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Biomedical subjects

S M Walker

Publications and source records attributed to S M Walker.

At least 19 recordsLinked to original sources
PubMed1999

Long-term clinical efficacy of grass-pollen immunotherapy.

BACKGROUND: Pollen immunotherapy is effective in selected patients with IgE-mediated seasonal allergic rhinitis, although it is questionable whether there is long-term benefit after the discontinuation of treatment. METHODS: We conducted a randomized, double-blind, placebo-controlled trial of the discontinuation of immunotherapy for grass-pollen allergy in patients in whom three to four years of this treatment had previously been shown to be effective. During the three years of this trial, primary outcome measures were scores for seasonal symptoms and the use of rescue medication. Objective measures included the immediate conjunctival response and the immediate and late skin responses to allergen challenge. Cutaneous-biopsy specimens obtained 24 hours after intradermal allergen challenge were examined for T-cell infiltration and the presence of cytokine-producing T helper cells (TH2 cells) (as evidenced by the presence of interleukin-4 messenger RNA). A matched group of patients with hay fever who had not received immunotherapy was followed as a control for the natural course of the disease. RESULTS: Scores for seasonal symptoms and the use of rescue antiallergic medication, which included short courses of prednisolone, remained low after the discontinuation of immunotherapy, and there was no significant difference between patients who continued immunotherapy and those who discontinued it. Symptom scores in both treatment groups (median areas under the curve in 1995, 921 for continuation of immunotherapy and 504 for discontinuation of immunotherapy; P=0.60) were markedly lower than those in the group that had not received immunotherapy (median value in 1995, 2863). Although there was a tendency for immediate sensitivity to allergen to return late after discontinuation, there was a sustained reduction in the late skin response and associated CD3+ T-cell infiltration and interleukin-4 messenger RNA expression. CONCLUSIONS: Immunotherapy for grass-pollen allergy for three to four years induces prolonged clinical remission accompanied by a persistent alteration in immunologic reactivity.

Adult↗
PubMed1999

The use of transvaginal power Doppler ultrasonography to evaluate the relationship between perifollicular vascularity and outcome in in-vitro fertilization treatment cycles.

The aim of this prospective study of the use of transvaginal power Doppler ultrasound was to assess the subjectivity of the grading system and to elucidate, on a much larger series (200) of treatment cycles, the findings of previous authors. Vascular perfusion was studied using a grading system based on the percentage of follicular circumference (grade 1 < 25%, grade 2 < 50%, grade 3 < 75% and grade 4 > 75%) that depicted an echo signal. Interobserver variation was low (k = 0.81 + 0.08). A total of 1285 follicles were studied, of which 64% were of high (grades 3 or 4) and 36% were of low (grades 1 or 2) grade vascularity. Mean follicular diameter, oocyte retrieval rate, number of mature oocytes recovered and fertilization rates were all significantly higher (P < 0.05) and triploidy rate significantly lower (P < 0.05) from the cohort of follicles with high grade vascularity. There was no correlation between embryo morphology and vascularity grade. The pregnancy rate for cycles where the embryos transferred were derived from follicles with uniformly high grade (3 or 4 only) vascularity was significantly higher than for those cycles where the embryos transferred were derived from mixed (1 to 4) or low (1 or 2 only) grade follicles [24/72 (34.7%) versus 22/122 (18%); P < 0.05]. There were no significant differences in uterine artery or intraovarian pulsatility index values between the pregnant and non-pregnant treatment cycles. This study suggests that follicles with high grade vascularity are associated with better outcome variables. Thus, follicular assessment may be used prospectively to improve the outcome in in-vitro fertilization treatment cycles.

Female↗
PubMed1999

Why are infertile patients not using psychosocial counselling?

The purpose of this study was to examine the sources of support that infertile patients relied on when distressed, and the factors that prevented them from using psychosocial counselling. The sample consisted of 143 infertile patients (49 couples plus 45 additional women) who were in their mid-thirties and had been infertile for approximately 6 years. Before their clinic appointment, participants completed (anonymously) a short questionnaire concerning various sources of support and factors related to the uptake of counselling. The results showed that patients relied primarily on their spouse and family when distressed, rather than on formal support resources such as psychosocial counselling. The principal reason preventing patients from using counselling varied as a function of current distress level. Less distressed patients reported that the coping resources available to them were sufficient to cope with the strains of infertility, while the more distressed patients failed to initiate contact with a counsellor because of practical concerns such as knowing who to contact and/or the cost of counselling. The findings of this study indicate that alternative ways of intervening with infertile patients would need to be developed, as few use the type of psychosocial services most frequently offered.

