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Biomedical subjects

C Hoy

Publications and source records attributed to C Hoy.

At least 19 recordsLinked to original sources

Natural experiments: an underused tool for public health?

Policymakers and public health researchers alike have demanded better evidence of the effects of interventions on health inequalities. These calls have been repeated most recently in the UK in the final Wanless report, which spoke of the "almost complete lack of an evidence base on the cost-effectiveness of public health interventions", and pointed more generally to the limited evidence base for public health policy and practice. Wanless and others have suggested that the gaps may be partially filled by exploiting the opportunities offered by "natural experiments", such as changes in employment opportunities, housing provision, or cigarette pricing. Natural experiments have an important contributions to make within the health inequalities agenda. First, they can play an important role in investigating the determinants of health inequalities. Second, they can assist in the identification of effective interventions, an area where it is widely acknowledged that the evidence-base is currently sparsely populated. This paper discusses some of the benefits and limitations of using this type of evidence, drawing on two ongoing quasi-experimental studies as examples.

Cost-Benefit Analysis↗

Adolescents in China.

This paper reviews the nature and explores the context of, and reactions to, reproductive health education in China by both the target population of adolescents at school and the wider public. The debate about reproductive health education and its content is taking place within the context of rapid behavioural and sociological changes in China which, in turn is, generating conflicting demands concerning the need for education by the population and the control of the population by the government. Foucault's theories on sexuality and discipline are found to be useful in exploring the subject of reproductive health education in China.

Adolescent↗

Multiple cell culture factors can affect the glycosylation of Asn-184 in CHO-produced tissue-type plasminogen activator.

Human tissue-type plasminogen activator (t-PA) contains a variably occupied glycosylation site at Asn-184 in naturally produced t-PA and in t-PA produced in recombinant Chinese hamster ovary (CHO) cells. The presence of an oligosaccharide at this site has previously been shown to reduce specific activity and fibrin binding. In this report, the site occupancy of t-PA is shown to increase gradually over the course of batch and fed-batch CHO cultures. Additional cell culture factors, including butyrate and temperature, are also shown to influence the degree of glycosylation. In each of these cases, conditions with decreased growth rate correlate with increased site occupancy. Investigations using quinidine and thymidine to manipulate the cell cycle distribution of cultures further support this correlation between site occupancy and growth state. Comparison of the cell cycle distribution across the range of cell culture factors investigated shows a consistent relationship between site occupancy and the fraction of cells in the G(0)/G(1) phase of the cell cycle. These results support a correlation between growth state and site occupancy, which fundamentally differs from site occupancy trends previously observed and illustrates the importance of the growth profile of CHO cultures in producing consistently glycosylated recombinant glycoproteins.

Animals↗

A five year outbreak of methicillin-susceptible Staphylococcus aureus phage type 53,85 in a regional neonatal unit.

We identified a 5-year outbreak of a methicillin-susceptible Staphylococcus aureus (MSSA) strain, affecting 202 babies on a neonatal unit, by routine weekly phage typing all S. aureus isolates. Multiple staged control measures including strict emphasis on hand hygiene, environmental and staff surveillance sampling, and application of topical hexachlorophane powder failed to end the outbreak. S. aureus PT 53,85 (SA5385) was found on opened packs of Stomahesive, used as a neonatal skin protectant. Only following the implementation of aseptic handling of Stomahesive, and the use of topical mupirocin for staff nasal carriers of SA5385, and for babies colonized or infected with S. aureus, did the isolation rate of SA5385 decline. DNA fingerprinting indicated that > or =, 95% of SA5385 isolates were clonal. In vitro death rates of SA5385 on Stomahesive with human serum were significantly lower than on Stomahesive alone (P = 0.04), and on cotton sheet with serum (P = 0.04), highlighting the potential of this material as a survival niche. Phage typing remains a valuable, inexpensive and simple method for monitoring nosocomial MSSA infection.

Bacteriophage Typing↗

Association of specific cytomegalovirus genotypes with death from myelosuppression after marrow transplantation.

