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Biomedical subjects

C Jenkins

Publications and source records attributed to C Jenkins.

At least 37 records · Page 2Linked to original sources
PubMed2000

Evidence of a T(H) 1 type response associated with recurrent miscarriage.

OBJECTIVE: To determine whether the T(H) 1 cytokine interferon (IFN)-gamma is associated with miscarriage whereas the T(H) 2 cytokine interleukin (IL)-10 is associated with successful pregnancy. DESIGN: Controlled clinical study. SETTING: Healthy volunteers in an academic setting. PATIENT(S): Group 1 comprised 10 nonpregnant women; group 2, 10 first-trimester primigravid women; group 3, 10 first-trimester primigravid women suffering spontaneous abortion; and group 4, 10 first-trimester pregnant women with a history of miscarriage. All women were pregnant at the time of sampling, but 5 miscarried later in the first trimester. INTERVENTION(S): None of the patients received any medication. MAIN OUTCOME MEASURE(S): Serum levels of IL-10 and IFN-gamma. RESULT(S): Levels of IL-10 were significantly raised in normal pregnancy. Levels of IFN-gamma were raised in the recurrent-miscarriage group as compared with normal pregnancy. When patients in group 4 were divided into those whose pregnancies went to term and those who miscarried, we found that successful pregnancy was associated with a statistically significant increase in IL-10, whereas miscarriage was associated with significantly increased levels of IFN-gamma. CONCLUSION(S): These results support the view that miscarriage is associated with a T(H) 1 type response.

Abortion, Habitual↗
PubMed2000

Virus-like gene transfer into cells mediated by polyoma virus pseudocapsids.

Mouse polyoma virus-like particles (or pseudocapsids) are composed solely of recombinant viral coat protein. They can interact with DNA and transport it to cells, resulting in gene expression both in tissue culture and in mice. We demonstrate that DNA transfer in vitro depends on partial packaging of DNA within the virus-like capsid. Cell surface sialic acid residues and an intact microtubule network, required for viral infectivity, are also necessary for pseudocapsid-mediated gene expression from heterologous DNA. Thus, gene delivery in this system requires pathways utilised by polyoma virions, rather than proceeding via the 'nonspecific' endosomal route typical of nonviral systems such as liposomes or calcium phosphate precipitates. Despite the fact that all cells appear to internalise pseudocapsid/DNA complexes, only a proportion show productive gene delivery. Bulk internalisation of complexes is dependent on actin fibres, but not cell surface sialic acid or microtubules, indicating that a second transport pathway exists for pseudocapsids which is nonproductive for gene transfer. The model suggested by these data demonstrates the virus-like properties of the pseudocapsid system, and provides a basis for further development to produce a highly effective gene delivery vehicle. Gene Therapy (2000) 7, 2122-2131.

Animals↗
PubMed2000

Salmeterol/fluticasone propionate combination therapy 50/250 microg twice daily is more effective than budesonide 800 microg twice daily in treating moderate to severe asthma.

Three hundred and fifty-three asthmatic patients who remained symptomatic despite treatment with budesonide 800-1200 microg day(-1) (or equivalent) were randomized to a new combination therapy comprising salmeterol 50 microg and fluticasone propionate 250 microg (Seretide, Advair, Viani 50/250 microg) twice daily or budesonide 800 microg twice daily for 24 weeks. Patients kept daily records of their morning and evening peak expiratory flow (PEF), daytime and night-time symptom scores and daytime and night-time use of rescue salbutamol. Mean morning PEF increased by 451 min(-1) (baseline 361 l min(-1)) in the salmeterol/fluticasone propionate combination (SFC) group and by 19 l min(-1) (baseline 358 l min(-1)) in the budesonide group over the 24 weeks. The adjusted mean morning PEF over weeks 1 to 24 was significantly greater in the SFC group, despite the > three-fold lower corticosteroid dose (406 vs. 380 l min(-1); P < 0.001). A significantly greater improvement in evening PEF was also seen in the SFC group (adjusted mean 416 vs. 398 l min(-1); P<0.001). SFC also provided significantly better control of daytime symptoms and a significantly greater reduction in the requirement for rescue salbutamol compared with budesonide. These results demonstrate that SFC 50/250 microg twice daily is superior to budesonide 800 microg twice daily in the management of patients with moderate to severe asthma who are symptomatic on their existing dose of corticosteroid.

Adolescent↗
PubMed2000

Cost-effectiveness of salmeterol/fluticasone propionate combination product 50/250 microg twice daily and budesonide 800 microg twice daily in the treatment of adults and adolescents with asthma. International Study Group.

