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Biomedical subjects

D Gillis

Publications and source records attributed to D Gillis.

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

The clinical associations of mitotic spindle autoantibodies in a South Australian cohort.

BACKGROUND: The mitotic spindle apparatus (MSA) is a unique structure of microtubules and associated proteins involved in the segregation and reorganisation of chromosomes during cell division. Autoantibodies to the MSA (anti-MSA) are reported to occur rarely, but are easily identified during the immunofluorescent detection of anti-nuclear antibodies (ANA), and are generally reported as part of that investigation. AIMS: As the clinical significance of these antibodies is unknown, our aim was to identify the clinical features of subjects identified with anti-MSA, and in a subset investigate the co-association with organ specific anti-thyroid antibodies. METHODS: All ANA results from the three major immunology laboratories serving South Australia between January 1993 and June 1998 were retrospectively reviewed to identify anti-MSA subjects. Clinical details were extracted from hospital or general practice records using a standard proforma. Thyroid autoantibodies were measured using standard technique. A control group of consecutive ANA positive, anti-MSA negative individuals had anti-thyroid antibodies measured. Statistical comparison used chi2 test. RESULTS: Fifty-five subjects (43F) were identified with mean age 59.8 (range 17-91); 39 had specific diagnoses, with 16 identified as part of non-specific investigations. 'Arthritis' broadly accounted for the largest group, transient inflammatory arthritis n=7, degenerative joint disease n=6, rheumatoid arthritis n=5. Adenocarcinoma and mesothelioma accounted for one case each. Thirty-two subjects had anti-thyroid antibodies tested, with ten of 21 and two of 11 positive among the groups with anti-MSA titre >1:80 and <1:40 respectively, chi2=2.7, p=0.1. Anti-thyroid antibodies were detected more frequently among the high titre anti-MSA group (ten of 21) compared with high titre positive ANA, negative anti-MSA group (two of 11), RRisk 4.4, chi2=5.34, p=0.02. CONCLUSION: This study confirmed the relative rarity of anti-MSA and that its association is primarily with rheumatic diseases. The coincidence of mesothelioma is novel with only two previous reports of malignancy and anti-MSA. The co-association of high titre anti-MSA and thyroid autoantibodies suggest that the latter should be a follow up investigation if the former is identified as part of an investigative screen.

Adolescent↗
PubMed1999

ELISA is the superior method for detecting antineutrophil cytoplasmic antibodies in the diagnosis of systemic necrotising vasculitis.

BACKGROUND: Antineutrophil cytoplasmic antibodies (ANCA) have been used as a diagnostic marker for systemic necrotising vasculitis, a disease classification which includes Wegener granulomatosis, microscopic and classic polyarteritis nodosa, and Churg Strauss disease. OBJECTIVE: To compare the diagnostic value of the two methods for detecting these antibodies--immunofluorescence and enzyme linked immunosorbent assay (ELISA)--with respect to biopsy proven active systemic necrotising vasculitis in a clinically relevant population. METHODS: A prospective study to ascertain the patient's diagnosis at the time of each of the 466 requests for ANCA received at one laboratory over a nine month period, and allocate each to one of five diagnostic groups: active and inactive biopsy proven systemic necrotising vasculitis, suspected systemic necrotising vasculitis, low probability systemic necrotising vasculitis, and not systemic necrotising vasculitis. RESULTS: ELISA was superior to immunofluorescence in the diagnosis of systemic necrotising vasculitis because it was less likely to detect other diseases. This was reflected in its specificity of 97% and positive predictive value of 73%, compared with 90% and only 50% for immunofluorescence (p = 0.0006 and p = 0.013, respectively). ELISA had a negative predictive value of 98% which was not significantly different to immunofluorescence. ELISA was technically superior. CONCLUSIONS: ELISA is the superior method of ANCA detection in the diagnosis of systemic necrotising vasculitis and should be used in conjunction with a compatible clinical picture and histological evidence.

Adolescent↗
PubMed1999

The effect of blood transfusion protocol on retinopathy of prematurity: A prospective, randomized study.

