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Biomedical subjects

L A Williams

Publications and source records attributed to L A Williams.

At least 37 records · Page 2Linked to original sources
PubMed1999

Programmed cell death without DNA fragmentation in the jimpy mouse: secreted factors can enhance survival.

Jimpy is one of many related mutations affecting the myelin proteolipid protein gene that causes severe hypomyelination in the central nervous system (CNS). Underlying the hypomyelination is a failure of oligodendrocytes (OLs) to differentiate, and the premature death of large numbers of OLs during the developmental period. Previous light and electron microscopic evidence suggested that jimpy OLs die in a manner consistent with programmed cell death. We have used TUNEL staining as a biochemical marker for apoptosis in conjunction with immunostaining for OL and myelin markers. At 13 - 14 days postnatal, a time when the number of dying OLs in jimpy CNS is increased more than five times normal, there are only modest increases (70% in spinal cord; 20% in cerebral cortex) in TUNEL labeled cells in mutant CNS tissues. The results in vitro are similar, and only a small per cent of TUNEL labeled cells have the antigenic phenotype of OLs. The discrepancy between numbers of dying and TUNEL labeled cells suggests either that most jimpy OLs do not undergo programmed cell death or that the biochemical pathways leading to their death do not involve DNA fragmentation which is detected by the TUNEL method. We also present evidence that jimpy OLs show increased survival and enhanced differentiation when they are grown in vitro in medium conditioned by cells lines which express products of the proteolipid protein gene. Cell lines expressing proteolipid protein and the alternatively spliced DM20 protein have differential effects on cell numbers and production of myelin-like membranes.

Animals↗
PubMed1999

Preventing acute respiratory infections and diarrhoea in child care centres.

This study was designed to explore the physical characteristics and child care practices of child care centres as potential risk factors for respiratory infections and diarrhoea in children 3-35 mo of age. A dynamic cohort averaging 667 children from 40 child care centres in Campinas (Brazil) was followed up for 8 mo. Direct structured observations were made to collect information on the centres' physical structure, child activities and child care practices. Despite their good infrastructures, hand washing in the centres was infrequent, and nearly 30% of diaper changes were unhygienic. Risk factors for diarrhoea included the presence of flies during meals, infrequent child hand washing before meals, and infrequent child hand washing after defecation, with relative risks of 1.33, 1.73 and 1.63, respectively. There was 33% less diarrhoea in classes where soap was frequently used during diapering. Contrary to our hypotheses, ventilation, group size and child density were not associated with respiratory infections, as was the case for most other factors studied. Only mixing of groups and a larger classroom area were found to be negatively associated with lower and upper respiratory infections, respectively. The results indicate that improving hygiene practices is the only intervention in child care centre characteristics with good potential to reduce diarrhoea among attendees. For respiratory infections, no modifiable characteristic with intervention potential was identified.

Brazil↗
PubMed1999

Developing a video-mediated communication system for hospitalized children.

When a student is away from school for an extended time due to illness, he/she is provided with a tutor or access to in-hospital classrooms to keep up with his/her studies. This isolates the child from normal classroom experiences. A remote-control videoconferencing system (VCS), P.E.B.B.L.E.S.trade mark (Providing Education by Bringing Learning Environments to Students), was developed to allow a student access to his/her regular classroom from the hospital. Remote control is provided by a game pad, which allows the student to direct the system. The first iteration, P.E.B. B.L.E.S. I, tested feasibility. The design of P.E.B.B.L.E.S. II provides an integrated version of the system with user interface aimed at children. Four studies examined its efficacy in allowing a student to participate in typical classroom activities and in providing him/her a sense of presence in the classroom. Results indicate that the system can be used with relatively few errors when set to perform the majority of required activities. The study-participants reported positive experiences using the system, and remote users appeared to have a sense of presence in the classroom.

Attitude↗
PubMed1999

Elimination and reintroduction of primary and secondary syphilis.