Adult↗
PubMed1998

Introducing ICD-10-AM in Australian hospitals.

The introduction of casemix funding systems has focused attention on the reliability and validity of coded health data. Defining and classifying medical and health related terms are the core activities of the National Centre for Classification in Health (NCCH), which has recently published the Australian modification of the International statistical classification of diseases and health related problems, 10th revision (ICD-10-AM). An important feature is a classification of procedures (MBS-E) based on the Commonwealth Medical Benefits Schedule. Clinicians have made major contributions to the new classification through a network of 21 Clinical Coding and Classification Groups, which advise the NCCH. Major advantages of ICD-10-AM for clinicians include the ability to update the classification within Australia with continued clinical consultation, the familiarity of the procedure codes based on MBS, and the possibility of having one classification for use in public and private healthcare facilities.

Australia↗
PubMed1998

Interleukin-6 levels in serum and lung lavage fluid of children undergoing open heart surgery correlate with postoperative morbidity.

OBJECTIVE: To evaluate the relationship of perioperative levels of interleukin 6 (IL-6) in serum and bronchoalveolar fluid with morbidity and mortality in children undergoing cardiopulmonary bypass (CPB). DESIGN: Prospective, noninterventional study. SETTING: Operating room and pediatric intensive care unit (PICU) of a university hospital. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: IL-6 levels were measured in serum and lung lavage fluid obtained before, during, and after CPB using the B9.9 bioassay. Alveolar epithelial lining fluid (AELF) volume was calculated using the urea correction method. Mean intraoperative AELF IL-6 levels increased fourfold compared to preoperative levels, and mean serum IL-6 levels increased fivefold after CPB. Mean intraoperative AELF IL-6 levels correlated with intraoperative blood transfusion (r2 = 0.18; p = 0.049) and duration of inotropic support (r2 = 0.29; p = 0.009), mechanical ventilation (r2 = 0.24; p = 0.019), and PICU stay (r2 = 0.29; p = 0.008). Mean serum IL-6 levels 2 h after CPB correlated with intraoperative blood transfusion (r2 = 0.3;p = 0.007), and with Pediatric Risk of Mortality score on postoperative day 3 (r2 = 0.24; p = 0.022), and were higher in patients with massive fluid retention (p = 0.014) and in nonsurvivors (p = 0.003). CONCLUSIONS: Serum and alveolar IL-6 levels increase after CPB, and correlate with postoperative morbidity. Serum IL-6 levels also correlate with mortality. They may be useful in assessing the severity of the systemic inflammatory response after CPB.

Adolescent↗
PubMed1997

Increases in IL-12 messenger RNA+ cells accompany inhibition of allergen-induced late skin responses after successful grass pollen immunotherapy.

IL-12, a novel cytokine produced by tissue macrophages and B lymphocytes, stimulates proliferation of TH1-type T lymphocytes. We recently showed that in patients with summer hay fever, immunotherapy was effective and was associated with inhibition of allergen-induced late skin responses and increases in local interferon-gamma messenger RNA-positive cells. In this study 10 patients were reassessed after 4 years of immunotherapy and compared with 10 untreated patients with hay fever. Intradermal grass pollen challenge was performed, the late response was measured, and biopsies were performed at 24 hours. In situ hybridization of biopsy sections was performed by using a riboprobe coding for IL-12 mRNA. When immunotherapy and control subjects were compared, there was a marked reduction in the size of the late skin response (p = 0.0001). Significant increases in allergen-induced IL-12 mRNA+ cells in cutaneous biopsy specimens occurred only in the immunotherapy-treated group (all 10 patients, p = 0.002). At allergen-challenged sites, IL-12+ cells correlated positively with interferon-gamma + cells (r = 0.64, p < 0.05) and inversely with IL-4+ cells (r = -0.67, p < 0.05). The principal cell source (55% to 80%) of IL-12 message was the tissue macrophage (CD68+ cells). We suggest that IL-12 may promote TH1 responses and inhibit late-phase responses after successful immunotherapy.

Adult↗
PubMed1997

Follicular vascularity--the predictive value of transvaginal power Doppler ultrasonography in an in-vitro fertilization programme: a preliminary study.