OBJECTIVE: Controversy exists regarding the potential influence of anemia and blood transfusions on the rate of retinopathy of prematurity (ROP) in premature infants. A prospective, randomized, masked trial was performed to determine the influence of red blood cell transfusion protocol on ROP incidence and severity in a population of high-risk infants. METHODS: A total of 50 infants with birth weights <1251 g were divided randomly into two groups beginning on day of life 29. Group 1 (n = 24) received red cell transfusions during the 6-week study period, only if certain symptom-based guidelines were met. Group 2 (n = 26) received red cell transfusions to maintain the hematocrit level above 40% for the entire 6 weeks. Infants were monitored for ROP, growth, and associated morbidity. Serial measurements of serum glucose, lactate, ferritin, total iron-binding capacity, and iron were performed. RESULTS: ROP occurred in 83% of infants in group 1, and 73% of infants in group 2. There were no statistically significant differences in ROP severity, intraventricular hemorrhage, bronchopulmonary dysplasia, necrotizing enterocolitis, or any of the laboratory values except hemoglobin (10.8 vs 13.2 g/dL) and hematocrit (33.9% vs 41.8%) between the groups. Combining data from both groups, there was no association between hemoglobin or hematocrit ratios and ROP incidence or severity. CONCLUSIONS: A transfusion policy aimed at limiting the amount of blood given to premature infants (symptom-based) during the neonatal period does not impart a significantly different risk for ROP or other associated conditions, than does a policy in which transfusions are given more liberally for replacement purposes.

Erythrocyte Transfusion↗
PubMed1998

Parathyroid adenoma after radiation in an 8-year-old boy.

We describe an 8-year-old boy who had asymptomatic hypercalcemia 4 years after radiotherapy involving the left orbit and lungs. A right parathyroid adenoma was diagnosed, and normocalcemia was achieved after its removal. Routine monitoring of serum calcium and phosphate levels is recommended for children after head and neck irradiation.

Adenoma↗
PubMed1998

A young boy with a thyroid yo-yo.

We describe a boy with Hashimoto's thyroiditis and Addison's disease who was initially hypothyroid, developed hyperthyroidism and eventually became euthyroid. A rise and fall in thyroid binding inhibitory immunoglobulin and thyroid stimulating antibodies were demonstrated to have correlated with the appropriate changes in thyroid status. The fact that Hashimoto's thyroiditis can evolve in such a way emphasizes the importance of lifetime follow-up in these patients.

Addison Disease↗
PubMed1997

The effect of substrate utilization, manipulated by nicotinic acid, on excess postexercise oxygen consumption.

Increased fat oxidation during the recovery period from exercise is thought to be a contributing factor for excess postexercise oxygen consumption (EPOC). In an attempt to study the effect of serum free fatty acid (FFA) availability during exercise and recovery on the EPOC, nicotinic acid, a potent inhibitor of FFA mobilization from adipose tissue, was administered to five trained male cyclists prior to, during, and after a bout of cycling at 65% VO2max. In the nicotinic acid trial, a 500 mg dose of nicotinic acid was ingested prior to exercise, and 100 mg doses were ingested at 15, 30, and 45 min exercise, and 30 min recovery. The cyclists also completed a trial under control conditions. Serum FFA, serum glycerol, RER and VO2 were monitored during rest, exercise, and recovery, each of which was 1-h in duration. Nicotinic acid ingestion prevented the increase in serum FFA that occurred during exercise in the control trial. FFA levels during the nicotinic acid trial were significantly lower than control values during both exercise and recovery. Serum glycerol levels were also significantly lower during exercise in the nicotinic acid trial, indicative of a reduction in lipolysis. RER was not significantly different at rest or during exercise; however, RER values were significantly lower during recovery in the control trial, indicative of greater fat oxidation. For both treatments, postexercise VO2 remained elevated above resting levels at the completion of the 1-h recovery period. However, the magnitude of EPOC was significantly reduced after FFA blockade with nicotinic acid (3.4 +/- 0.61 vs 5.5 +/- 0.71). These results support the hypothesis that increased FFA metabolism during exercise and recovery is an important contributing factor to the magnitude of EPOC.

Adipose Tissue↗
PubMed1997

Expression and function of the leucine zipper protein Par-4 in apoptosis.