OBJECTIVES: This study was conducted to define factors associated with the epidemic spread, elimination, and reintroduction of primary and secondary syphilis in King County, Washington, from 1987 through 1998. METHODS: Reports of primary and secondary syphilis in King County from 1987 through 1998 were reviewed retrospectively. RESULTS: During the epidemic spread of syphilis, only 15.8% of cases were imported. A total of 24.0% of patients reported cocaine use, and 18.3% of female patients reported having commercial sex. During the elimination of syphilis, significantly higher percentages of cases were imported and lower percentages of patients reported cocaine use or female commercial sex. During the reintroduction of syphilis in 1997-1998, 68% of patients were men who reported sex with men; of this 68%, 66% were sero-positive for HIV. Most men reporting sex with men were 30 years or older and recruited many anonymous partners. CONCLUSIONS: As syphilis wanes, local control must focus on outbreaks following its reintroduction. Resurgence of syphilis among men reporting sex with men recapitulates the epidemiology of syphilis before the historical advent of AIDS, warranting immediate attention to this problem.

Adult↗
PubMed1998

A comparison of bone scintigraphy and MRI in the early diagnosis of the occult scaphoid waist fracture.

OBJECTIVE: To determine the accuracy of MRI in the assessment of the radiographically occult scaphoid fracture. DESIGN: This prospective study compared the sensitivity and specificity of MRI for detection of radiographically occult scaphoid fractures with bone scintigraphy (BS), the currently accepted imaging modality of choice. Consecutive patients with clinical signs of a scaphoid injury but no evidence of fracture on plain radiographs at presentation and after 7-10 days were evaluated by MRI and BS. All images were reported in masked fashion and the sensitivities and specificities of the imaging modalities determined. All patients with a scaphoid fracture demonstrated by MRI or BS were followed for at least a year after injury. PATIENTS: Forty-three subjects (aged 12-74 years) had both MRI and BS carried out on average 19 days from the injury date. RESULTS AND CONCLUSIONS: Six patients (14%) had scaphoid waist fractures. There were other bony injuries in a further six. In 40 patients there was agreement between the BS and MRI findings. In three cases there was discrepancy between the imaging modalities; in all three MRI was found to be the more sensitive and specific. MRI could become the investigation of choice for this injury.

Adolescent↗
PubMed1998

Magnetic resonance imaging of acute intraosseous disc herniation.

Schmorl's nodes, the result of previous intraosseous disc herniation (IODH), are a common incidental finding on plain radiographs, computed tomography (CT) and magnetic resonance imaging (MRI). Acute IODH can, however, cause severe back pain, and the radiological features may also lead to inappropriate suspicion of malignancy or infection. We present eight cases of acute IODH in order to illustrate how the correct diagnosis can be made by MRI. In six cases isotope bone scintigraphy had been performed, demonstrating focal increased activity at the site of IODH. MRI can reinforce the concern about serious underlying pathology by the demonstration of marrow oedema, which may be localized around the disc herniation or extensive, extending throughout the vertebral body and into the pedicles. The key to the correct diagnosis is the recognition of the endplate defect and disc herniation. In three cases the diagnosis may have been possible from plain radiographs in which disc calcification visible on previous radiographs had migrated into an intraosseous location.

Acute Disease↗
PubMed1998

A long-term five-year randomized controlled trial of hydroxychloroquine, sodium aurothiomalate, auranofin and penicillamine in the treatment of patients with rheumatoid arthritis.

OBJECTIVE: To compare the efficacy of hydroxychloroquine, penicillamine, sodium aurothiomalate and auranofin in the treatment of active rheumatoid arthritis over a period of 5 yr. METHOD: Five hundred and forty-one patients with definite or classical rheumatoid arthritis were entered into an open randomized controlled trial with a flexible dose regimen designed to reflect clinical practice. Decisions to stop treatment with any one of the disease-modifying anti-rheumatic drugs (DMARDs) were based on an agreed trial protocol which defined criteria for adverse reactions and therapeutic failure. The managing physicians' decisions were confirmed in a separate monitor clinic. RESULTS: The proportion of patients who remained on their first DMARD or who were in remission at 5 yr was 53% for penicillamine, 34% for sodium aurothiomalate, 31%, for auranofin and 30% for hydroxychloroquine (P < 0.001). In patients who stayed on their first DMARD, all groups showed a 30-50% improvement in C-reactive protein, erythrocyte sedimentation rate, Ritchie Index and joint stiffness, and a deterioration in their Larsen score. There was no evidence of physician bias to explain the larger proportion of patients remaining on penicillamine for 5 yr. CONCLUSION: Despite the increased popularity of sulphasalazine and inmmunosuppressives, the drugs in this study continue to be used worldwide. The natural history of rheumatoid arthritis requires long-term follow up to establish drug efficacy. Evidence is needed as to whether the newer regimens will prove to be more effective and safer in the longer term than the commonly prescribed DMARDs. The data from this trial will provide a reference for comparison with future studies.