The aim of this prospective study was to investigate the ability of transvaginal power Doppler ultrasonography to assess the relationship between follicular vascularity and outcome in women undergoing in-vitro fertilization. Each of 38 subjects underwent a single transvaginal power Doppler ultrasound scan on the day of oocyte collection, where the vascularity of individual ovarian follicles was assessed, using a subjective system, and graded 1 to 4. In addition, conventional pulsatility indices (PI) of the uterine and intra-ovarian (stromal) arteries were calculated, which showed no significant differences between the pregnant and non-pregnant groups. Using power Doppler ultrasonography, a total of 188 follicles was studied. The follicular vascularity grade was found to be independent of follicular size and there was no significant difference in fertilization rates with different degrees of vascularity, although there was a trend towards higher fertilization rates with higher grade vascularity. There were 10 pregnancies, giving a pregnancy rate of 26.3% per embryo transfer. Pregnancies were confined to those women whose embryos were derived from follicles with grade 3 and 4 vascularity (pregnancy rates per embryo transfer of 12.5 and 61.5% respectively), with only those from grade 4 follicles resulting in livebirths. This preliminary study suggested that high grade follicular vascularity is associated with increased pregnancy rate and that there is a possible link between follicular vascularity and implantation potential.

Adult↗
PubMed1997

The use of laparoscopic ovarian electrocautery in preventing cancellation of in-vitro fertilization treatment cycles due to risk of ovarian hyperstimulation syndrome in women with polycystic ovaries.

Fifty women with polycystic ovaries took part in a prospective randomized study. All women required treatment by in-vitro fertilization (IVF) for reasons other than anovulation. They had all previously undergone ovarian stimulation with gonadotrophin therapy which had failed to result in pregnancy or had been abandoned due to high risk of developing ovarian hyperstimulation syndrome (OHSS). Twenty-five women were treated by long-term pituitary desensitization followed by gonadotrophin therapy, oocyte retrieval and embryo transfer (group 1). Twenty-five women underwent laparoscopic ovarian electrocautery after pituitary desensitization followed by gonadotrophin therapy, oocyte retrieval and embryo transfer (group 2). A significantly higher number of women in group 1 had to have the treatment cycle abandoned due to impending or actual OHSS, determined by endocrine and clinical findings. In addition, the development of moderate or severe OHSS in completed cycles was higher in group 1. The pregnancy rate and miscarriage rates in the two treatment groups were similar. The authors propose that laparoscopic ovarian electrocautery is a potentially useful treatment for women who have previously had an IVF treatment cycle cancelled due to risk of OHSS or who have suffered OHSS in a previous treatment cycle.

Abortion, Spontaneous↗
PubMed1997

Complex regional pain syndromes: including "reflex sympathetic dystrophy" and "causalgia".

"Reflex sympathetic dystrophy" and "causalgia" are now classified by the International Association for the Study of Pain as Complex Regional Pain Syndromes I and II. Sympathetically maintained pain is a frequent but variable component of these syndromes, as the sympathetic and somatosensory pathways are no longer functionally distinct. Pain is the cardinal feature of CRPS, but the constellation of symptoms and signs may also include sensory changes, autonomic dysfunction, trophic changes, motor impairment and psychological changes. Diagnosis is based on the clinical picture, with additional information regarding the presence of sympathetically maintained pain or autonomic dysfunction being provided by carefully performed and interpreted supplemental tests. Clinical experience supports early intervention with sympatholytic procedures (pharmacological or nerve block techniques), but further scientific data is required to confirm the appropriate timing and relative efficacy of different procedures. Patients with recurrent or refractory symptoms are best managed in a multi-disciplinary pain clinic as more invasive and intensive treatment will be required to minimize ongoing pain and disability.

Causalgia↗
PubMed1997

A comparison of sevoflurane with halothane for paediatric day case surgery.

A phase III, open label randomized study was conducted in 50 patients comparing halothane and sevoflurane for paediatric day case surgery. A graded inhalational induction resulted in only slightly more rapid induction with sevoflurane (3.34 +/- 0.92 versus 3.85 +/- 1.02 minutes; P > 0.05). In children receiving sevoflurane, systolic blood pressure decreased to a lesser extent during induction (143 +/- 19.2 versus 26.9 +/- 10.9 percent decrease from resting values; P < 0.01) and heart rate was maintained. Respiratory events (coughing, breath-holding, bronchospasm, laryngospasm) were more common during induction with halothane, and excitement more common in children receiving sevoflurane. Emergence times were significantly more rapid in children who had received sevoflurane (21.4 +/- 10.9 versus 33.1 +/- 13.7 minutes; P < 0.01). Objective pain/discomfort scores were higher in patients receiving sevoflurane at 10, 20, 30 and 40 minutes after arrival in the recovery room, and the incidence of excitement during emergence was higher in this group. It is concluded that sevoflurane is well tolerated for inhalational induction and has an improved cardiovascular profile compared to halothane. Emergence was significantly more rapid following sevoflurane.