Despite a good understanding of the disease and its treatments, asthma continues to place a large economic burden on healthcare systems. As such, it is important to consider the economic impact of alternative therapeutic options for the treatment of this condition to ensure that scarce resources are used in the most efficient manner possible. Thus, the aim of asthma management from an economic perspective is to reduce the burden of this disease through maximizing health gain with available resources. A prospective economic analysis was conducted as part of a multicentre, randomized, double-blind, comparative trial of salmeterol/fluticasone propionate combination product (SFC) 50/250 microg twice daily vs. budesonide (800 microg twice daily) in adults and adolescents with asthma who were symptomatic despite treatment with inhaled corticosteroids at doses of 800-1200 microg day(-1). Treatment effectiveness was measured in terms of successfully-treated weeks, defined as a > or =5% improvement in morning peak expiratory flow, episode-free days (a day without the need for rescue medication, no nocturnal awakening or adverse events) and symptom-free days. Cost-effectiveness analyses were performed using direct healthcare and drug costs, from the perspective of the Swedish healthcare system (1998 prices), with appropriate sensitivity analyses to test the robustness of the findings. Overall, SFC produced significantly higher (P<0.001) proportions of successfully-treated weeks, episode-free days and symptom-free days. Direct asthma management costs were similar between the two groups [SEK19.6 ($US2.4) for SFC vs. SEK18.5 (SUS2.2) for budesonide]. The cost per successfully-treated week was lower for SFC than for budesonide [SEK204 ($US24.8) vs. SEK300 ($US36.4) per week], as were the costs per episode-free day [SEK51.1 ($US6.2) vs. SEK75.1 ($US9.1) per day] and symptom-free day [SEK42.2 ($US5.1) vs. SEK53.0 ($US6.4) per day]. Incremental cost-effectiveness ratios showed that the additional costs to achieve additional benefits with SFC were minimal. Costs per additional successfully-treated week, symptom-free day and episode-free day with SFC were SEK31.6 ($US3.9), SEK9.2 ($US1.1) and SEK7.7 ($US0.9), respectively, relative to budesonide. Sensitivity analysis showed that the results were stable over a wide range of assumptions. The results suggest that SFC is a more cost-effective treatment than budesonide in the management of moderate to severe asthma.

Adult↗
PubMed2000

Antioxidants: their role in pregnancy and miscarriage.

The aim of this study was to examine the role of antioxidants within the normal menstrual cycle, in healthy pregnancy, and in women suffering first-trimester miscarriage. The antioxidants chosen comprised of two from peripheral blood-plasma thiol and ceruloplasmin-and two extracellular parameters-superoxide dismustase (SOD) and red cell lysate thiol. We found that antioxidant levels varied little throughout the menstrual cycle. Pregnancies that went successfully to term were associated with increased levels of ceruloplasmin and SOD early in the first trimester. These changes were thought to offer the cell protection from the damage caused by the increased oxidative stress associated with pregnancy. First-trimester miscarriage was associated with significantly reduced levels of SOD. A subgroup of patients who miscarried in their first pregnancy, but whose second pregnancies were successful, had higher levels of plasma thiol and significantly reduced levels of red cell lysate thiol in the on-going pregnancy compared to levels at the time of miscarriage. Miscarriage and pregnancy appear to be associated with increased oxidative stress. In a successful pregnancy, however, changes occurred within the peripheral blood that offered protection from oxidant attack.

Abortion, Spontaneous↗
PubMed2000

Recommending analgesics for people with asthma.

Asthma is a common condition, affecting approximately 7% of people worldwide. However, the prevalence varies among countries, and in Australia, asthma affects 10% of adults and approximately 20% of children. For some of these patients, ingredients in some over-the-counter analgesics may pose problems. Aspirin sensitivity, defined as urticaria, angioedema, or rhinitis after aspirin ingestion, affects only 0.3% of the general population. However, certain patient groups, such as asthmatics, are at an increased risk, with reports of an incidence as high as 20% in this patient population. This phenomenon is not restricted to aspirin, as all nonsteroidal anti-inflammatory drugs (NSAIDs) that inhibit the enzyme cyclooxygenase display a high incidence of cross-sensitivity. In contrast, paracetamol (acetaminophen) is well tolerated by the majority of people with asthma and is seldom associated with cross-sensitivity. Determining who is likely to be affected is difficult because the sequence of symptoms is hard to predict, and patients often do not associate an asthma attack with the use of aspirin or an NSAID. The only definitive way to diagnose sensitivity is by provocation tests. In view of these difficulties, it is important for health care practitioners to take a pro-active stance by asking questions to determine whether aspirin sensitivity is a problem, counseling people about the risks, and helping them make an appropriate analgesic choice.

Acetaminophen↗
PubMed2000

Histological features of ocular adnexal lymphoma (REAL classification) and their association with patient morbidity and survival.