Adult↗
PubMed1997

Prospective cohort study of factors influencing the relative weights of the placenta and the newborn infant.

OBJECTIVES: To determine the demographic, environmental, and medical factors that influence the relative weights of the newborn infant and the placenta and compare this ratio with other factors known to predispose to adult ill health. DESIGN: Prospective cohort study. SETTING: The tertiary referral centre for perinatal care in Perth, Western Australia. SUBJECTS: 2507 pregnant women who delivered a single live infant at term. MAIN OUTCOME MEASURES: Placental weight, birth weight, and the ratio of placental weight to birth weight. RESULTS: By multiple regression analysis the placental weight to birthweight ratio was significantly and positively associated with gestational age, female sex, Asian parentage, increasing maternal body mass index, increased maternal weight at booking, lower socioeconomic status, maternal anaemia, and increasing number of cigarettes smoked daily. There were no consistent relations between the placental weight to birthweight ratio and measures of newborn size. CONCLUSIONS: The ratio of placental weight to birth weight is not an accurate marker of fetal growth. In its role as a predictor of adult disease the ratio may be acting as a surrogate for other factors which are already known to influence health and may act before or after birth. Determining the role that relative growth rates of the fetus and placenta have in predisposing to adult disease requires prospective study to account for the many confounding variables which complicate this hypothesis.

Adult↗
PubMed1997

Catecholaminergic innervation of interscapular brown adipose tissue in the naked mole-rat (Heterocephalus glaber).

The thermogenic potential of the interscapular brown fat pad in the naked mole-rat Heterocephalus glaber, that exhibits poikilothermic thermal responses to changing temperatures is reported. Histological and ultrastructural study of the brown fat pad showed that it consists of layers of skeletal muscle interposed between the layers of brown adipose tissue with both unilocular and multilocular adipocytes. Large numbers of mitochondria were present between and around the lipid droplets of these cells. Glyoxylic acid condensation, used to demonstrate catecholaminergic nerves, was evident in low concentrations in the connective tissue between the brown adipocytes. A 3-dimensional computer-aided reconstruction of the fat pad showed the extent and ramification of nerves and blood vessels between the adipocytes. These findings show that although the naked mole-rat is regarded as an endothermic poikilotherm, it possesses anatomical features usually found in homeothermic mammals, which are essential for thermogenesis.

Adipocytes↗
PubMed1997

The impact of charging for insecticide on the Gambian National Impregnated Bednet Programme.

During the second year of the Gambian National Impregnated Bednet Programme (NIBP) charges for insecticide ($0.50 per net) were introduced into the half of the primary health care villages in the country where insecticide have been provided free of charge the previous year. Free insecticide was provided in the remaining villages that had acted as controls during the previous year. In villages where insecticide was provided free, 77% of nets were treated with insecticide. In contrast, in villages where charges were made coverage was only 14%. During the first year of the NIBP, mortality in children was significantly lower in villages where insecticide was provided free than in the control villages. Introduction of a charge for insecticide into the first group of villages and the provision of free insecticide in the latter abolished this difference. The cash income of rural Gambians is very limited and payment of even $2-3 for insecticide treatment for all the bednets in a household represents a substantial outlay. Further education on the benefits of treatment of nets and/or the provision of cheaper insecticide will be required before the full benefits of this powerful new malaria control measure can be fully realised in the Gambia.