A retrospective analysis of cytomegalovirus (CMV) genotype was conducted on 281 CMV isolates obtained from marrow transplant recipients. The genotyping was based on sequence variations in the gene encoding envelope glycoprotein B (gB) as detected by restriction analysis of polymerase chain reaction (PCR)-amplified gB DNA. Among all isolates studied, the distribution of gB types 1-4 was 48.4%, 16.4%, 24.6%, and 8.2%, respectively, with only 2.5% of all isolates containing more than one gB type. The association of gB types with acute graft-versus-host-disease (GVHD) and death related to myelosuppression was examined using appropriate multivariable regression models. Covariables in addition to gB type included underlying disease type, donor-recipient HLA matching, donor CMV serostatus, and age as a continuous variable. Death associated with myelosuppression occurred in 2.9% or 4 of 136 patients with gB1, 0% or 0 of 46 patients with gB2, 21.7% or 15 of 69 patients with gB3, and 17.4% or four of 23 patients with gB4. The significant association of CMV gB type with death due to myelosuppression was maintained in a multivariable analysis (P < .001). In addition, the data also suggested that gB types 3 and 4 may be associated with a reduced hazard of grades II to IV acute GVHD.

Adult↗

Hickman catheters: left-sided insertion, male gender, and obesity are associated with an increased risk of complications.

BACKGROUND: Semipermanent tunnelled silicone rubber Hickman catheters are widely used to provide durable central venous access for patients with cancer or haematological disease. AIMS: To document the frequency and severity of Hickman catheter related adverse events and to identify predisposing factors. METHODS: A retrospective review was undertaken of 153 sequential Hickman catheters inserted into patients receiving treatment for cancer or haematological disease. All Hickman catheters were inserted percutaneously in a radiology department under local anaesthesia and fluoroscopic control. The exact position of the catheter tip was determined by reviewing post-insertion radiographs. RESULTS: The median duration of catheter use was 55 days (range one-650). Complications led to the removal of 32% of catheters. Exit site infection complicated 22% of catheters, septicaemia 7%, migration or dislodgment 7%, and venous thrombosis 8%. Complications were more common in male patients (exit site infection and catheter loss), in patients with acute leukaemia (septicaemia) and in obese patients (catheter migration). Left sided catheters caused more venous thrombosis and were more likely to malfunction or block. Left sided catheters required removal more frequently than right sided catheters. Termination of the Hickman catheter within the high superior vena cava (SVC) resulted in loss of function earlier when compared to termination with the low SVC or right atrium (RA). CONCLUSIONS: Right-sided Hickman catheters terminating in the low SVC/RA offer the best chance of durable function. The use of subcutaneously tunnelled catheters in obese patients poses unique problems with catheter migration. Vigilance in the placement and care of Hickman catheters remains essential.

Catheterization, Central Venous↗

Transforming growth factor-beta enhances the in vivo effector function and memory phenotype of antigen-specific T helper cells in experimental autoimmune encephalomyelitis.

Transforming growth factor-beta (TGF-beta) had a profound effect on the in vitro phenotypic development of Ag-activated Th cells and enhanced the in vivo effector function of these cells upon adoptive transfer. Previous studies have shown that there are two types of Th cell populations found in unimmunized animals, naive helper cells, which are short-lived and express low levels of CD44 and high levels of CD45R and Mel-14, and memory helper cells, which have a long life span and express high levels of CD44 and low levels of CD45R and Mel-14. Culturing of Ag-specific murine Th cell lines and clones in the presence of TGF-beta greatly enhanced both the memory phenotype of the cultured cells and the effector function upon adoptive transfer in experimental autoimmune encephalomyelitis. Histologic evaluation of spinal cords from recipients receiving passively transferred murine T cell lines cultured with TGF-beta revealed large demyelinated plaques (multiple sclerosis-like) that were not present in animals receiving cells cultured with Ag alone. TGF-beta also enhanced the capability of myelin basic protein-specific Lewis rat T cell lines to transfer experimental autoimmune encephalomyelitis and potentiated a purified protein derivative-specific rat helper cell line to transfer delayed type hypersensitivity. Thus, the effects of TGF-beta did not appear to be limited by species specificity, Ag specificity, or in vivo T cell function. This is the first study showing that TGF-beta can potentiate the development and maintenance of the Th cell memory phenotype in vitro and enhance their in vivo effector function in an animal disease model.