Adolescent↗
PubMed1997

MHC class II positive retinal pigment epithelial (RPE) cells can function as antigen-presenting cells for microbial superantigen.

Retinal pigment epithelial (RPE) cells induced to express MHC class II (HLA-DR) by incubation with interferon gamma (IFN-gamma) were investigated for their ability to present a microbial superantigen to T lymphocytes. Superantigens bind to MHC class II antigens and appear to play a role in a number of infectious and autoimmune diseases through stimulation of large numbers of T cells. Primary cultures of human RPE cells treated with IFN-gamma for three days to induce HLA-DR expression bound staphylococcal enterotoxin E (SEE) via HLA-DR and presented SEE to T cells as measured by proliferation of purified peripheral blood T cells and IL-2 synthesis by the Jurkat T cell line. Untreated RPE cells were essentially ineffective as superantigen presenting cells. These results suggest that MHC class II expressing RPE cells could contribute to immune and inflammatory activity in the eye by presenting superantigens to T lymphocytes.

Antigen Presentation↗
PubMed1997

Effect of a 15-minute infusion of DDAVP on the pharmacokinetics and pharmacodynamics of REVASC during a four-hour intravenous infusion in healthy male volunteers.

Plasma pharmacokinetics, effect on coagulation parameters, and safety and tolerability of an intravenous infusion of REVASC before, during and after a DDAVP infusion were investigated. Twelve healthy volunteers were given an intravenous bolus dose followed by a constant rate four-hour infusion of REVASC. Fifteen-minute infusions of 0.9% saline and DDAVP were started two and three hours respectively after the start of the REVASC infusion. Plasma REVASC concentrations were not affected by either the saline or DDAVP infusion. REVASC infusion produced an increase in APTT which plateaued between 0.5 and 3 hours. After the DDAVP infusion there was a tendency towards a new lower plateau whilst the REVASC infusion continued. There were no serious adverse events or bleeding episodes throughout the study. In conclusion, the co-administration of intravenous DDAVP has no effect on the plasma pharmacokinetics of REVASC and partially reverses the REVASC-induced increase in APTT. This may represent a role for DDAVP in the partial reversal of anticoagulation induced by REVASC.

Adult↗
PubMed1996

Vitreous body affects activation and maturation of monocytes into macrophages.

BACKGROUND: Macrophages play an important role in several ocular diseases. Because macrophages localized in ocular tissues may be derived from blood monocytes, the effect of vitreous [containing transforming growth factor-beta 2 (TGF-beta 2) and hyaluronic acid] on blood monocytes, maturating in the tissue to macrophages, was determined. METHODS: Human monocytes were cultured with and without vitreous in RPMI 1640 medium containing human AB serum. As a parameter of activation the release of interleukin-6 was measured by the B9 bioassay; as an indication of maturation, the content of acid phosphatase and the increase in cell size were assessed. RESULTS: Monocytes in vitreous-containing medium grew more slowly than did control monocytes. Monocytes cultured in 10% vitreous released 51% less, and in 20% vitreous 73% less, interleukin-6 than control monocytes. Vitreous at 20% significantly (P = 0.0075) reduced the amount of acid phosphatase by 80% over a 4-day culture period. This reduction was partially eliminated with neutralizing antibodies to TGF-beta (P = 0.0014). Furthermore, human recombinant TGF-beta 2 increased the activity of acid phosphatase in monocytes at 1.25 ng/ml and reduced it (P < 0.0001) at higher concentrations (5-10 ng/ml). Hyaluronic acid showed an effect additive to that of TGF-beta in further diminishing the amount of acid phosphatase (P = 0.026). CONCLUSION: Vitreous exerts a regulatory effect on monocyte activation and maturation by its content of TGF-beta and possibly hyaluronic acid and may, thus, modify the inflammatory or immune response in the eye.

Acid Phosphatase↗
PubMed1995

Grass pollen immunotherapy: efficacy and safety during a 4-year follow-up study.