Bedding and Linens↗
PubMed1997

The Oklahoma bombing. Lessons learned.

The Oklahoma City bombing experience in April of 1995 provided a unique opportunity to test the effectiveness of an existing disaster plan. The critical care nurses at Columbia Presbyterian Hospital learned valuable lessons about managing intense activity, equipment and supplies, staffing resources, and visitor issues. The degree to which the bombing affected the emotional state of personnel was unanticipated, and leaders learned that critical stress management interventions should be included in every emergency preparedness plan. Additionally, recommendations include using runners for communication; assigning specific roles (supplies, staffing, triage); keeping additional staff in reserve for shift relief; ensuring ample hospital staff members are available to coordinate visitors and media; and setting up record systems to preserve continuity. The unique lessons learned as a result of this terrorist attack can be used by other critical care nurses to understand and refine disaster plans.

Critical Care↗
PubMed1996

Human T lymphocytes and hematopoietic cell lines express CD24-associated carbohydrate epitopes in the absence of CD24 mRNA or protein.

The CD24 surface antigen is a small glycophosphatidylinositol (GPI)-anchored glycoprotein found on human granulocytes and most B lymphocytes. Many CD24 monoclonal antibodies (MoAbs) have been described that identify several epitopes, with the majority of them related to carbohydrate structures associated with the CD24 molecule. Considerable variation has been observed in the apparent tissue distribution of the CD24 antigen depending on the MoAb used, and hence the CD24 epitope studied. In this study, CD24 expression by human cell lines and normal hematopoietic call populations was assessed using a panel of carbohydrate and protein core-specific CD24 MoAbs and reverse transcriptase polymerase chain reaction (RT-PCR) analysis. A number of CD24 carbohydrate epitope-reactive MoAbs bound to both T lymphocytes and several hematopoietic cell lines, despite the absence of concomitant CD24 mRNA or detectable surface CD24 core protein in the same cells. This additional CD24 MoAb reactivity on T lymphocytes was, in common with that observed on granulocytes (CD24 protein+), specifically inhibited by the presence of both sialyllactose and mucin. Similarly, the binding of carbohydrate epitops-reactive CD24 MoAb was reduced on both T lymphocytes and granulocytes by pretreatment with phospholipase C, pronase, or neuraminidase. Together, the data indicate that a number of CD24-associated carbohydrate epitopes have a broader tissue distribution than the CD24 protein and are expressed on additional GPI-linked molecule(s). These findings have immediate implications for both leukemia phenotyping and attempts to examine CD24 function with CD24 MoAb.

Animals↗
PubMed1996

Waiting list management in general practice: a review of orthopaedic patients.

OBJECTIVE: To review all patients on a current general practice orthopaedic waiting list for outpatient appointments with regard to accuracy of the list, clinical priority, and need for further radiological investigation before hospital attendance. DESIGN: Record review by one general practitioner and a radiologist, and discussion with patients of management alternatives. SETTING: Six partner city centre urban fund-holding general practice, list size 8651 (29% low deprivation payment status). SUBJECTS: 116 adults on an orthopaedic waiting list. MAIN OUTCOME MEASURES: List accuracy (patient details and status on waiting list); clinical priority (severity of condition); further investigations (results of tests after radiological review). RESULTS: 32 patients (28%) were removed from the waiting list because of inaccuracies. 14 patients were considered to be high priority and referred to other hospitals by utilising waiting list initiative funds. Of these patients, five agreed to referral to another hospital (treatment completed on average within three months of rereferral), six did not wish to be rereferred, and two did not attend to discuss the offer and remained on the original waiting list. One prioritised patient had further radiological investigations, was reassured, and was taken off the waiting list. 10 patients had further investigations. These resulted in six patients being referred to other hospitals, three being taken off the waiting list, and one seeking private care. CONCLUSIONS: Systematic review of patients on an orthopaedic waiting list of one general practice, though time consuming, led to the identification of inaccuracies in the list and changes in management. Costs need further evaluation, but if the findings occur widely substantial benefits could be achieved for patients.