The prostate apoptosis response-4 (par-4) gene was identified by differential screening for genes that are upregulated when prostate cancer cells are induced to undergo apoptosis. The par-4 gene is induced by apoptotic signals but not by growth-arresting, necrotic, or growth-stimulatory signals. The deduced amino acid sequence of par-4 predicts a protein with a leucine zipper domain at its carboxy terminus. We have recently shown that the Par-4 protein binds, via its leucine zipper domain, to the zinc finger domain of Wilms' tumor protein WT1 (R. W. Johnstone et al., Mol. Cell. Biol. 16:6945-6956, 1996). In experiments aimed at determining the functional role of par-4 in apoptosis, an antisense par-4 oligomer abrogated par-4 expression and activator-driven apoptosis in rat prostate cancer cell line AT-3, suggesting that par-4 is required for apoptosis in these cells. Consistent with a functional role for par-4 in apoptosis, ectopic overexpression of par-4 in prostate cancer cell line PC-3 and melanoma cell line A375-C6 conferred supersensitivity to apoptotic stimuli. Transfection studies with deletion mutants of Par-4 revealed that full-length Par-4, but not mutants that lacked the leucine zipper domain of Par-4, conferred enhanced sensitivity to apoptotic stimuli. Most importantly, ectopic coexpression of the leucine zipper domain of Par-4 inhibited the ability of Par-4 to enhance apoptosis. Finally, ectopic expression of WT1 attenuated apoptosis, and coexpression of Par-4 but not a leucine zipperless mutant of Par-4 rescued the cells from the antiapoptotic effect of WT1. These findings suggest that the leucine zipper domain is required for the Par-4 protein to function in apoptosis.

Amino Acid Sequence↗
PubMed1996

Maximal effort during functional capacity evaluations: an examination of psychological factors.

BACKGROUND AND PURPOSE: Patients with low back pain are often administered a Functional Capacity Evaluation (FCE) to determine levels of physical functioning at the conclusion of their rehabilitation program. The purpose of this study was to examine the relationship between psychological factors (ie, self-reported disability, anxiety, depression, self-efficacy) and maximal effort exerted during the FCE. SUBJECTS AND METHODS: Sixty-four patients with low back pain were administered the the Oswestry Low Back Disability Questionnaire, Beck Depression Inventory, State-Trait Anxiety Inventory, and the FCE Self-Efficacy Scales before administration of the FCE. RESULTS: Compared with patients who gave maximal effort during the FCE, patients who did not exert maximal effort reported significantly more anxiety and self-reported disability, and reported lower expectations for both their FCE performance and for returning to work. There was also a trend for these patients to report more depressive symptomatology. CONCLUSIONS AND DISCUSSION: Results provide evidence for the relationship between self-reported disability, depression, anxiety, self-efficacy, and patients' performance on the FCE. Suggestions for addressing the psychological factors in a comprehensive pain treatment program are provided.

Activities of Daily Living↗
PubMed1996

Clinical associations of anti-lamin autoantibodies.

BACKGROUND: The clinical associations of anti-lamin autoantibodies were first described in 1973. Since then a number of individual case reports and two small series have been published. These have suggested an association with connective tissue disorders and autoimmune liver disease. AIMS: To identify the clinical and laboratory associations of anti-lamin autoantibodies in an Australian population. METHODS: Retrospective review of routine antinuclear antibody testing between 1990-1994 for characteristics linear staining of nuclear envelope on indirect immunofluorescence on HEp-2 cells with clinical status defined by retrospective review of case records. RESULTS: Twenty-eight patients were identified and the clinical status of 27 patients defined. Eleven patients had associated IgG anti-cardiolipin antibodies; anti-phospholipid syndrome was present in nine. Seven further patients had liver disease; five had autoimmune liver disease, with associated autoantibodies. The remaining nine patients had a diverse group of diseases. There was no correlation between the titre of the autoantibody and clinical status. An association with anti-cardiolipin antibodies was found although the cause remains obscure. CONCLUSION: Anti-lamin autoantibodies, as identified by indirect immunofluorescence, are associated with a diverse group of diseases but particularly with anti-phospholipid syndrome and liver disease. Testing for anti-phospholipid antibodies and more specific markers of systemic lupus erythematosus and autoimmune disease, for example anti-dsDNA antibodies, anti-smooth muscle antibodies and anti-mitochondrial antibodies should be pursued when anti-lamin autoantibodies are detected.