Animals↗

Quantitative changes in faecal microflora preceding necrotising enterocolitis in premature neonates.

Quantitative studies of faecal bacterial flora were carried out during the week preceding the clinical onset of 12 episodes of neonatal necrotising enterocolitis. There were considerable quantitative changes in the faecal flora preceding the clinical onset of both definite and possible episodes of necrotising enterocolitis. There was a decline in the numbers of some species from up to 72 hours before the clinical onset of the disease. Enterobacteriaceae were isolated from samples collected during the 48 hours preceding the clinical onset of all four definite episodes of necrotising enterocolitis. These were 'new' isolates in two episodes, and considerably increased numbers in another. The changes that we found are probably the result of changes in intraluminal conditions that precede the clinical onset of necrotising enterocolitis.

Bacteria↗

Thrombolytic therapy in canine pulmonary embolism. Comparative effects of urokinase and recombinant tissue plasminogen activator.

We compared thrombolytic and pulmonary hemodynamic effects of recombinant tissue plasminogen activator (rtPA) and urokinase (UK) in canine micropulmonary thromboembolism. Dogs were embolized with radioactive autologous blood clot to increase mean pulmonary artery pressure (from 13 to 34 mm Hg, p less than 0.005) and decrease cardiac output (2.5 to 1.6 L min, p less than 0.005). Four groups of six dogs were treated. We employed two doses of UK, 30,000 U/kg (UK30) and 60,000 U/kg (UK60), and two doses of rtPA, 1 mg/kg (rtPA1) and 2 mg/kg (rtPA2). Drugs were infused over 15 min. Rate and extent of pulmonary thrombolysis were assessed by continuously counting over both lung fields with a gamma camera. Compared with treatment with UK, both rtPA regimes significantly increased thrombolysis. Mean total pulmonary thrombolysis was 14 and 23% with UK30 and UK60, respectively, and 35 and 43% with rtPA1 and rtPA2. Corresponding to the increased thrombolysis, pulmonary hemodynamics improved most with rtPA. From 90 min to 3 h, pulmonary artery pressure was significantly lower with both rtPA regimes than with either UK regime. These results indicate, at least in the model employed, that compared with treatment with UK, pulmonary thrombolysis and corresponding hemodynamic improvement are greatest with rtPA.

Animals↗

Referencing: the cohesive use of pronouns in the written narrative of college underprepared writers, nondisabled writers, and writers with learning disabilities.

The purpose of this study was to explore whether college normally achieving writers (n = 35), writers with learning disabilities (n = 35), and underprepared writers (n = 35) demonstrated any differences in their ability to utilize the semantic roles and syntactic rules needed to apply cohesive referencing in written text. Cohesive referencing (the ability to assign roles to the speaker and addressee in written communication) is a critical aspect of written language. In addition, the study explored the relation between referential cohesion and the quality and coherence of a written text.

Adult↗

Transient hypoxia enhances the frequency of dihydrofolate reductase gene amplification in Chinese hamster ovary cells.

Exposure of Chinese hamster cells to reduced oxygen partial pressure results in a marked enhancement in the frequency of methotrexate resistance and dihydrofolate reductase gene amplification. The frequency of enhanced resistance is a function of the length of exposure to hypoxic conditions and the time after recovery from hypoxia when cells are plated into methotrexate-containing medium. Hypoxia results in an inhibition of DNA synthesis; upon return to normal oxygen atmosphere, greater than 60% of cells in S phase at the time hypoxia was started subsequently undergo overreplication of DNA within a single cell cycle. The cells with the increased frequency of gene amplification are derived from this subset of overreplicated cells. These results are discussed within the context of the hypoxic state of many solid tumors and the high frequency of aneuploidy, chromosomal aberrations, and spontaneously occurring resistances to a number of cancer chemotherapeutic agents.

Anaerobiosis↗