BACKGROUND: The histological characteristics of ocular adnexal lymphomas have previously provided only a limited guide to clinical outcome for affected patients. This clinicopathological relation was re-examined using the Revised European American Lymphoma (REAL) system to classify the tumours in a large cohort of patients. METHODS: The biopsies and clinical follow up data for 192 patients with ocular adnexal lymphoma were reviewed, the biopsies being regraded in accordance with the REAL classification. For each of five histological groups, logistic regression analysis was used to determine the odds ratios (OR) for the presence of systemic disease at the time of orbital diagnosis and Cox regression analysis was used to assess the hazard ratios (HR) for disseminated disease and lymphoma related death. For 108 patients in whom extraorbital spread occurred, the histological category of lymphoma was compared with the sites of dissemination. RESULTS: At presentation, the frequency of previous or concurrent extraorbital disease increased from marginal zone lymphoma (OR 1.0), diffuse lymphoplasmacytic/lymphoplasmacytoid lymphoma (OR 2.3), follicle centre lymphoma (OR 3.8), diffuse large B cell lymphoma (OR 4.0) to other histological lymphoma variants (OR 26.8). For all histological types, the estimated risk of extraorbital disease and lymphoma related death continued for many years and the proportion of patients with at least one extraorbital recurrence after 5 years was 47% for MZL, 48% for LPL, 64% for FCL, 81% for DLCL, and 95% for other lymphoma variants. The corresponding estimated rates for 5 year lymphoma related mortality were 12%, 19%, 22%, 48%, and 53% respectively. CONCLUSIONS: Patients with ocular adnexal lymphoma can be classified by REAL into five distinct groups, which show a progressive increase in the risks of extraorbital disease at diagnosis, of disease dissemination with time, and of tumour related death.

Adolescent↗
PubMed1999

Differences between asthma exacerbations and poor asthma control.

BACKGROUND: Increased variation in peak expiratory flow (PEF) is characteristic of poorly controlled asthma, and measurement of diurnal variability of PEF has been recommended for assessment of asthma severity, including during exacerbations. We aimed to test whether asthma exacerbations had the same PEF characteristics as poor asthma control. METHODS: Electronic PEF records from 43 patients with initially poorly controlled asthma were examined for all exacerbations that occurred after PEF reached a plateau with inhaled corticosteroid treatment. Diurnal variability of PEF was compared during exacerbations, run-in (poor asthma control), and the period of stable asthma before each exacerbation. FINDINGS: Diurnal variability was 21.3% during poor asthma control and improved to 5.3% (stable asthma) with inhaled corticosteroid treatment. 40 exacerbations occurred in 26 patients over 2-16 months; 38 (95%) of exacerbations were associated with symptoms of clinical respiratory infection. During exacerbations, consecutive PEF values fell linearly over several days then improved linearly. However, diurnal variability during exacerbations (7.7%) was not significantly higher than during stable asthma (5.4%, p=0.1). PEF data were consistent with impaired response to inhaled beta2-agonist during exacerbations but not during poorly controlled asthma. INTERPRETATION: Asthmatics remain vulnerable to exacerbations during clinical respiratory infections, even after asthma is brought under control. Calculation of diurnal variability may fail to detect important changes in lung function. PEF variation is strikingly different during exacerbations compared with poor asthma control, suggesting differences in beta2-adrenoceptor function between these conditions.

Adolescent↗
PubMed1999

Serodiagnosis of infection with verocytotoxin-producing Escherichia coli.

Human sera (167) were screened for antibodies to lipopolysaccharide (LPS) prepared from strains of Verocytotoxin-producing Escherichia coli (VTEC) belonging to a range of serogroups, secreted proteins expressed by attaching and effacing VTEC, enterohaemolysin and H = 7 flagellar proteins. Twelve sera (about 7%) contained antibodies to the LPS of E. coli 05 (one), 026 (two), 0115 (two), 0145 (one), 0163 (one) and 0165 (five). Sera containing antibodies to the LPS of E. coli O26 and O145 also contained antibodies to secreted proteins of 100 and 40 kDa. An additional 34 sera, known to contain antibodies to the lipopolysaccharide of E. coli O157, were examined for antibodies to enterohaemolysin, H = 7 flagellar antigens and bacterial cell surface-associated proteins of 5, 6 and 22 kDa. Three sera contained antibodies to enterohaemolysin and one serum contained antibodies to flagellar proteins. Antibodies to membrane-associated proteins were not detected. It was concluded that enterohaemolysin, H = 7 flagellar proteins and the cell surface-associated proteins were unsuitable for use in immunoassays for providing evidence of infection with VTEC.

Adolescent↗
PubMed1999

The serodiagnosis of infections caused by Verocytotoxin-producing Escherichia coli.

Patients with haemolytic uraemic syndrome (HUS) and haemorrhagic colitis (HC) produce serum antibodies to the lipopolysaccharides (LPS) of Escherichia coli O157 and certain other E. coli serogroups. Patients may also make salivary antibodies to the LPS of E. coli O157. Serological tests based on these antibodies can be used to provide evidence of infection in the absence of culturable VTEC or the toxins they produce. Serum antibodies to LPS persist for several months following onset of disease, enabling both current and retrospective serological testing. The LPS of E. coli O157 shares epitopes with strains of Brucella abortus, Yersinia enterocolitica O9, Vibrio cholerae O1 Inaba, group N Salmonella and certain strains of Citrobacter freundii and E. hermanni. Serological tests for serum antibodies to E. coli O157 should be evaluated in the light of these cross-reactions. Serological tests to supply evidence of infection with E. coli O157 have been shown to provide a valuable adjunct to bacteriological procedures for detecting culturable VTEC and VT. The use of well characterized LPS antigens in association with the techniques of ELISA and immunoblotting provide valuable procedures for detecting evidence of infection with E. coli O157 and possibly other VTEC.

Antibodies, Bacterial↗