Adult↗
PubMed1996

Isolation and characterization of the Schizosaccharomyces pombe gene encoding transcript elongation factor TFIIS.

A gene designated tfs1 has been isolated from Schizosaccharomyces pombe based on its similarity to genes encoding transcription elongation factor TFIIS. The nucleotide sequence of the tfs1 gene predicts a polypeptide with similarity to mammalian. Drosophila and Saccharomyces cerevisiae TFIIS. A haploid Sz. pombe strain with tfs1 deleted from the genome is viable. Thus, tfs1 is not essential for viability. However, deletion of tfs1 results in slow growth and increased sensitivity to the drug 6-azauracil, a phenotype similar to that of a S. cerevisiae strain deleted for the gene encoding TFIIS. The DNA sequence of tfs1 has been deposited in GenBank under Accession Number U20526.

Base Sequence↗
PubMed1996

Expression and function of CD80 and CD86 costimulator molecules on synovial dendritic cells in chronic arthritis.

OBJECTIVE: To examine CD86 expression on dendritic cells isolated from the synovial fluid (SFDC) of patients with chronic arthritis, and to determine the importance of both CD80 and CD86 molecules in SFDC-T lymphocyte interactions. METHODS: CD86 messenger RNA (mRNA) and surface expression were analyzed in SFDC using reverse transcriptase-polymerase chain reaction and flow cytometry, respectively. The costimulator activity of the SFDC CD80 and CD86 molecules was determined by allogeneic mixed lymphocyte reaction (MLR). CD80 and CD86 induction on SFDC during in vitro culture was also examined. RESULTS: Fresh SFDC either lacked or showed very weak surface expression of CD86 molecules (as shown previously for CD80), yet contained CD86 mRNA. CD80 antibodies minimally inhibited an allogeneic MLR, whereas CD86 antibodies and CTLA-4 Ig showed significant inhibition. Both CD80 and CD86 molecules were inconsistently induced on SFDC following culture in either media, interferon-gamma, or granulocyte-macrophage colony-stimulating factor. CONCLUSION: SFDC may be defective antigen-presenting cells in vivo. The ability of CD80 and CD86 molecules to be induced and become functional on SFDC in vitro implies the presence of a negative regulatory compound(s) in the synovial environment.

Abatacept↗
PubMed1996

Human dendritic cells activate T lymphocytes via a CD40: CD40 ligand-dependent pathway.

The CD40:CD40 ligand (CD40L) interaction provides T lymphocyte-mediated help for B lymphocyte and monocyte function but has also been shown to serve as a co-stimulus for T lymphocyte activation. In this report, we studied the regulation of CD40 expression and its functional relevance for the human dendritic cell (DC) stimulation of T lymphocytes. Only a small subpopulation of directly isolated blood DC expressed CD40. However, CD40 was rapidly up-regulated by culture, and its expression was further enhanced by interleukin (IL)-1 alpha, IL-1 beta, IL-3, tumor necrosis factor-alpha and granulocyte/macrophage-colony-stimulating factor. Expression of CD40L on DC was not detected. The proliferation of T lymphocytes in an allogeneic mixed leukocyte reaction, stimulated by blood DC or epidermal Langerhans cells, was significantly reduced in the presence of the CD40 immunoglobulin (CD40Ig) fusion protein or CD40L monoclonal antibodies. Cross-linking of CD40 on directly isolated DC with mouse CD40L trimer (mCD40LT) markedly augmented CD80 and CD86 up-regulation. Nevertheless, the same cross-linking mCD40LT inhibited DC stimulated T lymphocyte proliferation. When CD40Ig was added simultaneously with CTLA-4Ig, only minimal and variable additional inhibition of DC-stimulated allogeneic T lymphocyte proliferation and IL-2 secretion was observed, compared to each fusion protein alone. These results suggest that both CD80/CD86-dependent and -independent components of DC-T lymphocyte CD40:CD40L co-stimulation exist and further emphasize that the majority of blood DC have to differentiate or be activated to express co-stimulatory molecules.

Abatacept↗