.

Kanner (1943), in his classic account, described autism as a specific impairment in interpersonal relations which leaves the child's uses of objects relatively unaffected. This combination of the difficulties in relating to people and the supposedly "excellent" relations to objects figures centrally within many of the current theories of autism, which have had relatively little to say on the question of object use. This paper draws attention to evidence of widespread impairments in relating to objects, not only in interpersonal aspects of object use but also in early sensorimotor exploration and the functional and conventional uses of objects. In stressing these problems with objects, our purpose is not to downplay the social dimension of autism, but rather to highlight the reciprocal nature of the interactions between the child, other people, and objects. Given the evidence that other people play an important role in introducing objects to children, we propose that an impairment in interpersonal relations should itself lead us to expect corresponding disruption in the autistic child's use of objects. Conversely, an unusual use of objects is likely to manifest itself in disturbances in relating to other people, given the importance of a shared understanding and use of objects in facilitating interaction.

Autistic Disorder↗
PubMed1999

Effects of father participation in child rearing: twenty-year follow-up.

Follow-up data were obtained on the young adult children of fathers of intact, white, middle-class families who had been closely involved in early child rearing. The extent to which their locus of control, expectations about gender roles in career and family contexts, and academic competence differed from those of peers reared in more traditional families was examined. Greater paternal involvement was found to contribute to a more internal locus of control, particularly in sons.

Adolescent↗
PubMed1999

Effects of a pneumonia clinical pathway on time to antibiotic treatment, length of stay, and mortality.

OBJECTIVES: A clinical pathway standardizing management for patients with an admission diagnosis of pneumonia was initiated after a previous study found delayed time to initial antibiotic administration, a longer length of stay, and higher mortality rate for the authors' patients as compared with those in a "benchmark" hospital. The current study was undertaken to determine whether implementation of the clinical pathway resulted in statistically significant decreases for these measures, both in the initial year following pathway implementation and two years later. METHODS: A retrospective chart review was completed for three cohorts of pneumonia patients admitted via the ED: 1) three months immediately prior to pathway implementation, 2) 10-12 months after implementation of the pathway, and 3) 34-36 months after implementation of the pathway. Four standard antibiotic regimens were used following pathway implementation: community-acquired, community-acquired penicillin-allergic, nursing home-acquired, and nursing home-acquired penicillin-allergic. Demographics, medical history, presentation signs and symptoms, process of care, and outcome data were abstracted from each patient's medical record. RESULTS: The mean time to antibiotic administration decreased from 315 minutes prepathway to approximately 175 minutes during the first postpathway period and 171 minutes at three years (ANOVA, p < 0.0001). The percentage of patients who received antibiotics in the ED increased from 58% prepathway to 94% during the first postpathway period and 97% at three years (chi square, p < 0.0001). Length of stay decreased from 9.7 prepathway to 8.9 days during the first postpathway period and 6.4 days at three years (ANOVA, p < 0.0001). There was no significant change of in-hospital mortality (9.6% prepathway to 5.2% and 4.9%) in the two respective periods. CONCLUSIONS: This study demonstrates that implementation of a pneumonia clinical pathway for the management of hospitalized patients admitted via the ED decreases the time to initial antibiotic treatment and increases the proportion of patients initially treated with antibiotics in the ED. These effects were evident in the first year following pathway implementation and sustained at the three-year study interval.

Aged↗
PubMed1999

Ability of the digene hybrid capture II test to identify Chlamydia trachomatis and Neisseria gonorrhoeae in cervical specimens.

The Digene Hybrid Capture II (HCII CT/GC) test is a combination test designed to detect Chlamydia trachomatis and Neisseria gonorrhoeae in a single specimen. It is a nucleic acid hybridization test which uses signal amplification to increase sensitivity. We compared its performance to that of culture on cervical specimens from 1,370 women. Direct fluorescent-antibody assay was used to resolve discrepant results for C. trachomatis. Samples were collected with a proprietary cervical brush or with endocervical swabs. The HCII CT/GC test proved to be sensitive and specific in detecting these organisms. Compared to N. gonorrhoeae culture, it had a sensitivity of 93% (87/94) and a specificity of 98.5% (1,244/1,263). Compared to C. trachomatis culture, the sensitivity was 97.7% (129/132) and specificity was 98.2% (1,216/1,238). Testing of some specimens with discrepant results by PCR suggested that the test would actually prove to be even more specific if it were compared to a nucleic acid amplification test (NAAT). The sensitivity of C. trachomatis culture was somewhat less, at 88.6% (117/132). The endocervical brush appeared to be better than Dacron swabs for collecting specimens. The HCII CT/GC test offers an attractive format that allows simultaneous detection of C. trachomatis and N. gonorrhoeae with a single specimen. An initial positive result is followed by repeat tests with probes to identify chlamydiae or gonococci. This test is more sensitive than C. trachomatis culture and is at least as sensitive as culture for gonococci. It deserves further evaluation and comparison with NAATs and may well offer an attractive alternative for diagnosis and screening of these infections.

Bacteriological Techniques↗
PubMed1999

Brief behavioural skills building intervention for female controlled methods of STD-HIV prevention: outcomes of a randomized clinical field trial.