Adult↗
PubMed1995

Neutrophils activated by granulocyte-macrophage colony-stimulating factor express receptors for interleukin-3 which mediate class II expression.

Freshly isolated peripheral blood neutrophils, unlike monocytes and eosinophils, do not bind interleukin-3 (IL-3) or respond to IL-3). We show that neutrophils cultured for 24 hours in granulocyte-macrophage colony-stimulating factor (GM-CSF) express mRNA for the IL-3 receptor (R) alpha subunit, as shown by RNase protection assays, and IL-3R alpha chain protein, as shown by cytometric analysis using two different specific monoclonal antibodies. This effect was selective for GM-CSF, because granulocyte colony-stimulating factor, tumor necrosis factor-alpha, interferon-gamma, and IL-1 failed to induce the IL-3 receptor. Saturation binding curves with 125I-IL-3 and Scatchard transformation showed the presence of about 100 high-affinity and 4,000 low-affinity receptors. Because neutrophils have been shown to express human leukocyte antigen (HLA)-DR in response to GM-CSF, we examined the possibility that IL-3 could augment HLA-DR expression on GM-CSF-treated cells. We found that neutrophils incubated with 30 ng/mL IL-3 as well as 0.1 ng/mL GM-CSF expressed a mean of 2.1-fold higher levels of HLA-DR than with GM-CSF alone (P < .005), confirming the signaling competence of the newly expressed IL-3R. This increase was seen even at maximal concentrations of GM-CSF and IL-3 can have an additive effect on mature human cells. The augmentation of HLA-DR by IL-3 was specific because it could be inhibited by a blocking anti-IL-3R antibody. Expression of class II molecules by neutrophils under these conditions may have significance for antigen presentation. These results provide further evidence for the role of GM-CSF as an amplification factor in inflammation by inducing neutrophil responsiveness to IL-3 produced by T cells or mast cells.

Cells, Cultured↗
PubMed1995

Gymnasts exhibit higher bone mass than runners despite similar prevalence of amenorrhea and oligomenorrhea.

Female athletes exhibit a higher prevalence of exercise-associated amenorrhea and oligomenorrhea compared with nonathletic women, and both conditions are related to reduced bone mineral density (BMD), particularly at the spine. This study investigated bone mass and oligomenorrhea and amenorrhea in two groups of competitive female athletes with different skeletal loading patterns: gymnasts and runners. Bone mineral density (g/cm2) of the femoral neck, lumbar spine (L2-4), and whole body was assessed by dual energy X-ray absorptiometry (QDR-1000/W, Hologic Inc., Waltham, MA) in collegiate gymnasts (n = 21) and runners (n = 20), and nonathletic college women (n = 19). The runners and gymnasts had similar values for percent body fat (14.7 +/- 2.2% and 15.6 +/- 2.9%, respectively), which were lower (p < 0.001) than controls (22.3 +/- 3.0%). Lean body mass (LBM) did not differ among the groups, but when adjusted for body surface area, gymnasts had a higher LBM/height2 (p = 0.0001) compared with runners and controls. Muscle strength was significantly greater (p < 0.05) in gymnasts for quadriceps, biceps, and hip adductor force, compared with runners and controls. Gymnasts had a significantly later menarche age (16.2 +/- 1.7 years) compared with runners (14.4 +/- 1.7 years) and controls (13.0 +/- 1.2 years). The prevalence of oligo- and amenorrhea was 47% for gymnasts (6 amenorrheic, 4 oligomenorrheic), 30% for runners (3 amenorrheic, 3 oligomenorrheic), and 0% for controls. Furthermore, athletic groups had similar menstrual histories given the higher proportion of gymnasts who had experienced primary amenorrhea. When evaluated since menarche, however, runners had somewhat longer histories due to an earlier age at menarche and slightly older ages. Dietary calcium intake did not differ among groups, although mean values were below the RDA of 1200 mg/day. By athletic group, BMD at any site did not differ among women with amenorrhea versus oligomenorrhea versus eumenorrhea, although there was a trend for the regularly menstruating athletes in both groups to have slightly higher values. Lumbar spine BMD was lower (p = 0.0001) in runners (0.98 +/- 0.11 g/cm2) compared with both gymnasts and controls (1.17 +/- 0.13 and 1.11 +/- 0.11 g/cm2, respectively). Femoral neck BMD differed among all groups (p = 0.0001): gymnasts = 1.09 +/- 0.12 g/cm2 > controls = 0.97 +/- 0.10 g/cm2 > runners = 0.88 +/- 0.11 g/cm2. Whole body BMD was lower (p < 0.01) in runners (1.04 +/- 0.06 g/cm2) compared with gymnasts and controls (1.11 +/- 0.08 and 1.09 +/- 0.06 g/cm2, respectively).(ABSTRACT TRUNCATED AT 400 WORDS)