Grass pollen immunotherapy is effective, although efficacy must be balanced against side-effects. In a double-blind, placebo-controlled trial of 40 adult patients with summer hay fever, immunotherapy with a depot grass pollen extract (Phleum pratense, Alutard SQ) reduced symptoms and medication requirements with an acceptable minimal level of side-effects (31). The original placebo group, as well as the actively treated group, have now received active immunotherapy in an open fashion for a further 3 years. An important question was whether continued injection treatment was accompanied by maintained clinical improvement. By analysis of diary symptoms, rescue medication, and visual analogue scores during the pollen season, we show that efficacy was maintained throughout the 3-4-year study period. Clinical improvement was accompanied by a sustained and marked decrease in immediate conjunctival allergen sensitivity and a further significant decrease in the size of the allergen-induced late cutaneous response. In contrast, an initial decrease in the allergen-induced immediate cutaneous response was not maintained at 3-4 years. Of the patients, 37/40 completed the first year, 33/40 the second year, and 32/40 the third year of treatment. Patients dropped out for reasons other than the outcome of immunotherapy. During a total of 2598 injections, five immediate systemic reactions were observed, all during the induction (not maintenance) phase, and all occurred within 10 min of injection and responded promptly to adrenaline. Grass pollen immunotherapy is effective and safe, provided it is performed on carefully selected patients by trained physicians with immediate access to resuscitative measures.

Adult↗
PubMed1995

CCAAT box-dependent activation of the TATA-less human DNA polymerase alpha promoter by the human cytomegalovirus 72-kilodalton major immediate-early protein.

Human cytomegalovirus (HCMV) immediate-early (IE) proteins are known potent transregulators of viral and cellular gene expression upon HCMV infection. HCMV is known to activate a number of cellular genes intimately associated with the cell cycle and DNA replication by mechanisms involving the viral major IE 86-kDa protein (IE2). We have recently shown that IE2 mediates this activation in a TATA-dependent manner and interacts directly with the TATA-binding protein. However, a number of TATA-less cellular promoters, e.g., DNA polymerase alpha and dihydrofolate reductase, are also activated by HCMV infection. Consequently, we have asked how HCMV mediates this activation. We show that, consistent with its known TATA dependency, IE2 does not activate the DNA polymerase alpha promoter. In contrast, this promoter is strongly activated by the major IE 72-kDa protein (IE1). Whilst deletion of ATF or E2F sites within the DNA polymerase alpha promoter had little effect on IE1-mediated activation, removal of the CCAAT box appeared to abolish high levels of activation by IE1. Consistent with this observation, we also find that IE1 interacts directly with the CCAAT box binding factor CTF1 in vitro and massively augments CTF1-mediated activation of the DNA polymerase alpha promoter in transient transfection assays.

Base Sequence↗
PubMed1995

SV40-immortalized and primary cultured human retinal pigment epithelial cells share similar patterns of cytokine-receptor expression and cytokine responsiveness.

Retinal pigment epithelial (RPE) cells produce and respond to a variety of cytokines; however, molecular and biochemical studies are restricted by the limited access to large numbers of pure cells and the variability associated with different donor sources. Despite success in establishing primary human RPE (HRPE) cell cultures, the inability to sustain consistent proliferation rates and morphology over several passages remains a concern. This problem was approached by using an immortalized line of simian virus (SV)40 transformed fetal HRPE cells (SVRPE). Cytokine production, receptor expression and responsiveness in the SVRPE cell line was analyzed to determine the usefulness of this model for studying HRPE-cytokine interactions. Using reverse transcriptase polymerase chain reaction (RT-PCR), HRPE and SVRPE cells demonstrated an identical pattern of interleukin-1 receptor (IL-1R), IL-2R (alpha sub-unit), IL-6R, interferon (IFN)-gamma R and tumor necrosis factor-alpha (TNF)R p55 expression. No amplification products for TNFR p75 or granulocyte/macrophage colony stimulating factor (GM-CSF)R were demonstrated in either population. IFN-gamma stimulation induced surface human leukocyte antigen (HLA)-DR in both SVRPE and HRPE, while TNF treatment induced surface expression of intercellular adhesion molecule (ICAM)-1 on SVRPE and upregulated ICAM from basal levels on HRPE. Both cell types showed amplification products for interleukin (IL)-1 beta, IL-6 and transforming growth factor (TGF)-beta 1 using RT-PCR. The bioassays demonstrated that both populations of unstimulated cells constitutively secrete very low levels of TGF-beta and no IL-6.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