The need for female controlled methods for preventing HIV infection is well recognized and women have been found to accept the female condom for these purposes. Women (n = 105) were randomly assigned to receive either (a) a 3-h behavioural skills building intervention that concentrated on educating women about the female condom, motivating female condom use, and building behavioural skills relevant to using the female condom, or (b) a time-matched broadly defined women's health education intervention. Women who received the female controlled skills building intervention used the female condom to a greater extent than did women in the health education condition. Importantly, the effects of the behavioural skills intervention were most pronounced for women who reported only one male sex partner in the previous 6 months compared to women with multiple sex partners. However, female condom use was modest, with only one in 5 vaginal intercourse acts being protected by female condoms among women with one partner who received skills training. Interventions are needed to further enhance use of the female condom and new female controlled methods are needed for the majority of women at risk who did not adopt the female condom.

Adult↗
PubMed1999

Enhanced nitric oxide synthesis reverses salt-induced alterations in blood flow and cGMP levels.

To understand the role of nitric oxide in salt-induced hypertension, we evaluated cardiovascular, hemodynamic and biochemical parameters in Dahl salt-sensitive rats fed low (0.3%) and high (8.0%) sodium diets. Two high salt groups received 1.25 and 2.5 g/L l-arginine in their drinking water. After three weeks of treatment, blood pressure was greater in the high salt groups. l-arginine did not modify salt-induced hypertension. Eicosapentaenoic acid (EPA) caused a smaller depressor response compared to normotensive rats. The increase in blood pressure was associated with decreases in aortic and renal blood flows. In renal artery, the reduction was counteracted by both l-arginine doses; whereas in the aorta, only the higher l-arginine one restored blood flow. The salt-induced reduction in aortic cyclic GMP level was only overcome by the higher l-arginine treatment. These data suggest that at the dose levels tested, nitric oxide reverses the reduction in cGMP and blood flow, but not the blood pressure changes associated with salt-induced hypertension.

Animals↗
PubMed1999

Malignant lymphoma of gastric mucosa-associated lymphoid tissue in Jamaica.

The recently appreciated concept of Mucosa-Associated Lymphoid Tissue (MALT) and the characteristics of the lymphomas arising therein are discussed with reference to the clinical, histological and immunohistochemical features of the first four cases of gastric MALT lymphomas diagnosed at the University Hospital of the West Indies. These tumours are low-grade B-cell lymphomas, which may undergo high-grade transformation. They are aetiologically associated with Helicobacter pylori (H pylori) infection in the stomach and may be cured in the early stages with antibiotics. Our cases were diagnosed from gastrectomy specimens removed for suspected carcinoma. All were high-grade, and associated with H pylori; 3 cases presented as advanced disease. Documentation of the features of these lymphomas will increase awareness and earlier recognition.

Aged↗
PubMed1999

The ectopic ACTH syndrome and superior vena cava obstruction due to a malignant carcinoid tumour of the thymus.

We report the case of a 28-year-old African Caribbean woman with Cushing's syndrome and superior vena cava obstruction secondary to an ACTH-secreting carcinoid tumour of the thymus. The case highlights the problems which may be encountered in performing the 2-day high dose dexamethasone suppression test but clinicians are reminded that this test or any other dynamic test is absolutely essential for elucidating the cause of ACTH-dependent Cushing's Syndrome.

ACTH Syndrome, Ectopic↗
PubMed1998

Possible mechanisms of salt-induced hypertension in Dahl salt-sensitive rats.

Genetic factors, diet, and salt sensitivity have all been implicated in hypertension. To further understand the mechanisms involved in salt-induced hypertension, cardiovascular, hemodynamics, and biochemical parameters in Dahl salt-sensitive rats were evaluated in animals on high- and low-sodium diets. During a 4-week treatment period, blood pressure was significantly elevated in the high (8.0%) salt group compared to the low (0.3%) salt group (p< or =0.05 for weeks 2 and 4, respectively). No significant changes were observed in heart rate. The increase in blood pressure was associated with significant increases in lower abdominal aortic and renal vascular resistance, along with a reduction in blood flow. A fourfold increase in arginine vasopressin was observed in animals on the high-salt diet. In contrast, there was no effect on plasma sodium, potassium, or aldosterone levels during the treatment period. As measured in isolated aortic rings, the high-salt diet also caused a significant elevation in stimulated norepinephrine release and a reduction in cyclic GMP levels. These data suggest that salt-induced elevation in blood pressure is due to activation of both the sympathetic and arginine vasopressin systems via mechanisms involving decreased cyclic GMP generation in vascular smooth muscle.

Aldosterone↗
PubMed1998

Severe transmural myocardial ischemia after dipyridamole administration implicating coronary steal.

Myocardial perfusion imaging with coronary vasodilators is routinely used for patients with suspected coronary disease who are unable to exercise. Since these agents work by increasing blood flow without significantly changing myocardial oxygen demand, they generally do not produce ischemia. A minority of patients show evidence of ischemia which some investigators suggest is due to a coronary steal phenomenon, but this has been challenged by several investigators. We present the case of a patient who developed severe transmural myocardial ischemia manifested by ST-segment elevation and severe perfusion defects which occurred after dipyridamole administration and which were reversed with aminophylline and nitroglycerin. This case supports the notion that coronary vasodilation with dipyridamole can induce a coronary steal.

Coronary Angiography↗