Absorptiometry, Photon↗
PubMed1994

Toxic epidermal necrolysis associated with Klebsiella pneumoniae sepsis.

Toxic epidermal necrolysis (TEN) is a rare condition in childhood usually attributed to drugs. We describe a 4-month-old infant who developed typical clinical and histologic findings of TEN concomitantly with Klebsiella pneumoniae sepsis. We emphasize that in cases of acute, severe exfoliative disease in infants, apart from staphylococcal infection, gram-negative bacterial sepsis must also be considered.

Bacteremia↗
PubMed1994

Screening and monitoring coeliac disease: multicentre trial of a new serum antibody test kit.

A multicentre trial was conducted to evaluate a new test for anti-gliadin antibodies (AGA) in serum (Coeliac Screening Kit, CSK, Medical Innovations Limited, Artarmon, NSW, Australia). The test showed excellent reproducibility for both anti-gliadin IgA and IgG detection. The average intraassay coefficient of variation (CV) was 3.0% for IgA and 2.4% for IgG (n = 6), while the average interassay CV was 6.4% for IgA and 4.3% for IgG (n = 3). By defining a positive test as both IgA and IgG elevated, a sensitivity of 93% in untreated coeliacs (n = 75) was observed. The corresponding specificities in healthy adults (n = 130) and healthy children (n = 77) were > 99% and 100% respectively, while in patients with other gastrointestinal disorders (disease controls) the specificity was 94% (n = 129). The test was also useful in monitoring patients, with anti-gliadin IgA and IgG falling for up to a year after commencing a gluten-free diet (GFD) (12 adults). In some patients however, antibody levels did not reach the normal cutpoint after many months on a GFD, which may reflect the patients' poor adherence to their gluten free diet. The test was superior to the Pharmacia anti-gliadin ELISA, and should be useful as an aid to the diagnosis of coeliac disease, as well as in the follow-up of treated patients.

Adult↗
PubMed1994

Recurrent mesangial IgA nephritis following renal transplantation.

Recurrence of mesangial IgA deposits in renal allografts of patients whose original disease was primary IgA nephropathy (IgAN) has been studied. Forty-six patients with primary IgAN received 51 renal allografts and have been followed for 3-183 months. A prospective study of 11 patients (11 biopsies) and a retrospective analysis of 17 patients (16 biopsies; 2 nephrectomy specimens) have been combined. Seventeen of the 29 allografts had recurrent mesangial IgA deposits and of these three patients have negative urinalysis, normal glomeruli by light microscopy, and stable renal function; six patients have microhaematuria, mesangial proliferative nephritis, but at present stable renal function; and five have mesangial proliferative glomerulonephritis with microhaematuria, heavy proteinuria, hypertension, and progressive allograft failure secondary to IgA disease alone, and one of these is now back on dialysis. Three other grafts with recurrent deposits are failing because of transplant glomerulopathy or rejection. The only predictor identified for recurrence of mesangial IgA deposits was length of time post-transplantation, with allograft tissue being studied at 45.9 +/- 10.0 versus 15.3 +/- 4.8 months (P = 0.008) post-transplantation in patients with and without recurrent deposits respectively. Cyclosporin A did not prevent recurrence. By virtue of a longer follow-up of patients post-transplantation than all other reported series, these results suggest that with increasing time post-transplantation recurrence of mesangial IgA disease will become increasingly important as a cause of progressive allograft dysfunction and failure unless effective treatment is found for the primary disease.

Complement C3↗